tacrolimus and Cat-Diseases

Cyclosporine and tacrolimus are potent immunosuppressant agents that have been used extensively in humans, primarily for prevention of transplant rejection but also for the treatment of autoimmune disorders. Both agents have similar mechanisms of action and pharmacokinetic profiles. However, the expected toxicity of the agents is dissimilar. Although cyclosporine usage in veterinary medicine is limited, it has been used enough for therapeutic guidelines to be established. Tacrolimus, however, has undergone limited use in veterinary medicine. The drug is too toxic in dogs for its use to be recommended in most clinical situations. This article reviews the mechanism of action, pharmacokinetics, expected drug interactions and toxicities, and clinical usage of cyclosporine and tacrolimus in veterinary medicine.

Topics: Animals; Autoimmune Diseases; Cat Diseases; Cats; Cyclosporine; Dog Diseases; Dogs; Dose-Response Relationship, Drug; Drug Interactions; Eye Diseases; Glomerulonephritis; Graft Rejection; Immunosuppressive Agents; Skin Diseases; Tacrolimus; Transplantation

To describe pharmacokinetics of multi-dose oral administration of tacrolimus in healthy cats and evaluate the efficacy of tacrolimus in the prevention of allograft rejection in cats with renal transplants.. 6 healthy research cats.. Cats received tacrolimus (0.375 mg/kg, PO, q 12 h) for 14 days. Blood tacrolimus concentrations were measured by a high performance liquid chromatography-mass spectrometry assay. Each cat received an immunogenically mismatched renal allograft and native kidney nephrectomy. Tacrolimus dosage was modified to maintain a target blood concentration of 5 to 10 ng/mL. Cats were euthanatized if plasma creatinine concentration exceeded 7 mg/dL, body weight loss exceeded 20%, or on day 50 after surgery. Kaplan-Meier survival curves were plotted for 6 cats treated with tacrolimus and for 8 cats with renal transplants that did not receive immunosuppressive treatment.. Mean (+/- SD) values of elimination half-life, time to maximum concentration, maximum blood concentration, and area under the concentration versus time curve from the last dose of tacrolimus to 12 hours later were 20.5 +/- 9.8 hours, 0.77 +/- 0.37 hours, 27.5 +/- 31.8 ng/mL, and 161 +/- 168 hours x ng/mL, respectively. Tacrolimus treated cats survived longer (median, 44 days; range, 24 to 52 days) than untreated cats (median, 23 days; range, 8 to 34 days). On histologic evaluation, 3 cats had evidence of acute-active rejection, 1 cat had necrotizing vasculitis, and 2 cats euthanatized at study termination had normal appearing allografts.. Tacrolimus may be an effective immunosuppressive agent for renal transplantation in cats.

Topics: Administration, Oral; Animals; Area Under Curve; Cat Diseases; Cats; Female; Graft Rejection; Half-Life; Kidney; Kidney Transplantation; Tacrolimus

