Autoantibodies against the processed ectodomain of collagen XVII (BPAG2, BP180) define a canine homologue of linear IgA disease of humans

Linear IgA disease (LAD) is an acquired autoimmune subepidermal blistering dermatosis that affects human children and adults. In contrast to bullous pemphigoid, in which autoantibodies recognize transmembrane type XVII collagen (BP180, BPAG2), LAD is associated with skin-fixed and circulating IgA autoantibodies that target LAD-1, the processed extracellular form of type XVII collagen. An immunologic homologue of LAD in humans was identified in two dogs according to the following criteria: 1) erosive, ulcerative, and crusted lesions seen on the face, in the oral cavity, and on the extremities, 2) dermoepidermal clefting present in the basement membrane lamina lucida without inflammation or with mild neutrophilic infiltration, 3) basement membrane-fixed IgG and/or IgA antibodies, and 4) circulating IgA and IgG autoantibodies that target the 120-kd soluble protein LAD-1. The present study establishes unequivocally the existence of a naturally occurring canine model of LAD of humans.     

Self-limiting subepidermal bullous disease in a neonatal foal

A 1-day-old Appaloosa colt developed vesicles/bullae involving the skin of the lips and prepuce and multiple mucous membranes. Histopathology revealed subepidermal vesicles/bullae that were clear or contained variable numbers of neutrophils and erythrocytes. The separated epidermis appeared viable. The denuded dermal papillae were often disrupted by microabscesses or coated with fibrinosuppurative debris. Fragmented basement membrane components were attached to exposed dermal papillae. Immunoperoxidase staining of sections for deposition of IgG, IgM, IgA, and C3 were positive for IgG at the basement membrane and intercellular bridges. Complete recovery ensued. The characteristics of the subepidermal bullous lesions and clinical course of lesion resolution in this foal suggested a drug-induced pathogenesis. The only known drug exposure of the foal or mare was topical application of 7% iodine to the umbilicus at the time of foaling. Similar reactions to iodine administration have been reported in humans.     

Clinical and immunological heterogeneity of canine subepidermal blistering dermatoses with anti‐laminin‐332 (laminin‐5) auto‐antibodies

Laminin‐332 (laminin‐5) is a basement membrane heterotrimeric protein composed of alpha‐3, beta‐3 and gamma‐2 laminin chains. Laminin‐332 polypeptides are targeted by auto‐antibodies in human patients with mucous membrane (cicatricial) pemphigoid or, more rarely, subepidermal vesicular diseases that resemble epidermolysis bullosa acquisita (EBA) or bullous pemphigoid (BP). The objectives of this report were to characterize the clinical, histopathological and immunological characteristics of nine dogs with auto‐antibodies targeting laminin‐332. Immunological investigations consisted of direct immunofluorescence (IF), indirect IF with intact and salt‐split canine gingival, and salt‐split normal or laminin‐332‐deficient human skin, immunoblotting with purified human laminin‐332 and immunoblotting with recombinant NC1 domain of human collagen VII. All dogs exhibited varying degrees of skin blistering and ulceration associated with microscopic subepidermal vesiculation with or without inflammatory cells. Indirect IF established that circulating IgG auto‐antibodies bound the dermal side of salt‐split canine lip and human skin. In five dogs, IgG variably recognized the basement membrane of laminin‐332‐deficient human skin (three dogs negative, two dogs positive). In all nine dogs, IgG auto‐antibodies detected purified human laminin‐332 by immunoblotting. In two dogs, additional targeting of collagen VII‐NC1 was present. These observations establish laminin‐332 as a novel basement membrane antigen in dogs with autoimmune blistering diseases with variable clinical phenotypes. The names ‘acquired junctional epidermolysis bullosa’, ‘anti‐laminin‐332 mucous membrane pemphigoid (MMP)’ and ‘mixed auto‐immune subepidermal blistering dermatosis’ are proposed for dogs with clinical signs reminiscent of EBA, MMP or BP respectively.     

Recurrent skin problems in a manatee: the diagnostic approach

A 40-year-old manatee was referred with recurrent vesicular and ulcerative dermatosis for the past 15 years. During this period the animal was anorectic and lost weight. Differential diagnoses were formulated on the basis of the history and clinical signs. Skin scrapings, bacterial and fungal culture, cytological examination, blood examination, and histopathological examination of skin biopsies narrowed this list down to autoimmune dermatosis. Despite corticosteroid therapy the symptoms recurred and the animal died. Histopathological examination of post-mortem skin biopsies showed again autoimmune dermatosis, more specifically subepidermal bullous autoimmune dermatosis, as the most probable cause of the skin lesions. Post-mortem examination showed cardiac decompensation and chronic nephritis. It was impossible to estimate the possible contribution of the chronic dermatosis to the cause of death. The purpose of this case report is to show the importance of a systematic work-up of disease in exotic animals.     

