Prolonged remission after immunosuppressive therapy in six dogs with pemphigus foliaceus

Limited information is available on the long-term outcome of treatment of pemphigus foliaceus in dogs. The purpose of this study is to report that a prolonged remission can occur after discontinuation of immunosuppressive regimens in some animals with this disease. Six dogs were diagnosed with pemphigus foliaceus based on suggestive clinical signs and histopathology. These patients were treated either with immunosuppressive doses of oral glucocorticoids or with a combination of oral glucocorticoids and azathioprine. After clinical signs underwent complete remission, which occurred 1.5-5 months after immunosuppression was initiated, the drugs were tapered progressively and eventually withdrawn. The total duration of immunosuppressive therapy varied between 3 and 22 months. Skin lesions of pemphigus foliaceus did not recur for 1.5-6 years after treatment was stopped. These observations suggest that, in some dogs with pemphigus foliaceus, immunosuppression can lead to long-term remission of skin lesions, and that discontinuation of treatment is not necessarily followed by a recurrence of clinical signs.     

Clinical and histopathological features of pemphigus foliaceus with and without eosinophilic infiltrates: a retrospective evaluation of 40 dogs

The importance of cellular infiltrates in tissues has been investigated as a diagnostic tool, mechanism of pathogenesis, and prognostic indicator in certain human diseases. Eosinophils, in particular, have a distinct role in the development of cutaneous lesions in human autoimmune diseases. Identification of an eosinophilic infiltrate can aid the diagnosis of immunobullous disease in the early stages of the disease process. In canine pemphigus foliaceus, eosinophils are present to a variable degree within lesional tissue. This study retrospectively evaluated 40 dogs with pemphigus foliaceus, and examined clinical and histologic features and final outcomes in cases with and without eosinophilic infiltrates. Twenty‐five of 40 dogs (63%) had an eosinophilic infiltrate in either the pustules/crust, follicular infundibulum or dermis. There was no statistically significant difference in clinical distribution or appearance of dermatological lesions, response to treatment, or disease outcome in dogs with or without an eosinophilic infiltrate. However, dogs with concurrent disease were significantly more likely to have an eosinophilic infiltrate (P = 0.01). Dogs with adverse effects associated with immunosuppressive therapy were significantly more likely to have an eosinophilic infiltrate (P = 0.05). Fifteen of 40 dogs (38%) had a history of allergic disease and a significantly higher proportion of these dogs had an eosinophilic infiltrate (P = 0.04). An eosinophilic infiltrate was found in more than half of the dogs in this study. These findings justify further studies to investigate the role of eosinophils in the pathogenesis, therapy and prognosis in dogs with pemphigus foliaceus.     

Immune-mediated neutropenia suspected in five dogs

Five cases of suspected immune-mediated neutropenia in dogs are described. Clinical signs varied depending on whether the animals had a systemic infection or concurrent immune-mediated disease. Patients were diagnosed by excluding other causes of neutropenia, supportive bone marrow aspirate findings, an initial favourable response to corticosteroid administration in four of the cases, and concurrent immune-mediated disease. Four of the dogs were receiving medications at the time of diagnosis, and immune-mediated neutropenia secondary to drug therapy cannot be excluded. This study shows that appropriate immunosuppressive treatment can lead to a favourable outcome, however, care is required to avoid adverse effects associated with corticosteroid use. It is also imperative that medications are not withdrawn abruptly as a second remission may not always be achievable.     

Pemphigus foliaceus: a report of two cases in the dog

The clinical and diagnostic features of two cases of pemphigus foliaceus in the dog are described. Dermatohistopathology and direct immunofluorescence examination of skin biopsies were diagnostic for pemphigus foliaceus. Both dogs required immunosuppressive dosages of prednisolone to achieve control of the condition.     

