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.     

Day-blindness in three dogs: clinical and electroretinographic findings

A 6-month-old Rhodesian ridgeback-cross, a 6-year-old Chihuahua and a 12-month-old Australian cattle dog were presented to the authors with a history of colliding with obstacles in daylight. Ophthalmic examination was normal and all three dogs successfully negotiated obstacle courses in dim light. In daylight the dogs became suddenly blind and repeatedly collided with obstacles. Elecroretinography (ERG) revealed no retinal activity to high frequency (30 Hz), bright intensity blue light retinal stimulation by any dog, confirming cone dysfunction. Achromatopsia has previously been recorded in Alaskan malamutes and miniature poodles. This clinical case series illustrates the characteristic behavioral presentation and the electroretinographic findings of severe day-blindness and demonstrates that this condition may exist in other breeds of dogs.     

Ehlers-Danlos-like syndrome in 2 dogs: clinical,histologic, and ultrastructural findings

Background: Ehlers-Danlos syndrome comprises a group of rare inherited connective tissue diseases characterized by skin hyperextensibility, joint laxity, skin and vessel fragility, and poor wound healing.
Objective: The purpose of this report was to describe the clinical, histologic, and ultrastructural findings in 2 dogs with collagenopathies consistent with Ehlers-Danlos syndrome.
Methods: Two dogs were examined clinically; skin extensibility index was calculated. Skin biopsies obtained from the dorsum were examined by light and electron microscopy.
Results: Both dogs had clinical signs of skin hyperextensibility and fragility, lower skin elasticity, vessel fragility, and poor wound healing. One dog had a hip dislocation, and the other had bilateral medial patellar luxation (grade II), subcutaneous hematomas produced by minimal trauma, and generalized periodontitis. Histologic and ultrastructural examination confirmed abnormalities in the structure and arrangement of collagen fibrils. Fibroblasts were characterized by variable dilatation of the rough endoplasmic reticulum, and anomalous elastic fibers (elaunin fibers) were present in the dermis.
Conclusion: Although the primary defects underlying collagenopathies in animals are still unknown, analysis of the ultrastructural changes in collagen fibrils and clinical findings could facilitate better characterization of these disorders in dogs.     

Sertoli cell tumors associated with feminizing syndrome and spermatic cord torsion in two cryptorchid dogs

The association of cryptorchidism, functional Sertoli cell tumors, and spermatic cord torsion has been rarely reported in the literature. Two dogs were admitted for bilateral skin alopecia and weight loss. Both animals were cryptorchid and displayed a pendulous preputial sheath, prostate hypertrophy, and increased levels of circulating oestrogen. Transabdominal palpation and ultrasonography revealed the presence of neoplastic retained gonads. During surgery, spermatic cord torsion was also detected in the enlarged neoplastic testes of both dogs. Histologic examination confirmed the presence of Sertoli cell tumors that were primarily responsible for the feminizing syndrome. Complete remission of all symptoms occurred within 3 months after orchiectomy.     

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.     

Common allergens of atopic dermatitis in dogs: comparative findings based on intradermal tests

Intradermal tests were performed on 58 dogs diagnosed with atopic dermatitis from 2004~2008 at the Veterinary Medical Teaching Hospital of Konkuk University, Korea. To compare the allergen distribution observed in the present investigation to the results from other studies conducted in Korea and elsewhere, the allergens were grouped according to their kinds. There was no significant difference in gender distribution among the dogs. The most common breeds among the 58 dogs were Maltese (n = 11) and Shih-tzu (n = 11). The average age was 4.8 years. The most frequently produced a positive reaction on the intradermal tests was mold (67.3%) followed by house dust (54.5%) and house dust mites (49.1%). The present study found a low distribution of dogs allergic to various outdoor allergens compared to studies performed in other countries; this may reflect differences in living conditions for dogs living in Korea.     

Cutaneous paraneoplastic syndromes in dogs and cats: a review of the literature

Cutaneous paraneoplastic syndromes are a group of noncancerous dermatoses associated with internal malignancy. Their recognition can facilitate detection and timely treatment of underlying cancer. More than 30 such disorders have been identified in the human scientific literature, whereas only a few are described in veterinary medicine. This may reflect a lower incidence in animals than in people or may be the result of failure to recognize an association between certain skin lesions and neoplasia. Establishing a relationship between a cutaneous disorder and neoplasia can be difficult unless the skin lesions are rare and almost always associated with a particular tumour type, as is the case for most recognized veterinary paraneoplastic dermatoses. Among these are feline paraneoplastic alopecia, feline thymoma-associated exfoliative dermatitis, nodular dermatofibrosis, feminization syndrome associated with testicular tumours, superficial necrolytic dermatitis and paraneoplastic pemphigus. The aetiology of most cutaneous paraneoplastic syndromes has remained elusive in both people and animals.     

Chronic lymphocytic leukemia transformation into high‐grade lymphoma: a description of Richter's syndrome in eight dogs

Richter's syndrome (RS) is the development of an aggressive lymphoma in patients with chronic lymphocytic leukaemia (CLL). In humans, RS occurs in 2–20% of CLL, which transform into diffuse large B‐cell lymphoma but reports in dogs are scarce. This study retrospectively describes eight dogs with CLL progressing into RS. A database including 153 dogs with CLL (93T CD8+ and 55 B‐CLL) was interrogated and RS was demonstrated in eight cases (representing 5.2% of total CLL): two with T‐cell (2.2% of T CLL) and six with a B‐cell immunophenotype (10.9% of B‐CLL). When RS occurred, lymphocytes were decreased compared to CLL. Five dogs had anaemia and two dogs thrombocytopenia. Frequent clinical signs included lymph node swelling, coughing, vomiting, neurological signs and weight loss. Independently from the therapy, RS was associated with a short survival (median 41 days). RS should be considered as an unfavourable evolution in canine CLL.     

