Treatment of the feline atopic syndrome - a systematic review
[Review of ]. VETERINARY DERMATOLOGY, 32(1), 43-+.
Feline allergic skin disease and asthma occur regularly in small animal practice. To provide evidence-based recommendations for small animal practitioners on the treatment of feline atopic syndrome (FAS). The authors reviewed the literature available before February 2020, prepared a detailed evidence-based literature review and made recommendations based on the evaluated evidence. Sixty-six papers and abstracts were identified describing treatment interventions for FAS and evaluated to establish treatment recommendations. For many treatment options, the papers were retrospective, open studies or case reports. In this review, there was good evidence for the efficacy of systemic glucocorticoids and ciclosporin, and limited evidence for the efficacy of topical glucocorticoids, oclacitinib and allergen-specific immunotherapy in feline atopic skin syndrome. Evidence pointed to low-to-moderate efficacy for antihistamines, fatty acids and palmitoyl ethanolamide. In feline asthma, there was good evidence for the efficacy of oral and inhaled glucocorticoids, and limited evidence of moderate efficacy for allergen-specific immunotherapy. Evidence supported low-to-moderate efficacy of mesenchymal stem cells, inhaled lidocaine and oclacitinib as treatments for feline asthma. For almost all therapeutic options (with the exception of glucocorticoids and ciclosporin), more randomised controlled trials are needed. La maladie cutanée allergique féline et l’asthme sont fréquents en pratique vétérinaire. Fournir des recommandations basées sur les preuves pour les praticiens des petits animaux de compagnie sur le traitement du syndrome atopique félin (FAS). Les auteurs ont revu la littérature disponible avant février 2020, préparé une revue détaillée de la littérature basée sur les preuves et fait des recommandations à partir des niveaux de preuves. Soixante-six articles et résumés ont été identifiés décrivant les traitements pour FAS et évalués pour établir des recommandations de traitement. Pour de nombreuses options de traitement, les articles étaient rétrospectifs, des études ouvertes ou des cas cliniques. Dans cette revue, il y a un bon niveau de preuve de l’efficacité des corticoïdes systémiques et de la ciclosporine, et des preuves imitées de l’efficacité des corticoïdes topiques, de l’oclacitinib et de l’immunothérapie spécifique d’allergènes dans le syndrome cutané atopique félin. Les preuves montrent une efficacité faible à modérée des antihistaminiques, des acides gras essentiels et du palmytoyléthanolamide. Dans l’asthme félin, il y a de bonnes preuves de l’efficacité des corticoïdes oraux et inhalés, et peu de preuves d’efficacité modérée pour l’immunothérapie spécifique d’allergènes. Les preuves supportent une efficacité faible à modérée des cellules souches mésenchymateuses, de la lidocaïne inhalée et de l’oclacitinib comme traitements de l’asthme félin. Pour presque toutes les options thérapeutiques (à l’exception des corticoïdes et de la ciclosporine), davantage d’études contrôlées randomisées sont nécessaires. el síndrome atópico felino (FAS) describe un espectro de trastornos de hipersensibilidad caracterizados por presentaciones clínicas muy diversas que incluyen la piel, los sistemas gastrointestinal y respiratorio. Entre estos trastornos se encuentra el síndrome de piel atópica felina (FASS), en el que la hipersensibilidad se asocia típicamente con alérgenos ambientales, aunque la alergia alimentaria puede coexistir. También puede producirse la afectación de otros sistemas orgánicos (por ejemplo asma). Debido a su presentación clínica altamente heterogénea, el diagnóstico de FASS puede ser difícil. Se encomendó a un subgrupo del Comité Internacional sobre Enfermedades Alérgicas de los Animales (ICADA) que resumiera la información más actual sobre las presentaciones clínicas de FASS y que desarrollara pautas de diagnóstico recomendadas. Se realizaron búsquedas en la red de bases de datos de referencias y resúmenes de reuniones internacionales relacionadas con alergias felinas. Éstos se combinaron con la opinión de expertos cuando fue necesario. Se identificaron un total de 107 publicaciones relevantes para