Dermatosis suggesting a staphylococcic toxic shock syndrome in a golden retriever

Staphylococcal toxic shock syndrome (STSS) is a rare toxinic dermatosis recently described in dogs. In this syndrome, also known in man, the toxin TSST-1 (toxic shock syndrome toxin-1) acts as a superantigen and triggers the secretion of a large number of lymphocytic cytokines (IL1, IL6, TNFa…). A 5 year-old male golden retriever is presented for a sudden onset of painful skin lesions. Clinical examination shows a severe fever (40.5°C) and dehydration, as well as erythematous and erosive maculae on the abdomen and interdigital spaces. On the next day, epidermal necrolysis developed with spontaneous widespread sloughing (Nikolski sign+) on the face, abdomen and limbs, uncovering a red and oozing dermis. Hematology and biochemistry tests revealed a regenerative normocytic normochromic anemia, hyponatremia and hypochloremia. Hypoalbuminemia was evidenced by protein electrophoresis. Antinuclear antibody assays were within normal limits. A bacteriological culture showed the presence of coagulase-positive staphylococci, Staphylococcus intermedius. Massive epidermal neutrophilic exocytosis and apoptotic keratinocytes were found in skin biopsies, as well as neutrophilic satellitosis. A severe necrosis of the epidermis and of the upper half of all follicular ostia was noted. The detection by PCR on blood and skin biopsies of canine herpesvirus and distemper virus was negative. Chest x-rays and abdominal ultrasound examination found no evidence of an internal tumour. Finally, no iatrogenic cause could be identified. The initial treatment included an antibiotic (marbofloxacin 2 mg/kg SID), an anti-inflammatory and analgesic (ketoprofen 1 mg/kg SID), as well as an opioid analgesic (fentanyl 0.1mg/kg every 6 hours subcutaneously), with intravenous rehydration and daily antiseptic baths with chlorhexidine. The weight loss (10 kg in 10 days), anorexia, anemia and hypoalbuminemia justified an enteral nutrition for 1 week. The skin lesions, hematocrit, hemoglobinemia and albuminemia improved progressively. The dog was given back to its owner after three weeks. He was seen again three months later, cured and in good general health. Two years later, no relapse has occurred.Le syndrome du choc toxinique staphylococcique (SCTS) est une dermatose toxinique rare, de description récente chez le Chien. Dans ce syndrome, connu également chez l'Homme, une toxine, la toxic shock syndrome toxin-1 (TSST-1) pour le SCTS agit comme des superantigènes et déclenchent la sécrétion d'un grand nombre de cytokines lymphocytaires (IL1, IL6, TNFα) Un Golden Retriever mâle de 5 ans est présenté pour l'apparition soudaine de lésions cutanées douloureuses. L'examen clinique montre un syndrome fébrile sévère (40,5 °C) et une déshydratation. L'examen dermatologique révèle des macules érythémateuses et érosives de l'abdomen et des espaces interdigités. Le lendemain, une nécrolyse épidermique apparaît sous forme de décollements spontanés (signe de Nikolski +) de la face, du ventre et des membres. Ces vastes décollements découvrent un derme rouge et suintant. Les examens sanguins hématologiques et biochimiques montrent une anémie normochrome normocytaire régénérative, une hyponatrémie et une hypochlorémie. L'électrophorèse des protéines révèle une hypoalbuminémie. Le dosage des anticorps antinucléaires est conforme aux valeurs usuelles. La culture bactériologique montre la présence de staphylocoques coagulase +, Staphylococcus intermedius. Des biopsies cutanées montrent une exocytose importante de neutrophiles au sein de l'épiderme et des kératinocytes apoptotiques. Une satellitose neutrophilique est observée. Une sévère nécrose épidermique et de la moitié supérieure de tous les ostia folliculaires est notée. La recherche par PCR sur sang et biopsie cutanée de l'herpesvirus canin et du virus de la maladie de Carré est négative. Des radiographies thoraciques et une échographie abdominale ne montrent aucune modification susceptible d'évoquer une tumeur interne. Enfin, la démarche d'imputabilité médicamenteuse reste vaine. Le traitement initial fait appel à une antibiothérapie (marbofloxacine 2 mg/kg SID), un anti-inflammatoire et analgésique (kétoprofène 1 mg/kg SID) ainsi qu'à un analgésique opiacé (fentanyl 0,1 mg/kg SC toutes les 6 heures), une réhydratation intraveineuse et des bains antiseptiques quotidiens à la chlorhexidine. L'amaigrissement (perte de 10 kg en 10 jours), l'anorexie, l'anémie et l'hypoalbuminémie sont à l'origine d'une nutrition entérale pendant 1 semaine. L'hématocrite, l'hémoglobinémie et l'albuminémie remontent progressivement. Les lésions cutanées s'améliorent progressivement. Au bout de 3 semaines, le chien est rendu à ses propriétaires. Le chien est revu 3 mois plus tard, guéri et en bon état général. Le chien n'a pas rechuté en 2 ans

