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.     

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.     

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.     

Characterisation of the inflammatory reaction in equine idiopathic focal eosinophilic enteritis and diffuse eosinophilic enteritis

REASONS FOR PERFORMING STUDY: Idiopathic focal eosinophilic enteritis (IFEE) and diffuse eosinophilic enteritis (DEE) are primary eosinophilic intestinal conditions without a known cause that are associated with an increasing number of surgical colic cases. Histology may be helpful in defining disease aetiology and pathogenesis. OBJECTIVES: To characterise further the inflammatory infiltrate in equine IFEE and to compare the condition with DEE. METHODS: Twenty-three IFEE cases and 5 DEE cases were examined by light microscopy including immunohistology to identify infiltrating leucocytes. Inflammatory infiltrates in mucosa and submucosa were characterised in IFEE lesions (Group 1), the intestine distant from the lesions in IFEE (Group 2) and DEE (Group 3). RESULTS AND CONCLUSIONS: IFEE lesions represented an accumulation of leucocytes in submucosa and muscularis, with dominance of eosinophils and macrophages and smaller numbers of lymphocytes, plasma cells and neutrophils. T cells represented the dominant lymphocytes. The mucosa overlying the lesion and both mucosa and submucosa in IFEE nonlesion sites and in DEE exhibited a similar composition, with different prevalence of various cell types. Macrophages were significantly more prevalent in the mucosal and submucosal infiltrates in IFEE nonlesion sites than in DEE, and lymphocytes significantly more prevalent in the mucosa in DEE than in IFEE nonlesion sites. The findings confirm IFEE as a primary eosinophilic intestinal disorder and indicate that IFEE represents a focally exacerbated inflammatory reaction in horses with DEE, possibly due to functional changes in the macrophage and T cell components, with subsequent excessive recruitment of both eosinophils and macrophages.     

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.     

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.     

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.     

The longevity of immunoglobulin preservation in canine skin utilizing Michel's fixative

Skin biopsy specimens from 7 dogs with immune-mediated skin diseases diagnosed by routine histology and 5 dogs with other skin diseases were placed in Michel's transport medium for 4 to 9 years. Direct immunofluorescence yielded positive results in tissue samples from 3 dogs with pemphigus foliaceus and 2 dogs with discoid lupus erythematosus. Direct immunofluorescence was not seen in tissue samples from 1 dog with pemphigus foliaceus and 5 dogs with non immune-mediated skin diseases. Direct immunofluorescence was seen in skin biopsy specimens maintained in Michel's medium for 4 to 8 years.     

Pemphigus foliaceus in 91 dogs

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.     

Idiopathic Eosinophilic Masses of the Gastrointestinal Tract in Dogs

Background: Eosinophilic inflammation of the gastrointestinal tract of dogs occurs in numerous disorders, typically resulting in diffuse intestinal thickening. Rarely, eosinophilic masses have been reported.
Objective: Describe a series of dogs with 1 or more idiopathic eosinophilic gastrointestinal masses (IEGM) to better characterize the clinical features, treatment, and prognosis.
Animals: Seven dogs with 1 or more gastrointestinal masses composed primarily of eosinophilic infiltrates for which no underlying cause was found.
Methods: Retrospective case series.
Results: Rottweilers and purebred, large breed dogs predominated. Dogs were middle-aged and typically had chronic signs of upper or lower gastrointestinal disease. Decreased appetite, vomiting, and evidence of gastrointestinal hemorrhage were present in the majority of cases. An abdominal or rectal mass was frequently noted on physical examination. Common laboratory abnormalities included peripheral eosinophilia, mature neutrophilia, hypoproteinemia, and hypocholesterolemia. The masses were histologically composed of moderate to severe eosinophilic infiltrates, which were often transmural and accompanied by fibrosis. All dogs treated with surgery alone died of complications of their disease. Treatment with corticosteroids and ivermectin improved clinical signs, caused resolution of eosinophilic infiltrates, and prolonged survival in most dogs treated medically.
Conclusions and Clinical Importance: These findings suggest that the prognosis for dogs with IEGM may be good when recognized and managed appropriately. When surgery is performed, medical treatment should also be added.     

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.     

