Immunoelectronmicroscopic differentiation of linear IgA bullous dermatosis of adults with coexistence of IgA and IgG deposition from bullous pemphigoid.

BACKGROUND: The differentiation between linear IgA bullous dermatosis (LABD) and bullous pemphigoid (BP) is sometimes difficult in patients who have both IgA and IgG deposition in a linear pattern at the basement membrane zone. OBJECTIVE: We address whether two cases of acquired subepidermal blistering disease with coexistence of IgA and IgG deposition in a linear pattern at the basement membrane zone are LABD or BP. METHODS: The two cases were investigated by immunoelectron microscopy and compared with two typical cases of LABD. RESULTS: In both cases, the deposition of IgA and IgG was ultrastructurally localized below the lamina densa in close association with anchoring fibrils, as was seen in two cases of typical LABD. CONCLUSION: These findings indicate that our two cases of acquired blistering disease with co-existence of IgA and IgG deposition are LABD, rather than BP.     

Subepidermal blasenbildende Autoimmundermatose mit linearen Ablagerungen von IgA und IgG

A 29-year-old female patient with an autoimmune subepidermal blistering disease had linear deposits of both IgA and IgG at the basement membrane zone. Clinically, the patient presented with tense blisters on the face, trunk, extremities and oral mucosa. Histologically, we found a subepidermal blister formation and a predominantly neutrophilic infiltrate. Direct immunofluorescence showed linear deposits of IgA along the basement membrane zone, as well as linear deposits of IgG and C3 as typically found in bullous pemphigoid. Indirect immunofluorescence demonstrated circulating IgA and IgG autoantibodies. This case extends previous reports on a subgroup of patients with subepidermal blistering diseases characterized by the presence of both IgA and IgG anti-basement membrane antibodies. These patients reveal clinical, histological and immunopathological features of linear IgA disease and bullous pemphigoid.     

Vancomycin-associated linear IgA dermatosis. A report of three cases.

BACKGROUND: Linear IgA dermatosis is an autoantibody-mediated, subepidermal blistering disease that is rarely associated with drug exposure. OBJECTIVE: We report the development of linear IgA dermatosis in three patients associated with the administration of vancomycin and further characterize the immunopathology. METHODS: Direct and indirect immunofluorescence assays were performed to characterize the immunoreactants, determine the subclass of the IgA deposits, and map the site of antibody deposition. RESULTS: A subepidermal blistering disease developed in all patients shortly after vancomycin was initiated, which resolved on discontinuation of the drug. Immunofluorescence studies revealed linear deposits of IgA1 only at the basement membrane zone, below the lamina lucida. Circulating IgA anti-basement membrane zone antibodies were not detected. CONCLUSION: Three patients had linear IgA dermatosis in association with the administration of vancomycin. All patients had linear deposits of IgA1 localized to the sublamina densa zone. Immunophenotypically, the disease in these patients mimics the pattern of IgA deposits seen in the majority of patients with idiopathic linear IgA dermatosis.     

IgA linear dermatosis of childhood (chronic Bullous disease of childhood)

Of twenty-seven cases of subepidermal blistering disease of children twelve corresponded clinically, histologically and immunologically to dermatitis herpetiforms of adults, six to bullous pemphigoid, and eight to chronic bullous disease of childhood (CBDC), i.e. IgA linear dermatosis. This latter disease seems to be a distinct entity, different from both dermatitis herpetiformis and bullous pemphigoid, and is characterized immunopathologically by linear IgA deposits at the basement membrane zone. These cases usually do not show intestinal involvement and respond well to combined treatment with sulphones and corticosteroids, whereas sulphones or sulphapyridine alone are, even in very high doses, not sufficient for full control of the disease. CBDC or IgA linear dermatosis of childhood may be regarded as a counterpart of IgA linear dermatosis of adults.     

