Efficacy of verdinexor for the treatment of naïve canine epitheliotropic cutaneous T-cell lymphoma: An open-label pilot study.

BACKGROUND: Verdinexor (Laverdia-CA1; Dechra Veterinary Products), a selective inhibitor of nuclear export, has been utilised for treatment of non-Hodgkin T-cell lymphoma in dogs. However, the efficacy of verdinexor has not been evaluated for cutaneous epitheliotropic T-cell lymphoma (CETL). HYPOTHESIS/OBJECTIVES: To evaluate the efficacy of verdinexor for the treatment of CETL. ANIMALS: Eight client-owned animals with CETL. MATERIALS AND METHODS: Patients received between 1.28 and 1.45 mg/kg verdinexor per os twice weekly with a minimum of 72 h between doses until disease progression or voluntary withdrawal. Adjunctive therapy with lokivetmab or prednisone was permitted after Day (D)14. Assessment of clinical lesions (canine Response Evaluation Criteria in Solid Tumors [cRECIST v1.0] and novel Canine Epitheliotropic Lymphoma Extent and Severity Index [CELESI]), pruritus (Visual Analog Scale) and treatment efficacy (owner global assessment of treatment efficacy [OGATE]) were evaluated every 14 days for 3 months, then monthly thereafter (mean 70 ± 43.4 days). RESULTS: Seventy-five percent of patients achieved complete response, partial response or stable disease. The mean time to disease progression was 56 ± 41 days. There was a significant reduction (p = 0.026) in total CELESI score when the lowest score for each dog was compared to their score at D0. Verdinexor did not significantly reduce pruritus at any time point (p = 0.45), including when given as a monotherapy or concurrently with lokivetmab ± glucocorticoids. On D28, 75% of owners rated response to treatment as 'fair' to 'excellent'. The most common adverse effects included weight loss, inappetence, vomiting and lethargy. CONCLUSIONS AND CLINICAL RELEVANCE: Verdinexor could be considered a safe, palliative treatment for canine CETL.

Burkholderia gladioli deep pyoderma in a dog secondary to immunosuppressive ciclosporin and prednisone therapy.

A dog presented with deep pyoderma on the paw, following treatment with ciclosporin and prednisone for immune-mediated haemolytic anaemia. Cytological evaluation, skin biopsy, aerobic culture, next-generation DNA sequencing and PCR were used to detect the first reported case of Burkholderia gladioli in a dog.

Evaluation of clonality from multiple anatomic sites in canine epitheliotropic T cell lymphoma.

BACKGROUND: Canine epitheliotropic cutaneous T-cell lymphoma (eCTCL) is thought to represent a disease homologue to human mycosis fungoides (MF). In human MF, neoplastic cells are phenotypically consistent with resident effector memory T cells, a population that remains for an extended period within tissue without circulating. Dogs with eCTCL often present with lesions in multiple locations, raising the question of whether the neoplasm is of the same T-cell subpopulation or not. OBJECTIVES: To characterize the antigen receptor gene rearrangements of lymphocytes from skin and blood of dogs with eCTCL to determine if neoplastic clones are identical. ANIMALS: Fourteen dogs with eCTCL. MATERIALS AND METHODS: Histological and immunohistochemical examination, and PCR for antigen receptor rearrangement (PARR) for T-cell receptor gamma (TRG) performed on multiple cutaneous biopsy samples and blood. RESULTS: All skin biopsies contained cluster of differentiation (CD)3-positive neoplastic lymphocytes. Within individual dogs, all skin biopsies revealed identical TRG clonality profiles, suggesting that the same neoplastic clone was present in all sites. In the blood, a matching clone was found in six of 14 dogs, a unique clone was observed in nine of 14 dogs, and no clone was detected in two of 14 dogs. CONCLUSIONS: These findings show that canine eCTCL lesions in multiple locations harbour the same neoplastic clone, neoplastic lymphocytes do not remain fixed to the skin and instead can circulate via blood, differing clones can be identified in skin versus blood, and circulating neoplastic cells can be detected without lymphocytosis.

