IgG autoantibodies directed against desmoglein 3 cause dissociation of keratinocytes in canine pemphigus vulgaris and paraneoplastic pemphigus

Pemphigus is a group of autoimmune blistering diseases of the skin and mucous membranes. In human patients with pemphigus vulgaris (PV) and paraneoplastic pemphigus (PNP), IgG autoantibodies against desmoglein (Dsg) 3 and Dsg1 play pathogenic roles in blister formation. In contrast, the target for IgG autoantibodies that induce keratinocyte dissociation has not been elucidated in canine pemphigus. The aim of the present study was to determine whether anti-Dsg IgG autoantibodies are present and disrupt the cell-cell adhesion of keratinocytes in canine PV and PNP. The extracellular domains of canine Dsg3 were recognized by IgG in 3/5 (60%) canine PV sera tested. IgG against the extracellular domains of canine Dsg1 was detected exclusively in two dogs that had PV with the mucocutaneous phenotype. In addition, anti-Dsg3 IgG was identified in canine PNP serum. Furthermore, incubation of normal human keratinocytes (NHK) with mucocutaneous canine PV serum and canine PNP serum resulted in dissociation of the NHK sheets, whereas the removal of anti-Dsg3 IgG from these canine sera blocked this dissociation. The present study indicates for the first time that circulating anti-Dsg3 IgG antibodies capable of dissociating keratinocytes are present in dogs with PV and PNP.     

Suspected polymyxin B-induced pemphigus vulgaris in a dog

A case of pemphigus vulgaris (PV), putatively induced by topical application of polymyxin B ear drops, is described. A 3-year-old, female Tosa Inu, presented with acute onset swelling, blistering and ulceration of the pinnae, nostrils, lips and oral mucous membranes. The dog was depressed, febrile and anorexic. For 7 days prior to the onset of the acute ulcerative disease, polymyxin B ear drops had been applied to both ears to treat an ear infection. Skin and mucosal biopsies showed suprabasilar cleft formation and acantholysis, indicative of PV. The polymyxin B ear drops were discontinued and the dog was treated with intravenous fluids, systemic and topical antibacterial therapy, and immunosuppressive therapy comprising prednisone and azathioprine. Complete remission was noted after 2 weeks, and the immunosuppressive therapy was discontinued one month later. No clinical signs of PV recurred over a 1 year follow-up period. As PV does not usually resolve spontaneously, or enter long-term remission, it was considered that the condition was most likely drug induced due to the aural application of polymyxin B.     

Pathogenesis of pemphigus vulgaris in dog and man - a review

Pemphigus vulgaris is a vesiculobullous disorder that predominantly involves the oral mucous membrane of the canine and human patients. The oral lesions are usually painful erosions and ulcers. This predilection for mucous membrane may reflect the smaller number of desmosomes in the oral epithelium as compared with the epidermis. The discovery of autoantibodies against the intercellular substance of stratified epithelium in patients with pemphigus vulgaris suggests that this disease represents an autoimmune disease. The exact role of these autoantibodies in the pathogenesis of pemphigus vulgaris is not clearly understood. The diagnosis is usually based on the presence of the characteristic flaccid bullae and erosions. Biopsy specimen taken from the edge of a fresh blister and adjacent epithelial layers is suitable for routine microscopic examination and direct immunofluorescence study. Combination of corticosteroids and immunosuppresive agents are used for treatment of this disease.     

Paraneoplastic pemphigus in a dog

This report presents a case of paraneoplastic pemphigus in a 7-year-old female Bouvier. The dog initially showed extensive oral ulcerations that exacerbated upon treatment with trimethoprim-sulfadiazine. Subsequently, the dog developed vesiculobullous and ulcerative lesions on the ear margins, the nose, periocular, and at the nail beds. Due to complete therapy resistance and a deteriorating general condition, the dog was euthanized. During post-mortem examination a thymic lymphoma was found. While an early biopsy of the oral cavity revealed features of erythema multiforme, skin lesions at necropsy were typical of pemphigus vulgaris. Indirect immunofluorescence of patient serum revealed an antikeratinocyte membrane pattern typical for pemphigus. The serum was also positive on bovine bladder epithelium. In a Western blot, autoantibodies to a 210 and a 190 kDa protein were detected.     