Unusual clinicopathological and immunological presentation of chronic bullous dermatosis of childhood (linear IgA dermatosis)

Linear IgA bullous dermatosis is a rare sulfone-responsive subepidermal blistering disorder of unknown etiology in which smooth linear deposits of IgA are found in the basement membrane zone. Chronic bullous dermatosis of childhood is equivalent to linear IgA disease of adulthood and is characterized by an abrupt onset of large, widespread and tense bullae on a normal or erythematous base. In this case, we describe an unusual presentation of chronic bullous dermatosis in a 14-month-old Saudi girl. Histopathological examination revealed subepidermal cell poor blisters with linear deposition of IgA, IgG, IgM, and C3 along the dermoepidermal junction. The unusual clinical, histopathological and immunofluorescence findings in this patient are discussed, with an account on the differential diagnosis in such cases along with a detailed review of the relevant literature.     

A case of cicatricial pemphigoid with circulating IgA and IgG antibodies directed against 280 kD, 165 kD and 120-130 kD epidermal antigens

A case of subepidermal autoimmune blistering disease in an 86-year-old woman is reported. Clinical features were those of a cicatricial pemphigoid, with prominent mucosal involvement leading to conjunctival and nasal scarring. Direct immunofluorescence findings were consistent with either cicatricial pemphigoid or linear IgA dermatosis, since both IgG and IgA linear deposits were found at the basal membrane zone. Immunoelectron microscopy of perilesional skin revealed IgA deposits within the lamina lucida and immunoblotting of the patient's serum disclosed IgA and IgG antibodies directed against epidermal antigens of 280, 165 and 120-130 kD.     

Scarring linear IgA dermatosis in the adult

A 54-year-old woman had a six-months history of a scarring blistering disease with clinical signs of dermatitis herpetiformis and bullous pemphigoid. Direct immunofluorescence examination showed homogeneously linear deposits of IgA along the dermo-epidermal junction. Electron microscopic studies revealed blistering above and beneath the lamina densa. Referring to this new case of a scarring linear IgA disease we discuss some other forms of scarring bullous diseases in adults.     

IgA bullous pemphigoid: a distinct blistering disorder

We report a patient with an eccrine carcinoma who developed localized blistering which clinically resembled pemphigoid, histologically showed subepidermal blistering with features of both dermatitis herpetiformis and bullous pemphigoid, responded to dapsone and exhibited linear IgA deposition on direct immunofluorescence. The nosological position of patients with linear IgA deposition and subepidermal blistering is not clear. A review of the literature reveals that in adults linear IgA deposition may occur in three separate situations: dermatitis herpetiformis, bullous pemphigoid and a third condition of which our case is an example which is best termed IgA bullous pemphigoid. This condition is distinguished from cases of dermatitis herpetiformis with linear IgA by the clinical features and the site of IgA deposition on immunoelectronmicroscopy. It is distinguished from cases of bullous pemphigoid with linear IgA by the absence of circulating IgG antibasement membrane zone antibody, the therapeutic response to dapsone and the frequent occurrence of circulating IgA antibasement membrane zone antibody. IgA bullous pemphigoid has not previously been reported with a carcinoma but the association lends further support to the concept that this eruption represents a variant of pemphigoid.     

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.     

Dermatitis herpetiformis Duhring with linear deposits of IgA (linear IgA dermatosis)

Three patients with linear deposits of IgA along the epidermal basement membrane were studied. The clinical and histopathological picture as well as the response to dapsone were typical of dermatitis herpetiformis. Two of the three patients were HLA-B8/DR3-positive. By immunoelectron microscopy, the previously reported two types of linear IgA deposits were confirmed: in one patient, the IgA precipitates were localized below the basal lamina as in dermatitis herpetiformis, in the other two above the basal lamina in the lamina lucida as in bullous pemphigoid. The immunoelectron microscopic findings imply that in some patients with linear IgA dermatosis a pathomechanism different from that in classical dermatitis herpetiformis may be operative.     

Childhood cicatricial pemphigoid with linear IgA deposits

Four cases showing a unique combination of scarring conjunctivitis and widespread blistering, commencing in childhood are described. In all cases linear deposits of IgA were present at the dermo-epidermal junction in association with low titres of circulating IgA antibasement membrane zone antibody in three cases. The relationship of this entity to chronic bullous disease of childhood, cicatricial pemphigoid and linear IgA disease of adults is as yet unclear and it may be a distinct bullous dermatosis.     

