Evaluation of the effect of two dose rates of cyclosporine on the severity of perianal fistulae lesions and associated clinical signs in dogs

OBJECTIVE: To investigate the effect of cyclosporine (2 or 5 mg/kg every 24 hours) on perianal fistulae (PAF) lesions. STUDY DESIGN: Blinded randomized, prospective trial. ANIMALS: Dogs (n = 20) with perianal fistulae. METHODS: Dogs were randomly assigned to administration of either 2 mg/kg (n = 10) or 5 mg/kg (n=10) of cyclosporine orally every 24 hours for 8 weeks. Lesion surface area was measured, lesion severity was graded using a visual analog scale, and the presence and severity of clinical signs recorded every 2 weeks. RESULTS: Lesion variables were significantly reduced in both groups after 8 weeks and owners also reported a reduction in clinical sign severity. The 5 mg/kg dose rate significantly accelerated lesion resolution compared with 2 mg/kg. In the 2 mg/kg group, 20% of dogs had complete resolution of clinical signs and 10% had resolution of lesions. In the 5 mg/kg group, 40% of dogs had complete resolution of clinical signs and 60% had resolution of lesions. CONCLUSIONS: A dose rate of 5 mg/kg every 24 hours was more effective at reducing the surface area and severity of PAF lesions than 2 mg/kg every 24 hours but less effective at resolving PAF lesions than previous studies using dose rates > or =5 mg/kg every 12 hours. CLINICAL RELEVANCE: Cyclosporine at 5 mg/kg every 24 hours may be useful for the palliation of PAF lesions.     

Disease conditions of canine anal sacs

The literature about the anal sacs of healthy dogs and the pathogenesis, diagnosis and therapy of anal sac impaction and sacculitis are reviewed. Knowledge about the physiological role of the anal sacs is still confusing. The colour and consistency of the anal sac contents are variable in healthy dogs and there are no pathognomonic signs of anal sac impaction or sacculitis. The wide variation in macroscopic detail of anal sac secretions may give rise to misinterpretation and thus overdiagnosis of sacculitis. Other diseases such as vaginitis, flea allergy, atopy, proctitis, parasites and perianal fistulae can lead to similar signs and must be eliminated from the differential diagnosis before the anal sacs are incited as the cause of the signs. Further research is necessary on the morphological, physical and biochemical aspects of the anal sacs and their secretions to define more precise criteria for the diagnosis of impaction and sacculitis. It is imperative that controlled therapeutic trials should be performed, and such studies are indispensable for the rational therapy of anal sac disease.     

Squamous cell carcinoma of the anal sac in five dogs

Tumors of the perianal area of dogs are common and include multiple tumor types. Whereas perianal adenomas occur often, adenocarcinomas of the apocrine glands of the anal sac occur less frequently. A review of the literature revealed no reports of squamous cell carcinomas arising from the epithelial lining of the anal sac. Squamous cell carcinomas originating from the lining of the anal sac were diagnosed in five dogs. Microscopically, the tumors consisted of variably sized invasive nests and cords of epithelial cells displaying squamous differentiation. Four of the five dogs were euthanatized because of problems associated with local infiltration by the tumors. In the fifth dog, there was no evidence of tumor 7 months after surgical removal, but further follow up was not available.     

Multicentric lymphoma in a dog after cyclosporine therapy

An 11-year-old, neutered male German shepherd dog was presented with perianal ulceration and fistulas. A clinical diagnosis of anal furunculosis was made, and the dog was treated with cyclosporine and ketoconazole. The perianal lesions resolved. However, after four weeks of therapy the dog developed multicentric lymphoma. Complete remission was achieved with combination chemotherapy (Wisconsin-Madison protocol). Cyclosporine administration is associated with an increased risk of development of lymphoma in humans and a similar increased risk might be expected in dogs. Although a causative relationship between cyclosporine administration and the development of lymphoma cannot be proven in this case, it is possible that cyclosporine therapy may have contributed to lymphomagenesis. As the use of cyclosporine in small animals is increasing, further work is required to substantiate and quantify the proposed increased risk.     