Immunohistochimie des lymphomes gastrointestinaux du chat

Chez le chat, les lymphomes sont les tumeurs les plus fréquentes du tractus digestif. La seule étude morphologique par l’examen cytologique et/ou histopathologique ne permet pas dans tous les cas de différencier un lymphome d’une lésion hyperplasique ou réactionnelle et elle n’autorise pas non plus le typage des tumeurs qui nécessite l’identification précise de la sous-population cellulaire à l’origine de la prolifération néoplasique. Actuellement, au moyen d’un nombre limité d’anticorps utilisables sur des prélèvements fixés par le formol et inclus en paraffine, c’est-à-dire dans les conditions de la pratique clinique courante, le recours à des techniques immunohistochimiques permet d’accroitre de manière sensible les informations obtenues par l’examen histologique pratiquées sur des biopsies, aussi bien pour le typage des tumeurs que pour le diagnostic différentiel des lésions non tumorales. Les principes, modalités, indications et limites de ce type de méthodes appliquées à la gastroentérologie du chat sont présentés dans cette synthèse

Comparative analysis of canine and human melanomas

This paper presents epidemiological and clinical data from 2350 cases of melanocytic tumours from dogs sampled in France. In addition, we present the histological and genetic characterization of subsets of melanoma cases (n=153 and n=100, respectively), with a comparative aspect to human melanomas. Dog melanomas occur at the same anatomical sites than human melanomas, but with different frequency and severity. We demonstrate that the specificities of dog melanomas make them good models to understand the non-UV pathways of human melanomas. Interestingly, somatic mutations in oral canine melanomas were detected in the NRAS and PTEN genes, precisely at the same hotspots as human mutations. In contrast, mutations in the BRAF gene were not detected. This paper highlights the similarities and differences of dog and human melanoma types and the strong potential of dog melanomas to decipher the non-UV light pathways in different melanoma types, especially mucosal and acral types.Cet article présente les données épidémiologiques et cliniques de 2350 cas de tumeurs mélanocytaires canines collectées en France. Nous avons réalisé la caractérisation histologique (n = 153) et génétique (n = 100) d'un sous-groupe de mélanomes dont les résultats ont été comparés aux données des mélanomes humains. Les mélanomes apparaissent aux mêmes sites anatomiques chez le chien et l'Homme, mais avec des fréquences et des sévérités différentes. Nous montrons les prédispositions raciales des mélanomes canins et l'intérêt de ce modèle pour rechercher les gènes prédisposant difficiles à identifier chez l'Homme. Des mutations somatiques dans les gènes NRAS et PTEN ont été détectées dans les mélanomes buccaux canins, précisément aux mêmes points chauds (hotspots) que les mutations de ces gènes chez l'homme. Au contraire, aucune mutation dans le gène BRAF n'a été retrouvée dans les échantillons canins analysés. Ce travail met en lumière les homologies et différences entre les types de mélanomes humains et canins et démontre la force du modèle canin pour analyser les voies de signalisation non UV-dépendantes des mélanomes humains, particulièrement dans les types muqueux et acraux

Pharmacokinetics and tolerance of repeated oral administration of 5-fluorocytosine in healthy dogs

International audienceBackground: 5-fluorocytosine is a pyrimidine and a fluorinated cytosine analog mainly used as an antifungal agent. It is a precursor of 5-fluorouracil, which possesses anticancer properties. To reduce systemic toxicity of 5-fluorouracil during chemotherapy, 5-fluorocytosine can be used as a targeted anticancer agent. Expression of cytosine deaminase by a viral vector within a tumor allows targeted chemotherapy by converting 5-fluorocytosine into the cytotoxic chemotherapeutic agent 5-fluorouracil. However, little is known about the tolerance of 5-fluorocytosine in dogs after prolonged administration. Results: In three healthy Beagle dogs receiving 100 mg/kg of 5-fluorocytosine twice daily for 14 days by oral route, noncompartmental pharmacokinetics revealed a terminal elimination half-life of 164.5 ± 22.5 min at day 1 and of 179.2 ± 11.5 min, after 7 days of administration. Clearance was significantly decreased between day 1 and day 7 with 0.386 ± 0.031 and 0.322 ± 0.027 ml/min/kg, respectively. Maximal plasma concentration values were below 100 µg/ml, which is considered within the therapeutic margin for human patients. 5-fluorouracil plasma concentration was below the limit of detection at all time points. The main adverse events consisted of depigmented, ulcerated, exudative, and crusty cutaneous lesions 10 to 13 days after beginning 5-fluorocytosine administration. The lesions were localized to the nasal planum, the lips, the eyelids, and the scrotum. Histological analyses were consistent with a cutaneous lupoid drug reaction. Complete healing was observed 15 to 21 days after cessation of 5-fluorocytosine. No biochemical or hematological adverse events were noticed. Conclusions: Long term administration of 5-fluorocytosine was associated with cutaneous toxicity in healthy dogs. It suggests that pharmacotherapy should be adjusted to reduce the toxicity of 5-fluorocytosine in targeted chemotherapy

Naturally occurring melanomas in dogs as models for non-UV pathways of human melanomas.

