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.     

Linear IgA bullous dermatosis in tunisian children: 31 cases

Background:

Linear IgA bullous dermatosis (LAD) of children is relatively frequent in Africa.

Aim:

We undertook this study to evaluate the frequency of this disease among autoimmune bullous diseases (AIBDs) in Tunisian children.

Materials and Methods:

We present a 32-year retrospective study (January 1976 to December 2007). Children with chronic acquired bullous diseases seen at the Charles Nicolle Hospital of Tunis and for who direct immunofluorescence (DIF) of the perilesional skin demonstrated linear IgA immunoglobulin deposits were included in the study population.

Results:

Thirty-one children with LAD were selected representing 65.9% of all AIBDs of children selected in the same period, with a mean age of 5.5 years and a sex ratio (M/F) of 2.4. Most of the children had generalized eruption (28/31), more profuse on the face, pelvic region, buttocks and limbs. Mucosal lesions happened in only four children (12.9%). The mean duration of the disease was 14 months. DIF demonstrated linear IgA deposits along the dermal–epidermal junction in all patients. IgG, IgM, and complement were also seen (20/31). Indirect immunofluorescence was negative in 67% of cases. Eight patients responded to dapsone; however, prednisone had to be added in seven children to control the disease and erythromycin in four others. A long-term remission period was achieved in 76.1% of patients.

Conclusion:

This study confirms that LAD is the most common AIBD in children in Tunisia which frequently occurs in preschool-aged males. Independently of the used drug, a long-term remission is frequently observed.     

线状IgA大疱性皮病研究进展

线状IgA大疱性皮病是一种以基底膜带存在连续性IgA抗体沉积为特点的罕见的自身免疫性大疱病,可能与遗传、药物、炎症性疾病、肿瘤等有关。线状IgA大疱性皮病的诊断依据临床表现、常规病理和免疫荧光。该病首选的治疗方案是口服氨苯砜,近年来也有生物制剂治疗该病的报道。本文从流行病学、病因、发病机制、临床表现、实验室检查、诊断及治疗等方面对线状IgA大疱性皮病进行总结。     

13例线状IgA大疱性皮病临床病理特征分析

收集2012年7月至2019年6月在本科室诊治的13例LABD,其中男11例,女2例.儿童型6例,成人7例.临床表现:红斑基础上或外观正常的皮肤上出现水疱和大疱,疱壁紧张,疱液清亮,尼氏征(-).皮损组织病理均见表皮下疱,直接免疫荧光见IgA线状沉积于基底膜带.1例患者合并类风湿关节炎,1例患者合并器质性焦虑障碍,1例...     

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。     

IgA autoantibodies in the pemphigoids and linear IgA bullous dermatosis

Please cite this paper as: IgA autoantibodies in the pemphigoids and linear IgA bullous dermatosis. Experimental Dermatology 2010; 19: 648–653. Background: Patients with bullous pemphigoid (BP), mucous membrane pemphigoid (MMP) and pemphigoid gestationis (PG) have IgG antibodies against BP180 and BP230, components of the hemidesmosomes. Patients with linear IgA bullous dermatosis (LABD) have IgA autoantibodies against a 97/120‐kDa protein which is highly homologous to a shedded fragment of the BP180‐ectodomain. Objectives: The aim of our study was to determine the incidence of IgA autoantibodies directed against BP180/BP230 in the pemphigoids and LABD and to determine the antigenic regions that are targeted by IgA autoantibodies. Methods: Utilizing baculovirus‐expressed recombinant BP180 and BP230 proteins, we performed immunoblot analyses for IgA reactivity of sera from patients with BP (n = 30), MMP (n = 10), PG (n = 6), LABD (n = 6) and from control patients with non‐related pruritic dermatoses (n = 8). Results: IgA reactivity against BP180 and/or BP230 was detected in 19/30 of the BP, in 7/10 of the MMP, in 6/6 of the LABD and in 3/6 of the PG sera, respectively, but not in the control group. In all subgroups, the major antigenic site recognized by IgA antibodies was located within the NH₂‐terminus of the BP180‐ectodomain, but only a minority of the sera showed also IgA reactivity against the BP180‐NC16a‐domain. IgA reactivity against the central domain of BP180 was more frequently seen than against its COOH‐terminus. IgA against the COOH‐ and NH₂‐terminus of BP230, respectively, was detected in 6/30 of the BP, 1/10 of the MMP, 1/6 of the LABD and 0/8 control sera. Conclusion: IgA reactivity against BP180 and/or BP230 is a common finding in the pemphigoids.     