esta revisión. La recopilación de estos datos permitió el desarrollo de una descripción detallada de las características clínicas de FASS y el desarrollo de pautas centradas en la eliminación sistemática de otras afecciones de la piel con características clínicas similares. Dado que los dermatólogos utilizan con frecuencia las pruebas de alergia para respaldar un diagnóstico clínico de FASS, también se realizó una breve revisión de estas metodologías. De manera similar a la dermatitis atópica en perros, FASS es un diagnóstico clínico basado en la presencia de signos clínicos compatibles y la exclusión de otras enfermedades con características clínicas similares. La eliminación o exclusión de pulgas/alergia a pulgas, otros parásitos, infecciones y alergia alimentaria es necesaria antes de llegar a un diagnóstico de FASS. Allergische Hauterkrankungen der Katzen sowie Asthma treten in der Kleintierpraxis häufig auf. Es war das Ziel, Evidenz-basierte Empfehlungen für Kleintierpraktiker bei der Behandlung des felinen atopischen Syndroms (FAS) zu liefern. Die Autoren führten eine Review der Literatur, die vor Februar 2020 zur Verfügung stand, durch und bereiteten eine detaillierte Evidenz-basierte Literatur Review vor und sprachen Empfehlungen, basierend auf der evaluierten Evidenz, aus. Sechsundsechzig Papers und Abstracts, die Behandlungen des FAS beschrieben, wurden identifiziert und evaluiert, um Behandlungsempfehlungen zu schaffen. Für viele Behandlungsoptionen standen retrospektive Papers, offene Studien und Fallberichte zur Verfügung. In dieser Review ergab sich eine gute Evidenz für die Wirksamkeit der systemischen Glucokortikoide und Ciclosporin, sowie eine limitierte Evidenz für die Wirksamkeit topischer Glucokortikoide, Oclacitinib und Allergen-spezifischer Immuntherapie für das feline atopische Hautsyndrom. Die Evidenz zeigte eine niedrig-bis-moderate Wirksamkeit von Antihistaminen, essentiellen Fettsäuren und Palmitoyl Ethanolamid. Bei Katzenasthma ergab sich eine gute Evidenz für orale oder inhalierte Glucokortikoide und eine limitierte Evidenz von moderater Wirksamkeit für Allergen-spezifische Immuntherapie. Die Evidenz stützte eine niedrig-bis-moderate Wirksamkeit der mesenchymalen Stammzellen, von inhaliertem Lidocain und Oclacitinib als Behandlungen für felines Asthma. Für fast alle therapeutischen Optionen (mit Ausnahme der Glucokortikoide und Ciclosporin) sind weitere, randomisierte kontrollierte Studien nötig. 猫のアレルギー性皮膚疾患および喘息は小動物の診療で定期的に発生する。 本研究の目的は、猫アトピー症候群 (FAS) の治療に関するエビデンスに基づく推奨事項を小動物の施術者に提供することであった。 著者は、2020年2月より前に入手可能な文献をレビューし、詳細なエビデンスに基づく文献レビューを作成し、評価されたエビデンスに基づいて推奨を行った。 FASの治療介入を説明する66の論文および要約を特定し、治療の推奨事項を確立するため評価した。多くの治療オプションについて、論文は遡及的、公開研究または症例報告であった。 本レビューでは、全身性糖質コルチコイド製剤およびシクロスポリン製剤の有効性に関するエビデンスがあり、猫アトピー性皮膚症候群における外用糖質コルチコイド製剤、オクラシチニブ、およびアレルゲン特異的免疫療法の有効性に関するエビデンスは限定的であった。エビデンスは、抗ヒスタミン薬、脂肪酸、パルミトイルエタノールアミドの有効性が低から中程度であることを示している。ネコ喘息では、経口および吸入糖質コルチコイド製剤の有効性に関する十分なエビデンスがあり、アレルゲン特異的免疫療法に対する中程度の有効性の限定的なエビデンスがあった。エビデンスは、ネコ喘息の治療としての間葉系幹細胞、吸入リドカインおよびオクラシチニブの低から中程度の有効性を支持した。ほぼすべての治療オプション (糖質コルチコイドおよびシクロスポリン製剤を除く) については、さらにランダム化比較試験が必要である。 宠物主人经常在线查阅兽医学信息来源。然而, 关于这些资源的可读性以及可读性是否适合宠物主人教育水平, 数据很有限。 评价美国养宠物人群的文化程度, 确定宠物过敏信息的可读性, 并比较在线宠物过敏信息与在线人类过敏信息的可读性。 208,525,282人中的4933名成人亚群, 回答国家健康和营养问卷调查(NHANES)的人类和宠物相关问题。过敏信息来自6个健康网站 (3个兽医网站, 3个人类网站) 中的54篇文章 (28篇兽医的, 26篇人类的) 。 对10294份NHANES问卷回答进行分析, 找出4933名拥有宠物的成人亚群。根据宠物和人类过敏信息计算Flesch阅读难易度评分和Flesch–Kincaid等级评分, 以评价可读性。 与无宠物的成人(78.5±1.5%,P < 0.0001)相比, 拥有宠物的成人(85.8±1.33%)高中毕业的年龄标化率更高。与人类健康网站相比, 兽医网站的过敏信息更难阅读(P = 0.0052), 撰写水平更高(P = 0.0047)。平均兽医学信息可读性评分为45.9±8.7 (“难以阅读”) , 且撰写水平在11级或以上 (范围:8级-高等职业学院水平) 。 兽医网站上的过敏信息比人类健康网站上的过敏信息更难阅读。在线兽医学信息的撰写水平与宠主的阅读水平不匹配。 