@article{jordan_bizikova_2025, title={Canine and Feline Pemphigus Foliaceus-an Update on Pathogenesis and Treatment}, volume={55}, ISSN={["1878-1306"]}, DOI={10.1016/j.cvsm.2024.11.010}, number={2}, journal={VETERINARY CLINICS OF NORTH AMERICA-SMALL ANIMAL PRACTICE}, author={Jordan, Tyler J. M. and Bizikova, Petra}, year={2025}, month={Mar}, pages={321–336} }
@article{spriggs_gedon_linder_bizikova_2024, title={Comparison of selected cytomorphological features of canine pemphigus foliaceus and superficial pyoderma}, volume={6}, ISSN={["1365-3164"]}, url={https://doi.org/10.1111/vde.13267}, DOI={10.1111/vde.13267}, abstractNote={Abstract Background Cytological detection of acantholytic keratinocytes (acantholytic cells [AC]) helps to identify canine pemphigus foliaceus (cPF) yet AC also occurs in superficial pyoderma (SP), the main differential diagnosis. Hypothesis/Objectives To compare selected cytomorphological features of cPF and SP and to establish cytological diagnostic criteria that could differentiate cPF from SP. Animals 40 and 51 client‐owned dogs with PF and SP, respectively. Materials and Methods Impression smears from cPF (64), impetigo (40) and exfoliative superficial pyoderma (ESP) (17) samples were stained with Romanowsky stain, randomised, blinded and evaluated by two investigators independently. The entire sample was screened (×500 or ×1000 magnification) for round (AC1), boat (AC2) and raft AC, eosinophils and bacteria. Interobserver agreements were calculated. Results The average number of the 10 highest ×500 fields for AC1 and AC2 was significantly higher in PF than SP ( p < 0.0001; Kruskal–Wallis test). Rafts and eosinophils were more common in PF than SP ( p < 0.0001; chi‐square test), while bacteria were rare in PF (5%; p < 0.0001; chi‐square test). Observations between the experienced and novice investigators were highly correlated. An ROC analysis identified five AC1/×500‐magnification field as a suitable cut‐off value for predicting PF diagnosis. This cut‐off value was tested by two additional investigators, who identified sensitivity of 84%–100%, specificity of 95%–97% and accuracy of 95%–96% for the diagnosis of cPF. Conclusions and Clinical Relevance Criterion‐based impression smear cytological evaluation can provide strong evidence to support the clinical diagnosis. Acantholytic cell morphology varies in cPF and SP, and experience can improve accuracy in cytological differentiation.}, journal={VETERINARY DERMATOLOGY}, author={Spriggs, Tyler S. and Gedon, Natalie K. Y. and Linder, Keith E. and Bizikova, Petra}, year={2024}, month={Jun} }
@article{jordan_mamo_olivry_liu_bizikova_2024, title={Re-evaluating the prevalence of anti-desmocollin-1 IgA autoantibodies in canine pemphigus foliaceus}, volume={273}, ISSN={["1873-2534"]}, DOI={10.1016/j.vetimm.2024.110773}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Jordan, Tyler J. M. and Mamo, Lisa B. and Olivry, Thierry and Liu, Zhi and Bizikova, Petra}, year={2024}, month={Jul} }
@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"]}, url={https://doi.org/10.1111/vde.13174}, DOI={10.1111/vde.13174}, abstractNote={Abstract Background 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. Hypothesis/Objectives This study describes the histopathological findings of trunk‐dominant PF, and compares the results to classic facial and insecticide‐triggered PF. Animals Skin biopsies from 103 dogs with clinically characterised trunk‐dominant (n = 33), classic facial (n = 26) and insecticide‐triggered PF (n = 44) were included. Materials and Methods 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. Results In trunk‐dominant PF, 77 intact pustules were predominantly subcorneal (0.0019–1.940 mm 2 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. Conclusions and Clinical Relevance 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.}, 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‐β, in dogs with atopic dermatitis}, volume={34}, ISSN={0959-4493 1365-3164}, url={http://dx.doi.org/10.1111/vde.13140}, 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.}, number={2}, journal={Veterinary Dermatology}, publisher={Wiley}, 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}, pages={107–114} }
@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}, volume={6}, ISSN={["1365-3164"]}, url={https://doi.org/10.1111/vde.13094}, DOI={10.1111/vde.13094}, abstractNote={Abstract Background Canine trunk‐dominant pemphigus foliaceus (PF) is mentioned rarely in the literature. Hypothesis/Objectives 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. Materials and methods 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. Results 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. Conclusions 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.}, journal={VETERINARY DERMATOLOGY}, publisher={Wiley}, 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"]}, url={https://doi.org/10.1111/vde.12982}, DOI={10.1111/vde.12982}, abstractNote={Background 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. Hypothesis/Objectives To describe the clinical features, laboratory analysis and histopathological features of an unique presentation of bullous disease in a horse. Animals A 17‐year‐old thoroughbred mare presented for weight loss and severe oral cavity ulcers. Methods and materials Investigations involved haematological evaluation, chemistry profiles, gastroscopy and serum protein electrophoresis, and, postmortem, histopathological evaluation, Congo‐red staining and transmission electron microscopy (TEM). Results 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. Conclusion and Clinical Importance 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.}, number={4}, journal={VETERINARY DERMATOLOGY}, publisher={Wiley}, 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={Background Junctional epidermolysis bullosa (JEB) is a group of congenital blistering skin diseases characterized by clefting through the lamina lucida of the basement membrane zone. Objectives 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. Animals 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. Methods and materials 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. Results 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. Conclusions and clinical relevance A novel variant in LAMA3 caused a generalized and severe phenotype of JEB with an unique clinical presentation of upper airway obstruction.