An immunohistochemical study of uveodermatologic syndrome in two Japanese Akita dogs

MATERIALS: Ocular and cutaneous tissues from two Japanese Akita dogs with uveodermatologic syndrome (UVD) were subjected to immunohistochemical analysis. RESULTS: Light microscopic examination of the globes confirmed the presence of panuveitis of different severity in each case. The infiltrate was primarily granulomatous with prominent perivascular lymphoid aggregates. Melanophages were present throughout the affected areas, and there were scattered plasma cells. Immunohistochemistry using CD79a, CD3, MAC387 and MHC class II markers indicated that there were relatively few T lymphocytes and that most lymphocytes were of the B-cell lineage. The two skin biopsies examined also appeared to represent different stages of cutaneous pathology. The biopsy from one case was consistent with the reported features of skin lesions of canine UVD syndrome, including granulomatous dermatitis with extensive T-cell infiltration extending into the epidermis. In contrast, the skin lesion from the second case showed less inflammation, more pigmentary incontinence and evidence of dermal fibrosis. There was no immunoglobulin or complement deposition at any level within the cutaneous or ocular lesions. CONCLUSIONS: The findings of these two cases suggest that the skin lesions of these two dogs with UVD syndrome were mediated by T cells and macrophages (Th1 immunity), whereas the ocular lesions were more consistent with a B cell and macrophage response (Th2 immunity). This is, however, a preliminary investigation and these features may not be the same for all cases of UVD syndrome.     

Possible immunodeficiency in related rottweiler dogs

A litter of eight rottweiler pups is described in which two dogs died before the age of six months from systemic inflammatory disease, and two further pups developed inflammatory skin disease. All seven pups tested had a markedly low serum immunoglobulin A (IgA) concentration (< 0.1 mg/ml) and six of these dogs also had subnormal serum IgG (< 0.1 to 6.4 mg/ml). Tissues taken from three diseased pups were examined immunohistochemically using a number of lymphoid markers. Secondary lymphoid tissues had a paucity of CD3+ T lymphocytes, although T cells were found within some inflammatory foci. B-lymphocyte follicles were present within lymphoid tissues, but there were irregularities of plasma cell development and a lack of plasma cells of all classes within mucosal and cutaneous sites. Inflammatory lesions were dominated by macrophages expressing class II molecules of the major histocompatibility complex. Serum immunoglobulins were also investigated in eight related, clinically normal adult dogs. Five of these dogs, from two separate breeding lines, had subnormal serum IgA (< 0.1 to 0.15 mg/ml). The spectrum of disease within the affected litter may be consistent with an underlying inherited immunological defect, and the observed immunological abnormalities suggest a more complex disorder than simple IgA deficiency.     

Hepatic Ultrasonography and Pathological Findings in Dogs With Hepatocutaneous Syndrome: New Concepts

In dogs, hepatocutaneous syndrome (superficial neurolytic dermatitis) belongs to a group of syndromes in which cutaneous signs signal the presence of systemic disease. It is characterized by parakeratosis, superficial necrolysis, and basilar hyperplasia of the epidermis, in association with an unusual hepatopathy accompanied by certain metabolic derangements. Hepatocutaneous syndrome was diagnosed in 3 dogs on the basis of typical dermatologic changes and clinicopathologic findings. Hepatic ultrasonography revealed a hyperechoic network surrounding hypoechoic areas of parenchyma, resulting in a Swiss cheese-like appearance. The ultrasonographic image corresponded to the pathological findings. The liver had a nodular appearance, both grossly and microscopically; this was attributed to collapse of the areas of parenchyma surrounding the nodules, rather than to the cirrhosis and/or nodular hyperplasia reported previously.     

Efficacy of once-daily clindamycin hydrochloride in the treatment of superficial bacterial pyoderma in dogs.

Twenty-one dogs with canine superficial bacterial pyoderma were treated with clindamycin at a dosage of approximately 11 mg/kg body weight, q 24 hours, given orally for 14 to 42 days. All dogs were reexamined on days 14, 28, and, if necessary, 42 and given a clinical score of excellent (i.e., complete remission), good (i.e., primary lesions resolved but secondary lesions evident), fair (i.e., partial improvement but primary lesions still evident), or poor (i.e., no improvement or worsening of the lesions). A clinical score of excellent was obtained in 71.4% (15/21) of the dogs in this study within 14 to 28 days.     

