Successful treatment of a novel generalized variant of canine discoid lupus erythematosus with oral hydroxychloroquine

Discoid lupus erythematosus (DLE) is a common canine autoimmune disease that usually manifests as a localized ulcerative and scarring nasal dermatitis. We report herein a generalized variant of canine DLE successfully treated with the antimalarial immunomodulator hydroxychloroquine (HCQ). A 9-year-old hairless Chinese crested dog was presented with annular and polycyclic hyperpigmented and scaly skin lesions with central erosions, hypopigmentation and/or scarring on the trunk, neck and lateral extremities. Associated systemic signs were not seen. The clinical diagnosis of generalized DLE was supported by the demonstration of lymphocyte-rich interface dermatitis with epidermal atrophy and dermo-epidermal deposition of immunoglobulins and activated complement. As for human DLE, treatment was initiated with HCQ at 5 mg/kg once daily along with 2 weeks of 0.1% tacrolimus ointment and restriction of sun exposure. Over the following year, complete remission was maintained with HCQ at 5 mg/kg orally once daily with the exception of three relapses; two occurred during treatment induction and the third arose when the frequency of HCQ administration was reduced to every other day. Disease flares were controlled with 0.1% tacrolimus ointment alternating with 0.1% prednicarbate cream once daily for 5-10 days. Altogether, adverse drug events were not seen with this regimen. In summary, clinically, histologically and immunologically, this dog's disease mirrored the generalized discoid variant of chronic cutaneous lupus erythematosus of humans. The apparent benefit of HCQ, its safety and low cost warrant future investigations of its use for treatment of canine cutaneous lupus variants.     

犬瘟抑制蛋白对犬瘟热的疗效观察

本试验研究不同剂量犬瘟抑制蛋白对犬瘟热的疗效,将犬瘟热试纸检测阳性的病犬24只,随机分为4组,每组6只,分别为对照组、试验1组、试验2组、试验3组。对照组治疗为犬瘟热单克隆抗体、犬干扰素及其对症输液治疗,试验1组为犬瘟抑制蛋白（20IU/kg）、犬干扰素,并结合输液（抗生素和能量合剂等）对症治疗。试验2组为犬瘟抑制蛋白（40IU/kg）、以下同上。试验3组为犬瘟抑制蛋白（60IU/kg）、以下同上。结果表明对照组与试验2组、试验3组其疗效比较明显。试验2组与试验3组的剂量不同,但其疗效一致,故试验2组为犬瘟抑制蛋白（40IU/kg）最佳使用剂量。     

Use of tetracycline and niacinamide for treatment of autoimmune skin disease in 31 dogs.

A combination of niacinamide and tetracycline was used to treat 31 dogs with various autoimmune skin diseases (discoid lupus erythematosus, pemphigus foliaceus, pemphigus erythematosus, and bullous pemphigoid). Of the 20 dogs with discoid lupus erythematosus, 70% had excellent or good response to treatment. Serious side effects were not noticed in any dog.     

Investigation of antibodies to extractable nuclear antigens in dogs.

Determination of antibodies to specific nuclear antigens, termed extractable nuclear antigen (ENA), was investigated in healthy dogs and in dogs with autoimmune, inflammatory, and neoplastic diseases. Using a counterimmunoelectrophoresis method, the dogs' sera were tested for antibodies against the nuclear antigens single-stranded DNA, Sm, Ro, La, ribonucleoprotein, Scl, and proliferating cell nuclear antigen. Antibodies to the Ro antigen were found in 1 dog with discoid lupus erythematosus, in 1 dog with pemphigus erythematosus, and in 1 dog with facial pyoderma and chronic superficial keratitis. In 15 dogs, antibodies were detected to ENA, but the precipitin lines were too weak to identify the specific ENA. These antibodies were found in some dogs with systemic lupus erythematosus, discoid lupus erythematosus, pemphigus erythematosus, dermatomyositis, vitiligo, lymphoma; in the dog with facial pyoderma and chronic superficial keratitis; and in 1 healthy dog. The highest percentage of dogs with antibodies to ENA in a large series (greater than 8) of this study was in dogs with systemic lupus erythematosus (4 of 13; 31%).     

Vesicular cutaneous lupus erythematosus in a Border Collie in New Zealand

A 3-year-old Border Collie was initially presented for a small ulcerative lesion on the left axilla. The lesion failed to respond to conservative treatment with antibiotics, and the dog was re-presented one week later with ulcerative lesions involving the inguinal and axillary areas bilaterally. Histology of a biopsy of these lesions revealed a lymphocytic ulcerative interface dermatitis. Apoptosis and degeneration of basaloid cells was evident, with clefting along the dermo–epidermal junction. Vesicular cutaneous lupus erythematosus was diagnosed. The dog was treated with prednisone and azathioprine, resulting in complete remission of signs. However, recurrence occurred when drugs were tapered, necessitating ongoing treatment. Vesicular cutaneous lupus erythematosus has been described in North America in Rough-coated Collies and Shetland Sheepdogs. However, in Australasia, it is most commonly observed in Border Collies.     