}, number={4}, journal={VETERINARY DERMATOLOGY}, publisher={Wiley}, 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"]}, url={https://doi.org/10.1111/vde.12933}, DOI={10.1111/vde.12933}, abstractNote={Background Feline allergic skin disease and asthma occur regularly in small animal practice. Objectives To provide evidence‐based recommendations for small animal practitioners on the treatment of feline atopic syndrome (FAS). Methods and materials The authors reviewed the literature available before February 2020, prepared a detailed evidence‐based literature review and made recommendations based on the evaluated evidence. Results 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. Conclusion and clinical relevance 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.}, number={1}, journal={VETERINARY DERMATOLOGY}, publisher={Wiley}, 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"]}, url={https://doi.org/10.1111/vde.12851}, 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}, publisher={Wiley}, 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"]}, url={https://doi.org/10.1111/vde.12861}, 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. HYPOTHÈSES/OBJECTIFS: 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. MATÉRIELS ET MÉTHODES: Les sera ont été testé par immunofluorescence indirecte sur les coussinets de chat et sur substrats de muqueuse buccale. RÉSULTATS: 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.INTRODUCCIÓN: 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. HIPÓTESIS/OBJETIVOS: Detectar autoanticuerpos anti-queratinocitos circulantes en gatos afectados por PF y determinar sus títulos y patrones de tinción de tejidos. ANIMALES: se compararon treinta gatos afectados por PF con 11 gatos libres de patógenos específicos, 15 gatos sanos y 31 alérgicos. MÉTODOS Y MATERIALES: los sueros se probaron por inmunofluorescencia indirecta en sustratos de almohadilla canina y de la mucosa bucal. RESULTADOS: 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. CONCLUSIONES E IMPORTANCIA CLÍNICA: 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.背景: 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。 仮説/目的: 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。 供試動物: 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。 材料と方法: 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。 結果: 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。 結論と臨床的重要性: 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。.背景: 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。 假设/目的: 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。 动物: 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。 方法和材料: 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。 结果: 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。 结论和临床重要性: 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. HIPÓTESE/OBJETIVOS: 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. MÉTODOS E MATERIAIS: 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. CONCLUSÕES E IMPORTÂNCIA CLÍNICA: 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.}, number={5}, journal={VETERINARY DERMATOLOGY}, publisher={Wiley}, 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"]}, url={https://doi.org/10.1111/vde.12841}, 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}, publisher={Wiley}, 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"]}, url={https://doi.org/10.1111/vde.12878}, DOI={10.1111/vde.12878}, abstractNote={Résumé Contexte 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. Objectifs Déterminer l'innocuité et l'efficacité de BTKi PRN 1008 dans le traitement de cPF. Sujets 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. Conclusions et importance clinique BTK1 PRN 1008 en monothérapie pourrait avoir des effets bénéfiques dans certains cas de cPF.}, number={5}, journal={VETERINARY DERMATOLOGY}, publisher={Wiley}, 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"]}, url={https://doi.org/10.1111/vde.12852}, DOI={10.1111/vde.12852}, abstractNote={Background 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. Objectives To describe successful treatment of HKEM in two dogs using oclacitinib. Animals A 7‐year‐old, spayed Havanese dog (Case 1) and a 1‐year‐old, intact cryptorchid Dachshund dog (Case 2). Methods Case characterization and clinical diagnoses were based on lesion character, surgical biopsy, cytological evaluation, culture, direct immunofluorescence (DIF) and expected responses to treatments. Results 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. Conclusion and Clinical Importance Oclacitinib could be considered as a fast‐acting and effective treatment option for HKEM in dogs.}, number={4}, journal={VETERINARY DERMATOLOGY}, publisher={Wiley}, 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"]}, url={https://doi.org/10.1186/s12917-018-1739-y}, 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.}, number={1}, journal={BMC VETERINARY RESEARCH}, publisher={Springer Science and Business Media LLC}, 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.}, 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.}, 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={Background 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. Objectives 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 . Results 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. Conclusion and clinical importance 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={Background 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. Hypothesis/Objectives The aim was to obtain information about the autoantibody isotype response in canine PF . Methods 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. Results 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. Conclusions and clinical importance 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.}, 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={Abstract 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={Abstract 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.}, 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={Abstract 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 (TCRγ) 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} }