IgA autoantibody may be the foremost pathogenic in three cases of linear IgA/IgG bullous dermatosis

Linear IgA/IgG bullous dermatosis (LAGBD) is a relatively rare autoimmune bullous disease characterized by both IgA and IgG antibodies to basement membrane zone. The heterogeneity and pathogenesis of antibodies and the relationship between IgA and IgG in LAGBD have not been fully elucidated. We observed clinical, histological and immunological features of three LAGBD cases at different time points in the disease course. In our cohort, two cases showed IgA antibodies to epidermal antigens vanished when their lesions cleared after 3 months of treatment. One refractory case showed increasing antigens targeted by IgA antibodies with the progression of the disease. Collectively, the results suggest that IgA antibodies may play a major role in LAGBD. In addition, epitope spreading may be related to disease relapse and treatment refractory.     

Successful treatment of a case of idiopathic linear IgA bullous dermatosis with oral sulfasalazine

Linear IgA bullous dermatosis (LABD) is a rare acquired autoimmune chronic vesiculobullous dermatosis affecting primarily young children and older adults. We report a 17‐year‐old Chinese boy with a 2‐month history of intense itching erythema or tense vesicles on healthy skin or on an erythematous base, with parts of lesions arising a characteristic “cluster of jewels” pattern. With the characteristics of vesicles or blisters on the skin, subepidermal blisters with neutrophilic infiltrate on histology, and linear IgA deposits on the basement membrane zone and absence of other immunoglobulins on direct immunofluorescence, LABD was dignosized. Sulfapyridine has also been reported as one of the best options of systemic therapy for LABD. Our patient successfully treated with only oral sulfasalazine (alternative medicine of sulfasalazine), which is safe and effective.     

Treatment of dermatitis herpetiformis and linear IgA bullous dermatosis

Dermatitis herpetiformis (DH) and linear IgA bullous dermatosis (LABD) are IgA-mediated autoimmune bullous diseases. They share an identical histopathology, but are differentiated on the basis of the pattern of IgA deposition on direct immunofluorescence. While DH responds to a gluten-free diet, LABD rarely responds to gluten restriction. In the management of DH, adhering to a gluten-free diet promotes healing of small intestine villus atrophy, resolution of cutaneous disease, and lowers the risk of lymphoma. Dapsone is palliative but not curative in the treatment of DH and LABD. Patients taking systemic dapsone or sulfa-based medication for the treatment of DH or LABD should have a reasonable knowledge of the inherent side effects.     

Coexistence of psoriasis and linear IgA bullous dermatosis

Linear IgA bullous dermatosis (LABD) is characterized by IgA autoantibodies against components of the basement membrane zone (BMZ). A 97-kDa protein is one of the major autoantigens associated with this disease. We report a 68-year-old man who developed LABD after a 3-year history of psoriasis and in the context of active hepatitis C virus infection. He had been treated with cyclosporin for psoriasis for about 9 months. Histologically, there was a subepidermal blister containing neutrophils and eosinophils with lymphocytes infiltrating predominantly in the dermis. Direct immunofluorescent staining showed linear IgA deposition at the BMZ. The patient's IgA autoantibodies bound exclusively to the epidermal side of 1 mol/L salt-split normal human skin. Immunoblot analysis identified a 97-kDa autoantigen in epidermal extracts. This appears to be the first case of LABD with IgA autoantibodies against a 97-kDa autoantigen, associated with psoriasis and hepatitis C virus infection.     