FC-20 Efficacy of griseofulvin for juvenile cellulitis in dogs

Medical records of 97 dogs with pemphigus foliaceus were evaluated. The average age of onset was 6.3 years (range 0.5–16 years). Crusts were the most common lesions in 79 dogs; pustules were observed in 36 dogs. No gender predisposition was identified. The trunk was the most commonly involved area (51 dogs), followed by the inner pinnae (46), dorsal muzzle (37), footpads (32), periocular area (26), outer pinnae (23) and planum nasale (23). Facial involvement only was noted in 15 dogs. Of the 48 dogs in which cytology was recorded, concurrent infections were identified in 32 dogs, acantholytic cells were seen in 37 dogs, numerous neutrophils in 35 dogs, and numerous eosinophils in eight cases. Final control of the disease was achieved with: glucocorticoids (24 dogs); azathioprine (9); chlorambucil (1); aurothioglucose (1); a combination of glucocorticoids and azathioprine (31); glucocorticoids and aurothioglucose (2); tetracycline/doxycycline and niacinamide (8); prednisolone, tetracycline and niacinamide (1); fatty acid supplementation (2); and tacrolimus (1). One dog was completely tapered off drugs and stayed in remission. Average time to improvement was 6 weeks, and average time to remission was 9.3 months. Forty-three dogs were followed for <12 months, and 12 of these were euthanized: eight for other diseases and four due to a lack of response or adverse effects of treatment. In 54 dogs, the follow up was >12 months; four of these dogs were euthanized (one due to an unrelated cause, one due to neoplastic disease and two related to pemphigus foliaceus).
Funding: Self-funded.     

FC‐18 Pemphigus foliaceus in 97 dogs

Medical records of 97 dogs with pemphigus foliaceus were evaluated. The average age of onset was 6.3 years (range 0.5–16 years). Crusts were the most common lesions in 79 dogs; pustules were observed in 36 dogs. No gender predisposition was identified. The trunk was the most commonly involved area (51 dogs), followed by the inner pinnae (46), dorsal muzzle (37), footpads (32), periocular area (26), outer pinnae (23) and planum nasale (23). Facial involvement only was noted in 15 dogs. Of the 48 dogs in which cytology was recorded, concurrent infections were identified in 32 dogs, acantholytic cells were seen in 37 dogs, numerous neutrophils in 35 dogs, and numerous eosinophils in eight cases. Final control of the disease was achieved with: glucocorticoids (24 dogs); azathioprine (9); chlorambucil (1); aurothioglucose (1); a combination of glucocorticoids and azathioprine (31); glucocorticoids and aurothioglucose (2); tetracycline/doxycycline and niacinamide (8); prednisolone, tetracycline and niacinamide (1); fatty acid supplementation (2); and tacrolimus (1). One dog was completely tapered off drugs and stayed in remission. Average time to improvement was 6 weeks, and average time to remission was 9.3 months. Forty‐three dogs were followed for <12 months, and 12 of these were euthanized: eight for other diseases and four due to a lack of response or adverse effects of treatment. In 54 dogs, the follow up was >12 months; four of these dogs were euthanized (one due to an unrelated cause, one due to neoplastic disease and two related to pemphigus foliaceus). Funding: Self‐funded.     

Pemphigus foliaceus of the footpads in three dogs

Severe hyperkeratinization and villous hypertrophy of the footpads were seen in 3 middle-aged dogs. Peeling, fissuring, swelling, and ulcerations were noted on the margins of severely affected pads. Pain was evident in palpation and ambulation. Lesions were compatible with the traditional diagnosis of "hard pad disease". Histopathologic findings were diagnostic for canine pemphigus foliaceus in all 3 dogs, and direct immunofluorescence in an intercellular pattern was seen in both dogs that were tested. All 3 dogs responded to immunosuppressive dosages of corticosteroids.     

Clinicopathologic findings, sensitivity to house dust mites and efficacy of milbemycin oxime treatment of dogs with Cheyletiella sp. infestation

Twenty-three dogs with positive skin scrapings for Cheyletiella sp. were treated with milbemycin oxime using a protocol approximating 2 mg kg⁻¹ orally once weekly for three weeks. Nineteen of these dogs belonged to a household of 41 dogs and two dogs were in households with one other dog. All in-contact dogs were treated. Pre-treatment intradermal skin tests showed positive reactions to D. farinae in 13 dogs and to D. pteronyssinus in 12 dogs; these became negative post-treatment in four and seven dogs, respectively. All dogs showed a dramatic reduction in clinical signs one week after the third treatment. Eighteen dogs no longer had mites on skin scrapings, three had dead mites and two had deformed eggs. Recurrence of clinical signs necessitated two additional courses of the protocol in the multiple dog household and for a dog receiving immunosuppressive treatment for pemphigus foliaceus. Possible adverse reactions to the milbemycin (vomiting, lethargy) were noted once in two dogs.     

