Evaluation of papillomaviruses associated with cyclosporine-induced hyperplastic verrucous lesions in dogs

OBJECTIVE: To determine whether cyclosporine A-induced hyperplastic skin lesions of dogs were associated with papillomavirus infections. ANIMALS: 9 dogs that were treated with cyclosporine A and developed hyperplastic skin lesions. PROCEDURE: History and clinical and histopathologic data were collected. Paraffin-embedded skin biopsy specimens from hyperplastic skin lesions were immunostained for common papillomavirus genus-specific structural antigens by use of a polyclonal rabbit anti-bovine papillomavirus type 1 antiserum. Sections from each tissue block underwent DNA extraction, and polymerase chain reaction (PCR) assays were performed with several sets of primers to amplify a wide range of papillomavirus DNA from humans and other animals. RESULTS: In 7 of 9 dogs, there were more than 10 hyperplastic skin lesions that microscopically resembled those of psoriasiform lichenoid dermatosis. In those dogs, results of testing for papillomavirus via immunohistochemical analyses and PCR assays were negative. In the other 2 dogs, there were only 1 and 3 verrucous lesions, and in those dogs, histologic evaluation revealed koilocytes and nuclear viral inclusions that were immunoreactive for papillomavirus antigens. Papillomavirus DNA was amplified from both dogs. One of the sequences was characteristic for the canine oral papillomavirus, whereas the other had similarities with the recently described canine papillomavirus 2. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, hyperplastic skin lesions occasionally develop during treatment with cyclosporine A. Most of the lesions resemble those of psoriasiform lichenoid dermatosis, although papillomavirus can be detected in some instances.     

Cutaneous neosporosis in two adult dogs on chronic immunosuppressive therapy.

Antemortem diagnosis of generalized ulcerative and pyogranulomatous dermatitis with numerous intralesional tachyzoites was made from skin biopsy specimens from 2 adult dogs on chronic immunosuppressive therapy. A 9-year-old Italian Greyhound was on long-term corticosteroid therapy for the treatment of a lupus-like systemic autoimmune disorder, and a 7-year-old Labrador Retriever had received several months of chemotherapy for lymphosarcoma. The tachyzoites were identified as Neospora caninum by immunoperoxidase immunohistochemistry. Both dogs were treated with clindamycin. Lesions in the Greyhound resolved; however, the Labrador Retriever was euthanized because of evidence of neuromuscular disease, despite improvement of the skin lesions. These 2 cases indicate that cutaneous neosporosis can occur in adult dogs on chronic immunosuppressive therapy. The disease may result from reactivation of a congenital infection and/or a recently acquired primary infection.     

Alterations of epidermal proliferation and cytokeratin expression in skin biopsies from heavy draught horses with chronic pastern dermatitis

We report the historical, clinical and histopathological characteristics of skin lesions in biopsies from 37 heavy draught horses with chronic pastern dermatitis. The skin lesions were divided into four macroscopic groups: scaling (group I, n=5), hyperkeratotic and hyperplastic plaque-like lesions (group II, n=14), nodular skin masses (group III, n=16) and verrucous skin lesions (group IV, n=2). The principal histological findings were hyperkeratosis and epidermal hyperplasia. There was a gradual increase in epidermal hyperplasia from groups I to IV, suggesting that the lesions represent different stages of disease. In all cases, there was perivascular dermatitis dominated by T lymphocytes with an increase in MHC class II-positive dendritic-like cells. Immunohistochemical labelling for cytokeratins CK5/6(4), CK10 and CK14 indicated a change in their expression pattern. This correlated with the degree of epidermal hyperplasia, indicating abnormal differentiation of keratinocytes. There was a statistically significant correlation between the severity of skin lesions and several other factors including increasing age, increasing cannon circumference, prominence of anatomical structures such as fetlock tufts of hairs, ergots and chestnuts, and bulges in the fetlock region.     

Recurrent zinc-responsive dermatosis in a Siberian Husky

Zinc-responsive dermatosis was diagnosed in a Siberian Husky. Oral therapy with zinc sulphate (50 mg essential zinc) resulted in complete clinical recovery, proven by histological examination after one month. Discontinuation of a one-year-lasting treatment resulted in relapse with identical skin lesions within two months, but resumption of the therapy once more resulted in complete healing.     

