Protocolo de Tratamento do Pênfigo Canino

Transcrição

1 Protocolo de Tratamento do Pênfigo Canino Profilaxia com Antimicrobianos Aumenta Taxa de Sobrevivência Predinisona + Azatioprina é Eficaz no Tratamento e Não Promove Efeitos Adversos Significativos

2 Pênfigo Canino Doença Autoimune que se Apresenta Sob Diferentes Formas Descrição O pênfigo é a doença mais comum mediada por anticorpos da pele em cães, sendo uma doença autoimune que pode apresentarse numa variedade de formas e pode ser desafiadora para gerir e tratar. Entre as diferentes formas de pênfigos, podem ser citados o foliáceo (PF), o eritematoso (PE), o panepidermal pustular (PPP), o vulgar (PV) e o paraneoplásico (PNP) (Rosenkrantz, 2004). Pênfigo Paraneoplásico O pênfigo paraneoplásico (PNP) ou síndrome paraneoplásica de múltiplos órgãos autoimune (PAMS) é uma doença fatal comumente associada com neoplasias linfoproliferativas (Frew e Murrell, 2004). Pênfigo Vulgar O pênfigo vulgar é uma doença autoimune caracterizada por bolhas flácidas e erosões dolorosas das mucosas e pele. O tratamento do PV atualmente consiste no uso de corticóides sistêmicos e adjuvantes imunossupressores. Foi descrito por Büsing et al. (2010) o sucesso do uso de tacrolimus sistêmico, o qual foi bem tolerado e levou à melhora clínica, sendo uma alternativa terapêutica para o PV recalcitrante. Tratamento Entre a terapêutica, os tratamentos mais comumente utilizados são glicocorticoides, azatioprina, clorambucil, tetraciclina e niacinamida. Entre as alternativas terapêuticas atuais, são empregados o micofenolato de ciclosporina e tacrolimus, e entre as alternativas terapêuticas adicionais utilizam-se ciclofosfamida, dapsona, sulfasalazina e terapia com imunoglobulina intravenosa (IVIG) (Rosenkrantz, 2004). Referências Bizikova P, Dean GA, Hashimoto T, Olivry T. Cloning and establishment of canine desmocollin-1 as a major autoantigen in canine pemphigus foliaceus. Vet Immunol Immunopathol Oct 15;149(3-4): Rosenkrantz WS. Pemphigus: current therapy. Vet Dermatol Apr;15(2):90-8. Frew JW, Murrell DF. Current management strategies in paraneoplastic pemphigus (paraneoplastic autoimmune multiorgan syndrome). Dermatol Clin Oct;29(4): doi: /j.det Epub 2011 Aug 15. Büsing V, Kern JS, Bruckner-Tuderman L, Hofmann SC. Recalcitrant pemphigus vulgaris responding to systemic tacrolimus. Dermatology. 2010;221(2): doi: / Epub 2010 Jun 26.