A asma e a dermatopatia alérgica felina ocorrem regularmente na clínica de pequenos animais. Fornecer recomendações baseadas em evidências para clínicos de pequenos animais sobre o tratamento da síndrome atópica felina (SAF). Os autores revisaram a literatura disponível até fevereiro de 2020, prepararam uma revisão de literatura baseada em evidências e fizeram recomendações baseadas nas evidências avaliadas. Sessenta e seis artigos e resumos foram identificados descrevendo o tratamento da SAF e avaliados para estabelecer as recomendações de tratamento. Para muitas opções de tratamento, os artigos foram retrospectivos, estudos abertos ou relatos de caso. Nessa revisão, houve boa evidência de eficácia de do uso de corticoides sistêmicos e ciclosporina, e evidência limitada da eficácia de glicocorticoides tópicos, oclacitinib e imunoterapia alérgeno-específica na síndrome atópica cutânea felina. Houve evidência de eficácia baixa a moderada para anti-histamínicos, ácidos graxos palmitoil etanolamida. Na asma felina, houve boa evidência de eficácia para glicocorticoides por via oral ou inalada, e evidência limitada de eficácia moderada para imunoterapia alérgeno-específica. As evidências demonstraram eficácia baixa a moderada para a para células-tronco mesenquimais, lidocaína inalada e oclacitinib no tratamento da asma felina. Para quase todas as opções terapêuticas (com exceção dos glicocorticoides e ciclosporina), são necessários mais estudos randomizados e controlados. Feline atopic syndrome (FAS) is the newly-proposed terminology encompassing allergic diseases of the skin, gastrointestinal and respiratory tract in the cat. Feline atopic skin syndrome (FASS) describes allergic skin disease associated with environmental allergies.1-3 Allergic dermatitis in the cat presents with multiple cutaneous reaction patterns that all may be caused by environmental, food and/or insect allergens, as well as other diseases. Those reaction patterns include miliary dermatitis, self-induced alopecia/hypotrichosis, the eosinophilic granuloma complex (eosinophilic granuloma, eosinophilic plaque, indolent ulcer) and/or excoriations-ulcers on the head and neck.3 Consequently, the treatment of these reaction patterns will depend on their aetiology, and other causes such as food allergy or flea bite hypersensitivity must be ruled out before diagnosing FASS. Feline asthma is a common lower airway inflammatory condition in cats with significant morbidity and occasional mortality. From a clinical and pathogenetic point of view, feline asthma is remarkably similar to the human disease. As in humans, affected cats exhibit a spontaneous and natural hyper-reactivity of the airways resulting in a reversible bronchoconstriction, airway inflammation and chronic remodelling.4 Intradermal and serum testing for allergen-specific immunoglobulin (Ig)E is not suitable for the diagnosis of FAS. Similar to dogs, the FASS is diagnosed based on the history, clinical signs and exclusion of differential diagnoses appropriate to each case.5 Over the last decades, different treatments have been reported for FAS variants, yet to the best of the authors' knowledge, a systematic review of all available therapeutic and preventive interventions has not been published. The aim of this review was therefore to summarise and review the published evidence for the various treatment options for the cutaneous and respiratory components of FAS. It was not within the remit of this paper to discuss the aetiology, pathogenesis and diagnosis of these diseases. These subjects are reviewed in other papers in this series and readers are directed to them for more information.1-3 In order to evaluate the efficacy and safety of treatments for the two main FAS manifestations (FASS and asthma), online bibliographic databases (PUBMED and WEB OF SCIENCE) and scientific meeting proceedings were searched for relevant published studies or abstracts of sufficient detail for analysis. The bibliographies of identified studies and of main veterinary dermatology textbooks were further evaluated. Studies were analysed and their value determined based on the quality of their evidence (QOE). They were summarised and, based on the available data, a given treatment's efficacy was determined and its reported adverse effects listed. Thereafter a recommendation about each treatment option was given, with the strength of recommendation (SOR) based on the QOE (Table 1). Data evaluation and strength of recommendations were modelled after previous practice guidelines for human6, 7 and canine atopic dermatitis (cAD).8 We found a total of 72 papers and abstracts describing treatment interventions for FAS. These included 58 clinical trials and eight case reports evaluating efficacy of treatments,9-16 five safety and pharmacokinetic studies in healthy cats,17-21 and one retrospective safety study (without reporting efficacy).22 