Anatomic predisposition to perianal fistulae formation in the German shepherd dog

Gross and microanatomic features which may predispose the German Shepherd Dog to perianal fistulae formation were studied in 2 groups of clinically healthy dogs: a predisposed group (German Shepherd Dogs) and a control group comprising breeds not ordinarily affected by perianal fistulae. The dimensions of the anal crypts (depth, base width, and length), measured and compared statistically between samples, identified no significant variation between groups (P greater than 0.05). Major tissue components of the anal canal were measured microscopically and were similarly evaluated: epithelial height in each zone, thickness of the lamina propria in each zone, thickness of the internal and external anal sphincter muscles, and density of the circumanal, sebaceous, and apocrine sweat glands. The only significant finding was an increase in density of apocrine sweat glands in the zona cutanea in the pre-disposed dog group. In a semiquantitative analysis of the inflammatory responses frequently seen in the anal glands, more mature fibroplasia was seen in the German Shepherd Dogs, indicating that inflammation was more longstanding in this group.     

Cyclosporine treatment of anal furunculosis in 26 dogs

OBJECTIVES: To evaluate the effect of cyclosporine on anal furunculosis lesions in 26 dogs. METHODS: Lesions were graded as mild in 11 dogs, moderate in eight and severe in seven. Each dog was treated with approximately 4 mg/kg cyclosporine orally every 12 hours until the lesions resolved or showed no further improvement. Residual lesions were resected surgically. RESULTS: Eighteen dogs (69 per cent) experienced complete resolution, seven (27 per cent) improved but had residual lesions and one (4 per cent) showed no improvement. The mean duration of treatment until resolution or no further improvement was 8.8 weeks (range four to 24 weeks). Nine dogs (35 per cent) experienced recurrence. Six were from the group that had shown complete resolution and three were from the group that had surgery. Fifteen dogs (58 per cent) developed side effects to cyclosporine, although none required treatment to be discontinued. Mean duration of follow-up was 6.8 months (range one to 20 months). CLINICAL SIGNIFICANCE: Cyclosporine was effective at resolving or reducing anal furunculosis lesions in 25 of 26 dogs (96 per cent). However, residual or recurrent lesions remain a potential problem, and surgical resection or long-term cyclosporine treatment may be necessary in some dogs.     

Comparison of anal sac cytological findings and behaviour in clinically normal dogs and those affected with anal sac disease

No previous study has explored the relationship between cytology and the frequency of behaviours associated with anal sac disease (ASD). The goals of the study were: (i) to compare the cytological findings between anal sac secretions from normal dogs with no history of ASD to those with non-neoplastic ASD; (ii) to determine whether anal sac cytological findings can be used to differentiate between normal dogs and dogs with ASD; (iii) to explore the correlation of anal sac cytology and behaviour between normal dogs and dogs with ASD; and (iv) to describe behaviours typical of ASD as reported by owners. Thirty dogs were selected for this study, based on their behavioural history as detailed in a questionnaire completed by their owners. Of the thirty dogs, ten were considered normal insofar as they had no history of ASD clinical signs. The remaining 20 dogs were characterized as having ASD, with a chronic history of perianal pruritus, but no other pruritus. All dogs had their anal sacs manually expressed, and the discharge was examined microscopically in a blinded manner. A total of 171 oil immersion fields (OIFs) were examined from normal dogs and 333 OIFs from dogs with ASD. The behavioural results for dogs with ASD revealed that scooting recurred with a median frequency of 3 weeks post-anal sac expression. There were no clinically statistically significant cytological differences between normal dogs and those with ASD, thereby leading to the conclusion that cytology is an ineffective tool for diagnosing ASD.     

Open versus closed bilateral anal sacculectomy for treatment of non-neoplastic anal sac disease in dogs: 95 cases (1969-1994)

OBJECTIVE: To determine complications associated with anal sacculectomy in dogs with non-neoplastic anal sac disease and compare complication rates for open versus closed techniques. DESIGN: Retrospective study. ANIMALS: 95 dogs. PROCEDURE: Medical records were reviewed for information on signalment, history, physical examination findings, type of anal sac disease, surgical technique (closed, standard open [surgery performed prior to 19801, or modified open [surgery performed after 19801), and postoperative complications. RESULTS: In 57 dogs, a closed technique was used, and in 38, an open technique was used. Only 3 dogs developed short-term complications (excessive drainage, scooting and inflammation, and seroma formation), and 14 developed long-term complications (continued licking of the surgery site, fecal incontinence, fistulation, and stricture formation). Development of postoperative complications was significantly associated with surgical technique. Dogs that underwent standard open sacculectomy prior to 1980 were 13.67 times as likely to have a long-term complication as were dogs that underwent closed sacculectomy. Weight of the dog, type of anal sac disease, age at the time of surgery, and whether the wound was closed surgically were not significantly associated with whether dogs developed postoperative complications. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that anal sacculectomy is a safe and effective treatment for non-neoplastic anal sac disease in dogs and is associated with a low rate of complications. The standard open technique was associated with the greatest number of complications, whereas complication rates for the closed and modified open techniques were similar to each other.     