Novel feline autoimmune blistering disease resembling bullous pemphigoid in humans: IgG autoantibodies target the NC16A ectodomain of type XVII collagen (BP180/BPAG2).

In humans and dogs, bullous pemphigoid (BP) is an autoimmune blistering disease associated with the production of basement membrane autoantibodies that target the 180-kd type XVII collagen (BP180, BPAG2) and/or the 230-kd plakin epidermal isoform BPAG1e (BP230). In two adult cats, an acquired dermatosis and stomatitis was diagnosed as BP subsequent to the fulfillment of the following criteria: 1) presence of cutaneous vesicles, erosions, and ulcers; 2) histologic demonstration of subepidermal vesiculation with inflammatory cells, including eosinophils; 3) in vivo deposition of IgG autoantibodies at the epidermal basement membrane zone; and 4) serum IgG autoantibodies targeting a 180-kd epidermal protein identified as type XVII collagen. In both cats, the antigenic epitopes targeted by IgG autoantibodies were shown to be situated in the NC16A ectodomain of type XVII collagen, a situation similar to that of humans and dogs with BP. Feline BP therefore can be considered a clinical, histopathologic, and immunologic homologue of BP in humans and dogs.     

Pyoderma caused by Pseudomonas aeruginosa infection in dogs: 20 cases

In this report we describe the historical, clinical, histopathological and microbiological features, as well as treatments and clinical outcome, of pyoderma where Pseudomonas aeruginosa alone was isolated on bacterial culture from lesional skin. Twenty dogs were included in this retrospective study. Seven dogs without prior history of systemic or skin disease presented with acute deep pseudomonal pyoderma characterized by a sudden onset of dorsal truncal pain. Skin lesions in these dogs consisted of erythematous papules, haemorrhagic bullae, ulcers and haemorrhagic crusts confined to the dorsum. An excellent clinical response was achieved with 3-4 weeks of treatment with oral fluoroquinolones. Thirteen dogs with a more gradual onset of skin lesions associated with pseudomonal pyoderma had a history of prior skin, ear or systemic disease and had previously been treated with antibiotics and/or immunomodulatory drugs. Skin lesions in these dogs were variable and similar to those described for superficial and deep staphylococcal pyoderma. In this group, one dog was euthanized prior to commencement of treatment, two dogs were lost to follow up, and 9 had resolution of lesions following treatment with topical silver sulfadiazine (one dog), fluoroquinolones (six dogs) or cephalexin (two dogs) administered orally for 3 to 12 weeks. Rod-shaped bacteria were not always detected on cytology. Histopathology of dogs with deep pseudomonal pyoderma was characterized by severe perforating suppurative folliculitis and furunculosis.     

Spontaneous pneumothorax caused by pulmonary blebs and bullae in 12 dogs

Spontaneous pneumothorax caused by pulmonary blebs and bullae was diagnosed in 12 dogs based on history, clinical examination, thoracic radiographs, surgical findings, and histopathological examination of resected pulmonary lesions. Radiographic evidence of blebs or bullae was seen in only one dog. None of the dogs responded to conservative treatment with thoracocentesis or thoracostomy tube drainage. A median sternotomy approach was used to explore the thorax in all dogs. Pulmonary blebs and bullae were resected with partial or complete lung lobectomy. Ten of the dogs had more than one lesion, and seven of the dogs had bilateral lesions. The cranial lung lobes were most commonly affected. Histopathology results of the blebs and bullae were consistent in all dogs and resembled lesions found in humans with primary spontaneous pneumothorax. None of the dogs developed recurrence of pneumothorax. Median follow-up time was 19 months. The outcome following resection of the pulmonary blebs and bullae was excellent.     

