Polyautoimmunity manifest as inflammatory myopathy, uveitis, and progressive cutaneous depigmentation in a mixed breed dog: a case report.

BACKGROUND: Polyautoimmunity is the expression of more than one autoimmune disease in a single patient. This report documents polyautoimmunity in a mixed breed dog with concurrent uveitis, cutaneous depigmentation, and inflammatory myopathy. CASE PRESENTATION: A 1-year-old male neutered mixed breed dog was presented for progressive generalized leukotrichia and leukoderma, bilateral panuveitis, and masticatory muscle atrophy. The latter progressed to myositis of lingual, pharyngeal, and masticatory muscles confirmed by biopsy. Temporalis muscle was completely replaced by adipose and fibrous tissue, and necrotic myofibers with extensive infiltration of mononuclear cells indicated active myositis of lingual muscle. Skin biopsies showed severe melanin clumping in epidermis, hair follicles, and hair shafts, and perifollicular pigmentary incontinence. Uveitis, depigmentation, and myositis affecting the masticatory, pharyngeal, and tongue muscles were diagnosed based on clinical, histological, and laboratory findings. CONCLUSIONS: To the authors' knowledge, this is the first report of concurrent uveitis, progressive cutaneous depigmentation, and inflammatory myopathy in a dog.

Evaluation of aural masses submitted as inflammatory polyps in 20 dogs (2000-2020).

BACKGROUND: Canine non-neoplastic aural polypoid masses (APMs) are uncommon, with few published studies. OBJECTIVES: The aim of this retrospective study was to characterise the clinical presentation, diagnostic imaging and histopathological results for APMs submitted as aural inflammatory polyps (AIPs). ANIMALS: Twenty dogs with APMs evaluated at a veterinary teaching hospital. MATERIALS AND METHODS: Cases were selected by searching computerised medical records from 2000 to 2020, using keywords 'canine', 'aural/otic polyp' and 'aural/otic inflammatory mass'. Histological samples and medical records were reviewed. RESULTS: In 14 of 20 dogs, external ear canal masses were characterised by keratinised squamous epithelium with or without adnexa. Tympanic bulla origin was confirmed in four of 20 dogs by the presence of cuboidal to ciliated columnar epithelium, with or without squamous epithelium. The site of origin could not be determined in two dogs. Diagnostic imaging (MRI or CT) confirmed APM presence in 14 of 20 dogs. Otitis media was diagnosed in four of four tympanic bulla APMs and seven of 13 ear canal APMs. In 18 of 20 dogs, debulking, traction avulsion, and total ear canal ablation and bulla osteotomy led to APM resolution in two of eight, four of six and four of four dogs, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Type of epithelium was a key feature in determining the APM origin, and interpretation in conjunction with video otoscopy and diagnostic imaging was crucial. Canine APMs more commonly arose from the ear canal. Tympanic bulla APMs and APMs of undetermined origin were comparable to feline AIPs. Regardless of APM origin site, debulking had the greatest likelihood of recurrence.

Retrospective case series: Necrotising fasciitis in 23 dogs.

BACKGROUND: Necrotising fasciitis (NF) is a rare, rapidly progressive subcutaneous bacterial infection. Few studies have characterised NF in dogs. HYPOTHESIS/OBJECTIVES: To retrospectively describe clinical and laboratory findings, with treatments and outcomes, in dogs with NF. ANIMALS: Twenty-three client-owned dogs treated at a veterinary teaching hospital between 1998 and 2021. MATERIALS AND METHODS: Medical records and laboratory data from 23 dogs diagnosed with NF were reviewed. RESULTS: Male dogs were significantly over-represented (p = 0.003). The most common presenting complaint was sudden lameness. Infection occurred in one or two limbs in 19 of 23 dogs, with right hindlimbs most often affected (13 of 23). Pitting oedema was evident in 14 of 23 dogs. Antibiotic and nonsteroidal anti-inflammatory drugs were administered before presentation in nine and 13 of 23 dogs, respectively. Common clinicopathological abnormalities included hypoalbuminemia, hyponatremia, elevated liver enzymes, elevated creatine kinase, increased bands and lymphopenia. Streptococcus canis was isolated from 18 of 23 dogs. Histopathological features included acute necrosis and severe neutrophilic inflammation. Fifteen dogs were euthanised or died, while surgical intervention led to survival in eight of 23 dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Dogs presenting for acute swelling of a limb with oedema should have the diagnosis of NF considered and early surgical intervention might increase survival.

