@article{bizikova_linder_anderson_2023, title={Erosive and ulcerative stomatitis in dogs and cats: which immune-mediated diseases to consider?}, volume={261}, ISSN={["1943-569X"]}, DOI={10.2460/javma.22.12.0573}, abstractNote={Abstract Immune-mediated and autoimmune diseases of the skin often present with oral cavity involvement. Autoimmune subepidermal blistering diseases and pemphigus vulgaris are classic examples. While the primary lesions (vesicles and bullae) are relatively specific, these fragile lesions evolve rapidly into erosions and ulcers, which are lesion types that overlap with many diseases. Furthermore, some immune-mediated diseases such as severe adverse drug reactions, lupus diseases, canine uveodermatological syndrome, and vasculitis, may or may not involve the oral cavity, and often nonoral clinical manifestations are more diagnostic. In these situations, disease knowledge combined with signalment, lesion distribution, and history help to narrow the differentials. Surgical biopsy is required for confirmation in most diseases, while immunosuppressive treatments most typically involve glucocorticoids with or without nonsteroidal immunosuppressants.}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Bizikova, Petra and Linder, Keith E. and Anderson, Jamie G.}, year={2023}, month={Jun}, pages={S48–S57} }
 @article{gedon_bizikova_olivry_mendoza-kuznetsova_oberkirchner_robertson_linder_2023, title={Histopathological characterisation of trunk-dominant canine pemphigus foliaceus, and comparison with classic facial and insecticide-triggered forms}, volume={6}, ISSN={["1365-3164"]}, DOI={10.1111/vde.13174}, abstractNote={While the clinical features were described recently, the histopathological characterisation of trunk-dominant canine pemphigus foliaceus (PF) is lacking, and whether it differs from classic facial or insecticide-triggered PF is unknown. This study describes the histopathological findings of trunk-dominant PF, and compares the results to classic facial and insecticide-triggered PF. Skin biopsies from 103 dogs with clinically characterised trunk-dominant (n = 33), classic facial (n = 26) and insecticide-triggered PF (n = 44) were included. Histological sections, randomised and blinded, were scored for over 50 morphological parameters of pustules, epidermis, dermis, adnexa and crusts. Intact pustule area and width were measured by digital microscopy. In trunk-dominant PF, 77 intact pustules were predominantly subcorneal (0.0019–1.940 mm2 area, 0.0470–4.2532 mm wide), and contained from one to over 100 acantholytic keratinocytes. Pustules had boat acantholytic cells, corneocytes, perinuclear eosinophilic rings, neutrophil rosettes, acantholytic cell necrosis, rafts, cling-ons and/or eosinophils. Peripustular epidermal spongiosis, necrosis and lymphocyte exocytosis occurred, as did follicular pustules. Mixed dermal inflammation often contained eosinophils. Trunk-dominant PF did not differ from the other PF groups except for few parameters, such as having fewer rafts (p = 0.003). Additional autoimmune inflammatory patterns occurred in all PF groups. Trunk-dominant PF and other canine PF variants are histologically similar, which indicates shared pathomechanisms. The identification of common boat acantholytic cells and corneocyte separation has implications for the mechanisms of acantholysis. The diversity of histopathological and polyautoimmunity features support complicated immune mechanisms. Finally, results indicate that diagnostic biopsies cannot differentiate between these PF variants in dogs. 虽然最近对其临床特征进行了描述，但缺乏躯干显性犬落叶型天疱疮(PF)的组织病理学特征，也不知道它是否与经典的面部或杀虫剂引发的PF不同。 本研究描述了躯干显性PF的组织病理学发现，并将其结果与经典的面部和杀虫剂触发PF进行了比较。 包括103只具有临床特征的躯干显性(n=33)、典型面部(n=26)和杀虫剂触发PF(n=44)的犬的皮肤活检。 组织学切片，随机和盲法，对脓疱、表皮、真皮、毛囊附件和结痂的50多个形态学参数进行评分。通过数字显微镜测量完整的脓疱面积和宽度。 在躯干显性的PF中，77个完整的脓疱主要位于角质层下(面积0.0019–1.940 mm2，宽度0.0470–4.2532 mm)，包含1至100多个棘层松懈性角质细胞。脓疱有连片的棘层松懈细胞、角化细胞、核周嗜酸性粒细胞环、中性粒细胞花环、棘层松懈细胞坏死、筏状排列、紧靠和/或嗜酸性粒细胞。出现脓疱周围表皮海绵状水肿、坏死和淋巴细胞外排，毛囊性脓疱也是如此。混合性真皮炎症通常含有嗜酸性粒细胞。躯干显性PF与其他PF组没有差异，除了一些参数，例如筏状排列更少(p=0.003)。所有PF组都出现了额外的自身免疫炎症模式。 躯干显性PF和其他犬PF变体在组织学上相似，这表明共同的病理机制。常见连片棘层松懈细胞和分离角化细胞的鉴定，牵连出棘层松懈的机制。组织病理学和多重自身免疫特征的多样性支持复杂的免疫机制。最后，结果表明，诊断性活组织检查无法区分犬的这些PF变体。 Bien que les caractéristiques cliniques aient été décrites récemment, la caractérisation histopathologique du pemphigus foliacé (PF) canin à dominant tronculaire fait défaut, et on ne sait pas s'il diffère du PF facial classique ou induit par un insecticide. Cette étude décrit les résultats histopathologiques provenant de PF à dominante tronculaire et les compare à ceux de PF faciaux classiques et induits par un insecticide. les biopsies cutanées de 103 chiens présentant une PF à dominante tronculaire (n = 33), faciale classique (n = 26) et déclenchée par un insecticide (n = 44) sont étudiées. Des coupes histologiques, randomisées et en aveugle, sont évaluées pour plus de 50 paramètres morphologiques relatifs aux pustules, à l'épiderme, au derme, aux annexes et aux croûtes. La surface et la largeur des pustules intactes sont mesurées par microscopie numérique. Concernant les PF à dominante tronculaire, 77 pustules intactes sont principalement sous-cornéennes (surface de 0,0019 à 1,940 mm2, largeur de 0,0470 à 4,2532 mm) et contiennent de un à plus de 100 kératinocytes acantholytiques. Les pustules contiennent des cellules acantholytiques en radeau, des cornéocytes, des halos éosinophiles périnucléaires, des rosettes de neutrophiles, une nécrose des cellules acantholytiques, des radeaux, des amas et/ou des éosinophiles. Une spongiose épidermique péripustuleuse, une nécrose et une exocytose lymphocytaire sont observées, ainsi que des pustules folliculaires. L'inflammation cutanée mixte contient souvent des éosinophiles. Le PF à dominante tronculaire ne différe pas des autres groupes de PF, à l’exception de quelques paramètres, comme le fait de présenter moins de radeaux (p = 0,003). D’autres patterns inflammatoires auto-immuns ont été observés dans tous les groupes de PF. le PF à dominante tronculaire et les autres variants canins de PF sont histologiquement similaires, ce qui indique des mécanismes pathologiques communs. L'identification commune de cellules acantholytiques en radeau associée à la disruption des cornéocytes a des implications en termes de mécanisme acantholytique. La diversité des caractéristiques histopathologiques et de polyauto-immunité argue en faveur de mécanismes immunitaires complexes. Enfin, les résultats indiquent que l’examen des biopsies ne permet pas de différencier ces variants de PF chez le chien. Während die klinischen Merkmale jüngst beschrieben wurden, fehlt eine histopathologische Charakterisierung des Rumpf-dominierten Pemphigus foliaceus (PF) des Hundes, ebenso ist die Unterscheidung zum klassischen Gesichts- oder Insektizid-ausgelöstem PF unbekannt. Diese Studie beschreibt die histopathologischen Befunde des Rumpf-dominierten PF, und vergleicht die Ergebnisse zum klassischen Gesichts- und Insektizid-ausgelösten PF. Hautbiopsien von 103 Hunden mit klinisch beschriebenem Rumpf-dominierten PF (n = 33), klassischem Gesichts- (n = 26) und Insektizid-ausgelöstem PF (n = 44) wurden inkludiert. Histologische Schnitte, zufällig ausgewählt und geblindet, wurden auf über 50 morphologische Parameter wie Pusteln, Epidermis, Dermis, Adnexe und Krusten untersucht. Bei intakten Pusteln wurde die Stelle und der Durchmesser mittels Digitalmikroskopie gemessen. Beim Rumpf-dominierten PF traten intakte Pusteln vor allem subcorneal auf (0,0019-1,949 mm2; 0,0470-4,2532 mm Durchmesser) und enthielten zwischen einem und über 100 akantholytische Keratinozyten. Die Pusteln hatten Boot-ähnliche akantholytische Zellen, Korneozyten, perinukleäre eosinophile Ringe, neutrophile Rosetten, akantholytische Zellnekrosen, zusammenhängende Zellen, einzeln anhängende Zellen und/oder Eosinophile. Es trat eine peripustulöse epidermale Spongiose, Nekrose und Lymphozyten Exozytose auf, sowie follikuläre Pusteln. In der gemischten dermalen Entzündung traten auch häufig Eosinophile auf. Der Rumpf-dominierte PF unterschied sich nicht vom PF der anderen Gruppen außer in einigen wenigen Parametern, wie weniger zusammenhängende Zellen (p = 0,003). Zusätzliche autoimmune entzündliche Merkmale traten in allen PF-Gruppen auf. Der Rumpf-dominierte PF und andere PF-Varianten des Hundes sind histologisch ähnlich, was einen gemeinsamen Pathomechanismus deutlich macht. Die Identifizierung sogenannter akantholytischer Zellen in Boot-Form und eine Korneozyten Separierung hat auch eine Bedeutung im Bezug auf die Mechanismen der Akantholyse. Die Vielfalt der histopathologischen und polyautoimmunen Merkmale weist auf komplizierte immune Mechanismen hin. Letztendlich zeigen diese Ergebnisse, dass die diagnostischen Biopsien nicht zwischen den PF-Varianten des Hundes unterscheiden können. 体幹優位型犬落葉状天疱瘡(PF)の病理組織学的特徴は最近報告されているが、古典的な顔面型や駆虫薬誘発型PFと異なるかどうかは不明である。 本研究では、体幹優位型PFの病理組織学的所見を述べ、古典的顔面型PFおよび駆虫薬誘発型PFと比較することであった。 体幹優位型PF(n = 33)、古典的顔面型PF(n = 26)、駆虫薬誘発型PF(n = 44)の臨床的特徴を有する犬103頭の皮膚生検が対象となった。 組織切片を無作為に盲検化し、膿疱、表皮、真皮、付属器、痂皮の50以上の形態学的パラメータについてスコア化した。膿疱の面積と幅は、デジタル顕微鏡で測定した。 体幹優位型PFでは、77個の膿疱は主に角層下(面積0.0019-1.940mm2、幅0.0470-4.2532mm)で、1~100個以上の角化細胞が含まれていた。膿疱は、ボート状の棘融解細胞、角質細胞、核周囲の好酸性リング、好中球ロゼット、棘融解細胞壊死、ラフト、クリングオン、好酸球を有していた。毛包の膿疱と同様に、膿疱周囲表皮の海綿状変化、壊死、リンパ球のエクソサイトーシスが起こった。真皮の混合性炎症はしばしば好酸球を含んでいた。体幹優位型PFは、ラフトが少ない(p = 0.003)といったいくつかのパラメータを除いて、他のPFグループと差がなかった。自己免疫性炎症パターンは、すべてのPF群で発生した。 体幹優位型PFと他の犬PF変種は組織学的に類似しており、これは病態メカニズムを共有していることを示した。共通のボート状棘融解細胞および角質細胞の分離の特定は、棘融解のメカニズムを示唆していた。病理組織学的および多自己免疫学的特徴の多様性は、複雑な免疫機構を支持した。最後に、診断用生検では、犬におけるこれらのPF変種を区別することができないことが示された。 Enquanto as características clínicas foram descritas recentemente, ainda falta a caracterização histopatológica do pênfigo foliáceo (PF) canino predominante no tronco e não se sabe se ele difere do PF foliáceo facial clássico e do desencadeado por inseticida. Este estudo descreve os achados histopatológicos do PF predominante no tronco e compara os resultados com o PF clássico e com o desencadeado por inseticidas. Foram incluídas biópsias cutâneas de 103 cães com PF caracterizado clinicamente como predominante no tronco (n = 33), facial clássico (n = 26) e desencadeado por inseticidas (n = 44). Cortes histológicos randomizados e cegos foram classificados por mais de 50 parâmetros morfológicos de pústulas, epiderme, derme, anexos e crostas. A área e a largura das pústulas intactas foram mensuradas por microscopia digital. No PF predominante no tronco, as pústulas intactas foram principalmente subcórneas (0,0019–1,940 mm2 de área, 0,0470–4,2532 mm de largura), e continham de um a mais de cem queratinócitos acantolíticos. As pústulas apresentavam células acantolíticas em formato de barco, corneócitos, anéis eosinofílicos perinucleares, rosetas neutrofílicas, necrose de células acantolíticas, aglomerados de células acantolíticas, grupos de células do estrato granuloso aderidas ao estrato córneo (cling-on) e/ou eosinófilos. Ocorreram espongiose epidérmica peripustular, necrose e exocitose de linfócitos, bem como pústulas foliculares. No infiltrado inflamatório dérmico misto frequentemente continha eosinófilos. O PF predominante no tronco não diferiu dos outros grupos de PF exceto para poucos parâmetros, como por exemplo apresentar menos aglomerados de células acantolíticas (p = 0.003). Os outros padrões inflamatórios autoimunes ocorreram em todos os grupos de PF. O PF predominante no tronco e as outras variantes do PF canino são histologicamente similares, o que indica a existência de patomecanismos comuns. A identificação frequente de células acantolíticas em formato de barco e separação de corneócitos tem implicações nos mecanismos de acantólise. A diversidade as características histopatológicas e poliautoimunes corroboram com os mecanismos imunológicos complexos. Finalmente, os resultados indicam que as biópsias diagnósticas não são capazes de diferenciar essas variantes de PF em cães. si bien las características clínicas se describieron recientemente, falta la caracterización histopatológica del pénfigo foliáceo (PF) canino dominante en el tronco, y se desconoce si difiere del PF facial clásico o desencadenado por insecticidas. Este estudio describe los hallazgos histopatológicos de la PF predominante en el tronco y compara los resultados con PF facial clásico y el PF desencadenado por insecticidas. Se incluyeron biopsias de piel de 103 perros con PF predominante en el tronco clínicamente caracterizado (n = 33), PF facial clásico (n = 26) y el desencadenado por insecticida (n = 44). Las secciones histológicas se puntuaron para más de 50 parámetros morfológicos al azar y de forma ciega para las características de pústulas, epidermis, dermis, anejos y costras. El área y el ancho de la pústula intacta se midieron mediante microscopía digital. En la PF dominante de tronco 77 pústulas intactas fueron predominantemente subcorneales (0,0019–1,940 mm2 de área, 0,0470–4,2532 mm de ancho) y contenían de uno a más de 100 queratinocitos acantolíticos. Las pústulas tenían células acantolíticas agrupadas, corneocitos, anillos eosinófilos perinucleares, rosetas de neutrófilos, necrosis de células acantolíticas, acantolisis en línea, células acantoliticsas adheridas y/o eosinófilos. Se produjo espongiosis epidérmica peripustulosa, necrosis y exocitosis de linfocitos, así como pústulas foliculares. La inflamación dérmica mixta a menudo contenía eosinófilos. La PF de tronco dominante no se diferenció de los otros grupos de PF excepto por algunos parámetros, como tener menos células en línea (p = 0,003). Se produjeron patrones inflamatorios autoinmunitarios adicionales en todos los grupos de PF. El PF dominante en el tronco y otras variantes del PF canino son histológicamente similares, lo que indica mecanismos patogénicos compartidos. La identificación de células acantolíticas en grupos y la separación de corneocitos tiene implicaciones para los mecanismos de acantólisis. La diversidad de características histopatológicas y de poliautoinmunidad respalda mecanismos inmunitarios complicados. Finalmente, los resultados indican que las biopsias de diagnóstico no pueden diferenciar entre estas variantes de PF en perros. Trunk-dominant pemphigus foliaceus (tPF) is a clinical variant of canine pemphigus foliaceus (PF) that presents without dorsal muzzle/nasal planum involvement and, sometimes, without footpad involvement typically seen in classic facial PF (fPF).1 The trunk-dominant patterning of skin lesions and the acantholytic pustular reactions seen on cytological and histological evaluation also occur in canine superficial bacterial pyoderma, thus making this variant of PF more difficult, time-consuming and expensive to diagnose.1 Although the clinical and immunological features of tPF were recently described and compared with fPF,1 little is known about its histological features. Additionally, it is unclear if there are histopathological differences between tPF and the other clinical PF variants recognised in dogs that could suggest potential pathomechanisms of the lesion formation, explain the clinical variation, or help in differentiating these conditions. Therefore, the purpose of this study was to (i) describe the histopathological features of canine tPF and (ii) compare the histopathological features of tPF with those of classic fPF and insecticide-triggered PF (iPF). Skin biopsy specimens from client-owned dogs with active tPF and fPF collected for standard-of-care, routine diagnostic assessment between January 2004 and March 2022 were selected for the study (North Carolina State University and Cummings School of Veterinary Medicine at Tufts University). Client consent to use the diagnostic samples for study purposes was obtained. Case inclusion criteria and the majority of PF patients were clinically described in a previously published study.1 Briefly, patients had a pustular skin disease with cytological confirmation of keratinocyte acantholysis and lesion distributions of tPF or fPF.1 No potential drug or other trigger was identified. For fPF, symmetrical lesions affected the dorsal muzzle/nasal planum, with or without other body areas involved. For tPF, skin lesions affected the body, and not the dorsal muzzle/nasal planum. Dogs had a negative bacterial culture and/or clinical signs did not respond to oral antibiotics, complete remission was achieved with immunosuppressive therapy, and 3-month follow-up information was available. The type and dose of immunomodulatory drugs received during the 2-week period before biopsy collection were recorded and statistically assessed for impact on results. Previously published cases of iPF were included.2-4 Haematoxylin and eosin-stained biopsy sections were pre-screened to establish histological descriptive criteria and a scoring system, before being randomised (https://www.random.org), blinded and digitally scanned (Aperio AT2 microscope slide scanner; Leica Biosystems). Whole-slide image files were viewed with Aperio ImageScope (v.12.4.6; Leica Biosystems) and glass slides were viewed with an Olympus BX40 microscope. Pustules had to contain acantholytic cells, while granulocyte accumulations in the epidermis without acantholytic cells were classified as micropustules. Pustules with more than 50% of healing at the base by parakeratosis were classified as crusts. Using image files, each histological section and every pustule was individually identified and numbered for each case, and pustules were recorded as intact or ruptured (more than 15% disrupted or partially dried). Pustule descriptors were tracked to each pustule uniquely. The cross-sectional area of each intact pustule was calculated from manual morphometric tracings and the greatest pustule width was measured using Aperio ImageScope. Morphological descriptors are provided in Table 1, including the related scoring scheme used for each criterion. For parameters scored per case, the histological section with the most developed lesion was selected. Boat acantholytic cells were defined as separated keratinocytes in pustules that retained a flattened or ellipsoidal shape. These cells were further subcategorised into granulated boat cells and boat-like cells without keratohyalin granules. All slides were reviewed by two authors (Natalie Gedon and Keith Linder). Hyperplasia Hyperkeratosis Perivascular fibrina Fibrosis severitya Statistical analyses were carried out using Prism 9.5.0 (GraphPad). All multiple association statistics were performed in R Core Team (A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria, 2022). Statistical details are provided in Appendix S1 in the Supporting information. The histopathological description of 33 tPF cases is provided below and comparison to the most relevant findings of 26 fPF and 44 iPF cases is summarised in Table 2. Additional descriptive data and statistical analysis of the three groups can be found in Tables S1–S10 and Appendix S2. Thirty-three cases of tPF had 232 unique histological sections with a median number of seven unique sections per case (range: 2–12); 226 were from haired skin and six from footpad/margin. A total of 147 intact and ruptured pustules were evaluated in the epidermis. Seventy-seven intact pustules (Figure 1a) in the epidermis had a median width of 0.37 mm (range: 0.05–4.25 mm) and a median cross-sectional area of 0.04 mm2 (range: 0.002–1.94 mm2). While controlling for area of the intact pustules, there were no significant differences between groups in any of the pustule descriptive parameters (p = 0.37). Ruptured pustules spanned significantly higher number of hair follicles (median: 2, range: 0–12) than intact pustules (median: 0, range: 0–4; p < 0.0001; Wilcoxon–Mann–Whitney U-test); however, the follicle density varied greatly in biopsy samples. The epidermal level of pustules was identifiable in 130 pustules and was most often located from the stratum corneum (SC) to the stratum spinosum (SS; 94; Figure 1a); a few pustules extended from the SC to the stratum granulosum (SG) (four), the SG to the SS (five) or were within the SS (12). In some pustules, there was extension from the SC to the stratum basale (SB; 11), from the SG to the SB (three) or from the SS to the SB (one). Ruptured pustules contained a significantly higher number of acantholytic cells (median score 3) than intact pustules (median 1; p < 0.0001; Wilcoxon–Mann–Whitney U-test). Acantholytic cells contained keratohyalin granules (Figure 2d) in 59% of pustules (82 of 138). Rafts were present (Figure 3a) in 25% of pustules (36 of 143) and their size varied from three to 74 keratinocytes (median 5). Perinuclear eosinophilic rings (Figure 3a) occurred in 57% of pustules (81 of 142). These occurred specifically in acantholytic cells (72 of 142; 51%), in nondetached peripustular keratinocytes in the epidermal margin of pustules (57 of 142; 40%) and/or in rafts. In nondetached keratinocytes with perinuclear rings, cells were not always rounded or separated (Figure 3a) and occurred with or without adjacent neutrophil exocytosis. Boat acantholytic cells (Figures 2 and 3) occurred in most pustules (122 of 145; 84%) and were granulated boat cells (85 of 145; 59%) and/or nongranulated boat-like cells (112 of 145; 77%). Flatter boat cells with granules did not have perinuclear rings, or collapse of keratohyalin granules to around the nucleus, and formed just below the SC (Figures 2a–c and 3b). Wider boat cells sometimes had collapse of perinuclear rings only on the faces of the cell and not from the tapered periphery, granules were not collapsed towards the nucleus from the tapered periphery, and these cells formed deeper in the SG (Figure 2a–c). Corneocytes occurred often in pustules (99 of 145; 68%; Figure 2a,e) and were significantly more common in ruptured pustules (p < 0.0001; Fisher's exact test). Corneocytes delaminated from the inner surface of the stratum compactum (Figure 2a), sometimes with segmental complete loss of the stratum compactum and additional delamination of cells from the stratum disjunctum. Roof cling-on acantholytic cells were present in 30 of 105 (29%) pustules. Pustules always contained neutrophils and, often, eosinophils (92 of 146 [63%]; median severity score 1, range: 0–3). In some instances, eosinophils outnumbered neutrophils (19 of 146; 13%). Macrophages were common in pustules (126 of 146; 86%) and were usually in very low numbers (<5 macrophages); occasional cases had pustules with higher numbers of macrophages (Figure 2d). Degenerate granulocytes occurred in intact pustules (37 of 77; 48%), although the score was usually low (median 0.5; range: 1–3). Neutrophil rosettes of at least two acantholytic cells were present in around half of the pustules (74 of 144; 51%; Figure 3b). Neutrophil rosettes also occurred on free or partly detached boat acantholytic cells and corneocytes (Figures 2e and 3b). Lymphocytic exocytosis into the epidermis was always present, usually mild (median severity score 1, range: 1–3), and more often peripustular (28 of 32; 88%) with lymphocytes below or next to pustules (Table S3). A few micropustules, usually one to three, were present in the epidermis (Figure 1d) in the majority of cases (27 of 33; 82%), were peripustular and/or nonperipustular and were more often in the SS (24 of 27; 89%) than the subcorneal location (11 of 27; 41%). Micropustules contained neutrophils and often eosinophils (14 of 27; 52%) and macrophages (15 of 27; 56%). Eosinophils outnumbered neutrophils in micropustules in nine of 27 (33%) cases. Macrophage microaggregates, one to three, also occurred in the epidermis, yet were uncommon (5 of 33; 15%). Extension of epidermal pustules into hair follicle infundibula occurred in 48 of 134 (36%) pustules. Pustules in hair follicle infundibula (Figures 1c and 2d) occurred in 15 of 33 (45%) cases, although the numbers were low (median: 0; range: 0–17). Micropustules were present in follicles in 14 of 32 (44%) cases. The number of micropustules per case was generally low, one to two only, and thus micropustules were not enumerated per case. Crusts were present in infundibula (evidence of resolved pustule) in 12 of 33 (36%) cases. Pustules with hair follicle extension, follicular pustules and micropustules had similar morphological features to those in the epidermis, including the presence of eosinophils, and occasional macrophages. The total number of cases with evidence of any of the four features of follicular involvement was 27 of 33 (82%), indicating that some form of follicular involvement was common in tPF. Epidermal hyperplasia occurred in all cases (Figure 1a,b), ranged from mild to marked and was regular or irregular. Neither pseudocarcinomatous, papillary nor psoriasiform-like hyperplasia patterns occurred. Hyperkeratosis away from pustules and attached crusts was uncommon (six of 33; 18%), always mild, orthokeratotic and basket-weave to laminated. One or several ulcers occurred in a third of the cases. Ulcers were generally small (less than the width of 50 keratinocytes) and usually were associated with the base or margin of a pustule (92% of ulcers). Most cases (31 of 33; 94%) exhibited moderate epidermal spongiosis (median: 2, range: 0–3), which was predominantly peripustular (Figure 1b). Peripustular spongiosis did not affect all pustules in cases where it occurred. Spongiosis occurred along the base of pustules, below acantholysis and not above it. Spongiotic pustules (no acantholytic cells) were uncommon (four of 33; 12%), small and few in number (one to two per case). Mild laminar hydropic change of the epidermis was present in a few cases. Necrotic acantholytic keratinocytes (Figure 3a,c) with retained shape and nuclear profiles occurred in 39 of 75 (52%) of intact pustules. They were hypereosinophilic and lacked differential staining (coagulative necrosis). Nuclei were sometimes pyknotic. Low numbers of necrotic acantholytic keratinocytes were usually observed (median: 1, range: 0–3). Necrosis was occasionally observed in nondetached peripustular keratinocytes (13 of 75; 17%) within intact pustules. A few cases had similar, rounded, individual necrotic keratinocytes in the epidermis next to pustules and were satellited by neutrophils. Moderate numbers (11–25) of apoptotic keratinocytes were seen in the epidermis of most cases (31 of 33; 94%; median: 2, range: 0–3). They were more often away from pustules (29 of 30; 97%) than near pustules (14 of 30; 47%). Basal layer apoptosis (29 of 31; 94%) occurred more commonly (Figure 3d) than suprabasal apoptosis (20 of 31;65%) and basal layer apoptosis was usually more numerous (26 of 31; 84%) than suprabasal (five of 31; 16%) apoptosis. The basal layer of hair follicle infundibula often had apoptosis, which was not associated with pustules. Lymphocytic satellitosis of apoptotic keratinocytes was seen in nine of 31 (29%) cases and usually only on rare cells in the epidermis. Additional inflammatory patterns occurred in all three PF clinical phenotypes. Lymphocytic bulbitis (tPF; Figure 4a), subepidermal vesicular dermatitis (iPF; Figure S1b) and suprabasal clefting (iPF; Figure S1a) were all seen in one case each. Lymphocytic interface dermatitis was mild-to-marked in four fPF cases (Figure S1c), and mild in one iPF and in one tPF case. Vasculitis in the panniculus was neutrophilic, eosinophilic and/or fibrinous and moderate in one tPF case (Figure 4b), and mild in one iPF case (Figure S1d). Multifocal, neutrophilic to pyogranulomatous sebaceous gland (or duct) adenitis was mild in five tPF cases (Figure 4c), mild-to-marked in two fPF cases (Figure S1e) and mild in four iPF cases. Furunculosis was mild to marked and found in six tPF cases (Figure 4d and Figure S1f) and in one case each of fPF and iPF. Nodular pyogranulomatous dermatitis was mild-to-marked and occurred in two cases of tPF and one case each of fPF and iPF, which were likely to have been secondary to furunculosis in some cases. The histomorphological features of canine tPF are characterised for the first time and are similar to fPF and iPF. Some morphological features were statistically different, yet their incidence was relatively high in all PF groups and histological features were not identified that could confidently differentiate PF phenotypes. The shared morphological features support common molecular mechanisms in canine PF phenotypes, despite—presumably—different disease triggers. Indeed, PF phenotypes are thought to share desmocollin-1(DSC1) as a major autoantigen.1, 3, 5 Beyond this commonality, in-depth investigations of the molecular mechanisms of canine PF are lacking and the reason for clinical variations is still unknown. Likewise, clinical variations in human PF and pemphigus vulgaris (PV) are well-recognised.6 Differences in circulating autoantibodies (anti-DSG1 versus anti-DSG3) have been associated with clinical lesion location and epidermal depth of acantholysis.6, 7 In dogs, anti-desmoglein-1(DSG1) antibodies were demonstrated in only 5%–7% of fPF and tPF patients, and antibodies to other DSGs and DSCs have not been investigated.1, 5, 8, 9 In proteomics-based and protein-array investigations of human PF and PV, a much larger number of autoantibody targets and autoreactive B cell clones have been identified; which also might relate to clinical phenotypes.10 Potentially, the clinical differences in tPF versus fPF are partly to the result of differences in target tissues, nasal planum and footpad being more similar anatomically and less targeted in tPF than haired skin.1 In fact, some canine PF patients present only with nasal planum or footpad lesions.11, 12 Based on keratinocyte morphology, different mechanisms of keratinocyte acantholysis are likely to occur in canine PF variants. Perinuclear eosinophilic rings occurred in acantholytic and peripustular keratinocytes, and these rings are thought to indicate active mechanisms of cell separation.13, 14 Ultrastructurally, desmosomes are reduced in number and size, and keratin intermediate filaments retract towards the nucleus to form the ring.14 Mechanistically, it is thought that autoantibodies induce cell separation by depletion of the membrane pool of cadherins, thus limiting desmosome formation, and by desmosome dismantling and internalisation, mediated partly by active cell signalling via calcium, protein kinase-C and phospholipase-C.15, 16 In this study, pustule margin keratinocytes formed rings before cell detachment, with or without adjacent neutrophils, suggesting neutrophil proximity is not needed to initiate this process. A role for secreted neutrophil enzymes/mediators from distant neutrophils in pustules is not excluded, however. Our study identified boat acantholytic cells and individualised corneocytes in pustules which indicate that nonactive mechanisms of cell separation also occur. Active acantholysis cannot separate corneocytes because of terminal differentiation and covalent cross-linking of corneodesmosomes and intermediate filaments by transglutaminases.17 Boat acantholytic cells formed in the SG and have intermediate features. These cells remain partially flattened, retain tapered edges, contain a nucleus and fail to fully round when separated, suggesting that the cytoskeleton is partly stabilised, possibly by transglutaminase activity and/or by interactions with tight junctions that occur at the cell periphery in SG2 and SG1 layer cells.17, 18 Tight junction interactions could explain collapse of inte}, journal={VETERINARY DERMATOLOGY}, author={Gedon, Natalie Katharina Yvonne and Bizikova, Petra and Olivry, Thierry and Mendoza-Kuznetsova, Ekaterina and Oberkirchner, Ursula and Robertson, James Benjamin and Linder, Keith Emerson}, year={2023}, month={Jun} }