Steroid-sparing effect of mycophenolate mofetil in the treatment of a subepidermal blistering autoimmune disease in a dog

A 7-year-old female Cocker spaniel-cross was referred with an 8-month history of mucocutaneous erosive dermatitis. On physical examination, skin lesions affected the eyelids and periocular area, lips and vulva. Lesions were symmetrical with small diffuse superficial ulcers, haemorrhagic crusts, adherent purulent exudation in haired skin, and alopecia with hyperpigmentation and scarring. Histopathologic evaluation showed multiple, non-intact dermoepidermal junction vesicles and ulceration associated with a dermal lichenoid infiltrate. Immunohistochemistry showed strong to moderate reactivity in the dermoepidermal junction for the antibodies directed against canine IgG, human IgG lambda light chains and C3, respectively. A diagnosis of autoimmune subepidermal blistering dermatosis was made. Treatment with oral prednisone at 2 mg/kg and mycophenolate mofetil (MMF) at 20 mg/kg twice daily was initiated and after 4 weeks the ulcers and erosions were cured. During the rest of treatment, MMF was maintained at 10 mg/kg twice daily and prednisone could be tapered to 0.25 mg/kg once every other day without recurrences. In conclusion, this case report shows that MMF was well tolerated and might be effective as steroid-sparing agent in the long-term treatment of this autoimmune subepidermal blistering disease.     

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.     

Canine epidermolysis bullosa acquisita: circulating autoantibodies target the aminoterminal non-collagenous (NC1) domain of collagen VII in anchoring fibrils

The classification of autoimmune blistering skin diseases is based on the skin antigen(s) targeted by pathogenic autoantibodies. In humans and dogs, there is increasing evidence that autoimmune subepidermal bullous diseases represent different nosological entities. This study establishes the existence of the canine equivalent of epidermolysis bullosa acquisita (EBA) in humans. Canine EBA, like the inflammatory variant of its human counterpart, is characterized by spontaneous vesicles arising from an inflammatory eruption. Dermo-epidermal separation occurs in association with neutrophilic infiltration in the superficial dermis. Tissue-fixed and circulating IgA and IgG autoantibodies specific for the lower basement membrane zone can be detected by immunofluorescence methods. Using immunoelectron microscopy, autoantibodies are shown to target the distal end of anchoring fibrils in the sublamina densa. ELISA and immunoblotting utilizing eukaryotically expressed recombinant collagen VII subdomains confirm that the circulating autoantibodies are specific for the aminoterminal globular non-collagenous NC1 domain of type VII collagen.     

Thoracoscopic treatment of bullous emphysema in 3 dogs

OBJECTIVE: To report thorascopic partial lobectomy for treatment of bullous emphysema in dogs. STUDY DESIGN: Prospective clinical study. ANIMALS: Three dogs with spontaneous pneumothorax. METHODS: Thoracoscopy without pulmonary exclusion was used to identify bulla. The thorascope was introduced into the thorax lateral to the xyphoid process, and instrument portals were made at different levels along the thoracic wall between the third and tenth intercostal spaces. The thorascope was passed through the mediastinum to view the opposite pleural cavity. After identification of bullae, the affected lung was excised using an endoscopic stapler, and the incision line was checked for air leakage. Thoracic drains were used for air aspiration for 2 days after surgery. RESULTS: Bullae were confirmed histologically as emphysematous lesions. Lung inflation did not interfere with identification of bullae or with surgery. All dogs had full recovery without recurrence for 18 to 29 months after surgery. CONCLUSIONS: Identification and ablation of bulla can be performed thoracoscopically without pulmonary exclusion in dogs. CLINICAL RELEVANCE: Thoracoscopy offers several advantages compared with thoracotomy for treatment and diagnosis of idiopathic pneumothorax, including ease of identification of bullae and reduced postoperative pain and morbidity.     

Vesiculobullous skin reaction temporally related to firocoxib treatment in a white rhinoceros (Ceratotherium simum)

A 40 yr-old female white rhinoceros (Ceratotherium simum) suffered from chronic nail-bed abscesses. Due to worsening of clinical signs, the animal's nonsteroidal anti-inflammatory treatment was switched to firocoxib. Approximately 7 days after this change, the animal developed multifocal vesicles and bullae along the lateral aspects of the thorax and abdomen, the dorsum, and the proximal limbs. Cytology and culture did not identify an infectious etiology. Histologically, the lesions consisted of a severe, subacute vesiculobullous dermatitis with intraepidermal to subepidermal clefting with areas of individual keratinocyte necrosis and minor neutrophilic epidermal infiltrates. These findings are similar to those seen in some drug reactions in people; therefore an adverse drug reaction to the firocoxib was suspected.     

