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: current therapy

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).     

Influence of long-term treatment with tetracycline and niacinamide on antibody production in dogs with discoid lupus erythematosus

OBJECTIVE: To evaluate the effect of long-term treatment with tetracycline and niacinamide on antibody production in dogs by measuring postvaccinal serum concentrations of antibodies against canine parvovirus and canine distemper virus. ANIMALS: 10 dogs receiving long-term treatment with tetracycline and niacinamide (treatment group) and 10 healthy dogs (control group). PROCEDURE: The treatment group included 9 dogs with discoid lupus erythematosus and 1 dog with pemphigus foliaceus on long-term treatment (> 12 months) with tetracycline and niacinamide. The control group included 10 healthy dogs with no clinical signs of disease and no administered medications for the past 3 months. Blood samples were obtained from all dogs by jugular venipuncture. Serum antibody titers against canine parvovirus and canine distemper virus antigens were measured, using hemaglutination inhibition and serum neutralization, respectively, and compared between groups. RESULTS: A significant difference in antibody titers between treatment- and control-group dogs was not found. All dogs had protective antibody titers against canine distemper virus, and 8 of 10 dogs from each group had protective titers against canine parvovirus infection. CONCLUSION AND CLINICAL RELEVANCE: These results provide evidence that long-term treatment with tetracycline and niacinamide does not interfere with routine vaccinations and thus does not seem to influence antibody production in dogs.     

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.     

P-52 A case of juvenile cellulitis concurrent with hindlimb paresis in an English cocker spaniel puppy

Pemphigus vegetans is a very rare cutaneous autoimmune blistering acantholytic disease of humans that combines features of both pemphigus foliaceus and mucosal lesions of pemphigus vulgaris. We report here the clinical, histopathological and immunological findings in a dog whose lesions resembled those of pemphigus vegetans of humans. A 4-year old, greater Swiss mountain dog was presented with verrucous papules and crusts on the axillae and inguinal region. Within 3 months, lesions progressed to involve the thorax and ear pinnae, and then became generalized. Ulcers were observed in the oral cavity, anus and prepuce. Microscopic examination of mucosal and cutaneous biopsy specimens revealed a mixed pattern of deep intraepidermal neutrophilic and eosinophilic pustules with isolated and clustered acantholytic keratinocytes, along with suprabasal epidermal clefts leaving rounded basal keratinocytes at the bottom of the vesicles. These dual changes were also observed within the hair follicle epithelium. Dermal inflammation was mixed and perivascular. Direct immunofluorescence revealed IgG deposited around epidermal keratinocytes. Indirect immunofluorescence performed on normal canine gingival substrate uncovered antikeratinocyte IgG autoantibodies with a serum titre of 1:2500. Immunoblotting confirmed that circulating IgG autoantibodies recognized the extracellular segment of canine desmoglein-1 and human desmoglein-3. Treatment with azathioprine and oral glucocorticoids resulted in long-lasting complete remission. In this dog, clinical signs, microscopic skin lesions and immunological findings were deemed analogous to those of human Neumann-type pemphigus vegetans.
Funding: Self-funded.     

Cutaneous reactive histiocytosis in dogs: a retrospective evaluation of 32 cases

Thirty-two cases of canine cutaneous histiocytosis were retrospectively evaluated. Median age at onset was 4 years. Lesions included nodules and plaques affecting the head/face, trunk and limbs, and erythema, swelling and depigmentation of the nasal planum/nares. Systemic involvement was not ruled out in all cases. All dogs had complete resolution of dermatological lesions after initial treatment (median 45 days). Initial treatment included prednisone +/- antibiotics (12 of 32 dogs), prednisone and tetracycline/niacinamide (four of 32), prednisone and azathioprine (three of 32), tetracycline/niacinamide +/- vitamin E/essential fatty acids (six of 32), antibiotics +/- antihistamines (three of 32), cyclosporine and ketoconazole (one of 32), topical therapy (two of 32), and no treatment (one of 32). Seventeen dogs received maintenance therapy which consisted of tetracycline/niacinamide +/- vitamin E/essential fatty acids (12 of 17), cyclosporine/ketoconazole (two to three times a week) (two of 17), azathioprine daily (one of 17), prednisone/azathioprine (two times a week) (one of 17), and prednisone daily (one of 17). Median follow up was 25 months. Nine dogs had a recurrence of cutaneous histiocytosis (median days to recurrence 130 days), with seven of nine having more than one recurrence. At study completion, six dogs were deceased (no lesions at the time of death) and 26 of 32 were alive with no lesions. Ten of 26 dogs were on maintenance treatment (eight tetracycline/niacinamide, one azathioprine, one vitamin E). Previous dermatological disease and season had no detectable influence on recurrence. Recurrence was significantly more likely in dogs with nasal planum/nares lesions than dogs without these lesions. Tetracycline/niacinamide was an effective treatment option for dogs in this study population.     