Burn-induced linear IgA dermatosis

There have been several reports of linear IgA dermatosis (LAD) associated with drug exposure and lymphoproliferative malignancy, but trauma and burns have been suggested only in patients with bullous pemphigoid. We present a case of burn-induced LAD in a 48-year-old caucasian male presenting with a recent history of blistering eruption on the periphery of a cicatricial area caused by boiling methyl alcohol. Clinically, he presented a widespread bullous eruption. The direct immunofluorescence examination of a perilesional biopsy revealed an intense homogeneous linear pattern of IgA deposition consistent with the diagnosis of LAD. The patient responded to therapy with systemic steroids.     

Linear IgA bullous dermatosis associated with ulcerative colitis

A 41-year-old woman developed skin vesicles one week before examination. She had been suffering from ulcerative colitis since the age of 30. Histologic examination of a vesicle showed a subepidermal bulla accompanied by mononuclear leukocyte infiltration intermingled with eosinophils and neutrophils. Eosinophilia was also noted. Direct immunofluorescent test revealed linear deposits of IgA in the basement membrane zone.     

氨苯砜治疗成人线状IgA大疱性皮病一例

患者,女,42岁.周身红斑水疱3个月.经病理和免疫病理确诊为线状IgA大疱性皮病.既往曾使用中等剂量糖皮质激素治疗,效果不佳.经加用氨苯砜后病情得以控制,之后激素逐渐减量之停用,目前单用氨苯砜治疗控制中.     

Linear IgA dermatosis: Report of an infantile case and analysis of 213 cases in Japan

A 3‐year‐old boy presented with multiple vesicles, showing a rosette‐like arrangement around the crusts. Histopathological and immunohistochemical examinations demonstrated subepidermal blistering with neutrophilic infiltration associated with deposition of IgA, but not IgG, linearly distributed along the basement membrane zone (BMZ) of the epidermis. Indirect immunofluorescence revealed circulating antibodies (IgA class, ×160) against the BMZ of guinea pig lip skin. Based on the diagnosis of linear IgA dermatosis (LAD) of childhood, administration of dexamethasone (2 mg/day) was started, and the eruptions diminished immediately. Western blot analysis using extract of the HaCaT cell as a substrate, demonstrated the corresponding antigen at 120‐kDa molecular weight. There have been 213 cases of LAD reported in Japan including conference abstracts and these were studied to determine whether infantile cases differed from adult ones, and whether cases associated with IgG as well as IgA (IgA/G type), differed from the cases associated with IgA only (IgA type). IgG contributed less frequently to the infantile type (age of onset, ≤15 years) than to the adult type (age of onset, ≥16 years). Clinical appearance did not show any obvious difference between the IgA/G type and IgA type. However, three‐quarters of cases showing localization of antigen to the dermal side were the IgA/G type.     

Phenytoin-induced linear IgA dermatosis mimicking toxic epidermal necrolysis

A 60-year-old woman developed a severe widespread blistering eruption that also involved the palms and soles, but spared the mucosae, approximately 7 days after starting phenytoin. Phenytoin was commenced postoperatively after a craniotomy resection of a glioblastoma multiforme. The clinical features resembled that seen in toxic epidermal necrolysis. However, the patient was systemically well and the histology and immunofluorescence revealed linear IgA dermatosis. The skin lesions began to slowly heal 2 weeks after discontinuation of the phenytoin.     

The lesional skin of linear IgA bullous dermatosis expresses growth-regulated peptide (GRO)-alpha

The patient was a 62-year-old man with erythema with tense vesiculobullae and erosions on the bilateral elbows, right knee, and one buttock. A skin biopsy specimen revealed subepidermal blister formation with a predominant infiltration of neutrophils and papillary neutrophilic microabscesses. Direct immunofluorescence study showed linear deposition of IgA and weak deposition of IgG at the basement membrane zone of the lesional skin, and indirect immunofluorescence study showed linear deposition of IgA at the epidermal side of the 1M NaCl-separated normal skin. He was diagnosed with linear IgA bullous dermatosis. Immunohistochemical study revealed that the lesional and perilesional keratinocytes expressed growth-regulated peptide (GRO) -alpha, a potent chemoattractant for neutrophils. This suggests that GRO-alpha plays a role in the infiltration of neutrophils into the lesional skin and in bulla formation in linear IgA bullous dermatosis.     