In vivo long-term effects of retinoic acid exposure in utero on induced hyperplastic epidermal foci in murine skin

Adult Naval Medical Research Institute (NMRI) mice, after prenatal exposure to retinoic acid (RA), were treated with a standard two-stage skin carcinogenesis regime to characterize hyperplastic epidermal foci that precede the appearance of cutaneous papillomas, and to investigate the in vivo long-term action of RA on adult mouse skin treated with DMBA (7,12 dimethyl benz[a]anthracene) and TPA (12-O-tetradecanoylphorbol 13-acetate). The results demonstrate that RA administered to pregnant mice had a long-term inhibitory action on the cell differentiation and development of hyperplastic lesions occurring prior to cancer on the adult skin of their offspring as well as a stimulatory effect on cell proliferation of these hyperplastic lesions.     

Cutaneous papillomatosis and carcinomatosis in the Western barred bandicoot (Perameles bougainville)

A progressive wart-like syndrome in both captive and wild populations of the Western barred bandicoot (WBB) is hindering conservation efforts to prevent the extinction of this endangered marsupial. In this study, 42 WBBs exhibiting the papillomatosis and carcinomatosis syndrome were examined. The disease was characterized by multicentric proliferative lesions involving cutaneous and mucosal surfaces, which were seen clinically to increase in size with time. Grossly and histologically the smaller skin lesions resembled papillomas, whereas the larger lesions were most commonly observed to be squamous cell carcinomas. Large amphophilic intranuclear inclusion bodies were observed in hyperplastic conjunctival lesions of 8 WBBs under light microscopy. Conjunctival lesions from 2 WBBs examined using transmission electron microscopy contained a crystalline array of spherical electron-dense particles of 45-nm diameter, within the nucleus of conjunctival epithelial cells, consistent with a papillomavirus or polyomavirus. Conjunctival samples from 3 bandicoots that contained intranuclear inclusion bodies also demonstrated a positive immunohistochemical reaction after indirect immunohistochemistry for papillomavirus structural antigens. Ultrastructural and/or immunohistochemical evidence of an etiologic agent was not identified in the nonconjunctival lesions examined. Here we describe the gross, histopathologic, ultrastructural, and immunohistochemical findings of a papillomatosis and carcinomatosis syndrome recently identified in the WBB.     

Pulmonary congestion and edema (marble spleen disease) of chickens produced by group II avian adenovirus

"Marble spleen disease" of chickens was diagnosed in 22-week-old chickens. Total mortality was 8.9%. Deaths occurred over a period of 2 months. Gross lesions included pulmonary congestion, splenomegaly, hepatomegaly, and congestion of egg follicles. Microscopic lesions included pulmonary congestion and edema, and reticuloendothelial cell hyperplasia of the spleen with concurrent white-pulp necrosis and lymphocyte depletion. The pulmonary lesions were of sufficient intensity to have caused the death of fatally affected birds. Many of the hyperplastic reticuloendothelial cells contained basophilic intranuclear inclusions similar to those that characterize hemorrhagic enteritis of turkeys, marble spleen disease of pheasants, and adenovirus group II splenomegaly of chickens. These characteristic lesions, plus serologic identification of the causal virus, indicate that "marble spleen disease" caused by avian group II adenovirus was affecting the flock under study. This appears to be the first report of death of chickens due to pulmonary congestion and edema caused by spontaneous infection with avian group II adenovirus.     