Of the 55 clinical trials, six were available only as abstracts23-28 and 49 had been published in peer-reviewed journals. There were 48 prospective and 10 retrospective studies.23, 35 Of the prospective studies, 19 were open and uncontrolled24, 52 while 29 were randomised, controlled53-59 and often blinded.26, 42, 79 These studies included clinical trials on allergen avoidance, allergen(-specific) immunotherapy (ASIT), topical, inhaled and systemic glucocorticoids, ciclosporin, oclacitinib, bronchodilators, H1-receptor (H1R) antihistamines, essential fatty acids (EFA) and palmytoylethanolamide, antibiotics, inhaled lidocaine and mesenchymal stem cells. Thirty-three of the reports focused on the reaction patterns of FASS, while 23 studies evaluated feline asthma. Eleven of those latter studies originated from the same research group using cats experimentally sensitised to various allergens and five from another colony of cats sensitised to Ascaris suum. In some reports, cats with respiratory or cutaneous manifestations were included.15, 29 In one retrospective study of 29 asthmatic cats35 and one prospective study on 20 asthmatic cats,47 avoidance of allergens was reported for individual cases. We could not find any such evidence for FASS. In the above-mentioned studies, one cat sensitised to human dander improved after access to the owner's bedroom was restricted.35 Changing from dry food to a moist diet led to the complete remission of clinical signs in three cats allergic to storage mites.47 Although allergen avoidance is common sense and should be effective (QOE 3; SOR C), it is often unfeasible in cats sensitised to environmental allergens. There is only limited evidence for the benefit of allergen avoidance in asthmatic cats,35, 47 and no such information exists for FASS. Eleven reports evaluated ASIT in a total of 197 cats with FASS.12, 32 Five retrospective studies specifically evaluated ASIT in 70 cats with different reaction patterns of FASS.23, 25, 30, 32 Seventeen cats had miliary dermatitis, 21 had noninflammatory alopecia, 18 had eosinophilic lesions16, 25, 30, 32 and in one study the clinical signs were not detailed.23 Two of these reports were abstracts in proceedings from World Congresses of Veterinary Dermatology and thus not sufficiently detailed.23, 25 Likewise, one prospective open study evaluating sublingual ASIT was a conference abstract.28 One report described the response to ASIT in three littermates with atopic skin disease,12 one case series described four cats with miliary dermatitis and eosinophilic granuloma,16 and another focused on rush immunotherapy (RIT) in four atopic cats,13 although treatment outcomes were not described in the latter report. One larger study was based on a questionnaire sent out by a laboratory after serum testing for allergen-specific IgE and subsequent orders for ASIT in 81 cats, six of which had lower respiratory tract disease.29 The last study evaluated 45 cats with FASS, 23 of which underwent AIT.31 Definitions of a good, moderate, partial or no response varied and often were unclear. In one study, an excellent response was described as complete remission of the patient with no concurrent medication and was seen in 26% of the cats.23 In the study using a survey sent out to veterinarians treating cats with ASIT after serum testing for allergen-specific IgE, lesional scores were assigned and the percentage of improvement calculated.29 In another study, concurrent medications were not discussed;32 in many reports concurrent medications were mentioned and details not given. Five studies evaluated cats with respiratory disease/asthma. In an older retrospective study, veteriarians submitting feline serum specimens for allergen-specific IgE testing were asked to complete a follow-up questionnaire, six cats with respiratory clinical signs undergoing ASIT were included.29 One study focussed on ASIT as treatment for 12 asthmatic cats showing sensitization to aeroallergens based on intradermal testing.47 Three studies were performed in an experimental model of feline asthma in which cats were sensitised to Bermuda grass and house dust mites.59, 65, 76 In the first randomised controlled trial (RCT), intranasal or subcutaneous RIT were compared.59 In a second study using