Proliferative and necrotising otitis externa (PNOE) is a rare disorder in cats with poorly understood pathogenesis. Extra-auricular (EA) lesions recently have been mentioned in a textbook and in one case report.. To describe EA lesions associated with PNOE in three kittens.. A 6-month-old female domestic short hair (DSH) cat (Case 1), an 8-month-old female DSH cat (Case 2) and a 5-month-old female DSH cat (Case 3).. All cases exhibited classical lesions of PNOE associated with EA lesions, generalised (cases 1 and 3) or limited to eyelids (Case 2). Lesions were characterised by thick, adherent, hyperkeratotic papules coalescing to plaques and attempts to remove the hyperkeratotic plaques resulted in erosions. Histopathological examinations revealed classical features of PNOE: severe acanthosis associated with a marked lymphocytic exocytosis, satellitosis and apoptotic keratinocytes at all levels of the epidermis and the outer root sheath of hair follicles. Cases 2 and 3 resolved spontaneously. Case 1 remained stable with topical tacrolimus and oral prednisolone after a short course of ciclosporin.. This report describes EA lesions of PNOE in three kittens. Such lesions may be underdiagnosed, and this report emphasises the role of a thorough clinical inspection in PNOE cases.. L’otite externe proliférative et nécrosante (PNOE) est un rare trouble chez le chat avec une pathogénie mal comprise. Les lésions extra-auriculaires (EA) ont récemment été mentionnées dans un livre et dans un cas clinique.. Décrire les lésions EA associées avec PNOE chez trois chattons.. Un chat européen (DSH) femelle de 6 mois (cas 1), un chat DSH femelle de 8 mois (cas 2) et un chat DSH femelle de 5 mois (cas 3). MATÉRIELS ET MÉTHODES: Tous les cas ont montré des lésions classiques de PNOE associées à des lésions EA, généralisées (cas 1 et 3) ou limitées aux paupières (cas 2). Les lésions ont été caractérisées par des papules hyperkératosiques, adhérentes et épaissies coalescentes en plaques dont le retrait résultaient en des érosions. Les examens histopathologiques ont révélé les critères classiques de PNOE : acanthose sévère associée à une exocytose lymphocytaire marquée, une satellitose et des kératinocytes apoptotiques à tous les niveaux de l’épiderme et au niveau de la gaine épithéliale externe des follicules pileux. Les cas 2 et 3 se sont résolus spontanément. Le cas 1 est resté stable avec du tacrolimus topique et de la prednisolone orale après une courte période de ciclosporine.. Cet article décrit les lésions d’EA de PNOE chez trois chattons. De telles lésions peuvent être sous diagnostiquées et cet article se concentre sur le rôle de l’examen clinique complet dans les cas de PNOE.. INTRODUCCIÓN: la otitis externa proliferativa y necrotizante (PNOE) es un trastorno poco común en gatos con una patogenia poco conocida. Lesiones extraauriculares (EA) se han descrito recientemente en un libro de texto y en un informe de caso. OBJETIVOS: Describir lesiones EA asociadas con PNOE en tres gatitos. ANIMALES: Una gata doméstica de pelo corto (DSH) de 6 meses (Caso 1), una gata DSH de 8 meses (Caso 2) y una gata DSH de 5 meses (Caso 3). MÉTODOS Y RESULTADOS: Todos los casos presentaron lesiones clásicas de PNOE asociadas a lesiones de EA, generalizadas (casos 1 y 3) o limitadas a párpados (caso 2). Las lesiones se caracterizaron por pápulas hiperqueratósicas adherentes gruesas que se fusionaron en placas y los intentos de eliminar las placas hiperqueratósicas dieron como resultado erosiones. Los exámenes histopatológicos revelaron características clásicas de PNOE: acantosis severa asociada con una exocitosis linfocítica marcada, satelitosis y queratinocitos apoptóticos en todos los niveles de la epidermis y la vaina radicular externa de los folículos pilosos. Los casos 2 y 3 se resolvieron espontáneamente. El caso 1 permaneció estable con tacrolimus tópico y prednisolona oral después de un ciclo corto de ciclosporina. CONCLUSIONES E IMPORTANCIA CLÍNICA: este informe describe las lesiones EA de PNOE en tres gatitas. Estas lesiones pueden estar infradiagnosticadas