Detection of circulating anti-keratinocyte autoantibodies in feline pemphigus foliaceus.

BACKGROUND: Circulating anti-keratinocyte immunoglobulin (Ig)G targeting desmosomal proteins have been identified in people and dogs with pemphigus foliaceus (PF). By contrast, detection attempts in PF-affected cats have been largely unsuccessful. HYPOTHESIS/OBJECTIVES: To detect circulating anti-keratinocyte autoantibodies in PF-affected cats and determine their titres and tissue-staining patterns. ANIMALS: Thirty PF-affected cats were compared to 11 specific-pathogen free, 15 healthy and 31 allergic cats. METHODS AND MATERIALS: Sera were tested by indirect immunofluorescence on canine footpad and buccal mucosal substrates. RESULTS: Circulating, anti-keratinocyte IgG with a suprabasilar, web-like (intercellular) pattern were detected in the majority of PF-affected cats (23 of 30, 77%), some allergic cats (six of 31, 19%) and one healthy cat (7%). Both footpad epidermis and buccal mucosa were positive in the majority of seropositive PF-affected cats (21 of 23, 91%), and in only one of six (17%) seropositive allergic cats. Staining was limited to the footpad in the remaining seropositive PF-affected and allergic cats and one seropositive healthy cat. Reciprocal IgG titres were significantly higher in PF-affected cats compared to controls (Dunn's post-test, P < 0.0001). Anti-keratinocyte IgM, IgA or IgE were not detected in any sera. CONCLUSIONS AND CLINICAL IMPORTANCE: These results confirm the presence of circulating anti-keratinocyte IgG in a majority of PF-affected cats and in a small percentage of healthy and allergic cats. Although the molecular target and pathogenic nature of the antibodies remains unknown, the detection of positive immunostaining on buccal mucosal tissue, in addition to the footpad, suggests that the major target antigen of feline PF differs from that reported in dogs.

Cutaneous polyautoimmunity in two unrelated dogs: pemphigus foliaceus and generalized discoid lupus erythematosus.

BACKGROUND: Polyautoimmunity, the concurrent expression of two or more distinct autoimmune diseases (ADs) in a single individual, is a known phenomenon in humans and has been rarely reported in dogs. To the best of the authors' knowledge, comorbid pemphigus foliaceus (PF) and generalized discoid lupus erythematosus (GDLE) has not been reported in dogs. HYPOTHESIS/OBJECTIVES: To describe the clinical, histological and immunological features and treatment outcome of two unrelated dogs with comorbid PF and GDLE. ANIMALS: One 10-year-old, spayed German shepherd dog and one 8-year-old, castrated American Staffordshire terrier presented for evaluation of a symmetrical, facial- and/or pedal-dominant pustular dermatitis with concurrent, truncal scaly plaques. METHODS: For each dog, clinicopathological characterization included physical examination, lesion cytological evaluation, bacterial culture and sensitivity testing, skin histopathological investigation and direct and indirect immunofluorescence testing. Additional diagnostic imaging and haematological testing was performed to exclude extracutaneous disease. RESULTS: Both dogs exhibited lesions clinically and histologically compatible with PF and GDLE. Moreover, one dog exhibited generalized leucotrichia and chronic superficial keratitis. Remission was achieved with immunosuppressive dosages of prednisolone [high-dose pulse (Case 1) or standard immunosuppressive dosage (Case 2)] and ciclosporin (5-6 mg/kg/day). Tissue-bound antikeratinocyte immunoglobulin (Ig)G and IgM were detected in both dogs. A weak basement membrane zone deposit of C3 was seen in one dog. Circulating antikeratinocyte and anti-desmocollin-1 IgG were detected in one dog. CONCLUSIONS AND CLINICAL IMPORTANCE: Cutaneous polyautoimmunity can occur in the dog. Depending on the specific disease combinations, overlapping clinical features may present diagnostic and/or therapeutic challenges. Moreover, these cases should be monitored for development of additional cutaneous or extra-cutaneous AD(s).

Rapid response of hyperkeratotic erythema multiforme to oclacitinib in two dogs.

BACKGROUND: Hyperkeratotic erythema multiforme (HKEM) is a clinically distinct dermatosis and poorly characterized syndrome, comprised of hyperkeratotic plaques with variable symmetry and apoptosis similar to "classic" erosive canine EM. Hyperkeratotic EM has a protracted clinical course and, although treatments with glucocorticoids, azathioprine and/or ciclosporin have been tried, rates of remission are low. OBJECTIVES: To describe successful treatment of HKEM in two dogs using oclacitinib. ANIMALS: A 7-year-old, spayed Havanese dog (Case 1) and a 1-year-old, intact cryptorchid Dachshund dog (Case 2). METHODS: Case characterization and clinical diagnoses were based on lesion character, surgical biopsy, cytological evaluation, culture, direct immunofluorescence (DIF) and expected responses to treatments. RESULTS: Both cases exhibited multifocal, often symmetrical hyperkeratotic plaques with adherent scale. Histological findings revealed prominent epidermal hyperplasia, parakeratotic hyperkeratosis, lymphocytic dermatitis and transepidermal apoptosis with lymphocytic satellitosis. DIF revealed fine, patchy IgG, IgM and IgA basement membrane deposits (Case 2). Both dogs exhibited rapid improvement with oral oclacitinib (0.6-0.9 mg/kg twice daily) with a complete remission of clinical signs observed in 12 and seven weeks in cases 1 and 2, respectively. CONCLUSION AND CLINICAL IMPORTANCE: Oclacitinib could be considered as a fast-acting and effective treatment option for HKEM in dogs.

The role of oclacitinib in the management of ischaemic dermatopathy in four dogs.