Progressive polysystemic immune-mediated disease in a dog

A dog with polyarthritis, angular joint deformities, and a high serum antinucleolar antibody titer was treated over a period of 20 months. During the clinical course, leukopenia, thrombocytopenia, Coombs' positive hemolytic anemia, and a pemphigus-type skin disorder developed, all of which responded to immunosuppressive therapy. It is not known whether the polysystemic disease in this dog represents a pleomorphic manifestation of canine systemic lupus erythematosus or multiple autoimmune disorders occurring in the same animal.     

Systemic lupus erythematosus in a filly

Systemic lupus erythematosus (SLE) was diagnosed in a 2-year-old Standardbred filly. Clinical signs of SLE included weight loss, bilateral symmetric alopecia, seborrhea, oral ulceration, and lymphadenopathy. Abnormal laboratory findings included a Coombs test-positive hemolytic anemia and positive antinuclear antibody test result. Histologic evaluation of multiple skin biopsy specimens revealed interface dermatitis with linear deposition of IgG at the basement membrane zones of the epidermis and hair follicles. The filly did not respond to glucocorticoid treatment and was euthanatized. Necropsy findings included membranous glomerulonephritis and fibrous synovitis. On the basis of these findings, SLE should be considered in the differential diagnosis of immune-mediated skin disease in horses. Definitive diagnosis of SLE relies on recognition of multisystemic disease and confirmatory histopathologic and immunopathologic findings.     

Noninfectious canine arthritis: the inflammatory, nonerosive arthritides.

Noninfectious, nonerosive arthritis was seen as an important manifestation of a number of chronic systemic diseases of the dog. Sixty-three dogs with this type of arthritis were seen at the Veterinary Medical Teaching Hospital during an 18-month period between 1973 and 1975. Of these dogs, 29 had systemic lupus erythematosus, 15 had arthritis in association with some chronic infectious disease process, and 19 had a similar type of arthritis, but without serologic evidence of systemic lupus erythematosus or any chronic infectious disease process.     

Eleven cases of vesicular cutaneous lupus erythematosus in Shetland sheepdogs and rough collies: clinical management and prognosis

Abstract   A cutaneous ulcerative disease is recognized to affect the adult Shetland sheepdog and rough collie. This has a distinct clinical and histological appearance consistent with a vesicular variant of cutaneous lupus erythematosus (VCLE). Retrospective information on the clinical outcome and response to therapy was collected from 11 cases of histologically confirmed VCLE. In 8/11 dogs the onset of disease was in the summer; in three dogs recrudescence occurred in subsequent summers. In eight dogs the skin disease was judged to be 75–100% controlled with therapy after a minimum follow-up of 9 months. Successful treatment in seven of these cases comprised immunosuppressive doses of oral glucocorticoids, alone (one dog), in combination with azathioprine (five dogs) and doxycycline (one dog). One case responded to topical fluocinolone. Three dogs were euthanased for reasons directly related to the disease, one prior to initiating any therapy. Vesicular cutaneous lupus erythematosus in the rough collie and Shetland sheepdog can be a debilitating skin disease which is best managed with aggressive immunosuppressive therapy. Sun avoidance or the use of sunscreens is an important additional management recommendation.     

Bullous systemic lupus erythematosus (type I) in a dog.

In human patients with systemic lupus erythematosus, cutaneous subepidermal blistering can occur because of the production of antibodies specific for basement membrane antigens. This condition is referred to as bullous systemic lupus erythematosus (BSLE). A dog was diagnosed with BSLE because it fulfilled the following criteria: (i) a diagnosis of systemic lupus erythematosus by standard methods; (ii) an acquired, vesicular, erosive and ulcerative eruption; (iii) microscopical subepidermal vesicles with neutrophil-predominant inflammation at the dermo-epidermal junction; (iv) deposition of IgG at the epidermal basement membrane zone; and (v) circulating IgG autoantibodies against type VII collagen. Anti-collagen VII type I-BSLE therefore needs to be considered as a possible differential diagnosis for canine autoimmune subepidermal blistering diseases.     

