Fluorescence overlay antigen mapping using laser scanning confocal microscopy differentiates linear IgA bullous dermatosis from epidermolysis bullosa acquisita mediated by IgA

Background Linear IgA bullous dermatosis (LABD) and epidermolysis bullosa acquisita (EBA) mediated by IgA antibodies belong to the group of autoimmune subepidermal bullous diseases mediated by IgA autoantibodies. Early and correct diagnosis is crucial because the management and prognosis of the diseases are different. Objectives To determine whether fluorescence overlay antigen mapping using laser scanning confocal microscopy (FOAM‐LSCM) is helpful in the differentiation between these diseases. Methods FOAM‐LSCM and immunoblot studies were performed in 19 patients with disseminated tense blisters who presented with in vivo bound and circulating IgA antibasement membrane zone (BMZ) antibodies on immunofluorescence. Results Using FOAM‐LSCM, in vivo bound IgA above type IV collagen, which is characteristic for LABD, was seen in 14 of the 19 cases, whereas five of the 19 cases had IgA deposits below type IV collagen, typical for EBA. Immunoblot studies showed that IgA antibodies in 11 of the 14 patients with deposits above type IV collagen reacted with different epitopes on BP180, mainly with LAD‐1, which is a target antigen in LABD. Among the five patients with deposits below type IV collagen, one showed IgA antibodies to the 200‐kDa laminin γ‐1 and one had antibodies to the 290‐kDa type VII collagen, EBA antigen. Additionally, enzyme‐linked immunosorbent assay with recombinant type VII collagen was positive in three of the five cases who presented with IgA deposits below type IV collagen on FOAM‐LSCM. Conclusions The results using FOAM‐LSCM were consistent with those obtained on immunoblotting. FOAM‐LSCM is useful in routine diagnostics in cases with undetectable circulating anti‐BMZ antibodies, and can differentiate LABD from IgA‐EBA, the former with in vivo bound IgA above type IV collagen and the latter with IgA deposits below type IV collagen.     

药物诱导的成人线状IgA疱病一例

患者男,28岁。就诊前6 d因外伤骨折至浙江大学医学院附属邵逸夫医院行左锁骨骨折切开复位内固定术,术中使用帕洛诺司琼、苯磺顺阿曲库铵、右美托咪定、艾司洛尔、羟考酮、瑞芬太尼、麻黄碱、地佐辛、佛比洛芬等麻醉用药,术前后使用阿莫西林克拉维酸钾预防感染……     

儿童获得性大疱性表皮松解症一例

报道1例儿童获得性大疱性表皮松解症.患者女,12岁,因全身反复水疱、大疱和糜烂面3个月入院.患者弱智,父母非近亲结婚,无家族史.入院时表现全身大片糜烂面,包括手足、膝关节周围和股臀部,同时躯干、四肢正常或水肿性红斑基础上紧张性水疱、大疱.治疗过程中突然发生躯干、四肢大量紧张性水疱.组织病理提示,表皮下水疱,免疫荧光结果见表皮基底膜带IgG和C3线状沉积,盐裂后沉积限于真皮侧.ELISA检测BP180和BP230阴性.采用大剂量糖皮质激素联合四环素口服取得满意疗效.

Abstract：

A case of epidermolysis bullosa acquisita (EBA) in childhood is reported. A 12-year-old girl was hospitalized for a 3-month history of recurrent blisters, bullae and erosions on the trunk and limbs. The girl had mental retardation but no family history of similar disorders. The marriage between her parents was not consanguineous. Physical examination on admission revealed large erosions with moderate oozing on the hands and feet, around the knees and on the buttock and thighs. There were scattered tense blisters and bullae arising in normal skin or edematous erythema on the trunk and limbs. During the treatment course the patient suddenly developed a number of tense blisters over the whole integument on the trunk and limbs. Skin biopsy showed subepidermal bullae with moderate perivascular infiltration of neutrophils and eosinophils. Direct immunofluorescence (DIF) revealed linear IgG and C3 deposition along the basal membrane zone, which was on the dermal side of salt-split skin on indirect immunofluorescence (IIF). ELISA detected no serum antiBP180 or -BP230 antibodies in the patient. A diagnosis of EBA was made. The patient was successfully controlled by intravenous steroids combined with oral tetracycline.     