Correlation of cytologic and histopathologic findings with perinodal echogenicity of abdominal lymph nodes in dogs and cats

Abdominal lymphadenopathy in dogs and cats is routinely investigated with ultrasound. As the determination between benign and neoplastic etiologies of lymphadenopathy affects patient management, specific sonographic characteristics associated with both benign and neoplastic lymph nodes have been suggested. However, a significant overlap between these characteristics exists, necessitating a cytologic or histopathologic diagnosis in most instances. The objectives of this retrospective, cross‐sectional study were to evaluate whether echogenicity of perinodal fat could be a discriminator between benign and neoplastic abdominal lymphadenopathy and to assess if additional sonographic features associated with malignancy could be identified in lymph nodes with hyperechoic perinodal fat. Small animal patients (257 dogs and 117 cats) with sonographic evidence of abdominal lymphadenopathy and a cytological or histopathological diagnosis were evaluated for differences in the proportions of sonographic features between benign and neoplastic groups. Greater maximum long axis diameter (in dogs and cats) and a greater number of abnormal lymph nodes (in cats) were associated with malignancy in lymph nodes with hyperechoic perinodal fat. Canine lymph nodes with round cell neoplasia were significantly more likely to have hyperechoic perinodal fat. Lymph nodes affected with other neoplasia or with lymphadenitis were equally likely to have normal or hyperechoic perinodal fat. Reactive lymph nodes were significantly less likely to have hyperechoic perinodal fat in both species. These results suggest that though echogenicity of perinodal fat is a nonspecific finding, abdominal lymph nodes with hyperechoic perinodal fat are less likely to be reactive and sampling of these lymph nodes may be indicated.     

Clinical findings, rhinoscopy and histological evaluation of 54 dogs with chronic nasal disease

Nasal diseases are very common in dogs and rhinoscopy is often required for a definitive diagnosis. Rhinoscopy, while superficial in nature, can guide the clinician to the final diagnosis. In this study, rhinoscopy was performed on 54 dogs with symptoms of chronic nasopharyngeal disease. The endoscopic diagnosis of neoplasia or chronic nasal inflammation was validated with histological examination of pathological samples, in order to evaluate the degree of concordance between endoscopic findings and histological diagnosis. The agreement between endoscopy and histology was tested by application of Cohen''s kappa coefficient. We conclude that correlation between endoscopic results and histological diagnosis, expressed by a Cohen''s kappa coefficient of 0.73, is only possible with a constant cooperation between the clinician and the pathologist.     

Treatment of myeloid neoplasia with doxorubicin and cytarabine in 11 dogs

Myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) are primary myeloid neoplasms in dogs generally considered to have a poor outcome. In this study, we assessed toxicity, efficacy and outcome of concurrent administration of doxorubicin and cytarabine in 11 dogs with myeloid neoplasia. Bone marrow specimens were reviewed by three pathologists and classified as either MDS (n = 2), high grade MDS/early AML (MDS/AML; n = 4) or AML (n = 5). The median number of treatment cycles was 5 (range 1–9) and resolution of cytopenia was reported in 7 of 11 dogs including 2 dogs with MDS, 2 dogs with MDS/AML, and 3 dogs with AML. The median duration of remission in the seven responders was 344 days (range 109–1428) and the median overall survival for all dogs was 369 days. Adverse events consisted of predominantly low-grade gastrointestinal illness and myelosuppression. Three dogs developed grade V toxicity manifesting with heart failure (n = 2) at 369 and 1170 days after diagnosis and acute gastrointestinal side effects (n =1). Despite a limited sample size, these results suggest that a doxorubicin and cytarabine protocol may be considered as a therapeutic option in dogs with myeloid neoplasia. Protocol safety, in particular regarding myocardial toxicity, and efficacy should be further investigated.     

Acute respiratory distress syndrome in dogs and cats: a review of clinical findings and pathophysiology

Objective: To review the clinical and pathophysiologic aspects of acute respiratory distress syndrome (ARDS) in dogs and cats. Data sources: Data from human and veterinary literature were reviewed through Medline and CAB as well as manual search of references listed in articles pertaining to acute lung injury (ALI)/ARDS. Human data synthesis: Since the term ARDS was first coined in 1967, there has been a abundance of literature pertaining to this devastating syndrome in human medicine. More complete understanding of the complex interactions between inflammatory cells, soluble mediators (e.g., tumor necrosis factor, interleukin (IL)‐6, IL‐8, platelet activating factor) and the clinical patient has provided for timely recognition and mechanistically based protective strategies decreasing morbidity and mortality in human patients with ARDS. Veterinary data synthesis: Although little is known, ARDS is becoming a more commonly recognized sequela in small animals. Initial case reports and retrospective studies have provided basic clinical characterization of ARDS in dogs and cats. Additionally, information from experimental models has expanded our understanding of the inflammatory mechanisms involved. It appears that the inflammatory processes and pathologic changes associated with ARDS are similar in dogs, cats, and humans. Conclusions: Unfortunately, current mortality rates for ARDS in small animals are close to 100%. As our capability to treat patients with advanced life‐threatening disease increases, it is vital that we develop a familiarity with the pathogenesis of ARDS. Understanding the complex inflammatory interactions is essential for determining effective preventative and management strategies as well as designing novel therapies for veterinary patients.     

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.