Immunoperoxidase staining for the detection of autoantibodies in canine autoimmune skin disease; comparison to immunofluorescence results

Skin sections from 22 dogs with autoimmune skin disease were stained with anti-canine IgG, IgM and IgA using an immunobridge immunoperoxidase method. Eight cases of lupus erythematosus, three cases of pemphigus vulgaris, and 11 cases of pemphigus foliaceus were included. Results of previously performed, direct immunofluorescence tests for the detection of canine immunoglobulin on skin were available on 17/22 cases. The immunoperoxidase method yielded an overall positive result in 59% (5/8 lupus erythematosus, 2/3 pemphigus vulgaris and 6/11 pemphigus foliaceus) versus an overall positive result of 47% for direct immunofluorescence (3/5 lupus erythematosus, 2/2 pemphigus vulgaris and 2/10 pemphigus foliaceus). The immunobridge immunoperoxidase method compared favorably to direct immunofluorescence testing of canine skin for autoantibody in cases of lupus erythematosis and pemphigus vulgaris, and was superior in cases of pemphigus foliaceus. This method should prove useful as an aid in the diagnosis of canine autoimmune skin disease.     

Acquired bilateral laryngeal paralysis associated with systemic lupus erythematosus in a dog

A 4 yr old spayed female Labrador retriever was referred for acute respiratory distress and was found to have bilateral laryngeal paralysis. Physical examination and biochemical testing were consistent with systemic lupus erythematosus (SLE) and did not reveal a likely alternative cause for the laryngeal paralysis. Following immunosuppressive and supportive treatment, the dog regained normal laryngeal function. At a scheduled follow-up examination 6 wk later, normal laryngeal function was confirmed via sedated laryngeal examination. Laryngeal paralysis associated with SLE has been reported in humans, but this is the first known report of acquired laryngeal paralysis associated with SLE in the dog.     

Collie eye anomaly in a mixed-breed dog

A 5-year-old, mixed-breed dog was presented for tetraparesis. Neurologic alterations included a decreased menace response in both eyes. Therefore, an ophthalmic examination was requested. The dog was visual, but menace response, dazzle and pupillary light reflexes were reduced bilaterally. Indirect ophthalmoscopy revealed bilateral optic nerve coloboma and severe choroidal hypoplasia. These lesions closely resembled the ophthalmoscopic features of Collie eye anomaly (CEA). In spite of treatment, the dog's condition worsened and the animal was therefore euthanized. Histology of the globes confirmed severe choroidal hypoplasia and optic disc coloboma in both eyes. The dog was diagnosed to have a lymphoma involving the spinal cord. The two entities were considered not related. As only moderate sight impairment was caused by the posterior segment anomalies, it is by chance that these lesions resembling CEA were found in this mixed-breed dog.     

Penile self-mutilation as an unusual sign of a separation-related problem in a crossbreed dog

A two-year-old, male, crossbreed dog was presented for evaluation of licking, biting and severe self-mutilation of its penis, which resulted in ulcers and haemorrhagic preputial discharge. History revealed signs of separation anxiety such as active greeting behaviour, excessive vocalisation and intermittent episodes of licking of the penis when the dog was left alone. The owner reported that he had been hospitalised after a car accident, and he had no chance of seeing the dog. During that time, the behaviour progressed to frequent episodes of licking and biting of the penis. Three weeks of treatment with clomipramine in addition to the presence of the dog's brother, who was brought into the dog's living environment, appeared to produce a considerable degree of improvement. The purpose of this report is to contribute to an increased awareness within veterinary practice of unusual signs of separation anxiety such as penile self-mutilation.     

Pemphigus foliaceus in association with systemic lupus erythematosus, and subsequent lymphoma in a cocker spaniel

A seven-year-old neutered male cocker spaniel was presented with an 11-month history of generalised bacterial dermatitis. There were skin lesions over the entire body, which were round, slightly raised and encrusted. Skin biopsies were collected and the histological findings were consistent with pemphigus foliaceus. Immunohistochemical staining by the indirect immunoperoxidase method was positive, with desmosomal deposition of immunoglobulin (Ig) G. Haematological analysis revealed a regenerative anaemia and profound thrombocytopenia, while a Coombs' test was positive for polyvalent canine Coombs' reagent and anti-dog IgG. An antinuclear antibody test was positive, with a titre of 10,240. An ophthalmic examination demonstrated low tear production (keratoconjunctivitis sicca). Seven months after initial referral, the dog was re-presented with severe generalised peripheral lymphadenopathy. Radiographic evaluation of the thorax and abdomen revealed enlarged cranial mediastinal and sublumbar lymph nodes. Tru-Cut biopsy from an enlarged lymph node confirmed the diagnosis of lymphoma, which was phenotyped as a B-cell tumour. The diagnosis in this case was systemic lupus erythematosus, with the unusual feature of pemphigus foliaceus, and subsequent development of B-cell lymphoma. The case adds further to knowledge of the protean clinical presentations of canine autoimmune diseases and provides additional evidence for the potential association between autoimmunity and immune-system neoplasia in this species.     