Superficial eosinophilic gastritis in laboratory beagle dogs attributable probably to diet

Stomach tissues from 222 beagle dogs, which were used for toxicological studies, were examined histopathologically. Out of 190 dogs fed the same diet, 185 had gastric lesions, whereas all of 32 dogs fed another diet were free from them. The gastric lesions were noted as an accumulation of eosinophils, infiltration of inflammatory cells including lymphocytes, plasma cells and histiocytes in the gastric lamina propria, formation of foreign body type multinucleated giant cells, focal desquamation and papillary proliferation of mucosal epithelium. The lesions were confined to the superficial layer of the antral and pyloric mucosa, and neither desmoplasia nor clinical signs were seen. Multinucleated giant cells often contained amphophilic foreign bodies of varying appearance with inconsistent reaction for periodic acid-Schiff (PAS), but no definite causal agents were detected.     

Clinical considerations on canine visceral leishmaniasis in Greece: a retrospective study of 158 cases (1989-1996).

The medical records of 158 dogs with visceral leishmaniasis confirmed cytologically and/or serologically were reviewed. Ages of affected dogs varied from nine months to 15 years, with a male-to-female ratio of 1.3. The most common clinical manifestations of the disease were variable cutaneous lesions such as exfoliative dermatitis and skin ulcerations, chronic renal failure, peripheral lymphadenopathy or lymph node hypoplasia, masticatory muscle atrophy (i.e., chronic myositis), ocular lesions (i.e., conjunctivitis, keratoconjunctivitis sicca, blepharitis, and uveitis), and poor body condition. Ascites, nephrotic syndrome, epistaxis, polyarthritis, and ulcerative stomatitis were seen only in a small number of cases. Clinical splenomegaly was not a common finding. The clinicopathological abnormalities were nonregenerative anemia, hyperproteinemia, glomerular proteinuria, and symptomatic or asymptomatic azotemia. In this study, an indirect immunofluorescence assay's diagnostic sensitivity was found to be higher than that of lymph node aspiration cytology.     

Chronic hypertrophic pyloric gastropathy as a cause of pyloric obstruction in the dog

Six small-breed, middle-age dogs with a history of chronic intermittent vomiting had benign pyloric lesions causing gastric outlet obstruction. Marked similarities were found in clinical signs, pathologic changes, and treatment results. The condition was classified as a syndrome and was named chronic hypertrophic pyloric gastropathy. The appearance of the obstructive lesions at surgery were various forms of mucosal hypertrophy. Microscopically, the syndrome was characterized by mucosal foveolar and glandular hyperplasia, cystic glandular dilatation, superficial mucosal ulcerations, and various cellular infiltrates. The affected dogs were successfully treated by surgical correction of the gastric outlet obstruction.     

Immunohistochemical evidence for immunoglobulin and complement deposition in spinal cord lesions in degenerative myelopathy in German shepherd dogs.

The purpose of this study was to examine the distribution of immunoglobulin and complement component C3 in spinal cord tissues of dogs with degenerative myelopathy. Sections of formalin-fixed paraffin-embedded spinal cord from five German Shepherd dogs with clinical and histological features consistent with degenerative myelopathy (DM) and one normal dog were tested immunohistochemically for deposition of immunoglobulin G (IgG) and the third component of complement (C3). In all dogs there was staining associated with large and small blood vessels. In addition, in the dogs with DM there was focal staining for IgG and C3 in spinal nerve tracts characteristically affected in DM. Deposition of IgG and C3 was found in histological lesions, and in addition, in other areas independent of visible lesions, suggesting that IgG and C3 deposition may precede histological evidence of spinal cord damage. These findings suggest a role for immune-mediated destruction of the spinal cord which may contribute to the pathogenesis of DM in German Shepherd dogs.     

Use of human immunoglobulin for treatment of severe erythema multiforme in a cat

A 5-month old female domestic shorthair cat developed lethargy and severe ulcerative skin lesions that covered more than half of its body after routine administration of rabies vaccine, anthelmintic, and ear medication. Clinical and histologic findings were consistent with a severe cutaneous drug reaction or erythema multiforme. The cat's condition continued to deteriorate despite drug withdrawal and supportive care. Administration of human intravenous immunoglobulin was well tolerated by the cat and led to rapid resolution of ulcerative cutaneous lesions, accompanied by substantial improvement in the cat's demeanor within 8 days. Human intravenous immunoglobulin appears to be a novel promising treatment for life-threatening cutaneous drug reactions.     