Locally extensive follicular hamartomas with concurrent follicular cysts and dermoid cysts on the head of a dog.

A 5-month-old, male intact Australian shepherd dog was presented with nodular lesions affecting the dorsal head. A locally diffuse form of follicular hamartomas, with concurrent dermoid cysts and follicular cysts, was diagnosed by histopathological examination. Complete surgical excision of the affected skin and closure with a subdermal plexus advancement flap led to long-term resolution.

Un berger australien mâle intact âgé de 5 mois a été présenté avec des lésions nodulaires affectant la face dorsale de la tête. Une forme localement diffuse d'hamartomes folliculaires, avec des kystes dermoïdes et des kystes folliculaires concomitants, a été diagnostiquée par examen histopathologique. L'éxérèse chirurgicale complète de la peau atteinte et la fermeture avec un lambeau d'avancement du plexus sous-cutané ont conduit à une résolution à long terme.

Un perro pastor australiano macho entero de 5 meses de edad se presentó con lesiones nodulares que afectaban el dorso de la cabeza. Mediante examen histopatológico se diagnosticó una forma localmente difusa de hamartomas foliculares, con quistes dermoides y quistes foliculares concurrentes. La escisión quirúrgica completa de la piel afectada y el cierre con una zona avanzada en colgajo del plexo subdérmico condujo a una resolución a largo plazo.

Pathology in Practice.

In collaboration with the American College of Veterinary Pathologists.

Preclinical Efficacy and Anti-Inflammatory Mechanisms of Action of the Bruton Tyrosine Kinase Inhibitor Rilzabrutinib for Immune-Mediated Disease.

Bruton tyrosine kinase (BTK) is expressed in B cells and innate immune cells, acting as an essential signaling element in multiple immune cell pathways. Selective BTK inhibition has the potential to target multiple immune-mediated disease pathways. Rilzabrutinib is an oral, reversible, covalent BTK inhibitor designed for immune-mediated diseases. We examined the pharmacodynamic profile of rilzabrutinib and its preclinical mechanisms of action. In addition to potent and selective BTK enzyme and cellular activity, rilzabrutinib inhibited activation and inflammatory activities of B cells and innate cells such as macrophages, basophils, mast cells, and neutrophils, without cell death (in human and rodent assay systems). Rilzabrutinib demonstrated dose-dependent improvement of clinical scores and joint pathology in a rat model of collagen-induced arthritis and demonstrated reductions in autoantibody-mediated FcγR signaling in vitro and in vivo, with blockade of rat Arthus reaction, kidney protection in mouse Ab-induced nephritis, and reduction in platelet loss in mouse immune thrombocytopenia. Additionally, rilzabrutinib inhibited IgE-mediated, FcεR-dependent immune mechanisms in human basophils and mast cell-dependent mouse models. In canines with naturally occurring pemphigus, rilzabrutinib treatment resulted in rapid clinical improvement demonstrated by anti-inflammatory effects visible within 2 wk and all animals proceeding to complete or substantial disease control. Rilzabrutinib is characterized by reversible covalent BTK binding, long BTK residence time with low systemic exposure, and multiple mechanistic and biological effects on immune cells. Rilzabrutinib's unique characteristics and promising efficacy and safety profile support clinical development of rilzabrutinib for a broad array of immune-mediated diseases.

Preliminary study of the stability of dexamethasone when added to commercial veterinary ear cleaners over a 90 day period.

BACKGROUND: Topical corticosteroids are commonly used in the management of allergic otitis externa to diminish inflammation. A common strategy is to make compounded solutions of dexamethasone in ear cleaner. HYPOTHESIS/OBJECTIVES: The objective of this study was to determine the stability of dexamethasone when added to four commercial ear cleaners (ec): designated ecA, ecB, ecC and ecD. METHODS AND MATERIALS: Two concentrations (0.1 and 0.25 mg/mL) of dexamethasone were formulated for each cleaner solution from a 2 mg/mL solution and stored in the original manufacturers' bottles at two temperatures: room (22 ËšC) and refrigerated (4 ËšC). Samples were evaluated in triplicate, using liquid chromatography-tandem mass spectrometry at 10 time points over 90 days. The mean and standard deviation were calculated for each time point. RESULTS: A solution was considered stable if the dexamethasone value remained >90% of the target concentration. All dexamethasone solution values were stable to 90 days, except two solutions for ecA; the 0.25 mg/mL dexamethasone concentration was only stable to 14 (4 ËšC) and 21 days (22 ËšC). CONCLUSIONS AND CLINICAL IMPORTANCE: These results provide preliminary evidence in support of pharmaceutical stability data for dexamethasone when included in the above compounded solutions at the noted concentrations and temperatures.