Acute pancreatitis in two dogs given azathioprine and prednisone

Acute pancreatitis was diagnosed in 2 dogs given azathioprine and prednisone. Prednisone and azathioprine had been given as immunosuppressive therapy for pemphigus foliaceus in dog 1 and for polymyositis in dog 2. Azathioprine was discontinued in both dogs. In dog 1, prednisone was reinstituted on day 6 of hospitalization. Prednisone was continued throughout the period of hospitalization in dog 2. Both dogs recovered without complication. Glucocorticoid therapy has been associated with the development of pancreatitis. In human beings, a common side effect of azathioprine is the development of drug-induced pancreatitis. Definitive identification of azathioprine as the cause of pancreatitis in these dogs was not possible; the owners refused to permit retreatment with the drug. Therefore, the synergistic action between these 2 drugs could not be ruled out as the cause of pancreatitis.     

Hepatocellular toxicosis associated with the alternate administration of carprofen and meloxicam in a siberian husky

A 4-year-old female Siberian Husky was diagnosed with pyogranulomatous steatitis at the site of a recurrence of left anal sac rupture (day 1). Carprofen and orbifloxacin were given for 13 days without improvement. A single dose of meloxicam was administered prior to surgical resection of the anal sac, and based on elevated liver enzyme activity, liver supportive therapy was initiated. The dog received carprofen and orbifloxacin orally on the evening of day 14. The dog became anorectic the following morning, and began vomiting. Despite supportive therapy, the dog was unresponsive to treatment and died on day 16. Postmortem examination revealed severe vacuolar change and acute necrosis of hepatocytes consistent with carprofen and meloxicam induced-toxicosis.     

Long-term evaluation of canine perianal fistula disease treated with exclusive fish and potato diet and surgical excision

The records of 33 dogs that had perianal fistula disease treated with en bloc surgical excision and bilateral anal saculectomy, and that were perioperatively administered an exclusive white fish and potato diet, were reviewed to determine outcome. By 1 year after surgery, 87.9% of the dogs had complete or near-complete resolution of visible fistula disease, while only 20.7% continued to have mild intermittent clinical signs. Fecal incontinence was not reported in any dog. Overall, complications were considerably less in both severity and frequency when compared with previous reports.     

Interleukin-2 and interferon-gamma mRNA expression in canine anal furunculosis lesions and the effect of ciclosporin therapy

German Shepherd Dogs have an increased incidence of anal furunculosis (AF), which is a disease characterised by inflammation and ulceration of the perianal tissues. Ciclosporin, an immunosuppressive drug, has been successfully used to treat AF, suggesting that the pathogenesis of disease is likely to have an immune-mediated component. Previous research has shown that the cytokine mRNA profile in AF lesions is consistent with T cell-mediated inflammation. The aims of the current study were to quantify IL-2 and IFNgamma mRNA expression in AF biopsies taken before and after treatment with ciclosporin and to compare cytokine expression with lesion severity. Twenty-two dogs with AF were recruited into the study and lesional biopsies were taken prior to ciclosporin therapy. Lesion severity was graded using a visual analogue scale. All dogs were evaluated after 4 weeks of ciclosporin therapy and, in 10 dogs with persistent disease, residual lesions were resected. RNA was extracted from AF-lesional tissue and control perianal tissue samples (n=10), which was used as the template for RT-PCR. Analysis of IL-2 and IFNgamma mRNA expression was performed using real-time PCR. IL-2 and IFNgamma mRNA was consistently detected in pre-treatment AF biopsies and, when quantified, this was significantly increased compared to control tissue (P<0.05). However, no correlation was seen between lesion severity and pre-treatment cytokine mRNA expression. In the ten paired pre- and post-treatment samples, IL-2 mRNA expression was significantly reduced in residual disease tissue following ciclosporin therapy (P=0.013). Treatment with ciclosporin seemed to result in decreased expression of IFNgamma mRNA in AF lesions but this was not statistically significant. In six of the 10 dogs with persistent disease, T cell cytokine mRNA could still be detected in the tissues, suggesting that there was inadequate immunosuppression. The absence of a correlation between T cell cytokine expression and the severity of disease suggests that tissue destruction observed in AF might be a consequence of other inflammatory mediators or downstream effects of T cell activation.     