Paraneoplastic pemphigus in a dog with splenic sarcoma

Paraneoplastic pemphigus (PNP) is an autoimmune blistering skin disease of humans that consists of characteristic skin lesions associated with concurrent neoplasia. In this study we provide histologic and serologic evidence to support a diagnosis of PNP in a dog with splenic sarcoma. Skin lesions consisted of widespread erosions involving haired skin, mucocutaneous junctions, and oral mucosa. Microscopic examination of skin and mucosae revealed lesions consistent with both pemphigus vulgaris and erythema multiforme. Immunoprecipitation confirmed that circulating IgG autoantibodies from this patient recognized five distinct antigens, presumed to represent epidermal plakins. Clinical, histopathologic, and immunologic findings in this patient were similar to those observed in human patients with PNP. The splenic neoplasia in this dog was diagnosed as a phenotypically variable spindle cell sarcoma. To date, only one other dog has been reported with PNP. This is the second reported case of canine PNP and the first patient in whom skin lesions were identified in association with splenic neoplasia.     

Canine pemphigus vulgaris treated with gold salt therapy

A nine year old spayed female Collie was diagnosed as having pemphigus vulgaris. Response to corticosteroid and antibiotic therapies was unsatisfactory. Aurothioglucose therapy was used later as the sole treatment. The dog achieved a complete remission lasting at least ten months.     

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.     

Cutaneous neosporosis during treatment of pemphigus foliaceus in a dog

A 4-year-old, intact male rottweiler was presented with a 10-day history of papulonodular dermatitis. At the time of presentation, the dog was receiving prednisone and azathioprine to treat pemphigus foliaceus. Cutaneous neosporosis was diagnosed by immunohistochemistry on skin biopsy specimens and a high serum antibody titer to Neospora caninum by Neospora agglutination test. Electron microscopy examination of skin specimens further supported the diagnosis. Clindamycin therapy, together with withdrawal of immunosuppressive medication, resulted in prolonged clinical remission. This report documents cutaneous neosporosis in an adult dog and suggests that immunosuppressive therapy might be a predisposing factor.     

Topical 0.03% tacrolimus for treatment of pemphigus erythematosus in a Korea Jindo dog

Topical 0.03% tacrolimus was used for treatment of a Korea Jindo dog diagnosed with pemphigus erythematosus. The dog was slowly improved following application of tacrolimus but did not achieve complete remission until end of this study. No adverse effects on clinical or laboratory parameters were noted during the topical tacrolimus therapy period.     

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.     

Detection of circulating autoantibodies using living keratinocyte staining on MCA-B1 method in dogs with pemphigus foliaceus

In this study, we compared the sensitivity and specificity of three immunofluorescence techniques used to detect circulating autoantibodies in dogs with pemphigus foliaceus (PF); living keratinocyte staining on a canine keratinocyte cell line, MCA-B1, indirect immunofluorescence (IIF) on canine lip and IIF on bovine esophagus. Sera from canine PF cases were positive in four out of 27 dogs (14.8%) using living keratinocyte staining on MCA-B1 cells method, and five (18.5%) and eight sera (29.6%) using IIF on canine lip and bovine esophagus methods, respectively. By contrast, none of the 31 sera from dogs with non-pemphigus dermatoses reacted with MCA-B1 cells, whereas two (6.5%) as well as five sera (16.1%) obtained from those dogs showed positive reactivity with IIF on canine lip and bovine esophagus, respectively. Our results suggest that, although it exhibits the least sensitivity, the positive reactivity obtained by living keratinocyte staining on MCA-B1 cells can support the diagnosis of canine PF.     

Two cases of pemphigus erythematosus (the Senear-Usher syndrome) in the dog

The clinical and diagnostic features of two cases of pemphigus erythematosus in the dog are described. This disease, which is one of the autoimmune bullous skin diseases, should be included in the differential diagnosis of nasal dermatitis or of so-called ‘Collie-nose’.     

Lymphosarcoma with hypercalcemia and osteolysis in a dog

Lymphosarcoma in a six year old male Doberman pinscher was accompanied by hypercalcemia, generalized osteolysis and renal calcification. Tumor involvement of bone marrow was extensive. The possible pathogenesis of hypercalcemia was thought to be the result of a locally active bone-resorbing factor secreted by the tumor cells.