Contexte - On pense que le lymphome T cutané épithéliotrope canin (eCTCL) représente une maladie homologue au mycosis fongoïde (MF) humain. Dans le MF humain, les cellules néoplasiques sont phénotypiquement compatibles avec les cellules T mémoire effectrices résidentes, une population qui reste pendant une période prolongée dans les tissus sans circuler. Les chiens atteints d'eCTCL présentent souvent des lésions à plusieurs endroits, ce qui soulève la question de savoir si le néoplasme appartient ou non à la même sous-population de lymphocytes T. Objectifs - Caractériser les réarrangements du gène du récepteur antigénique des lymphocytes de la peau et du sang des chiens atteints d'eCTCL afin de déterminer si les clones néoplasiques sont identiques. Animaux - Quatorze chiens avec eCTCL. Matériels et méthodes - Examen histologique et immunohistochimique, et PCR pour le réarrangement des récepteurs antigéniques (PARR) pour le récepteur gamma des lymphocytes T (TRG) effectués sur plusieurs échantillons de biopsie cutanée et de sang. Résultats - Toutes les biopsies cutanées contenaient des amas de lymphocytes néoplasiques positifs à la différenciation (CD)3. Chez les chiens individuels, toutes les biopsies cutanées ont révélé des profils de clonalité TRG identiques, suggérant que le même clone néoplasique était présent dans tous les sites. Dans le sang, un clone correspondant a été trouvé chez six des 14 chiens, un clone unique a été observé chez neuf des 14 chiens et aucun clone n'a été détecté chez deux des 14 chiens. Conclusions - Ces résultats montrent que les lésions eCTCL canines à plusieurs endroits abritent le même clone néoplasique, les lymphocytes néoplasiques ne restent pas fixés à la peau et peuvent plutôt circuler par le sang, différents clones peuvent être identifiés dans la peau par rapport au sang, et les cellules néoplasiques circulantes peuvent être détecté sans lymphocytose.

Introducción- se cree que el linfoma epiteliotrópico cutáneo de células T canino (eCTCL) representa una enfermedad homóloga a la micosis fungoide (MF) humana. En la MF humana, las células neoplásicas son fenotípicamente consistentes con las células T de memoria efectoras residentes, una población que permanece durante un período prolongado dentro del tejido sin circular. Los perros con eCTCL a menudo presentan lesiones en múltiples ubicaciones, lo que plantea la cuestión de si la neoplasia es de la misma subpoblación de células T o no. Objetivos- caracterizar los reordenamientos del gen del receptor de antígeno de los linfocitos de la piel y la sangre de perros con eCTCL para determinar si los clones neoplásicos son idénticos. Animales- catorce perros con eCTCL. Materiales y métodos - Examen histológico e inmunohistoquímico, y PCR para el reordenamiento del receptor de antígeno (PARR) para el receptor de células T gamma (TRG) realizado en múltiples muestras de biopsia cutánea y sangre. Resultados- todas las biopsias de piel contenían linfocitos neoplásicos positivos para grupos de diferenciación (CD)3. Dentro de perros individuales, todas las biopsias de piel revelaron perfiles de clonalidad de TRG idénticos, lo que sugiere que el mismo clon neoplásico estaba presente en todos los sitios. En la sangre, se encontró un clon compatible en seis de 14 perros, se observó un clon único en nueve de 14 perros y no se detectó ningún clon en dos de 14 perros. Conclusiones- estos hallazgos muestran que las lesiones de eCTCL canino en múltiples ubicaciones albergan el mismo clon neoplásico, los linfocitos neoplásicos no permanecen fijados a la piel y, en cambio, pueden circular a través de la sangre, se pueden identificar diferentes clones en la piel versus la sangre y las células neoplásicas circulantes pueden ser identificadas sin presencia de linfocitosis.