3 Pênfigo em Cães Tratamento e Complicações De acordo com o Hospital Veterinário da Faculdade de Medicina Veterinária e Zootecnia-USP, não há significante predisposição sexual. No entanto, verifica-se evidente predisposição racial. Dentre aquelas mais acometidas, encontram-se as raças Cocker Spaniel, Poodle, Dachshund e Akita. A faixa etária de maior incidência foi aquelas dos 4 aos 9 anos, sendo que a média etária foi de 4 anos. As três regiões mais acometidas foram a dorsal (95,3%), abdominal e ventral (93%) e axilar (88,7). A generalização lesional foi observada em 91% dos casos em período de um a seis meses de evolução. Os quatro tipo lesionais mais frequentemente observados foram: crostas hemo-melicéricas (100%), pústulas (76,7%), pápulas (76,7%) e escamas (67,4%). O protocolo de terapia empregado já há anos no HOVET é similar ao classicamente empregado em todas as latitudes. Inicia-se sempre com a prednisona na dose de 1-2mg/kg/diariamente durante cerca de 45 dias. Aqueles que não demonstrarem melhora evidente neste período habitualmente são submetidos à terapia heterodoxa com a associação prednisona e azatioprina. Dos animais acompanhados, 97,4% apresentaram melhora tanto com a terapia ortodoxa como com a heterodoxa. Apenas 4,6% dos animais submetidos à terapia associada à azatioprina apresentaram trombocitopenia como único efeito adverso e, portanto, pode-se concluir que esta associação é efetiva e segura nos tratamento do PF. Complicações Moretti et al. (2004) descrevem um caso clínico de candidíase cutânea em um cão com lesões dermatológicas, caracterizadas por alopecia persistente, crostas, úlceras e escaras. Fatores de predisposição, tais como o uso de corticosteroides, a presença concomitante de uma doença autoimune (pênfigo foliáceo) e uma infecção de erliquiose causada por Ehrlichia canis foram observados. Referências Balda, AC; Ikeda, MO; Junior, CEL; Michalany, NS; Larsson, CE. Pênfigo foliáceo canino: estudo retrospectivo de 43 casos clínicos e terapia ( ). Pesq. Vet. Bras. vol.28 no.8 Rio de Janeiro Aug Moretti A, Posteraro B, Boncio L, Mechelli L, De Gasperis E, Agnetti F, Raspa M. Diffuse cutaneous candidiasis in a dog. Diagnosis by PCR-REA. Rev Iberoam Micol Sep;21(3):

4 Estudos Avaliação de Casos de Pênfigo Foliáceo Sinais Clínicos e Resposta à Terapia Mueller et al. (2006) conduziram um estudo retrospectivo envolvendo 91 cães com pênfigo foliáceo. Os sinais clínicos da doença incluíam crostas (n=79), pústulas (n=36) e alopecia (n=33). As lesões foram mais comuns no tronco (n=53), interior das pinas (n=46) face (n=37) e pés de apoio (n= 32). A avaliação citológica revelou queratinócitos acantolíticos em 37 de 48 cães. Os resultados do tratamento combinado com prednisolona e azatioprina foram comparáveis aos resultados obtidos com a terapia prednisolona isoladamente. Mais de metade dos cães em remissão com o tratamento adequado e outros 25% melhoraram significativamente. Fatores que Influenciam a Taxa de Sobrevivência De acordo com um estudo conduzido por Gomez et al. (2004), levando em conta 43 casos de pênfigo foliáceo, a taxa de letalidade foi de 60,5%. O tratamento profilático com antimicrobianos concomitantemente ao início do uso de imunossupressores e a baixa ocorrência de efeitos adversos foram fatores significativamente correlacionados com a taxa de sobrevivência. Também houve relação entre a sobrevivência e duração do tratamento superior a 10 meses a partir do diagnóstico. Conclusão: A administração de antiobióticos concomitantemente ao início da terapia imunossupressora pode ser uma boa alternativa para a garantia da sobrevivência ao pênfigo foliáceo. Referências Mueller RS, Krebs I, Power HT, Fieseler KV. Pemphigus foliaceus in 91 dogs. J Am Anim Hosp Assoc May-Jun;42(3): Gomez SM, Morris DO, Rosenbaum MR, Goldschmidt MH. Outcome and complications associated with treatment of pemphigus foliaceus in dogs: 43 cases ( ). J Am Vet Med Assoc Apr 15;224(8):

5 Como Prescrever? Opções de Tratamento do Pênfigo Canino Tratamento Usual (Ortodoxo) Cápsulas Imunossupressoras de Prednisona Prednisona 1 a 2mg/kg Cápsula qsp 1UN Administrar 1 cápsula ao dia ou conforme orientação do médico veterinário. De acordo com Balda et al. (2008), uma vez confirmado o diagnóstico de pênfigo foliáceo, a terapia clássica consiste na administração de prednisona em dose imunossupressora (1 a 2 mg/kg/dia) até eventual melhora do quadro lesional ( 3 a 4 semanas). Após esse período, deve-se iniciar a redução gradual do esteroide, tentando-se manter a manutenção dos resultados, sempre com a menor dose e o maior intervalo posológico possível. Prednisona + Azatioprina Tratamento Heterodoxo Prednisona 1 a 2mg/kg Cápsula qsp 1UN Administrar 1 cápsula ao dia ou conforme orientação do médico veterinário. + Azatioprina 1,5 a 2,5mg/kg Cápsula qsp 1UN Administrar 1 cápsula ao dia ou conforme orientação do médico veterinário. Quando a melhora não é alcançada com o uso isolado de prednisona, deve-se proceder com a terapia heterodoxa, em associação com azatioprina (1,5 a 2,5 mg/kg/dia). Após a melhora sintômato-lesional, inicia-se o esquema de redução gradual e aumento do intervalo posológico (Balda et al., 2008). Referências Balda, AC; Ikeda, MO; Junior, CEL; Michalany, NS; Larsson, CE. Pênfigo foliáceo canino: estudo retrospectivo de 43 casos clínicos e terapia ( ). Pesq. Vet. Bras. vol.28 no.8 Rio de Janeiro Aug. 2008