Mycobacterial nodular granulomas affecting the subcutis and skin of dogs (canine leproid granuloma syndrome)

Objective To obtain a better understanding of a disease affecting dogs in which nodular mycobacterial granulomas are present in the subcutis or skin. Design Retrospective survey Procedure A diagnosis of an unidentified mycobacterial infection was made in 45 dogs following detection of acid-fast bacilli surrounded by granulomatous or pyogranulomatous inflammation in tissue sections. Eight cases were identified from the records of our diagnostic laboratory. In all cases culture for mycobacteria was unsuccessful. Another 37 cases were identified by practitioners and veterinary pathologists in response to a survey mailed to veterinary clinics throughout Australia. Data from these 45 cases were entered into a data base. The data set was incomplete, as some respondents did not answer all questions. Results Over 90% of affected dogs had short coats and about half were Boxers or Boxer-cross dogs. A weak seasonal trend for the development of primary lesions in autumn and winter was identified. Cases were recorded from New South Wales (35 dogs), Western Australia (4), Queensland (4), Tasmania (1) and New Zealand (1). The subcutis and skin of the ears and head (including the ears) were involved in 64% and 85% of cases, respectively, for which lesion site was recorded. Culture was attempted but was unsuccessful in 19 cases, including 11 cases where material was submitted to our laboratory and/or a Mycobacteria Reference Laboratory. Lymph node enlargement, internal organ involvement or constitutional signs were not a feature of the syndrome, and most lesions did not worry the dogs. Although many practitioners recorded a favourable response to therapy with doxycycline (response rate 57%) or amoxycillin-clavulanate (63%), spontaneous resolution of infection was thought to have occurred in six of seven dogs (86%) not given systemic antimicrobials, and three dogs where antimicrobials had failed previously. A minority of cases failed to respond to antimicrobial therapy and continued to have chronic lesions. There was no discernible trend for dogs of a particular age or sex to be affected. Conclusion This syndrome is caused by saprophytic mycobacteria of limited pathogenicity that give rise to lesions restricted principally but not exclusively to the subcutis and skin of body extremities. Fastidious growth requirements have prevented their isolation on synthetic media used for culture of mycobacteria. Organisms presumably enter the subcutis following a breach in integrity of the epidermal barrier and produce self-limiting disease in immunocompetent dogs. Lesions tend to resolve spontaneously. The possibility of a public health threat from affected dogs is highly unlikely.     

Use of lufenuron for treating fungal infections of dogs and cats: 297 cases (1997-1999)

OBJECTIVE: To evaluate use of lufenuron for treating cutaneous fungal infections in dogs and cats. DESIGN: Retrospective study. ANIMALS: 156 dogs and 201 cats with dermatophytosis or superficial dermatomycoses. PROCEDURE: Medical records were reviewed for dogs and cats that had been treated for dermatophytosis or other fungal infections by administration of lufenuron and 18 dogs and 42 cats that were not treated and served as a control group. RESULTS: Dogs were treated once by oral administration of lufenuron tablets at doses ranging from 54.2 to 68.3 mg/kg (24.6 to 31.0 mg/lb) of body weight. Samples of skin, scrapings, and hair were obtained daily from 14 dogs with dermatophytosis; mean durations from time of treatment to time of negative fungal culture results and resolution of gross lesions were 14.5 and 20.75 days, respectively. In all treated dogs, gross lesions resolved within approximately 21 days. Cats were treated once by oral administration of lufenuron suspension in doses ranging from 51.2 to 266 mg/kg (23.3 to 120.9 mg/lb). Samples were obtained daily from 23 cats; mean durations from time of treatment to time of negative fungal culture results and resolution of gross lesions were 8.3 and 12 days, respectively. Time to resolution of lesions in most untreated control animals was approximately 90 days. Adverse effects of treatment were not detected. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study suggest that lufenuron provides an effective, convenient, and rapid method for treating fungal infections in dogs and cats.     

Iatrogenic hyperadrenocorticism in 28 dogs.

Twenty-eight dogs with iatrogenic hyperadrenocorticism were studied. The most common clinical signs were cutaneous lesions (27/28), polydipsia (21/28), polyuria (19/28), and lethargy (16/28). The most predominant findings on biochemical profile were elevated alkaline phosphatase (ALP, 15/28) and alanine transferase (ALT, 14/28); hypercholesterolemia (14/28); elevated aspartate transferase (AST, 12/28); and elevated triglycerides (12/18). Baseline cortisol levels of all 28 dogs were at the lower end of the reference range and exhibited suppressed or no response to adrenocorticotropic hormone (ACTH) stimulation. The mean time for each dog to show initial improvement of clinical signs after corticosteroid withdrawal was six weeks, with another mean time of 12 weeks to demonstrate complete remission.     