International audienceSpontaneously occurring melanomas are frequent in dogs. They appear at the same localizations as in humans, i.e. skin, mucosal sites, nail matrix and eyes. They display variable behaviors: tumors at oral localizations are more frequent and aggressive than at other anatomical sites. Interestingly, dog melanomas are associated with strong breed predispositions and overrepresentation of black-coated dogs. Epidemiological analysis of 2350 affected dogs showed that poodles are at high risk of developing oral melanoma, while schnauzers or Beauce shepherds mostly developped cutaneous melanoma. Clinical and histopathological analyses were performed on a cohort of 153 cases with a 4-yr follow-up. Histopathological characterization showed that most canine tumors are intradermal and homologous to human rare morphological melanomas types - 'nevocytoid type' and 'animal type'-. Tumor cDNA sequencing data, obtained from 95 dogs for six genes, relevant to human melanoma classification, detected somatic mutations in oral melanoma, in NRAS and PTEN genes, at human hotspot sites, but not in BRAF. Altogether, these findings support the relevance of the dog model for comparative oncology of melanomas, especially for the elucidation of non-UV induced pathways

Prognostic value of somatic focal amplifications on chromosome 30 in canine oral melanoma

International audienceCanine oral melanoma is the first malignancy of the oral cavity in dogs and is characterized by a local invasiveness and a high metastatic propensity. A better knowledge of genetic alterations is expected to improve management of this tumour. Copy number alterations are known characteristics of mucosal melanomas both in dogs and humans. The goal of this study was to explore the prognostic value of somatic focal amplifications on chromosomes (Canis Familiaris [CFA]) 10 and 30 in canine oral melanoma. The cohort included 73 dogs with oral melanoma confirmed by histology, removed surgically without adjuvant therapy and with a minimal follow‐up of 6 months. Epidemiological, clinical and histological data were collected and quantitative‐PCR were performed on formalin‐fixed paraffin‐embedded (FFPE) samples to identify specific focal amplifications. The 73 dogs included in the study had a median survival time of 220 days. Focal amplifications on CFA 10 and 30 were recurrent (49.3% and 50.7% of cases, respectively) and CFA 30 amplification was significantly associated with the amelanotic phenotype (P = .046) and high mitotic index (MI; P = .0039). CFA 30 amplification was also linked to poor prognosis (P = .0005). Other negative prognostic factors included gingiva location (P = .003), lymphadenomegaly (P = .026), tumour ulceration at diagnosis (P = .003), MI superior to 6 mitoses over 10 fields (P = .001) and amelanotic tumour (P = .029). In multivariate analyses using Cox proportional hazards regression, CFA 30 amplification (Hazard ratio [HR] = 2.08; P = .011), tumour location (HR = 2.20; P = .005) and histological pigmentation (HR = 1.87; P = .036) were significantly associated with shorter survival time. Focal amplification of CFA 30 is linked to an aggressive subset and constitutes a new prognostic factor

A Spontaneous KRT16 Mutation in a Dog Breed: A Model for Human Focal Non-Epidermolytic Palmoplantar Keratoderma (FNEPPK).

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PNPLA1 mutations cause autosomal recessive congenital ichthyosis in golden retriever dogs and humans.

International audienceIchthyoses comprise a heterogeneous group of genodermatoses characterized by abnormal desquamation over the whole body, for which the genetic causes of several human forms remain unknown. We used a spontaneous dog model in the golden retriever breed, which is affected by a lamellar ichthyosis resembling human autosomal recessive congenital ichthyoses (ARCI), to carry out a genome-wide association study. We identified a homozygous insertion-deletion (indel) mutation in PNPLA1 that leads to a premature stop codon in all affected golden retriever dogs. We subsequently found one missense and one nonsense mutation in the catalytic domain of human PNPLA1 in six individuals with ARCI from two families. Further experiments highlighted the importance of PNPLA1 in the formation of the epidermal lipid barrier. This study identifies a new gene involved in human ichthyoses and provides insights into the localization and function of this yet uncharacterized member of the PNPLA protein family