Canine neuropathies: powerful spontaneous models for human hereditary sensory neuropathies.

In humans, hereditary sensory neuropathies (HSN), also known as hereditary sensory and autonomic neuropathies (HSAN), constitute a clinically and genetically heterogeneous group of disorders characterized by progressive sensory loss, often accompanied by chronic skin ulcerations and nail dystrophic changes. To date, although around 20 genes have already been discovered, they do not explain the genetic causes of all patients. In dogs, similar neuropathies are also diagnosed, several breeds being predisposed to specific forms of the disease. Indeed, the breed specificity of most canine genetic diseases is due to the small numbers of founders and high levels of inbreeding. Recent knowledge and tools developed to study the canine genome efficiently allows deciphering the genetic bases of such diseases. To date, a dozen breeds are recognized to develop specific HSN. For the Border collie and hunting dog breeds, the genes involved have recently been discovered. Other affected breeds thus constitute potential genetic models, with new genes to be found in dogs that can be considered as candidate genes for human HSAN/HSN. Here, we review the different forms of human and canine HSAN/HSN and we present a novel form in Fox terrier cases, highlighting the advantages of the dog model for such rare human diseases.

A Point Mutation in a lincRNA Upstream of GDNF Is Associated to a Canine Insensitivity to Pain: A Spontaneous Model for Human Sensory Neuropathies.

Human Hereditary Sensory Autonomic Neuropathies (HSANs) are characterized by insensitivity to pain, sometimes combined with self-mutilation. Strikingly, several sporting dog breeds are particularly affected by such neuropathies. Clinical signs appear in young puppies and consist of acral analgesia, with or without sudden intense licking, biting and severe self-mutilation of the feet, whereas proprioception, motor abilities and spinal reflexes remain intact. Through a Genome Wide Association Study (GWAS) with 24 affected and 30 unaffected sporting dogs using the Canine HD 170K SNP array (Illumina), we identified a 1.8 Mb homozygous locus on canine chromosome 4 (adj. p-val = 2.5x10-6). Targeted high-throughput sequencing of this locus in 4 affected and 4 unaffected dogs identified 478 variants. Only one variant perfectly segregated with the expected recessive inheritance in 300 sporting dogs of known clinical status, while it was never present in 900 unaffected dogs from 130 other breeds. This variant, located 90 kb upstream of the GDNF gene, a highly relevant neurotrophic factor candidate gene, lies in a long intergenic non-coding RNAs (lincRNA), GDNF-AS. Using human comparative genomic analysis, we observed that the canine variant maps onto an enhancer element. Quantitative RT-PCR of dorsal root ganglia RNAs of affected dogs showed a significant decrease of both GDNF mRNA and GDNF-AS expression levels (respectively 60% and 80%), as compared to unaffected dogs. We thus performed gel shift assays (EMSA) that reveal that the canine variant significantly alters the binding of regulatory elements. Altogether, these results allowed the identification in dogs of GDNF as a relevant candidate for human HSAN and insensitivity to pain, but also shed light on the regulation of GDNF transcription. Finally, such results allow proposing these sporting dog breeds as natural models for clinical trials with a double benefit for human and veterinary medicine.

A mutation in the SUV39H2 gene in Labrador Retrievers with hereditary nasal parakeratosis (HNPK) provides insights into the epigenetics of keratinocyte differentiation.

Hereditary nasal parakeratosis (HNPK), an inherited monogenic autosomal recessive skin disorder, leads to crusts and fissures on the nasal planum of Labrador Retrievers. We performed a genome-wide association study (GWAS) using 13 HNPK cases and 23 controls. We obtained a single strong association signal on chromosome 2 (p(raw) = 4.4×10⁻¹4). The analysis of shared haplotypes among the 13 cases defined a critical interval of 1.6 Mb with 25 predicted genes. We re-sequenced the genome of one case at 38× coverage and detected 3 non-synonymous variants in the critical interval with respect to the reference genome assembly. We genotyped these variants in larger cohorts of dogs and only one was perfectly associated with the HNPK phenotype in a cohort of more than 500 dogs. This candidate causative variant is a missense variant in the SUV39H2 gene encoding a histone 3 lysine 9 (H3K9) methyltransferase, which mediates chromatin silencing. The variant c.972T>G is predicted to change an evolutionary conserved asparagine into a lysine in the catalytically active domain of the enzyme (p.N324K). We further studied the histopathological alterations in the epidermis in vivo. Our data suggest that the HNPK phenotype is not caused by hyperproliferation, but rather delayed terminal differentiation of keratinocytes. Thus, our data provide evidence that SUV39H2 is involved in the epigenetic regulation of keratinocyte differentiation ensuring proper stratification and tight sealing of the mammalian epidermis.