BACKGROUND: Ischaemic dermatopathy represents a heterogenous and poorly-characterized canine syndrome that is often refractory to conventional immunosuppression. Janus-kinase inhibitors (JAKinibs) are used for the treatment of various human autoimmune diseases, including dermatomyositis. Oclacitinib is a generally well-tolerated, veterinary-approved, nonselective JAKinib that has therapeutic potential as an immunosuppressant. HYPOTHESIS/OBJECTIVES: To describe four cases of treatment refractory juvenile-onset ischaemic dermatopathy that rapidly and durably responded to oclacitinib administration. ANIMALS: Four mixed-breed dogs, three 9-month-old male littermates and one 6-month-old female, were presented for generalized patchy alopecia, scarring and ulcerative dermatitis. Microscopic skin lesions were consistent with a severe ischaemic dermatopathy. METHODS AND MATERIALS: A complete remission of skin lesions could not be achieved in any dog with glucocorticoids alone, nor when these were combined with adjuvant immunosuppressants. Oclacitinib treatment was then initiated at the dosage of 0.4-0.7 mg/kg twice daily, along with a tapering regimen of oral prednisolone. RESULTS: A full clinical remission was achieved within four weeks of starting this combination therapy, with prednisolone being stopped within eight weeks thereof. Remission was maintained in two dogs with lower doses or dosing frequencies of oclacitinib, whereas the two others required persistent twice daily administration of this JAKinib. CONCLUSIONS AND CLINICAL IMPORTANCE: Oclacitinib was a useful immunosuppressive adjuvant to oral glucocorticoids for the treatment of refractory or severe cases of ischaemic dermatopathy in these four dogs. Such observation warrants further studies of the safety, efficacy and mechanism of action of oclacitinib as an immunosuppressant.

A preliminary study of serum IgE against cross-reactive carbohydrate determinants (CCD) in client-owned atopic dogs.

BACKGROUND: Cross-reactive carbohydrate determinants (CCD) are defined carbohydrate portions of glycoprotein cell surface molecules common to many plant and insect species. Mammalian species recognize CCD as foreign antigens and can mount humoral immune responses against them. Approximately 20-37% of grass and venom allergic people possess circulating IgE against CCD; these antibodies are generally considered clinically irrelevant. Anti-CCD IgE is, however, recognized as a cause of false positive, clinically incongruent serum allergen test results in people; this phenomenon has not been investigated in animals. OBJECTIVE: To determine if anti-CCD IgE could be detected in sera of client-owned atopic dogs and how frequently it is found. ANIMALS: Sera from 38 dogs with a clinical diagnosis of atopic dermatitis and prior serological evidence of IgE antibodies, defined as a positive result to at least one mite and pollen (of any type). METHODS: Sera were analysed for IgE against CCD and environmental allergens with a commercially available multiplex enzyme-labelled allergen-specific IgE assay. RESULTS: Anti-CCD IgE was detected in nine of 38 (24%) of atopic dog sera. As with their human counterparts, all dogs with anti-CCD IgE had strong serological reactivity to grass pollens. CONCLUSIONS AND CLINICAL IMPORTANCE: Anti-CCD IgE can confound serological allergen testing in people; the same might be true in dogs. Further studies are warranted to investigate the clinical implications of anti-CCD IgE in dogs, including the potential for these antibodies to affect serum allergen-specific IgE assays used for clinical diagnosis, and whether they are relevant to clinical disease.

Multimodal treatment of a dog with disseminated cutaneous viral papillomatosis.

BACKGROUND: Canine papillomaviruses (CPVs) are associated with varied cutaneous manifestations. Spontaneous resolution typically occurs within one to 12 months. This case report describes multimodal treatment of a dog with severe disseminated papillomatosis. CLINICAL SUMMARY: An eight-month-old, female spayed, mixed breed dog was presented with a two month history of rapidly progressing papillomatosis and lack of response to oral azithromycin therapy. The dog was severely pruritic and malodorous; the weight and growth of lesions had progressed to affect the dog's gait and vision, and led to decreased quality of life. The dog was treated with substantial surgical debulking of lesions, followed by daily topical 5% imiquimod cream applied to nonexcisable lesions, and received five doses of an experimental recombinant CPV2 L1 vaccine every 14 days for 10 weeks. At the end of the 10 weeks, two lesions remained and were excised. No additional treatment was needed and 10 months post-treatment the dog was lesion free. CONCLUSION: New therapies need to be developed and assessed, in controlled treatment trials, to determine the efficacy of single modality therapeutic interventions for severe, persistent canine cutaneous papillomatosis.

Transient photoreceptor deconstruction by CNTF enhances rAAV-mediated cone functional rescue in late stage CNGB3-achromatopsia.

Achromatopsia is a genetic disorder of cones, and one of the most common forms is a channelopathy caused by mutations in the ß-subunit, CNGB3, of the cone cyclic nucleotide-gated (CNG) channel. Recombinant adeno-associated virus of serotype 5 (rAAV5)-mediated gene transfer of human CNGB3 cDNA to mutant dog cones results in functional and structural rescue in dogs <0.5 years of age, but treatment is minimally effective in dogs >1 year. We now test a new therapeutic concept by combining gene therapy with the administration of ciliary neurotrophic factor (CNTF). Intravitreal CNTF causes transient dedifferentiation of photoreceptors, a process called deconstruction, whereby visual cells become immature with short outer segments, and decreased retinal function and gene expression that subsequently return to normal. Cone function was successfully rescued in all mutant dogs treated between 14 and 42 months of age with this strategy. CNTF-mediated deconstruction and regeneration of the photoreceptor outer segments prepares the mutant cones optimally for gene augmentation therapy.