Dermatophytic pseudomycetomas in four cats

The aim of this retrospective study was to describe the clinical characteristics and treatment of four cats with dermatophytic pseudomycetoma. Four Persian cats, one female and three males, with age ranging from 1.4 to 5 years, were diagnosed with dermatophytic pseudomycetoma by histological examination and fungal culture. Wood's lamp examination revealed positive fluorescence of hairs in all four cats. Characteristic skin lesions consisted of multifocal, raised, firm and nodular to dome-shaped lesions varying in size from 1 to 8 cm in diameter, with ulcers or fistulas in some of the lesions. One cat was treated and cured with 3 months of oral itraconazole; lesions completely regressed, and at the time of writing there has been no recurrence. One cat was treated with surgical excision alone, and recurrence of lesions occurred after a disease-free interval of 15 months. Two cats were treated with surgical excision and systemic itraconazole therapy. Itraconazole therapy was started 1-2 months before surgery and continued for 3 months after surgery. Surgical margins were wide in both cats, and underlying adipose tissue and/or deeper fascia was removed. One cat relapsed, but had a disease-free interval of 18 months. The other cat has been disease free for 32 months. This case series suggests that aggressive, wide surgical excision and concurrent oral itraconazole are highly beneficial in treating dermatophytic pseudomycetoma in cats.     

Severe persistent orf in young goats.

Orf (contagious ecthyma) is a viral disease of small and wild ruminants, humans, and less frequently other species. In sheep and goats, the disease is characterized by the formation of vesiculo-proliferative lesions in the skin of lips and nostril. Here, a form of generalized orf in 16 goat kids from 2 different locations in west Texas is described. The disease was characterized by multifocal, severe, proliferative dermatitis that persisted from about 2 months of age until the goat kids were euthanized 3 months later. All affected goats were Boer or Boer crosses under 1 year of age. The mean immunoglobulin concentration in sera of affected goats was elevated compared with healthy control goats. Severe to moderate lymphadenomegaly of the nodes draining the areas of the skin affected with orf lesions was present in all 16 goat kids. Suppurative arthritis, chronic fibrinous pneumonia, and premature thymic involution were found in 3, 5, and 7 of the goat kids, respectively. The skin lesions of 3 goat kids were infested with larvae of the opportunistic black garbage fly (Ophira sp.). The orf virus was identified in skin lesions by isolation in Marbin-Darby ovine kidney cells, electron microscopy, and amplification of viral DNA by polymerase chain reaction. The orf virus was not detected in peripheral blood or lymph node mononuclear cells of any of the goats. Cross-neutralization experiments showed that an ovine orf virus antiserum raised in sheep was more effective in neutralizing a sheep orf virus isolate than a caprine orf virus isolate. The clinical and epidemiological characteristics of these orf cases may be the result of susceptibility factors within some individuals of the Boer breed of goats.     

Emperipolesis of hematopoietic cells within megakaryocytes in bone marrow of the rat

Emperipolesis of hematopoietic cells within megakaryocytes was found in rats. The incidence was less than 0.3% in young rats (2 to 12 months old) but increased to 2-5% among the aging rats (18 to 24 months old). The incidence increased markedly in hyperplastic bone marrow secondary to chronic suppurative or neoplastic lesions. Mature neutrophils appeared to be the most common marrow cell engulfed by megakaryocytes. By light microscopy, engulfed cells were separated from megakaryocyte cytoplasm by a narrow pericellular space. By electron microscopy, marrow cells engulfed by megakaryocytes were located in the open canalicular system. Cell membranes of both engulfed cells and megakaryocytes were intact, and there was no fusion of cell membranes or phagosome formation in the megakaryocytes.     

Dermatographism in a horse,responsive to cetirizine treatment

Dermatographism is a common condition in man that occurs when pressure is applied to the skin and mast cells are triggered to release histamine, causing local urticarial lesions. This case report concerns a 4-year-old Quarter Horse gelding that was presented with pressure induced urticaria. Moderate pressure on the skin induced nonpruritic urticaria-like swelling after approximately 3–5 min, which lasted for approximately 2–3 h. Initial treatment with cyproheptadine gave an incomplete response and unacceptable sedation as a side effect. On the second generation antihistamine cetirizine (0.2 mg/kg bwt twice daily), dermatographism was no longer present and no side effects occurred. Treatment was continued for 4 months, with at least three attempts to discontinue therapy resulting in recurrence of lesions within 24 h. Lesions resolved each time within 24 h of recommencing therapy. Dermatographism did not recur after the horse was moved to another location despite discontinuation of therapy. This report describes a case of equine dermatographism responsive to cetirizine.     