 @misc{bizikova_olivry_linder_rybnicek_2023, title={Spontaneous autoimmune subepidermal blistering diseases in animals: a comprehensive review}, volume={19}, ISSN={["1746-6148"]}, url={https://doi.org/10.1186/s12917-023-03597-1}, DOI={10.1186/s12917-023-03597-1}, abstractNote={Abstract Autoimmune subepidermal blistering diseases (AISBDs) are rare skin disorders of animals that were first identified in dogs but several AISBDs are now recognised in other companion animal species. Most AISBDs in animals are homologues of the human diseases and are thought to share similar pathomechanisms of epidermal and/or mucosal blister formation caused by autoantibodies targeting structural proteins of the basement membrane zone (BMZ). Disruption of their structural function by the autoantibodies and/or recruited inflammation leads to BMZ fragility, which presents clinically as vesicles, bullae and, later, deep erosions and ulcers. Canine AISBDs are the best characterised, particularly the more common variants such as mucous membrane pemphigoid (48%), epidermolysis bullosa acquisita (EBA) (26%), and bullous pemphigoid (10%). Exceedingly rare AISBDs in the dog are junctional EBA, mixed AISBD, type-1 bullous systemic lupus erythematosus, linear IgA dermatosis, and pemphigus gestationis. The diagnosis of a specific AISBD is made by combining the clinical features (breed, age, lesion distribution) with histological evidence of subepithelial clefting, but not all AISBDs can be differentiated in this manner and specialised immunological testing is required. This latter, unfortunately, is not readily available and, therefore, the specific AISBD diagnosis often remains unconfirmed. While this limits further understanding of these diseases, it does not prevent clinicians from treating their patients, as the treatment approaches are similar for the different AISBDs in dogs. This review primarily focuses on canine AISBDs, the species for which these diseases have been best characterised, and shorter descriptions of variants in other species are also provided.}, number={1}, journal={BMC VETERINARY RESEARCH}, author={Bizikova, Petra and Olivry, Thierry and Linder, Keith and Rybnicek, Jan}, year={2023}, month={Feb} }
 @article{herrmann_mamo_holmes_mohammed_murphy_bizikova_2022, title={Long-term effects of ciclosporin and oclacitinib on mediators of tolerance, regulatory T-cells, IL-10 and TGF-beta, in dogs with atopic dermatitis}, ISSN={["1365-3164"]}, DOI={10.1111/vde.13140}, abstractNote={Atopic dogs often are managed with allergen-specific immunotherapy (AIT) and concurrent dosages of ciclosporin (CSA) or oclacitinib to alleviate their clinical signs. Both drugs might affect proper tolerance induction by inhibiting regulatory T-cell (Treg) induction.We evaluated Treg cell numbers and serum interleukin (IL)-10 and transforming growth factor-beta (TGF-β)1 levels in dogs diagnosed with atopic dermatitis (AD) and successfully treated with either CSA or oclacitinib for nine or more months.We included 15 dogs receiving oclacitinib, 14 dogs treated with CSA, 15 healthy dogs, 13 dogs with untreated moderate-to-severe AD and 15 atopic dogs controlled with AIT.Peripheral blood CD4+CD25+FOXP3+ T-cell percentages were determined using flow cytometry. Serum concentrations of IL-10 and TGF-β1 were measured by enzyme-linked immunosorbent assay.The percentage of Treg cells in the CSA group was significantly lower in comparison with the healthy group (p = 0.0003), the nontreated AD group (p = 0.0056) or the AIT group (p = 0.0186). There was no significant difference in Treg cell percentages between the CSA and oclacitinib groups, nor between the oclacitinib and the healthy, nontreated AD or AIT-treated dogs. No significant differences were detected in IL-10 and TGF-β1 serum concentrations between the five groups.Lower Treg cell percentages in the CSA-treated dogs suggest an impact of this drug on this cell population; however, it does not necessarily mean that it diminishes tolerance. Functionality and cytokine production may be more important than the number of Treg cells. Further studies evaluating the treatment outcome of dogs receiving AIT and concurrent drugs are needed to show clinical relevance.Les chiens atopiques sont souvent traités avec une immunothérapie spécifique d'allergène (AIT) et des doses concomitantes de ciclosporine ou d'oclacitinib pour atténuer leurs signes cliniques. Les deux médicaments pourraient affecter l'induction de la tolérance appropriée en inhibant l'induction des lymphocytes T régulateurs (Treg). HYPOTHÈSE/OBJECTIFS: Nous avons évalué le nombre de cellules Treg et les taux sériques d'interleukine (IL)-10 et de TGF-β-1 chez des chiens diagnostiqués avec une dermatite atopique (DA) et traités avec succès par la ciclosporine ou l'oclacitinib pendant neuf mois ou plus.Nous avons inclus 15 chiens recevant de l'oclacitinib, 14 chiens traités par ciclosporine, 15 chiens sains, 13 chiens atteints de DA modérée à sévère non traitée et 15 chiens atopiques contrôlés par AIT. MATÉRIELS ET MÉTHODES: Les pourcentages de lymphocytes T CD4+CD25+FOXP3+ du sang périphérique ont été déterminés par cytométrie de flux. Les concentrations sériques d'IL-10 et de TGF-β1 ont été mesurées par dosage immuno-enzymatique. RÉSULTATS: Le pourcentage de cellules Treg dans le groupe ciclosporine était significativement plus faible par rapport au groupe sain (p = 0,0003), au groupe AD non traité (p = 0,0056) ou au groupe AIT (p = 0,0186). Il n'y avait pas de différence significative dans les pourcentages de cellules Treg entre le groupe ciclosporine et oclacitinib, ni entre l'oclacitinib et les chiens sains non traités AD ou traités AIT. Aucune différence significative n'a été détectée dans les concentrations sériques d'IL-10 et de TGF-β1 entre les cinq groupes.Des pourcentages de cellules Treg plus faibles chez les chiens traités à la ciclosporine suggèrent un impact de ce médicament sur cette population cellulaire ; cependant, cela ne signifie pas nécessairement qu'il diminue la tolérance. La fonctionnalité et la production de cytokines peuvent être plus importantes que le nombre de cellules Treg. D'autres études évaluant les résultats du traitement des chiens recevant l'AIT et des médicaments concomitants sont nécessaires pour montrer la pertinence clinique.INTRODUCCIÓN: los perros atópicos a menudo se tratan con inmunoterapia específica para alérgenos (AIT) y dosis simultáneas de ciclosporina u oclacitinib para aliviar sus signos clínicos. Ambos fármacos podrían afectar la inducción de tolerancia adecuada al inhibir la inducción de células T reguladoras (Treg). HIPÓTESIS/OBJETIVOS: Evaluamos el número de células Treg y los niveles séricos de interleuquina (IL)-10 y factor de crecimiento transformante-beta (TGF-β)1 en perros diagnosticados con dermatitis atópica (AD) y tratados con éxito con ciclosporina u oclacitinib durante nueve o mas meses ANIMALES: Incluimos 15 perros que recibieron oclacitinib, 14 perros tratados con ciclosporina, 15 perros sanos, 13 perros con AD de moderada a grave no tratada y 15 perros atópicos controlados con AIT. MATERIALES Y MÉTODOS: Los porcentajes de células T CD4+CD25+FOXP3+ en sangre periférica se determinaron mediante citometría de flujo. Las concentraciones séricas de IL-10 y TGF-β1 se midieron mediante ensayo inmunoabsorbente ligado a enzimas. RESULTADOS: El porcentaje de células Treg en el grupo de ciclosporina fue significativamente menor en comparación con el grupo sano (p = 0,0003), el grupo AD no tratado (p = 0,0056) o el grupo AIT (p = 0,0186). No hubo diferencias significativas en los porcentajes de células Treg entre el grupo de ciclosporina y oclacitinib, ni entre el oclacitinib y los perros sanos, no tratados con AD o tratados con AIT. No se detectaron diferencias significativas en las concentraciones séricas de IL-10 y TGF-β1 entre los cinco grupos. CONCLUSIONES Y RELEVANCIA CLÍNICA: Los porcentajes más bajos de células Treg en los perros tratados con ciclosporina sugieren un impacto de este fármaco en esta población celular; sin embargo, no significa necesariamente que disminuya la tolerancia. La funcionalidad y la producción de citoquinas pueden ser más importantes que el número de células Treg. Se necesitan más estudios que evalúen el resultado del tratamiento de perros que reciben AIT y medicamentos concurrentes para mostrar relevancia clínica.Atopische Hunde werden oft mit Allergen-spezifischer Immuntherapie (AIT) gemanagt, wobei gleichzeitig Ciclosporin oder Oclacitinib verabreicht werden, um ihre klinischen Zeichen zu lindern. Beide Medikamente können die Toleranzinduktion durch eine Inhibition der regulatorischen T Zellen (Treg) Induktion beeinflussen.Wir evaluierten die Treg Zellzahlen und Serum Interleukin (IL)-10 und Transforming Growth Factor-beta (TGF-β) Werte bei Hunden, die mit einer atopischen Dermatitis (AD) diagnostiziert worden waren und entweder mit Ciclosporin oder mit Oclacitinib für neun Monate oder länger erfolgreich behandelt worden waren.Wir inkludierten 15 Hunde, die Oclacitinib erhielten, 14 Hunde, die mit Ciclosporin behandelt worden waren, 15 gesunde Hunde, 13 Hunde mit unbehandelter moderater-bis-hochgradiger AD und 15 atopische Hunde, die mit AIT kontrolliert waren.Periphere Blut CD4+CD25+FOXP3+ T-Zell Prozentanteile wurden mittels Flowzytometrie bestimmt. Serumkonzentrationen von IL-10 und TGF-β wurden mittels Enzym-linked Immunosorbent Assay gemessen.Der Prozentanteil der Treg Zellen in der Ciclosporingruppe war signifikant niedriger im Vergleich zur gesunden Gruppe (p = 0,0003), zur nichtbehandelten AD-Gruppe (p = 0,0056), oder der AIT-Gruppe (p = 0,0186). Es bestand kein signifikanter Unterschied zwischen den prozentualen Anteilen der Treg Zellen zwischen Ciclosporin und der Oclacitinib Gruppe, und auch nicht zwischen der Oclacitinib und der gesunden, nichtbehandelten AD-Gruppe, oder den AIT-behandelten Hunden. Es wurden keine signifikanten Unterschiede zwischen IL-10 und TGF-β1 Serumkonzentrationen zwischen den fünf Gruppen gefunden.Niedrigere Prozentanteile der Treg Zellen bei den Ciclosporin-behandelten Hunden weisen darauf hin, dass dieses Medikament auf diese Zellpopulation einen Einfluss hat; es bedeutet jedoch nicht unbedingt, dass es die Toleranz vermindert. Die Funktionalität und die Ciclosporin Produktion könnte wichtiger sein als die Anzahl der Treg Zellen. Weitere Studien sind nötig, die den Behandlungserfolg bei Hunden, die AIT und gleichzeitig Medikamente erhalten, evaluieren, um die klinische Relevanz zu zeigen.背景: アトピー犬は、しばしばアレルゲン特異的免疫療法(AIT)を行い、同時にシクロスポリンやオクラシチニブを投与して臨床症状を軽減している。両薬剤は、制御性T細胞(Treg)の誘導を阻害することにより、適切な寛容誘導に影響を与える可能性がある。 仮説/目的: 本研究の目的は、 アトピー性皮膚炎(AD)と診断され、シクロスポリンまたはオクラシチニブによる9ヶ月以上の治療に成功した犬において、Treg細胞数、血清インターロイキン(IL)-10およびトランスフォーミング増殖因子-β(TGF-β)1レベルを評価することであった。 供試動物: オクラシチニブ投与犬15頭、シクロスポリン投与犬14頭、健常犬15頭、未治療の中等度から重度のAD犬13頭、AITでコントロールしたアトピー犬15頭を対象とした。 材料と方法: 末梢血CD4+CD25+FOXP3+ T細胞の割合をフローサイトメトリーで測定した。血清中のIL-10およびTGF-β1濃度は、酵素結合免疫吸着法で測定した。 結果: シクロスポリン投与群では、健常群(p=0.0003)、AD未治療群(p=0.0056)、AIT群(p=0.0186)と比較して、Treg細胞の割合が有意に低下した。シクロスポリン群とオクラシチニブ群、オクラシチニブ群と健常群、AD未治療群、AIT治療群との間でもTreg細胞の割合に有意差はなかった。IL-10およびTGF-β1血清濃度には5群間で有意差は検出されなかった。 結論と臨床的関連性: シクロスポリン投与犬におけるTreg細胞の割合の低下は、シクロスポリンがこの細胞集団に影響を与えることを示唆していた。しかし、それは必ずしも耐性を低下させることを意味するものではない。機能性やサイトカイン産生は、Treg細胞数よりも重要である可能性がある。臨床的な関連性を示すためには、AITと併用薬を投与された犬の治療成績を評価する更なる研究が必要である。.背景: 特应性犬通常通过过敏原特异性免疫治疗 (AIT) 和同时给予环孢素或奥拉替尼缓解其临床症状。两种药物均可能通过抑制调节性 T 细胞 (Treg) 诱导影响适当的耐受诱导。 假设/目的: 我们在诊断为特应性皮炎 (AD) 并成功接受环孢素或奥拉替尼治疗9个月或以上的犬中评价了 Treg 细胞数量以及血清白细胞介素 (IL)-10 和转化生长因子-β (TGF-β)1水平。 动物: 我们纳入了15只接受奥拉替尼的犬、14只接受环孢素治疗的犬、15只健康犬、13只未治疗的中度至重度 AD 犬和15只接受 AIT 控制的特应性犬。 材料和方法: 使用流式细胞术测定外周血CD4 + CD25 + FOXP3 + T细胞百分比。采用酶联免疫吸附法检测血清 IL-10 和TGF-β1的浓度。 结果: 环孢素组的 Treg 细胞百分比显著低于健康组 (p = 0.0003)、未治疗 AD 组 (p = 0.0056) 或 AIT 组 (p = 0.0186)。环孢素和奥拉替尼组、奥拉替尼和健康、未治疗 AD 或 AIT 治疗犬之间的 Treg 细胞百分比无显著差异。5组间 IL-10 和TGF-β1血清浓度未检测到明显差异。 结论和临床相关性: 环孢素给药犬中较低的 Treg 细胞百分比表明该药物对该细胞群有影响；然而，这并不一定意味着其会降低耐受性。功能和细胞因子的产生可能比 Treg 细胞的数量更重要。需要进一步研究评价接受 AIT 和伴随药物的犬的治疗结果，以显示临床相关性。.Cães atópicos geralmente são tratados com imunoterapia alérgeno-específica (AIT) e dosagens concomitantes de ciclosporina ou oclacitinib para aliviar seus sinais clínicos. Ambas as drogas podem afetar a indução de tolerância adequada ao inibir a indução de células T reguladoras (Treg). HIPÓTESE/OBJETIVOS: Avaliamos o número de células Treg e os níveis séricos de interleucina (IL)-10 e fator transformador de crescimento beta (TGF-β)1 em cães diagnosticados com dermatite atópica (DA) e tratados com sucesso com ciclosporina ou oclacitinib por nove ou mais meses.Foram incluídos 15 cães recebendo oclacitinib, 14 cães tratados com ciclosporina, 15 cães saudáveis, 13 cães com DA moderada a grave não tratada e 15 cães atópicos controlados com AIT. MATERIAIS E MÉTODOS: As porcentagens de células T CD4+CD25+FOXP3+ do sangue periférico foram determinadas por citometria de fluxo. As concentrações séricas de IL-10 e TGF-β1 foram medidas por ensaio imunoenzimático.A porcentagem de células Treg no grupo ciclosporina foi significativamente menor em comparação ao grupo saudável (p = 0,0003), ao grupo DA não tratado (p = 0,0056) ou ao grupo AIT (p = 0,0186). Não houve diferença significativa nas porcentagens de células Treg entre o grupo ciclosporina e oclacitinib, nem o oclacitinib e os cães saudáveis, ou oclacitinib e os cães com DA não tratados ou tratados com AIT. Não foram detectadas diferenças significativas nas concentrações séricas de IL-10 e TGF-β1 entre os cinco grupos. CONCLUSÕES E RELEVÂNCIA CLÍNICA: Percentagens mais baixas de células Treg nos cães tratados com ciclosporina sugerem um impacto deste fármaco nesta população de células; no entanto, isso não significa necessariamente que diminui a tolerância. A funcionalidade e a produção de citocinas podem ser mais importantes do que o número de células Treg. Mais estudos avaliando o resultado do tratamento de cães recebendo AIT e drogas concomitantes são necessários para mostrar a relevância clínica.}, journal={VETERINARY DERMATOLOGY}, author={Herrmann, Ina and Mamo, Lisa B. and Holmes, Jenny and Mohammed, Javid P. and Murphy, K. Marcia and Bizikova, Petra}, year={2022}, month={Dec} }
 @article{bizikova_linder_mamo_2022, title={Trunk-dominant and classic facial pemphigus foliaceus in dogs - comparison of anti-desmocollin-1 and anti-desmoglein-1 autoantibodies and clinical presentations}, ISSN={["1365-3164"]}, DOI={10.1111/vde.13094}, abstractNote={Canine trunk-dominant pemphigus foliaceus (PF) is mentioned rarely in the literature. The goal of this study was to provide clinical description of trunk-dominant PF and to demonstrate the prevalence of serum antikeratinocyte, anti-desmocollin-1 (DSC1) and anti-desmoglein-1 (DSG1) antibodies, and determine their diagnostic value in this particular PF phenotype. Clinically relevant information was collected from 31, 25 and 34 dogs with trunk-dominant and facial PF and superficial pyoderma (SP), respectively. Sera from these dogs were tested for antikeratinocyte, anti-DSC1 and anti-DSG1 antibodies using indirect immunofluorescence on canine tissues and DSC1- and DSG1-transfected cells. Sera from healthy dogs and dogs with clinically irrelevant diseases served as controls. Footpad involvement and grouped/polycyclic lesion organisation were identified as features of both PF phenotypes, and not of SP. Antikeratinocyte immunoglobulin (Ig)G was not specific for canine PF. By contrast, antigen-specific IgG was detected only in PF sera; anti-DSC1 IgG in 100% and 58% of dogs with facial and trunk-dominant PF, respectively, and anti-DSG1 IgG in 7% of dogs with trunk-dominant PF only. Trunk-dominant PF shares DSC1 as a major autoantigen with facial PF. The ability to detect anti-DSC1 IgG is lower in trunk-dominant PF, yet despite the lower sensitivity, the positive predictive value and accuracy of this particular anti-DSC1 IgG test are high. A negative test result, however, cannot exclude the diagnosis, and characteristic clinical features such as footpad involvement and/or grouped/polycyclic lesions must be considered when distinguishing trunk-dominant PF from its most relevant differential diagnosis: SP. Contexte – Le pemphigus foliacé (PF) dominant le tronc chez le chien est rarement mentionné dans la littérature. Hypothèse/Objectifs – Le but de cette étude était de fournir une description clinique du PF dominant le tronc et de démontrer la prévalence des anticorps sériques anti-kératinocytes, anti-desmocolline-1 (DSC1) et anti-desmogléine-1 (DSG1), et de déterminer leur valeur diagnostique dans ce phénotype particulier de PF. Matériels et méthodes - Des informations cliniquement pertinentes ont été recueillies auprès de 31, 25 et 34 chiens atteints respectivement de PF à dominante tronculaire et faciale et de pyodermite superficielle (SP). Les sera de ces chiens ont été testés pour les anticorps anti-kératinocytes, anti-DSC1 et anti-DSG1 en utilisant l'immunofluorescence indirecte sur des tissus canins et des cellules transfectées avec DSC1 et DSG1. Des sera de chiens sains et de chiens atteints de maladies cliniquement non pertinentes ont servi de témoins. Résultats - L'implication du coussinet plantaire et l'organisation des lésions groupées / polycycliques ont été identifiées comme des caractéristiques des deux phénotypes PF, et non de SP. L'immunoglobuline antikératinocytaire (Ig)G n'était pas spécifique du PF canin. En revanche, l'IgG spécifique de l'antigène n'a été détectée que dans les sera de PF ; IgG anti-DSC1 chez 100 % et 58 % des chiens atteints de PF faciale et tronc-dominante, respectivement, et anti-DSG1 IgG chez 7 % des chiens avec PF tronc-dominant uniquement. Conclusions - Le PF à dominante tronculaire partage DSC1 comme auto-antigène majeur avec le PF facial. La capacité à détecter les IgG anti-DSC1 est plus faible chez les PF à dominante tronculaire, mais malgré la sensibilité plus faible, la valeur prédictive positive et la précision de ce test IgG anti-DSC1 particulier sont élevées. Cependant, un résultat de test négatif ne peut pas exclure le diagnostic, et les caractéristiques cliniques caractéristiques telles que l'atteinte du coussinet plantaire et/ou les lésions groupées/polycycliques doivent être prises en compte lors de la distinction entre la PF à dominante tronculaire et son diagnostic différentiel le plus pertinent : la SP. Introducción- el pénfigo foliáceo (PF) de distribución truncal predominante se describe raramente n la literatura. Hipótesis/Objetivos- el objetivo de este estudio fue proporcionar una descripción clínica del PF truncal y demostrar la prevalencia de anticuerpos séricos antiqueratinocitos, antidesmocolina-1 (DSC1) y antidesmogleína-1 (DSG1), y determinar su valor diagnóstico en este fenotipo PF particular. Materiales y métodos- se recopiló información clínicamente relevante de 31, 25 y 34 perros con PF dominante truncal, PF dominante facial y pioderma superficial (PS), respectivamente. Los sueros de estos perros se analizaron en busca de anticuerpos antiqueratinocitos, anti-DSC1 y anti-DSG1 mediante inmunofluorescencia indirecta en tejidos caninos y células transfectadas con DSC1 y DSG1. Sueros de perros sanos y perros con enfermedades clínicamente irrelevantes sirvieron como controles. Resultados- la afectación de la almohadilla plantar y la organización de lesiones agrupadas/policíclicas se identificaron como características de ambos fenotipos de PF y no de SP. La inmunoglobulina (Ig)G antiqueratinocitos no fue específica para la PF canina. Por el contrario, la IgG específica de antígeno se detectó solo en sueros PF; IgG anti-DSC1 en el 100 % y el 58 % de los perros con PF predominante en la cara y el tronco, respectivamente, y IgG anti-DSG1 en el 7 % de los perros con PF predominante en el tronco solamente. Conclusiones- el PF dominante truncal comparte DSC1 como un autoantígeno importante con el PF facial. La capacidad para detectar IgG anti-DSC1 es menor en la PF dominante truncal; sin embargo, a pesar de la menor sensibilidad, el valor predictivo positivo y la precisión de esta prueba de IgG anti-DSC1 en particular son altos. Sin embargo, un resultado negativo de la prueba no puede excluir el diagnóstico, y deben tenerse en cuenta las características clínicas, como la afectación de las almohadillas plantares y/o las lesiones agrupadas/policíclicas, al distinguir la PF dominante truncal de su diagnóstico diferencial más relevante: SP. Hintergrund – Pemphigus foliaceus (PF), der dominant am Rumpf des Hundes vorkommt wird in der Literatur selten erwähnt. Hypothese/Ziele – Das Ziel dieser Studie war es, eine klinische Beschreibung des Pemphigus foliaceus (PF), der dominant am Rumpf des Hundes vorkommt, zu liefern und die Prävalenz von Serum Antikeratinozyten, Anti-Desmocollin-1 (DSC1) und Anti-Desmoglein-1 (DSG1) Antikörper zu demonstrieren und ihren diagnostischen Wert bei diesem, speziellen PF Phänotyp festzustellen. Materialien und Methoden – Es wurden klinisch relevante Informationen von 31, 25 und 34 Hunden mit Pemphigus foliaceus (PF), der dominant am Rumpf vorkommt, sowie von Gesichts PF und oberflächlicher Pyodermie (SP) gesammelt. Sera dieser Hunde wurden mittels indirekter Immunfluoreszenz in caninem Gewebe und in DSC-1 und DSG1-transfizierten Zellen auf Antikeratinozyten, Anti-DSC1 und Anti-DSG1 Antikörper getestet. Sera von gesunden Hunden und Hunden mit klinisch irrelevanten Krankheiten dienten als Kontrollen. Ergebnisse – Eine Beteiligung der Fußballen und eine gruppierte/polyzyklische Organisation der Veränderungen wurden als Merkmale beider PF Phänotypen identifiziert, jedoch nicht für SP. Antikeratinozyten Immunglobulin (Ig) G war nicht spezifisch für caninen PF. Im Gegenteil Antigen-spezifisches IgG wurde nur in PF Sera; anti-DSC1 IgG in 100% bzw. 58% der Hunde mit Gesichts- bzw. Rumpf-dominantem PF und anti-DSG1 IgG in 7% der Hunde mit ausschließlich Rumpf-dominantem PF gefunden. Schlussfolgerungen – Der PF, welcher dominant am Rumpf des Hundes vorkommt, teilt sich DSC1 als Major Autoantigen mit dem Gesichts PF. Die Fähigkeit anti-DSC1 IgG zu finden ist beim Rumpf-dominanten PF niedriger, dennoch ist trotz der niedrigeren Sensibilität, der positive prädiktive Wert und die Genauigkeit dieses speziellen anti-DSC1 IgG Tests hoch. Ein negatives Testergebnis kann jedoch die Diagnose nicht ausschließen und die charakteristischen klinischen Merkmale wie Beteiligung der Fußballen und/oder gruppierte/polyzyklische Veränderungen müssen beachtet werden, wenn eine Rumpf-dominate PF Form von seiner wesentlichsten Differentialdiagnose, der SP, unterschieden werden soll. 背景 - 犬の体幹優位型落葉状天疱瘡(PF)は、文献上ほとんど言及されていない。 仮説/目的 - 本研究の目的は、体幹優位型落葉状天疱瘡の臨床情報を提供し、血清中の抗ケラチノサイト抗体、抗デスモコリン-1(DSC1)抗体および抗デスモグレイン-1(DSG1)抗体の陽性率を明らかにし、この特殊なPF表現型における診断的価値を決定することであった。 材料と方法 - 体幹優位型、顔面優位型のPFおよび表在性膿皮症(SP)の犬31頭、25頭および34頭からそれぞれ臨床的に関連する情報を収集した。これらの犬の血清を、犬組織とDSC1-およびDSG1-トランスフェクト細胞に対する間接免疫蛍光法を用いて、抗ケラチノサイト抗体、抗DSC1抗体および抗DSG1抗体について検査した。健常犬および臨床的に無関係な病気の犬の血清を対照とした。 結果 - 足蹠の浸潤と群発性/多発性病変の編成が両PF表現型の特徴として確認され、SPの特徴とはならなかった。抗ケラチノサイト免疫グロブリン(Ig)Gは、犬のPFに特異的ではなかった。一方、抗原特異的IgGはPFの血清にのみ検出された。顔面および体幹優位のPF犬では、それぞれ100%および58%に抗DSC1 IgGが、体幹優位のPFの犬のみでは7%に抗DSG1 IgGが検出された。 結論 - 体幹優位型PFは、顔面優位型PFと同様にDSC1が主要な自己抗原である。体幹優位型PFでは抗DSC1 IgGの検出能力は低いが、感度が低いにもかかわらず、この特殊な抗DSC1 IgG検査の陽性適中率と精度は高い。しかし、検査結果が陰性でも診断を除外することはできず、体幹優位型PFをその最も関連性の高い鑑別診断であるSPから鑑別する際には、足蹠病変および/または群発/多発性病変などの特徴的な臨床症状を考慮しなければならない。 背景-文献中很少提及犬躯干显性落叶型天疱疮(PF)。 假设/目的-本研究的目的是提供躯干显性PF的临床描述，并证明血清抗角质细胞、抗桥粒芯糖蛋白-1(DSC1)和抗桥粒芯糖蛋白-1(DSG1)抗体的流行率，并确定其在该特定PF表型中的诊断价值。 材料和方法-分别从31、25和34只躯干显性和面部PF以及浅表性脓皮病(SP)犬中收集临床相关信息。使用犬组织以及DSC1和DSG1转染细胞的间接免疫荧光法，检测这些犬血清中的抗角质形成细胞、抗DSC1和抗DSG1抗体。健康犬和临床无关疾病犬的血清作为对照。 结果-爪垫受累和分组/多环病变组织被确定为PF表型的特征，而不是SP的特征。抗角质细胞免疫球蛋白(Ig)G对犬PF无特异性。相比之下，仅在PF血清中检测到抗原特异性IgG；面部和躯干显性PF犬中抗DSC1 IgG分别占100%和58%，仅躯干显性PF犬中抗DSG1 IgG占7%。 结论-躯干显性PF与面部PF共享DSC1作为主要的自身抗原。在躯干显性PF中检测抗DSC1 IgG的能力较低，然而尽管敏感性较低，但这种特殊的抗DSC1 IgG检测的阳性预测值和准确性较高。然而，阴性检测结果不能排除诊断，在区分躯干显性PF与其最相关的鉴别诊断:SP时，必须考虑爪垫受累和(或)成群/多环病变等特征性临床特征。 Contexto – O pênfigo foliáceo (PF) canino predominante no tronco é raramente relatado na literatura. Hipótese/Objetivos – O objetivo deste estudo foi apresentar a descrição clínica do PF predominante no tronco e demonstrar a prevalência de anticorpos anti-queratinócitos, anti-desmocolina-1 (DSC1) e anti-desmogleína-1 (DSG1), e determinar o seu potencial diagnóstico neste tipo particular de PF. Materiais e métodos – Informações clinicamente relevantes foram coletadas de 31, 25 e 34 cães com PF predominante no tronco, PF facial e piodermite superficial (PS), respectivamente. Os soros destes cães foram testados para anticorpos anti-queratinócitos, anti-DSC1 e anti-DSG1 utilizando imunofluorescência indireta em tecidos caninos e em células DSC1 e DSG1 transfectadas. Os soros de cães saudáveis e cães com doenças clinicamente irrelevantes serviram de controle. Resultados – O acometimento dos coxins e a organização agrupada/policíclica das lesões foram identificadas como características de ambos os fenótipos de PF, não de PS. A imunoglobulina (Ig)G anti-queratinócitos não foi específica para PF. Em contraste, IgG antígeno-específica foi detectada apenas no soro de PF; IgG anti-DSC1 em 100% e 58% dos cães com PF facial e predominante no tronco, respectivamente, e IgG anti-DSG1 em 7% dos cães somente acometidos pelo PF predominante no tronco. Conclusões – O PF predominante no tronco compartilha DSC1 como um autoantígeno principal com PF facial. A capacidade de detectar IgG anti-DSC1 é menor no PF predominante no tronco, mas apesar da sensibilidade mais baixa, o valor preditivo positivo e a precisão do teste IgG anti-DSC1 específico são altos. Um resultado de teste negativo, no entanto, não pode excluir o diagnóstico, e características clínicas típicas, como envolvimento do coxim plantar e/ou lesões agrupadas/policíclicas, devem ser consideradas ao distinguir PF predominante no tronco de seu diagnóstico diferencial mais relevante: PS. APPENDIX S1 Indirect immunofluorescence methods TABLE S1 Secondary antibodies used in the indirect immunofluorescence experiments FIGURE S1 Indirect immunofluorescence examples (a) Green, intercellular, web-like pattern confirming the presence of antikeratinocyte IgG using healthy canine footpad tissue and serum from a dog with pemphigus foliaceus; (b) green, stippled fluorescence confirming the presence of anti-DSC1 IgG using DSC1-transfected 293 T cells and serum from a dog with pemphigus foliaceus; (c) negative control using nontransfected 293 T cells and serum from a dog with pemphigus foliaceus. Blue staining depicts the nuclei (Vectashield-DAPI, Vector Laboratories; Burlingame, CA, USA) Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.}, journal={VETERINARY DERMATOLOGY}, author={Bizikova, Petra and Linder, Keith E. and Mamo, Lisa B.}, year={2022}, month={Jun} }
