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.

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.

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.

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.

Skin disease in goats (Capra aegagrus hircus): a retrospective study of 358 cases at a university veterinary teaching hospital (1988-2020).

BACKGROUND: Goats are important worldwide as a source of milk, meat, fibre and hide, and as show animals and pets. HYPOTHESIS/OBJECTIVES: To document the type, signalment associations and prevalence of skin disease in a referral hospital population. ANIMALS: Case population at a university veterinary teaching hospital. METHODS AND MATERIALS: Retrospective study by searching computerised medical records of goats seen between 1 January 1988 and 1 January 2021. Key words employed were "alopecia, caseous lymphadenitis, Chorioptes, dermatitis, dermatophyte, dermatophytosis, goat, lice, louse, mange, mite, pemphigus foliaceus, Psoroptes, ringworm, seborrhea, skin" RESULTS: Of 1,488 records reviewed, 358 (24%) goats had skin disease recorded. Seventy-nine (22.1%) of 358 goats presented primarily for skin disease. The Nigerian Dwarf goat breed was at higher risk of developing skin disease (P < 0.0002). As goats aged, the odds for developing skin disease was higher [odds ratio (OR) = 1.07 per year, 95% confidence interval (1.04, 1.12)] as was the predilection for malignant skin tumours (P < 0.001). Sex was not associated with skin disease (P = 0.98). The most common clinical sign was exfoliative dermatitis, noted in 94 (26.4%) of 358 goats. The most common diagnoses were pediculosis, bacterial skin disease and squamous cell carcinoma. Less frequent diagnoses were Chorioptes spp. infestation, contagious ecthyma (orf), coronitis/interdigital dermatitis, demodicosis, dermatophytosis, Psoroptes spp. infestation, dermatophilosis and pemphigus foliaceus. CONCLUSIONS AND CLINICAL IMPORTANCE: Skin diseases are common in goats. Nigerian Dwarf goats and older goats are at greater risk of developing skin disease; Nigerian Dwarf goats had a predilection for malignant skin tumours. Clinicians should include a dermatological examination in goats regardless of the reason for presentation.

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.

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.

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.

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.

Examination of Fluconazole-Induced Alopecia in an Animal Model and Human Cohort.

Fluconazole-induced alopecia is a significant problem for patients receiving long-term therapy. We evaluated the hair cycle changes of fluconazole in a rat model and investigated potential molecular mechanisms. Plasma and tissue levels of retinoic acid were not found to be causal. Human patients with alopecia attributed to fluconazole also underwent detailed assessment and in both our murine model and human cohort fluconazole induced telogen effluvium. Future work further examining the mechanism of fluconazole-induced alopecia should be undertaken.

Skin disease in donkeys (Equus asinus): a retrospective study from four veterinary schools.

BACKGROUND: Donkeys are important throughout the world as work animals and occasionally as pets or a meat source. Most descriptions of skin disease in donkeys are reported in small case series, textbooks or review articles. HYPOTHESIS/OBJECTIVES: To document skin diseases and their prevalence in donkeys and to investigate predilections for the most common conditions. ANIMALS: Case populations at four veterinary schools totalling 156 donkeys. METHODS AND MATERIALS: A retrospective study was performed by searching computerized medical records, using the key word "donkey", at the School of Veterinary Medicine, University of California, Davis (UCD). Records of donkeys from the veterinary schools in Nantes, France; Utrecht, Netherlands and Ghent, Belgium were searched in a similar manner. The time periods included in the searches varied by institution. RESULTS: At UCD, 83 of 346 (24%) of donkeys had skin disease noted in their records. The most common diagnoses were insect bite hypersensitivity, sarcoid and habronemiasis. At Nantes, 36 of 144 (25%) had skin disease and the most common diagnoses were sarcoid and superficial pyoderma. At Utrecht 23 of 143 (16%) had skin disease and the most common diagnosis was dermatophytosis. At Ghent, 14 of 320 (4%) had skin disease and the most common diagnosis was sarcoid. CONCLUSIONS AND CLINICAL IMPORTANCE: Cutaneous conditions in donkeys are common. Age, sex and breed predisposition and the most common diagnoses varied with geographical location. Clinicians should include a dermatological examination regardless of the reason for presentation.

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.

Companion rats (Rattus norvegicus) with cutaneous lesions: a retrospective study of 470 cases at two university veterinary teaching hospitals (1985-2018).