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.     

IgA linear dermatosis (author's transl)]

Besides the typical forms of dermatitis herpetiformis (DH) and bullous pemphigoid (BP) of adults and children, there are cases combining clinical, histological and electronmicroscopic features of both. Linear continuous IgA deposits along basement membrane zone (BMZ) are a most characteristic finding. They differ from the granular IgA deposits in DH, even if these are also distributed along the BMZ (however, preserving as a rule their granular pattern). IgG circulating anti-BMZ antibodies are absent, whereas in some cases IgA anti-BMZ antibodies may be found. In contrast to DH, there is no gluten-sensitive enteropathy, and the gluten-free diet is ineffective. The recognition of this bullous disease as a distinct entity is of practical significance because these cases respond well to combined treatment with sulfones and corticosteroids, all in small doses. Because of diagnostic importance of linear IgA deposits at BMZ we have proposed the name IgA linear dermatosis. In children a counterpart of IgA linear dermatosis of adults is chronic bullous disease of childhood (CBDC), which we propose to call IgA linear dermatosis of childhood.     

Cutaneous IgA deposits in bullous diseases function as ligands to mediate adherence of activated neutrophils

Linear IgA bullous dermatosis and dermatitis herpetiformis are inflammatory subepidermal blistering diseases characterized by IgA deposits at the cutaneous epithelial basement membrane and in dermal papillae, respectively. Inflammation in both disorders localizes to sites of IgA deposition and is characterized by a predominance of neutrophils. From these observations we postulate that IgA deposits in both diseases may contribute to the recruitment and/or localization of neutrophils. In this study we examined the ability of in vitro and in vivo bound IgA anti-basement membrane autoantibodies from patients with linear IgA bullous dermatosis and in vivo bound IgA deposits in dermal papillae from patients with dermatitis herpetiformis to mediate adherence of neutrophils stimulated by granulocyte macrophage colony-stimulating factor. The study showed that stimulated neutrophils adhered to basement membranes and dermal papillae containing IgA deposits. Adherence was IgA anti-basement membrane antibody concentration dependent and correlated with the immunofluorescence staining intensity of IgA deposits in dermal papillae. Adherence to IgA deposits but not IgG deposits could be inhibited by purified exogenous secretory IgA but not IgG and adherence to IgG deposits could be inhibited by purified exogenous IgG but not secretory IgA. These results provide direct experimental evidence that cutaneous IgA deposits in linear IgA bullous dermatosis and dermatitis herpetiformis can function as ligands for neutrophil adherence and have a role in the localization of inflammation in these disorders.     

Autoimmune subepidermal blistering diseases in Uganda: correlation of autoantibody class with age of patients

BACKGROUND: No data are available on the incidence and immunoreactivity of autoimmune subepidermal blistering skin diseases in East Africa. METHODS: All patients with frank blisters/erosions on the skin and/or mucous membranes that attended the Department of Dermatology at Mbarara University, Uganda, from May 2000 to June 2002, were investigated. The diagnosis was based on the clinical presentation and on the presence of circulating autoantibodies detected by indirect immunofluorescence microscopy on 1 m NaCl-split human skin and by Western blotting of recombinant and cell-derived forms of BP180, BP230, and type VII collagen. RESULTS: Twenty-two patients with autoimmune subepidermal blistering skin disorders were identified, including nine with bullous pemphigoid (41%), four with linear immunoglobulin A (IgA) disease (18%), three with mucous membrane pemphigoid (14%), two with linear IgG/IgA bullous dermatosis (9%), and one each with cicatricial pemphigoid and epidermolysis bullosa acquisita (5%). In addition, two patients with immunoreactivity to both the epidermal and dermal side of salt-split skin by indirect immunofluorescence microscopy, who were unreactive to type VII collagen, were provisionally diagnosed as "mixed pemphigoid" (9%). In patients with subepidermal blistering diseases, IgG reactivity correlated significantly with old age, whereas younger patients preferentially developed IgA autoantibodies (P = 0.024). CONCLUSIONS: The age of patients with autoimmune subepidermal blistering diseases appears to influence the immunoglobulin class of autoantibodies. The high frequency of IgA autoantibodies in Ugandan patients may be explained by the age distribution of the Ugandan population.     