 @article{fussell_bizikova_breuhaus_harris_moore_chen_linder_2021, title={Bullous amyloidosis in a horse: first description in veterinary medicine}, volume={6}, ISSN={["1365-3164"]}, DOI={10.1111/vde.12982}, abstractNote={Bullous amyloidosis is a rare disease in humans that has not been described in a veterinary species in the peer-reviewed literature. The human disease is characterised by haemorrhagic vesicles and bullae on the skin and mucosae, which form due to amyloid deposition.To describe the clinical features, laboratory analysis and histopathological features of an unique presentation of bullous disease in a horse.A 17-year-old thoroughbred mare presented for weight loss and severe oral cavity ulcers.Investigations involved haematological evaluation, chemistry profiles, gastroscopy and serum protein electrophoresis, and, postmortem, histopathological evaluation, Congo-red staining and transmission electron microscopy (TEM).Haemorrhagic vesicles and bullae occurred on the mucosa of the oral cavity, lips, oesophagus and stomach, and much less the muzzle, face and mucocutaneous areas of the perineum, where scarring was evident. Histopathological evaluation and Congo-red staining confirmed the presence of amyloid deposits in dermis and submucosa, in association with vesicle and bulla formation, consistent with bullous amyloidosis. TEM confirmed amyloid fibril deposition in the dermis and along the basement membrane zone. Clefts occurred in the superficial dermis and submucosa, which explained haemorrhage and scarring. The presence of a polyclonal gammopathy and the rapid abolishment of Congo-red staining with performate pretreatment supported serum amyloid A and secondary amyloidosis.Bullous amyloidosis is a novel disease of the horse and a newly recognised differential for bullous disease, for which the haemorrhagic nature of bullae, scarring and deep secondary ulcers are considered clinical clues to the condition.L’amyloïdose bulleuse est une maladie rare chez l’homme qui n’a pas encore été décrite dans une espèce vétérinaire dans la littérature avec comité de lecture. La maladie de l’homme est caractérisée par des vésicules et bulles hémorragiques de la peau et des muqueuses qui se forment après dépôt d’amyloïde. HYPOTHÈSES/OBJECTIFS: Décrire les données cliniques, les analyses de laboratoires et les critères histopathologiques d’une présentation unique de maladie bulleuse chez un cheval.Une jument de race de 17 ans présentée pour perte de poids et ulcères sévères de la cavité buccale. MÉTHODES: Les investigations comprenaient une évaluation hématologique, des profils biochimiques, une gastroscopie et une électrophorèse des protéines sériques et, post mortem, un examen histopathologique, une coloration au rouge Congo et une microscopie à transmission électronique (TEM). RÉSULTATS: Les vésicules et bulles hémorragiques se sont développées sur les muqueuses de la cavité orale, les lèvres, l’œsophage et l’estomac et moins au niveau des narines, de la face et des jonctions cutanéo-muqueuses du périnée où des cicatrices étaient évidentes. Une évaluation histopathologique et une coloration au rouge Congo ont confirmé la présence d’amyloïde dans le derme et les muqueuses, en association avec la formation des vésicules et des bulles, compatible avec l’amyloïdose bulleuse. La TEM a confirmé le dépôt de fibrilles d’amyloïdes dans le derme et au niveau de la membrane basale. Un clivage était présent dans le derme superficiel et les sous muqueuses, expliquant l’hémorragie et les cicatrices. La présence d’une gammapathie polyconale et du rapide disparition de la coloration au rouge Congo avec réalisation d’un prétraitement, soutenaient une amyloïde A sérique et une amyloïdose secondaire.L’amyloïdose bulleuse est une nouvelle maladie du cheval et un nouveau différentiel dans les dermatoses bulleuses pour laquelle la nature hémorragique des bulles, des cicatrices et des ulcères secondaires profonds est considérée comme une donnée clinique évocatrice de l’atteinte.INTRODUCCIÓN: la amiloidosis bullosa es una enfermedad rara en humanos que no se ha descrito en ninguna especie veterinaria en la literatura revisada. La enfermedad humana se caracteriza por vesículas y ampollas hemorrágicas en la piel y las mucosas, que se forman debido al depósito de amiloide. HIPÓTESIS/OBJETIVOS: describir las características clínicas, análisis de laboratorio y características histopatológicas de una presentación única de enfermedad bullosa en un caballo. ANIMALES: una yegua pura sangre de 17 años que se presentó por pérdida de peso y úlceras severas en la cavidad oral. MÉTODOS: Las investigaciones incluyeron evaluación hematológica, perfiles químicos, gastroscopia y electroforesis de proteínas séricas y, post mortem, evaluación histopatológica, tinción con rojo Congo y microscopía electrónica de transmisión (TEM). RESULTADOS: Se observaron vesículas y ampollas hemorrágicas en la mucosa de la cavidad oral, labios, esófago y estómago, y mucho menos en el hocico, la cara y las áreas mucocutáneas del perineo, donde las cicatrices eran evidentes. La evaluación histopatológica y la tinción con rojo Congo confirmaron la presencia de depósitos de amiloide en dermis y submucosa, en asociación con formación de vesículas y ampollas, compatibles con amiloidosis bullosa. TEM confirmó el depósito de fibrillas de amiloide en la dermis y a lo largo de la zona de la membrana basal. Se produjeron hendiduras en la dermis superficial y la submucosa, lo que explica la hemorragia y la cicatrización. La presencia de una gammapatía policlonal y la rápida desaparición de la tinción con rojo Congo con el pretratamiento con permanganato potásico confirmaron amiloide A sérico y la amiloidosis secundaria. CONCLUSIÓN E IMPORTANCIA CLÍNICA: la amiloidosis bullosa es una enfermedad nueva del caballo y un diferencial recientemente reconocido de enfermedades bullosas. La naturaleza hemorrágica de las ampollas, la presencia de cicatrices y de úlceras secundarias profundas se consideran indicios clínicos de esta enfermedad.Die bullöse Amyloidose ist eine seltene Erkrankung beim Menschen, die noch bei keiner tierischen Spezies in Peer-Review Literatur beschrieben wurde. Die Erkrankung ist beim Menschen durch hämorrhagische Bläschen und Blasen auf der Haut und den Schleimhäuten gekennzeichnet, die sich aufgrund von Amyloid Ablagerung bilden.Die Beschreibung der klinischen Merkmale, der Laboranalyse und der histopathologischen Merkmale einer einzigartigen Präsentation einer bullösen Erkrankung bei einem Pferd.Eine 17 Jahre alte Vollblutaraberstute wurde wegen Gewichtsverlust und hochgradigen Ulzera in der Mundhöhle vorgestellt.Die Untersuchungen beinhalteten Hämatologie, Biochemie, Gastroskopie und eine Serumelektrophorese, sowie post mortem eine histopathologische Evaluierung, Kongorotfärbung und Transmissionselektronenmikroskopie (TEM).Hämorrhagische Bläschen und Blasen traten an der Mundschleimhaut, an den Lippen, der Speiseröhre und im Magen auf, sowie etwas weniger ausgeprägt an der Nase, dem Gesicht und den mucokutanen Übergängen des Perneums, wo Narbenbildung evident war. Die histopathologische Evaluierung und die Kongorotfärbung bestätigten das Vorkommen von Amyloidablagerungen in der Dermis und Submukosa, im Zusammenhang mit Bläschen- und Blasenbildung, was mit einer bullösen Amyloidose übereinstimmte. Die TEM bestätigte Amyloidfasernablagerungen in der Dermis und entlang der Basalmembranzone. In der oberflächlichen Dermis und Submukosa bestand eine Spaltenbildung, die die Blutung und die Narbenbildung erklärten. Das Auftreten eine polyklonalen Gammopathie sowie das rasche Verschwinden der Kongorotfärbung nach performativer Vorbehandlung stützte die Diagnose einer Serum Amyloid A und einer sekundären Amyloidose.Die bullöse Amyloidose ist eine neue Erkrankung des Pferdes und eine neu erkannte Differentialdiagnose für bullöse Erkrankungen, bei der die hämorrhagische Natur der Blasen, die Narbenbildung und die tiefen sekundären Ulzera als klinische Hinweise für diesen Zustand gelten.背景: 水疱性アミロイドーシスは、ヒトではまれな疾患で、獣医学的にはまだ報告されていない。本疾患は、アミロイド沈着により皮膚や粘膜に形成される出血性の小水疱や水疱が特徴である。 仮説/目的: 本研究の目的は、1頭の馬に認められた水疱疾患のユニークな症状の臨床的特徴、実験室解析および病理組織学的特徴を説明することであった。 供試動物: 17歳のサラブレッドの雌馬が体重減少および重度の口腔内潰瘍のために来院した。 方法: 血液学的評価、化学的プロファイル、胃内視鏡検査、血清タンパク質電気泳動を行い、死後、組織学的評価、コンゴレッド染色、透過型電子顕微鏡 (TEM) を行った。 結果: 出血性小水疱および水疱は口腔、口唇、食道、胃の粘膜に発生し、鼻口部、顔面、会陰粘膜皮膚領域にはほとんど発生せず、瘢痕が認められた。病理組織学的評価およびコンゴレッド染色により、水疱性アミロイドーシスと一致した、小水疱や水疱の形成と関連する真皮および粘膜下層のアミロイド沈着の存在が確認された。TEMでは、真皮および基底膜帯に沿ってアミロイド線維の沈着が確認された。表層の真皮および粘膜下層に裂け目が生じており, 出血および瘢痕化が説明できた。ポリクローナルガンモパシーの存在と、前治療の実施によるコンゴレッド染色の急速な廃絶は、血清アミロイド A および続発性アミロイドーシスを支持した。 結論と臨床的重要性: 水疱性アミロイドーシスは馬の新しい病気であり、水疱症の鑑別として新たに認識された。水疱の出血性の性質、瘢痕、深い二次的な潰瘍がこの病気の臨床的な手がかりと考えられる。.背景: 大疱性淀粉样变性是一种人类罕见疾病, 动物发病尚未在兽医同行评审文献中描述过。人类疾病的特征是皮肤和粘膜上的出血性水疱和大疱, 其由淀粉样蛋白沉积形成。 假设/目的: 描述马大疱性疾病独特表现的临床特征、实验室分析和组织病理学特征。 动物: 只17岁的纯种母马因体重减轻和严重的口腔溃疡而就诊。 方法: 研究涉及血液学评价、化学特征、胃镜检查和血清蛋白电泳, 以及尸检、组织病理学评价、刚果红染色和透射电子显微镜(TEM)。 结果: 口腔、嘴唇、食管和胃的粘膜上发生出血性水疱和大疱, 更少发生在有明显瘢痕的口鼻、面部和会阴皮肤粘膜区域。组织病理学评价和刚果红染色证实真皮和粘膜下层存在淀粉样沉积物, 与水泡和大疱形成相关, 与大疱性淀粉样变性一致。TEM证实淀粉样纤维沉积于真皮, 并沿基底膜区沉积。裂隙发生在真皮浅层和粘膜下层, 这解释了出血和瘢痕形成。多克隆丙种球蛋白病的存在和进行预处理后刚果红染色的快速消除,支持了血清淀粉样蛋白a和继发性淀粉样变性。 结论和临床意义: 大疱性淀粉样变性是马的一种新型疾病, 并发现与大疱性疾病存在差异, 大疱的出血性质、瘢痕和深部继发性溃疡被认为是该疾病的临床线索。.A amiloidose bolhosa é uma doença rara em humanos que não foi descrita em espécies veterinárias na literatura com sistema de revisão por pares. A doença humana é caracterizada por vesículas e bolhas hemorrágicas na pele e mucosas, que se formam devido à deposição de substância amiloide. HIPÓTESE/OBJETIVOS: Descrever as características clínicas, exames laboratoriais e histopatológicos de uma doença bolhosa com apresentação singular em um cavalo.Uma égua da raça puro-sangue inglês de 17 anos de idade foi apresentada devido a um quadro de perda de peso e úlceras graves da cavidade oral. MÉTODOS: As investigações consistiram de avaliação hematológica, perfil bioquímico, gastroscopia e eletroforese de proteínas séricas e, postmortem, avaliação histopatológica, coloração com vermelho do Congo e microscopia eletrônica de transmissão (TEM).Vesículas e bolhas hemorrágicas estavam presentes na mucosa da cavidade oral, lábios, esôfago e estômago, e, em menor quantidade, no focinho, face e regiões mucocutâneas do períneo, onde a presença de tecido cicatricial era evidente. A avaliação histopatológica e a coloração com vermelho do Congo confirmaram a presença de depósitos de substância amiloide na derme e submucosa, associados à formação de vesículas e bolhas, compatível com amiloidose bolhosa. A TEM confirmou a deposição de fibrila amiloide na derme e ao longo da zona da membrana basal. Observou-se a presença de fissuras na derme superficial e submucosa, justificando a hemorragia e as cicatrizes. A presença de uma gamopatia policlonal e a rápida descoloração do vermelho do Congo após pré-tratamento corroboraram com a amiloide A sérica e a amiloidose secundária. CONCLUSÃO E IMPORTÂNCIA CLÍNICA: A amiloidose bolhosa é uma nova doença descrita em equinos e representa um diagnóstico diferencial recentemente reconhecido para quadros bolhosos, sendo que a natureza hemorrágica das bolhas, presença de cicatrizes e úlceras profundas secundárias são consideradas indícios clínicos da condição.}, journal={VETERINARY DERMATOLOGY}, author={Fussell, Devin and Bizikova, Petra and Breuhaus, Babetta and Harris, R. Adam and Moore, A. Russell and Chen, Laura and Linder, Keith E.}, year={2021}, month={Jun} }
 @article{herrmann_linder_meurs_friedenberg_cullen_olby_bizikova_2021, title={Canine junctional epidermolysis bullosa due to a novel mutation in LAMA3 with severe upper respiratory involvement}, volume={32}, ISSN={["1365-3164"]}, url={https://doi.org/10.1111/vde.12972}, DOI={10.1111/vde.12972}, abstractNote={Junctional epidermolysis bullosa (JEB) is a group of congenital blistering skin diseases characterized by clefting through the lamina lucida of the basement membrane zone.To characterize the clinical and morphological features of a congenital mechanobullous disease in a litter of puppies with severe upper respiratory involvement, and to identify an associated genetic variant.Five of eight puppies in an Australian cattle dog cross-bred litter showed signs of skin fragility. Three were stillborn and one died at one month of age. The two surviving puppies were presented with blistering skin disease and severe respiratory distress. Additionally, one unaffected sibling was examined and blood was obtained for genetic testing.Post-mortem examination, histopathological evaluation and electron microscopy were performed. Whole genome sequencing (WGS) of one affected puppy was compared to a database of 522 dogs of 55 different breeds for variant analysis. Sanger sequencing of one additional affected and one unaffected sibling confirmed the variant.Clinically, severe mucocutaneous ulcers occurred in frictional areas with claw sloughing. Histopathological results revealed subepidermal clefts and electron microscopy confirmed the split in the lamina lucida. Post-mortem examination documented extensive pharyngeal and laryngeal lesions with granulation tissue and fibrinous exudate obscuring the airway. Moderate tracheal hypoplasia contributed. The WGS revealed a novel missense variant in the laminin α3-chain XP_537297.2p(Asp2867Val), with an autosomal recessive mode of inheritance.A novel variant in LAMA3 caused a generalized and severe phenotype of JEB with an unique clinical presentation of upper airway obstruction.L’épidermolyse bulleuse jonctionnelle (JEB) est un groupe de dermatoses cutanées congénitales vésiculeuses caractérisées par un clivage au niveau de la lamina lucida de la membrane basale.Caractériser les critères cliniques et morphologiques de maladies bulleuses congénitales dans une portée de chiots avec troubles respiratoires sévères et identifier un variant génétique associé.Cinq des huit chiots d’une portée de chiens croisés bouvier australien ont montré des signes de fragilité cutanée. Trois étaient mort-nés et un est mort à l’âge d’un mois. Les deux chiots survivants ont été présentés avec une dermatose vésiculeuse et des troubles respiratoires sévères. En outre, un chiot sain a été examiné et du sang a été prélevé pour tests génétiques. MATÉRIELS ET MÉTHODES: Un examen post-mortem, une évaluation histopathologique et electro-microscopique ont été réalisés. Le séquençage complet du génome (WGS) d’un chiot atteint a été comparé à une base de données de 522 chiens de 55 races différentes pour une analyse de variant. Le séquençage de Sanger d’un autre chiot atteint et un chiot sain a confirmé le variant. RÉSULTATS: Cliniquement, les ulcères cutanéo-muqueux sévères étaient observés aux zones de friction avec pertes des griffes. Les résultats histopathologiques révélèrent des séparations sous épidermiques et l’électro-microscopie a confirmé le clivage au sein de la lamina lucida. L’examen post mortem a documenté des lésions laryngées et pharyngées extensives avec tissue de granulation et exsudat fibrineux dissimulant les voies aériennes. Une hypoplasie trachéale modérée y contribuait. Le WGS a révélé un nouveau variant contre-sens dans la chaine α3 de laminine XP_537297.2p(Asp2867Val), avec un mode autosomal récessif de transmission.Un nouveau variant cause un phénotype de JEB sévère et généralisé avec une présentation clinique unique d’obstruction des voies respiratoires supérieures.INTRODUCCIÓN: la epidermólisis bullosa de la unión (JEB) es un grupo de enfermedades cutáneas congénitas con formación de ampollas caracterizadas por una hendidura a lo largo de la lámina lúcida de la zona de la membrana basal. OBJETIVOS: establecer las características clínicas y morfológicas de una enfermedad mecanobullosa congénita en una camada de cachorros con afectación respiratoria superior grave e identificar una variante genética asociada. ANIMALES: cinco de los ocho cachorros en una camada mestiza de perros de ganado australiano mostraron signos de fragilidad de la piel. Tres nacieron muertos y uno murió al mes de edad. Los dos cachorros supervivientes presentaron una enfermedad cutánea con ampollas y dificultad respiratoria grave. Además, se examinó a un hermano no afectado y se extrajo sangre para realizar pruebas genéticas. MÉTODOS Y MATERIALES: Se realizó examen post-mortem, evaluación histopatológica y microscopía electrónica. La secuenciación del genoma completo (WGS) de un cachorro afectado se comparó con una base de datos de 522 perros de 55 razas diferentes para el análisis de variantes. La secuenciación de Sanger de un hermano afectado adicional y un hermano no afectado confirmó la variante. RESULTADOS: Clínicamente, se produjeron úlceras mucocutáneas graves en áreas de fricción con desprendimiento de garras. Los resultados histopatológicos revelaron hendiduras subepidérmicas y la microscopía electrónica confirmó la escisión en la lámina lúcida. El examen post-mortem documentó extensas lesiones faríngeas y laríngeas con tejido de granulación y exudado fibrinoso que oscurecía las vías respiratorias. A las lesions también se añadía una hipoplasia traqueal moderada. El WGS reveló una nueva variante sin sentido en la cadena α3 de laminina XP_537297.2p (Asp2867Val), con un modo de herencia autosómico recesivo. CONCLUSIÓN Y RELEVANCIA CLÍNICA: una nueva variante genética causó un fenotipo generalizado y severo de JEB con una presentación clínica única de obstrucción de las vías respiratorias superiores.Die Junctional Epidermolysis Bullosa (JEB) umfasst eine Gruppe kongenitaler blasenbildender Hauterkrankungen, die durch eine Spaltbildung durch die Lamina lucida der Basalmembranzone charakterisiert sind. ZIEL: Die Charakterisierung klinischer und morphologischer Merkmale einer kongenitalen mechanobullösen Erkrankung bei einem Wurf von Welpen mit hochgradiger respiratorischer Beteiligung sowie eine Identifizierung der damit zusammenhängenden genetischen Variante.Fünf von acht Welpen eines Australian cattle Dog Mischlingswurfes zeigten Zeichen von Hautfragilität. Drei waren totgeboren und ein Welpe starb mit einem Monat. Die zwei überlebenden Welpen wurden mit einer blasenbildenden Hauterkrankung und hochgradiger respiratorischer Not vorgestellt. Zusätzlich wurde ein nicht betroffenes Geschwister untersucht und Blut zur genetischen Analyse genommen.Eine Post Mortem Untersuchung, eine histopathologische Evaluierung und Elektronenmikroskopie wurden durchgeführt. Eine Ganz-Genom Sequenzierung (WGS) eines erkrankten Welpen wurde mit der Datenbank von 522 Hunden 55 verschiedener Rassen zur Varianzanalyse verglichen. Mittels Sanger Sequenzierung eines der weiteren betroffenen und eines nicht erkrankten Geschwisters wurde die Variante bestätigt.Klinisch traten hochgradige mukokutane Ulzera an Reibungsstellen auf, wobei sich die Krallen ablösten. Die histopathologische Untersuchung ergab subepidermale Spalten und mittels Elektronenmikroskopie wurde der Spalt in der Lamina lucida bestätigt. Die Post mortem Untersuchung dokumentierte ausgedehnte Läsionen in Pharynx und Larynx, wobei Granulationsgewebe und fibrinöses Exsudat die Luftwege behinderten. Eine moderate tracheale Hypoplasie trug zu dem Problem bei. Die WGS zeigte eine neue Missense Mutation in der Laminin α3-Kette XP_537297.2p(Asp2867Val), bei autosomal rezessiver Vererbung.Eine neue Variante bedingte eine generalisierte Form einer JEB mit einem stark betroffenen Phänotyp und einer einzigartigen klinischen Präsentation der Obstruktion der oberen Atemwege.背景: Junctional epidermolysis bullosa（JEB）は，基底膜領域のlamina lucidaを介した間隙を特徴とする先天性水疱性皮膚疾患の一群である。 目的: 本研究の目的は、重度の上気道病変を有する子犬集団における先天性機械的水疱性疾患の臨床的および形態学的特徴を明らかにし，関連する遺伝子変異を同定することであった。 供試動物: オーストラリアン・キャトル・ドッグとの交配で生まれた子犬8頭のうち、5頭に皮膚脆弱性の兆候が見られた。3頭は死産し、1頭は生後1ヶ月で死亡した。生き残った2頭の子犬は、水ぶくれのある皮膚病と重度の呼吸困難を呈していた。さらに、罹患していない1頭の同腹仔を診察し、遺伝子検査のために血液を採取した。 材料と方法: 死後検査、病理組織学的評価および電子顕微鏡検査を行った。罹患子犬1頭の全ゲノム塩基配列（WGS）を、55種の犬522頭のデータベースと比較し、バリアント解析を行った。さらに罹患した1頭の同腹仔と罹患していない1頭の同腹仔のサンガーシークエンス法により、変異が確認された。 結果: 臨床的には、重度の粘膜皮膚潰瘍が摩擦部位に発生し、爪が剥がれた。病理組織学的には表皮下の間隙を認め、電子顕微鏡ではlamina lucidaの間隙が確認された。死後検査では、肉芽組織および線維性滲出液が気道を塞いでいる広範囲の咽頭および喉頭の病変が記録された。中等度の気管低形成が認められた。WGSの結果、ラミニンα3鎖のXP_537297.2p(Asp2867Val)という新規ミスセンス変異が見つかり、常染色体劣性遺伝であることが判明した。 結論と臨床的妥当性: 新規変異は、上気道閉塞というユニークな臨床症状を伴うJEBの全般的で重篤な表現型の原因となった。.背景: 交界性大疱性表皮松解症(Junctional epidermolysis bullosa，JEB)是一组先天性水疱性皮肤病，以基底膜区透明层裂隙为特征。 目的: 描述一窝严重上呼吸道发病幼犬先天性机械大疱病的临床和形态学特征，并确定相关的遗传变异。 动物: 澳大利亚杂交牛犬8只同窝幼犬中的5只显示出皮肤脆弱症状。3只为死胎，1例在1月龄时死亡。2只存活幼犬表现为水疱性皮肤病和严重呼吸窘迫。此外，检查了1只未发病的同窝犬，并采集血液用于基因检测。 方法和材料: 进行尸检、组织病理学评价和电子显微镜检查。将1只发病幼犬的全基因组测序(WGS)与55个不同品种的522只犬的数据库进行比较，进行变异分析。对另外一个发病和一个未发病的同窝犬进行Sanger测序，证实了该变异。 结果: 临床上，重度皮肤粘膜溃疡发生在摩擦区域，伴爪脱落。组织病理学结果显示表皮下裂隙，电子显微镜检查证实透明层开裂。尸检记录了广泛的咽部和喉部病变，伴有肉芽组织和纤维蛋白性渗出物阻塞气道。导致中度气管发育不全。WGS揭示了层粘连蛋白α3-链XP_537297.2p(Asp2867Val)的一个新的错义变体，具有常染色体隐性遗传模式。 结论和临床相关性: 种新变体引起JEB的广泛和严重表型，具有上呼吸道阻塞的独特临床表现。.A epidermólise bolhosa juncional (EBJ) é um grupo de doenças cutâneas congênitas apresentando lesões bolhosas caracterizadas por fissuras ao longo da lâmina lúcida da zona da membrana basal.Detalhar as características clínicas e morfológicas de uma doença mecanobolhosa congênita em uma ninhada de filhotes de cães com comprometimento respiratório superior grave e identificar uma variante genética associada.Cinco dos oito filhotes em uma ninhada com cães boideieros australianos mestiços apresentaram sinais de fragilidade da pele. Três nasceram mortos e um morreu com um mês de idade. Os dois cachorros sobreviventes apresentaram dermatopatia bolhosa e dificuldade respiratória grave. Além disso, um irmão não afetado foi examinado e o sangue foi obtido para teste genético. MÉTODOS E MATERIAIS: Foram realizados exame post-mortem, avaliação histopatológica e microscopia eletrônica. O sequenciamento do genoma completo (WGS) de um filhote afetado foi comparado a um banco de dados de 522 cães de 55 raças diferentes para análise de variantes. O sequenciamento de Sanger de um irmão afetado adicional e um irmão não afetado confirmou a variante.Clinicamente, úlceras mucocutâneas graves ocorreram em áreas de fricção com arranhadura pelas unhas. Os resultados histopatológicos revelaram fissuras subepidérmicas e a microscopia eletrônica confirmou a fissura na lâmina lúcida. O exame post-mortem documentou lesões laríngeas e faríngeas extensas com tecido de granulação e exsudato fibrinoso obscurecendo as vias aéreas. Hipoplasia traqueal moderada contribuiu. O WGS revelou uma nova variante missense na cadeia α3 da laminina XP_537297.2p (Asp2867Val), com um modo de herança autossômico recessivo. CONCLUSÃO E RELEVÂNCIA CLÍNICA: Uma nova variante causou um fenótipo generalizado e grave de EBJ com uma apresentação clínica única de obstrução das vias aéreas superiores.}, number={4}, journal={VETERINARY DERMATOLOGY}, author={Herrmann, Ina and Linder, Keith E. and Meurs, Kathryn M. and Friedenberg, Steven G. and Cullen, Jonah and Olby, Natasha and Bizikova, Petra}, year={2021}, month={Aug}, pages={379-+} }