6 Tratamentos Disponíveis Outras Opções de Tratamento Para o Pênfigo Canino De acordo com Rosenkrantz (2004), entre os tratamentos mais comumente utilizados, encontram-se a glicocorticoides, tetraciclina e niacinamida. Entre as alternativas terapêuticas atuais, são empregados micofenolato de ciclosporina e tacrolimus, e entre as alternativas adicionais, utilizam-se dapsona e sulfasalazina. 1. Cápsulas de Tetraciclina Tetraciclina 15 a 20 mg/kg Cápsula qsp 1UN Administrar 1 cápsula de 8 em 8 horas, de acordo com o médico veterinário. 2. Cápsulas de Dapsona Dapsona 1 mg/kg Cápsula qsp 1UN Administrar 1 cápsula 2 ou 3 vezes ao dia, de acordo com o médico veterinário. 3. Tratamento Tópico - Pomada de Tacrolimus Tacrolimus 0,1% Pomada PEG qsp 50g Aplicar diretamente sobre as lesões uma ou duas vezes ao dia ou conforme orientação do médico veterinário. Pomada PEG: Lavável Segura se ingerida O tacrolimus é um fármaco imunossupressor com ação semelhante à ciclosporina que pode produzir imunossupressão sem citotoxicidade ou mielossupressão (Misseghers et al., 2000). Referências Rosenkrantz WS. Pemphigus: current therapy. Vet Dermatol Apr;15(2):90-8. Misseghers BS, Binnington AG, Mathews KA. Clinical observations of the treatment of canine perianal fistulas with topical tacrolimus in 10 dogs. Can Vet J Aug;41(8):623-7.

7 s Vet Immunol Immunopathol Oct 15;149(3-4): doi: /j.vetimm Epub 2012 Jul 23. Cloning and establishment of canine desmocollin-1 as a major autoantigen in canine pemphigus foliaceus. Bizikova P, Dean GA, Hashimoto T, Olivry T. Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC 27607, USA. 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. Copyright 2012 Elsevier B.V. All rights reserved. PMID: [PubMed - in process] Vet Dermatol Apr;15(2):90-8. Pemphigus: current therapy. Rosenkrantz WS. Animal Dermatology Clinic, Tustin, CA 92780, USA. AnDerm1@aol.com Pemphigus is an autoimmune skin disease that can present in a variety of forms and can be a challenging disease to manage and treat. An overview of the different forms of pemphigus and diagnostics are discussed including pemphigus foliaceus (PF), pemphigus erythematosus (PE), panepidermal pustular pemphigus (PPP), pemphigus vulgaris (PV) and paraneoplastic pemphigus (PNP). Emphasis on therapy is presented. Included are the most current commonly used therapeutics (glucocorticoids, azathioprine, chlorambucil and tetracycline and niacinamide); current alternative therapeutics (cyclosporin and tacrolimus and mycophenolate mofetil) and additional alternative therapeutics (cyclophosphamide, chrysotherapy, dapsone, sulfasalazine and intravenous immunoglobulin (IVIG) therapy). PMID: [PubMed - indexed for MEDLINE] Dermatol Clin Oct;29(4): doi: /j.det Epub 2011 Aug 15. Current management strategies in paraneoplastic pemphigus (paraneoplastic autoimmune multiorgan syndrome). Frew JW, Murrell DF.