the same model, cats received RIT with an allergen that they were not sensitised to or with only one of the two allergens they were sensitised to.76 The third study evaluated the influence of oral and inhaled glucocorticoids on the outcome of RIT.65 In one conference abstract, a cat with cutaneous and respiratory sign was treated with ASIT using a recombinant Der f 2-based vaccine.15 The results of ASIT for FASS were reported in 210 cats (Table 2). The reported efficacy was between 45 and 75%, similar to what is reported for dogs.80, 81 One of the studies did not evaluate treatment outcome, and looked only at the safety of RIT in four cats with FASS.13 References Type of study Martin et al. 201915 Case report Foj et al. 201928 Abstract of case series Ravens et al. 201431 ReSt Schnabl et al. 200616 Case series Moriello 200112 Case report Bettenay 199823 ReSt Results of ASIT in 80 cats with asthma are listed in Table 3. In one study a complete remission of clinical signs was observed in eight of 12 cats with naturally occurring asthma (67%) in which symptomatic therapy with glucocorticoids could be discontinued on ASIT. Four cats still required pharmacotherapy, including inhaled corticosteroids and bronchodilators.47 In a retrospective study, veterinarians treating 12 cats with suspected feline asthma reported a good response via questionnaire.29 References Type of study Lee-Fowler et al. 200959 RCT Chang et al. 201326 RCT Reinero et al. 201276 RCT Prost 200847 Case series Three studies evaluated ASIT in cats with experimentally induced asthma.59, 65, 76 In the first RCT, intranasal or subcutaneous RIT improved clinical signs and dampened eosinophilic inflammation of the airways.59 However, intranasal RIT had fewer adverse effects and a decreased interleukin (IL)-4/interferon-gamma ratio in the bronchoalveolar lavage fluid (BALF).59 In the second study, airway eosinophilia decreased and the percentage of regulatory T cells and IL-10-producing cells increased in cats treated with RIT compared to controls independent of their sensitisation status and content of the allergen extract, indicating nonspecific effects. However, only matched allergens could potentially induce an immunological cure.76 In the same model of feline asthma, cats given oral prednisolone at 10 mg once daily over the first six months of ASIT showed an increased percentage of eosinophils in the BALF after nine months of ASIT by contrast with inhaled fluticasone at 220 mcg twice daily.65 Adverse effects were not mentioned in ten reports.12, 76 After RIT, two of four cats showed increased pruritus and in two of four a dermal alopecic nodule developed one week after initiation of therapy.13 ASIT seems to be an efficacious therapy for FASS (QOE 2; SOR B). However, some studies were presented only as abstracts with very limited information,23, 25 none of the studies were controlled or randomised, and all were characterised by unclear outcome measures, making final assessment difficult. By contrast, there is evidence of moderate-to-good efficacy of ASIT in naturally occurring feline asthma (QOE 2; SOR B) and moderate efficacy of RIT in cats with experimental asthma (QOE 1; SOR A). Adverse effects seem to be rare (QOE 1; SOR A). More studies on ASIT in cats are needed urgently. Three prospective double-blinded RCTs evaluated systemic glucocorticoid treatment in cats with FASS.60, 62, 64 One prospective study looked at the diabetogenic potential of prednisolone and dexamethasone in healthy cats.56 The three clinical trials included 63 cats: 11 treated with prednisolone, 36 with methylprednisolone and 16 with triamcinolone. The treatment regimens used dosages of 1 mg/kg once daily of prednisolone, 0.77 mg/kg twice daily (20 cats) to 1.4 mg/kg once daily (16 cats) of methylprednisolone, and 0.18 mg/kg once daily of triamcinolone acetonide for 2862, 64 to 8460 days. The latter study used daily treatment for ≤14 days to achieve remission and then tapered treatment resulting in final alternate day dosages of 0.54 mg/kg methylprednisolone and 0.08 mg/kg triamcinolone.60 Pruritus was assessed using a 0–10 Visual Analog Scale82 (pVAS) in two studies60, 62 and a 0–5 Linear Analog Scale in one.64 Lesion scores were assessed using the Canine Atopic Dermatitis Extent and