 @article{halliwell_pucheu-haston_olivry_prost_jackson_banovic_nuttall_santoro_bizikova_mueller_2021, title={Feline allergic diseases: introduction and proposed nomenclature}, volume={32}, ISBN={1365-3164}, url={https://doi.org/10.1111/vde.12899}, DOI={10.1111/vde.12899}, abstractNote={Feline allergic diseases present as challenging problems for clinicians, not least because of the number of reaction patterns of the feline skin, none of which are specific for allergy. Furthermore, there is some controversy over the nomenclature that should be used in their description.To review the literature, assess the status of knowledge of the topic and the extent to which these diseases could be categorized as atopic in nature, and make recommendations concerning nomenclature.Atopic diseases in humans and cats were researched. A comparison then was made of the essential features in the two species.There were sufficient similarities between human atopic diseases and the manifestations of feline diseases of presumed allergic aetiology to justify the use of "atopic" to describe some of the feline conditions affecting the skin, respiratory and gastrointestinal tract. However, none of the allergic skin diseases showed features consistent with atopic dermatitis as described in man and the dog.The term "Feline Atopic Syndrome" (FAS) is proposed to encompass allergic diseases of the skin, gastrointestinal tract and respiratory tract, and "Feline atopic skin syndrome" (FASS) proposed to describe allergic skin disease associated with environmental allergies. We are not aware of any adverse food reactions in cats that are attributable to causes other than immunological reactions against the food itself. We therefore propose an aetiological definition of "Food Allergy" (FA) to describe such cases.Une nouvelle anomalie congénitale de la tige pilaire ressemblant au phénotype nu des rongeurs est décrite dans une portée de quatre chats européens (DSH). Les données relatives aux anomalies de la tige pilaire et des follicules pileux sont rares en médecine vétérinaire.Décrire et comparer les anomalies structurelles de ces chats avec d’autres dystrophies félines et d’autres mammifères.Une portée de chats DSH avec alopécie progressive non-inflammatoire. MÉTHODES: L’évaluation histopathologique, la microscopie électronique à transmission et l’analyse des éléments par rayons X définissaient les changements pilaires et cutanés des chats nés alopéciques. Les données ont été comparées aux archives de chats normaux et de souris mutantes Dsg4lahJ et Krt75tm1Der . RÉSULTATS: La microscopie électronique à lumière et à balayage des poils a révélé des défauts de forme de l’extrémité de la tige pilaire en pointe ou en lance. Les données histopathologiques consistaient en des tiges pilaires enflées, initialement au dessus de la matrice du bulbe pilaire et ensuite retrouvé dans les parties distales des follicules pileux télogènes, semblables à ceux observés chez les souris mutantes Dsg4lahJ Krt75tm1Der . La microscopie électronique à transmission de la tige pilaire et des follicules pileux a révélé une perte de la structure normale des poils de garde chez les chats alopéciques. Il y a avait une diminution statistiquement significative du contenu en sulfure juste au dessous des défauts des tiges pilaires (trichothiodystrophie). CONCLUSIONS ET IMPORTANCE CLINIQUE: une forme rare d’alopécie congénitale résultant en une dystrophie folliculaire est décrite chez le chat, comparable aux changements de la tige pilaire et du follicule pileux décrits dans plusieurs souches de souris mutantes avec une mutation génétique unique des gènes des molécules d’adhésion ou de kératine.ANTECEDENTES: se describe una nueva anomalía congénita del pelo que se asemeja al fenotipo de pelo lanceolado de los roedores en una camada de cuatro gatos domésticos de pelo corto (DSH). Los datos relacionados con los trastornos del pelo y los folículos siguen siendo escasos en medicina veterinaria. OBJETIVOS: Describir y comparar anomalías estructurales en estos gatos con otras distrofias capilares en gatos y otros mamíferos. ANIMALES: una camada de gatos DSH con alopecia no inflamatoria progresiva. MÉTODOS: evaluación histopatológica, por microscopía electrónica de barrido y de transmisión y el análisis de elementos basados en rayos X definieron los cambios en el pelo y la piel de los gatos nacidos con alopecia. Los hallazgos se compararon con datos de archivo de gatos normales y ratones mutantes de pelo lanceolado (Dsg4lahJ ) y queratina 75 (Krt75tm1Der ). RESULTADOS: la microscopía óptica y electrónica de barrido de los pelos reveló defectos en la punta del cabello en forma de lanza o punta de lanza. Los hallazgos histológicos fueron pelos hinchados, inicialmente por encima de la matriz del bulbo piloso y luego encontrados en las partes distales de los folículos pilosos telógenos, similares a los observados en ratones mutantes Dsg4lahJ Krt75tm1Der . La microscopía electrónica de transmisión del pelo y los folículos pilosos mostró una pérdida en la estructura normal de los pelos primarios en los gatos alopécicos. Hubo una disminución estadísticamente significativa en el contenido de azufre justo por debajo de los defectos en los tallos del cabello (tricotiodistrofia). CONCLUSIÓN E IMPORTANCIA CLÍNICA: en gatos se describe una forma poco común de alopecia congénita que da como resultado distrofia folicular, similar a los cambios en el folículo piloso y el tallo del pelo descritos en varias cepas de ratones mutantes con mutaciones de un solo gen en moléculas de adhesión o genes de queratina.Es wird eine neue angeborene Haarschaft Abnormalität bei einem Wurf von vier Hauskatzen (DSH) beschrieben, die dem lanzenförmigen Haar Phänotyp von Nagern gleicht. Daten über Haarschaft- und Follikelstörungen bleiben in der Veterinärmedizin rar.Eine Beschreibung der Strukturabnormalitäten bei diesen Katzen und ein Vergleich mit anderen Haardystrophien bei Katzen und anderen Säugern.Ein Wurf von Hauskatzen mit einer progressiven nichtentzündlichen Alopezie.Mittels histopathologischer Evaluierung, Raster- und Transmissionselektronenmikroskopie, und Röntgen-basierter Elementanalyse wurden die Haar- und Hautveränderungen bei Katzen, die mit einer Alopezie geboren worden waren, definiert. Die Befunde wurden mit archivierten Daten von normalen Katzen und lanzenförmigen Haaren (Dsg4lahJ ) und Keratin 75 (Krt75tm1Der ) von mutanten Mäusen verglichen.Die Licht- und Rasterelektronenmikroskopie der Haare zeigte Lanzen- oder Speer-Kopf geformte Defekte der Haarspitzen. Die histologischen Befunde zeigten geschwollene Haarschäfte, ursprünglich oberhalb der Haarwurzelmatrix und später auch in den distalen Teilen der telogenen Haarfollikel, ähnlich denen bei Dsg4lahJ Krt75tm1Der mutanten Mäusen. Die Transelektronenmikroskopie von Haarschaft und Haarfollikeln zeigte ein Verschwinden der normalen Struktur der Deckhaare bei haarlosen Katzen. Es bestand eine statistisch signifikante Abnahme des Schwefelgehaltes unmittelbar unter den Defekten in den Haarschäften (Trichothiodystrophie).Eine seltene Form einer angeborenen Alopezie, resultierend aus einer follikulären Dystrophie wird bei Katzen in einer ähnlichen Form beschrieben, wie es bereits bei einigen mutanten Mausstämmen mit einer Einzelgenmutation in Adhäsionsmolekülen oder Keratingenen publiziert worden war.背景: げっ歯類の槍状の毛の表現型に似た新しい先天性毛幹異常が4頭のドメスティック・ショートヘア（DSH）の同腹子で記述されている。毛幹および毛包の障害に関連するデータは、獣医学ではまだ不足している。 目的: 本研究の目的は、これらの猫の構造異常を説明し、猫や他の哺乳類の他の毛髪ジストロフィーと比較することであった。 動物: 進行性の非炎症性脱毛症を伴うDSH猫の同腹子。 方法: 組織病理学的評価、走査型および透過型電子顕微鏡法、およびX線ベース元素解析により、脱毛症で生まれた猫の毛および皮膚の変化が定義された。調査結果は、健常猫と披針形の毛（Dsg4lahJ ）およびケラチン75（Krt75tm1Der ）変異マウスからのアーカイブデータと比較された。 結果: 毛髪の光学顕微鏡および走査型電子顕微鏡検査により、毛先の槍または槍の頭の形をした欠陥が明らかになった。組織学的所見は、Dsg4lahJ Krt75tm1Der 変異マウスで観察されたものと同様に、最初は毛球マトリックス上にあり、後に休止期毛包の遠位部分に見られた、膨張した毛幹であった。毛幹および毛包の透過型電子顕微鏡検査は、脱毛猫のガード毛の正常な構造の喪失を示した。毛幹の欠陥（トリコチオジストロフィー）のすぐ下で硫黄含有量の統計的に有意な減少があった。 結論と臨床的重要性: 接着分子またはケラチン遺伝子に単一遺伝子変異を有するいくつかの変異マウス系統で報告された毛包および毛幹の変化に類似した、毛包ジストロフィーを引き起こすまれな形態の先天性脱毛症が猫で説明されている。.背景: 在4只同窝家养短毛(DSH)猫中，发现了类似啮齿动物披针形毛发表型，这是一种新的先天性毛干异常。与毛干和毛囊疾病相关的数据在兽医学中仍然很少。 目的: 描述这些猫的结构异常，并与猫和其他哺乳动物的其他毛发形成不良进行比较。 动物: 患有进行性非炎性脱毛症的一窝DSH猫。 方法: 组织病理学评价、扫描和透射电子显微镜以及基于X射线的元素分析，定义了新生脱毛猫的毛发和皮肤变化。将结果与正常猫、披针形毛发(Dsg4lahJ)和角质75(Krt75tm1Der)突变小鼠的存档数据进行比较。 结果: 毛发的光学和扫描电子显微镜检查显示，毛尖存在披针形或矛头形缺陷。组织学发现毛干肿胀，最初在毛球基质上方，后来在终止期毛囊的远端部分发现，与在Dsg4lahJ Krt75tm1Der突变小鼠中观察到的相似。毛干和毛囊的透射电镜显示脱毛猫护毛的正常结构缺失。毛干缺损正下方的硫含量在统计学上显著降低（毛发硫营养不良）。 结论和临床重要性: 发现了猫的罕见先天性脱发形式，由毛囊发育不良所导致，与粘附分子或角质基因中单基因突变的几种突变小鼠品系中报告的毛囊和毛干变化类似。.Uma nova anomalia congênita da haste pilosa semelhante ao fenótipo de pelo lanceolado dos roedores foi descrita em uma ninhada de quatro gatos domésticos de pelo curto (DSH). Dados relacionados a enfermidades da haste e folículo piloso permanecem escassos na medicina veterinária.Descrever e comparar as anomalias estruturais nestes gatos com outras distrofias pilosas em gatos e outros mamíferos.Um gato DSH apresentando alopecia não inflamatória progressiva. MÉTODOS: Avaliação histopatológica, microscopia eletrônica de varredura e transmissão e análise elementar baseada em raio-X foram utilizadas para caracterizar as alterações de pele e pelos em gatos nascidos com alopecia. Os achados foram comparados a dados arquivados de gatos normais e ratos com mutação de pelo lanceolado (Dsg4lahJ ) e Queratina 75 (Krt75tm1Der ).À microscopia de varredura e óptica, observou-se pelos com defeitos nas pontas, que se apresentavam em formato de lança ou ponta de lança. Os achados histológicos foram hastes pilosas dilatadas, inicialmente acima da matriz do bulbo piloso e posteriormente nas partes distais dos folículos pilosos telógenos, similar ao observado nos ratos mutantes Dsg4lahJ Krt75tm1Der .Ao microscópio eletrônico de transmissão, as hastes pilosas e os folículos pilosos demonstraram perda na estrutura normal dos pelos guardiães nos gatos alopécicos. Houve uma redução significativa no conteúdo de enxofre imediatamente abaixo dos defeitos nas hastes pilosas (tricotiodistrofia). CONCLUSÃO E IMPORTÂNCIA CLÍNICA: Uma forma rara de alopecia congênita resultante de distrofia folicular descrita em gatos é similar às alterações nos folículos pilosos e hastes pilosas em diversas linhagens de ratos com mutações de um único gene em genes de moléculas de adesão ou queratina.}, number={1}, journal={VETERINARY DERMATOLOGY}, publisher={Wiley}, author={Halliwell, Richard and Pucheu-Haston, Cherie M. and Olivry, Thierry and Prost, Christine and Jackson, Hilary and Banovic, Frane and Nuttall, Tim and Santoro, Domenico and Bizikova, Petra and Mueller, Ralf S.}, year={2021}, month={Feb}, pages={8-+} }
 @article{didomenico_fowler_horne_bizikova_schnabel_stowe_2021, title={Pathology in Practice}, volume={258}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.258.9.961}, DOI={10.2460/javma.258.9.961}, number={9}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={DiDomenico, Amy E. and Fowler, Alexander W. and Horne, Caitlyn R. and Bizikova, Petra and Schnabel, Lauren V. and Stowe, Devorah M.}, year={2021}, month={May}, pages={961–964} }
 @misc{mueller_nuttall_prost_schulz_bizikova_2021, title={Treatment of the feline atopic syndrome - a systematic review}, volume={32}, ISSN={["1365-3164"]}, DOI={10.1111/vde.12933}, abstractNote={Feline allergic skin disease and asthma occur regularly in small animal practice.To provide evidence-based recommendations for small animal practitioners on the treatment of feline atopic syndrome (FAS).The authors reviewed the literature available before February 2020, prepared a detailed evidence-based literature review and made recommendations based on the evaluated evidence.Sixty-six papers and abstracts were identified describing treatment interventions for FAS and evaluated to establish treatment recommendations. For many treatment options, the papers were retrospective, open studies or case reports.In this review, there was good evidence for the efficacy of systemic glucocorticoids and ciclosporin, and limited evidence for the efficacy of topical glucocorticoids, oclacitinib and allergen-specific immunotherapy in feline atopic skin syndrome. Evidence pointed to low-to-moderate efficacy for antihistamines, fatty acids and palmitoyl ethanolamide. In feline asthma, there was good evidence for the efficacy of oral and inhaled glucocorticoids, and limited evidence of moderate efficacy for allergen-specific immunotherapy. Evidence supported low-to-moderate efficacy of mesenchymal stem cells, inhaled lidocaine and oclacitinib as treatments for feline asthma. For almost all therapeutic options (with the exception of glucocorticoids and ciclosporin), more randomised controlled trials are needed.背景: 猫特应性综合征(FAS)涵盖了一系列超敏反应疾病, 以高度多样化的临床表现为特征, 包括皮肤、胃肠道和呼吸系统。这些疾病包括猫特应性皮肤综合征(FASS), 其中超敏反应通常与环境过敏原相关, 尽管食物过敏可能同时存在。也可能累及其他器官系统 (如哮喘)。由于其高度异质性的临床表现, FASS的诊断可能具有挑战性。 目的: 国际动物过敏性疾病委员会(ICADA)的一个亚组的任务是总结FASS临床表现的最新信息, 并制定诊断指南。 方法: 检索在线引文数据库和国际会议摘要中与猫过敏相关的出版物。必要时结合专家意见。 结果: 共找出107篇与本综述相关的出版物。汇编这些资料能够制定FASS临床特征的详细描述和制定指南, 重点是系统性消除具有相似临床特征的其他皮肤疾病。由于皮肤科医生经常使用过敏试验来支持FASS的临床诊断, 因此还对这些方法进行了简要综述。 结论和临床重要性: 与犬特应性皮炎相似, FASS的临床诊断是基于相符的临床症状,并排除具有相似临床特征的其他疾病。在确诊FASS之前, 必须消除或排除跳蚤/跳蚤过敏、其他寄生虫、感染和食物过敏。.CONTEXTE: le syndrome atopique félin (FAS) décrit un spectre d’hypersensibilités caractérisées par diverses présentations cliniques comprenant la peau, le système digestif et le système respiratoire. Parmi ces atteintes, il y a le syndrome cutané atopique félin (FASS), pour lequel l’hypersensibilité est typiquement associée à des allergènes environnementaux, bien que l’allergie alimentaire puisse coexister. D’autres organes (par exemple asthme) peuvent être aussi impliqués. En raison de cette grande hétérogénéité clinique, le diagnostic du FASS peut être un défi. OBJECTIFS: Un sous-groupe de l’ICADA (International Committee on Allergic Diseases of Animals) a été chargé de résumer les informations les plus actuelles sur les présentations cliniques du FASS et de développer des recommandations de diagnostic. MÉTHODES: Les citations des bases de données en ligne et les résumés des congrès internationaux ont été recherchés pour les publications en lien avec les allergies félines. Ceci a été combiné avec des opinions d’experts quand nécessaire. RÉSULTATS: Un total de 107 publications pertinentes a été identifié. La compilation de ces données a permis le développement d’une description détaillée des critères cliniques du FASS et le développement de recommandations ciblant une élimination systématique des autres atteintes cutanées avec des caractéristiques cliniques semblables. Alors que les tests allergiques sont fréquemment utilisés par les dermatologues pour soutenir le diagnostic clinique du FASS, une revue rapide de ces méthodologies a aussi été réalisée. CONCLUSIONS ET IMPORTANCE CLINIQUE: De façon semblable à la dermatite atopique canine, le FASS est un diagnostic clinique basé sur la présence compatible avec les signes cliniques et l’exclusion d’autres maladies ayant des critères cliniques semblables. L’élimination ou l’exclusion des puces/de l’allergie aux puces, d’autres parasites, des infections et de l’allergie alimentaire est necessaire avant d’établir un diagnostic de FASS.Das Feline atopische Syndrom (FAS) beschreibt ein Spektrum von Hypersensibilitätserkrankungen, die durch sehr unterschiedliche klinische Präsentationen auf der Haut, dem Gastrointestinaltrakt und dem Respirationstrakt charakterisiert sind. Unter diesen Erkrankungen ist auch das Feline Atopische Haut Syndrom (FASS), bei dem eine Hypersensibilität typisch mit Umweltallergenen in Zusammenhang steht, obwohl eine Futterallergie gleichzeitig bestehen könnte. Es können auch andere Organsysteme mit involviert sein (z.B. Asthma). Aufgrund der hochgradig heterogenen klinischen Präsentation kann die Diagnose der FASS eine Herausforderung darstellen.Eine Untergruppe des International Committee on Allergic Diseases of Animals (ICADA) sollte die gängigste Information über die klinischen Präsentationen vom FASS zusammenfassen und diagnostische Richtlinien entwerfen.Es wurden Online Literaturstellen und Abstracts von internationalen Treffen auf Publikationen über Allergien der Katze durchsucht. Diese wurden, wenn nötig, mit einer Expertenmeinung kombiniert.Es wurden insgesamt 107 Publikationen, die für dieses Thema relevant waren, identifiziert. Eine Erfassung dieser Daten erlaubte die Entwicklung einer detaillierten Beschreibung der klinischen Merkmale des FASS und die Entwicklung von Richtlinien, die sich auf die systematische Eliminierung von anderen Hauterkrankungen mit ähnlichen klinischen Charakteristika konzentrieren. Da Allergietests von Dermatologen häufig verwendet werden, um eine klinische Diagnose des FASS zu untermauern, wurde eine kurze Review dieser Methoden durchgeführt.In einer ähnlichen Weise wie bei der atopischen Dermatitis der Hunde, ist das FASS eine klinische Diagnose, die auf dem Vorkommen von kompatiblen klinischen Zeichen und einem Ausschluss anderer Krankheiten mit ähnlichen klinischen Merkmalen beruht. Eine Eliminierung von Flöhen/Flohspeichelallergie, anderer Parasiten, Infektionen und Futterallergie sind zwingend notwendig, bevor die Diagnose einer FASS getroffen werden kann.背景: ネコアトピー症候群 (FAS) は、皮膚、胃腸、呼吸器系を含む非常に多様な臨床症状を特徴とする一連の過敏症を説明している。これらの障害の中には、食物アレルギーが共存する可能性があるものの、過敏症が通常環境アレルゲンと関連しているネコアトピー性皮膚症候群 (FASS) がある。他の臓器系 (喘息など) の関与も発生する可能性がある。その非常に不均一な臨床症状のために、FASSの診断は困難な場合がある。 目的: 動物のアレルギー性疾患に関する国際委員会 (ICADA) のサブグループは、FASSの臨床症状に関する最新情報を要約し、診断ガイドラインを作成する任務を負った。 方法: オンライン引用データベースと国際会議の要約を検索して、猫アレルギーに関連する出版物を探した。これらは、必要に応じて専門家の意見と組み合わされた。 結果: このレビューに関連する合計107の出版物が特定された。これらのデータの編集により、FASSの臨床的特徴の詳細な説明の開発および、同様の臨床的特徴を持つ他の皮膚状態の体系的な排除に焦点を当てたガイドラインの開発が可能になった。アレルギー検査はFASSの臨床診断をサポートするために皮膚科医によって頻繁に使用されるため、これらの方法論の簡単なレビューも行われた。 結論と臨床的重要性: 犬アトピー性皮膚炎と同様に、FASSは、互換性のある臨床徴候の存在と、同様の臨床的特徴を持つ他の疾患の除外に基づく臨床診断である。 FASSの診断に達する前に、ノミ/ノミアレルギー、他の寄生虫、感染症、および食物アレルギーの排除または排除が義務付けられている。.A síndrome atópica felina (SAF) descreve um espectro de distúrbios de hipersensibilidade caracterizados por uma apresentação clínica altamente diversa, incluindo a pele, sistema gastrointestinal e respiratório. Dentre esses distúrbios está a síndrome atópica cutânea felina (FASS, feline atopic skin syndrome), na qual hipersensibilidade é tipicamente associada a alérgenos ambientais, apesar de alimentos poderem coexistir. O envolvimento de outros sistemas (ex: asma) pode também ocorrer. Devido a essa apresentação clínica altamente heterogênea, o diagnóstico da FASS pode ser desafiador.Um subgrupo do International Committee on Allergic Diseases of Animals (ICADA) foi designado a sintetizar as informações mais recentes sobre as apresentações clínicas da FASS, e a desenvolver diretrizes diagnósticas. MÉTODOS: Bancos de dados de citações online e resumos de congressos internacionais foram utilizados para buscar publicações relacionadas a alergias em felinos. Quando necessário, estes foram combinados com as opiniões dos experts.Um total de 107 publicações relevantes a essa revisão foram identificados. A compilação desses dados permitiu o desenvolvimento de uma descrição detalhada das características clínicas da FASS e o desenvolvimento de diretrizes focando a eliminação sistemática de outras dermatopatias com características similares. Como os testes alérgicos são frequentemente utilizados por dermatologistas para apoiar o diagnóstico clínico de FASS, uma rápida revisão destas metodologias foi realizada. CONCLUSÕES E IMPORTÂNCIA CLÍNICA: Semelhante à dermatite atópica em cães, a FASS é um diagnóstico clínico baseado nos sinais clínicos compatíveis e exclusão de outras doenças com características clínicas similares. A eliminação de pulgas/alergia à picada de pulgas, outros parasitas, infecções e alergia alimentar é mandatória antes de se fechar o diagnóstico da FASS.INTRODUCCIÓN: el síndrome atópico felino (FAS) describe un espectro de trastornos de hipersensibilidad caracterizados por presentaciones clínicas muy diversas que incluyen la piel, los sistemas gastrointestinal y respiratorio. Entre estos trastornos se encuentra el síndrome de piel atópica felina (FASS), en el que la hipersensibilidad se asocia típicamente con alérgenos ambientales, aunque la alergia alimentaria puede coexistir. También puede producirse la afectación de otros sistemas orgánicos (por ejemplo asma). Debido a su presentación clínica altamente heterogénea, el diagnóstico de FASS puede ser difícil. OBJETIVOS: Se encomendó a un subgrupo del Comité Internacional sobre Enfermedades Alérgicas de los Animales (ICADA) que resumiera la información más actual sobre las presentaciones clínicas de FASS y que desarrollara pautas de diagnóstico recomendadas. MÉTODOS: Se realizaron búsquedas en la red de bases de datos de referencias y resúmenes de reuniones internacionales relacionadas con alergias felinas. Éstos se combinaron con la opinión de expertos cuando fue necesario. RESULTADOS: Se identificaron un total de 107 publicaciones relevantes para esta revisión. La recopilación de estos datos permitió el desarrollo de una descripción detallada de las características clínicas de FASS y el desarrollo de pautas centradas en la eliminación sistemática de otras afecciones de la piel con características clínicas similares. Dado que los dermatólogos utilizan con frecuencia las pruebas de alergia para respaldar un diagnóstico clínico de FASS, también se realizó una breve revisión de estas metodologías. CONCLUSIONES E IMPORTANCIA CLÍNICA: De manera similar a la dermatitis atópica en perros, FASS es un diagnóstico clínico basado en la presencia de signos clínicos compatibles y la exclusión de otras enfermedades con características clínicas similares. La eliminación o exclusión de pulgas/alergia a pulgas, otros parásitos, infecciones y alergia alimentaria es necesaria antes de llegar a un diagnóstico de FASS.}, number={1}, journal={VETERINARY DERMATOLOGY}, author={Mueller, Ralf S. and Nuttall, Tim and Prost, Christine and Schulz, Bianka and Bizikova, Petra}, year={2021}, month={Feb}, pages={43-+} }
 @article{levy_linder_mamo_herrmann_bizikova_2020, title={Cutaneous polyautoimmunity in two unrelated dogs: pemphigus foliaceus and generalized discoid lupus erythematosus}, volume={31}, ISSN={["1365-3164"]}, DOI={10.1111/vde.12851}, abstractNote={Polyautoimmunity, the concurrent expression of two or more distinct autoimmune diseases (ADs) in a single individual, is a known phenomenon in humans and has been rarely reported in dogs. To the best of the authors' knowledge, comorbid pemphigus foliaceus (PF) and generalized discoid lupus erythematosus (GDLE) has not been reported in dogs.To describe the clinical, histological and immunological features and treatment outcome of two unrelated dogs with comorbid PF and GDLE.One 10-year-old, spayed German shepherd dog and one 8-year-old, castrated American Staffordshire terrier presented for evaluation of a symmetrical, facial- and/or pedal-dominant pustular dermatitis with concurrent, truncal scaly plaques.For each dog, clinicopathological characterization included physical examination, lesion cytological evaluation, bacterial culture and sensitivity testing, skin histopathological investigation and direct and indirect immunofluorescence testing. Additional diagnostic imaging and haematological testing was performed to exclude extracutaneous disease.Both dogs exhibited lesions clinically and histologically compatible with PF and GDLE. Moreover, one dog exhibited generalized leucotrichia and chronic superficial keratitis. Remission was achieved with immunosuppressive dosages of prednisolone [high-dose pulse (Case 1) or standard immunosuppressive dosage (Case 2)] and ciclosporin (5-6 mg/kg/day). Tissue-bound antikeratinocyte immunoglobulin (Ig)G and IgM were detected in both dogs. A weak basement membrane zone deposit of C3 was seen in one dog. Circulating antikeratinocyte and anti-desmocollin-1 IgG were detected in one dog.Cutaneous polyautoimmunity can occur in the dog. Depending on the specific disease combinations, overlapping clinical features may present diagnostic and/or therapeutic challenges. Moreover, these cases should be monitored for development of additional cutaneous or extra-cutaneous AD(s).La poly-auto-immunité, l’expression concomitante de deux ou plus de maladies auto-immunes (ADs) chez un même individu est un phénomène connu chez l’homme ; c’est rarement décrit chez le chien. A la connaissance des auteurs, l’association d’un pemphigus foliacé (PF) et d’un lupus érythémateux discoïde (GDLE) n’a pas été décrit chez le chien. HYPOTHÈSES/OBJECTIFS: Décrire les données clinques, histologiques et immunologiques ainsi que l’évolution de deux chiens non liés atteints de PF et GDLE.Une chienne berger allemand stérilisée de 10 ans et un american staffordshire terrier castré de 8 ans présentés en consultation pour une dermatite pustuleuse à dominante faciale/podale symétrique associée à des plaques squameuses tronculaires. MÉTHODES: Pour chaque chien, un examen physique incluait une caractérisation clinicopathologique, une évaluation cytologique, une culture bactériologique et des tests de sensibilité, un examen histopathologique et des tests d’immunofluorescence directes et indirectes. Des test d’imagerie et hématologiques supplémentaires ont été réalisés pour exclure des maladies extra-cutanées. RÉSULTATS: Les deux chiens ont montré des lésions cliniques et histologiques compatibles avec PF et GDLE. En outre, un chien a montré une leucotrichie généralisée et une kératite superficielle chronique. Une rémission a été obtenue avec des doses immunosuppressives de prednisolone [doses élevées pulsées (Cas 1) ou dose immunosuppressive standard (Cas 2)] et ciclosporine (5-6 mg/kg/jour). Des immunoglobulines (Ig)M et IgG antikératinocytes ont été détectées chez les deux chiens. Un dépot faible de C3 au niveau de la membrane basale a été observé chez un chien. Les antikératinocytes circulants et IgG anti-desmocolline 1 ont été détectés chez un chien.La poly-auto-immunité cutanée peut se produite chez le chien. En fonction des combinaisons spécifiques des maladies, un recoupement des lésions cliniques peut représenter un défit diagnostic et/ou thérapeutique. En outre, ces cas devraient être suivis pour le développement d’autres atteintes cutanées ou extracutanées.INTRODUCCIÓN: la poliautoinmunidad, la expresión conjunta de dos o más enfermedades autoinmunes (ADs) distintas en un solo individuo, es un fenómeno conocido en humanos; rara vez se ha reportado en perros. A entender de los autores, pénfigo foliáceo (PF) y lupus eritematoso discoide generalizado (GDLE) no se han reportado en perros en aparición conjunta. HIPÓTESIS/OBJETIVOS: describir las características clínicas, histológicas e inmunológicas y el resultado del tratamiento de dos perros no relacionados con PF y GDLE de aparición conjunta. ANIMALES: un perro pastor alemán castrado de 10 años de edad y un American Staffordshire terrier castrado de 8 años de edad presentados para evaluación de una dermatitis predominantemente pustular simétrica, facial y/o podal y placas escamosas truncales concomitantes. MÉTODOS: en cada perro, la caracterización clínico-patológica incluyó examen físico, evaluación citológica de la lesión, cultivo bacteriano y pruebas de sensibilidad, investigación histopatológica de la piel y pruebas de inmunofluorescencia directa e indirecta. Se realizó un diagnóstico por imagen adicional y una investigación hematológica para excluir enfermedades extracutáneas. RESULTADOS: Ambos perros exhibieron lesiones clínicamente e histológicamente compatibles con PF y GDLE. Además, un perro presentó leucotrichia generalizada y queratitis superficial crónica. La remisión se logró con dosis inmunosupresoras de prednisolona [pulso de dosis alta (caso 1) o dosis inmunosupresora estándar (caso 2)] y ciclosporina (5-6 mg/kg /día). Se detectaron inmunoglobulinas (Ig) G e IgM antiqueratinocitos unidas a tejidos en ambos perros. Se observó un depósito débil de C3 en la membrana basal epidermal en un perro. Se detectaron IgG antiqueratinocitos y anti-desmocollin-1 circulantes en un perro. CONCLUSIONES E IMPORTANCIA CLÍNICA: la poliautoinmunidad cutánea puede ocurrir en el perro. Dependiendo de las combinaciones de enfermedades específicas, las características clínicas superpuestas pueden presentar dificultades diagnósticas y/o terapéuticas. Además, estos casos deben ser controlados por el posible desarrollo de AD(s) cutáneas o extracutáneas adicionales.Die Polyautoimmunität, der momentane Ausdruck für zwei oder mehr unterschiedliche Autoimmunerkrankungen (ADs) in einem einzigen Individuum ist ein bekanntes Phänomen beim Menschen; es wird bei Hunden nur selten beschrieben. Nach bestem Wissen der Autoren, wurde bisher eine Komorbidität von Pemphigus foliaceus (PF) und generalisiertem discoiden Lupus Erythematosus (GDLE) bei Hunden nicht beschrieben.Die Beschreibung der klinischen, histologischen und immunologischen Merkmale und Behandlungserfolge zweier nicht verwandter Hunde mit Komorbidität von PF und GDLE.Eine 10 Jahre alte kastrierte Deutsche Schäferhündin und ein 8 Jahre alter kastrierter American Staffordshire Terrier wurden zur Evaluierung einer symmetrischen, Gesichts und/oder die Füsse-dominierender pustulöser Dermatitis mit gleichzeitigen schuppigen Plaques am Rumpf vorgestellt.Für jeden Hund beinhaltete die klinisch-pathologische Charakterisierung eine physische Untersuchung, eine zytologische Evaluierung der Läsionen, eine Bakterienkultur und Antibiogramm, eine histopathologische Untersuchung der Haut und direkte und indirekte Immunfluoreszenz. Zusätzliche Bildgebende Diagnostik und hämatologische Untersuchungen wurden durchgeführt, um Erkrankungen, die nicht mit der Haut im Zusammenhang standen, auszuschließen.Beide Hunde zeigten Hautveränderungen, die klinisch und histologisch mit PF und GDLE vergleichbar waren. Zusätzlich zeigte ein Hund eine generalisierte Leukotrichie und eine chronische superfizielle Keratitis. Eine Remission wurde mit immunsuppressiven Dosen von Prednisolon [hochdosierte Pulstherapie (Fall 1) oder eine Standard immunsuppressive Dosis (Fall 2)] und Ciclosporin (5-6 mg/kg/Tag) erzielt. An Gewebe gebundene Antikeratinozyten Immunglobulin (Ig) G und IgM wurden bei beiden Hunden gefunden. Eine schwache Ablagerung in der Basalmembran von C3 wurde bei einem Hund gefunden. Bei einem Hund wurden zirkulierende Antikeratinozyten und Anti-Desmocollin-1 IgG festgestellt.Eine kutane Polyautoimmunität kann beim Hund auftreten. Abhängig von den spezifischen Krankheitskombinationen, könnten überlappende klinische Merkmale diagnostische und/oder therapeutische Herausforderungen darstellen. Darüber hinaus sollten diese Erkrankungen auf die Entwicklung zusätzlicher kutaner oder extra-kutaner AD(s) untersucht werden.背景: 単一個体における2つ以上の異なる自己免疫疾患（AD）を同時発現する多発性自己免疫性疾患は、人医療においては既知の現象である。犬ではほとんど報告されていない。著者の知る限り、落葉性天疱瘡（PF）および全身性円板状エリテマトーデス（GDLE）を併発した犬は報告されていない。 仮説/目的: 本研究の目的は、PFとGDLEが併発した血縁のない2頭の犬の臨床的、組織学的、免疫学的特徴と治療成績を説明することであった。 供試動物: 1頭の10歳避妊雌ジャーマン・シェパード・ドッグおよび1頭の8歳去勢雄アメリカン・スタッフォードシャー・テリアが、左右対称性の顔面および/または肢を主要病変とする膿疱性皮膚炎と同時発生した体幹の鱗状局面の評価のため来院した。 方法: 各犬の臨床病理学的特性の評価には、身体検査、病変細胞学的評価、細菌培養および薬剤感受性検査、皮膚組織病理学的検査、直接および間接免疫蛍光検査を含んだ。皮膚以外の疾患を除外するため、追加画像診断および血液学的調査を実施した。 結果: どちらの犬においても、PFおよびGDLEと臨床的および組織学的に適合した病変を示した。さらに、1頭の犬は、全身性白毛症および慢性表在性角膜炎を呈した。免疫抑制量のプレドニゾロン[高用量パルス（症例1）または標準免疫抑制量（症例2）]およびシクロス​​ポリン（5-6 mg / kg /日）によって寛解に至った。組織結合抗ケラチノサイト免疫グロブリン（Ig）GおよびIgMがどちらの犬でも検出された。 C3の基底膜領域における弱い沈着が1頭の犬に認められた。循環抗角化細胞および抗デスモコリン-1 IgGが1頭の犬で検出された。 結論と臨床的重要性: 犬では皮膚自己免疫疾患が起こる。特定の疾患の組み合わせに応じて、重複する臨床的特徴は診断および/または治療上の課題が認められる場合がある。さらに、本症例は皮膚または皮膚以外のADの追加の発生を監視する必要がある。.背景: 多发性自身免疫是已知的人类疾病，一个病患同时表现两种或两种以上不同的自体免疫病 (ADs)；在犬鲜有报道。据作者所知，尚未有过关于犬并发落叶型天疱疮 (PF) 和全身性盘状红斑狼疮 (GDLE) 的报告 。 假设/目的: 描述两只无血缘关系、并发PF和GDLE的犬，报告其临床、组织学和免疫学特征以及治疗效果。 动物: 一只10岁切除卵巢的德国牧羊犬和一只8岁去势的美国斯塔福德郡㹴犬，评估其对称性面部和/或爪部脓疱性皮炎，以及并发的躯干鳞屑性斑块。 方法: 对于每只犬，临床病理学表征包括体格检查、病变细胞学评估、细菌培养和药敏试验、皮肤组织病理学研究以及直接和间接免疫荧光试验。另外进行影像学诊断和血液学检查，以排除皮肤系统外疾病。 结果: 两只犬均表现出与PF和GDLE临床和组织学相符的病变。此外，一只犬表现出全身性白毛病和慢性浅表性角膜炎。使用免疫抑制剂量的泼尼松龙 [高剂量脉冲（病例 1），或标准免疫抑制剂量（病例 2）] 和环孢素（5-6 mg/kg/天）达到缓解。在两只犬身上均检测到组织结合的抗角质细胞免疫球蛋白 (Ig) G 和 IgM。在一只犬身上观察到C3的弱基底膜带沉积。在一只犬身上检测到循环抗角质细胞和抗桥粒糖蛋白-1 IgG。 结论和临床重要性: 皮肤多发性自体免疫可发生在犬身上。根据特定的疾病组合、重叠的临床特征可能带来诊断和/或治疗挑战。此外，应监测这些病例是否发生其他皮肤或皮肤系统外ADs。.A poliautoimunidade, expressão simultânea de duas ou mais doenças autoimunes (DAs) distintas em um único indivíduo, é um fenômeno conhecido em humanos; este raramente é relatado em cães. De acordo com o conhecimento dos autores, ainda não há relatos em cães de pênfigo foliáceo (PF) e o lúpus eritematoso discóide generalizado (GDLE) em comorbidade. HIPÓTESE/OBJETIVOS: Descrever as características clínicas, histológicas e imunológicas e o resultado do tratamento de dois cães não relacionados com PF e GDLE em comorbidade.Um cão pastor alemão de 10 anos, castrado e um American Staffordshire terrier castrado de 8 anos de idade foram apresentados para avaliação de uma dermatite pustular simétrica, predominantemente facial e/ou a podal com placas descamativas concomitantes no dorso. MÉTODOS: Para cada cão, a caracterização clínico-patológica incluiu exame físico, avaliação citológica lesional, cultura bacteriana e teste de sensibilidade, investigação histopatológica da pele e teste direto e indireto de imunofluorescência. Diagnóstico por imagem adicional e investigação hematológica foram realizadas para excluir doença extracutânea.Ambos os cães apresentaram lesões clinica e histologicamente compatíveis com PF e GDLE. Além disso, um cão exibiu leucotriquia generalizada e ceratite superficial crônica. A remissão foi alcançada com dosagens imunossupressoras de prednisolona [pulso de alta dose (Caso 1) ou dosagem imunossupressora padrão (Caso 2)] e ciclosporina (5-6 mg / kg / dia). Detectou-se a presença de imunoglobulina (Ig) anti-queratinócito G e a IgM ligadas ao tecido em ambos os cães. Um depósito fraco de C3 na zona da membrana basal foi observado em um cão. Anticorpos IgG anti-queratinócitos e anti-desmocolina-1 circulantes foram detectados em um cão. CONCLUSÕES E IMPORTÂNCIA CLÍNICA: A poliautoimunidade cutânea pode ocorrer no cão. Dependendo das combinações específicas de doenças, as características clínicas sobrepostas podem apresentar desafios diagnósticos e/ou terapêuticos. Além disso, esses casos devem ser monitorados quanto ao desenvolvimento de Das cutâneas ou extra-cutâneas adicionais.}, number={4}, journal={VETERINARY DERMATOLOGY}, author={Levy, Britt J. and Linder, Keith E. and Mamo, Lisa B. and Herrmann, Ina and Bizikova, Petra}, year={2020}, month={Aug}, pages={325-+} }