Evaluation of azathioprine on lesion severity and lymphocyte blastogenesis in dogs with perianal fistulas

Fourteen dogs with perianal fistulas were entered into a prospective clinical study to investigate the effects of long-term azathioprine on clinical outcome and to determine if the clinical results correlated with lymphocyte blastogenesis tests. Complete remission of perianal fistulas was seen in eight (57%) of 14 dogs; partial remission occurred in one (7%) dog; and no response was detected in five (36%) dogs. The results of lymphocyte blastogenesis assays did not correlate with therapeutic response.     

Management of Perianal Fistulae A Retrospective Study of 23 Cases

The records of all dogs surgically treated for perianal fistulae during a S-year period were reviewed. The findings indicated that perianal fistulae occur predominantly in middle aged, intact male German shepherd dogs. The dogs were treated by superficial surgical excision of the involved skin, anorectal mucosa, and anal sacculectomy. Deeper fistulous tracts were flushed two to three times weekly with 10% Lugol's solution until healed by granulation. Fecal incontinence, the most common postoperative complication, was seen initially in 20% of cases. Fifty per cent of these animals regained fecal continence by the sixth month postoperatively, at which time they were considered acceptable house pets. The complication rate with this treatment regimen was less than that reported for techniques in which all diseased tissue is surgically excised.     

Effects of an oral vasopressin receptor antagonist (OPC-31260) in a dog with syndrome of inappropriate secretion of antidiuretic hormone

OBJECTIVE: The syndrome of inappropriate secretion of antidiuretic hormone is a rare disorder in dogs characterised by hypo-osmolality and persistent arginine vasopressin production in the absence of hypovolaemia and/or hypotension. The study describes the efficacy and safety of the nonpeptide selective arginine vasopressin V2 receptor antagonist OPC-31260 in a dog with the naturally occurring syndrome. DESIGN: The detailed case history of a dog with spontaneous syndrome of inappropriate secretion of antidiuretic hormone that received long-term therapy with oral OPC-31260 is presented. Effects of the first dose of OPC-31260 and of a dose administered after a continuous dosing period of 12 days are reported. PROCEDURE: Packed cell volume, plasma sodium, total protein, arginine vasopressin, renin activity, atrial natriuretic peptide, urine specific gravity, urine output, heart rate and body weight were monitored for 2 h before, and for 4 h after, the first dose of OPC-31260. The same parameters plus plasma osmolality and urine osmolality were monitored when an identical dose was administered after 12 days of therapy. RESULTS: Oral administration of OPC-31260 at 3 mg/kg body weight resulted in marked aquaresis with increased urine output and decline in urine specific gravity within 1 h. Corresponding increases in concentrations of plasma sodium, plasma osmolality and plasma renin activity were recorded over a 4 h period. Arginine vasopressin concentration remained inappropriately elevated throughout the study. Results were similar when the trial procedure was repeated after a stabilisation period of 12 days. Long-term therapy with OPC-31260 at a dose of 3 mg/kg body weight orally every 12 h resulted in good control of clinical signs with no deleterious effects detected during a 3-year follow-up period. Despite sustained clinical benefits observed in this case, plasma sodium did not normalise with continued administration of the drug. CONCLUSIONS: Treatment of a dog with naturally occurring syndrome of inappropriate secretion of antidiuretic hormone with OPC-31260 at 3 mg/kg body weight orally every 12 h resulted in marked aquaresis and significant palliation of clinical signs with no discernible side-effects detected over a 3-year period. Thus, OPC-31260 appears to offer a feasible medical alternative to water restriction for treatment of dogs with syndrome of inappropriate secretion of antidiuretic hormone. Higher doses of OPC-31260 may be required to achieve and maintain normal plasma sodium in dogs with this syndrome.     