Identification of 5α-reductase isoenzymes in canine skin.

BACKGROUND: Alopecia X in dogs is a noninflammatory alopecia that may be caused by a hormonal dysfunction. It may be similar to androgenic alopecia in men that is caused by the effect of dihydrotestosterone (DHT). The 5α-reductase isoenzymes, 5αR1 and 5αR2, and a recently described 5αR3, are responsible for the conversion of testosterone into DHT. However, which 5α-reductases are present in canine skin has not yet been described. OBJECTIVES: The main objective of this study was to determine the pattern of expression of 5α-reductase genes in canine skin. METHODS: Skin biopsies were obtained from healthy, intact young-mature beagles (three males, four females) at three anatomical sites normally affected by alopecia X (dorsal neck, back of thighs and base of tail) and two sites generally unaffected (dorsal head and ventral thorax). Prostate samples (n = 3) were collected as positive controls for 5α-reductase mRNA abundance measurement by real-time PCR. RESULTS: We detected mRNA encoding 5αR1 and 5αR3 but not 5αR2. There were no significant differences in 5αR1 and 5αR3 mRNA levels between the different anatomical sites, irrespective of gender (P > 0.05). Moreover, the mean mRNA abundance in each anatomical site did not differ between males and females (P > 0.05). CONCLUSIONS AND CLINICAL IMPORTANCE: To the best of the authors' knowledge, this is the first study demonstrating the expression of 5α-reductases in canine skin and the expression of 5αR3 in this tissue. These results may help to elucidate the pathogenesis of alopecia X and to determine more appropriate treatments for this disorder.

Treatment of demodicosis in dogs: 2011 clinical practice guidelines.

BACKGROUND AND OBJECTIVES: These guidelines were written by an international group of specialists with the aim to provide veterinarians with current recommendations for the diagnosis and treatment of canine demodicosis. METHODS: Published studies of the various treatment options were reviewed and summarized. Where evidence in form of published studies was not available, expert consensus formed the base of the recommendations. RESULTS: Demodicosis can usually be diagnosed by deep skin scrapings or trichograms; in rare cases a skin biopsy may be needed for diagnosis. Immune suppression due to endoparasitism or malnutrition in young dogs and endocrine diseases, neoplasia and chemotherapy in older dogs are considered predisposing factors and should be diagnosed and treated to optimize the therapeutic outcome. Dogs with disease severity requiring parasiticidal therapy should not be bred. Secondary bacterial skin infections frequently complicate the disease and require topical and/or systemic antimicrobial therapy. There is good evidence for the efficacy of weekly amitraz rinses and daily oral macrocyclic lactones such as milbemycin oxime, ivermectin and moxidectin for the treatment of canine demodicosis. Weekly application of topical moxidectin can be useful in dogs with milder forms of the disease. There is some evidence for the efficacy of weekly or twice weekly subcutaneous or oral doramectin. Systemic macrocyclic lactones may cause neurological adverse effects in sensitive dogs, thus a gradual increase to the final therapeutic dose may be prudent (particularly in herding breeds). Treatment should be monitored with monthly skin scrapings and extended beyond clinical and microscopic cure to minimize recurrences.

The ABCB1-1Delta mutation is not responsible for subchronic neurotoxicity seen in dogs of non-collie breeds following macrocyclic lactone treatment for generalized demodicosis.

P-glycoprotein (P-gp), encoded by the multiple drug resistance gene ABCB1 (also known as MDR1), is an integral component of the blood brain barrier crucial in limiting drug uptake into the central nervous system. Altered expression or function of P-gp, as seen in dogs of the collie lineage homozygous for the nt228(del4) mutation of the ABCB1 gene (ABCB1-1Delta), can result in potentially fatal neurotoxicosis, especially following administration of systemic macrocyclic lactones (SML). Occasionally, dogs from unrelated breeds develop subchronic signs of neurotoxicity when receiving SML to treat generalized demodicosis. It is possible that these dogs are heterozygous carriers of the ABCB1-1Delta mutation, resulting in decreased P-gp activity and central neurotoxicosis. Cheek swabs were collected from 28 dogs with generalized demodicosis that had shown subchronic signs of neurotoxicity following daily oral administration of ivermectin or other SML. Ten of these animals received concurrent systemic treatment with other confirmed or putative P-gp substrates. After DNA extraction, the relevant portion of the ABCB1 gene was amplified by polymerase chain reaction, and sequenced. Twenty-seven dogs were homozygous normal while one dog was heterozygous for the ABCB1-1Delta mutation. Therefore, with the exception of one dog, the observed neurotoxicity could not be attributed to the ABCB1-1Delta mutation. Possible explanations for the adverse reactions observed include pharmacological interactions (administration of SML with other P-gp substrates or inhibitors), excessively high doses, polymorphisms in P-gp expression, uncharacterized mutations in the ABCB1 gene or in another gene, or phenomena unrelated to the SML-P-gp interaction.