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.     

Autoantibodies in a subgroup of patients with linear IgA disease react with the NC16A domain of BP1801

Linear IgA disease is an autoimmune subepidermal blistering disease characterized by IgA deposits at the cutaneous basement membrane zone. IgA antibodies from linear IgA disease sera react with antigens of 97 kDa (LABD97) and 120 kDa (LAD-1), both of which appear to be fragments of the extracellular domain of bullous pemphigoid 180 (type XVII collagen). The aim of this study was to determine whether linear IgA disease sera react with the immunodominant region of BP180 (NC16A domain), which is a major target of IgG autoantibodies produced by patients with bullous pemphigoid. Indeed, 11 of 50 linear IgA disease sera were found to contain IgA autoantibodies that recognized a recombinant form of NC16A by immunoblotting. The same sera also reacted with NC16A by enzyme-linked immunosorbent assay. An epitope mapping analysis uncovered four linear IgA disease-associated epitopes located within the 45 amino acid N-terminal stretch of NC16A, all of which were previously identified as antigenic sites targeted by bullous pemphigoid autoantibodies. Eight of the linear IgA disease sera that were reactive with NC16A also recognized LAD-1 secreted by the SCC-25 cell line, and five sera recognized BP180 extracted from keratinocytes. Linear IgA disease sera depleted of reactivity to NC16A by immunoadsorption continued to react with both the LAD-1 antigen and BP180 by immunoblotting and with the basement membrane zone by indirect immunofluorescence microscopy. Our results demonstrate that IgA autoantibodies from a subset of linear IgA disease patients react with the same sites on BP180 that are targeted by IgG autoantibodies in bullous pemphigoid.     

线状IgA大疱皮病8例分析

线状IgA大疱皮病是一种少见的自身免疫性大疱性皮肤病 ,近 10年在我科的临床患者中 ,通过临床表现、皮肤病理检查及免疫荧光检查明确诊断为线状IgA皮病并长期随访的患者仅 8例 ,男 5例 ,女 3例 ;儿童型 5例 ,成人型 3例。 7例患者使用DDS治疗 ,皮疹得到完全控制 ,无不良作用发生。DDS可作为治疗线状IgA大疱皮病的首选药物。     

Linear IgA Bullous Dermatosis in a Neonate

Abstract: A newborn black boy had two facial blisters at birth that progressed to bullous lesions over the trunk, genitals, extremities, and oral and tracheal mucosa. A biopsy specimen demonstrated a subepidermal bulla with mixed eosinophilic and neutrophille, inflammatory infiltrate. Direct immunofluorescence showed linear IgA, IgG, and C3 depositions along the basement membrane zone, consistent with a diagnosis of childhood linear IgA bullous dermatosis (chronic bullous dermatosis of childhood). The skin disease was controlled with combined prednisone and dipsone. This is the youngest reported patient with the disease. Linear IgA bullous dermatosis should be considered in the differential diagnosis of blistering diseases of the newborn, and immunofluorescence should be performed on a skin biopsy specimen.     

Linear IgA bullous dermatosis of adults and children: an immunoelectron microscopic study

The ultrastructural localization of the IgA deposits in the skin of 15 patients with linear IgA bullous dermatosis of adults (LAD), 13 with chronic bullous dermatosis of childhood (CBDC) and three with childhood cicatricial pemphigoid (CCP) were studied. The site of the antigen was determined using sera from two LAD, 13 CBDC and two CCP patients. In all 31 patients the IgA was located predominantly below the lamina lucida (sublamina densa). Similarly, the indirect immunoelectron microscopic studies demonstrated the antigen to be present at the same site, below the lamina densa. This suggests that in linear IgA bullous dermatosis the antibody reacts with the antigen in the sublamina densa region of the basement membrane zone.