Contexto - Acredita-se que o linfoma epiteliotrópico cutâneo de células T canino (eCTCL) representa uma doença análoga à micose fungoide (MF) humana. Na MF humana, as células neoplásicas são fenotipicamente consistentes com células T efetoras de memória residentes, uma população que permanece por um período extenso no tecido sem entrar na circulação. Os cães com eCTCL frequentemente apresentam lesões em múltiplos locais, levantando a questão de se a neoplasia é da mesma subpopulação de células T ou não. Objetivos - Caracterizar os rearranjos dos genes receptores de antígenos dos linfócitos da pele e do sangue de cães com eCTCL para determinar se os clones neoplásicos são idênticos. Animais - Quatorze cães com eCTCL. Materiais e métodos - Exame histológico e imunohistoquímico, e PCR para rearranjo de receptor de antígeno (PARR) para o receptor Gama de células T (TRG) realizado em múltiplas amostras de biópsia cutânea e sangue. Resultados - Todas as biópsias cutâneas continham clusters de diferenciação linfócitos T (CD)3- positivos. Entre os indivíduos, todas as biópsias cutâneas revelaram perfis de clonalidade de TGR idênticos em seis dos 14 cães, sugerindo que a mesma célula neoplásica estava presente em todos os locais. No sangue, um clone correspondente foi encontrado em seis dos 14 cães, um clone único foi observado em nove dos 14 cães e nenhum clone foi detectado em dois dos 14 cães. Conclusões - Estes achados demonstraram que as lesões de eCTCL em múltiplos locais possuem o mesmo clone neoplásico, linfócitos neoplásicos não permanecem fixos na pele e podem circular por via sistêmica , diversos tipos de clones podem ser identificados na pele versus sangue, e as células neoplásicas circulantes podem ser detectadas sem linfocitose.

Age- and breed-matched retrospective cohort study of malignancies and benign skin masses in 660 dogs with allergic dermatitis treated long-term with versus without oclacitinib.

OBJECTIVE: To compare the cumulative incidences of malignancies and benign skin masses and the mean age at death or euthanasia in dogs with allergic dermatitis treated long-term with versus without oclacitinib. ANIMALS: 660 client-owned dogs. PROCEDURES: Medical records were searched to identify dogs with allergic dermatitis treated for ≥ 6 months with oclacitinib (exposed dogs; n = 339) versus other available treatments before the introduction of oclacitinib (nonexposed dogs; 321) and with ≥ 24 months of follow-up information available. Nonexposed dogs were age and breed matched with 321 of the exposed dogs; data for the remained 18 exposed dogs were included in statistical analyses. Results for cumulative incidences of malignancies and other variables were compared between groups, and the effect of daily maintenance dosage of oclacitinib on cumulative incidences of malignancies and other skin masses was evaluated within the exposed group. RESULTS: No meaningful differences were detected in the cumulative incidences of malignancies and overall skin masses or the mean age at death or euthanasia for dogs in the exposed group (16.5% [56/339], 56.6% [192/339], and 11.2 years [n = 80], respectively) versus the nonexposed group (12.8% [41/321], 58.3% [187/321], and 11.8 years [71], respectively). There was no association identified between daily maintenance dosage of oclacitinib and odds of malignancy or benign skin masses for dogs in the exposed group. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that long-term treatment with oclacitinib did not pose additional risk for malignancy in dogs; however, veterinarians should continue to observe FDA-approved label warning and precaution statements for oclacitinib and regularly screen for neoplasia in dogs with allergic skin disease treated with or without oclacitinib.

Persistent papilloma treated with cryotherapy in three dogs.