8 St George Hospital, Gray Street, Kogarah, Sydney, NSW 2217, Australia. Paraneoplastic pemphigus (PNP) or paraneoplastic autoimmune multiorgan syndrome (PAMS) is a life-threatening autoimmune blistering disease commonly associated with lymphoproliferative neoplasms. This article focuses on current management strategies in PNP/PAMS, and reported instances of their treatment successes and failures. Due to the rarity of the condition and the high rates of treatment failure, no randomized control trials exist to guide the evidence-based treatment of this condition; all evidence to date on the efficacy of therapeutic modalities has been gained from individual case reports, small case series, and expert recommendations. Copyright 2011 Elsevier Inc. All rights reserved. PMID: [PubMed - indexed for MEDLINE] Dermatology. 2010;221(2): doi: / Epub 2010 Jun 26. Recalcitrant pemphigus vulgaris responding to systemic tacrolimus. Büsing V, Kern JS, Bruckner-Tuderman L, Hofmann SC. Department of Dermatology, University Medical Center Freiburg, Freiburg, Germany. Pemphigus vulgaris (PV) is an auto-immune blistering skin disease characterized by flaccid blisters and painful erosions of mucous membranes and skin. Suprabasal blister formation results from a loss of epidermal cohesion induced by auto-antibodies against the desmosomal protein desmoglein 3. Treatment of PV currently consists of systemic glucocorticosteroids and adjuvant immunosuppressive drugs such as azathioprine, mycophenolate mofetil, cyclophosphamide or dapsone. Due to the low incidence of PV, there are insufficient data to conclude which treatment is the most effective and safest. Thus far, systemic tacrolimus (FK506, Prograf) has not yet been reported as adjuvant medication for PV. Here, we describe the successful use of systemic tacrolimus in 2 patients with recalcitrant PV of the oral mucosa. Tacrolimus was well tolerated, and clinical improvement allowed tapering of corticosteroids. Thus, oral tacrolimus may be a therapeutic alternative for patients with recalcitrant PV. Copyright 2010 S. Karger AG, Basel. PMID: [PubMed - indexed for MEDLINE]

9 Rev Iberoam Micol Sep;21(3): Diffuse cutaneous candidiasis in a dog. Diagnosis by PCR-REA. Moretti A, Posteraro B, Boncio L, Mechelli L, De Gasperis E, Agnetti F, Raspa M. Dipartimento di Scienze Biopatologiche Veterinarie, Facoltà di Medicina Veterinaria, Perugia, Italy. moretti@unipg.it The authors describe a clinical case of cutaneous candidiasis in a dog with dermatological lesions, characterized by persistent alopecia, crusts, ulcers and scales. Predisposing factors such as the use of corticosteroids, the concomitan presence of an autoimmune disease (pemphigus foliaceus) and an infection of ehrlichiosis caused by Ehrlichia canis were observed. Histopathological findings included signs of orthokeratotic hyperkeratosis, moderate follicular keratosis and light epidermic acanthosis. The reactive process included an infiltrative superficial dermatitis and a mural folliculitis with prevalent participation of macrophages and lymphocytes. The application of PCR-Restriction Enzyme Analysis (REA) method on cutaneous specimens in veterinary medicine is an extremely interesting diagnostic tool. Its use, together with other techniques, such as mycologic, cytologic and histological examinations, allowed us to identify Candida albicans as aetiological agent in this particular case. PMID: [PubMed - indexed for MEDLINE] J Am Anim Hosp Assoc May-Jun;42(3): Pemphigus foliaceus in 91 dogs. Mueller RS, Krebs I, Power HT, Fieseler KV. Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523, USA. A retrospective study of 91 dogs with pemphigus foliaceus was performed. Clinical signs of the disease included crusts (n=79), pustules (n=36), and alopecia (n=33). Lesions were most common on the trunk (n=53), inner pinnae (n=46), face (n=37), and foot pads (n=32). Cytological evaluation revealed acantholytic keratinocytes in 37 of 48 dogs. Results of combination treatment with prednisolone and azathioprine were comparable to results with prednisolone therapy alone. More than half of the dogs achieved remission with appropriate therapy, and another 25% significantly improved. PMID: [PubMed - indexed for MEDLINE]