Use of recombinant human thyroid-stimulating hormone for thyrotropin stimulation test in healthy, hypothyroid and euthyroid sick dogs.

Recombinant human thyroid-stimulating hormone (rhTSH) was evaluated for the diagnosis of canine hypothyroidism, using TSH response tests. Phase I stimulation tests were performed in 6 healthy dogs weighing over 20 kg, using 50 and then 100 microg of freshly reconstituted rhTSH administered intravenously. In phase II, the same dogs were stimulated by using 100 microg of rhTSH frozen for 3 months at -20 degrees C. Phase III stimulation tests were performed by using 50 or 100 microg of freshly reconstituted or frozen rhTSH in healthy (n = 14), euthyroid sick (n = 11) and hypothyroid dogs (n = 9). A dose of 100 microg of rhTSH was judged more appropriate for dogs weighing more than 20 kg. Biological activity of rhTSH after freezing at -20 degrees C for up to 12 weeks was maintained. When stimulated, significant (P < 0.05) increases in total thyroxine concentration were observed only in healthy and euthyroid sick dogs. Results of this study show that the rhTSH stimulation test is able to differentiate euthyroidism from hypothyroidism in dogs.

Topical (pour-on) ivermectin in the treatment of chronic generalized demodicosis in dogs.

Twelve privately owned dogs with chronic generalized demodicosis were treated topically along the dorsal midline with 1.5 mg kg-1 of 0.5% pour-on ivermectin for cattle three times per week for 3-6 months. All 12 dogs had a substantial reduction in clinical signs and in the number of Demodex canis mites found on skin scrapings. Only two dogs, however, became skin-scrapings negative after 3 and 5 months of treatment, respectively. In these two dogs treatment was prolonged for an additional 4 weeks past the negative scrapings. One dog relapsed 2 months after cessation of therapy; the other is still free of symptoms 1.5 years later. The cure rate, based on the lack of recurrence of clinical signs for 12 months after discontinuation of ivermectin administration, was 1 of 12 dogs (8%). Adverse reactions were not seen.

The Efficacy of Clemastine (Tavist), a Fatty Acid-containing Product (Derm Caps), and the Combination of Both Products in the Management of Canine Pruritus.