 @article{levy_mamo_bizikova_2020, title={Detection of circulating anti-keratinocyte autoantibodies in feline pemphigus foliaceus}, volume={31}, ISSN={["1365-3164"]}, DOI={10.1111/vde.12861}, abstractNote={Circulating anti-keratinocyte immunoglobulin (Ig)G targeting desmosomal proteins have been identified in people and dogs with pemphigus foliaceus (PF). By contrast, detection attempts in PF-affected cats have been largely unsuccessful. To detect circulating anti-keratinocyte autoantibodies in PF-affected cats and determine their titres and tissue-staining patterns. Thirty PF-affected cats were compared to 11 specific-pathogen free, 15 healthy and 31 allergic cats. Sera were tested by indirect immunofluorescence on canine footpad and buccal mucosal substrates. Circulating, anti-keratinocyte IgG with a suprabasilar, web-like (intercellular) pattern were detected in the majority of PF-affected cats (23 of 30, 77%), some allergic cats (six of 31, 19%) and one healthy cat (7%). Both footpad epidermis and buccal mucosa were positive in the majority of seropositive PF-affected cats (21 of 23, 91%), and in only one of six (17%) seropositive allergic cats. Staining was limited to the footpad in the remaining seropositive PF-affected and allergic cats and one seropositive healthy cat. Reciprocal IgG titres were significantly higher in PF-affected cats compared to controls (Dunn’s post-test, P < 0.0001). Anti-keratinocyte IgM, IgA or IgE were not detected in any sera. These results confirm the presence of circulating anti-keratinocyte IgG in a majority of PF-affected cats and in a small percentage of healthy and allergic cats. Although the molecular target and pathogenic nature of the antibodies remains unknown, the detection of positive immunostaining on buccal mucosal tissue, in addition to the footpad, suggests that the major target antigen of feline PF differs from that reported in dogs. Les immunoglobulines circulantes anti-kératinocytes (Ig)G ciblant les protéines desmosomales ont été identifiées chez l’homme et le chien atteint de pemphigus foliacé (PF). En revanche, les essais de détection chez le chat ont été largement inefficaces. Détecter les auto-anticorps anti-kératinocytes circulants chez les chats atteints de PF et déterminer leurs titres et patrons de coloration tissulaires. Trente chats atteints de PF ont été comparés à 11 chats pathogènes spécifiques free, 15 chats sains et 31 chats allergiques. Les sera ont été testé par immunofluorescence indirecte sur les coussinets de chat et sur substrats de muqueuse buccale. Les IgG anti-kératinocytes circulants avec patron intercellulaire, suprabasal ont été détectés dans la majorité des chats atteints de PF (23 sur 30, 77%), certains chats allergiques (six sur 31, 19%) et un chat sain (7%). L’épiderme des coussinets et muqueuse buccale étaient positifs dans la majorité des chats PF séropositifs (21 sur 23, 91%), et pour seulement un sur six (17%) chats allergiques séropositifs. La coloration était limitée aux coussinets pour les chats PF et allergiques séropositifs restants, et un chat séropositif sain. Les titres d’IgG inversés étaient significativement plus élevés chez les chats atteints de PF comparé aux contrôles (Dunn’s post-test, P < 0.0001). Les IgM, IgA ou IgE anti-kératinocytes n’ont été détectés pour aucun des sera. Ces résultats confirment la présence d’IgG anti-kératinocytes circulants dans la majorité des chats atteints de PF, et dans un petit pourcentage de chats sains et allergiques. Bien que la cible moléculaire et la nature pathogénique des anticorps restent inconnues, la détection d’immunomarquages positifs sur la muqueuse buccale, en plus des coussinets, suggère que le principal antigène cible du PF félin diffère de ceux identifiés chez le chien. se han identificado inmunoglobulinas anti-queratinocitos (Ig) G circulantes dirigidas a proteínas desmosomales en personas y perros con pénfigo foliáceo (PF). Por el contrario, los intentos de detección en gatos afectados por PF no han tenido éxito. Detectar autoanticuerpos anti-queratinocitos circulantes en gatos afectados por PF y determinar sus títulos y patrones de tinción de tejidos. se compararon treinta gatos afectados por PF con 11 gatos libres de patógenos específicos, 15 gatos sanos y 31 alérgicos. los sueros se probaron por inmunofluorescencia indirecta en sustratos de almohadilla canina y de la mucosa bucal. en la mayoría de los gatos afectados por PF (23 de 30, 77%), algunos gatos alérgicos (seis de 31, 19%) y un gato sano (7%) se detectaron IgGs circulantes anti-queratinocitos con un patrón suprabasilar reticular (intercelular) Tanto la epidermis de la almohadilla plantar como la mucosa bucal fueron positivas en la mayoría de los gatos seropositivos afectados por PF (21 de 23, 91%), y solo en uno de seis (17%) gatos alérgicos seropositivos. La tinción se limitó a la almohadilla plantar en el resto de gatos seropositivos y alérgicos y en un gato seropositivo sano. Los títulos de IgG recíproca fueron significativamente mayores en los gatos afectados por PF en comparación con los controles (prueba posterior de Dunn, P <0,0001). No se detectaron IgM, IgA o IgE anti-queratinocitos en ningún suero. estos resultados confirman la presencia de IgG anti-queratinocitos circulantes en la mayoría de los gatos afectados por PF y en un pequeño porcentaje de gatos sanos y alérgicos. Aunque el objetivo molecular y la naturaleza patogénica de los anticuerpos siguen siendo desconocidos, la detección de inmunotinción positiva en el tejido de la mucosa bucal, además de la almohadilla del pie, sugiere que el antígeno diana principal del PF felino difiere del identificado en los perros. Zirkulierende Anti-Keratinozyten Immunglobulin (Ig) G, die auf desmosomale Proteine abzielen, wurden bei Menschen und Hunden mit Pemphigus foliaceus (PF) identifiziert. Im Kontrast dazu waren Versuche, diese bei PF-erkrankten Katzen zu bestimmen, weitgehend erfolglos. Eine Bestimmung zirkulierender Anti-Keratinozyten Autoantikörper bei PF-erkrankten Katzen und eine Bestimmung ihrer Titer und ihrer Färbemuster im Gewebe. Dreißig PF-erkrankte Katzen wurden mit 11 spezifisch pathogenfreien, 15 gesunden und 31 allergischen Katzen verglichen. Die Sera wurden mittels indirekter Immunfluoreszenz an den caninen Fussballen und an Substrat von Wangenschleimhaut getestet. Zirkulierende, anti-Keratinozyten IgG mit einem suprabasalen, Netz-ähnlichen (interzellulärem) Muster wurden bei der Mehrheit der PF-erkrankten Katzen (23 von 30, 77%), einigen allergischen Katzen (sechs von 31, 19%) und einer gesunden Katze (7%) gefunden. Es war sowohl die Epidermis der Fussballen wie auch die Wangenschleimhaut bei der Mehrheit der seropositiven PF-erkrankten Katzen (21 von 23, 91%) und nur bei einer von sechs (17%) der seropositiven allergischen Katzen positiv. Die Färbung war bei den übrigen seropositiven PF-erkrankten Katzen und einer seropositiven gesunden Katze auf die Fussballen limitiert. Reziproke IgG Titer lagen bei den PF-erkrankten Katzen und bei einer seropositiven gesunden Katze signifikant höher (Dunn´s Post-Test, P < 0,0001). Anti-Keratinozyten IgM, IgA oder IgE konnten in den Sera nicht gefunden werden. Diese Ergebnisse bestätigen das Auftreten von zirkulierenden Anti-Keratinozyten IgG bei der Mehrheit der PF-betroffenen Katzen, sowie bei einem kleinen Prozentsatz von gesunden und allergischen Katzen. Obwohl das molekulare Ziel und die pathogene Natur der Antikörper unbekannt bleibt, deutet der Nachweis von positiver Immunfärbung des Gewebes der Wangenschleimhaut, zusätzlich zu jenem der Fussballen darauf hin, dass das hauptsächliche Zielantigen für den felinen PF sich von jenem der Hunde unterscheidet. デスモソームタンパクを標的とする循環抗ケラチノサイト免疫グロブリン（Ig）Gは、落葉状天疱瘡（PF）に罹患した人および犬で確認されている。対照的に、PF罹患猫での検出の試みは、大部分が失敗している。 本研究の目的は、PF罹患猫の循環抗ケラチノサイト自己抗体を検出し、その力価および組織染色パターンを決定することであった。 30頭のPF罹患猫は、特定病原菌を含まない猫11頭、健常猫15頭、アレルギー猫31頭と比較された。 血清は、犬の肉球および頬粘膜の基質に対する間接免疫蛍光法によってテストされた。 PF罹患猫の大多数（30頭のうち23頭、77％）、一部のアレルギー猫（31頭のうち6頭、19％）および健常猫1頭（7％）で、基底層上のクモの巣様（細胞間）パターンを持つ循環抗ケラチノサイトIgGが検出された。血清反応陽性のPF罹患猫の大部分（23頭中21頭、91％）、および血清反応陽性のアレルギー猫の6頭うち1頭（17％）だけが肉球表皮および頬粘膜の両方とも陽性であった。染色は、残りの血清陽性PF罹患アレルギー猫、および1頭の血清陽性健常猫の肉球に限定されていた。相互IgG力価は、コントロールと比較してPF罹患猫で有意に高かった（ダンの事後テスト、P <0.0001）。抗ケラチノサイトIgM、IgAまたはIgEはどの血清からも検出されなかった。 これらの結果は、PF罹患猫の大多数、健常およびアレルギー猫のごく一部に循環抗ケラチノサイトIgGの存在を確認している。抗体の分子標的および病原性の性質は不明のままであるが、肉球に加え頬粘膜組織での免疫染色の陽性検出は、猫PFの主要な標的抗原が犬で同定されたものとは異なることを示唆している。 循环抗角质细胞免疫球蛋白 (Ig) G 靶向桥粒蛋白，已在落叶型天疱疮 (PF) 病人和患犬中确定。相比之下，在PF患猫中的检测尝试基本上未能实现。 检测PF患猫中的循环抗角质细胞自身抗体，并确定其滴度和组织染色模式。 将30只PF患猫与11只无特定病原体、15只健康和31只过敏猫进行比较。 通过间接免疫荧光法在犬爪垫和口腔粘膜基质上检测血清。 在大多数PF患猫 (23/30，77%)、一些过敏猫 (6/31，19%) 和1只健康猫 (7%) 中，检测到具有基底上、网状（细胞间）模式的循环抗角质细胞IgG。大多数血清阳性PF猫 (21/23，91%) 的爪垫表皮和口腔粘膜均为阳性，6只血清阳性过敏猫中仅1只 (17%) 为阳性。在其余血清阳性PF猫和过敏猫以及1只血清阳性健康猫中，染色仅限于爪垫。与对照组相比，PF猫中的 IgG 滴度倒数显著较高（Dunn后检验，P<0.0001）。血清中均未检出抗角质细胞IgM、IgA或IgE。 这些结果证实了大多数PF猫以及一小部分健康和过敏猫，存在循环抗角质细胞IgG。尽管抗体的分子靶点和致病性质仍不清楚，但除爪垫外，口腔粘膜组织免疫染色阳性的检测表明，猫PF的主要靶抗原与在犬中鉴定的不同。 Imunoglobulinas (Ig) G circulantes anti-queratinócitos direcionadas a proteínas desmossômicas foram identificadas em pessoas e cães com pênfigo foliáceo (PF). Por outro lado, as tentativas de detecção das mesmas em gatos afetados por PF não foram bem-sucedidas. Detectar auto-anticorpos anti-queratinócitos circulantes em gatos afetados por PF e determinar seus títulos e padrões de coloração de tecidos. Trinta gatos afetados por PF foram comparados com 11 gatos livres de patógenos específicos, 15 saudáveis ​​e 31 alérgicos. Os soros foram testados por imunofluorescência indireta em substratos de coxins e mucosa oral de caninos. Detectou-se IgG anti-queratinócitos circulantes com padrão suprabasilar, com distribuição em rede (intercelular) na maioria dos gatos afetados por PF (23 de 30, 77%), alguns gatos alérgicos (seis de 31, 19%) e um gato saudável (7%). Tanto a epiderme dos coxins como a mucosa oral foram positivas na maioria dos gatos soropositivos afetados por PF (21 de 23, 91%) e em apenas um dos seis (17%) gatos alérgicos soropositivos. A coloração foi limitada aos coxins no restante dos gatos alérgicos e afetados por PF soropositivos e em um gato soropositivo saudável. Os títulos de IgG recíprocos foram significativamente maiores em gatos afetados por PF em comparação aos controles (pós-teste de Dunn, P <0,0001). Não foram detectados anticorpos anti-queratinócitos do tipo IgM, IgA ou IgE em nenhum soro. Esses resultados confirmam a presença de IgG anti-queratinócitos circulantes na maioria dos gatos afetados por PF e em uma pequena porcentagem de gatos saudáveis ​​e alérgicos. Embora o alvo molecular e a natureza patogênica dos anticorpos permaneçam desconhecidos, a detecção de imunocoloração positiva no tecido da mucosa oral, além de coxins, sugere que o principal antígeno alvo do PF felino difere do identificado em cães. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.}, number={5}, journal={VETERINARY DERMATOLOGY}, author={Levy, Britt J. and Mamo, Lisa B. and Bizikova, Petra}, year={2020}, month={Oct}, pages={378-+} }
 @article{mowat_avelino_bowyer_parslow_westermeyer_foster_fogle_bizikova_2020, title={Detection of circulating anti-retinal antibodies in dogs with sudden acquired retinal degeneration syndrome using indirect immunofluorescence: A case control study}, volume={193}, ISSN={["1096-0007"]}, DOI={10.1016/j.exer.2020.107989}, abstractNote={Sudden acquired retinal degeneration syndrome (SARDS) in dogs is proposed to have an immune-mediated etiology. However, there is conflicting evidence regarding the presence of antiretinal antibodies, as assessed by western blotting, in the serum of SARDS patients. Because of the possibility that antibodies recognize only conformational epitopes, we hypothesized that a more sensitive method to investigate circulating retinal autoantibodies in SARDS is immunofluorescence. Sera from 14 dogs with early SARDS, and 14 age- and breed-matched healthy control dogs were screened for circulating antiretinal IgG, IgM, IgE and IgA using indirect immunofluorescence on lightly fixed frozen sections of normal canine retina. Controls without canine serum were also performed. A nuclear counterstain was used to identify cellular retinal layers. Images were obtained using a fluorescence microscope, and 2-3 separate masked observers graded retinal layers for fluorescence staining intensity using a 0–3 scale. Total circulating IgG and IgM was assessed by radial immunodiffusion. Statistical analysis was performed using 2-way ANOVA, paired 2-tailed student's t-test and correlation analysis. Intensity of IgG staining of photoreceptor outer segments was significantly higher using serum from dogs with SARDS compared with healthy controls in 2/3 observers (P < 0.05). Intensity of IgM staining throughout the retina was higher in SARDS dogs compared to matched healthy controls (P < 0.0001), although no specific retinal layer was statistically significant. There were no differences in staining intensity for IgE or IgA. Dogs with SARDS had a comparably lower circulating IgG and higher IgM than healthy controls (P = 0.01 and 0.001 respectively) and IgG and IgM were negatively correlated (r = −0.69, P = 0.007). Despite having decreased serum IgG compared with healthy controls, circulating IgG in dogs with SARDS binds photoreceptor outer segments to a greater extent. Dogs with SARDS have a relatively higher circulating IgM than matched healthy controls. The pathogenic nature of these antibodies is unknown.}, journal={EXPERIMENTAL EYE RESEARCH}, author={Mowat, Freya M. and Avelino, Janelle and Bowyer, Ashley and Parslow, Vanessa and Westermeyer, Hans D. and Foster, Melanie L. and Fogle, Jonathan E. and Bizikova, Petra}, year={2020}, month={Apr} }
 @article{goodale_varjonen_outerbridge_bizikova_borjesson_murrell_bisconte_francesco_hill_masjedizadeh_et al._2020, title={Efficacy of a Bruton's Tyrosine Kinase Inhibitor (PRN-473) in the treatment of canine pemphigus foliaceus}, volume={31}, ISSN={["1365-3164"]}, DOI={10.1111/vde.12841}, abstractNote={Bruton's tyrosine kinase (BTK) is important in B-cell signalling. Efficacy has been reported for BTK inhibitors (BTKi) in human autoimmune diseases. Canine pemphigus foliaceus (cPF) is the most common canine autoimmune skin disease.To determine the safety and efficacy of a BTKi in cPF treatment.Nine privately owned dogs.Nine dogs diagnosed with PF were administered BTKi PRN473. Initial dosages were ≈15 mg/kg once daily, increased to twice daily if inadequate response was seen. Treatment continued for a maximum of 20 weeks, attempting decrease to every other day. Dogs were monitored with complete blood counts, serum biochemistry panels, urinalyses and evaluated with a modified version of a validated human Pemphigus Disease Activity Index (cPDAI). Anti-desmocollin-1 (DSC-1) and desmoglein-1 (DSG-1) immunoglobulin G (IgG) titres were performed before and after the treatment period. Drug bound to target was measured in peripheral blood mononuclear cells.All nine dogs showed reduction in lesions and cPDAI score during the first two weeks of treatment. At the end of the study, four responses were considered "good", two "fair", two "poor" and one dog withdrawn due to recurrence of a previously excised mast cell tumour. Four dogs continued to improve by Week 4; three sustained near complete remission by study's end. The anti-DSC-1 IgG titre decreased in three dogs, increased in two, was undetected in three and was not performed in the withdrawn dog. No dogs had detectable IgG to DSG1. Possible adverse effects occurred in three dogs.Bruton's tyrosine kinase inhibitor monotherapy may have beneficial effects in some cases of cPF.La BTK (Bruton's tyrosine kinase) est une voie importante d'activation des cellules B. L'efficacité a été rapportée pour les inhibiteurs de BTK (BTKi) dans les maladies auto-immunes de l'homme. Le pemphigus foliacé du chien (cPF) est la dermatite auto-immune la plus fréquente du chien.Déterminer l'efficacité et l'innocuité d'un BTKi dans le traitement d'un cPF.Neufs chiens de propriétaires. MATÉRIELS ET MÉTHODES: Neuf chiens diagnostiqués avec PF ont reçu du BTKi PRN473. Les doses initiales étaient ≈15 mg/kg une fois par jour, augmenté à deux fois par jour si une réponse inadéquate était observée. Le traitement était poursuivi au maximum 20 semaines, tentant de réduire à jours alternés. Les chiens étaient monitorés par une formule sanguine, un profil biochimique, une analyse urinaire et évalués par une version modifiée de cPDAI (Pemphigus Disease Activity Index) validée chez l'homme. Les concentrations d'immunoglobuline G (IgG) anti-desmocolline-1 (DSC-1) et desmogléine-1 (DSG-1) ont été réalisées avant et après traitement. Le portage de la molécule à sa cible a été mesuré dans les cellules mononuclées sanguines périphériques. RÉSULTATS: Tous les neuf chiens ont montré une diminution des lésions et du score cPDAI au cours des deux premières semaines de traitement. A la fin de l’étude, quatre réponses ont été considérées comme « bonnes », deux « moyennes, deux « faibles » et un chien a été retiré en raison d'une récidive d'un mastocytome précédemment retiré. Quatre chiens ont continué à s'améliorer jusqu’à la semaine 4 ; trois étaient presque en rémission complète à la fin de l’étude. La concentration d'IgG anti-DSC-1 a diminué pour trois chiens, augmenté pour deux et était non détectable pour trois et n'a pas été réalisée pour le chien exclu. Aucun chien n'avait d'IgG détectable pour DSG1. Les effets secondaires se sont produits chez trois chiens.Le traitement unique par inhibiteur de tyrosine kinase de Bruton pourrait avoir des effets bénéfiques pour certains cas de cPF.INTRODUCCIÓN: la tirosina quinasa (BTK) de Bruton es importante en las señales de células B. Se ha informado de resultados beneficiosos de los inhibidores de BTK (BTKi) en enfermedades autoinmunes humanas. El pénfigo foliáceo canino (cPF) es la enfermedad cutánea autoinmune canina más común. OBJETIVOS: Determinar la seguridad y eficacia de un BTKi en el tratamiento de cPF. ANIMALES: Nueve perros de propietarios particulares. MÉTODOS Y MATERIALES: nueve perros diagnosticados con PF recibieron BTKi PRN473. Las dosis iniciales fueron de ≈ 15 mg/kg una vez al día, aumentadas a dos veces al día si se observaba una respuesta inadecuada. El tratamiento continuó durante un máximo de 20 semanas, intentando disminuirlo cada dos días. Los perros fueron evaluados con recuentos sanguíneos completos, paneles de bioquímica en suero, análisis de orina y una versión modificada de un índice de actividad validado de la enfermedad del pénfigo humano (cPDAI). Los títulos de inmunoglobulina G (IgG) de anti-desmocolina-1 (DSC-1) y desmogleína-1 (DSG-1) se analizaron antes y después del período de tratamiento. La cantidad de fármaco unido a su diana se midió en células mononucleares de sangre periférica. RESULTADOS: los nueve perros mostraron una reducción en las lesiones y de los valores de cPDAI durante las primeras dos semanas de tratamiento. Al final del estudio, cuatro respuestas se consideraron “buenas”, dos “aceptables”, dos “pobres” y un perro fue retirado debido a la recidiva de un mastocitoma previamente extirpado. Cuatro perros continuaron mejorando en la semana 4; y tres mostraron una remisión casi completa al final del estudio. El título de IgG anti-DSC-1 disminuyó en tres perros, aumentó en dos, no se detectó en tres y no se realizó en el perro retirado. Ningún perro tenía IgG detectable a DSG1. Posibles efectos adversos se observaron en tres perros. CONCLUSIONES E IMPORTANCIA CLÍNICA: la monoterapia con el inhibidor de la tirosina quinasa de Bruton puede tener efectos beneficiosos en algunos casos de cPF.Die Bruton Tyrosinkinase (BTK) spielt beim Signalweg der B-Zellen eine wichtige Rolle. Von der Wirksamkeit der BTK Inhibitoren (BTKi) bei Autoimmunerkrankungen des Menschen wurde bereits berichtet. Pemphigus foliaceus beim Hund (cPF) ist die häufigste autoimmune Hauterkrankung des Hundes.Feststellung der Sicherheit und Wirksamkeit eines BTKi bei der Behandlung des cPF.Neun Hunde in Privatbesitz.Neun Hunden, die mit PF diagnostiziert worden waren, wurde BTKi PRN473 verabreicht. Anfangsdosen waren ≈ 15 mg/kg einmal täglich, bei einer unzureichenden Antwort wurde eine Erhöhung auf zweimal täglich durchgeführt. Die Behandlung wurde für ein Maximum von 20 Wochen fortgeführt, wobei eine Dosisreduktion auf jeden zweiten Tag versucht wurde. Die Hunde wurden mit Blutbild, Serumbiochemie, Urinanalyse überwacht und wurden mit einer modifizerten Version eines validierten humanen Pemphigus Disease Activity Index (cPDAI) evaluiert. Es wurden Immunglobulin-G (IgG)-Titer auf Anti-Desmocollin-1 (DSC-1) und Desmoglein-1 (DSG-1) vor und nach einer jeden Behandlungsperiode bestimmt. Der Wirkstoff, welcher an das Target gebunden war, wurde in den peripheren Blutmononuklearzellen bestimmt.Alle neun Hunde zeigten eine Verminderung ihrer Läsionen und des cPDAI Werts während der ersten zwei Wochen der Behandlung. Am Ende der Studie wurden vier Hunde als „gut“, zwei als „moderat“, zwei als „geringgradig“ und zwei als „schlecht“ eingestuft, ein Hund wurde aufgrund eines wiederaufgetretenen, zuvor entfernten, Mastzelltumors aus der Studie genommen. Vier Hunde verbesserten sich weiterhin bis zur Woche 4; bei dreien bestand eine fast vollständige Remission zu Studienende. Der Anti-DSC-1 IgG Titer nahm bei drei Hunden ab, bei zwei Hunden zu, konnte bei drei weitere Hunden nicht bestimmt werden und wurde bei dem ausgefallenen Hund nicht bestimmt. Keiner der Hunde hatte feststellbare IgG gegenüber DSG1. Mögliche Nebenwirkungen traten bei drei Hunden auf.Eine Bruton Tyrosinkinase-Inhibitor Monotherapie könnte günstige Auswirkungen auf einige Fälle von cPF bei Hunden haben.背景: ブルトン型チロシンキナーゼ(BTK)はB細胞シグナル伝達において重要である。人の自己免疫性疾患においてBTK阻害剤(BTKi)の有効性が報告されている。犬の落葉状天疱瘡(cPF)は、最も一般的な犬の自己免疫性皮膚疾患である。 目的: 本研究の目的は、cPF治療におけるBTKiの安全性と有効性を決定することである。 供試動物: 9頭の飼育犬。 材料と方法: PFと診断した9頭の犬にBTKi PRN473を投与した。初期用量は1日1回≈15mg / kgであったが、反応が不十分な場合は1日2回に増量した。治療は最大20週間継続し、1日おきの減量を試みた。犬を、全血球計算、血清生化学パネル、尿検査でモニターし、検証済みの人天疱瘡疾患活動性指数(cPDAI)の修正版で評価した。治療期間の前後で、抗デスモコリン-1(DSC-1)およびデスモグレイン-1(DSG-1)免疫グロブリンG(IgG)力価を測定した。標的に結合した薬物を、末梢血単核細胞で測定した。 結果: 9頭すべての犬が、治療の最初の2週間で病変とcPDAIスコアの減少を認めた。研究終了時に4頭が「良」、2頭が「可」、2頭が「不良」とみなし、1頭が以前に切除されたマスト細胞腫瘍の再発により離脱した。 4頭の犬は4週目まで改善し続けた。 3頭は研究終了時までにほぼ完全寛解を維持した。抗DSC-1 IgG力価は3頭の犬で減少し、2頭で増加し、3頭で検出されず、離脱した犬では実施されなかった。 DSG1に対するIgGは検出されなかった。 3頭の犬で副作用の可能性が生じた。 結論と臨床的重要性: ブルトン型チロシンキナーゼ阻害剤の単独療法は、cPFのいくつかの症例で有益な効果をもたらす可能性がある。.背景: Bruton酪氨酸激酶 (BTK) 在B细胞信号转导中很重要。已报告BTK抑制剂(BTKi)在人类自身免疫性疾病中的疗效。犬落叶型天疱疮(cPF)是最常见的犬自身免疫性皮肤病。 目的: 确定BTKi治疗cPF 的安全性和疗效。 动物: 9只私家犬。 方法和材料: 对诊断为PF的9只犬给予BTKi PRN473。初始剂量约为15mg/kg,每日一次,如果观察到反应不足,则增加至每日两次。治疗最长持续20周,尝试降低到隔日一次。通过全血细胞计数、血清生化全项、尿分析对犬进行监测,并使用改良版本的经验证的人天疱疮疾病活动指数(cPDAI)进行评估。在治疗期前后进行抗桥粒糖蛋白-1(DSC-1)和桥粒芯蛋白-1(DSG-1)免疫球蛋白G(IgG)滴度检测。在外周血单核细胞中检测与靶点结合的药物。 结果: 在治疗前两周,所有9只犬均显示病变和cPDAI评分减少。研究结束时,认为4例缓解为“良好”,2例为“一般”,2例为“较差”,1只犬因既往切除的肥大细胞瘤复发而退出研究。4只犬在第4周时持续改善;3只犬在研究结束时持续接近完全缓解。3只犬的抗 DSC-1 IgG滴度降低,2只犬的抗 DSC-1 IgG滴度升高,3只犬中未检测到,退出犬中未进行检测。所有犬均未检出DSG1 IgG。3只犬可能发生不良反应。 结论和临床重要性: Bruton酪氨酸激酶抑制剂单药治疗可能对某些cPF病例有益。.A tirosina quinase de Bruton (BTK) é importante na sinalização de células B. Tem sido relatada em humanos a eficácia de inibidores da BTK (BTKi) em doenças autoimunes. O pênfigo foliáceo canino (cPF) é a doença de pele autoimune canina mais comum.Determinar a segurança e a eficácia de um BTKi no tratamento de cPF.Nove cães de propriedade privada. MÉTODOS E MATERIAIS: Nove cães diagnosticados com PF receberam BTKi PRN473. As doses iniciais foram de ≈ 15 mg / kg uma vez ao dia, e aumentadas para duas vezes ao dia caso fosse observada resposta inadequada. O tratamento foi mantido por no máximo 20 semanas, tentando reduzir para dias alternados. Os cães foram monitorados com hemograma, painéis de bioquímica sérica, urinálise e avaliados com uma versão modificada de um Índice de Atividade de Doença do Pênfigo Humano validado (cPDAI). Os títulos de imunoglobulina G (IgG) anti-desmocolina-1 (DSC-1) e desmogleina-1 (DSG-1) foram realizados antes e após o período de tratamento. O fármaco ligado ao alvo foi medido em células mononucleares do sangue periférico.Todos os nove cães apresentaram redução nas lesões e escore de cPDAI durante as duas primeiras semanas de tratamento. No final do estudo, quatro respostas foram consideradas “boas”, duas “justas”, duas “ruins” e um cão foi retirado devido à recorrência de um mastocitoma previamente extirpado. Quatro cães continuaram a melhorar na semana 4; três apresentaram remissão quase completa até o final do estudo. O título de IgG anti-DSC-1 diminuiu em três cães, aumentou em dois, não foi detectado em três e não foi realizado no cão retirado. Nenhum cão apresentou IgG detectável para DSG1. Possíveis efeitos adversos ocorreram em três cães. CONCLUSÕES E IMPORTÂNCIA CLÍNICA: A monoterapia com inibidores de tirosina quinase de Bruton pode ter efeitos benéficos em alguns casos de cPF.}, number={4}, journal={VETERINARY DERMATOLOGY}, author={Goodale, Elizabeth C. and Varjonen, Katarina E. and Outerbridge, Catherine A. and Bizikova, Petra and Borjesson, Dori and Murrell, Dedee F. and Bisconte, Angelina and Francesco, Michelle and Hill, Ronald J. and Masjedizadeh, Mohammad and et al.}, year={2020}, month={Aug}, pages={291-+} }