Treatment of canine leproid granuloma syndrome: preliminary findings in seven dogs

OBJECTIVE: To determine effective treatment strategies for patients with refractory canine leproid granuloma syndrome. DESIGN: Multi-institutional retrospective/prospective case series using client-owned dogs. PROCEDURE: Seven dogs (four Boxers, one Dobermann, one Bullmastiff and one Bullmastiff cross-bred; ages 3 to 11 years) with leproid granulomas were treated successfully using a variety of treatment regimens. These cases were recruited because: lesions were either widely distributed over the dog; progressive, despite routine therapy, or were associated with particularly disfiguring lesions. The treatment regimen evolved during the course of the clinical study. RESULTS: Combination therapy using rifampicin (5 to 15 mg/kg p.o., every 24 h) and clarithromycin (8 to 24 mg/kg p.o. daily; dose divided every 8 or every 12 h) was used most frequently and proved to be effective and free from side effects. Total daily doses of clarithromycin in excess of 14 mg/kg were considered optimal and long treatment courses, in the order of 1 to 3 months, were used. Combination therapy using rifampicin (25 mg/kg; that is, higher than the recommended dose) and clofazimine was effective in one case, but resulted in hepatotoxicity. A topical formulation of clofazimine in petroleum jelly was used as an adjunct to oral rifampicin and doxycycline in another patient treated successfully. CONCLUSION: Based on our evolving clinical experience, a combination of rifampicin (10 to 15 mg/kg p.o., every 24 h) and clarithromycin (15 to 25 mg/kg p.o. total daily dose; given divided every 8 to 12 h) is currently recommended for treating severe or refractory cases of canine leproid granuloma syndrome. Treatment should be continued (typically for 4 to 8 weeks) until lesions are substantially reduced in size and ideally until lesions have resolved completely. A topical formulation, containing clofazimine in petroleum jelly may be used as an adjunct to systemic drug therapy. Further work is required to determine the most cost effective treatment regimen for this condition.     

Treatment of Tumor-Bearing Dogs With Actinomycin D

Fifty dogs with advanced malignancies were treated with actinomycin D at doses ranging from 0.5 to 1.1 mg/m² every 3 weeks. The greatest number of responses was noted in dogs with lymphoma, including dogs that had received prior chemotherapy. Other responding tumor types included anal sac adenocarcinoma, perianal adenocarcinoma, squamous cell carcinoma, thyroid carcinoma, and transitional cell carcinoma. The median time to maximum response for dogs with lymphoma was 7 days, with a median duration of 42 days. Gastrointestinal toxicity was the most frequently observed side effect. A dose of 0.6 to 0.7 mg/m² appears to be appropriate for treating various malignancies in dogs.     

Corticosteroid (methylprednisolone sodium succinate) pulse therapy in five dogs with autoimmune skin disease

Corticosteroid pulse therapy is the parenteral administration of suprapharmacologic doses of methylprednisolone sodium succinate for short periods. Five dogs diagnosed as having autoimmune skin disease were treated, using pulse therapy, with subsequent dramatic and rapid improvement of skin lesions. The dogs had no adverse clinical signs attributable to the treatment. All dogs had a relapse of clinical signs after a maintenance protocol (0.5 mg/kg, q 48 h) of orally administered prednisone was started. Skin lesions on 4 of 5 dogs eventually were controlled by prednisone, azathioprine, or gold therapy.     

Surgery of metastatic anal sac adenocarcinoma in five dogs

OBJECTIVE: To identify survival and morbidity information after surgery for metastases from apocrine gland anal sac adenocarcinomas (AGACA). STUDY DESIGN: Retrospective study. ANIMALS: Five dogs with AGACA. METHODS: Medical records of dogs that had surgery for treatment of metastatic AGACA between 1993 and 2003 were reviewed. Criteria for inclusion required that dogs had lymphadenectomy, with or without further debulking, as part of their treatment for metastatic AGACA and that the tissue was histologically confirmed as consistent with the primary AGACA. Signalment, history, physical examination findings, clinicopathologic data, imaging findings, surgical complications, number of surgeries, survival times, and cause of death were recorded. All dogs had a complete blood count, serum biochemical profile, serum electrolytes, 3-projection thoracic radiographs, abdominal radiographs and/or abdominal ultrasonography, and histologic confirmation of metastatic AGACA invading the regional lymph nodes and caudal abdomen. RESULTS: No surgical complications occurred. Three dogs were euthanatized; median survival, 20.6 months. One dog was alive for 19 months postoperatively. One dog had 5 sequential surgical procedures: 1 iliac lymphadenectomy and 4 debulking procedures of metastatic neoplastic tissue around and dorsal to the iliac vessels extending into the pelvic cavity, and was alive 54 months after initial surgery. CONCLUSION: Dogs with anal sac adenocarcinoma metastases to the iliac lymph nodes can experience long-term survival after surgical excision of the metastatic lesion. CLINICAL RELEVANCE: Lymphadenectomy may afford long-term survival to patients with metastatic anal sac adenocarcinoma.