Hyperadrenocorticism in 10 dogs with skin lesions as the only presenting clinical signs

Ten dogs that had skin lesions as the only presenting signs of hyperadrenocorticism (HAC) and as the owners' primary complaint are described. Dogs were included if the initial examination was for skin disease, there were no signs of systemic illness on initial presentation and there was a confirmed diagnosis of HAC by specific screening tests. Dogs were excluded if they had a severe disease that might interfere with screening tests for HAC or if the screening tests were not diagnostic. There were five males and five females; six dogs were intact. Nine dogs were diagnosed at ≥7 years. Eight dogs weighed ≤10 kg. Alopecia was present in nine dogs. Eight dogs had bacterial pyoderma, five had hyperpigmentation, and four had thin skin. One dog had unresolved dermatophytosis. Skin lesions resolved after treatment in eight dogs. One dog was not treated and one was lost to follow-up. This study showed that skin lesions may be the only clinical signs of HAC. The presence of the more common clinical signs of HAC, such as a non-pruritic, truncal alopecia and/or thin skin, without any systemic signs of HAC and/or the presence of poorly responsive skin infections warrant screening for this disease.     

Diagnosing new autoimmune blistering skin diseases of dogs and cats

Autoimmune blistering skin diseases have been recognized for decades in humans and dogs. In the dog, most of these diseases unfortunately were grouped under the generic denomination of bullous pemphigoid without any confirmation that the autoantibodies targeted bullous pemphigoid antigens. In recent years, advanced diagnostic methods have permitted the recognition of new autoimmune blistering skin diseases in humans and companion-animal species. At this time, the diagnosis of these entities is made by combining clinical signs and results of histopathology. Immunologic methods serve to establish the presence of skin-fixed and circulating autoantibodies that target various epidermal or basement membrane antigens. In this article, salient features of the most common canine and feline subepidermal blistering dermatoses (mucous membrane pemphigold, bullous pemphigold, epidermolysis bullosa acquisita) and new variants of cutaneous lupus (type I bullous systemic lupus erythematosus and vesicular cutaneous lupus erythematosus) are presented.     

FC-23 Feline plasma cell pododermatitis: a retrospective study of 26 cases

The objective of this open pilot study was to evaluate the efficacy of topical tacrolimus ointment for treatment of plantar fistulae in German shepherd dogs. Seven dogs (four males, three females) were included. All subjects had a 6-month to 2-year history of plantar fistulae involving the plantar aspect of two to four metatarsi/metacarpi. No other skin lesions were present and the dogs appeared otherwise healthy. Before treatment with tacrolimus, all dogs received antibiotics for 4–8 weeks. Hair was clipped to visualise the lesions. The presence of erythematous papules, oedema and fistulae was recorded for each foot. All dogs served as their own controls. Dogs with four legs involved had one front and one hind leg treated. Dogs with two to three feet affected had only one foot treated. Tacrolimus 0.1% ointment (Protopic^®) was applied twice daily onto the site of lesions. Partial improvement of treated lesions was seen in all cases within 3 weeks. After 6 weeks, treated lesions were in complete remission in four dogs, while the other three subjects had palpable but invisible lesions. Signs had not improved on the untreated legs. Follow-up varied between 4 months and 2 years. Lesion remission persisted in six dogs with the intermittent application of tacrolimus. Adverse effects of treatment were not seen. In conclusion, the application of topical tacrolimus seems to provide a safe and effective treatment option for plantar fistulae in German shepherd dogs.
Funding: Self-funded.     

FC‐21 Efficacy of topical tacrolimus ointment for treatment of plantar fistulae in German shepherd dogs

The objective of this open pilot study was to evaluate the efficacy of topical tacrolimus ointment for treatment of plantar fistulae in German shepherd dogs. Seven dogs (four males, three females) were included. All subjects had a 6‐month to 2‐year history of plantar fistulae involving the plantar aspect of two to four metatarsi/metacarpi. No other skin lesions were present and the dogs appeared otherwise healthy. Before treatment with tacrolimus, all dogs received antibiotics for 4–8 weeks. Hair was clipped to visualise the lesions. The presence of erythematous papules, oedema and fistulae was recorded for each foot. All dogs served as their own controls. Dogs with four legs involved had one front and one hind leg treated. Dogs with two to three feet affected had only one foot treated. Tacrolimus 0.1% ointment (Protopic^®) was applied twice daily onto the site of lesions. Partial improvement of treated lesions was seen in all cases within 3 weeks. After 6 weeks, treated lesions were in complete remission in four dogs, while the other three subjects had palpable but invisible lesions. Signs had not improved on the untreated legs. Follow‐up varied between 4 months and 2 years. Lesion remission persisted in six dogs with the intermittent application of tacrolimus. Adverse effects of treatment were not seen. In conclusion, the application of topical tacrolimus seems to provide a safe and effective treatment option for plantar fistulae in German shepherd dogs. Funding: Self‐funded.     