Serum immunoglobulin E responses to aeroallergens in cats with naturally occurring airway eosinophilia compared to unaffected control cats.

BACKGROUND: Eosinophilic airway disease in cats is sometimes described as allergic in origin, but controversy exists in the documentation of allergy in cats and the utility of allergy testing for respiratory tract diseases. OBJECTIVE: To examine serum immunoglobulin E (IgE) response to aeroallergens in cats with airway eosinophilia. ANIMALS: Fifteen cats with idiopathic eosinophilic airway inflammation and 9 control cats. METHODS: Prospective, case-control study. Surplus serum from cats with airway eosinophilia documented by bronchoscopic bronchoalveolar lavage was submitted for IgE measurement using ELISA polyclonal antibody methodology. Responses for regional allergens (fungal organisms, weeds, grasses, trees, mites, insects) were assessed. Results were reported as ELISA absorbance units with scores 0 to 79 considered negative, scores between 80 and 300 considered intermediate, and scores >300 considered positive. RESULTS: Cats with airway eosinophilia had significantly more positive serum IgE responses (25/720) than did healthy controls (5/432, P = .02); however, the number of cats with positive IgE responses (5/15) did not differ from controls (1/9, P = .35). The allergen that most commonly resulted in positive serum IgE response in cats with airway eosinophilia was dust mite (n = 4) followed by 2 types of storage mites (n = 3 each). No control cat tested positive for these allergens. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum IgE production against aeroallergens was found in some cats with eosinophilic airway inflammation, but the number of affected cats with positive results did not differ from controls. Further investigation in cats with eosinophilic, mixed, and neutrophilic airway disease in comparison to control cats is warranted.

Open trial of Bruton's tyrosine kinase inhibitor (PRN1008) in the treatment of canine pemphigus foliaceus.

BACKGROUND: Bruton's tyrosine kinase (BTK) is important in B-cell signalling. Efficacy has been reported for BTK inhibitors (BTKi) in human autoimmune diseases. Canine pemphigus foliaceus (cPF) is one of the most common canine autoimmune skin diseases. OBJECTIVES: To determine the safety and efficacy of the BTKi PRN1008 in the treatment of cPF. ANIMALS: Four privately owned dogs. METHODS AND MATERIALS: Four dogs diagnosed with PF were administered BTKi PRN1008. Initial dosages approximated to 15 mg/kg once daily, increased to twice daily if inadequate response was seen. Treatment continued for 20 weeks, attempting to decrease to every other day. Dogs were monitored with complete blood counts, serum biochemistry panels and urinalyses, and evaluated with a modified version of a validated human Pemphigus Disease Activity Index (cPDAI). Serum anti-desmocollin-1 (DSC-1) and desmoglein-1 (DSG-1) immunoglobulin (Ig)G titres were performed before and after the treatment period. Drug bound to target was measured in peripheral blood mononuclear cells (PBMC). RESULTS: All four dogs showed reduction in lesions and cPDAI score during the first two weeks of treatment. Three dogs continued to improve and sustained near complete remission by 20 weeks, at which point three responses were considered "good" and one "fair". Final daily dosages were in the range 17-33 mg/kg. Anti-DSC-1 IgG titre decreased dramatically in one dog, was undetectable in two and was uninterpretable in one dog. No dogs had detectable IgG to DSG1. A possible adverse event occurred in one dog. CONCLUSIONS AND CLINICAL IMPORTANCE: BTKi PRN1008 monotherapy may have some beneficial effects in some cases of cPF.

A case of atypical multifocal nodular eosinophilic dermatosis in a Labrador retriever dog.