Drug-induced linear IgA bullous dermatosis

A 73-year-old man was admitted to the University of California Davis Medical Center for treatment of a pleural effusion and congestive heart failure. His hospital course was complicated by asymptomatic sustained ventricular tachycardia requiring placement of an implantable cardiac defibrillator. The patient was treated with vancomycin and cefazolin during the procedure. After 3 days he developed tense vesicles over the dorsal aspect of the hands. Perilesional skin biopsy showed subepidermal cleavage with a neutrophilic infiltrate. Direct immunofluorescence revealed granular IgA and C3 deposition along the dermal epidermal junction. A diagnosis of drug-induced linear IgA bullous dermatosis secondary to vancomycin was established. Linear IgA bullous dermatosis is a rare autoimmune blistering disorder with clinical features that can overlap with bullous pemphigoid and dermatitis herpetiformis. Drug-induced linear IgA bullous dermatosis is a less common variant that is correspondingly less well characterized. Although a variety of medications have been implicated, vancomycin is the most common associated drug.     

新生儿线状IgA大疱性皮病

患儿男, 生后10 d, 因皮肤红斑、水疱6 d就诊入院。皮肤科检查:全身皮肤散在或融合分布红斑, 在正常皮肤或红斑基础上可见大小不等的紧张性水疱, 部分水疱破溃、糜烂;口腔黏膜可见血疱、红色糜烂面。组织病理检查示表皮下水疱, 疱内可见中性粒细胞及少量嗜酸性粒细胞。直接免疫荧光检查显示:沿基底膜带有均质型线状IgA和颗粒状C3沉积, IgG阴性。诊断:新生儿线状IgA大疱性皮病。给予营养支持、防感染等综合治疗后, 皮肤红斑、水疱消退, 黏膜损害减轻出院。患儿出院后16个月电话随访, 一般情况良好, 皮肤黏膜皮损消退、愈合, 无新发皮疹, 生长发育正常。     

Drug-induced linear IgA bullous dermatosis

We report the case of a 69-year-old Japanese woman with multiple blistering lesions covering almost her whole body. Linear IgA and C3 depositions were seen at the basement membrane zone on direct immunofluorescence (IF). Linear IgA bullous dermatosis (LABD) is one of the autoimmune diseases resulting in subepidermal blisters. It is clinically similar to bullous pemphigoid and IF is required to distinguish the two diseases. In this case, the blistering lesions appeared after vancomycin treatment. This drug was strongly suspected as a cause of LABD in light of the clinical course of the patient even though a drug-lymphocyte stimulating test was negative. Among the various implicated causative drugs, vancomycin is the most commonly associated with LABD.     

Captopril-triggered linear IgA bullous dermatosis

A 57-year-old African–American woman with a history of long-standing asthma, hypertension, and congestive heart failure was referred for an intensely pruritic, blistering eruption of 2 months duration. The blistering began 2 weeks after the initiation of captopril for essential hypertension. It was localized predominantly on the thighs and legs, but had recently spread to the upper extremities. Previously, the patient had been treated with albuterol and furosemide. She had been admitted to the hospital with a diagnosis of acute varicella, which was ruled out by a negative Tzanck preparation. Clarithromycin was prescribed upon discharge. Physical examination revealed multiple healed and crusted erosions ranging in size from 1 to 7 cm on the anteromedial aspect of the thighs and legs ( Fig. 1 ). Discrete and confluent tense vesicles, some forming arciform or rosette-like patterns, were noted ( Fig. 2 ). Multiple hypopigmented macules and patches were seen. On the flexural aspect of the forearms, there were multiple small erosions, some of which appeared excoriated. There were no urticarial lesions, and the oral mucosa and scalp were spared.

Figure 1 Open in figure viewer PowerPoint Multiple healed and crusted erosions on the anteromedial aspect of the left thigh. Hypopigmented macules and patches are also evident     

成人面部线状IgA大疱性皮病一例

临床资料患者,男,28岁。主因面部反复出现红斑、水疱伴瘙痒6年,加重10d,于2012年1月31日就诊。     

Childhood epidermolysis bullosa acquisita

We report a 6-year-old boy suffering from acquired epidermolysis bullosa, who presented with extensive lesions of the mucous membranes and disseminated, herpetiform and‘cluster of jewels' like vesicles and bullae arising on erythematous plaques. Direct immunofluorescence showed linear deposits of IgG and C3 at the epidermal basement membrane zone. Indirect immunofluorescence demonstrated circulating autoantibodies(titre 1:128–1:256) directed at the blister floor of human NaCl-split skin, and reacting specifically with collagen VII of the anchoring fibrils, as demonstrated by immunoblotting. The disease was controlled with a combination of dapsone and prednisone. This case demonstrates the importance of modern immunological techniques in classifying childhood autoimmune bullous diseases, as precise diagnosis is important in determining an appropriate therapeutic regimen.     

泛发性获得性大疱性表皮松解症

报告2例泛发性获得性大疱性表皮松解症.2例患者均为40岁后发病,皮损泛发全身,表现为张力性大疱,易误诊为大疱性类天疱疮.盐裂皮肤间接免疫荧光和皮损组织病理检查可资鉴别诊断.