A case of diet-related lymphocytic mural folliculitis in a cat

A 5-year-old cat developed a raised hair coat and adherent crusting lesions involving the skin of the head, dorsal neck and abdomen. Erosions were present on the lips and eyelids. The footpads were dry and scaly. Histopathology revealed infiltrative lymphocytic folliculitis, moderate lymphocytic infiltration into the epidermis and apoptotic epidermal cells. A restricted diet as the only therapy resulted in gradual resolution of the skin lesions. Despite an improvement in the dermatological condition, the cat increasingly lost all appetite and marked weight loss occurred. The cat died 4 months after presentation. Post-mortem revealed a perforated gastric ulcer and a mild to moderate inflammatory bowel disease. The clinical course of lesion resolution in this cat suggested a diet-related pathogenesis. The late finding of intestinal disease in a patient with diet-related skin disease is still interesting and needs to be evaluated by further case studies.     

Cutaneous inverted papillomas in dogs

Inverted papillomas of the skin occurred in five dogs. Lesions were 1-2 cm, circumscribed, flask-like structures below the level of the surrounding normal skin. Walls of the structures consisted of hyperplastic epidermis, forming thin papillary projections on thin fibrovascular stalks. Cells in the stratum granulosum had clear cytoplasm, numerous keratohyalin-like granules of various sizes, and poorly defined intranuclear inclusions. These cells stained positively for papillomavirus group-specific antigens by both the peroxidase-antiperoxidase and avidin-biotin methods. Virions with a mean diameter of 35.7 nm were present within nuclei in cells of the stratum granulosum when examined by electron microscopy. In situ DNA hybridization, using a canine oral papillomavirus probe, localized papillomavirus DNA in canine oral papillomas, but not in canine cutaneous squamous or inverted papillomas, suggesting that a different papillomavirus type was present in the latter lesions. Although these lesions resembled intracutaneous cornifying epitheliomas (keratoacanthomas), they appear to be a distinct lesion, probably with a different etiology.     

Long‐Term Management with Adipose Tissue‐Derived Mesenchymal Stem Cells and Conventional Treatment in a Dog with Hepatocutaneous Syndrome

Hepatocutaneous syndrome (HS) is an uncommon skin disorder that occurs in conjunction with liver disease and is diagnosed based on decreased plasma concentrations of amino acids and the histopathology of skin lesions. The survival period generally is <6 months. A 10‐year‐old castrated male Maltese dog was presented for evaluation of lethargy, polyuria, polydipsia, and skin lesions including alopecia, erythema, and crusts. Based on increased liver enzyme activity, low plasma amino acid concentrations, and findings from liver cytology and skin biopsy, the dog was diagnosed with HS. In addition to administration of antioxidants, hepatoprotective agents, and amino acids IV, allogenic adipose tissue‐derived mesenchymal stem cells were infused 46 times over a 30‐month period: 8 times directly into the liver parenchyma guided by ultrasonography and the remainder of the times into peripheral veins. After commencing stem cell therapy, the dog's hair re‐grew and the skin lesions disappeared or became smaller. During ongoing management, the patient suddenly presented with anorexia and uncontrolled vomiting, and severe azotemia was observed. The dog died despite intensive care. On necropsy, severe liver fibrosis and superficial necrolytic dermatitis were observed. The dog survived for 32 months after diagnosis. A combination of amino acid and stem cell therapy may be beneficial for patients with HS.     

Morphea-like lesion in a cat

Scleroderma is a rare chronic disease of connective tissues, involving the skin and/or internal organs in humans, and rarely described in the dog. A case is reported of localised scleroderma in a cat which presented with two well delineated alopecic, sclerotic, raised and shiny lesions localised on the trunk. Diagnosis was made by histopathological examination of skin biopsies which showed the replacement of all dermal components by dense thick collagen bundles. No therapy was instituted and a spontaneous recovery occurred three months later. Clinical and histopathological aspects of this feline dermatosis are compared with human and canine morphea.     