BACKGROUND: A dog with gastrointestinal signs and a history of administration of multiple drugs developed acute multifocal to coalescing ulcerative nodules and a large plaque. OBJECTIVE: To describe abnormal nodular clinical lesions with an unexpected superficial and deep severe eosinophilic perivascular to interstitial inflammation. ANIMAL: A 7-year-old spayed female Labrador retriever METHODS AND MATERIALS: Blood tests, faecal and urinalysis, and abdominal radiographs were performed; skin biopsy samples were taken for cytological, culture and histopathological analyses. RESULTS: The blood tests, faecal, urinalysis and radiographs were within normal limits. Cytological results revealed inflammatory cells and cultures had no growth. Histopathological evaluation revealed dermal and subcutaneous oedema, mucin deposition and perivascular to interstitial inflammation predominated by eosinophils with occasional very small intralesional dense aggregates of eosinophils centred on collagen bundles, eosinophilic exocytosis and small eosinophilic pustules. Focal subepidermal fibrin exudation and haemorrhage resulted in epidermal detachment and ulceration. Clinical resolution of the dermatological and gastrointestinal signs was seen with the withdrawal of prior medications and administration of a tapering course of anti-inflammatory doses of prednisolone. CONCLUSIONS AND CLINICAL IMPORTANCE: To the best of the authors' knowledge, this is a novel nodular clinical and eosinophilic histopathological pattern combination. This case offers evidence of a spectrum of sterile eosinophilic dermatoses rather than multiple different disease processes.

Multicentric B-cell lymphoma with presumed paraneoplastic generalized cutaneous sclerosis in a dog.

BACKGROUND: Reports of dermal sclerosis in dogs include scleroderma or morphea of unknown cause, cicatricial alopecia and congenital/hereditary fibrosis. CLINICAL SUMMARY: A 12-year-old, male castrated chihuahua-mix dog was evaluated for skin lesions of unknown duration. The dog had severe alopecia, skin thickening and marked peripheral lymphadenopathy. Lymph node cytological investigation, immunohistochemical investigation and clonality testing demonstrated an intermediate to large B-cell lymphoma. The thickened skin had severe collagen deposition, effacing adnexal structures. The dog's lymphoma was treated but the skin lesions remained unchanged. The dog was euthanized. CONCLUSIONS AND CLINICAL IMPORTANCE: To the best of the authors' knowledge, this is the first report of multicentric B-cell lymphoma in a dog with concurrent diffuse cutaneous sclerosis, similar to a human paraneoplastic reaction.

Efficacy of a Bruton's Tyrosine Kinase Inhibitor (PRN-473) in the treatment of canine pemphigus foliaceus.

BACKGROUND: Bruton's tyrosine kinase (BTK) is important in B-cell signalling. Efficacy has been reported for BTK inhibitors (BTKi) in human autoimmune diseases. Canine pemphigus foliaceus (cPF) is the most common canine autoimmune skin disease. OBJECTIVES: To determine the safety and efficacy of a BTKi in cPF treatment. ANIMALS: Nine privately owned dogs. METHODS AND MATERIALS: Nine dogs diagnosed with PF were administered BTKi PRN473. Initial dosages were ≈15 mg/kg once daily, increased to twice daily if inadequate response was seen. Treatment continued for a maximum of 20 weeks, attempting decrease to every other day. Dogs were monitored with complete blood counts, serum biochemistry panels, urinalyses and evaluated with a modified version of a validated human Pemphigus Disease Activity Index (cPDAI). Anti-desmocollin-1 (DSC-1) and desmoglein-1 (DSG-1) immunoglobulin G (IgG) titres were performed before and after the treatment period. Drug bound to target was measured in peripheral blood mononuclear cells. RESULTS: All nine dogs showed reduction in lesions and cPDAI score during the first two weeks of treatment. At the end of the study, four responses were considered "good", two "fair", two "poor" and one dog withdrawn due to recurrence of a previously excised mast cell tumour. Four dogs continued to improve by Week 4; three sustained near complete remission by study's end. The anti-DSC-1 IgG titre decreased in three dogs, increased in two, was undetected in three and was not performed in the withdrawn dog. No dogs had detectable IgG to DSG1. Possible adverse effects occurred in three dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Bruton's tyrosine kinase inhibitor monotherapy may have beneficial effects in some cases of cPF.

Clinicopathological findings and clinical outcomes in 49 cases of feline pemphigus foliaceus examined in Northern California, USA (1987-2017).