BACKGROUND: Rats are popular companion animals that are often presented to veterinarians for treatment of skin diseases. However, descriptions of dermatoses in rats have primarily been limited to case reports and text books. HYPOTHESIS/OBJECTIVES: To document skin diseases and their prevalence in companion rats examined in northern California, USA and Nantes, France and to investigate predilections for the most common conditions over a 33 year or 15 year period, respectively. ANIMALS: Four hundred and seventy rats from two hospital populations met the inclusion criteria. METHODS AND MATERIALS: A retrospective study was performed by searching computerized medical records of rats seen at the School of Veterinary Medicine at University of California, Davis (UCD), USA from 1 January 1985 to 1 January 2018 using the key words "skin" and "dermatitis". The medical records of rats presenting to Ecole Nationale Vétérinaire, Agroalimentaire et de l'Alimentation Nantes-Atlantique (ONIRIS), France from 1995 to 2016 were reviewed for evidence of skin disease. The presence of lesions as noted in the key search words for the UCD records were used as the inclusion criteria for both institutions. RESULTS: Of 494 rats examined at UCD, 231 (47%) had skin disease, with neoplasia the most common diagnosis. Of the 619 rats examined at ONIRIS, 239 (39%) had skin disease, with ectoparasitism being the most common diagnosis. CONCLUSIONS AND CLINICAL IMPORTANCE: Cutaneous conditions in companion rats are common. Clinicians should include a dermatological examination when examining these rodents, especially in regard to neoplasia, ectoparasites and pyoderma.

Companion hamsters with cutaneous lesions; a retrospective study of 102 cases at two university veterinary teaching hospitals (1985-2018).

BACKGROUND: Hamsters are popular companion animals which may present to veterinarians for treatment of skin diseases. Most descriptions of dermatoses in hamsters have primarily been in case reports and in text books. HYPOTHESIS/OBJECTIVES: To document skin diseases and their prevalence in companion hamsters examined in northern California, USA, and Nantes, France, and to investigate predilections for the most common conditions documented in medical records over a 33 year or 15 year period, respectively. ANIMALS: One hundred and one hamsters from two hospital populations. METHODS AND MATERIAL: A computerized search of medical records of all hamsters seen at the School of Veterinary Medicine at UC-Davis in California, USA, from 1 January 1985 to 1 January 2018, was performed using the key search words "skin" and "dermatitis". The medical records of all hamsters presenting to the Ecole Nationale Vétérinaire, Nantes, from 1 September 1998 to 1 December 2013, were reviewed for skin diseases. The presence of lesions noted in key search words for the California records were used as inclusion guidelines for both institutions. Cases of suspected mammary neoplasia were excluded. RESULTS: Of the 65 hamsters seen in California, 34 (54%) had skin disease; of a total of 164 hamsters in Nantes, 67 (41%) had skin disease. Nodules were the most common lesions noted by both institutions. CONCLUSIONS AND CLINICAL IMPORTANCE: Cutaneous conditions in companion hamsters are common. Clinicians should include a dermatological examination when examining these rodents.

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.

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.

Aspergillus otitis in small animals--a retrospective study of 17 cases.

BACKGROUND: Aspergillus spp. are saprophytic opportunistic fungal organisms and are a common cause of otomycosis in humans. Although there have been case reports of Aspergillus otitis externa in dogs, to the best of the authors' knowledge, this is the first retrospective case series describing Aspergillus otitis in dogs and cats. OBJECTIVE: To characterize signalment, putative risk factors, treatments and outcomes of a case series of dogs and cats with Aspergillus otitis. ANIMALS: Eight dogs and nine cats diagnosed with Aspergillus otitis. METHODS: A retrospective review of medical records from 1989 to 2014 identified animals diagnosed with Aspergillus otitis based on culture. RESULTS: All dogs weighed greater than 23 kg. The most common putative risk factors identified in this study were concurrent diseases, therapy causing immunosuppression or a history of an otic foreign body. Aspergillus otitis was unilateral in all study dogs and most cats. Concurrent otitis media was confirmed in three dogs and one cat, and suspected in two additional cats. Aspergillus fumigatus was the most common isolate overall and was the dominant isolate in cats. Aspergillus niger and A. terreus were more commonly isolated from dogs. Animals received various topical and systemic antifungal medications; however, otic lavage under anaesthesia and/or surgical intervention increased the likelihood of resolution of the fungal infection. CONCLUSION: Aspergillus otitis is uncommon, typically seen as unilateral otitis externa in cats and larger breed dogs with possible risk factors that include immunosuppression and otic foreign bodies; previous antibiotic usage was common.

Alopecia universalis in a dog with testicular neoplasia.