Comparison of Two Regimens for the Treatment of Meningoencephalomyelitis of Unknown Etiology

Background: The optimal treatment for meningoencephalomyelitis of unknown etiology (MUE) remains unknown, despite the widespread use of a variety of immunosuppressive drugs.
Objective/Hypothesis: To compare the efficacy of prednisolone combined with either vincristine and cyclophosphamide (COP group; n = 10) or with cytosine arabinoside (AraC group; n = 9).
Animals: Nineteen dogs with neurological deficits, neuroimaging, and cerebrospinal fluid abnormalities consistent with a diagnosis of MUE.
Methods: Prospective, blinded, and randomized clinical trial. Dogs fulfilling the inclusion criteria were randomly allocated to receive 1 drug regimen.
Results: Four of 10 dogs in the COP group and 5/9 in the AraC group survived > 12 months but neither the survival time nor the time-to-treatment failure differed between the 2 groups. Treatment with COP resulted in an unacceptable incidence of adverse effects.
Conclusions: The adverse effects of COP make it an unsuitable treatment for MUE. Although survival of animals treated with AraC was broadly similar to that reported in recently published studies describing this treatment, it remains unclear whether it confers any benefit over using prednisolone alone.     

Use of tetracycline and niacinamide for treatment of autoimmune skin disease in 31 dogs.

A combination of niacinamide and tetracycline was used to treat 31 dogs with various autoimmune skin diseases (discoid lupus erythematosus, pemphigus foliaceus, pemphigus erythematosus, and bullous pemphigoid). Of the 20 dogs with discoid lupus erythematosus, 70% had excellent or good response to treatment. Serious side effects were not noticed in any dog.     

Immunoperoxidase staining for the detection of autoantibodies in canine autoimmune skin disease; comparison to immunofluorescence results

Skin sections from 22 dogs with autoimmune skin disease were stained with anti-canine IgG, IgM and IgA using an immunobridge immunoperoxidase method. Eight cases of lupus erythematosus, three cases of pemphigus vulgaris, and 11 cases of pemphigus foliaceus were included. Results of previously performed, direct immunofluorescence tests for the detection of canine immunoglobulin on skin were available on 17/22 cases. The immunoperoxidase method yielded an overall positive result in 59% (5/8 lupus erythematosus, 2/3 pemphigus vulgaris and 6/11 pemphigus foliaceus) versus an overall positive result of 47% for direct immunofluorescence (3/5 lupus erythematosus, 2/2 pemphigus vulgaris and 2/10 pemphigus foliaceus). The immunobridge immunoperoxidase method compared favorably to direct immunofluorescence testing of canine skin for autoantibody in cases of lupus erythematosis and pemphigus vulgaris, and was superior in cases of pemphigus foliaceus. This method should prove useful as an aid in the diagnosis of canine autoimmune skin disease.     

Lomustine and prednisone as a first-line treatment for dogs with multicentric lymphoma: 17 cases (2004-2005)

OBJECTIVE: To assess response rate, median duration of response, adverse effects, and prognostic factors associated with concurrent administration of lomustine and prednisone as a first-line treatment for dogs with multicentric lymphoma. DESIGN: Retrospective case series. ANIMALS: 17 dogs. PROCEDURES: Medical records were reviewed. Information obtained included signalment, physical examination findings, results of diagnostic testing, stage and substage, initial lomustine and prednisone dosages, and total number of lomustine doses administered. RESULTS: Lomustine was administered at a median starting dosage of 67 mg/m(2), PO, every 21 days until 5 doses were given or disease progression was observed. Prednisone was administered at a median starting dosage of 1.8 mg/kg/d (0.82 mg/lb/d), PO, with dosage tapered during the first month of treatment. Six dogs had a complete response, and 3 had a partial response. Mean and median durations of response were 48.8 and 39.5 days, respectively. Median survival time was 111.2 days. In multivariate analyses, female sex and higher total lomustine dose were significantly associated with a longer disease-free inter-val. Neutropenia was the dose-limiting factor, with 4 dogs developing clinically important neutropenia 1 week after administration of a dose of lomustine. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that concurrent treatment with lomustine and prednisone was well tolerated in dogs with multicentric lymphoma, but findings did not support the use of this combination for first-line treatment of affected dogs.     

Thymidine kinase assay in canine lymphoma

The aim of the study was to evaluate if thymidine kinase (TK) correlated with duration of first remission (DFR) or survival in dogs with lymphoma and if initial TK levels correlated with stage and substage; and also to assess if TK level at diagnosis correlated with immunophenotype. TK was assayed in 73 dogs with treatment naïve lymphoma, then again after treatment; 47% had an initial TK above the reference interval. Dogs with B‐cell lymphoma had higher initial TK activities than dogs with T‐cell lymphoma. TK levels were not higher in dogs with higher stage disease and TK activity prior to treatment was not associated with DFR or survival. Where TK was elevated at diagnosis, it fell into the reference range during remission. TK was normal in 53% dogs at diagnosis, which is higher than previously reported. Further studies are warranted to assess the utility of TK in dogs with lymphoma.     