湘桂地区犬皮肤病流行病学调查

对来自湘桂地区6个宠物医院的48 127个确诊病例进行调查,对犬皮肤病的种类、发病率及其与年龄和季节的相关性进行分析。结果表明,皮肤病发病率为28.53%。在皮肤病中,脓皮病和疥螨最为常见,分别占28.03%和26.18%。皮肤病的发病率随着年龄增长而下降。不同季节流行的皮肤病种类也有区别,但各皮肤病在冬季发病率最低。     

Hormonal abnormalities in Pomeranians with normal coat and in Pomeranians with growth hormone-responsive dermatosis

Clinical status, skin biopsy specimens, and endocrine function were evaluated in normal-coated Pomeranians (n = 12) and Pomeranians affected with growth hormone (GH)-responsive dermatosis (n = 7), then were compared with values in mixed-breed dog controls (n = 19). All Pomeranians were clinically normal; however, the Pomeranians with GH-responsive dermatosis had bilateral alopecia and hyperpigmentation of the trunk, caudal portion of the thighs, and ventral neck region. Skin biopsy specimens from the affected Pomeranians had decreased-to-normal epidermal thickness and follicular atrophy, compared with normal-coated Pomeranians. Numerous elastin fibers were observed in the skin biopsy specimens of unaffected and affected Pomeranians. Both groups of Pomeranians had normal results of thyrotropin-releasing hormone (TRH) and thyrotropin (TSH) response, adrenocorticotropin (ACTH) stimulation, and dexamethasone suppression testing. There was no significant increase in serum GH concentration in either group of Pomeranians after xylazine or human GH-releasing factor (GHRF) administration, whereas control dogs had significant (P less than or equal to 0.05) increase in serum GH concentration after administration of either agent. Baseline plasma ACTH concentration in unaffected and affected Pomeranians was increased above the normal range (40 to 90 pg/ml). Post-ACTH administration serum progesterone, 17-hydroxyprogesterone, and androgen (dehydroepiandrosterone sulfate or androstenedione) concentrations were consistently high in unaffected and affected Pomeranians, compared with values in control dogs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Calcinosis cutis secondary to percutaneous penetration of calcium chloride in dogs

Accidental exposure of the skin of a dog to a commercial hygroscopic landscaping product (77-80% CaCl2) caused contact-irritant dermatitis within 24 hours. Papules and eroded to ulcerated plaques with hyperproliferative margins developed on various areas of the skin that had come in contact with CaCl2. Histopathologic findings were typical of calcinosis cutis. Reproducible lesions similar to those observed on the referred dog were induced on 5 clinically normal dogs exposed to small amounts of the compound. Histopathologic documentation of the percutaneous penetration of CaCl2, with evidence of calcinosis cutis, was found in the dogs as early as 24 hours after continuous skin contact with the offending substance. Electron-microscopic evidence of crystalline deposits within dermal collagen also was found in skin biopsy specimens obtained 24 hours after contact with CaCl2. Serum calcium and phosphorus concentrations in the 5 dogs remained within normal limits before and after topical application of CaCl2.     

Prospective study of bacterial overgrowth syndrome in eight dogs

Eight dogs with cutaneous lesions, clinical signs and cytological findings compatible with bacterial overgrowth syndrome were compared with four healthy dogs. The affected dogs were treated for 28 days with 30 mg/kg/day cephalexin. The results showed that the syndrome was a superficial cutaneous disorder characterised by marked pruritus, greasy seborrhoea, offensive odour, erythema, lichenification, hyperpigmentation, excoriations and alopecia involving principally the ventral aspect of the body, but no papules, pustules, epidermal collarettes or crusts; it was caused by overgrowths of Staphylococcus intermedius all over the body surface. Histopathological findings included a superficial, perivascular, hyperplastic and spongiotic dermatitis with a mixed inflammatory infiltrate, but no lesions suggestive of a true pyoderma. In the affected dogs, anti-staphylococcal immunoglobulin G levels were high, but anti-staphylococcal immunoglobulin E levels were low, suggesting that staphylococcal hypersensitivity is not the underlying pathogenic process. The antibiotic treatment improved the condition of all the dogs, but five of the eight had an underlying allergic skin disease.