Severity Index, 2nd iteration (CADESI-02),64, 83 a Feline Erythema, Excoriation and Alopecia score (FEEAS; a modified CADESI-03 score omitting lichenification),60 and a Scoring Feline Allergic Dermatitis (SCORFAD) scale.62 Only the SCORFAD scale had been validated for pruritic and eosinophilic skin lesions in cats.84, 85 One study62 included a validated Quality of Life (QoL) score.86 The cats presented with pruritus and a variety of the recognised reaction patterns associated with FASS. Most cats presented with more than one type of lesion. The seasonality of the clinical signs was not recorded. One cross-over RCT compared oral prednisolone at 10 mg/day with inhaled flunisolide at 250 µg twice daily in six cats with feline asthma experimentally sensitised to Bermuda grass.66 Another cross-over RCT treated six cats sensitised to A. suum with either oral prednisolone at 1 mg/kg twice daily, 500 mcg of inhaled fluticasone proprionate twice daily, or a combination of inhaled fluticasone propionate and salbutamol at 500 mcg and 50 mcg, respectively, for four consecutive days.71 A study with 14 client-owned cats with lower airway disease assessed airway function before and after prednisolone therapy.48 Treatment outcome data were available for 63 cases with FASS (see Table 4). Cats that responded to treatment were reported to do so within 7–14 days. There was no association between the responses to treatment and the type of lesions. References Type of study Methylprednisolone (n = 16, not all cats had an elimination diet) Ganz 201260 RCT Methylprednisolone (n = 20) Noli 201962 RCT Triamcinolone (n = 16, not all cats had an elimination diet) Ganz 201260 RCT Wisselink 200964 RCT Although prednisolone decreased allergen-specific IgE and the percentage of eosinophils in the BALF of cats experimentally sensitised to Bermuda grass, it did not improve airway hyper-reactivity in response to methacholine.66 In the A. suum-sensitised cats there were no significant differences in respiratory rate or Penh [an estimate of airflow limitation measured by conventional barometric whole body plethysmography (BWBP)] between the treatment groups.71 Allergen-induced airway hyper-responsiveness was significantly inhibited by the oral prednisolone, inhaled fluticasone proprionate and inhaled fluticasone propionate/salbutamol. The mean BALF eosinophil percentage was lower after oral and inhaled corticosteroid treatment and these changes were significant for groups receiving prednisolone and the combination of inhaled fluticasone propionate/salbutamol,71 although the dose of inhaled fluticasone was fairly high. In the study with client-owned cats with lower airway disease, a significantly decreased peak to mid-expiratory flow and no significant changes in other BWBP parameters were noted after at least three weeks of therapy with prednisolone at 1.2–2 mg/kg once daily.48 Clinical adverse effects were uncommon, with one case each of vomiting and lethargy among the 20 cats treated with methylprednisolone.62 Clinicopathological abnormalities included increased liver enzymes in one of 16 triamcinolone- and eight of 36 methylprednisolone-treated cats.60, 62 Hyperglycaemia was seen in four, altered haematological parameters in four, and glycosuria in one of the 36 methylprednisolone-treated cats. Mean albumin and fructosamine levels significantly increased in triamcinolone- (n = 16) and methylprednisolone-treated cats (n = 16) and remained within the reference ranges.60 Amylase was elevated above the reference range in 10 of 15 triamcinolone- and two of 14 methylprednisolone-treated cats at the end of the induction phase, and returned to normal during the every other day maintenance phase.60 The safety study evaluated 14 cats treated with either 4.4 mg/kg once daily of prednisolone or 0.55 mg/kg once daily of dexamethasone for 56 days.56 Dexamethasone treatment resulted in significantly increased fructosamine concentration, decreased insulin sensitivity and secretion, and increased glycosuria, although the cats did not become hyperglycaemic at any point. No adverse effects were mentioned in most of the studies evaluating asthmatic cats.48, 66, 71 One study evaluated long-term effects of glucocorticoids in asthmatic cats and found adverse effects such