Demonstration of papillomatosis in nutrias (Myocastor coypus Molina)]

The occurrence of the papillomatous disease of the coypu having a contagious character was recorded for the first time in Czechoslovakia in 1975. The papillomatous lesions of the size of a pea to bean occurred on the skin of the extremities, tail head and in the oral and nasal cavities. The females were affected first, followed by their young and then by the young borne by healthy mothers after contact with the diseased animals. On the whole the disease affected 57 animals (60%). The disease spontaneously disappeared within 2.5 to 3.5 months of the occurrence of the papillomatous lesions. The virus etiology of the disease was demonstrated by means of the electron-microscopic detection of virus particles the structure of which corresponded to that of the papillomatous viruses.     

Treatment of equine onchocerciasis with ivermectin paste

SUMMARY A single oral dose of ivermectin paste was administered to 12 horses with dermatitis and clinical signs typical of onchocerciasis. Two of the horses also had lesions of Queensland itch. Microfilarias of Onchocerca cervicalis were identified in fresh, macerated, skin biopsies from the neck, brisket or umbilical regions of all horses and microfilarias of O. gutturosa from the neck of 2. Eight of the horses developed skin reactions 4 to 24 h after the administration of the ivermectin, notably weals over the neck, shoulders and flanks and pitting oedema of the ventral midline and intermandibular space. Regression of the onchocerciasis lesions was evident within 7 days of treatment and affected skin had returned to normal within 3 months. The lesions of Queensland itch were not affected by the ivermectin treatment. Microfilarias were present in biopsies of skin, particularly in the superficial dermis, before treatment, but were absent from all skin biopsies taken one week after treatment. In some horses transient skin sensitivity reactions developed. Microfilarias began to reappear in the biopsies of some of the horses 2 months after treatment. It is concluded that the oral paste formulation of ivermectin, although not effective against adult onchocerca, is useful for the therapeutic control of microfilarias in the skin lesions of equine onchocerciasis.     

Mammary tumors in a colony of beagle dogs

In a lifetime study, female beagle dogs in a closed colony were administered 226radium and 90strontium. An unirradiated control group was included in the study. A total of 223 of 356 dogs at risk developed 1,112 mammary proliferative growths (hyperplastic nodules and neoplasms). There was no correlation between occurrence and types of lesions in radiation and control groups. The age range for first occurrence of lesions was 10.4 to 13.9 years; hyperplastic nodule and benign mixed tumor occurred 1 to 2 years earlier than other lesions. A multiplicity of growths of similar or different morphological type were common throughout the lifetime of the dog. The female beagles, collectively, developed 244 hyperplastic nodules, 78 adenomas, 694 benign mixed tumors, 78 carcinomas, 14 malignant mixed tumors, and four myoepitheliomas. Proliferations occurred with increasing frequency from the cranial to caudal mammary glands. Metastasis was found in 77% of the dogs with carcinoma. The median time from diagnosis to metastasis was 10 months, but was shorter in dogs with infiltrative carcinoma.     

Generalised granulomatous disease in a horse

A 6-year-old gelding was referred with a 3-month history of recurrent fever, inappetance, lethargy and weight loss. On clinical examination major findings were depression, thin condition, thrombophlebitis, nodules on the scrotal skin, leukocytosis, hyperfibrinogenaemia and hyperglobulinaemia. Pleural fluid and areas of lung consolidation were seen on ultrasonographic examination of the thorax. A diagnosis of chronic respiratory disease was made. Initially there was a response to antibiotic therapy but the horse was presented 3 months later with continued weight loss, recurrent fever and multifocal skin lesions, characterised by scales, crusts and nodules, affecting the nasal bridge, jugular grooves, ventral neck, withers, scrotum, prepuce, and medial gaskins. Histological evaluation of skin biopsies indicated a granulomatous reaction. On ultrasonographic examination of the thorax multiple hypoechoic lesions consistent with granulomas were seen in both lungs. A diagnosis of generalised granulomatous disease was made. The horse was euthanased at the owner's request. On necropsy examination the main findings were multiple nodules of fibrotic granulomatous inflammation in the lung, heart, liver, gastrointestinal tract and mesenteric lymph nodes, supporting the diagnosis of generalised granulomatous disease.