Eumycotic mycetoma caused by Pseudallescheria boydii in a dog

Abdominal eumycotic mycetoma caused by Pseudallescheria boydii was diagnosed in a 3-year-old male Siberian Husky. The dog was examined because of weight loss and signs of depression. Initially, pyrexia was the only clinical finding. Antibiotic and corticosteroid treatment was ineffective. Two weeks later, the dog's appetite had decreased, it had vomited a few times, and the caudal portion of the abdomen was sensitive to palpation. Hematologic and serum biochemical abnormalities consisted of anemia, leukocytosis, hypoglycemia, hypoalbuminemia, hyperglobulinemia, and high alkaline phosphatase activity. One week later, the dog's condition continued to worsen, and testicular swelling was observed. The dog was castrated. Microscopic examination of specimens obtained at surgery revealed pyogranulomatous periorchitis with mycetoma granules. Ketoconazole treatment was initiated and continued until the dog died one month later. Necropsy revealed multifocal duodenal ulcers, with transmural pyogranulomatous enteritis, pancreatitis, and peritonitis. This case is unique because the etiologic agent apparently entered via the intestinal tract rather than by contamination of an external wound.     

Fatal thrombocytopenic hemorrhagic diathesis associated with dapsone administration to a dog

Dapsone was given for six days to a dog with chronic skin disease. The dog then became weak and anorectic, and it vomited and had purpura caused by severe thrombocytopenic hemorrhagic diathesis. Despite treatment, the dog died a week later. There were clinical and pathologic evidence that the dog's platelets and megakaryocytes had been destroyed during the first few days of dapsone therapy. It was concluded that the syndrome was dapsone-induced and that thrombocytopenia should be considered among the adverse reactions to dapsone in the dog.     

Lupus-Type "Anticoagulant" in a Dog With Hemolysis and Thrombosis

A circulating anticoagulant was detected in a 2-year-old Chesapeake Bay Retriever with hemolytic anemia, nephrotic syndrome, thrombocytopenia, polyarthropathy, and pulmonary thromboembolism. A persistent prolongation of the activated partial thromboplastin time (aPTT) was detected, and it did not correct with repeated administration of fresh frozen plasma. The aPTT was still prolonged, with a 1:1 mixture of patient's plasma and normal dog plasma in vitro, suggesting the presence of a circulating inhibitor. Results of assays to characterize the inhibitor were compatible with those described for the lupus anticoagulant in human patients with systemic lupus erythematosus. Paradoxically, patients having the lupus anticoagulant are at increased risk for thrombosis. Pulmonary thromboembolism has been described as a frequent complication of immune-mediated hemolytic anemia in the dog, and the presence of a circulating anticoagulant should be considered as a potential mechanism.     

某警犬基地警犬死亡情况调查及原因分析

犬病防治一直是警犬工作的一个重要内容,直接关系到警犬的繁殖、训练和使用.近几年某警犬基地犬大量死亡情况时有发生,临床症状多种多样,死亡年龄大多在出生后2月龄以内,虽然在饲养管理、饲养方式和疾病防治上都采取了多种措施,但效果都不明显.笔者根据以往临床资料和临诊报告,对该基地警犬近几年的死亡情况进行了调查分析.结果表明,从2005年-2008年2月以来,死亡警犬共337头,死亡年龄主要集中在1月龄到2月龄的仔犬,不同年份死亡数量为:2005年59头,2006年73头,2007年165头,2008年仅2月份之前达36头;死亡类别可分为初生死胎114头,先天发育不良死亡47头,因病死亡153头,死因不明23头;引起死亡的主要疾病为犬细小病毒感染性疾病.     

The longevity of immunoglobulin preservation in canine skin utilizing Michel's fixative

Skin biopsy specimens from 7 dogs with immune-mediated skin diseases diagnosed by routine histology and 5 dogs with other skin diseases were placed in Michel's transport medium for 4 to 9 years. Direct immunofluorescence yielded positive results in tissue samples from 3 dogs with pemphigus foliaceus and 2 dogs with discoid lupus erythematosus. Direct immunofluorescence was not seen in tissue samples from 1 dog with pemphigus foliaceus and 5 dogs with non immune-mediated skin diseases. Direct immunofluorescence was seen in skin biopsy specimens maintained in Michel's medium for 4 to 8 years.