BACKGROUND: Canine papillomaviruses can affect the mucous membranes and skin of young, old and immunocompromised dogs. Most lesions regress spontaneously over a four to eight week interval; however, in some cases the lesions may persist or progress. Cryotherapy is used as a treatment for papillomavirus induced lesions in veterinary practice but there is limited published evidence regarding its use. OBJECTIVES: To describe the history, lesions and treatment outcomes of three dogs with persistent viral papillomas treated with cryotherapy. ANIMALS: Three client owned dogs. METHODS: Canine viral papilloma lesions were treated with five to six freeze-thaw cycles using liquid nitrogen cryotherapy. RESULTS: All lesions in each case resolved with cryotherapy treatment. Two cases required one treatment and one case required two treatment courses. CONCLUSIONS AND CLINICAL IMPORTANCE: The apparent resolution of these papilloma lesions with cryotherapy suggests that this may be a useful treatment intervention for persistent canine papilloma lesions. Spontaneous resolution may still have taken place; consequently, large scale clinical trials are required to demonstrate unequivocally that this mode of therapy, as with other therapeutic modalities, is really effective in the treatment of canine papillomatosis.

Comparison of parasitic mite retrieval methods in a population of community cats.

Objectives This study compared methods of mite retrieval from community cats in the Ohio River Valley region of the USA and determined incidence of parasitic mites in this region. Methods In total, 493 community cats were humanely trapped and anesthetized for a trap-neuter-return program. Cats received a dermatologic examination, ear swabs, superficial skin scraping, flea combing, acetate tape preparation and feces collection. All samples were examined microscopically. Large volumes of hair and scale from flea combing were dissolved in 10% potassium hydroxide and centrifuged with Sheather's solution. Fecal samples were mixed with Sheather's solution, filtered and centrifuged. Results Ear swabs were significantly ( P <0.05) better than other methods for finding chigger mites and Otodectes cynotis, and skin scraping was significantly better than ear swabs for finding Cheyletiella species. Only cats with O cynotis had clinical lesions. Mites remained identifiable for 6 months at room temperature. Mite incidence rates were as follows: Notoedres cati (1/493 cats), 0.002 (95% confidence interval [CI] 0-0.006); Lynxacarus radovskyi (2/493 cats), 0.004 (95% CI 0-0.01); Demodex gatoi (5/493 cats), 0.01 (95% CI 0.001-0.019); chigger mites (10/493 cats), 0.02 (95% CI 0.008-0.033); Cheyletiella species (12/493 cats), 0.024 (95% CI 0.011-0.038); and O cynotis (124/493 cats), 0.252 (95% CI 0.213-0.29). Conclusions and relevance Ear swabs are recommended when O cynotis or chigger mites are suspected. Skin scraping is more likely to yield positive results than ear swabs, but was not significantly better than acetate tape preparations, flea combing or fecal flotation for finding Cheyletiella species. Mites can remain identifiable for prolonged periods at room temperature. With the exception of O cynotis, the incidence of feline parasitic mites in the Ohio River Valley region of the USA is low; however, D gatoi and L radovskyi were present in the area and should be considered in cats with dermatologic disease attributable to them. In this population of community cats, asymptomatic carriage of mites was common.

Clinical efficacy of low-level laser therapy on localized canine atopic dermatitis severity score and localized pruritic visual analog score in pedal pruritus due to canine atopic dermatitis.

BACKGROUND: Canine atopic dermatitis is a genetically predisposed inflammatory skin disease often requiring multimodal treatment. There is a need to find further low-risk adjunctive therapies. HYPOTHESIS/OBJECTIVES: To evaluate the localized effect of low-level laser therapy (LLLT) on the paws of dogs with atopic dermatitis using a localized canine atopic dermatitis severity score (LCADSS) and owner localized pruritic visual analog score (LPVAS) in comparison to treatment with a placebo. ANIMALS: Thirty client-owned dogs with symmetrical pedal pruritus due to canine atopic dermatitis. METHODS: Dogs were randomly assigned into two groups. In each group, one paw was treated with LLLT and one paw treated with a placebo laser (comparing either both fore- or hindpaws). Treatments were administered at 4 J/cm(2) (area from carpus/tarsus to distal aspect of digit 3) three times per week for the first 2 weeks and two times per week for the second 2 weeks. Scores were assessed for each paw at weeks 0, 2, 4 and 5. RESULTS: There were no significant differences in LCADSS or LPVAS between LLLT and placebo treatments between weeks 0 and 5 (P = 0.0856 and 0.5017, respectively). However, LCADSS and LPVAS significantly decreased from week 0 at weeks 2, 4 and 5 in both LLLT and placebo groups (P < 0.0001 for all). CONCLUSIONS AND CLINICAL IMPORTANCE: Low-level laser therapy is not an effective localized treatment for pedal pruritus in canine atopic dermatitis.