 @article{anderson_kol_bizikova_stapelton_ford_villarreal_jimenez_vasilatis_murphy_2020, title={Immunopathogenesis of canine chronic ulcerative stomatitis}, volume={15}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0227386}, abstractNote={Canine Chronic Ulcerative Stomatitis is a spontaneously occurring inflammatory disease of the oral mucosa. An immune-mediated pathogenesis is suspected though not yet proven. We have recently reported on the clinical and histologic features, and identification of select leukocyte cell populations within the lesion. A clinical and histologic similarity to oral lichen planus of people was proposed. In the present study, these initial observations are extended by examining lesions from 24 dogs with clinical evidence of chronic ulcerative stomatitis. Because dogs with chronic ulcerative stomatitis often have concurrent periodontal disease, we wondered if dental plaque/biofilm may be a common instigator of inflammation in both lesions. We hypothesized that dogs with chronic ulcerative stomatitis would exhibit a spectrum of pathologic changes and phenotype of infiltrating leukocytes that would inform lesion pathogenesis and that these changes would differ from inflammatory phenotypes in periodontitis. Previously we identified chronic ulcerative stomatitis lesions to be rich in FoxP3+ and IL17+ cells. As such, we suspect that these leukocytes play an important role in lesion pathogenesis. The current study confirms the presence of moderate to large numbers of FoxP3+ T cells and IL17+ cells in all ulcerative stomatitis lesions using confocal immunofluorescence. Interestingly, the majority of IL17+ cells were determined to be non-T cells and IL17+ cell frequencies were negatively correlated with severity on the clinical scoring system. Three histologic subtypes of ulcerative stomatitis were determined; lichenoid, deep stomatitis and granulomatous. Periodontitis lesions, like stomatitis lesions, were B cell and plasma cell rich, but otherwise differed from the stomatitis lesions. Direct immunofluorescence results did not support an autoantibody-mediated autoimmune disease process. This investigation contributes to the body of literature regarding leukocyte involvement in canine idiopathic inflammatory disease pathogenesis.}, number={1}, journal={PLOS ONE}, author={Anderson, J. G. and Kol, A. and Bizikova, P. and Stapelton, B. P. and Ford, K. and Villarreal, A. and Jimenez, R. J. and Vasilatis, D. and Murphy, B. G.}, year={2020}, month={Jan} }
 @article{goodale_white_bizikova_borjesson_murrell_bisconte_francesco_hill_masjedizadeh_nunn_et al._2020, title={Open trial of Bruton's tyrosine kinase inhibitor (PRN1008) in the treatment of canine pemphigus foliaceus}, volume={31}, ISSN={["1365-3164"]}, DOI={10.1111/vde.12878}, abstractNote={Bruton's tyrosine kinase (BTK) is important in B-cell signalling. Efficacy has been reported for BTK inhibitors (BTKi) in human autoimmune diseases. Canine pemphigus foliaceus (cPF) is one of the most common canine autoimmune skin diseases.To determine the safety and efficacy of the BTKi PRN1008 in the treatment of cPF.Four privately owned dogs.Four dogs diagnosed with PF were administered BTKi PRN1008. Initial dosages approximated to 15 mg/kg once daily, increased to twice daily if inadequate response was seen. Treatment continued for 20 weeks, attempting to decrease to every other day. Dogs were monitored with complete blood counts, serum biochemistry panels and urinalyses, and evaluated with a modified version of a validated human Pemphigus Disease Activity Index (cPDAI). Serum anti-desmocollin-1 (DSC-1) and desmoglein-1 (DSG-1) immunoglobulin (Ig)G titres were performed before and after the treatment period. Drug bound to target was measured in peripheral blood mononuclear cells (PBMC).All four dogs showed reduction in lesions and cPDAI score during the first two weeks of treatment. Three dogs continued to improve and sustained near complete remission by 20 weeks, at which point three responses were considered "good" and one "fair". Final daily dosages were in the range 17-33 mg/kg. Anti-DSC-1 IgG titre decreased dramatically in one dog, was undetectable in two and was uninterpretable in one dog. No dogs had detectable IgG to DSG1. A possible adverse event occurred in one dog.BTKi PRN1008 monotherapy may have some beneficial effects in some cases of cPF.La BTK (Bruton’s tyrosine kinase) est une importante voie de signal des cellules B. L'efficacité des inhibiteurs de BTK (BTKi) a été rapportée dans les maladies auto-immunes chez l'homme. Le pemphigus foliacé (cPF) est la dermatose auto-immune la plus fréquente chez le chien.Déterminer l'innocuité et l'efficacité de BTKi PRN 1008 dans le traitement de cPF.Quatre chiens de propriétaires. MATÉRIELS ET MÉTHODES: Quatre chiens diagnostiqués PF ont reçus BTKi PRN 1008. Les doses initiales étaient approximativement de 15 mg/kg une fois par jour, augmenté à deux fois par jour si une réponse inadéquate était observée. Le traitement a été poursuivi pendant 20 semaines, avec essai de diminution à un jour sur deux. Les chiens ont été suivis avec une numération formule, biochimie complète et analyses urinaires et évalués avec une version modifiée de cPDAI (human Pemphigus Disease Activity Index). Les titres d'immunoglobulines (Ig) G anti-desmocolline 1 (DSC-1) et desmogléine-1 (DSG-1) ont été réalisés avant et après traitement. Le médicament lié à la cible a été mesuré dans les cellules mononuclées sanguines périphériques (PBMC). RÉSULTATS: Les quatre chiens ont montré une diminution des lésions et du score cPDAI au cours des deux premières semaines de traitement. Trois chiens ont continués à s'améliorer jusqu'à guérison presque complète à la semaine 20, à chaque point, trois réponses ont été considérées "bonne" et une "faible". Les dosages quotidiens finaux étaient dans les valeurs 17-33 mg/kg. Les titres d'IgG anti-DSC-1 ont diminués drastiquement chez un chien, étaient non détectable pour deux et étaient non interprétable pour un chien. Aucun chien n'avait d'IgG détectable à DSG1. Un effet indésirable possible a été observé chez un chien.BTK1 PRN 1008 en monothérapie pourrait avoir des effets bénéfiques dans certains cas de cPF.INTRODUCCIÓN: la tirosina quinasa de Bruton (BTK) es importante en las señales celulares de linfocitos B. Se ha publicado acerca de la eficacia de los inhibidores de BTK (BTKi) en enfermedades autoinmunes humanas. El pénfigo foliáceo canino (cPF) es una de las enfermedades cutáneas autoinmunes caninas más comunes. OBJETIVOS: Determinar la seguridad y eficacia del BTKi PRN1008 en el tratamiento de cPF. ANIMALES: cuatro perros de propietarios particulares. MÉTODOS Y MATERIALES: cuatro perros diagnosticados con PF recibieron BTKi PRN1008. Las dosis iniciales fueron de aproximadamente 15 mg/kg una vez al día, que se aumentaron a dos veces al día si se observaba una respuesta inadecuada. El tratamiento continuó durante 20 semanas, intentando disminuir a cada dos días. Los perros fueron evaluados con recuentos sanguíneos completos, paneles de bioquímica sérica y análisis de orina, y valorados con una versión modificada de un índice de actividad de la enfermedad del pénfigo humano validado (cPDAI). Los títulos séricos de inmunoglobulina (Ig)G anti-desmocolina-1 (DSC-1) y desmogleina-1 (DSG-1) se realizaron antes y después del período de tratamiento. El fármaco unido a la proteína diana se midió en células mononucleares de sangre periférica (PBMC). RESULTADOS: los cuatro perros mostraron una reducción en las lesiones y del valor de cPDAI durante las primeras dos semanas de tratamiento. Tres perros continuaron mejorando y mantuvieron una remisión casi completa a las 20 semanas, momento en el que tres respuestas se consideraron "buenas" y una "regular". Las dosis diarias finales estuvieron en el rango de 17-33 mg/kg. El título de IgG anti-DSC-1 disminuyó drásticamente en un perro, fue indetectable en dos y no fue interpretable en un perro. Ningún perro tenía IgG detectable a DSG1. Un posible evento adverso ocurrió en un perro. CONCLUSIONES E IMPORTANCIA CLÍNICA: la monoterapia con BTKi PRN1008 puede tener algunos efectos beneficiosos en algunos casos de cPF.Die Bruton Tyrosinkinase (BTK) ist wichtig bei der Signalgebung von B-Zellen. Bei Autoimmunerkrankungen des Menschen wurde bereits eine Wirksamkeit für BTK Inhibitoren (BTKi) beschrieben. Der Pemphigus foliaceus (cPF) des Hundes ist eine der häufigsten caninen Autoimmunerkrankungen.Eine Bestimmung der Sicherheit und der Wirksamkeit der BTKi PRN1008 bei der Behandlung des cPF.Vier Hunde in Privatbesitz.Vier Hunden, die mit PF diagnostiziert worden waren, wurde BTKi PRN1008 verabreicht. Anfangsdosen waren annähernd 15 mg/kg einmal täglich, wurden allerdings bei unzureichender Verbesserung auf zweimal täglich erhöht. Die Behandlung wurde 20 Wochen lang fortgesetzt, wobei versucht wurde, auf jeden zweiten Tag zu reduzieren. Die Hunde wurden mittels Blutbild, Serumbiochemie und Urinanalyse kontrolliert, sowie mit einer modifizierten Version eines validierten humanen Pemphigus Disease Activity Index (cPDAI) evaluiert. Es wurden Serum Anti-Desmocollin-1 (DSC-1) und Desmoglein-1 (DSG-1) Immunglobulin (Ig)G Titer vor und nach der Behandlungsperiode bestimmt. Mittels peripherer Blutmononuklearzellen (PBMC) wurde das ans Zielmolekül gebundene Medikament bestimmt.Alle vier Hunde zeigten weniger Veränderungen und einen verringerten cPDAI Wert während der ersten zwei Wochen der Behandlung. Drei Hunde verbesserten sich weiterhin und blieben nach 20 Wochen nahezu in Remission, wodurch zu diesem Zeitpunkt die Verbesserung bei drei als „gut“ und einem als „fair“ eingestuft wurde. Am Ende lagen die Dosierungen im Bereich von 17-33 mg/kg. Anti-DSC-1 IgG Titer verringerten sich bei einem Hund drastisch, waren bei zwei anderen nicht feststellbar und bei einem Hund nicht interpretierbar. Keiner der Hunde hatte messbare IgG auf DSG-1. Eine mögliche Nebenwirkungsreaktion trat bei einem Hund auf.BTKi PRN1008 Monotherapie könnte in einigen Fällen von cPF eine günstige Auswirkung haben.背景: Bruton型チロシンキナーゼ（BTK）は、B細胞シグナル伝達において重要である。ヒト自己免疫疾患におけるBTK阻害剤（BTKi）の有効性が報告されている。犬の天疱瘡（cPF）は、最も一般的な犬の自己免疫性皮膚疾患の1つである。 目的: 本研究の目的は、cPF治療におけるBTKi PRN1008の安全性および有効性を判断することであった。 供試動物: 4頭の飼育犬。 材料と方法: PFと診断した4頭の犬にBTKi PRN1008を投与した。初期投与量は1日1回15 mg/kgと概算され、不十分な反応が見られた場合は1日2回に増量した。治療は20週間継続し、投与量を隔日に減量するよう試みた。供試犬を全血球計算、血清生化学パネルおよび尿検査でモニターし、修正されたヒト天疱瘡疾患活動指数（cPDAI）で評価した。血清抗デスモコリン-1（DSC-1）およびデスモグレイン-1（DSG-1）免疫グロブリン（Ig）G力価を、治療期間の前後で測定した。標的に結合した薬物を末梢血単核細胞（PBMC）で測定した。 結果: 治療開始2週間で、4頭の犬すべてが病変とcPDAIスコアの低下を示した。 3頭の犬は改善を続け、20週間までにほぼ完全寛解を維持した。その時点で、3頭の反応は「良」、1頭は「可」と見なされた。最終的な1日投与量は17〜33 mg/kgの範囲であった。抗DSC-1 IgG力価は1頭の犬で劇的に減少し、2頭では検出できず、1頭の犬では解釈できなかった。 DSG1に対するIgGが検出された犬はいなかった。 1頭の犬で有害事象の可能性が生じた。 結論と臨床的重要性: BTKi PRN1008単剤療法は、cPFの一部の症例でいくつかの有益な効果をもたらす可能性がある。.背景: Bruton酪氨酸激酶(BTK)在B细胞信号转导中很重要。已报告BTK抑制剂(BTKi)在人类自身免疫性疾病中的疗效。犬落叶型天疱疮(cPF)是最常见的犬自身免疫性皮肤病之一。 目的: 确定BTKi PRN1008治疗cPF的安全性和疗效。 动物: 四只私家犬。 方法和材料: 对诊断为PF的4只犬给予BTKi PRN1008。初始剂量约为15mg/kg，每日一次，如果观察到反应不足，则增加至每日两次。治疗持续20周，尝试降至隔日一次。通过全血细胞计数、血清生化全项和尿分析对犬进行监测，并使用经验证的人天疱疮疾病活动指数 (cPDAI) 的改良版进行评价。在治疗期前后进行血清抗桥粒胶糖蛋白-1(DSC-1)和桥粒芯糖蛋白-1(DSG-1)免疫球蛋白(Ig)G滴度检测。在外周血单核细胞(PBMC)中测定与靶标结合的药物。 结果: 在治疗的前两周，所有4只犬均显示病变减轻和cPDAI评分下降。3只犬持续改善并在20周时维持接近完全缓解，此时认为3只效果为“良好”，1只为“一般”。最终日剂量范围为17-33mg/kg。在1只犬中，抗DSC-1 IgG滴度显著降低，在2只犬中检测不到，在1只犬中无法判断。所有犬均未检出DSG1 IgG。一只犬可能发生了不良事件。 结论和临床重要性: BTKi PRN1008单药治疗在某些cPF病例中可能有一定效果。.HISTÓRICO: A tirosina quinase de Bruton (BTK) é importante na sinalização de células B. A eficácia de inibidores da BTK (BTKi) em doenças autoimunes humanas já foi relatada. O pênfigo foliáceo canino (cPF) é uma das doenças cutâneas autoimunes caninas mais comuns.Determinar a segurança e a eficácia do BTKi PRN1008 no tratamento de cPF.Quatro cães de proprietários. MÉTODOS E MATERIAIS: Quatro cães diagnosticados com PF receberam BTKi PRN1008.As dosagens iniciais foram aproximadamente 15 mg / kg uma vez ao dia, aumentadas para duas vezes ao dia se houvesse resposta inadequada. O tratamento continuou por 20 semanas, com a tentativa de diminuir a dose para dias alternados. Os cães foram monitorados por hemograma completo, perfis bioquímicos séricos e urinálise, e avaliados utilizando uma versão modificada de um Índice validado de Atividade de Doença para o Pênfigo humano (cPDAI). Os títulos séricos de anticorpos (Ig) G anti-desmocolina-1 (DSC-1) e anti-desmogleina-1 (DSG-1) foram realizados antes e após o período de tratamento. A ligação do fármaco ao alvo foi mensurada em células mononucleares do sangue periférico (PBMC).Todos os quatro cães apresentaram redução nas lesões e escore de cPDAI durante as duas primeiras semanas de tratamento. Três cães continuaram a melhorar e mantiveram a remissão quase completa em 20 semanas. Neste momento, três respostas foram consideradas “boas” e uma “razoável”. As dosagens diárias finais ficaram na faixa de 17 a 33 mg / kg. O título de IgG anti-DSC-1 diminuiu drasticamente em um cão, foi indetectável em dois e não foi interpretável em um cão. Nenhum cão apresentou IgG detectável para DSG1. Um possível efeito adverso ocorreu em um cão. CONCLUSÕES E IMPORTÂNCIA CLÍNICA: A monoterapia com BTKi PRN1008 pode ter efeitos benéficos em alguns casos de cPF.}, number={5}, journal={VETERINARY DERMATOLOGY}, author={Goodale, Elizabeth C. and White, Stephen D. and Bizikova, Petra and Borjesson, Dori and Murrell, Dedee F. and Bisconte, Angelina and Francesco, Michelle and Hill, Ronald J. and Masjedizadeh, Mohammad and Nunn, Philip and et al.}, year={2020}, month={Oct}, pages={410-+} }
 @article{high_linder_mamo_levy_herrmann_bizikova_2020, title={Rapid response of hyperkeratotic erythema multiforme to oclacitinib in two dogs}, volume={31}, ISSN={["1365-3164"]}, DOI={10.1111/vde.12852}, abstractNote={Hyperkeratotic erythema multiforme (HKEM) is a clinically distinct dermatosis and poorly characterized syndrome, comprised of hyperkeratotic plaques with variable symmetry and apoptosis similar to "classic" erosive canine EM. Hyperkeratotic EM has a protracted clinical course and, although treatments with glucocorticoids, azathioprine and/or ciclosporin have been tried, rates of remission are low.To describe successful treatment of HKEM in two dogs using oclacitinib.A 7-year-old, spayed Havanese dog (Case 1) and a 1-year-old, intact cryptorchid Dachshund dog (Case 2).Case characterization and clinical diagnoses were based on lesion character, surgical biopsy, cytological evaluation, culture, direct immunofluorescence (DIF) and expected responses to treatments.Both cases exhibited multifocal, often symmetrical hyperkeratotic plaques with adherent scale. Histological findings revealed prominent epidermal hyperplasia, parakeratotic hyperkeratosis, lymphocytic dermatitis and transepidermal apoptosis with lymphocytic satellitosis. DIF revealed fine, patchy IgG, IgM and IgA basement membrane deposits (Case 2). Both dogs exhibited rapid improvement with oral oclacitinib (0.6-0.9 mg/kg twice daily) with a complete remission of clinical signs observed in 12 and seven weeks in cases 1 and 2, respectively.Oclacitinib could be considered as a fast-acting and effective treatment option for HKEM in dogs.L’érythème polymorphe hyperkératosique (HKEM) est une dermatose cliniquement distincte et un syndrome peu caractérisé, comprenant des plaques hyperkératosiques de symétrie variable et de l'apoptose semblable à l’EM canine érosive « classique ». L’EM hyperkératosique a une évolution clinique au long cours et bien que des traitements avec corticoïdes, azathioprine et/ou ciclosporine aient été essayés, les taux de rémission sont faibles.Décrire un traitement efficace de l’HKEM chez deux chiens à l'aide d'oclacitinib.Un chien bichon havanais de 7 ans (Cas 1) et un teckel cryptorchide entier de 1 an (Cas 2). MÉTHODES: La caractérisation du cas et le diagnostic clinique ont été basés sur les lésions, les biopsies, la cytologie, la culture, l'immunofluorescence directe (DIF) et les réponses attendues aux traitements. RÉSULTATS: Les deux cas ont montré des plaques hyperkératosiques, souvent symétriques, multifocales avec squames adhérentes. Les données histologiques ont montré une hyperplasie épidermique proéminente, de l'hyperkératose parakératosique, une dermatite lymphocytaire et de l'apoptose transépidermique avec satellitose lymphocytaire. Le DIF a révélé des dépôts en patch d'IgG, IgM et IgA sur la membrane basale (Cas 2). Les deux chiens ont montré une amélioration rapide avec de l'oclacitinib oral (0.6-0.9 mg/kg deux fois par jour) avec rémission complète des signes cliniques observés en 12 et sept semaines respectivement dans les cas 1 et 2.L'oclacitinib pourrait être considéré comme une option thérapeutique rapide et efficace pour l’HKEM chez le chien.INTRODUCCIÓN: el eritema multiforme hiperqueratótico (HKEM) es una dermatosis clínicamente distinta y un síndrome mal caracterizado, compuesto por placas hiperqueratóticas con simetría variable y apoptosis similar a la EM canina erosiva “clásica”. La EM hiperqueratótica tiene un curso clínico prolongado y, aunque se han intentado tratamientos con glucocorticoides, azatioprina y/o ciclosporina, las tasas de remisión son bajas. OBJETIVOS: describir el tratamiento exitoso de HKEM en dos perros tratados con oclacitinib. ANIMALES: un perro Havanés esterilizado de 7 años de edad (caso 1) y un perro Dachshund criptórquido intacto de 1 año de edad (caso 2). MÉTODOS: la caracterización de casos y los diagnósticos clínicos se basaron en el carácter de la lesión, la biopsia quirúrgica, la evaluación citológica, el cultivo, la inmunofluorescencia directa (DIF) y las respuestas esperadas a los tratamientos. RESULTADOS: ambos casos exhibieron placas hiperqueratóticas multifocales, a menudo simétricas, con escamas adherentes. Los hallazgos histológicos revelaron hiperplasia epidérmica prominente, hiperqueratosis paraqueratótica, dermatitis linfocítica y apoptosis transepidérmica con satelitósis linfocítica. DIF reveló depósitos de membrana basal IgG, IgM e IgA finas y discontinuas (Caso 2). Ambos perros mostraron una mejoría rápida con oclacitinib oral (0,6-0,9 mg/kg dos veces al día) con una remisión completa de los signos clínicos observados en 12 y siete semanas en los casos 1 y 2, respectivamente. CONCLUSIÓN E IMPORTANCIA CLÍNICA: Oclacitinib podría considerarse como una opción de tratamiento de acción rápida y eficaz para HKEM en perros.Das hyperkeratotische Erythema multiforme (HKEM) ist eine klinisch deutlich abgegrenzte Dermatose, aber ein schlecht beschriebenes Syndrom, welches aus hyperkeratotischen Plaques mit unterschiedlicher Symmetrie und Apoptose, ähnlich dem „klassischen“ erosiven EM des Hundes, besteht. Das hyperkeratotische EM zeigt einen langwierigen klinischen Verlauf und, obwohl Behandlungen mit Glukokortikoiden, Azathioprin und/oder Ciclosporin versucht worden sind, sind die Remissionsraten niedrig.Die Beschreibung einer erfolgreichen Behandlung von HKEM bei zwei Hunden mittels Oclacitinib.Eine 7 Jahre alte kastrierte Havaneserhündin (Fall 1) und ein 1 Jahre alter intakter kryptorchider Dackelrüde (Fall 2).Die Fallbeschreibung sowie die Beschreibung der klinischen Diagnosen basierte auf dem Aussehen der Läsionen, der chirurgischen Biopsie, der zytologischen Evaluierung, der Kultur, der direkten Immunfluoreszenz (DIF) und der erwarteten Behandlungserfolge.Beide Fälle zeigten multifokale, oft symmetrische hyperkeratotische Plaques mit anhaftenden Schuppen. Die histologischen Befunde zeigten eine prominente epidermale Hyperplasie, eine parakeratotische Hyperkeratose, eine lymphozytäre Dermatitis und eine transepidermale Apoptose mit lymphozytärer Satellitenbildung. Die DIF zeigte feine, fleckige Ablagerungen von IgG, IgM und IgA in der Basalmembran (Fall 2). Beide Hunde zeigten eine schnelle Verbesserung mit Oclacitinib per os (0,6-0,9 mg/kg zweimal täglich), wobei eine völlige Remission der klinischen Zeichen innerhalb von 12 bzw sieben Wochen in den Fällen 1 bzw 2 gesehen wurden.Oclacitinib könnte als schnell-wirkende und wirksame Behandlungsoption für HKEM bei Hunden in Frage kommen.背景: 過角化性多形紅斑(HKEM)は、臨床的に異なる皮膚疾患であり、対称性で可変的な過角化性性局面および「古典的な」犬のびらん性EMに類似したアポトーシスで構成される、特徴が不十分な症候群である。過角化性EMは長期にわたる臨床経過をたどり、グルココルチコイド、アザチオプリン、および/またはシクロスポリンによる治療が試みられているが、寛解率は低い。 目的: 本研究の目的は、オクラシチニブ使用による2頭の犬のHKEMの成功した治療について説明することであった。 供試動物: 7歳、避妊雌、ハバニーズ(症例1)と1歳、停留精巣の雄、ダックスフンド(症例2)。 方法: 症例の特徴付けおよび臨床診断は、病変の特徴、外科的生検、細胞学的評価、培養、直接免疫蛍光法(DIF)、および治療に対する期待される反応に基づいた。 結果: どちらの症例も、付着性の鱗屑を伴う多巣性で、しばしば対称性の過角化性局面を示した。組織学的所見は、顕著な表皮過形成、不全角化性角化症、リンパ球性皮膚炎、およびリンパ球性サテライトーシスを伴う経皮アポトーシスを明らかにした。 DIFにより、細かいパッチ状のIgG、IgM、IgAの基底膜の沈着が明らかになった(症例2)。どちらの症例も経口オクラシチニブ(0.6-0.9 mg / kg 1日2回)で急速な改善を示し、症例1および2ではそれぞれ12週間および7週間で臨床症状の完全寛解が観察された。 結論と臨床的重要性: オクラシチニブは、犬のHKEMに即効性があり効果的な治療オプションと考えることができる。.背景: 过度角化性多形红斑 (HKEM) 是一种临床上独特的皮肤病,这种综合征的特征较少,包括可能对称发生的过度角化性斑块,以及类似于“典型”糜烂性犬EM的细胞凋亡。过度角化性 EM 的临床病程持久,尽管已尝试使用糖皮质激素、硫唑嘌呤和/或环孢素治疗,但缓解率较低。 目的: 报告使用奥拉替尼成功治疗的两只HKEM患犬。 动物: 一只 7 岁、切除卵巢的哈瓦犬(病例 1)和一只 1 岁、未去势隐睾腊肠犬(病例 2)。 方法: 病例特征和临床诊断基于病变特征、外科活检、细胞学评价、培养、直接免疫荧光 (DIF) 和预期的治疗反应。 结果: 两个病例均表现出多灶性、通常对称的过度角化性斑块,伴粘附性鳞屑。组织学的调查结果揭示了突出的表皮增生,角化不全性过度角化病,淋巴细胞性皮炎,以及伴随淋巴细胞性卫星现象的跨表皮细胞凋亡。DIF 显示点、片状 IgG、IgM 和 IgA 基底膜沉积(病例 2)。口服给予奥拉替尼(0.6-0.9 mg/kg,每日两次)后,两只犬均表现出快速改善,在病例 1 和 2 中,分别在 12 周和 7 周内观察到临床体征完全缓解。 结论和临床意义: 奥拉替尼可被认为是犬 HKEM 的一种速效和有效的治疗选择。.O eritema multiforme hiperqueratótico (HKEM) é uma dermatose clinicamente distinta e uma síndrome pouco caracterizada, composta por placas hiperqueratóticas com simetria e apoptose variáveis ​​semelhantes ao EM canino erosivo “clássico”. O EM hiperqueratótico apresenta um quadro clínico prolongado e, apesar de tratamentos com glicocorticóides, azatioprina e/ou ciclosporina tenham sido tentados, as taxas de remissão são baixas.Descrever o tratamento bem-sucedido do HKEM em dois cães usando oclacitinib.Um cão Havanese de 7 anos, castrado (Caso 1), e um cachorro Dachshund com criptorquidia intacto de 1 ano (Caso 2). MÉTODOS: A descrição do caso e o diagnóstico clínico foram baseados nas características da lesão, biópsia cirúrgica, avaliação citológica, cultura, imunofluorescência direta (IFD) e respostas esperadas aos tratamentos.Ambos os casos apresentaram placas hiperqueratóticas multifocais, muitas vezes simétricas, com escama aderida. Os achados histológicos revelaram hiperplasia epidérmica proeminente, hiperqueratose paraqueratótica, dermatite linfocítica e apoptose transepidérmica com satelitose linfocítica. A IFD revelou depósitos finos e irregulares de IgG, IgM e IgA na membrana basal (Caso 2). Ambos os cães apresentaram melhora rápida com oclacitinib oral (0,6-0,9 mg / kg duas vezes ao dia) com remissão completa dos sinais clínicos observados em 12 e sete semanas nos casos 1 e 2, respectivamente. CONCLUSÃO E IMPORTÂNCIA CLÍNICA: Oclacitinib pode ser considerado uma opção de tratamento de ação rápida e eficaz para HKEM em cães.}, number={4}, journal={VETERINARY DERMATOLOGY}, author={High, Endya J. and Linder, Keith E. and Mamo, Lisa B. and Levy, Britt J. and Herrmann, Ina and Bizikova, Petra}, year={2020}, month={Aug}, pages={330-+} }
 @misc{bizikova_burrows_2019, title={Feline pemphigus foliaceus: original case series and a comprehensive literature review}, volume={15}, ISSN={["1746-6148"]}, DOI={10.1186/s12917-018-1739-y}, abstractNote={Since the first description of feline pemphigus foliaceus (PF) more than 30 years ago, numerous case reports have been published, while larger case series have remained rare. This large body of information, if extrapolated, could address clinical discrepancies and expand our knowledge about the treatment of feline PF. This manuscript reviews cases of feline PF published between 1950 and 2016 and adds additional 35 original cases to provide further insight into the clinical aspect and treatment outcome of this disease.Feline PF, while being a primary acantholytic pustular dermatosis, presents most often with crusts and erosions that predominantly affect the face and feet. More than half of cats with active disease exhibits non-dermatological signs such as lethargy, fever and/or anorexia. The prognosis of feline PF is good as the majority of cats rapidly achieve disease control even with the most basic treatment such as glucocorticoid monotherapy. Most PF-affected cats, however, require long-term treatment and, like other autoimmune diseases, feline PF has a tendency to relapse spontaneously or with treatment changes.Therefore, despite the overall good prognosis cats with PF can be given, owners should be informed and prepared for these circumstances, which may reduce the risk of euthanasia in the case of disease relapse, and improve treatment compliance.}, journal={BMC VETERINARY RESEARCH}, author={Bizikova, Petra and Burrows, Amanda}, year={2019}, month={Jan} }
 @article{linder_bizikova_luff_zhou_yuan_breuhaus_nelson_mackay_2018, title={Generalized papillomatosis in three horses associated with a novel equine papillomavirus (EcPV8)}, volume={29}, number={1}, journal={Veterinary Dermatology}, author={Linder, K. E. and Bizikova, P. and Luff, J. and Zhou, D. and Yuan, H. and Breuhaus, B. and Nelson, E. and Mackay, R.}, year={2018} }
 @article{golly_breitschwerdt_balakrishnan_moore_bizikova_2017, title={Bartonella henselae, Bartonella koehlerae and Rickettsia rickettsii seroconversion and seroreversion in a dog with acute-onset fever, lameness, and lymphadenopathy followed by a protracted disease course}, volume={7}, ISSN={2405-9390}, url={http://dx.doi.org/10.1016/J.VPRSR.2016.12.002}, DOI={10.1016/J.VPRSR.2016.12.002}, abstractNote={Following recent tick exposure in Arkansas, a 2-year-old, female spayed Labradoodle was examined because of a one-week history of lethargy and shifting-leg lameness. The dog was febrile, had prominent lymph nodes, dull mentation, a stiff gait, and left forelimb lameness. Thrombocytopenia was the only initial hematological or biochemical abnormality. Despite treatment with doxycycline for suspected Rocky Mountain spotted fever, the dog continued to have waxing and waning clinical signs including inappetence, fever, shifting-leg lameness, lymphadenopathy, splenomegaly, and weight loss in association with moderate to severe hematological abnormalities, including anemia, thrombocytopenia, neutrophilia, and monocytosis. Sequential serological testing confirmed Bartonella henselae, Bartonella koehlerae and R. rickettsii seroconversion. Doxycycline, enrofloxacin and clarithromycin were administered in sequential combination for treatment of rickettsioses, B. henselae and B. koehlerae. Prednisone, thyroid supplementation and other drugs were administered to elicit symptomatic improvement. Based upon seroreversion, and the eventual resolution of all clinical and hematological abnormalities, therapeutic elimination of all three pathogens was seemingly achieved. Whether cortisol insufficiency due to adrenal exhaustion syndrome or post-infectious immune-mediated sequelae contributed to the symptoms and pathophysiological abnormalities reported in this dog was not determined, but are considerations for future cases.}, journal={Veterinary Parasitology: Regional Studies and Reports}, publisher={Elsevier BV}, author={Golly, Elizabeth and Breitschwerdt, Edward B. and Balakrishnan, Nandhakumar and Moore, Deedee and Bizikova, Petra}, year={2017}, month={Jan}, pages={19–24} }
 @article{levine_cianciolo_linder_bizikova_birkenheuer_brooks_salous_nordone_bellinger_marr_et al._2017, title={Endothelial alterations in a canine model of immune thrombocytopenia}, volume={30}, ISSN={0953-7104 1369-1635}, url={http://dx.doi.org/10.1080/09537104.2017.1378807}, DOI={10.1080/09537104.2017.1378807}, abstractNote={Bleeding heterogeneity amongst patients with immune thrombocytopenia (ITP) is poorly understood. Platelets play a role in maintaining endothelial integrity, and variable thrombocytopenia-induced endothelial changes may influence bleeding severity. Platelet-derived endothelial stabilizers and markers of endothelial integrity in ITP are largely underexplored. We hypothesized that, in a canine ITP model, thrombocytopenia would lead to alterations in the endothelial ultrastructure and that the Von Willebrand factor (vWF) would serve as a marker of endothelial injury associated with thrombocytopenia. Thrombocytopenia was induced in healthy dogs with an antiplatelet antibody infusion; control dogs received an isotype control antibody. Cutaneous biopsies were obtained prior to thrombocytopenia induction, at platelet nadir, 24 hours after nadir, and on platelet recovery. Cutaneous capillaries were assessed by electron microscopy for vessel thickness, the number of pinocytotic vesicles, the number of large vacuoles, and the number of gaps between cells. Pinocytotic vesicles are thought to represent an endothelial membrane reserve that can be used for repair of damaged endothelial cells. Plasma samples were assessed for vWF. ITP dogs had significantly decreased pinocytotic vesicle numbers compared to control dogs (P = 0.0357) and the increase in plasma vWF from baseline to 24 hours correlated directly with the endothelial large vacuole score (R = 0.99103; P < 0.0001). This direct correlation between plasma vWF and the number of large vacuoles, representing the vesiculo-vacuolar organelle (VVO), a permeability structure, suggests that circulating vWF could serve as a biomarker for endothelial alterations and potentially a predictor of thrombocytopenic bleeding. Overall, our results indicate that endothelial damage occurs in the canine ITP model and variability in the degree of endothelial damage may account for differences in the bleeding phenotype among patients with ITP.}, number={1}, journal={Platelets}, publisher={Informa UK Limited}, author={LeVine, Dana N. and Cianciolo, Rachel E. and Linder, Keith E. and Bizikova, Petra and Birkenheuer, Adam J. and Brooks, Marjory B. and Salous, Abdelghaffar K. and Nordone, Shila K. and Bellinger, Dwight A. and Marr, Henry and et al.}, year={2017}, month={Nov}, pages={88–97} }