BACKGROUND: Few studies have described the pathophysiology, clinical course, treatment outcomes and quality of life (QoL) of cats with pemphigus foliaceus (PF). OBJECTIVE: Describe clinicopathological features, treatment outcomes and impacts on QoL in feline PF. ANIMALS: Forty-nine client-owned cats with PF that presented to a veterinary teaching hospital between 1987 and 2017. METHODS AND MATERIALS: Medical records and histopathological reports were reviewed to obtain clinicopathological data and treatment outcomes. Owners were contacted and requested to complete a questionnaire to obtain long-term follow-up and evaluate the impacts of PF on QoL of cats and owners. RESULTS: Domestic short/medium/long hair breeds were most commonly affected, with pinnae, head, haired face, nasal planum and ungual folds most frequently involved. Associated pruritus and systemic signs of illness were common. Vasculopathological changes were noted in a small proportion of cats. Corticosteroid monotherapy was sufficient to induce complete remission in the majority of cats. Pemphigus foliaceus and its management had a negative impact on QoL of both cats and owners. Receiving/administering medications, attending veterinary appointments, and financial and time commitments were cited sources of stress for affected cats and/or owners. CONCLUSIONS AND CLINICAL IMPORTANCE: Results illustrate that affected cats generally respond favourably to treatment but do require long-term therapy. The exact aetiology of the vasculopathological changes was unclear; it may reflect the stage or severity of disease or suggest the presence of a cutaneous adverse drug reaction. Clinicians managing cats with PF should be aware of the potential negative impact on QoL of owners and cats and adjust management accordingly.

An unresponsive progressive pustular and crusting dermatitis with acantholysis in nine cats.

BACKGROUND: Between 2000 and 2012, nine cats were examined with a visually distinctive, progressive crusting dermatitis that was poorly responsive to all attempted therapies. OBJECTIVES: Documentation of clinical and histopathological findings of this disease. ANIMALS: Nine privately owned cats. METHODS: Retrospective study. RESULTS: Eight neutered males and one (presumably spayed) female ranging in age from two to eight years, presented for a progressive, well-demarcated, crusting dermatitis with variable pruritus of 1.5 months to five years duration. All cats lived in northern California, USA; seven lived within a 30 mile radius. Two males were littermates. Histopathological investigation showed both parakeratotic and orthokeratotic crusts, intraepidermal pustules and superficial folliculitis with rare to frequent acantholytic cells. Bacterial and fungal cultures were performed in six cats: meticillin-susceptible Staphylococcus pseudintermedius was isolated in three cats, two colonies of Trichophyton terrestre and three of Malassezia pachydermatis were isolated from one cat each. Treatment with various antibiotics, antifungal and a variety of immunosuppressive medications did not alter the progressive nature of the skin disease. CONCLUSIONS AND CLINICAL IMPORTANCE: The described disease shares some clinical and histopathological features with pemphigus foliaceus, but the lack of response to treatment, its progressive nature and the possible relatedness of some of the cats set it apart. The aetiology of this acantholytic dermatitis remains unknown.

Canine demodicosis: a retrospective study of a veterinary hospital population in California, USA (2000-2016).

BACKGROUND: Demodex spp. are cutaneous mites that cause clinical disease when present in increased numbers. There is an association in some dogs with underlying systemic disease or immunosuppressive medications. HYPOTHESIS/OBJECTIVES: Retrospective study to document breed predisposition, identify any concurrent diseases or underlying immunosuppressive conditions, and to determine the frequency of demodicosis recurrence after treatment completion. ANIMALS: There were 431 dogs with demodicosis presented to a veterinary teaching hospital in California, USA, from 2000 to 2016. METHODS: Inclusion in this study required a diagnosis of demodicosis based on direct demonstration of the mite. Records were reviewed for signalment, disease history, potential underlying aetiologies, diagnosed concurrent diseases, medications and demodicosis treatment. Analyses were performed to evaluate for potential breed predispositions and because of the large number of dogs with allergic dermatoses, analyses for this diagnosis as a disease associated with demodicosis was also performed. E-mailed surveys and follow-up telephone calls were used to assess for information about disease recurrence. RESULTS: The pit bull terrier group and West Highland white terrier, based on calculated odds ratio, were breeds predisposed to developing demodicosis. For dogs with demodicosis, allergic dermatoses was an associated disease. Relapse or recurrence of disease after treatment was uncommon, affecting 11% of the dogs with long-term follow-up. CONCLUSIONS/CLINICAL IMPORTANCE: This study identified, in dogs attending the institution based in California, USA, breed predilections for canine demodicosis and associated concomitant diseases. It also revealed a low occurrence of disease relapse, recurrence or persistence.