Abstract- Thirty dogs having pruritus associated with atopy or idiopathy were treated with the HI-blocking antihistamine, clemastine (Tavist), a fatty acid-containing nutritional supplement (Derm Caps/Derm Caps ES), and both products simultaneously. Each product, and the combination of the two, were given for a two week period. Tavist and Derm Caps/Derm Caps ES each afforded satisfactory control of pruritus in 26.7 per cent of the dogs. The combination appeared to produce a synergistic effect in three dogs. Pruritus was satisfactorily controlled in 43.7 per cent of the dogs when Tavist and Derm Caps/Derm Caps ES were administered concomitantly. Résumé- Trente chiens souffrant de prurit associé soit à de l'atopie ou soit de causes indéterminées furent traités avec l'antihistaminique bloqueur H1, clémastine (Tavist), un supplément nutritionnel contenant des acides gras (Derm Caps ou Derm Caps ES) ainsi que les deux produits simultanément. Chaque produit ainsi que la combinaison des deux ont été donnés durant deux semaines et 26.7% des chiens ont démontré un contrôle satisfaisant du prurit avec soit le Tavist soit le Derm Caps/Derm Caps ES. L'utilisation des produits en combinaison semble avoir produit un effet synergique chez trois chiens. e prurit fut contrôlé de façon satisfaisante dans 43,7% des cas quand le Tavist et de Derm Caps. Derm Caps ES étaient administrés simultanément. Zusammenfassung- 30 Hunde mit Pruritus-durch Atopie oder idiopathisch bedingtwurden mit dem die H1 -Rezeptoren blockierenden Antihistaminikum Clemastin (Tavist), mit einem fettsäurehaltigen Futterzusatz (Derm Caps) und mit einer Kombination aus diesen beiden behandelt. Jedes dieser Produkte allein sowie beide zusammen wurden jeweils 2 Wochen gegeben. Tavist und Dermcaps alleine führten jeweils zu einer zufriedenstellenden Kontrolle des Pruritus in 26.7% der Fälle. Beide Produkte zusammen schienen einen synergistischen Effekt bei drei Tieren zu haben. Der Pruritus wurde mit der Kombination von Tavist und Derm Caps in 43.7% der Fälle zufriedenstellend kontrolliert. Resumen Treinta perros que padecían cuadros pruriginosos asociados a atopia canina o de origen idiopático se trataron con un antihistamínico bloqueador de los receptores H1, la clemastina (Tavist), con un suplemento nutricional que contenía ácidos grasos (Derm Caps) y con ambos productos simultáneamente. Cada producto y la combinación de ambos se administró durante un periodo de dos semanas de duración. El Tavist y Derm Caps consiguieron un control satisfactorio del prurito en el 26,7% de los casos. La combinación de ambos productos parecía producir un efecto sinergístico en 3 perros. El prurito se controló de forma satisfactoria en el 43,7% de los perros cuando se administraba concomitantemente el Tavist y el Derm Caps.

Efficacy of Enrofloxacin in the Treatment of Canine Bacterial Pyoderma.

Abstract- Bacterial pyoderma was diagnosed in 30 dogs which were subsequently treated with enrofloxacin administered orally at 2.5 mg.kg-1 of body weight every 12 h, for 2 to 14 weeks. Dogs were re-examined at the conclusion of antibiotic treatment and 28 (93.3 per cent) were found to have an excellent response. Relapses were seen in 25 per cent of these dogs after follow up periods of 1 to 4 months. Minor side effects were seen in only 1 dog. On the basis of this study, enrofloxacin is an excellent antibiotic for the treatment of canine bacterial pyoderma but must be administered well beyond the manufacturer's maximum recommendation for duration of therapy. Résumé- Une pyodermite bactérienne a été diagnostiquée chez 30 chiens qui furent traités avec de l'enrofloxacine administrée par voie orale à la dose de 2.5 mg/Kg toutes les 12 heures, pour une durée allant de 2.5 à 14 semaines. Les chiens furent réexaminés à la fin de l'antibiothérapie et 28 d'entre eux (93.3%) présentaient une excellente réponse au traitement. Des rechutes furent observées chez 25% des chiens lors de suivis portant sur des périodes de 1 à 4 mois. Des effets secondaires mineurs furent observés chez l'un des chiens. Cette étude montre que l'enrofloxacine est un excellent antibiotique pour le traitement des pyodermites canines mais, qu'il doit être administré pendant des délais beaucoup plus longs que ceux qui sont indiqués par le fabricant. Zusammenfassung- 30 Hunde mit bakteríellen Pyodermien wurden zweieinhalb bis vierzehn Wochen lang oral mit Enrofloxacin behandelt (2 täglich 2.5 mg/kg KGW). Nach Abschluß der Behandlung wurden die Tiere erneut untersucht. Bei 28 Patienten (93.3%) wurden hervorragende Ergebnisse erzielt. Bei 25% kam as nach 1 bis 4 Monaten zu Rezidiven. Geringe Nebenwirkungen wurden nur in einem Fall beobachtet. Die vorliegende Untersuchung zeigt, daß Enrofloxacin ein hervorragendes Antibiotikum für die Behandlung von Pyodermien ist, aber wesentlich länger als vom Hersteller angegeben verabreicht werden muß. Resumen Treinta perros, a los cuales se había diagnosticado una epiderma bacteriana, fueron tratado con Enrofloxacina via oral a una dosis de 2,5 mg/kg de peso corporal cada 12 horas durante un período de tiempo que oscíló entre las 2,5 semanas y las 14 semanas. Los perros se examinaron clínicamente de nuevo cuando acabó el tratamiento antibiótico y se observó en 28 (93,3%) una respuesta excelente. En un 25% de estos perros se observaron recidivas en un período comprendido entre uno y cuatro meses. Efectos colaterales de poca importancia se observaron úicamente en un animal. Según estos resultados puede concluirse que la Enrofloxacina es un antibiótico excelente para el tratamiento de las piodermas bacterianas del perro, aunque debe administrarse durante un período de tiempo superior al que recomiendan los productores.