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.     

P‐50 Clinical,histological and immunological characteristics of Neumann‐type pemphigus vegetans in a dog

Pemphigus vegetans is a very rare cutaneous autoimmune blistering acantholytic disease of humans that combines features of both pemphigus foliaceus and mucosal lesions of pemphigus vulgaris. We report here the clinical, histopathological and immunological findings in a dog whose lesions resembled those of pemphigus vegetans of humans. A 4‐year old, greater Swiss mountain dog was presented with verrucous papules and crusts on the axillae and inguinal region. Within 3 months, lesions progressed to involve the thorax and ear pinnae, and then became generalized. Ulcers were observed in the oral cavity, anus and prepuce. Microscopic examination of mucosal and cutaneous biopsy specimens revealed a mixed pattern of deep intraepidermal neutrophilic and eosinophilic pustules with isolated and clustered acantholytic keratinocytes, along with suprabasal epidermal clefts leaving rounded basal keratinocytes at the bottom of the vesicles. These dual changes were also observed within the hair follicle epithelium. Dermal inflammation was mixed and perivascular. Direct immunofluorescence revealed IgG deposited around epidermal keratinocytes. Indirect immunofluorescence performed on normal canine gingival substrate uncovered antikeratinocyte IgG autoantibodies with a serum titre of 1:2500. Immunoblotting confirmed that circulating IgG autoantibodies recognized the extracellular segment of canine desmoglein‐1 and human desmoglein‐3. Treatment with azathioprine and oral glucocorticoids resulted in long‐lasting complete remission. In this dog, clinical signs, microscopic skin lesions and immunological findings were deemed analogous to those of human Neumann‐type pemphigus vegetans. Funding: Self‐funded.     

A retrospective study regarding the treatment of lupoid onychodystrophy in 30 dogs and literature review

The treatment records of 30 dogs with lupoid onychodystrophy were evaluated retrospectively. Dogs were treated with fatty acid supplementation (n=18), doxycycline and niacinamide (n=12), tetracycline and niacinamide (n=10), pentoxifylline (n=6), prednisolone (n=5), azathioprine (n=1), clofazimine (n=1), or with combinations thereof. An excellent response was seen in almost half of the patients treated with tetra- or doxycycline in combination with niacinamide. Six of the dogs were maintained successfully on fatty acid supplementation. Spontaneous remissions and recurrences made evaluation of success rates difficult and emphasized the varied and often unclear etiology and natural course of the syndrome.     

Epidermolysis bullosa acquisita in a Great Dane

Autoimmune subepidermal blistering diseases in dogs were all classified as bullous pemphigoid until 1998. Since then, refinements in reagents and immunological techniques have allowed diseases which are histologically similar but which have a different molecular pathogenesis to be described. This report describes the first case of one such disease, epidermolysis bullosa acquisita, to be documented in the UK. The dog presented with a severe blistering and ulcerative disease affecting the oral cavity, pinnae and distal limbs. The diagnosis was confirmed by histopathology and direct and indirect immunofluorescent demonstration of immunoglobulin G reactivity to basement membrane antigens. Treatment with glucocorticoids, azathioprine, colchicine and an intravenous infusion of immunoglobulins resulted in complete resolution. The drugs were discontinued 12 months after the start of treatment and the dog remained in remission.     

Acute pancreatitis in two dogs given azathioprine and prednisone

Acute pancreatitis was diagnosed in 2 dogs given azathioprine and prednisone. Prednisone and azathioprine had been given as immunosuppressive therapy for pemphigus foliaceus in dog 1 and for polymyositis in dog 2. Azathioprine was discontinued in both dogs. In dog 1, prednisone was reinstituted on day 6 of hospitalization. Prednisone was continued throughout the period of hospitalization in dog 2. Both dogs recovered without complication. Glucocorticoid therapy has been associated with the development of pancreatitis. In human beings, a common side effect of azathioprine is the development of drug-induced pancreatitis. Definitive identification of azathioprine as the cause of pancreatitis in these dogs was not possible; the owners refused to permit retreatment with the drug. Therefore, the synergistic action between these 2 drugs could not be ruled out as the cause of pancreatitis.     

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.     