Use of modified ciclosporin in the management of feline pemphigus foliaceus: a retrospective analysis

Background – Glucocorticoids as sole therapy for pemphigus foliaceus (PF) in cats are not always successful, and it is common to need additional immunomodulating agents to manage the disease. Hypothesis/Objectives – This retrospective study evaluated the use of modified ciclosporin as an adjuvant or sole immunomodulating drug in cats with PF and compared their response to PF cats managed with chlorambucil. Animals – Fifteen client‐owned cats diagnosed with PF that received ciclosporin and/or chlorambucil as part of their treatment and had adequate follow‐up to assess treatment response were evaluated. Methods – Records were reviewed from feline PF patients presented between the years of 1999 and 2009. Cats were divided into two treatment groups: those treated with ciclosporin and those treated with chlorambucil. Most cats in both groups also received concurrent systemic glucocorticoids. Each group contained six patients. Three cats were treated with both medications and are discussed separately. Time to disease remission, remission‐inducing glucocorticoid dose, maintenance or final glucocorticoid dose, disease response and adverse effects were assessed. Results – There was no significant difference in remission times or disease response between groups. All six patients maintained with ciclosporin for PF management were weaned off systemic glucocorticoids, while glucocorticoid therapy was stopped in only one of the six cats receiving chlorambucil. Conclusions and clinical importance – Modified ciclosporin is effective in the management of feline pemphigus foliaceus and is glucocorticoid sparing.     

Altered immunohistochemical staining for desmoglein in skin biopsies in canine pemphigus foliaceus.

In this study, 50 cases of canine pemphigus foliaceus and 49 cases of canine superficial pyoderma were examined by immunohistochemical staining for patterns of desmoglein expression. In 31/50 (62%) of pemphigus foliaceus cases, there was an altered staining pattern for desmoglein consisting of distinct clumped deposits at the periphery of keratinocytes and/or dark cytoplasmic staining of acantholytic cells (consistent with internalization of desmoglein). In contrast, desmoglein staining in biopsies from cases of superficial pyoderma was diffusely pale without evidence for clumping or distinct internalization. This study demonstrates that epidermal desmoglein expression is altered in some cases of pemphigus foliaceus in dogs and suggests that immunohistochemical staining for this protein may be useful in diagnosis.     

Immunohistochemical analysis of the distribution of desmoglein 1 and 2 in the skin of dogs and cats

OBJECTIVE: To compare the distribution of desmoglein (Dsg) 1 and 2 in skin specimens obtained from dogs and cats to provide information about the possible role of the density of Dsg 1 and 2 in the localization of lesions attributable to pemphigus foliaceus in these 2 species. SAMPLE POPULATION: Skin biopsy specimens obtained from 4 dogs and 4 cats. PROCEDURE: Biopsy specimens were collected from the muzzle, bridge of the nose, ear, dorsum, abdomen, area adjacent to the teats, and footpads of each animal. Immunohistochemical analysis was performed on formalin-fixed, paraffin-embedded skin samples by use of a biotinylated mouse monoclonal anti-Dsg 1 and 2 antibody raised against bovine muzzle. Color development was performed by use of the streptavidin-biotin-peroxidase method with a chromogenic substrate. RESULTS: Immunohistochemical staining yielded a positive reaction in skin samples obtained from all anatomic sites. The intensity and distribution of staining were related to the number of layers of the stratum spinosum. No differences were detected between samples obtained from dogs and cats. CONCLUSIONS AND CLINICAL RELEVANCE: No differences in intensity of Dsg 1 and 2 antigen were observed in the stratum spinosum between skin samples obtained from dogs and cats. Analysis of this result suggests that factors other than the distribution of Dsg may be responsible for the differences in localization of primary clinical lesions in dogs and cats with pemphigus foliaceus.     