Efficacy of selamectin in the treatment of naturally acquired cheyletiellosis in cats.

The purpose of this study was to evaluate the efficacy of a topical formulation of selamectin in the treatment of cheyletiellosis in cats. Fifteen adult domestic cats from the same household with naturally occurring Cheyletiella sp. infestation were enrolled in the study. On each cat, 45 mg of selamectin was applied on days 0, 30, and 60. No other treatment or environmental decontamination was performed during the trial. On days 0, 30, 60, and 120, all cats were examined, epidermal debris was collected over the dorsal area of the body with flea combs for microscopic examination, and fecal flotations were done. Clinical signs had subsided by day 60 in all 15 cats and no signs of recurrence were apparent on follow-up 1 year later. All epidermal and fecal samples were negative by day 60. No adverse reactions were observed. Under the conditions of our study, topical selamectin was a practical and well-tolerated means of treatment for cheyletiellosis in cats.

Effects of moderate to severe osteoarthritis on canine thyroid function.

Several nonthyroidal illnesses in euthyroid dogs can affect the results of thyroid function testing, making interpretation of the results more difficult with an increased risk of overdiagnosing hypothyroidism. The purpose of this study was to evaluate the effect of chronic, moderate to severe, osteoarthritis on canine thyroid function. Ninety-six, healthy, client-owned dogs, 65 of which were suffering from moderate to severe osteoarthritis and 31 euthyroid dogs without any physical evidence of osteoarthritis, were used in this study. Blood samples were collected to evaluate serum basal total thyroxine (TT4), free thyroxine (FT4), and thyrotropin (TSHc) concentrations. Basal serum TT4 concentration was not affected by osteoarthritis in dogs. Mild, but statistically significant, differences were noticed in FT4 and TSHc concentrations among the 2 groups. However, this had limited clinical relevance, since virtually all values were within their reference range, and no dogs would have been misdiagnosed as hypothyroid. Therefore, based on the results of our study, osteoarthritis does not need to be considered a factor influencing thyroid function evaluation in dogs.

Effects of oral administration of meloxicam, carprofen, and a nutraceutical on thyroid function in dogs with osteoarthritis.

The purpose of this study was to evaluate the effect of the administration of meloxicam; carprofen; and a slow-acting disease modifying osteoarthritis agent, that contains chondroitin sulfate, purified glucosamine, and manganese ascorbate (CS-G-M), on thyroid function in dogs. Forty-six healthy (except for osteoarthritis) euthyroid dogs were blindly assigned to 3 treatment groups: meloxicam, carprofen, and CS-G-M. Each group received the recommended dose of the drug for 60 days. Sixteen other osteoarthritic euthyroid dogs, which received a placebo, were used as a control group to validate the study. For all groups, blood samples were collected on days 0, 30, and 60 to evaluate the serum total and free thyroxine, and endogenous thyrotropin concentrations. There were no significant differences among the treatment groups at each time or within each group over a 60-day period for all parameters. Moreover, none of these values were within the hypothyroid range. Based on the results of this study, the administration of meloxicam, carprofen, and CS-G-M did not affect canine thyroid function evaluation.

Acral mutilation and analgesia in 13 French spaniels.

Acral mutilation and analgesia (AMA) is reported in 13 French spaniels in Canada. This newly recognized disorder shares striking similarities in clinical features and biopsy findings to the other acral mutilation syndromes or hereditary sensory neuropathies reported in German short-haired pointer dogs, English pointer dogs and English springer spaniels. Clinical signs are first noted between 3.5 and 12 months of age. Affected dogs lick, bite and severely self-mutilate their distal extremities resulting in ulcers with secondary bacterial infection. Auto-amputation of claws, digits and footpads occurs in severe cases. Single or multiple feet can be affected. Affected dogs walked on their severely mutilated feet without evidence of pain, lameness, or ataxia. The majority of the dogs were euthanized within days to months of diagnosis.

Isotype determination of circulating autoantibodies in canine autoimmune subepidermal blistering dermatoses.