Pilot investigation of a model for canine atopic dermatitis: environmental house dust mite challenge of high-IgE-producing beagles, mite hypersensitive dogs with atopic dermatitis and normal dogs

Although canine atopic dermatitis (cAD) is common, few models are available. The aim of this study was to evaluate high-IgE beagles epicutaneously sensitized to house dust mite (HDM) as a possible model for cAD. Six high-IgE beagles were environmentally challenged with HDM using various doses and protocols. Similar challenge protocols were used in positive and negative control dogs: three dogs with naturally occurring cAD and positive intradermal skin test (IDT) to HDM and three normal dogs without history of skin disease and negative IDT to HDM. All high-IgE beagles and all atopic dogs developed severe cutaneous lesions and pruritus after challenge. Lesions were erythematous papules and macules in contact areas such as face, ears, ventral abdomen, groin, axillae and feet. They were first visible after 6 h and increased in severity over time. No normal dog developed pruritus or lesions. Biopsies of representative lesions in the high-IgE beagles were taken for histopathology and immunohistochemistry. There was superficial perivascular dermatitis with mononuclear infiltrates and spongiosis. Lymphocytes and eosinophils accumulated in small epidermal micro-abscesses with hyperplasia of epidermal IgE-bearing dendritic cells. These findings suggest that this colony of high-IgE beagles develops a dermatitis that clinically, histopathologically and immunologically resembles the naturally occurring canine disease. It is also concluded that this modality of challenge is not irritating to normal dogs but induces flare-ups in hypersensitive atopic dogs.     

Idiopathic telangiectasia in a Golden Retriever

A case report of a 12-year-old spayed female Golden Retriever with a 4-month history of persistent diffuse erythema involving the right and left antebrachia is presented. Cutaneous biopsies revealed superficial dermal vascular dilation and proliferation with moderate epidermal acanthosis. Diagnostic tests failed to reveal an underlying aetiology. Telangiectasia is defined as a permanent dilation of pre-existing blood vessels creating small focal lesions. Generalized essential telangiectasia of humans is common in women of middle-age and can involve entire segments of the body. Lesions predominantly affect the extremities and can persist for years without any systemic effects. The cutaneous lesions in this case have remained static for 3 years with no manifestation of systemic signs. A diagnosis of idiopathic telangiectasia was made based on the clinical and histological findings in the dog of this report. The lesions described in this dog resemble generalized essential telangiectasia of humans.     

Clinicopathologic characterization of canine juvenile cellulitis

The syndrome of canine juvenile cellulitis was observed and characterized throughout its clinical course when it occurred spontaneously in a litter of dogs. Histologically, pyogranulomatous inflammation was seen in facial skin and mandibular and superficial cervical lymph nodes of affected dogs. The predominant inflammatory cell characterized by light and electron microscopy and by immunohistochemical staining was an epithelioid macrophage. The same pyogranulomatous inflammatory process was seen in a lymph node anatomically distant from the site of apparent disease. Interestingly, a littermate with neither clinically evident dermal lesions nor lymphadenopathy had histologic evidence of a milder, but similar inflammatory process in a mandibular lymph node. The observation of canine juvenile cellulitis in clusters of dogs between 1 and 4 months of age and its apparent systemic nature suggest an infectious etiology. Bacterial, fungal, or viral agents were not isolated from affected lymph nodes. Attempts to transfer the disease by inoculation of neonatal puppies with tissue from affected dogs were also unsuccessful.     

Familial cutaneous vasculopathy of German shepherds: clinical, genetic and preliminary pathological and immunological studies.

A genodermatosis affecting the German shepherd breed has been recognized in 26 dogs in Ontario since 1991. Clinical signs, first noted in young puppies, are manifested as pyrexia and lethargy. The main cutaneous lesions are footpad swelling and depigmentation, but there is also crusting and ulceration of ear tips and tail tips, and focal depigmentation of the nasal planum. Affected puppies show no consistent abnormalities in hematological or biochemical parameters, and immunological tests (antinuclear antibody and rheumatoid factor titer, immunoglobulin levels, and CD4+ and CD8+ T-lymphocyte percentages) are normal. Bone marrow analysis has shown myeloid hyperplasia in 5 of 7 cases and myelofibrosis has been detected in 1 case. All but 3 of the 19 clinical cases have been strongly positive for platelet factor-3; however, normal puppies routinely develop positive platelet factor-3 tests. Furthermore, affected pups all had normal numbers of platelets on repeat complete blood counts. Light microscopic examination of footpad biopsies reveals a multifocal nodular dermatitis in which neutrophils and mononuclear inflammatory cells surround foci of dermal collagenolysis, and degenerative and inflammatory vessel lesions. Depigmented lesions have a mild, cell-poor, interface dermatitis, characterized by single cell necrosis of the basal cells, in addition to the nodular dermatitis. Similarities and differences between this disease, a condition known as collagen disorder of the footpads of German shepherds and other forms of cutaneous vasculitis in the dog are discussed. The cause and the pathogenesis of the disease are yet to be elucidated; however, pedigree analysis indicates an autosomal recessive inheritance pattern.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of prednisone and azathioprine on circulating immunoglobulin levels and lymphocyte subpopulations in normal dogs.