A prospective study of clopidogrel therapy in dogs with primary immune-mediated hemolytic anemia

Background: A major cause of death in dogs with primary immune‐mediated hemolytic anemia (pIMHA) is thrombotic disease. Ultralow‐dose aspirin (ULDA) is commonly used to prevent thrombosis in dogs with pIMHA; however, the efficacy of antiplatelet agents in dogs with pIMHA is unknown. Hypothesis: The use of clopidogrel (CL), alone or in combination with ULDA, would improve survival to discharge and at 90 days without important adverse effects compared with ULDA alone in dogs with pIMHA treated with standard immunosuppressive therapy. Animals: Twenty‐four client‐owned dogs with pIMHA. Methods: Prospective, positive‐controlled, unmasked clinical trial with dogs randomized in 3 treatment groups to receive PO ULDA or CL or both. Results: There was no identifiable adverse reaction, evidence of hemorrhage, or increase in transfusion requirements associated with CL therapy, either alone or combined with ULDA, compared with ULDA alone. There was no significant difference between treatment groups with respect to survival to discharge and at 90 days. Conclusions and Clinical Importance: This study suggests that CL therapy, alone or in combination with ULDA, was safe and had similar short‐term survival compared with ULDA alone in a small group of dogs with pIMHA able to tolerate oral medications and treated with standard immunosuppressive treatment.     

Putative drug-related pemphigus foliaceus in four dogs

Four dogs developed cutaneous lesions following the administration of various antibiotics. Histopathology of the lesions was compatible with pemphigus foliaceus, although apoptotic cells suggestive of erythema multiforme were seen in two cases. In two dogs the lesions resolved after 7.5-8.5 months of immune-suppressive treatment. No recurrence was seen during the follow-up period (3 and 4.5 years). The lesions in the other two dogs resolved within 3 weeks to 3 months following discontinuation of the antibiotic. No recurrence of clinical signs occurred during the follow-up period (1 and 4 years, respectively).     

Comparative analysis of canine dermatophytosis and superficial pemphigus for the prevalence of dermatophytes and acantholytic keratinocytes: a histopathological and clinical retrospective study

Acantholytic dermatophytosis is a rarely reported condition of dogs that clinically and histopathologically mimics superficial pemphigus (erythematosus, foliaceus). Histologically, periodic acid-Schiff (PAS) and Grocott's methenamine-silver (GMS) are often necessary to show the fungus. A retrospective histopathological study was conducted on 190 canine skin biopsy specimens: 95 each with the diagnosis of canine dermatophytosis or of superficial pemphigus. All specimens were stained with haematoxylin and eosin, PAS, and GMS. Dermatophytes were not seen in any superficial pemphigus cases. Acantholytic keratinocytes were noted in 14% of the dermatophytosis cases, none of which had clinical signs consistent with superficial pemphigus. Among cases with acantholytic keratinocytes, superficial pemphigus had significantly more acantholytic cells than dermatophytosis (P = 0.02). When comparing face and nonface cases, there was no difference in prevalence of acantholytic keratinocytes in dermatophytosis or number of acantholytic keratinocytes in superficial pemphigus. All dermatophyte cases were both GMS and PAS positive with neither stain being visually superior. No dermatophyte cases where acantholytic keratinocytes were noted had a history, clinical signs and histopathological features compatible with acantholytic dermatophytosis.     

Procarbazine as adjunctive therapy for treatment of dogs with presumptive antemortem diagnosis of granulomatous meningoencephalomyelitis: 21 cases (1998-2004)

BACKGROUND: Granulomatous meningoencephalomyelitis (GME) is an idiopathic inflammatory disease of the central nervous system. Remission often is short-lived in dogs treated with glucocorticoids. Procarbazine is T cell-specific and crosses the blood-brain barrier. HYPOTHESIS: Dogs with presumptive antemortem diagnosis of GME given procarbazine as adjunctive therapy to prednisone will have improved long-term outcome compared with dogs given no treatment or glucocorticoids alone. ANIMALS: Two groups were studied: (1) Dogs with presumptive antemortem diagnosis of GME treated with procarbazine and prednisone (n = 21); (2) Dogs that had a histologic diagnosis of GME at postmortem examination and received no treatment (n = 11). METHODS: Dogs with presumptive GME treated with procarbazine were identified retrospectively from medical records of 2 veterinary referral hospitals. Selection criteria required all dogs have a neurologic examination, blood work, cerebrospinal fluid analysis, and brain imaging (MRI or CT). RESULTS: Median survival time for all dogs studied was 5.0 months. Median survival time for dogs treated with procarbazine was 14.0 months and for untreated dogs, 0.73 months. Treatment with procarbazine was significantly correlated with survival time (P < .001). Procarbazine was the only independent predictor of survival. Prednisone was reduced in dosage or discontinued in 17 dogs. Adverse reactions to procarbazine therapy included myelosuppression in 7 dogs and hemorrhagic gastroenteritis in 3 dogs. CONCLUSION: These data suggest that procarbazine treatment of presumptive GME may result in greater improved long-term outcome than has been previously reported for glucocorticoid treatment alone and may complement other immunomodulatory therapies. Procarbazine-treated dogs must be monitored for adverse reactions.