y este informe enfatiza el papel de una revisión clínica exhaustiva en los casos de PNOE.. Die proliferative und nekrotisierende Otitis externa (PNOE) ist eine seltene Erkrankung bei Katzen, bei der die Pathogenese noch wenig verstanden wird. Unlängst wurden extra-aurikuläre (EA) Veränderungen in einem Textbuch sowie in einem Fallbericht beschrieben.. Die Beschreibung der EA Veränderungen bei drei Kätzchen mit PNOE.. Eine 6 Monate alte weibliche Kurzhaarkatze (DSH) (Fall 1), eine 8 Monate alte weibliche DSH (Fall 2) und eine 5 Monate alte weibliche DSH (Fall 3).. Alle Fälle zeigten die klassischen Veränderungen der PNOE im Zusammenhang mit EA Veränderungen, die generalisiert (Fall 1 und 3) oder begrenzt auf die Augenlider (Fall 2) auftraten. Die Veränderungen waren durch dicke, anhaftende, hyperkeratotische Papeln, die zu Plaques koaleszierten, charakterisiert. Versuche, die hyperkeratotischen Plaques zu entfernen, resultierten in Erosionen. Eine histopathologische Untersuchung ergab die klassischen Merkmale der PNOE: hochgradige Akanthose im Zusammenhang mit ausgeprägter lymphozytärer Exozytose, Satellitose und apoptotische Keratinozyten in allen Ebenen der Epidermis und in der äußeren Haarwurzelscheide der Haarfollikel. Fall 2 und 3 heilten spontan ab. Fall 1 blieb mit topischer Applikation von Takrolimus und Prednisolon per os nach einer kurzen Gabe von Cyclosporin stabil.. Dieser Fallbericht beschreibt EA Veränderungen der PNOE bei drei Kätzchen. Derartige Veränderungen könnten mangelhaft diagnostiziert werden und dieser Bericht verdeutlicht die Rolle einer genauen klinischen Untersuchung Fällen von PNOE.. 背景: 増殖性・壊死性外耳炎 (PNOE) は、猫では稀な疾患であり、その発症メカニズムはよくわかっていない。最近では、耳介以外の病変(EA)が教科書や1つの症例報告で取り上げられている。 目的: 本研究の目的は、3頭の子猫のPNOEに伴うEA病変を記述することであった。 供試動物: 生後6ヶ月の雌のドメスティック・ショート・ヘア (DSH) (症例1) 、生後8ヶ月の雌のDSH猫 (症例2) 、生後5ヶ月のメスのDSH猫 (症例3) 。 方法と結果: 全症例はEA病変を伴うPNOEの古典的な病変を示し、汎発性(症例1および3) または眼瞼に限定されていた (症例2) 。病変は厚く付着した角質化した丘疹が局面状に合体しているのが特徴で、角質化した局面を除去しようとするとびらんが生じた。病理組織学的検査では、PNOEの典型的な特徴が認められた。すなわち、表皮および毛包の外毛根鞘のすべてのレベルで、著しいリンパ球のエクソシトーシス、サテライトーシス、アポトーシスしたケラチノサイトを伴う重度のアカントーシスであった。症例2および3は自然治癒した。症例1はシクロスポリンを短期間投与した後、タクロリムス外用およびプレドニゾロン内服で安定していた。 結論と臨床上の重要性: 本報告は、3頭の子猫におけるPNOEのEA病変について述べている。このような病変は過小評価されている可能性があり、この報告はPNOEの症例における徹底的な臨床検査の役割を強調するものである。.. 背景: 增生性坏死性外耳炎(PNOE)是一种罕见的猫疾病, 发病机制知之甚少。最近在教科书和一份病例报告中提到了耳外(EA)病变。 目的: 描述3只幼猫的PNOE相关EA病变。 动物: 6月龄雌性短毛家 (DSH) 猫 (病例1) 、8月龄雌性DSH猫 (病例2) 和5月龄雌性DSH猫 (病例3) 。 方法和结果: 所有病例均表现出典型PNOE伴随EA病变,全身 (病例1和3) 或仅限于眼睑 (病例2) 。病变的特征为厚的、粘连的、角化过度的融合性丘疹或斑块, 试图去除角化过度的斑块导致糜烂。组织病理学检查显示PNOE的典型特征: 重度棘皮症伴表皮和毛囊外根鞘各级明显的淋巴细胞外溢、卫星状和凋亡角质细胞。病例2和3自发消退。病例1在短期环孢素治疗后外用他克莫司和口服泼尼松龙保持稳定。 结论和临床重要性: 本报告描述了3只小猫中PNOE的EA病变。这类病变可能诊断不足, 本报告强调了全面临床检查在PNOE病例中的作用。.. A otite externa proliferativa e necrosante (PNOE) é uma doença rara em gatos com patogênese mal compreendida. Lesões extra-auriculares (EA) foram mencionadas recentemente em um livro e em um relato de caso.. Descrever as lesões EA associadas a PNOE em três gatinhos.. Uma gata fêmea doméstica de pêlo curto (DSH) de 6 meses de idade (Caso 1), uma gata DSH de 8 meses (Caso 2) e uma gata DSH de 5 meses de idade (Caso 3). MÉTODOS E RESULTADOS: Todos os casos exibiram lesões clássicas de PNOE associadas a lesões EA, generalizadas (casos 1 e 3) ou limitadas às pálpebras (Caso 2). As lesões foram caracterizadas por pápulas hiperqueratóticas aderentes e espessas que se aglutinam em placas e as tentativas de remover as placas hiperqueratóticas resultaram em erosões. Os exames histopatológicos revelaram características clássicas de PNOE: acantose grave associada a uma exocitose linfocítica acentuada, satelitose e queratinócitos apoptóticos em todos os níveis da epiderme e na bainha externa da raiz dos folículos pilosos. Os casos 2 e 3 resolveram-se espontaneamente. O caso 1 permaneceu estável com tacrolimus tópico e prednisolona oral após um curto período de ciclosporina. CONCLUSÕES E IMPORTÂNCIA CLÍNICA: Este relatório descreve as lesões EA de PNOE em três gatinhos. Essas lesões podem ser subdiagnosticadas, e este relato enfatiza o papel de uma inspeção clínica minuciosa nos casos de PNOE.