This study investigates serum immunoglobulin (SIg) levels and lymphocyte subpopulations in normal dogs in response to putative immunosuppressive doses of prednisone and/or azathioprine. The objectives were to quantify SIg levels and lymphocyte subpopulations, including Thy-1+, CD4+, CD8+ and B cells, in normal dogs both before and after the administration of prednisone and/or azathioprine at 2 mg/kg, PO, each. Eighteen beagles were divided into 3 groups of 6 dogs each. Blood samples for radial immunodiffusion assay of IgG, IgM and IgA, complete blood count (CBC)and flow cytometry were collected prior to the administration of any drugs and again after 14 d of azathioprine, prednisone or azathioprine and prednisone. Peripheral blood mononuclear cells were isolated using density centrifugation and were incubated with monoclonal antibodies reacting with CD4+, CD8+, Thy-1+ and membrane immunoglobulin. Lymphocyte subsets were quantified using flow cytometry. Azathioprine-treated dogs had no significant changes in SIg levels or lymphocyte subpopulations. Prednisone-treated dogs had significant (P < 0.05) decreases in all SIg levels, all lymphocyte subpopulations and erythrocyte numbers, and had an increase in neutrophil counts. Prednisone and azathioprine-treated dogs had significant (P < 0.05) decreases in serum IgG levels and Thy-1+ and CD8+ lymphocyte subpopulations, with an increase in the CD4:CD8. These dogs also had a significant decrease in erythrocyte number and a significant increase in the monocyte count. These findings suggest that azathioprine and prednisone in combination or prednisone alone may be useful for the treatment of T cell-mediated diseases since decreased circulating T cell levels were demonstrated following treatment. The combination of drugs or azathioprine alone may not be appropriate for treatment of acute or autoantibody-mediated immune disease, because SIg levels were minimally affected by treatment.     

An immunohistochemical investigation of canine idiopathic granulomatous scleritis

The clinical, histopathologic and immunohistochemical findings in three dogs with granulomatous scleritis are reported. The lesions of granulomatous scleritis were characterized by vasculitis, collagenolysis, granulomatous inflammation and perivascular lymphoplasmacytic aggregation. There was evidence of vascular immune complex deposition, and the inflammatory aggregates contained T lymphocytes, IgG plasma cells and macrophages expressing class II molecules of the major histocompatibility complex (MHC). There was no evidence for an infectious etiology in any case, and one of the dogs subsequently developed cutaneous vascular disease consistent with a systemic immune-mediated disorder. Canine granulomatous scleritis has an immunopathogenesis likely involving primary type IV hypersensitivity, with a probable underlying type III involvement.     

Treatment of severe adverse cutaneous drug reactions with human intravenous immunoglobulin in two dogs

Severe adverse cutaneous reactions were documented in two dogs with acute skin lesions and systemic signs after exposure to several oral and injectable drugs. Because of the high morbidity and mortality rates of many severe cutaneous drug reactions and a poor response to supportive care, wound management, and conventional immunosuppressive therapy, human intravenous immunoglobulin (IVIG) was infused on 2 consecutive days (1 g/kg per day) after informed consent was received. Human IVIG, with supportive care, resulted in rapid resolution of dermatological and systemic signs in both dogs; this treatment may be considered in other cases of severe cutaneous drug reactions.     

The cutaneous histology of dermatomyositis in collie dogs

Cutaneous lesions of 36 collie dogs affected with dermatomyositis were reviewed. The most common histologic features were follicular atrophy and perifollicular inflammation in 30 dogs, which correlated with alopecia clinically. Other less common findings included formation of colloid bodies, basal cell vacuolation, and subepidermal vesiculation. Results indicated that the most diagnostic cutaneous histologic features of dermatomyositis may be follicular atrophy and inflammation.