Pemphigus foliaceus in two Shetland sheepdog littermates

Two female Shetland Sheepdog littermates simultaneously developed pemphigus foliaceus at 6 months of age. Three other littermates were not affected. One bitch (tricolored) was not treated, and the disease has remained active for 2 years. The other bitch (blue merle) has been successfully managed with glucocorticoids and gold salts.     

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 dogs: a review of 37 cases

Thirty-seven dogs with pemphigus foliaceus were seen over a span of 9 years in a veterinary medical teaching hospital. Four breeds of dogs (Bearded Collie, Akita, Newfoundland, Schipperke) were at significant elevated risk when compared with both the dermatology canine case population and the hospital canine population. The mean age of onset was 4.2 years. The dorsal part of the muzzle was the most common site of initial involvement in over 50% of the dogs, and lesions of the head were seen first in 81% of the dogs. Disease progression was gradual (greater than 3 months) in 73% of the dogs. Somewhat bilaterally symmetric scaling, crusting, and alopecia were seen in all of the dogs. Vesicles, pustules, and bullae were not seen commonly, but target lesions with peripheral collarettes were seen frequently. Most dogs had characteristic footpad lesions, with erythematous swelling at the pad margins, cracking, and villous hypertrophy. Generalized exfoliative dermatitis was seen in dogs with widespread disease. Pruritus was noted in less than one half of the dogs. Typical histopathologic findings included subcorneal and intragranular cell layer epidermal pustules, or intrafollicular pustules with prominent acantholysis. Direct immunofluorescence in an intercellular pattern was noted in 76% of the dogs tested and indirect immunofluorescence was noted in 75% of a much smaller sample. Thirty-nine percent of the dogs responded to corticosteroid therapy alone, and 50% and 55% responded, respectively, to prednisone and cytotoxic drugs, and to prednisone with aurothioglucose. Aurothioglucose was successful alone in 27% of the dogs. One-year survival was achieved in 53% of the dogs.     

P-29 Pustular dermatosis caused by fire ant (Solenopsis invicta) stings in a dog

The purpose of this study was to evaluate 55 clinical cases of canine demodicosis and to compare the results of treatment using amitraz (solution), selamectin (spot-on), ivermectin (injection) and cythioate (oral tablets). Data from the 55 cases was collected and evaluated after clinical and microbiological examination. Treatment was selected depending on the severity of demodicosis and compliance of the owner. The cases were followed for 12 months and the status of the patients was grouped on two levels: recovered (58%), or relapsed (42%). Five dogs (9%) were euthanized. The disease was commonly diagnosed in purebred dogs. Demodicosis was more common in dogs under 2 years of age (65%), in males (64%), and in the short-haired breeds (75%). Demodicosis was generalized in 73% of cases, localised in 23% and affected the feet (pododemodicosis) in 4% of cases. Recovery was the highest in dogs between 1 and 2 years of age (73%), and in the localized cases (92%). Nonspecific treatment with glucocorticoids prior to the diagnosis lowered the rate of recovery (4%), but treatment with glucocorticoids for proven atopic dermatitis improved the rate of recovery (41%). All drugs (amitraz, selamectin, cythioate) administered for the localized form were effective (100% recovered). Recovery in generalized demodicosis was 60% using ivermectin, 55% using amitraz, 44% with the combination of amitraz and selamectin (two treatments with amitraz followed by selamectin), and 43% in cases where selamectin was used alone.
Funding: Pfizer Animal Health.     

Azathioprine therapy for acquired myasthenia gravis in five dogs.

Five dogs with acquired myasthenia gravis (MG), verified via positive serum acetylcholine (ACh) receptor antibody concentrations, were treated with a drug protocol including azathioprine (AZA). Four of the five dogs were concurrently treated with pyridostigmine. Azathioprine was used as the sole immunosuppressive agent in four dogs. One dog was temporarily treated with a combination of an immunosuppressive dose of prednisone and AZA, then maintained on AZA as the sole immunosuppressive drug. Three patients experienced complete remission of clinical signs within three months of therapy. In the four dogs for which follow-up serum ACh receptor antibody concentrations were available, initial versus final concentrations decreased substantially (81%), coincident with clinical improvement. One dog died suddenly due to a suspected myasthenic crisis before attaining the target dose of AZA. Two of the four surviving dogs were euthanized approximately one and seven years after diagnosis. One of these two dogs was euthanized because of a rib osteosarcoma, and the other dog was euthanized because of paraparesis of undetermined cause. The remaining two dogs were alive and doing well at the time of final follow-up evaluation, approximately six months and one year after diagnosis. The use of AZA as a therapeutic agent for acquired canine MG has not been investigated. The cases presented in this report suggest a potentially important role for AZA in the treatment of acquired MG in dogs.     

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.     

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).