Topics: Animals; Cat Diseases; Cats; Female; Keratinocytes; Otitis Externa; Prednisolone; Tacrolimus

Tacrolimus (Tac) is a core immunosuppressive drug in human organ transplantation. In feline kidney transplantation, however, the cost of Tac therapy is a significant obstacle. Clarithromycin (CLM) increases the blood trough level of Tac, effectively reducing the Tac dosage in human transplant patients. The interaction between CLM and Tac in cats has not been reported. In this study, the effect of multiple CLM dosing on the pharmacokinetics of Tac in three healthy cats was investigated. The treatments included Tac at 0.3 mg/kg and Tac at 0.3 mg/kg + multiple-dose CLM at 10 mg/kg. Co-administration of CLM and Tac resulted in significant increases in the oral bioavailability of Tac. These preliminary findings suggest that administration of multiple doses of CLM may decrease the required Tac dosage in Tac-based immunosuppressive therapy used as an alternative to the classic cyclosporine-based protocol for feline renal transplantation.

Topics: Animals; Biological Availability; Cat Diseases; Cats; Clarithromycin; Dose-Response Relationship, Drug; Drug Synergism; Immunosuppression Therapy; Kidney Failure, Chronic; Kidney Transplantation; Male; Tacrolimus

Proliferative and necrotising otitis externa is a rare and recently described disease affecting the ear canals and concave pinnae of kittens. This article describes a case of proliferative and necrotising otits externa in a young adult cat. In this case, the lesions did not affected the pinnae, but both ear canals were severely involved. Video-otoscopy revealed a digitally proliferative lesion, growing at 360° all around the ear canals for their entire length, without involvement of the middle ear. Histopathological examination confirmed the diagnosis, and the cat responded completely to a once-daily application of 0.1% tacrolimus ointment diluted in mineral oil in the ear canals. Video-otoscopy findings, not described previously, were very peculiar and may help clinicians to diagnose this rare disease.

Topics: Animals; Cat Diseases; Cats; Ear; Immunosuppressive Agents; Male; Necrosis; Otitis Externa; Tacrolimus; Treatment Outcome

Topics: Animals; Cat Diseases; Cats; Ear; Immunosuppressive Agents; Male; Necrosis; Otitis Externa; Tacrolimus; Treatment Outcome

Otitis externa in cats is relatively uncommon. This report describes a case of a rare, visually distinctive, proliferative and necrotising otitis in a three-month-old Persian kitten. The cat had proliferative, erythematous and necrotic tissue covering most of the proximal pinnae and vertical ear canals. On histopathological examination, the most striking feature was the existence of scattered apoptotic-appearing keratinocytes within severely hyperplastic epithelium. For the first time, immunohistochemistry was used to show a closed association between CD3(+) T cells and caspase-3 stained keratinocytes, consistent with a keratinocyte apoptosis by epidermal-infiltrating T cells. Treatment was initiated using topical tacrolimus twice daily and an ear cleanser once daily. A marked improvement was observed after 10 days of treatment and the lesions completely resolved over a period of three weeks. The origin of T cells directed against keratinocytes is currently unknown.

Topics: Animals; Apoptosis; Caspase 3; Cat Diseases; Cats; CD3 Complex; Female; Immunohistochemistry; Immunosuppressive Agents; Keratinocytes; Necrosis; Otitis Externa; T-Lymphocytes; Tacrolimus

A 3-year-old, neutered male Persian cat with chronic ulcerative facial dermatitis was diagnosed with feline idiopathic facial dermatitis based on signalment, clinical history and diagnostic test results, including dermatohistopathological evaluation. Initial treatment started with 4 weeks of oral antifungal/antibiotic medication for severe secondary infectious dermatitis of Malassezia and bacteria. As the lesions gradually improved, the oral medication was withdrawn, leaving only 0.1% topical FK506 (tacrolimus) ointment for the remaining lesions. Topical treatment was administered just in case any new lesions developed. The patient has been managed effectively with topical tacrolimus and no side-effects were observed during treatment. Feline idiopathic facial dermatitis is known as a difficult dermatosis to manage successfully, but our experience suggests that it may respond to topical tacrolimus.

Topics: Administration, Topical; Animals; Antifungal Agents; Cat Diseases; Cats; Dermatomycoses; Immunosuppressive Agents; Malassezia; Male; Tacrolimus

Proliferative and necrotizing feline otitis externa is a rare disorder of unknown aetiology. This condition was diagnosed by skin biopsy in three adult domestic shorthair cats (3-5 years old) and one kitten (6 months old). The affected cats had large tan to dark brown-black coalescing plaques covering the concave surface of the pinnae and external ear canals. Friable material from the plaques and a thick exudate occluded the ear canals. The cats had a secondary bacterial and/or yeast otitis. Prior to the histopathological diagnosis, all cats received numerous otic preparations as well as oral antibiotics and corticosteroids without resolution. Histologically, all cases had strikingly similar changes; acanthosis with pronounced hair follicle outer root sheath hyperplasia and neutrophilic luminal folliculitis, follicular keratosis and individually necrotic keratinocytes in the outer root sheath of hair follicles. One case was documented via skin biopsy to have persisted for 4 years. The adult cats were treated with topical 0.1% tacrolimus and all showed marked improvement although one cat was lost to follow up. The lesions completely resolved with topical tacrolimus alone in one cat and topical tacrolimus in addition to oral prednisolone in another cat.

Topics: Administration, Cutaneous; Animals; Cat Diseases; Cats; Diagnosis, Differential; Female; Immunosuppressive Agents; Male; Necrosis; Otitis Externa; Severity of Illness Index; Tacrolimus