Immune-mediated dermatoses.

Pemphigus foliaceus is the most common autoimmune skin disease in horses and is associated with the production of autoantibodies directed against surface proteins of the keratinocyte. Pemphigus vulgaris is a rare autoimmune skin disease in horses. Systemic lupus erythematosus and cutaneous lupus erythematosus are recognized in horses and both are rare. Bullous pemphigoid is a rare autoimmune disease in horses caused by immunologic attack of the basement membrane zone by autoantibodies. Erythema muliforme is an immunologic reaction in the skin in which keratinocyte cell death is the prominent change seen on biopsy. Purpura hemorrhagica is thought analogous to nonthrombocytopenic purpura in humans.

Cutaneous viral dermatoses in dogs and cats.

Cutaneous viral dermatoses are often underdiagnosed in dogs and cats because they are rare, and because it is difficult to identify an exact causative agent. Even so, practitioners in primary care may encounter some characteristic clinical features. This article reviews commonly encountered dermatoses, particularly papillomavirus-associated dermatoses in dogs and cats. It also provides a brief overview of several other dermatoses associated with feline herpesvirus, feline calicivirus, FeLV, and feline poxvirus.

Response of feline eosinophilic plaques and lip ulcers to amoxicillin trihydrate-clavulanate potassium therapy: a randomized, double-blind placebo-controlled prospective study.

In this study, we evaluated the treatment of feline eosinophilic plaques and lip ulcers with amoxicillin trihydrate-potassium clavulanate (Clavamox(®); Pfizer Animal Health). Nineteen cats with clinical and cytological findings consistent with eosinophilic plaques and/or lip ulcers were enrolled. Lesions were photographed and their areas measured in square centimetres before and after 21 days of therapy with either flavoured amoxicillin-clavulanate suspension or flavoured placebo suspension. Sixteen cats completed the study, with nine plaque lesions (four treatment and five placebo) and eight lip ulcer lesions (four treatment and four placebo) included in the analysis. All lesions were shown to have infection, with bacterial phagocytosis present on cytological examination. Coagulase-positive staphylococci were the most commonly isolated bacteria. The amoxicillin-clavulanate-treated eosinophilic plaque group had a statistically significant 96.2% reduction in mean lesion size (-7.60 cm(2), P = 0.0078) and an 80% reduction in mean percentage of microscopic fields demonstrating evidence of bacterial infection (P < 0.0001), whereas the placebo group did not. The amoxicillin-clavulanate-treated lip ulcer group had a 42.6% decrease in mean lesion size (-0.25 cm(2), P = 0.4125) and the placebo group a 36.6% increase (+0.49 cm(2), P = 0.1575), although neither change was statistically significant. The amoxicillin-clavulanate-treated lip ulcer group had a statistically significant 65.0% reduction in mean percentage of microscopic fields demonstrating evidence of bacterial infection (P < 0.0001), while no significant reduction was observed in the placebo group. A suspension of amoxicillin trihydrate-potassium clavulanate is an effective monotherapy for the treatment of feline eosinophilic plaques.

Detection of novel papillomaviruslike sequences in paraffin-embedded specimens of invasive and in situ squamous cell carcinomas from cats.