 @article{adamovicz_kennedy-stoskopf_talley_cullen_cohen_bizikova_grunkemeyer_2017, title={MYCOBACTERIUM INTRACELLULARE INFECTION CAUSING A RETROPERITONEAL MASS IN A BINTURONG (ARCTICTIS BINTURONG)}, volume={48}, ISSN={["1937-2825"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85026496685&partnerID=MN8TOARS}, DOI={10.1638/2016-0117r.1}, abstractNote={A 19-yr-old castrated male binturong (Arctictis binturong) with a history of recurrent pyogranulomatous panniculitis, lymphangitis, and dermatitis was presented for evaluation of hyporexia and tenesmus. A large caudal abdominal mass was palpated on physical examination. On ultrasound, the mass encircled and obstructed the left ureter, resulting in hydroureter and hydronephrosis. The animal was euthanized, and necropsy revealed a large retroperitoneal pyogranuloma with acid-fast organisms identified in both the mass and the perineal skin. The acid-fast organisms within the retroperitoneal mass were identified as Mycobacterium intracellulare by PCR. This case represents an unusual presentation of M. intracellulare in a novel species.}, number={2}, journal={JOURNAL OF ZOO AND WILDLIFE MEDICINE}, author={Adamovicz, Laura and Kennedy-Stoskopf, Suzanne and Talley, Ashley and Cullen, John M. and Cohen, Eli B. and Bizikova, Petra and Grunkemeyer, Vanessa}, year={2017}, month={Jun}, pages={544–548} }
 @article{bizikova_olivry_2016, title={A randomized, double-blinded crossover trial testing the benefit of two hydrolysed poultry-based commercial diets for dogs with spontaneous pruritic chicken allergy}, volume={27}, ISSN={["1365-3164"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84987925072&partnerID=MN8TOARS}, DOI={10.1111/vde.12302}, abstractNote={Hydrolysed protein diets are used to diagnose and treat dogs with cutaneous adverse food reactions (CAFR). Little is known about what proportion of dogs hypersensitive to the native protein would react to its hydrolysed form. To determine the clinical allergenicity of hydrolysed poultry feather (RCU) and chicken liver diets (HZD) in dogs with chicken induced CAFR. In this randomized, double-blinded, crossover trial, ten dogs with chicken induced CAFR were selected after a positive oral challenge to chicken meat and a negative one to corn. Test diets were fed for 14 days separated by a 14 day wash-out period. Owners rated pruritus daily with a Visual Analog Scale (PVAS). The challenge was ended if a flare in pruritus occurred (i.e. PVAS ≥5/10). The median PVAS scores before feeding RCU and HZD were 0.9 and 1.7, respectively (Wilcoxon signed rank test, P = 0.46). Pruritus scores increased significantly after feeding HZD (Friedman's test, P < 0.001) but not after feeding RCU (P = 0.895). None of the dogs fed RCU, but four dogs fed HZD (40%), were withdrawn after a flare in pruritus developed (Fisher's test, P = 0.04). The maximal PVAS score was significantly higher after HZD (median: 4.7) compared to RCU (2.5) (Wilcoxon signed rank test, P = 0.01). One dog in each group was withdrawn due to diarrhoea. The hydrolysed poultry feather diet did not induce pruritus flares in dogs allergic to chicken in contrast to the hydrolysed chicken liver diet that led to pruritus flares in 40% of these dogs. Les régimes d'hydrolysats de protéines sont utilisés pour le diagnostic et le traitement des réactions cutanées indésirables liées à l'alimentation (CAFR). On sait peu de chose sur la proportion de chiens hypersensibles à la protéine naïve qui réagirait à sa forme hydrolysée. Déterminer l'allergénicité clinique des plumes de volaille (RCU) et du foie de poulet hydrolysés (HDZ) chez les chiens présentant une CAFR liée au poulet. Dans cette étude croisée, randomisée, en double aveugle, dix chiens avec une CAFR induite par le poulet ont été sélectionnés après un test oral positif à la viande de poulet et un test négatif au maïs. Les tests alimentaires duraient 14 jours et étaient séparés d'une période de wash out de 14 jours. Les propriétaires ont évalué le prurit chaque jour à l'aide d'une échelle visuelle analogue (PVAS). Le test était stoppé si une poussée de prurit se développait (i.e. PVAS ≥5/10). Les scores médians de PVAS après RCU et HZD étaient respectivement de 0.9 et 1.7 (Wilcoxon signed rank test, P = 0.46). Les scores de prurit augmentaient significativement après l’HZD (Friedman's test, P < 0.001) mais pas après le RCU (P = 0.895). Aucun des chiens nourris avec RCU, mais quatre des chiens recevant du HZD (40%), ont été retirés après une poussée de prurit (Fisher's test, P = 0.04). Le score de PVAS maximal était significativement plus élevé après HZD (médiane: 4.7) comparé au RCU (2.5) (Wilcoxon signed rank test, P = 0.01). Un chien de chaque groupe a été retiré de l’étude pour cause de diarrhée. L'alimentation à base de plume de volaille hydrolysée n’ a pas entrainé de poussée de prurit chez les chiens allergiques au poulet à la différence du foie de poulet hydrolysé qui a entrainé une poussée de prurit pour 40% des chiens. las dietas de proteínas hidrolizadas se utilizan para el diagnóstico y tratamiento de perros con reacciones cutáneas adversas alimentarias (CAFR). Se conoce poco acerca de la proporción de perros con hipersensibilidad a las proteínas nativas que reaccionarían a las formas hidrolizadas. determinar la alergenicidad clínica de plumas hidrolizadas de aves domésticas (RCU) dietas de hígado de pollo (HZD) en perros con CAFR inducida al pollo. en este estudio al azar, doble ciego y cruzado, 10 perros con CAFR inducida al pollo se seleccionaron tras una exposición oral positiva a carne de pollo y negativa a maíz. Las dietas probadas fueron administradas durante 14 días separadas por un periodo de lavado de 14 días. Los propietarios valoraron el prurito diariamente con una escala visual análoga (PVAS). La reexposición se terminó si ocurría un incremento intenso del prurito (PVAS≥ 5/10). los valores medios de PVAS antes de administrar RCU y HZD fueron de 0,9 y 1,7 respectivamente (prueba de rangos determinados de Wilcoxon, P = 0,46). Los valores de prurito aumentaron significativamente tras la administración de HZD (prueba de Friedman, P < 0,001) pero no tras la administración de RCU (P = 0,895). Ninguno de los perros administrado RCU, pero cuatro perros administrado HZD (40%) fueron eliminados tras desarrollar un incremento intenso del prurito (prueba de Fisher, P = 0,04). El valor máximo de PVAS fue significativamente mayor tras HZD (media: 4,7) comparado con RCU(2,5) (prueba de rangos determinados de Wilcoxon, P = 0,01). Un perro de cada grupo fue eliminado debido al desarrollo de diarrea. la dieta hidrolizada de plumas de aves domésticas no indujo incremento del prurito en perros alérgicos a pollo, en contraste con la dieta hidrolizada del hígado de pollo que produjo incremento intenso del prurito en un 40% de los perros. Diäten mit hydrolysierten Proteinen werden zur Diagnose und zur Behandlung von Hunden mit kutanen Futterunverträglichkeiten (CAFR) verwendet. Es ist wenig bekannt über den Anteil der Hunde, die auf die hydrolysierte Form reagieren würden, wenn sie auf das natürliche Protein hypersensibel sind. Das Ziel dieser Studie war es die klinische Allergenität auf hydrolysierte Putenfeder- (RCU) und Hühnerleberdiäten (HZD) bei Hunden, die eine durch Huhn induzierte CAFR haben, festzustellen. In dieser randomisierten, doppel-geblindeten, Cross-over Studie wurden zehn Hunde mit einer durch Huhn induzierten CAFR nach einer positiven oralen Provokation mit Hühnerfleisch und einer negativen Provokation zu Mais ausgewählt. Die Testdiäten wurden jeweils 14 Tage lang gefüttert, wobei eine 14 tägige Auswaschperiode dazwischen eingehalten wurde. Die BesitzerInnen beurteilten täglich den Juckreiz mittels einer Visuellen Analog Skala (PVAS). Die Provokation wurde beendet, sobald ein Juckreizschub auftrat (i.e. PVAS ≥5/10). Die medianen PVAS Werte vor der Fütterung von RCU bzw HZD betrugen 0,9 bzw 1,7 (Wilcoxon-Vorzeichen-Rang Test, P = 0,46). Die Juckreizwerte nahmen nach der Fütterung der HZD signifikant zu (Friedman′s Test, P < 0,001), aber nicht nach der Fütterung von RCU (P = 0,895). Keiner der Hunde, die RCU bekamen, musste aus der Studie genommen werden. Vier Hunde, denen HZD (40%) gefüttert wurde, wurden nach einem Juckreizschub aus der Studie genommen (Fisher′s Test, P = 0,04).Der maximale PVAS Wert war nach HZD Fütterung signifikant höher (median: 4,7) im Vergleich zu RCU Fütterung (2,5)(Wilcoxon -Vorzeichen-Rang Test, P = 0,01). Ein Hund aus jeder Gruppe wurde wegen Durchfall aus der Studie genommen. Die hydrolysierte Putenfederdiät induzierte keine Juckreizschübe bei Hunden, die auf Huhn allergisch waren, im Gegensatz zur hydrolysierten Hühnerleberdiät, die bei 40% dieser Hunde zu Juckreizschüben führte. 加水分解タンパク食は、皮膚食物有害反応(CAFR)のイヌを診断および治療するのに使用されている。本来のタンパクに過敏反応を示すイヌで、加水分解後のタンパクに反応する割合はほとんど知られていない。 鶏肉誘発性CAFRのイヌにおいて、加水分解家禽羽毛(RCU)および鶏肝臓食(HZD)の臨床的なアレルゲン性を究明すること。 このランダム化二重盲検交差試験では、鶏肉への経口暴露試験に陽性で、トウモロコシに陰性であった10頭の鶏肉誘発性CAFRを選出した。試験を行ったフードを14日間ウォッシュ・アウト期間で分け、14日間給餌した。飼い主はビジュアルアナログスケール(PVAS)を使って毎日そう痒について記録した。 RCUおよびHZDを給餌する前の平均PVASスコアはそれぞれ0.9と1.7であった(ウイルコクソンの符号付き検定、 P = 0.46)。そう痒スコアはHZDを給餌後有意に増加したが(フリードマン検定、P < 0.001)、RCU給餌後には増加しなかった(P = 0.895)。FCUを給餌したイヌは脱落しなかったが、HZDを給餌したイヌは4頭(40%)が、痒みの増悪が見られ、脱落した(フィッシャーの検定、 P = 0.04)。最大PVASスコアはHZD(平均:4.7)を給餌後、RCUの給餌後(2.5)と比較し、有意に高かった(ウイルコクソンの符号付き検定、 P = 0.01)。それぞれの群の1頭のイヌが下痢を理由に脱落した。 加水分解家禽羽毛フードは、鶏肉にアレルギーを示すイヌにおいてそう痒の再燃を誘発しなかった。一方、加水分解鶏肝臓フードはそれらのイヌの40%にそう痒の再燃を起こした。 水解蛋白粮用于诊断和治疗犬食物副反应(CAFR)。但对导致犬过敏的天然蛋白的水解形式,对其过敏比例研究甚少。 确定鸡肉过敏犬对水解家禽羽毛日粮(RCU)和鸡肝日粮(HZD)的临床变应原性。 设计随机、双盲、交叉实验,选择十只犬,激发试验发现对鸡肉反应阳性、谷物反应阴性,因而确诊为鸡肉过敏。分别饲喂实验日粮14日,隔14个间歇日。主人每日使用直观类比标度(PVAS)评估瘙痒。若爆发瘙痒则实验终止(如PVAS ≥5/10)。 饲喂RCU和HZD前,PVAS分数中值分别为0.9和1.7 (威氏符号秩次检验, P = 0.46)。饲喂HZD后瘙痒指数明显增长(弗氏检验, P < 0.001),但是饲喂RCU后未出现(P = 0.895)。零只饲喂RCU患犬,四只饲喂HZD患犬(40%)因爆发瘙痒退出实验(费希尔检验, P = 0.04)。HZD组(中值: 4.7)最高PVAS分数明显高于RCU组(2.5) (威氏符号秩次检验, P = 0.01)。每组中有一只犬因腹泻退出实验。 水解家禽羽毛日粮不会引起鸡肉过敏患犬瘙痒,而水解鸡肝日粮会导致40%鸡肉过敏患犬瘙痒。 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.}, number={4}, journal={VETERINARY DERMATOLOGY}, author={Bizikova, Petra and Olivry, Thierry}, year={2016}, month={Aug}, pages={289–E70} }
 @article{tham_jacob_bizikova_2016, title={Molecular confirmation of shampoo as the putative source of Pseudomonas aeruginosa-induced postgrooming furunculosis in a dog}, volume={27}, ISSN={["1365-3164"]}, DOI={10.1111/vde.12332}, abstractNote={An acute onset furunculosis due to Pseudomonas aeruginosa following grooming is a well recognized entity. Although contaminated shampoos have been suspected to be the source of the infection, a molecular confirmation of this association has been missing. This case report describes a dog with postgrooming furunculosis in which Pseudomonas aeruginosa with an identical genetic fingerprint was isolated from the skin lesions as well as from the shampoo used prior to the disease onset. The dog presented for lethargy, anorexia, pain and rapidly progressing skin lesions consistent with haemorrhagic papules, pustules, coalescing ulcers and crusts localized to the dorsal and lateral aspects of the thorax and gluteal region, which developed within 24 h after a bath. Cytology demonstrated suppurative inflammation with occasional intracellular rod-shaped bacteria. Bacterial culture from skin lesions and the shampoo bottle yielded Pseudomonas aeruginosa with an identical pulsed-field gel electrophoresis pattern. Treatment with oral ciprofloxacin and topical antimicrobial shampoo resulted in a complete resolution of skin lesions within eight weeks. Our clinical investigation suggests a link between Pseudomonas-contaminated shampoo and development of postgrooming furunculosis, and underscores the need for hygienic management of shampoos to help limit this disease. Une furonculose aiguë à Pseudomonas aeruginosa à la suite d'un toilettage est une entité bien reconnue. Bien que les shampoings contaminés aient été suspectés d’être la source de l'infection, une confirmation moléculaire de cette association n'a jamais été faite. Ce cas clinique décrit un chien avec furonculose post-toilettage pour lequel Pseudomonas aeruginosa, avec une empreinte génétique identique, a été isolée des lésions cutanées ainsi que du shampoing utilisé avant le développement de la maladie. Le chien a présenté léthargie, anorexie, douleur et progression rapide des lésions cutanées consistant en des papules hémorragiques, des pustules, des ulcères coalescents et des croûtes localisées sur les face dorsales et latérales du thorax et sur les fessiers qui se sont développées en 24h après un bain. La cytologie a révélé une inflammation suppurée avec des bactéries de type bacille intracellulaires. La culture bactériologique des lésions cutanées et de la bouteille de shampoing a révélé Pseudomonas aeruginosa avec un patron identique d’électrophorèse en gel en champ pulsé. Le traitement avec la ciprofloxacine orale et des shampooings antimicrobiens ont permis une complète résolution des lésions cutanées en huit semaines. Nos données cliniques confirment le lien entre les shampoings contaminés par Pseudomonas et le développement d'une furonculose post-toilettage et souligne le besoin d'une gestion hygiénique des shampooings afin de limiter cette atteinte. el desarrollo de la forunculosis aguda debido a la infección con Pseudomonas aeruginosa tras el aseado del pelo es una entidad bien reconocida. Aunque se sospecha que la contaminación champús es el foco de infección, aún falta la confirmación molecular de esta asociación. este caso clínico describe un perro con forunculosis tras el aseado del pelo en el cual se aisló Pseudomonas aeruginosa con idéntico patrón genético de las lesiones de la piel y del champú utilizado antes de desarrollar la enfermedad. el perro se presentó con letargia, anorexia, dolor, y lesiones de rápida progresión en la piel consistentes con pápulas hemorrágicas, pústulas, úlceras confluentes y costras localizadas en las zonas laterales y dorsales del tórax y de la región glútea que se desarrollaron a las 24 horas tras un baño. La citología demostró inflamación supurativa con algunas bacterias ocasionales de morfología bacilar intracelulares. El cultivo bacteriano de las lesiones de la piel y del champú desarrolló Pseudomonas aeruginosa con un patrón idéntico en gel de electroforesis de campo pulsátil. El tratamiento con el ciprofloxacina oral y champú tópico antimicrobiano resultó en resolución completa de las lesiones de la piel en ocho semanas. nuestra investigación clínica sugiere una asociación entre el champú contaminado con Pseudomonas y el desarrollo de forunculosis tras el aseado y resalta la necesidad de un manejo higiénico de los champús para limitar la incidencia de esta enfermedad. Eine akute Furunkulose durch Pseudomonas aeruginosa nach der Schur ist eine gut bekannte Erkrankung. Obwohl verunreinigte Shampoos als Ursache für die Infektion verdächtigt worden sind, ist bisher eine molekulare Bestätigung dieses Zusammenhangs noch nicht erbracht worden. Dieser Fallbericht beschreibt einen Hund mit einer Furunkulose nach der Schur, bei der Pseudomonas aeruginosa mit einem identischen genetischen Fingerabdruck aus den Hautveränderungen sowie aus dem Shampoo isoliert werden konnte, welches vor der Erkrankung verwendet worden war. Der Hund wurde mit Lethargie, Anorexie, Schmerz und sich rasch ausbreitenden Hautveränderungen, die aus hämorrhagischen Papeln, Pusteln, koaleszierenden Ulzera und Krusten am dorsalen und lateralen Thorax und der Glutealregion bestanden und sich innerhalb von 24h nach dem Bad entwickelt hatten, vorgestellt. Zytologisch wurde eine suppurative Entzündung mit gelegentlichen intrazellulären Stäbchen-förmigen Bakterien gefunden. Die Bakterienkultur aus den Hautveränderungen und der Shampooflasche wiesen beide Pseudomonas aeruginosa mit einem identischen Puls-Feld-Gelelektrophorese Muster auf. Eine Behandlung mit Ciprofloxacin per os und topische antimikrobielle Shampoos resultierten innerhalb von acht Wochen in einer kompletten Remission der Hautveränderungen. Unsere klinische Untersuchung zeigt einen Zusammenhang zwischen Pseudomonas-verunreinigten Shampoos und der Entstehung einer Furunkulose nach der Schur und unterstreicht die Notwendigkeit eines entsprechenden Hygienemanagements der Shampoos, um die Erkrankung zu limitieren. トリミング後の緑膿菌に起因する急性発症のフルンケローシスはよく認められる事象である。汚染したシャンプーが感染の原因と疑われているが、この関係性の分子的な裏付けはなされていない。 この症例報告は、発症前に使用したシャンプーからだけでなく、皮膚病変からも同一の遺伝子パターンを示す緑膿菌が分離された、トリミング後フルンケローシスのイヌについて記述する。 イヌは元気消失、食欲不振、疼痛および胸部背側と体側および臀部領域に出血性丘疹、膿疱、癒合性潰瘍ならびに痂皮から成る急速に進行する皮膚病変を呈し、それらは洗浄後24時間以内に発生した。細胞診では時折、細胞内桿菌を伴った化膿性炎症が明らかとなった。皮膚病変およびシャンプーボトルからの細菌培養によりパルスフィールドゲル電気泳動パターンが一致する緑膿菌が検出された。経口シプロフロキサシンおよび外用抗菌シャンプーを用いた治療の結果、8週間以内に皮膚病変は完全に治癒した。 筆者らの臨床的な調査は緑膿菌汚染シャンプーとトリミング後フルンケローシスの発生の関連を示唆しており、この疾患を防ぐためにシャンプーの衛生的な管理の必要性を強調する。 急性疖病由剃毛后假单胞菌感染导致,已是公认的病因。尽管被污染的香波是可疑的感染来源,但却没有进行分子学认证。 该病例报告描述了一只患有假单胞菌感染的剃毛后疖病,其皮肤病变处分离的假单胞菌,与其发病前使用的香波中细菌的基因一致。 该犬在洗澡后24h内表现出精神沉郁、厌食、疼痛和快速发展的皮肤病变,出血性丘疹、脓疱、聚结性溃疡和结痂。细胞学显示化脓性炎症,偶见细胞内杆菌。皮肤病变处和香波中假单胞菌脉冲场凝胶电泳模式一致。口服环丙沙星和使用抗菌香波八周后皮肤病变消失。 临床研究支持受假单胞菌污染香波和剃毛后疖病存在关联,需要对香波进行卫生管理来帮助控制该疾病。}, number={4}, journal={VETERINARY DERMATOLOGY}, author={Tham, Heng L. and Jacob, Megan E. and Bizikova, Petra}, year={2016}, month={Aug}, pages={320–E80} }
 @article{tham_olivry_linder_bizikova_2016, title={Mucous membrane pemphigoid in dogs: A retrospective study of 16 new cases}, volume={27}, number={5}, journal={Veterinary Dermatology}, author={Tham, H. L. and Olivry, T. and Linder, K. E. and Bizikova, P.}, year={2016}, pages={376-} }
 @article{bizikova_linder_wofford_mamo_dunston_olivry_2015, title={Canine epidermolysis bullosa acquisita: A retrospective study of 20 cases}, volume={26}, number={6}, journal={Veterinary Dermatology}, author={Bizikova, P. and Linder, K. E. and Wofford, J. A. and Mamo, L. B. and Dunston, S. M. and Olivry, T.}, year={2015}, pages={441-} }
 @article{bizikova_moriello_linder_sauber_2015, title={Dinotefuran/pyriproxyfen/permethrin pemphigus-like drug reaction in three dogs}, volume={26}, number={3}, journal={Veterinary Dermatology}, author={Bizikova, P. and Moriello, K. A. and Linder, K. E. and Sauber, L.}, year={2015}, pages={206-} }
 @article{pucheu-haston_eisenschenk_bizikova_marsella_nuttall_santoro_2015, title={Introduction to the review articles by ICADA on the pathogenesis of atopic dermatitis in dogs}, volume={26}, ISSN={["1365-3164"]}, DOI={10.1111/vde.12207}, abstractNote={In 2001 the then American College of Veterinary Dermatology Task Force on Canine Atopic Dermatitis published a comprehensive review covering what was then known about the pathogenesis of the atopic disease in dogs.1 In the years following this landmark publication the committee evolved into ‘The International Committee on Allergic Diseases of Animals’ (ICADA; www.ICADA.info), which has been actively publishing further reviews of allergic disease in animals.2 The purpose of the following collection of review papers is to provide an update to the original ‘Task Force’ review articles on canine allergic dermatitis, as much has been learned in the last 13 years. This update was prepared by searching online databases and abstracts from international veterinary dermatology meetings and congresses from 2001 to 2013 for articles relating to allergic and/or atopic diseases in dogs. Older works were also included when appropriate to provide background information and historical perspective. The manuscripts developed from this search were subsequently submitted to the entire ICADA membership for review and commentary prior to submission to this journal for a final peer review. The six manuscripts in this collection are: clinical and histological manifestations of canine (AD); lymphocytes, cytokines, chemokines and the Th1/Th2 balance in canine AD; innate immunity, lipid metabolism and nutrition in canine AD; the role of antibodies, autoantigens and food allergens in canine AD; pathogenesis of canine atopic dermatitis: skin barrier and host-microorganism interaction; and the role of genetics and the environment in the pathogenesis of canine AD. Since the 2001 publication, there has been a revision of the terminology used to refer to allergic diseases in dogs.3 Canine AD is currently defined as ‘a genetically predisposed inflammatory and pruritic allergic skin disease with characteristic clinical features associated with IgE antibodies most commonly directed against environmental allergens’.3 Canine atopic-like dermatitis (ALD) is an ‘inflammatory and pruritic skin disease with clinical features identical to those seen in canine atopic dermatitis in which an IgE response to environmental or other allergens cannot be documented’.3 This condition may be similar to ‘intrinsic atopic dermatitis’ (IAD) in humans, which refers to patients with symptoms clinically indistinguishable from AD but in which elevated allergen-specific IgE or demonstrable immediate hypersensitivity to allergens cannot be documented.4 Unfortunately, in dogs it is not known whether this perceived lack of detectable allergen-specific IgE reactivity is truly associated with the absence of IgE-mediated disease or simply reflects a failure to test for relevant allergens. As will be discussed in more detail, dogs do not show a consistent elevation in allergen-specific IgE levels with atopic dermatitis and total IgE levels can be highly variable even in non-atopic dogs.5 In addition, healthy, clinically non-atopic dogs can have skin and serum reactivity to environmental allergens.6-10 Because canine AD and ALD cannot be definitively differentiated clinically (and in many of the studies reviewed here the two are either not separated or not specified) the two diseases will be collectively referred to as canine AD throughout these papers. These review papers summarize the increasing amount of new knowledge in the subject of atopic dermatitis in dogs. However, there is still very much to learn. While the overall knowledge of the histopathology associated with canine AD has not changed much over the past few years, new studies have further defined the clinical phenotypes associated with AD. Great strides have also been made in further understanding the immunopathogenesis of AD in humans and in dogs. The cells of the innate immune system play much larger roles than we had previously suspected, while the role of total or allergen-specific antibodies appears to be smaller than previously thought. Although the central player in immunopathogenesis remains the T cell, new work has shown that the old Th1/Th2 paradigm is greatly oversimplified. We now also understand much more about the important role the epidermal barrier plays in the skin, both in health and in disease. Even so, there is controversy about whether the barrier dysfunction that has been described in canine AD is its cause or its effect. Studies to determine the role of genetics in the pathogenesis of canine AD have provided us with some information, but may have triggered more questions than they have answered, largely due to the complex interactions of genes with the environment and immune system of individuals. The development of large health records databases (such as those kept by pet medical insurance companies) can facilitate the identification of environmental risk factors, but mining of these databases is still a fairly new approach in veterinary medicine. Finally, we have learned much about the interactions and overlap between canine AD and other conditions that we previously considered to be entirely separate (such as adverse food reactions), but these interactions still remain imperfectly understood. In conclusion, these articles represent a concise review and summary of the most important papers on the pathogenesis of canine atopic dermatitis in the last 13 years. It is hoped that this collection of articles will lead to better prevention, diagnosis and treatments of this disease for our canine friends as well as help to increase knowledge of other hypersensitivity disorders common in many species of animals, including humans. Much has been learned, but there is still so much to discover, and it is our hope that this collection contains the springboards for future research in the amazing and exciting topic of allergic skin disease.}, number={2}, journal={VETERINARY DERMATOLOGY}, author={Pucheu-Haston, Cherie M. and Eisenschenk, Melissa N. C. and Bizikova, Petra and Marsella, Rosanna and Nuttall, Tim and Santoro, Domenico}, year={2015}, month={Apr}, pages={77–78} }
 @article{bizikova_olivry_2015, title={Oral glucocorticoid pulse therapy for induction of treatment of canine pemphigus foliaceus - a comparative study}, volume={26}, number={5}, journal={Veterinary Dermatology}, author={Bizikova, P. and Olivry, T.}, year={2015}, pages={354-} }
 @article{tham_linder_tucker_maggi_bizikova_2015, title={Protozoal nodular dermatitis and panniculitis in a Rottweiler puppy caused by Caryospora bigenetica}, volume={27}, ISSN={0959-4493}, url={http://dx.doi.org/10.1111/vde.12271}, DOI={10.1111/vde.12271}, abstractNote={Caryospora bigenetica is an intracellular protozoan parasite in snakes and raptors (primary hosts) and rodents (secondary host). Experimental infection has been documented in mice, pigs and goats; natural infection in dogs is rare.To describe the clinical presentation, histological features, treatment and outcome of a case of protozoal nodular dermatitis and panniculitis in a Rottweiler puppy caused by C. bigenetica.The puppy presented with generalized subcutaneous nodules measuring up to 2 cm in diameter. Histopathology revealed marked suppurative to pyogranulomatous dermatitis and panniculitis with intralesional protozoal organism. PCR and DNA sequencing confirmed infection with C. bigenetica. Treatment with a combination of oral trimethoprim-sulfamethoxazole (TMS), pyrimethamine and high-dose clindamycin (20 mg/kg twice daily) resulted in resolution of lesions in 6 weeks. Discontinuation of the treatment 2 weeks later was followed by a rapid relapse of skin lesions. Clindamycin and TMS were restarted and all lesions resolved within 2 weeks; TMS was discontinued 4 weeks later due to adverse effects. The lesions remained in remission for 2 months while the puppy received clindamycin monotherapy before a second relapse of skin lesions occurred.To the best of the authors' knowledge, this is the first documentation of the treatment and outcome of C. bigenetica cutaneous infection in a dog. Although remission of clinical signs can be achieved with combination therapy of clindamycin and TMS, long-term management is challenging and relapses should be anticipated.}, number={1}, journal={Veterinary Dermatology}, publisher={Wiley}, author={Tham, Heng L. and Linder, Keith E. and Tucker, Alison and Maggi, Ricardo and Bizikova, Petra}, year={2015}, month={Nov}, pages={44–e12} }
 @misc{bizikova_santoro_marsella_nuttall_eisenschenk_pucheu-haston_2015, title={Review: Clinical and histological manifestations of canine atopic dermatitis}, volume={26}, number={2}, journal={Veterinary Dermatology}, author={Bizikova, P. and Santoro, D. and Marsella, R. and Nuttall, T. and Eisenschenk, M. N. C. and Pucheu-Haston, C. M.}, year={2015} }
 @misc{pucheu-haston_santoro_bizikova_eisenschenk_marsella_nuttall_2015, title={Review: Innate immunity, lipid metabolism and nutrition in canine atopic dermatitis}, volume={26}, number={2}, journal={Veterinary Dermatology}, author={Pucheu-Haston, C. M. and Santoro, D. and Bizikova, P. and Eisenschenk, M. N. C. and Marsella, R. and Nuttall, T.}, year={2015} }
 @misc{pucheu-haston_bizikova_marsella_santoro_nuttall_eisenschenk_2015, title={Review: Lymphocytes, cytokines, chemokines and the T-helper 1-T-helper 2 balance in canine atopic dermatitis}, volume={26}, number={2}, journal={Veterinary Dermatology}, author={Pucheu-Haston, C. M. and Bizikova, P. and Marsella, R. and Santoro, D. and Nuttall, T. and Eisenschenk, M. N. C.}, year={2015} }
 @misc{santoro_marsella_pucheu-haston_eisenschenk_nuttall_bizikova_2015, title={Review: Pathogenesis of canine atopic dermatitis: skin barrier and host-micro-organism interaction}, volume={26}, number={2}, journal={Veterinary Dermatology}, author={Santoro, D. and Marsella, R. and Pucheu-Haston, C. M. and Eisenschenk, M. N. C. and Nuttall, T. and Bizikova, P.}, year={2015} }