Investigations on the nature and pathogenicity of circulating antikeratinocyte antibodies in dogs with pemphigus foliaceus

In humans with pemphigus foliaceus (PF), pathogenic autoantibodies are principally of IgG4 subclass and they cause superficial vesiculation when injected into neonatal mice. The objectives of this study were to determine the isotypes of circulating antikeratinocyte antibodies in dogs with PF, to assess whether serum antikeratinocyte antibody titres decreased during successful treatment, and to study whether such antibodies were pathogenic in passive transfers. Using indirect immunofluorescence with neonatal mouse skin substrates, circulating antikeratinocyte IgG antibodies were detected in 36 of 44 dogs with PF (82%). Serum autoantibodies belonged predominantly to IgG4 (three of 44; 80%) and IgG1 (30 of 44; 68%) subclasses. Antikeratinocyte IgG antibodies were detected in 16 of 20 normal dogs (80%), and these antibodies were IgG1 (16 of 20, 80%) but rarely IgG4 (two of 20; 10%) isotypes. In four dogs, IgG4 antikeratinocyte antibody titres decreased concomitantly to lesions nearing or reaching complete remission. In contrast, IgG or IgG1 titres remained stable or increased when lesions abated. Antikeratinocyte antibodies targeted mainly intercellular autoantigen(s) in the stratum granulosum, while in fewer dogs, such antibodies bound to cytoplasmic basal antigen(s). Intradermal injections of PF or pemphigus vulgaris (PV) IgG into neonatal mice caused subgranular or suprabasal acantholytic vesiculation without granulocyte infiltration, respectively. Similar transfers of normal dog IgG did not cause vesiculation. These observations suggest that antikeratinocyte IgG4 antibodies could be relevant to disease pathogenesis. Importantly, canine PF or PV IgG appear to be pathogenic when transferred passively into mice, causing vesiculation at epidermal levels similar to those of the natural disease.     

Eosinophilic dermatitis with edema in nine dogs, compared with eosinophilic cellulitis in humans.

A unique eosinophilic dermatitis with edema in dogs is characterized by extremely erythematous coalescing macules and plaques with associated edema, and is similar to eosinophilic cellulitis (Wells' syndrome) in humans. Histopathologic features include a profound eosinophilic dermal infiltrate, focal areas of collagen fiber degeneration surrounded by eosinophils (flame figures), dilated vessels, and dermal edema. Etiopathogenesis is unknown, but a hypersensitivity reaction to medications, arthropod bites, or other foreign antigens is suspected.     

Complement immunofluorescence in sera of dogs with pemphigus foliaceus

Sera from 14 dogs with active pemphigus foliaceus were tested for the presence of circulating antiepithelial antibodies. These antibodies could not be detected in the dogs with indirect immunofluorescent staining or in vitro complement-staining methods.     

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.     

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.     

Immunopathology of analfurunculosis in the dog

Perianal tissue obtained from 10 normal dogs and 40 dogs with anal furunculosis was immunostained in order to determine the number and distribution of B lymphocytes/plasma cells (expressing IgG, IgM or IgA) and T lymphocytes (expressing the CD3 marker) within the inflammatory infiltrates. Differences in these parameters between tissue obtained from affected German shepherd dogs (n = 20) and affected dogs of other breeds (n = 20) were recorded. The immunological phenotype of cells comprising lymphoid follicles and associated with ductal eosinophilic pustules observed in the anal sacs of dogs with anal furunculosis is described. The results of this study suggest that a simple immunological defect does not underlie the predisposition of dogs of the German shepherd breed for anal furunculosis.     

Outcome and complications associated with treatment of pemphigus foliaceus in dogs: 43 cases (1994-2000)

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.     

Ultrastructural localization of pemphigus vulgaris antigen on canine keratinocytes in vivo and in vitro

Pemphigus antigens were localized, by use fo immunoelectron microscopy, on canine keratinocytes in vivo on esophageal mucosa and in vitro on established cultured keratinocytes. Convalescent sera from a human being with pemphigus vulgaris and a human being with pemphigus foliaceus reacted with the interdesmosomal cytoplasmic keratinocyte membrane of canine esophagus. Cultured canine keratinocytes expressed the pemphigus vulgaris antigen in a similar pattern, but did not carry the pemphigus foliaceus antigen. The differential presence of cell surface antigens and its relation to various forms of the disease are discussed.     

Efficacy of the treatment of dogs with leishmaniosis with a combination of metronidazole and spiramycin

Twenty-seven dogs infected naturally with Leishmania infantum were used in a randomised controlled trial to compare the clinical and parasitological efficacy of an oral treatment with a combination of metronidazole and spiramycin (13 dogs) with the efficacy of conventional treatment with meglumine antimonate and allopurinol (14 dogs) as controls. In the test group one dog had to be withdrawn from the treatment because it developed pemphigus foliaceus; 10 of the dogs were clinically responsive but none was cured parasitologically. In the control group four dogs were withdrawn from the treatment because of side effects; eight of the dogs were clinically responsive but none was cured parasitologically. The control group showed signs of improvement after an average of 30 days, whereas the test group did not show signs of improvement until after an average of 45 days.