German Shorthaired Pointer dogs with exfoliative cutaneous lupus erythematosus develop immune-complex membranous glomerulonephropathy.

German Shorthaired Pointer (GSHP) dogs with a UNC93B1 gene mutation develop exfoliative cutaneous lupus erythematosus (ECLE) and kidney disease resembling lupus nephritis in humans. The objective of this study was to characterize the kidney disease by light microscopy, immunofluorescence, and electron microscopy in a population of GSHP dogs with ECLE. Medical records were reviewed, and light microscopy of kidneys from 7 GSHP dogs with a previous histologic diagnosis of ECLE was performed. Immunofluorescence of fresh-frozen kidney from 1 dog and transmission electron microscopy of kidney from that dog and 2 additional dogs were performed. Five of 7 dogs had proteinuria diagnosed by urinalysis or urine protein-to-creatinine ratio. Two of 7 dogs were intermittently hypoalbuminemic, and none were azotemic. Histologic findings included early (2 dogs) to late (5 dogs) membranous glomerulonephropathy characterized by mild-to-severe glomerular capillary loop thickening and tubular proteinosis. In all 7 cases, trichrome staining revealed red granular immune deposits on the subepithelial surface of the glomerular basement membrane. Immunofluorescence revealed strong granular labeling for immunoglobulins and complement protein C3. Electron microscopy demonstrated subepithelial electron-dense immune deposits encircled by the remodeled glomerular basement membrane. These findings are diagnostic of immune-complex membranous glomerulonephropathy and are similar to class V lupus in humans. This cohort of GSHP dogs with ECLE developed immune-complex membranous glomerulonephropathy, which we hypothesize is a manifestation of systemic lupus erythematosus. GSHP dogs with ECLE should undergo clinical evaluation of renal function for early identification and treatment.

Long-term successful treatment of a donkey with cutaneous lupus erythematous with methotrexate.

Cutaneous lupus erythematosus (CLE) is a rare immune-mediated dermatitis. To the best of the authors' knowledge it has not been described in donkeys. A 5-year-old male neutered donkey, living in south-east France, was diagnosed with CLE. Clinical signs included generalized symmetrical areas of alopecia, erythema, crusting and scales. Diagnostic tests included examination of skin biopsy samples by histopathological and immunohistochemical analysis which demonstrated an interface dermatitis with CD8+ T cells. The skin condition was successfully treated initially with glucocorticoids and methotrexate; successful long-term maintenance was associated with administration of methotrexate.

Le lupus cutané érythémateux (CLE) est une dermatite à médiation immune rare. A la connaissance des auteurs, il n'a pas été décrit chez le singe. Un singe mâle castré de 5 ans, vivant dans le sud-est de la France a été diagnostiqué avec CLE. Les signes cliniques incluaient des zones symétriques généralisées d'alopécie, d'érythème, de croûtes et de pellicules. Les tests diagnostics comprenaient un examen histopathologique et immunohistochimique de biopsies cutanées qui ont révélé une dermatite d'interface avec cellules T CD8+. La dermatose a été traitée avec succès initialement avec des corticoïdes et du méthotrexate; un traitement efficace au long cours a été associé avec l'administration de méthotrexate.

El lupus eritematoso cutáneo (CLE) es una rara dermatitis inmunomediada. A entender de los autores, esta enfermedad no se ha descrito en burros. Un burro castrado macho de 5 años de edad, que vive en el sureste de Francia fue diagnosticado con CLE. Los signos clínicos incluyeron áreas simétricas generalizadas de alopecia, eritema, costras y escamas. Las pruebas de diagnóstico incluyeron el examen de muestras de biopsia de piel mediante análisis histopatológico e inmunohistoquímico que demostró una dermatitis de interfase con células T CD8+. La condición de la piel se trató con éxito inicialmente con glucocorticoides y metotrexato; el control exitoso a largo plazo de la enfermedad se obtuvo con la administración de metotrexato.

O lúpus eritematoso cutâneo (LEC) é uma dermatite imunomediada rara. De acordo com os conhecimentos do autor, a doença ainda não foi descrita em jumentos. Um jumento macho castrado de cinco anos de idade, habitante do sul da França, foi diagnosticado com LEC. Os sinais clínicos incluíram alopecia, eritema, crostas e descamação generalizadas e simétricas. Os testes diagnósticos utilizados foram avaliação de amostras de biópsia por análise histopatológica e imunohistoquímica, que demonstraram dermatite de interface com células T CD8+. A dermatopatia foi tratada satisfatoriamente inicialmente com glicocorticoide e metotrexato; a manutenção satisfatória a longo prazo foi associada à administração de metotrexato.

Treatment of exfoliative cutaneous lupus erythematosus in a German shorthaired pointer dog with mycophenolate mofetil.