OBJECTIVE: To describe a case of testicular neoplasia and alopecia universalis in a dog, and successful treatment of the latter with ciclosporin. ANIMAL: Twelve-year-old intact male wirehaired fox terrier. METHODS: Castration, skin biopsy for histopathology, lymphocyte immunophenotyping and clonality analysis of the canine T-cell receptor gamma locus (TCRγ) rearrangement. RESULTS: The dog presented with symmetrical generalized alopecia. Testicular enlargement was noted which on castration was determined to be caused by bilateral interstitial cell tumours, Sertoli cell tumours and a unilateral seminoma. During the four months after castration the alopecia became more severe and widespread. Histopathology of the skin showed moderate, multifocal, mural folliculitis, peribulbar mucinosis and lymphocytic bulbitis, and targeting of anagen hair follicles. Immunophenotyping of the infiltrate showed a population of well-differentiated, small CD3-positive T lymphocytes, some expressing CD4 and others CD8. Molecular analysis revealed a polyclonal lymphocytic infiltrate, substantiating the diagnosis of alopecia areata rather than lymphoma. Treatment with ciclosporin (4.6 mg/kg) and ketoconazole (4.6 mg/kg) resulted in complete hair regrowth. CONCLUSION AND CLINICAL IMPORTANCE: Ciclosporin treatment, in combination with ketoconazole, can be effective for treatment of alopecia universalis in the dog. Alopecia universalis may present with clinically noninflammatory, symmetrical, generalized alopecia, mimicking an endocrine alopecia, and skin biopsies are needed to confirm the diagnosis.

Skin diseases in companion guinea pigs (Cavia porcellus): a retrospective study of 293 cases seen at the Veterinary Medical Teaching Hospital, University of California at Davis (1990-2015).

BACKGROUND: Guinea pigs (Cavia porcellus) are popular companion animals with reported skin diseases, but most reports are accessed from textbooks or review articles. HYPOTHESIS/OBJECTIVES: To document skin diseases and their prevalence in companion guinea pigs in northern California, USA, and to investigate predilections for the most common conditions over a 25 year period. ANIMALS: Two hundred and ninety three guinea pigs from the hospital population met inclusion criteria. METHODS: A retrospective study was performed by searching computerized medical records seen at the Veterinary Medical Teaching Hospital (VMTH), School of Veterinary Medicine, University of California from 1 January 1990 to 31 July 2015 using key words relevant to dermatology. RESULTS: Of the 580 guinea pigs seen at the VMTH, 50% (293) had skin disease. Of the 293 cases, 154 (52%) presented for nondermatological reasons. Guinea pigs with skin disease were significantly older than those without skin disease (P = 0.0002); females with skin disease were more likely to have cystic ovaries (P = 0.0203), although these were not always associated with alopecia. Pododermatitis and infestation with Trixacarus caviae or lice were the most common skin diseases. Ivermectin or selamectin was used for ectoparasite treatment. Abscesses unassociated with pododermatitis were the most common nodules. Benign follicular tumours were the most common neoplasm. Despite the frequent mention of dermatophytosis in the veterinary literature, only two cases of Trichophyton mentagrophytes were diagnosed. CONCLUSIONS AND CLINICAL IMPORTANCE: Cutaneous conditions in companion guinea pigs in the USA are common. Clinicians should include a dermatological examination when examining these rodents regardless of the reason for presentation.

A retrospective review of hyperaesthetic leucotrichia in horses in the USA.

BACKGROUND: Hyperaesthetic leucotrichia (HL) rarely affects horses and causes painful lesions on the dorsum that result in leucotrichia. This may be a variant of erythema multiforme (EM), but there are no studies investigating this condition. OBJECTIVES: Describe the clinical and histological features of HL and compare them to the histological features of EM. METHODS: A retrospective review of medical records from 1985 to 2015 identified 15 horses with HL. Thirteen biopsies of HL and five of EM were evaluated and compared. RESULTS: Arabian horses and their crosses (χ(2) (1)  = 8.56, P < 0.01) and American paint horses (χ(2) (1)  = 6.64, P < 0.05) were over represented. The onset of clinical signs was between April and September (14 of 15). The most common clinical signs were pain (15 of 15), leucotrichia (11 of 15), crusting (10 of 15) and alopecia (8 of 15) limited to darkly pigmented skin. The lesions recurred seasonally in 6 of 12 horses and unpredictably in 1 of 12 horse. The most common histological features were the presence of large stellate cells (13 of 13) and oedema (12 of 13) in the superficial dermis, perivascular to diffuse lymphocytic inflammation (13 of 13), pigmentary incontinence (12 of 13), apoptotic keratinocytes (9 of 13) and vesicle formation (8 of 13). Horses with EM (n = 5) had significantly more acanthosis (z = -2.40, P < 0.02) and lymphocytic exocytosis (z = -3.1, P < 0.004), satellitosis (Fisher's exact P = 0.02) and inflammation (z = -2.91, P < 0.004). Horses with HL had significantly more pigmentary incontinence (z = 2.13, P < 0.04) and superficial dermal oedema (z = 2.56, P < 0.002). CONCLUSIONS: HL affects primarily Arabian horses and American paint horses. It occurs mainly in summer and may recur. Histologically HL shares features with EM, but there are significant differences between them.