Linear IgA bullous dermatosis in a patient with renal cell carcinoma

Linear IgA bullous dermatosis (LABD) is an autoimmune subepidermal bullous disease with heterogeneous clinical manifestations, characterized by linear deposition of IgA along the epidermal basement membrane zone. We report a patient with a metastasized renal cell carcinoma who developed an extensive blistering eruption. The lesions showed immunopathological findings characteristic of LABD. The patient showed a fair response to prednisolone and dapsone. Treatment to control the LABD was no longer required when interferon-alfa was started as palliative therapy for the metastasized renal cell carcinoma. The association of LABD and malignancies has been documented before and is not due to mere chance alone.     

Depot sulfonamid associated linear IgA bullous dermatosis with erythema multiforme-like clinical features

A case of erythema multiforme-like reaction, following therapy with sulfadimethoxynum is reported in a 19-year-old male patient. Histological examination demonstrated a subepidermal bulla and direct immunofluorescence revealed linear deposition of IgA at the dermoepidermal junction. These observations illustrate that linear IgA bullous dermatosis can mimic the clinical features of erythema multiforme and suggest the possibility of drug-induced pathogenesis.     

儿童线状IgA/IgG大疱性皮病一例

患儿,男,7岁.因躯干、四肢散发红斑、水疱伴瘙痒2个月就诊.发病前有泳池"暴晒"史.背部水疱组织病理:表皮下水疱,真皮乳头中性粒细胞及少许嗜酸粒细胞小脓肿,浅层中性粒细胞、嗜酸粒细胞、淋巴细胞浸润.正常人皮肤盐裂间接免疫荧光:循环抗体IgA、IgG于表皮侧均有沉积,局部区域IgG表皮真皮双侧沉积.综上诊断为儿童线状Ig...     

IgG, IgA and IgE autoantibodies against the ectodomain of BP180 in patients with bullous and cicatricial pemphigoid and linear IgA bullous dermatosis

BACKGROUND: Bullous pemphigoid (BP), linear IgA bullous dermatosis (LABD) and cicatricial pemphigoid (CP) are clinically distinct autoimmune bullous skin diseases characterized by autoantibodies against components of the epidermal basement membrane. Like most patients with BP, a significant subgroup of patients with CP has circulating IgG specific for BP180, a transmembraneous protein of hemidesmosomes. Moreover, sera of patients with LABD contain IgA autoantibodies reactive with a 97/120-kDa protein, LABD antigen 1, which is highly homologous to the extracellular portion of BP180. OBJECTIVES: We aimed to determine whether, in these diseases, autoantibody reactivity to BP180 is restricted to distinct immunoglobulin subtypes. METHODS: Utilizing a baculovirus-encoded form of the ectodomain of BP180, sera from patients with BP (n = 10), CP (n = 9), LABD (n = 10) and normal human control sera (n = 10) were analysed by immunoblot for IgG, IgA and IgE reactivity against BP180. RESULTS: All of 10 BP sera displayed IgG, IgA and IgE reactivity with BP180. Six and seven of nine CP sera, respectively, contained IgG and IgA autoantibodies reactive with BP180, but none of nine sera contained BP180-specific IgE. Nine of 10 LABD sera contained IgA, and six of 10 IgG, which was reactive with BP180, but none of 10 sera showed IgE reactivity to BP180. CONCLUSIONS: The presence of IgG and IgA autoantibody responses to BP180 in patients with three clinically distinct autoimmune bullous diseases indicates that an autoimmune response to the same distinct adhesion protein may lead to different clinical manifestations. It is therefore conceivable that variable epitopes of BP180 are targeted by the different autoantibody isotypes, resulting in the distinct clinical pictures.