Protocolo de Tratamento do Pênfigo Canino

Transcrição

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
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. 2012 Oct 15;149(3-4):197-207
Rosenkrantz WS. Pemphigus: current therapy. Vet Dermatol. 2004 Apr;15(2):90-8.
Frew JW, Murrell DF. Current management strategies in paraneoplastic pemphigus (paraneoplastic autoimmune multiorgan syndrome). Dermatol Clin. 2011
Oct;29(4):607-12. doi: 10.1016/j.det.2011.06.016. Epub 2011 Aug 15.
Büsing V, Kern JS, Bruckner-Tuderman L, Hofmann SC. Recalcitrant pemphigus vulgaris responding to systemic tacrolimus. Dermatology. 2010;221(2):122-6.
doi: 10.1159/000314155. Epub 2010 Jun 26.
Ultrafórmulas Vet – Departamento de Veterinária da Farmácia de Manipulação Ultrafórmulas. Avenida Jabaquara, 1426 – Saúde | Tel./Fax:(11) 3058-5565
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 (2000-2005). Pesq. Vet. Bras. vol.28 no.8
Rio de Janeiro Aug. 2008
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. 2004 Sep;21(3):13942.
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. 2006 May-Jun;42(3):189-96.
Gomez SM, Morris DO, Rosenbaum MR, Goldschmidt MH. Outcome and complications associated with treatment of pemphigus foliaceus in dogs: 43 cases
(1994-2000). J Am Vet Med Assoc. 2004 Apr 15;224(8):1312-6.
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.
Tratamento Heterodoxo
Prednisona + Azatioprina
Prednisona__________________ 1 a 2mg/kg
Cápsula qsp________________________1UN
+
Azatioprina______________ 1,5 a 2,5mg/kg
Cápsula qsp________________________1UN
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 (2000-2005). Pesq. Vet. Bras. vol.28 no.8 Rio de Janeiro Aug. 2008
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
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. 2004 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.
2000 Aug;41(8):623-7.
Abstracts
Vet Immunol Immunopathol. 2012 Oct 15;149(3-4):197-207. doi: 10.1016/j.vetimm.2012.06.025.
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.
Abstract
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: 22884397 [PubMed - in process]
Vet Dermatol. 2004 Apr;15(2):90-8.
Pemphigus: current therapy.
Rosenkrantz WS.
Animal Dermatology Clinic, Tustin, CA 92780, USA. [email protected]
Abstract
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: 15030557 [PubMed - indexed for MEDLINE]
Dermatol Clin. 2011 Oct;29(4):607-12. doi: 10.1016/j.det.2011.06.016. Epub 2011 Aug 15.
Current management strategies in paraneoplastic pemphigus (paraneoplastic autoimmune multiorgan
syndrome).
Frew JW, Murrell DF.
St George Hospital, Gray Street, Kogarah, Sydney, NSW 2217, Australia.
Abstract
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.
Dermatology. 2010;221(2):122-6. doi: 10.1159/000314155. 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.
Abstract
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.
Rev Iberoam Micol. 2004 Sep;21(3):139-42.
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.
[email protected]
Abstract
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.
J Am Anim Hosp Assoc. 2006 May-Jun;42(3):189-96.
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.
Abstract
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.
J Am Vet Med Assoc. 2004 Apr 15;224(8):1312-6.
Outcome and complications associated with treatment of pemphigus foliaceus in dogs: 43 cases
(1994-2000).
Gomez SM, Morris DO, Rosenbaum MR, Goldschmidt MH.
Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania,
Philadelphia, PA 19104, USA.
Abstract
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.
Can Vet J. 2000 Aug;41(8):623-7.
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.
Abstract
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:10945128[PubMed - indexed for MEDLINE]
J Am Vet Med Assoc. 2009 Aug 15;235(4):397-404.
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.
Abstract
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:19681720[PubMed - indexed for MEDLINE]

Protocolo de Tratamento do Pênfigo Canino

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