as polyuria and polydipsia, diabetes mellitus and fungal infection in four of 34 cats.27 A study evaluating long-term safety (at least three years) of methylprednisolone in 25 cats detected an increase of triglycerides, amylase and monocytes, yet changes remained within the reference interval.87 Systemic glucocorticoids are rapid and effective in most cats with FASS (QOE 1; SOR A). Treatment with 1.4–1.5 mg/kg once daily of methylprednisolone-induced remission in 33 of 36 cats within 14 days. The similar response to 0.18 mg/kg once daily of triamcinolone acetonide suggests that this drug has seven-fold greater potency than methylprednisolone. It is therefore likely that equipotent doses of other glucocorticoids will be likewise effective (QOE 3; SOR C). By contrast, 1 mg/kg once daily of prednisolone (approximately 50% of the above dosages) was much less effective. Once in remission, treatment can be tapered to the lowest and least frequent dosage that maintains remission (QOE 1; SOR A). On average, this equated to 20–25% of the starting dosage. Once-daily treatment is advised (QOE 1; SOR A). There was no difference in the efficacy of methylprednisolone at 0.77 mg/kg twice daily and 1.4 mg/kg once daily. One study noted that twice-daily dosing reduced QoL scores.62 Systemic glucocorticoids at these doses were well-tolerated, although all of the studies were short-term. However, altered haematology, serum biochemistry and urinalysis parameters were frequent (particularly markers of glucose metabolism). Regular monitoring of cats on a long-term treatment with systemic glucocorticoids is therefore warranted, especially with more diabetogenic drugs such as dexamethasone (QOE 1, SOR A). In feline asthma, there is good evidence for clinical efficacy of oral glucocorticoids (QOE 1; SOR A) although most of this evidence is based on experimentally sensitised cats. There was one prospective open and uncontrolled clinical trial of topical 0.0584% hydrocortisone aceponate (HCA, Cortavance, Virbac; Carros, France) in 10 cats with perennial pruritus and lesions consistent with FASS.43 The cats were treated with two sprays per 10 x 10 cm area of affected skin from 10 cm away daily for 28 days, followed by every other day dosing up to Day (D).43 The outcome measures included a pVAS,82 a validated Feline Dermatitis Extent and Severity Index lesion score (FeDESI),84 and a five point categorical score for efficacy, tolerance and ease-of-administration. Four studies evaluated the use of inhaled glucocorticoids in an experimental model of feline asthma.65, 66, 68, 71 In one study, inhaled flunisolide at 250 µg twice daily was compared with oral prednisolone at 10 mg once daily in six cats.66 In the second blinded cross-over RCT the effect of three different dosages of inhaled fluticasone propionate delivered by a metered-dose inhaler was investigated in six cats with experimentally induced allergic airway inflammation.68 A third cross-over RCT treated six cats sensitised to A. suum with either prednisolone (1 mg/kg twice daily), inhaled fluticasone propionate (500 mcg twice daily), or a combination of inhaled fluticasone propionate and salbutamol (500 mcg/50 mcg twice daily) for four consecutive days.71 In another study, sensitised cats underwent RIT and for the first six months concurrently received either oral prednisolone at 10 mg/kg/day/cat or 220 mcg twice-daily inhaled fluticasone/cat.65 One study investigated the effects of 400 mcg of inhaled budesonide twice daily on 37 cats with naturally occurring asthma and chronic bronchitis in a retrospective study using client questionnaires.34 Three cats were withdrawn from the HCA study; two were lost to follow-up and one was removed owing to poor efficacy.43 Using an intention-to-treat analysis, there was a 77% reduction in FeDESI score and 76% reduction in pruritus by D56. Over 50% of the improvement was seen by D14. Ease-of-administration, tolerance and efficacy assessments were good-to-excellent in the seven cats that completed the study. Of these cats, six of seven could be maintained on every other day treatment and one required daily therapy. Although inhaled flunisolide decreased allergen-specific IgE and the number of eosinophils in the BALF of cats experimentally sensitised to Ber