OBJECTIVE: To detect and partially characterize papillomavirus (PV) DNA in squamous cell carcinoma (SCC) tumor specimens from cats. SAMPLE POPULATION: 54 formalin-fixed paraffinembedded skin biopsy specimens were examined. Specimens originated from Bowenoid in situ SCC (BISC; n = 21), invasive SCC (22), and skin affected by miscellaneous nonneoplastic conditions (11). PROCEDURES: Samples from each tissue block underwent DNA extraction after deparaffinization, and PCR assays were performed. Two sets of primers derived from PV E1 were used. The first set of primers was designed for the narrow-range PCR assay and was able to generate amplification products of feline PV (FePV), canine oral PV, or closely related PVs. The second set of primers was selected for the broad-range PCR assay because of its ability to amplify DNA from 64 human PVs. Sequence analysis of each amplified DNA was performed. RESULTS: 1 of the 21 specimens of BISC was positive for PV DNA on the basis of narrow-range PCR assay results, whereas all the other specimens (BISC, invasive SCC, and controls) had negative results for PV DNA. In contrast, 5 of 21 BISC specimens and 4 of 22 invasive SCC specimens were positive for PV DNA on the basis of broad-range PCR assay results. Sequence analysis revealed that only 1 specimen was infected by a virus closely related to classic FePV. In the 8 other specimens positive for PV DNA, DNA of unknown PVs was uncovered. CONCLUSIONS AND CLINICAL RELEVANCE: Bowenoid in situ SCC and invasive SCC of cats may be associated with PVs of genetic diversity.

Feline pyoderma therapy.

Feline pyoderma is a disease entity more prevalent than previously described. Diagnosis is made by finding bacteria in the presence of inflammatory cells or bacterial phagocytosis on routine cytological examination. Diseases leading to secondary bacterial pyoderma include allergic and inflammatory skin diseases, parasitosis, feline chin acne, and others. Lesions of feline pyoderma are variable and include crusted and eroded papules, pustules, furuncles, eroded to ulcerated plaques with variable exudation and crusting, and linear to nodular ulcerative granulomatous lesions. Three cases of feline pyoderma responsive to antimicrobial therapy are discussed: case 1, a 10.5-year-old male neutered domestic short hair with eosinophilic lip ulcer, case 2, a 7-year-old male neutered domestic short hair with multiple cutaneous eosinophilic plaques, and case 3, an 8-month-old male neutered domestic short hair cat with Pseudomonas dermatitis, vasculitis, and panniculitis. Antibiotic selection for treatment of feline pyoderma should be based on cytological examination, and culture and sensitivity in unresponsive cases.

Pemphigus: current therapy.

Pemphigus is an autoimmune skin disease that can present in a variety of forms and can be a challenging disease to manage and treat. An overview of the different forms of pemphigus and diagnostics are discussed including pemphigus foliaceus (PF), pemphigus erythematosus (PE), panepidermal pustular pemphigus (PPP), pemphigus vulgaris (PV) and paraneoplastic pemphigus (PNP). Emphasis on therapy is presented. Included are the most current commonly used therapeutics (glucocorticoids, azathioprine, chlorambucil and tetracycline and niacinamide); current alternative therapeutics (cyclosporin and tacrolimus and mycophenolate mofetil) and additional alternative therapeutics (cyclophosphamide, chrysotherapy, dapsone, sulfasalazine and intravenous immunoglobulin (IVIG) therapy).

Sebaceous adenitis in four domestic rabbits (Oryctatagus cuniculus).

Four domestic rabbits were presented with a history of nonpruritic scale. Multiple skin biopsies revealed findings compatible with sebaceous adenitis as reported in other species: inflammation directed at the sebaceous gland, and/or an absence of sebaceous glands, a perifollicular lymphocytic infiltrate at the level of the absent sebaceous glands, hyperkeratosis, follicular keratosis, follicular dystrophy, perifollicular fibrosis, and a mural infiltrative lymphocytic folliculitis. Histological changes not consistent with sebaceous adenitis in other species were interface dermatitis and interface folliculitis with single cell necrosis and basal cell hydropic degeneration.