 @misc{bizikova_pucheu-haston_eisenschenk_marsella_nuttall_santoro_2015, title={Review: Role of genetics and the environment in the pathogenesis of canine atopic dermatitis}, volume={26}, number={2}, journal={Veterinary Dermatology}, author={Bizikova, P. and Pucheu-Haston, C. M. and Eisenschenk, M. N. C. and Marsella, R. and Nuttall, T. and Santoro, D.}, year={2015} }
 @misc{pucheu-haston_bizikova_eisenschenk_santoro_nuttall_marsella_2015, title={Review: The role of antibodies, autoantigens and food allergens in canine atopic dermatitis}, volume={26}, number={2}, journal={Veterinary Dermatology}, author={Pucheu-Haston, C. M. and Bizikova, P. and Eisenschenk, M. N. C. and Santoro, D. and Nuttall, T. and Marsella, R.}, year={2015} }
 @article{bizikova_linder_olivry_2014, title={Fipronil-amitraz-S-methoprene-triggered pemphigus foliaceus in 21 dogs: clinical, histological and immunological characteristics}, volume={25}, number={2}, journal={Veterinary Dermatology}, author={Bizikova, P. and Linder, K. E. and Olivry, T.}, year={2014}, pages={103-} }
 @article{bizikova_2014, title={Localized demodicosis due to Demodex cati on the muzzle of two cats treated with inhalant glucocorticoids}, volume={25}, number={3}, journal={Veterinary Dermatology}, author={Bizikova, P.}, year={2014}, pages={222-} }
 @article{bizikova_olivry_mamo_dunston_2014, title={Serum autoantibody profiles of IgA, IgE and IgM in canine pemphigus foliaceus}, volume={25}, ISSN={["1365-3164"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84911375280&partnerID=MN8TOARS}, DOI={10.1111/vde.12143}, abstractNote={Pemphigus foliaceus (PF) is the most common IgG-mediated autoimmune skin disease in dogs. Studies of human PF have revealed the presence of other antigen-specific autoantibody isotypes, thereby uncovering new avenues of investigation of the disease pathomechanism. The aim was to obtain information about the autoantibody isotype response in canine PF. Sera from 34 dogs with PF were tested for the presence of antikeratinocyte, anti-desmocollin-1 and anti-desmoglein-1 IgA, IgE and IgM using indirect immunofluorescence. Using our indirect immunofluorescence technique, IgA, IgE and IgM autoreactivities were detected in six, one and zero of 34 sera from PF-affected dogs, respectively. Two of the six IgA-positive sera contained antikeratinocyte and anti-desmocollin-1 IgA, while the four remaining sera tested positive either for antikeratinocyte IgA (two of six) or for anti-desmocollin-1 IgA (two of six). A single serum contained anti-desmocollin-1 IgE. None of the six sera from healthy dogs contained detectable IgA, IgE or IgM autoantibodies. Our findings suggest that sera from dogs with PF rarely contain IgA or IgE autoantibodies at levels detectable by indirect immunofluorescence, while IgM autoreactivity appears not to be a feature of this disease. Considering these findings, it appears that canine PF is aetiologically and immunologically similar to that of the classic human PF, in which the IgG autoantibody response is also the predominant type. Le pemphigus foliacé (PF) est la dermatite auto-immune médiée par les IgG la plus fréquente chez le chien. Les études sur le PF humain ont révélé la présence d'autres isotypes d'auto-anticorps spécifiques d'antigènes. Le but était d'obtenir des informations sur l'isotype de réponse d'auto-anticorps dans le PF canin. Les sera de 34 chiens atteints de PF ont été testés pour la présence d'IgA, IgE et IgM anti-kératinocytes, anti-desmocolline-1 et anti-desmogléine par immunofluorescence indirecte. A l'aide de notre technique d'immunofluorescence indirecte, les auto-réactivités IgA, IgE et IgM ont été détectées respectivement pour six, un et zéro des 34 sera de chiens atteints de PF. Deux des six sera IgA-positifs contenaient des IgA anti-kératinocytes et anti-desmocolline-1 alors que les quatre autres sera testés étaient positifs soit pour les IgA anti-kératinocytes (deux sur six) et pour les IgA anti-desmocolline (deux sur six). Un seul serum contenait des IgE anti-desmocolline. Aucun des six sera issus de chiens sains de contenaient d'auto-anticorps IgA, IgG et IgM décelables. Nos données suggèrent que les sera des chiens atteints de PF contiennent rarement des auto-anticorps IgA et IgE à des niveaux décelables par immunofluorescence indirecte alors que l'auto-réactivité IgM semble ne pas être une caractéristique de cette maladie. Ainsi, il semble que le PF canin est étiologiquement et immunologiquement semblable au classique PF humain dans lequel les auto-anticorps IgG sont également le type prédominent. el pénfigo foliáceo (PF) es la enfermedad autoinmune más común mediada por IgG en perros. Los estudios de pénfigo foliáceo en humanos han desvelado la presencia de otros y isotipos de autoanticuerpos específicos del antígeno, por lo tanto abriendo nuevas avenidas en la investigación del patomecanismo de la enfermedad. el propósito fue obtener información acerca de isotipos de inmunoglobulina en la respuesta de autoanticuerpos en el pénfigo foliáceo canino. el suero de 34 perros con pénfigo foliáceo fue probado para la presencia de anticuerpos antiqueratinocitos, antidesmocolina-1 y antidesmogleina-1, de los isotipos IgA, IgE e IgM utilizando inmunofluorescencia indirecta. utilizando nuestro sistéma de inmunofluorescencia indirecta, se detectó autoreactividad de IgA, y IgE e IgM en 6, uno y ninguno de los 34 sueros de perros afectados con pénfigo foliáceo, respectivamente. Dos de los seis sueros positivos a IgA contenían IgA antiqueratinocitos y antidesmocolina-1, mientras que los 4 sueros restantes fueron positivos para IgA antiqueratinocitos (dos de seis) o para IgA antidesmocolina-1 (dos de seis). Un sólo suero contenía IgE antidesmocolina-1. Ninguno los seis sueros de los perros sanos contenía niveles detectables de autoanticuerpos IgA, IgE o IgM. nuestros hallazgos sugieren que el suero de perros con pénfigo foliáceo raramente contiene autoanticuerpos IgA o IgE a niveles detectables mediante inmunofluorescencia indirecta, mientras que la autoreactividad de IgM parece no ser una característica de esta enfermedad. Considerando estos hallazgos, parece que el pénfigo foliáceo canino es etiológicamente e inmunológicamente similar a la forma clásica de pénfigo foliáceo en humanos, en la cual la respuesta de autoanticuerpos IgG es también el tipo predominante. Pemphigus foliaceus (PF) ist die häufigste durch IgG-mediierte Autoimmunerkrankung bei Hunden. Studien über PF des Menschen haben das Vorkommen von anderen Antigen-spezifischen Autoantikörper Isotypen festgestellt, wobei neue Wege gezeigt wurden mit denen Pathomechanismen von Krankheiten untersucht werden können. Das Ziel dieser Studie war es, Information über die Antwort der Autoantikörper Isotypen beim PF des Hundes zu erlangen. Sera von 34 Hunden mit PF wurden auf das Vorkommen von Antikeratinozyten, Anti-desmocollin-1 und Anti-Desmoglein-1 IgA, IgE und IgM mittels indirekter Immunfluoreszenz getestet. Mithilfe unserer indirekten Immunfluoreszenztechnik wurden IgA, IgE bzw. IgM Autoreaktionen in sechs, einem bzw. keinem von 34 Sera von PF-betroffenen Hunden gefunden. Zwei der sechs IgA-positiven Sera wiesen Antikeratinzyten und Anti-Desmocollin-1 IgA auf, während die vier verbleibenden Sera entweder für Antikeratinozyten IgA (zwei von sechs) oder für Anti-Desmocollin-1 IgA (zwei von sechs) positiv waren. Ein einziges Serum wies Anti-Desmocollin-1 IgE auf. Keines der sechs Sera von gesunden Hunden wies messbare IgA, IgE oder IgM Autoantikörper auf. Unsere Ergebnisse zeigen, dass in Sera von Hunden mit PF selten IgA oder IgE Autoantikörper mittels indirekter Immunfluoreszenz gemessen werden können, während IgM Autoreaktivität kein Merkmal dieser Erkrankung sein dürfte. In Anbetracht dieser Ergebnisse scheint der PF des Hundes ätiologisch und immunologisch ähnlich zu sein, wie der klassische PF des Menschen, in welchem die IgG Autoantikörperantwort ebenfalls die vorherrschende Antwort darstellt.}, number={5}, journal={VETERINARY DERMATOLOGY}, author={Bizikova, Petra and Olivry, Thierry and Mamo, Lisa B. and Dunston, Stanley M.}, year={2014}, month={Oct}, pages={471–E75} }
 @article{olivry_bizikova_paps_dunston_lerner_yosipovitch_2013, title={Cowhage can induce itch in the atopic dog}, volume={22}, ISSN={["1600-0625"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84878344758&partnerID=MN8TOARS}, DOI={10.1111/exd.12158}, abstractNote={Itch is a cardinal symptom of atopic dermatitis in humans and dogs. Until now, experimental induction of itch in dogs has proven difficult. The objectives of this study were to determine whether protease-rich spicules, protein extracts and the protease mucunain of the tropical legume cowhage provoked itch and inflammation when rubbed onto canine skin. Native spicules variably induced itch manifestations in about half of the dogs, while challenges with protease-deactivated spicules remained negative. The epicutaneous application of cowhage extract and mucunain after microneedle roller usage also induced pruritus and inflammation. Importantly, there was an interindividual inconsistency in pruritus and inflammation induction and also marked differences in pruritus intensity after challenge. In conclusion, cowhage spicules, protein-rich extracts and mucunain can all induce pruritus and inflammation in dogs as in other species, but the inconsistency of provocation is currently a limitation of this challenge type for future studies of pruritus in dogs.}, number={6}, journal={EXPERIMENTAL DERMATOLOGY}, author={Olivry, Thierry and Bizikova, Petra and Paps, Judy S. and Dunston, Stan and Lerner, Ethan A. and Yosipovitch, Gil}, year={2013}, month={Jun}, pages={435–437} }
 @article{bizikova_dean_hashimoto_olivry_2012, title={Cloning and establishment of canine desmocollin-1 as a major autoantigen in canine pemphigus foliaceus}, volume={149}, ISSN={["0165-2427"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84866356195&partnerID=MN8TOARS}, DOI={10.1016/j.vetimm.2012.06.025}, abstractNote={Pemphigus foliaceus (PF) is the most common antibody-mediated autoimmune skin disease of dogs. Desmoglein-1 (DSG1), the major human PF antigen, represents only a minor autoantigen in canine PF (cPF). A recent immunomapping study proposed desmocollin-1 (DSC1) as a relevant candidate autoantigen for cPF. To investigate this hypothesis, 85 cPF sera were screened for the presence of anti-DSC1 IgG using indirect immunofluorescence (IIF) on live canine DSC1-transfected 293T cells. Seventy-five sera contained detectable antikeratinocyte IgG on IIF using footpad substrate (IIFpos cPF), while 10 did not (IIFneg cPF). Sera from 35 healthy dogs, eight from exfoliative superficial pyoderma (ESP)-affected dogs and 21 dogs with non-PF autoimmune blistering skin diseases served as controls. All sera were tested concurrently by IIF on canine DSG1-transfected as well as nontransfected cells. None of the healthy dog or ESP sera labelled any of the transfected or nontransfected cells. Fifty-seven of 75 IIFpos cPF (86%) and 7/10 of IIFneg cPF sera (70%) contained detectable anti-DSC1 IgG. None of these sera recognized nontransfected cells. Five cPF sera (6%) recognized DSG1 in addition to DSC1. Finally, 5/21 (24%) sera from dogs with non-PF autoimmune blistering diseases contained low anti-DSC1 IgG titers. In 7/10 dogs (70%), from whom serial serum samples were collected during treatment, anti-DSC1 IgG titers decreased in parallel with the reduction in disease clinical severity. Altogether, these findings suggest that DSC1 is a major autoantigen in cPF.}, number={3-4}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Bizikova, Petra and Dean, Gregg A. and Hashimoto, Takashi and Olivry, Thierry}, year={2012}, month={Oct}, pages={197–207} }
 @article{olivry_linder_wang_bizikova_bernstein_dunston_paps_casal_2012, title={Deficient plakophilin-1 expression due to a mutation in PKP1 causes ectodermal dysplasia-skin fragility syndrome in Chesapeake Bay Retriever dogs}, volume={7}, number={2}, journal={PLoS One}, author={Olivry, T. and Linder, K. E. and Wang, P. and Bizikova, P. and Bernstein, J. A. and Dunston, S. M. and Paps, J. S. and Casal, M. L.}, year={2012} }
 @article{olivry_linder_paps_bizikova_dunston_donne_mondoulet_2012, title={Validation of a novel epicutaneous delivery system for patch testing of house dust mite-hypersensitive dogs}, volume={23}, number={6}, journal={Veterinary Dermatology}, author={Olivry, T. and Linder, K. E. and Paps, J. S. and Bizikova, P. and Dunston, S. and Donne, N. and Mondoulet, L.}, year={2012} }
 @article{bizikova_linder_olivry_2011, title={Immunomapping of desmosomal and nondesmosomal adhesion molecules in healthy canine footpad, haired skin and buccal mucosal epithelia: comparison with canine pemphigus foliaceus serum immunoglobulin G staining patterns}, volume={22}, ISSN={["1365-3164"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-79952335927&partnerID=MN8TOARS}, DOI={10.1111/j.1365-3164.2010.00924.x}, abstractNote={Pemphigus foliaceus (PF) is the most common canine autoimmune skin disease. In contrast to human PF (hPF), desmoglein-1 is a minor autoantigen in the canine disease. The major autoantigen(s) of canine PF (cPF) remain(s) unknown, which limits the ability to perform mechanistic studies of lesion formation and the development of novel diagnostic and therapeutic strategies for this disease. The immunofluorescence patterns of selected desmosomal (desmoglein-1, desmoglein-3, desmocollin-1, desmocollin-3, desmoplakin-1/2, plakoglobin and plakophilin-1) and nondesmosomal adhesion proteins (E-cadherin, claudin-1, zona occludens-1 and occludin) in healthy canine footpad, haired skin and buccal mucosal epithelia were determined using hPF and pemphigus vulgaris sera and specific antibodies. The immunostaining patterns were then compared with that of indirect immunofluorescence staining with 66 cPF sera. Most cPF sera (58 of 66; 88%) exhibited positive staining along keratinocyte margins in the stratum spinosum and stratum granulosum of canine footpad. One serum contained autoantibodies binding solely to stratum granulosum keratinocytes. Concurrent intercellular fluorescence in the stratum basale was limited to seven of 66 cPF sera (11%). Only 12 of 66 cPF sera (18%) also exhibited positive IF staining of the buccal mucosa. This study confirms the immunological heterogeneity of cPF immunoglobulin G autoantibodies. Moreover, the major indirect immunofluorescence staining pattern and the inability of most cPF sera to label the buccal mucosa closely matched that of desmocollin-1. These observations warrant further investigation of desmocollin-1 as a potential major cPF autoantigen.}, number={2}, journal={VETERINARY DERMATOLOGY}, author={Bizikova, Petra and Linder, Keith E. and Olivry, Thierry}, year={2011}, month={Apr}, pages={132–142} }
 @article{oberkirchner_linder_dunston_bizikova_olivry_2011, title={Metaflumizone-amitraz (Promeris)-associated pustular acantholytic dermatitis in 22 dogs: evidence suggests contact drug-triggered pemphigus foliaceus}, volume={22}, ISSN={["0959-4493"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-80052525616&partnerID=MN8TOARS}, DOI={10.1111/j.1365-3164.2011.00974.x}, abstractNote={Promeris Duo (PD) is a novel topical flea and tick preventative for dogs, which is also licensed for treatment of canine demodicosis. In this article, we present 22 dogs that all developed pemphigus foliaceus (PF)-like cutaneous drug reactions at the site of PD application. In eight dogs, the lesions were restricted to the application site (localized group). Signs of systemic illness were reported in three dogs, and four required immunosuppressive treatment. Direct immunofluorescence for IgG was positive in four dogs, although circulating antikeratinocyte IgG could not be detected in any tested sera. Complete remission was achieved in all dogs, with one patient still remaining on treatment. Fourteen dogs developed skin lesions at the application site as well as other noncontiguous areas (distant group). Systemic signs were reported in 11 dogs, and immunosuppression was required in 10 cases. Direct and indirect immunofluorescence tests were positive for antikeratinocyte autoantibodies in 10 of 13 and six of 10 patients with distant disease, respectively. Complete remission was achieved in 10 of 13 dogs with distant disease; one-third are still on treatment. Histological changes were similar to canine PF. Desmosomal architectural changes, assessed by desmoglein-1 immunostaining, were also similar to those of dogs with spontaneous autoimmune PF. Apoptosis did not appear to contribute to lesion formation, in either autoimmune or PD-associated PF. In conclusion, PD has the potential of triggering a variant of PF that resembles spontaneously occurring autoimmune PF at clinical, morphological, immunological and treatment outcome levels. Le Promeris Duo (PD) est un nouveau topique préventif des puces et tiques pour chiens ayant également une indication pour le traitement de la démodécie canine. Dans cet article, nous présentons 22 chiens qui ont tous développé des réactions cutanées médicamenteuses PF-like (pemphigus foliaceus) au site d’application du PD. Chez huit chiens, les lésions étaient circonscrites au site d’application (groupe localisé). Des signes d’atteinte systémique ont été rapportés chez trois chiens et un traitement immunosuppressif a été nécessaire pour quatre chiens. Une immunofluorescence directe pour IgG était positive chez quatre chiens bien qu’aucun IgG anti-kératinocyte circulant n’ai été détecté quelque soit la zone testée. Il y a eu rémission complète pour tous les chiens, un d’entre eux restant encore sous traitement. Quatorze chiens ont développé des lésions cutanées sur le site d’application ainsi que sur d’autres zones non-contigües (groupe distant). Des signes systémiques ont été rapportés chez 11 chiens et une immunosuppression a été nécessaire dans 10 cas. Les tests d’immunofluorescence directe et indirecte étaient respectivement positifs pour les auto-anticorps anti-kératinocytes pour 10 sur 13 et 6 sur 10 des patients avec une atteinte à distance; un tiers sont encore sous traitement. Les modifications histologiques étaient identiques au PF canin. Les modifications architecturales desmosomales, mises en évidence par immunomarquage de la desmogléine-1, étaient également identiques à celles des chiens atteints de PF autoimmun spontané. L’apoptose ne semblait pas contribuer à la formation des lésions, ni pour les PF autoimmuns ni pour les PF associé au PD. En conclusion, le PD a le potentiel d’entrainer une variante de PF qui ressemble à un PF autoimmun spontané tant sur le plan clinique, morphologique, immunologique que sur les doses thérapeutiques nécessaires à sa résolution. Promeris Duo (PD) es un nuevo tratamiento tópico para pulgas y garrapatas para perros, también con licencia para el tratamiento de demodicosis. En este artículo se presentan 22 perros que desarrollaron lesiones similares a pénfigo foliáceo (PF) inducido por fármacos en las zonas de aplicación de PD. En ocho perros las lesiones se restringieron a la zona de aplicación (grupo localizado). Se observaron signos sistémicos en tres perros, y cuatro necesitaron tratamiento inmunosupresivo. Inmunofluorescencia directa para IgG fue positiva en cuatro perros, aunque no se detectó IgG circulante frente a queratinocitos en ninguno de los sueros probados. Se observo remisión completa en todos los perros, con un paciente aun bajo tratamiento. Catorce perros desarrollaron lesiones de la piel en el lugar de aplicación y en áreas no contiguas (grupo a distancia). Se observaron signos sistémicos en 11 perros, y se necesitó inmunosupresión en diez casos. Pruebas de inmunofluorescencia directa e indirecta resultaron positivas para autoanticuerpos frente a queratinocitos en diez de 13 y 6 de 10 pacientes con enfermedad a distancia, respectivamente. Se observó remisión completa en 10 de 13 perros con enfermedad a distancia; un tercio están aun en tratamiento. Los cambios histológicos fueron similares a PF canino. Cambios en la arquitectura de los desmosomas, demostrados mediante inmunotinción frente a desmogleina-1, fueron similares a aquellos con perros con PF espontáneo. Apoptosis no parecía contribuir a la formación de lesiones, ni en PF autoinmune ni en PF asociado a tratamiento con PD. En conclusión, PD tiene potencial de iniciar una variante de PF que se asemeja casos espontáneos de PF autoinmune a nivel clínico, morfológico, inmunológico y de respuesta al tratamiento. Promeris Duo (PD) ist ein neues topisches Produkt zur Floh- und Zeckenprophylaxe bei Hunden, welches auch für die Behandlung der caninen Demodikose lizenziert ist. In diesem Artikel präsentieren wir 22 Hunde, die alle Pemphigus foliaceus (PF)-ähnliche Hautreaktionen an der Stelle der PD Applikation entwickelten. Bei acht Hunden waren die Veränderungen auf die Applikationsstelle beschränkt (Gruppe: lokalisiert). Anzeichen von systemischer Erkrankung wurden bei drei Hunden beschrieben, bei vier Hunden war eine immunsuppressive Therapie nötig. Die direkte Immunfluoreszenz für IgG war bei vier Hunden positiv, obwohl zirkulierendes Antikeratinozyten IgG in keinem der untersuchten Seren gefunden werden konnte. Eine komplette Remission wurde bei allen Hunden erreicht, wobei ein Patient weiterhin behandelt wird. Vierzehn Hunde entwickelten Hautveränderungen an der Applikationsstelle, sowie an anderen nicht angrenzenden Stellen (Gruppe: entfernte Läsionen). Es wurden bei 11 Hunden systemische Symptome beschrieben und eine Immunsuppression war in zehn Fällen notwendig. Die direkten und indirekten Immunfluoreszenztests waren für Antikeratinozyten Autoantikörper bei zehn von 13 bzw. bei sechs der zehn Patienten mit Hautveränderungen an nicht angrenzenden Stellen positiv. Eine völlige Remission wurde bei 10 von 13 Hunden mit Hautveränderungen an nicht angrenzenden Stellen erreicht; ein Drittel dieser Hunde werden noch immer behandelt. Die histologischen Veränderungen waren ähnlich wie beim caninen PF. Architekturveränderungen der Desmosomen, die mittels Desmoglein-1 Immunfärbung erhoben wurden, waren ebenfalls jenen von Hunden mit spontanem autoimmunen PF ähnlich. Apoptose schien weder beim autoimmunen noch bei PD-assoziiertem PF an der Ausbildung der Läsionen beteiligt zu sein. Zusammenfassend kann man sagen, dass PD eine Variante von PF auslösen kann, die dem spontan auftretenden autoimmunen PF in klinischer, morphologischer und im Bezug auf Therapieerfolge ähnlich ist.}, number={5}, journal={VETERINARY DERMATOLOGY}, author={Oberkirchner, Ursula and Linder, Keith E. and Dunston, Stan and Bizikova, Petra and Olivry, Thierry}, year={2011}, month={Oct}, pages={436–448} }
 @article{olivry_bizikova_2010, title={A systematic review of the evidence of reduced allergenicity and clinical benefit of food hydrolysates in dogs with cutaneous adverse food reactions}, volume={21}, number={1}, journal={Veterinary Dermatology}, author={Olivry, T. and Bizikova, P.}, year={2010}, pages={31–40} }
 @article{olivry_bizikova_dunston_bond_halliwell_loeffler_pucheu-haston_chen_marinkovich_2010, title={Clinical and immunological heterogeneity of canine subepidermal blistering dermatoses with anti-laminin-332 (laminin-5) auto-antibodies}, volume={21}, number={4}, journal={Veterinary Dermatology}, author={Olivry, T. and Bizikova, P. and Dunston, S. M. and Bond, R. and Halliwell, R. and Loeffler, A. and Pucheu-Haston, C. M. and Chen, M. and Marinkovich, M. P.}, year={2010}, pages={345–357} }
 @article{bizikova_linder_suter_van wettere_olivry_2009, title={Canine cutaneous epitheliotropic T-cell lymphoma with vesiculobullous lesions resembling human bullous mycosis fungoides}, volume={20}, ISSN={0959-4493 1365-3164}, url={http://dx.doi.org/10.1111/j.1365-3164.2009.00760.x}, DOI={10.1111/j.1365-3164.2009.00760.x}, abstractNote={The broad spectrum of clinical signs in canine cutaneous epitheliotropic T-cell lymphoma mimics many inflammatory skin diseases and is a diagnostic challenge. A 13-year-old-male castrated golden retriever crossbred dog presented with multifocal flaccid bullae evolving into deep erosions. A shearing force applied to the skin at the periphery of the erosions caused the epidermis to further slide off the dermis suggesting intraepidermal or subepidermal separation. Systemic signs consisted of profound weight loss and marked respiratory distress. Histologically, the superficial and deep dermis were infiltrated by large, CD3-positive neoplastic lymphocytes and mild epitheliotropism involved the deep epidermis, hair follicle walls and epitrichial sweat glands. There was partial loss of the stratum basale. Bullous lesions consisted of large dermoepidermal and intraepidermal clefts that contained loose accumulations of neutrophils mixed with fewer neoplastic cells in proteinaceous fluid. The lifted epidermis was often devitalized and bordered by hydropic degeneration and partial epidermal collapse. Similar neoplastic lymphocytes formed small masses in the lungs associated with broncho-invasion. Clonal rearrangement analysis of antigen receptor genes in samples from skin and lung lesions using primers specific for canine T-cell receptor gamma (TCRgamma) produced a single-sized amplicon of identical sequence, indicating that both lesions resulted from the expansion of the same neoplastic T-cell population. Macroscopic vesiculobullous lesions with devitalization of the lesional epidermis should be included in the broad spectrum of clinical signs presented by canine cutaneous epitheliotropic T-cell lymphoma.}, number={4}, journal={Veterinary Dermatology}, publisher={Wiley}, author={Bizikova, Petra and Linder, Keith E. and Suter, Steven E. and Van Wettere, Arnaud J. and Olivry, Thierry}, year={2009}, month={Aug}, pages={281–288} }
 @article{bizikova_papich_olivry_2008, title={Hydroxyzine and cetirizine pharmacokinetics and pharmacodynamics after oral and intravenous administration of hydroxyzine to healthy dogs}, volume={19}, ISSN={["1365-3164"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-57449092680&partnerID=MN8TOARS}, DOI={10.1111/j.1365-3164.2008.00697.x}, abstractNote={Pharmacokinetic parameters of hydroxyzine and its active metabolite cetirizine were determined after oral and intravenous administration of 2 mg kg(-1) of hydroxyzine to six healthy dogs. Plasma drug levels were determined with high-pressure liquid chromatography. Pharmacodynamic studies evaluated the suppressive effect on histamine and anticanine IgE-mediated cutaneous wheal formation. Pharmacokinetic and pharmacodynamic correlations were determined with computer modelling. The mean systemic availability of oral hydroxyzine was 72%. Hydroxyzine was rapidly converted to cetirizine regardless of the route of administration. The mean area-under-the-curve was eight and ten times higher for cetirizine than hydroxyzine after intravenous and oral dosing, respectively. After oral administration of hydroxyzine, the mean peak concentration of cetirizine was approximately 2.2 microg mL(-1) and that of hydroxyzine 0.16 microg mL(-1). The terminal half-life for cetirizine varied between 10 and 11 h after intravenous and oral administration of hydroxyzine. A sigmoidal relationship was fit to the data comparing cetirizine plasma concentration to wheal suppression. Maximum inhibition (82% and 69% for histamine and anticanine IgE-mediated skin reactions, respectively) was observed during the first 8 h, which correlated with a plasma concentration of cetirizine greater than 1.5 microg mL(-1). Pharmacological modelling suggested that increasing either hydroxyzine dosages or frequencies of administration would not result in histamine inhibition superior to that obtained with twice daily hydroxyzine at 2 mg kg(-1). In conclusion, there was rapid conversion of hydroxyzine to cetirizine. The reduction of wheal formation appeared almost entirely due to cetirizine. Pharmacodynamic modelling predicted that maximal antihistamine effect would occur with twice daily oral administration of hydroxyzine at 2 mg kg(-1).}, number={6}, journal={VETERINARY DERMATOLOGY}, author={Bizikova, Petra and Papich, Mark G. and Olivry, Thierry}, year={2008}, month={Dec}, pages={348–357} }