BACKGROUND: Immune-modulating drugs show limited therapeutic efficacy in canine exfoliative cutaneous lupus erythematosus (ECLE); over half of ECLE dogs are eventually euthanized for their lack of response to therapy. OBJECTIVE: To describe a case of generalized ECLE in a dog in which mycophenolate mofetil (MMF) treatment achieved complete remission. ANIMAL: A 3-year-old, male castrated German shorthaired pointer was presented with a three months history of generalized scaling, erythematous macules and plaques, follicular casts and hypotrichosis affecting the head, trunk, ventrum and medial aspects of all limbs. The dog exhibited lameness and stiff gait. METHODS AND MATERIALS: Complete blood count, serum chemistry profile, urinalysis, serum antinuclear antibody test, histopathological examination and RT-qPCR of skin biopsies. RESULTS: Histologically, skin biopsy specimens revealed lymphocyte-rich interface dermatitis, infundibular interface mural folliculitis and periglandular lymphocytic infiltrate. The absence of systemic signs and unremarkable laboratory tests excluded concurrent systemic lupus erythematosus. Treatment of ECLE was initiated with oral MMF (22 mg/kg, twice daily). Within three weeks of starting MMF therapy, a marked improvement in lameness and a moderate decrease in erythema and scaling was observed. After four months, erythema, scaling and follicular casts had completely resolved, and at the time of writing the dog's ECLE remains in complete remission with twice daily MMF (10 mg/kg). The lesional skin transcriptome revealed predominant T helper 1 (Th1) lymphocytic inflammatory response with strong upregulation of interferon pathway. CONCLUSIONS AND CLINICAL IMPORTANCE: To the best of the authors' knowledge, this is the first reported case of successful treatment of ECLE with MMF as a single-agent therapy.

Mucocutaneous lupus erythematosus in dogs (21 cases).

BACKGROUND: The diagnosis of dogs with chronic juxtamucosal erosive lesions and histopathology typical of cutaneous lupus erythematosus (CLE) is unclear. HYPOTHESIS/OBJECTIVES: We report herein 21 dogs with mucocutaneous erosive lesions and lupus-specific histopathology that we propose to be affected with mucocutaneous lupus erythematosus (MCLE), another variant of chronic CLE. METHODS: Inclusion criteria were the presence of the following: (i) a >2 month history of chronic or recurrent skin lesions; (ii) erosions or ulcers predominating at mucosae or mucocutaneous junctions; (iii) microscopic lesions of CLE (i.e. a lymphocyte-rich interface dermatitis with basal keratinocyte damage); and (iv) a lack of complete remission following antimicrobials. Clinical questionnaires and skin biopsies were reviewed. Direct immunofluorescence and antinuclear antibody serology were performed whenever possible. RESULTS: More than half of the 21 dogs were German shepherds or their crosses. The disease affected mostly dogs in their mid-adulthood and there was an over-representation of females. Erosions and ulcers predominated at genital/perigenital and anal/perianal areas, with a lower frequency of involvement of periocular, perioral and perinasal regions. In these dogs, there were no clinical signs suggestive of an associated systemic lupus erythematosus. Microscopic lesions were specific for CLE, but they were patchy and often infected with bacteria. The most common immunological finding was focal IgG deposition at the basement membrane zone. Lesions responded to varying interventions, but oral glucocorticoids led to a shorter time to complete remission. Relapses were common upon treatment tapering. CONCLUSIONS AND CLINICAL IMPORTANCE: These observations support MCLE being another variant of canine CLE.

Exfoliative cutaneous lupus erythematosus in German shorthaired pointer dogs: disease development, progression and evaluation of three immunomodulatory drugs (ciclosporin, hydroxychloroquine, and adalimumab) in a controlled environment.

Six German shorthaired pointer dogs (two females, four males) with exfoliative cutaneous lupus erythematosus (ECLE) were studied in a controlled setting until disease progression necessitated euthanasia. During investigations into the heredity of disease, five dogs received immunomodulatory drugs to alleviate clinical signs (lameness, erythema, scaling, erosions/ulcers). One dog served as a control and received only baths and oral fatty acids. Four dogs received ciclosporin (5-10 mg/kg once daily) for 4.5 months to 2 years. Ciclosporin decreased erythema and arthralgia, but did not halt worsening of lesions. Three dogs received hydroxychloroquine (5-10 mg/kg once daily) for 8 weeks, 7 months, and 9 months, respectively, with no side effects. Hydroxychloroquine appeared to slow clinical progression in two dogs on extended treatment and normalized globulin levels in all three dogs while receiving the drug. Four dogs, including the control dog, were euthanized between 1 and 4.5 years of age. Two remaining male dogs received a tumour necrosis factor (TNF)-α antagonist, adalimumab, at 0.5 mg/kg every 2 weeks for 8 weeks then weekly for 8 weeks. Serum TNF-α levels were not significantly altered nor were quantifiable changes seen in skin lesions or lameness. Subsequently, the dogs were maintained on hydroxychloroquine for another year. This is the first study to evaluate the use of a TNF-α inhibitor for canine lupus and the first to address the safety of long-term administration of hydroxychloroquine, albeit in a small number of dogs. The study documents the progression of ECLE and generally poor response to therapy.

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.