10 J Am Vet Med Assoc Apr 15;224(8): Outcome and complications associated with treatment of pemphigus foliaceus in dogs: 43 cases ( ). Gomez SM, Morris DO, Rosenbaum MR, Goldschmidt MH. Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. OBJECTIVE: To identify factors affecting prognosis, outcome, and complications associated with pemphigus foliaceus in dogs. DESIGN: Retrospective study. ANIMALS: 43 dogs with pemphigus foliaceus. PROCEDURE: Medical records were reviewed for signalment, age at diagnosis, duration to diagnosis, body area affected, initial immunosuppressive regimens and concurrent use of antimicrobials and sucralfate or histamine receptor 2 blocking agent, adverse effects of treatment, duration of treatment, number of visits for follow-up care, cause of death, and credentials of the veterinarians responsible for continued care. RESULTS: The case fatality rate was 60.5%. Factors significantly correlated with survival time included concurrent use of antimicrobials during initiation of immunosuppressive treatment and a lower number of adverse effects to treatment. Treatment times lasting more than 10 months from diagnosis correlated significantly with survival. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment with or prophylactic use of antimicrobials may be warranted during initial immunosuppressive treatment. The inverse correlation between survival time and number of adverse treatment effects was not unexpected because it was reflective of the owners' decision to euthanatize their dogs and of corticosteroid-related secondary diseases. Survival beyond the tenth month of treatment predicted long-term survival, which suggests that dogs require careful management during the early months of treatment. PMID: [PubMed - indexed for MEDLINE] Can Vet J Aug;41(8): Clinical observations of the treatment of canine perianal fistulas with topical tacrolimus in 10 dogs. Misseghers BS, Binnington AG, Mathews KA. SourceDepartment of Clinical Studies, Ontario Veterinary College, University of Guelph, Ontario. Tacrolimus ointment, a potent immunosuppressive medication, was evaluated for efficacy in the treatment of perianal fistulas in dogs. Ten dogs with perianal fistulas were treated with topical tacrolimus ointment once to twice daily for 16 weeks. Full healing of the fistulas occurred in 50% and was noticeably improved in 90% of dogs. PMID: [PubMed - indexed for MEDLINE] J Am Vet Med Assoc Aug 15;235(4): Long-term prospective evaluation of topically applied 0.1% tacrolimus ointment for treatment of perianal sinuses in dogs. Stanley BJ, Hauptman JG. SourceDepartment of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.

11 OBJECTIVE: To evaluate effectiveness of a combination of topically applied tacrolimus, orally administered prednisone, and a novel-protein diet for treatment of perianal sinuses in dogs and to monitor clinical progress and owner management of the condition for 2 years. DESIGN: Noncontrolled clinical trial. Animals-19 dogs with perianal sinuses. Procedures-Perianal sinuses were diagnosed during physical examination, and dogs were placed on a 16-week treatment protocol consisting of topically applied 0.1% tacrolimus ointment, orally administered prednisone (tapering dose), and a novel-protein diet. Metronidazole was orally administered for the first 2 weeks. Anal sacculectomy was recommended whenever anal sacs were involved. Dogs were evaluated every month for the first 4 months and then every 6 to 12 weeks for 2 years. RESULTS: Perianal sinuses resolved completely in 15 of 19 dogs during the 16 weeks. In the remaining 4 dogs, the lesions markedly improved but failed to completely resolve. Three of these had anal sac involvement, and the owner of 1 dog had complied poorly with treatment instructions. During the 2 years following treatment, all dogs were maintained on intermittently applied tacrolimus ointment, 4 dogs also received prednisone every other day, and 11 dogs remained on the novelprotein diet. At the conclusion of the study, 13 of the 15 dogs that survived to that point were free of perianal disease. CONCLUSIONS AND CLINICAL RELEVANCE: The described protocol was effective and economical for resolving perianal sinuses. Dogs maintained on intermittent medications were unlikely to redevelop lesions. When the anal sacs were involved, anal sacculectomy appeared to improve the outcome. PMID: [PubMed - indexed for MEDLINE]