A de novo variant in the ASPRV1 gene in a dog with ichthyosis.

Ichthyoses are a heterogeneous group of inherited cornification disorders characterized by generalized dry skin, scaling and/or hyperkeratosis. Ichthyosis vulgaris is the most common form of ichthyosis in humans and caused by genetic variants in the FLG gene encoding filaggrin. Filaggrin is a key player in the formation of the stratum corneum, the uppermost layer of the epidermis and therefore crucial for barrier function. During terminal differentiation of keratinocytes, the precursor profilaggrin is cleaved by several proteases into filaggrin monomers and eventually processed into free amino acids contributing to the hydration of the cornified layer. We studied a German Shepherd dog with a novel form of ichthyosis. Comparing the genome sequence of the affected dog with 288 genomes from genetically diverse non-affected dogs we identified a private heterozygous variant in the ASPRV1 gene encoding "aspartic peptidase, retroviral-like 1", which is also known as skin aspartic protease (SASPase). The variant was absent in both parents and therefore due to a de novo mutation event. It was a missense variant, c.1052T>C, affecting a conserved residue close to an autoprocessing cleavage site, p.(Leu351Pro). ASPRV1 encodes a retroviral-like protease involved in profilaggrin-to-filaggrin processing. By immunofluorescence staining we showed that the filaggrin expression pattern was altered in the affected dog. Thus, our findings provide strong evidence that the identified de novo variant is causative for the ichthyosis in the affected dog and that ASPRV1 plays an essential role in skin barrier formation. ASPRV1 is thus a novel candidate gene for unexplained human forms of ichthyoses.

Mycobacterium nebraskense infection in a dog in Switzerland with disseminated skin lesions.

BACKGROUND: Cutaneous disseminated mycobacteriosis is rare in dogs. To the best of the authors' knowledge, the slowly growing mycobacterial species Mycobacterium nebraskense has not been described before in this species. OBJECTIVE: Description of clinical features, laboratory analyses and treatment regimen of this unusual case. ANIMAL: A 9-year-old female-spayed West Highland white terrier dog presented with progressive nodules and ulcerations on both sides of the thorax and the rostral aspect of the chest. METHODS AND MATERIALS: Investigations involved histopathological examination of skin biopsies (including special stains for fungi, bacteria and mycobacteria), standard and mycobacterial culture (including susceptibility testing), 16S/23S rRNA sequencing and BLAST similarity searching. RESULTS: Ziehl-Neelsen staining of decontaminated biopsy material revealed acid-fast bacteria morphologically consistent with mycobacteria. Treatment with clarithromycin and marbofloxacin achieved partial resolution. A change in the treatment regimen to pradofloxacin and azithromycin resulted in rapid deterioration of skin lesions. Final healing occurred with the addition of prednisolone at an anti-inflammatory dose. The results of mycobacterial culture and susceptibility testing were received 10 and 12 months, respectively, after the first presentation of the dog. Therapy was stopped after 16 months without recurrence of skin lesions. CONCLUSIONS AND CLINICAL IMPORTANCE: This case is noteworthy for the description of a new mycobacterial species contributing to disseminated panniculitis in a dog and for the difficulties experienced in the lengthy empirical treatment of slowly growing nontuberculous mycobacterial infections. The addition of prednisolone to induce complete healing raises the question of whether the mycobacterial infection was primary or whether it occurred secondarily to an ongoing sterile panniculitis.

Long-term effects of intralymphatic immunotherapy (ILIT) on canine atopic dermatitis.

BACKGROUND: Subcutaneous allergen immunotherapy (SCIT) is an established and efficacious therapy for canine atopic dermatitis (AD). In humans, intralymphatic immunotherapy (ILIT) was reported to be associated with fewer and less severe adverse effects than subcutaneous allergen immunotherapy and to be efficacious for several years after three intralymphatic injections. OBJECTIVE: To evaluate safety and effects of ILIT in a case series of dogs with (AD). ANIMALS: Fifty one privately owned dogs with AD. METHODS: Dogs received injections of 0.2 mL alum-precipitated allergen extract into the popliteal lymph nodes at monthly intervals for 3-5 months. Lesion scores, pruritus and medication scores were determined before and at three and 12 months after beginning immunotherapy, and compared in a per protocol analysis (PP) and an intention-to-treat analysis (ITT). RESULTS: Twenty two dogs completed the study and 29 dogs did not fulfil study completion criteria due to lack of a final study visit (21 of 29) or due to insufficient improvement (14 of 29). All scores improved during the study with both analyses. For pruritus and Quality of Life scores this improvement was significant with both analyses; for Canine Atopic Dermatitis Extent and Severity Index (CADESI)-03 values and medication scores only with PP. The only rare adverse effects observed included mild swelling of the lymph node post-injection and increased pruritus. CONCLUSION AND CLINICAL RELEVANCE: ILIT is safe and feasible, and provides long-lasting relief in some atopic dogs with a limited number of injections.

Unusual systemic signs in a dog with sterile neutrophilic-macrophagic lymphadenitis and nodular panniculitis.

A 7 mo old female English springer spaniel was presented with diarrhea, vomiting, apathy, and hyperthermia. Further examinations revealed generalized lymphadenomegaly consistent with sterile neutrophilic-macrophagic lymphadenitis and pulmonary involvement. Subcutaneous nodules developed one day after presentation. Histology was consistent with sterile idiopathic nodular panniculitis and vasculitis. No infectious organism was isolated. The dog responded to prednisolone, but relapsed during medication tapering. Cyclosporine had to be added to control the disease. No further relapse had occurred 98 wk after the first presentation. This is an unusual presentation of a systemic sterile neutrophilic-macrophagic lymphadenitis with nodular panniculitis and vasculitis associated with gastrointestinal and pulmonary signs.

Alopecia areata in Eringer cows.

Alopecia areata is a hair loss disorder in humans, dogs and horses with a suspected autoimmune aetiology targeting anagen hair follicles. Alopecia areata is only sporadically reported in cows. Recently, we observed several cases of suspected alopecia areata in Eringer cows. The aim of this study was to confirm the presumptive diagnosis of alopecia areata and to define the clinical phenotype and histopathological patterns, including characterization of the infiltrating inflammatory cells. Twenty Eringer cows with alopecia and 11 Eringer cows without skin problems were included in this study. Affected cows had either generalized or multifocal alopecia or hypotrichosis. The tail, forehead and distal extremities were usually spared. Punch biopsies were obtained from the centre and margin of alopecic lesions and normal haired skin. Histological examination revealed several alterations in anagen hair bulbs. These included peri- and intrabulbar lymphocytic infiltration, peribulbar fibrosis, degenerate matrix cells with clumped melanosomes and pigmentary incontinence. Mild lymphocytic infiltrative mural folliculitis was seen in the inferior segment and isthmus of the hair follicles. Hair shafts were often unpigmented and dysplastic. The large majority of infiltrating lymphocytes were CD3(+) T cells, whereas only occasional CD20(+) lymphocytes were present in the peribulbar infiltrate. Our findings confirm the diagnosis of T-cell-mediated alopecia areata in these cows. Alopecia areata appears to occur with increased frequency in the Eringer breed, but distinct predisposing factors could not be identified.