The three most common canine autoimmune blistering skin diseases (AISBD), bullous pemphigoid (BP), mucous membrane pemphigoid (MMP) and epidermolysis bullosa acquisita (EBA) have recently been separated based on clinical, histological and immunological grounds. The objectives of this study were to determine the isotype profiles of circulating autoantibodies in these dermatoses. Serum was collected from 5 dogs with BP, 15 with MMP and 11 with EBA. All sera were tested using an indirect immunofluorescence method using salt-split canine gingiva as substrate. Anti-basement membrane IgG autoantibodies were detected in all patients. Among the IgG autoantibodies, IgG1 and IgG4 were encountered most frequently, while IgG2 and IgG3 were uncovered in some dogs. IgE autoantibodies were detected more often than IgA or IgM autoantibodies in any of the three entities. The predominance of IgG1, IgG4 and IgE autoantibody isotypes in dogs with AISBD is very similar to the situation found in humans with the homologous diseases.

Résumé Il a été récemment possible de différencier les trois plus fréquentes dermatoses bulleuses sous-épidermiques (pemphigoide bulleuse [BP], pemphigoïde des muqueuses [MMP] et épidermolyse bulleuse acquise [EBA]) sur la base de critères cliniques, histologiques et immunologiques. Les buts de cette étude étaient de déterminer les profils isotypiques des autoanticorps circulants dans ces maladies. Le sérum de 5 chiens à BP, 15 chiens à MMP et 11 chiens à EBA a été collecté et testé en utilisant une méthode d'immunofluorescence indirecte avec comme substrat une gencive canine clivée par le sel. Des autoanticorps IgG anti-membrane basale ont été détectés chez tous les patients. Parmi ces IgG, les IgG1 et IgG4 étaient rencontrées le plus souvent, alors que les IgG2 et IgG3 étaient absentes chez certains chiens. Des autoanticorps IgE étaient plus fréquemment rencontrés que des IgA ou des IgM pour les trois maladies. La prédominance d'IgG1, IgG4 et IgE chez les chiens présentant une dermatose auto-immune bulleuse sous-épidermique est très semblable à la situation rencontrée chez les patients humains souffrant de maladies équivalentes.

Resumen Las tres enfermedades ampollosas y autoinmunes de la piel más frecuentes en la especie canina, penfigoide bulloso (PB), penfigoide de las membranas mucosas (PMM) y epidermólisis bullosa adquirida (EBA), se han separado recientemente en términos clínicos, histológicos e immunológicos. Los objetivos del estudio fueron determinar el perfil de isotipos de autoanticuerpos circulantes en estas dermatosis. Se tomaron muestras serológicas de cinco perros con PB, 15 con PMM y 11 con EBA. Todos los sueros fueron analizados mediante un método indirecto de immunofluorescencia utilizando separación por NaCl (salt-split) y encía canina como substrato. Se detectaron autoanticuerpos IgG antimembrana basal en todos los pacientes. De los autoanticuerpos IgG, los isotipos IgG1 e IgG4, se hallaron con más frecuencia, mientras que los IgG2 e IgG3 fueron detectados sólo en algunos perros. Autoanticuerpos IgE fueron detectados más a menudo que los autoanticuerpos IgA o IgM en las tres entidades. El predominio de los isotipos de autoanticuerpos IgG1, IgG4 e IgE en perros con enfermedades ampollosas autoinmunes de la piel es muy similar a la situación encontrada en humana con enfermedades homólogas.

Hereditary nasal parakeratosis in Labrador Retrievers.

Hereditary nasal dermatitis is reported in 14 Labrador Retrievers and 4 Labrador Retriever crosses. This appears to be a newly described inherited disorder for which an autosomal recessive mode of inheritance is suspected. The lesions were first noted between 6 and 12 months of age. Histopathological analysis revealed parakeratotic hyperkeratosis, often with marked multifocal accumulation of proteinaceous fluid between keratinocytes within the stratum corneum and superficial stratum spinosum. There was also a sub-basal lymphoplasmacytic infiltration within the superficial dermis. Immunohistochemistry staining for IgG (n = 4), distemper and papillomaviruses (n = 4) were negative, as were serum antinuclear antibody serology (n = 4) and fungal culture (n = 7). Electron microscopy revealed an altered cornification process: retention of nuclear chromatin, absence of lamellar bodies and marked intercellular oedema. Dogs did not respond to oral administration of zinc methionin (n = 3), cephalexin (n = 4), vitamin A alcohol (n = 1) or topical tretinoin (n = 1). Improvement of the lesions was obtained with topical vitamin E (n = 2), petroleum jelly (n = 2), and propylene glycol (n = 5).