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.     

Chronic bullous dermatosis of childhood.

A case of chronic bullous dermatosis of childhood in a 3-year-old boy is described. Immunoflourescence tests were negative and biopsy of the jejunal mucosa showed marked villous atrophy. The dermatosis was brought under control by a combination of diaminodiphenylsulphone and systemic steroids. The relationship with other bullous eruptions of childhood such as dermatitis herpetiformis and bullous pemphigoid is discussed.     

The ultrastructural localization of IgA deposits in chronic bullous disease of childhood (CBDC).

A case of bullous disease in a child with linear IgA immune deposits at the basement membrane zone and with some clinical, histological, and electron microscopic characteristics both of dermatitis herpetiformis and bullous pemphigoid, is described. The bulla formed between the basal lamina and basal cell membranes as in bullous pemphigoid, but at the same time there were numerous inflammatory cells in the dermis just below the partly destroyed basal lamina and also abundant fibrin deposits in very recent bulla and in the skin, all of which is rather characteristic of dermatitis herpetiformis. Ultrastructurally, the IgA deposits were located chiefly below the lamina basalis (the dermal type) but also, though less abundantly, in the lamina lucida, very much as we have seen them to be in adult cases with linear IgA immune deposits at the basement membrane zone. The investigations have supplied further evidence showing the chronic bullous disease of childhood to be actually a counterpart of the form in adults with the same linear localization of IgA deposits.     

Histology of linear IgA disease, dermatitis herpetiformis, and bullous pemphigoid

The histologic appearances of cutaneous biopsy specimens from 30 patients with linear IgA disease with a continuous band of IgA along the basement membrane, four patients with a linear pattern of granular IgA along the basement membrane, 26 patients with dermatitis herpetiformis who had IgA in the papillary dermis, and 23 patients with bullous pemphigoid who had IgG and/or C3 along the basement membrane were compared. Those with linear and granular IgA and dermatitis herpetiformis differed from those with bullous pemphigoid in five respects. Multiple microabscesses and fibrin at tips of papillae and leukocytoclasis were less common in bullous pemphigoid, whereas a dense infiltrate of eosinophils in and below bullae and a linear infiltrate of eosinophils along the basement membrane were more common in bullous pemphigoid. Also, multilocular bullae and acantholysis were more common in dermatitis herpetiformis than in bullous pemphigoid. Linear IgA disease differed from dermatitis herpetiformis in two respects. Acantholysis and fibrin at the tips of papillae and leukocytoclasis were more common in dermatitis herpetiformis. The specimens from patients with granular IgA did not differ significantly from those with linear IgA or dermatitis herpetiformis. The appearances of biopsy specimens of patch tests with potassium iodide taken from 11 patients with dermatitis herpetiformis and linear or granular IgA disease were similar to those taken from spontaneous lesions.     

Linear arrangement of neutrophils along the Basal layer in bullous pemphigoid: a unique histological finding

Bullous pemphigoid is an inflammatory autoimmune subepidermal bullous disease with distinct immunohistological features. We report an unusual case of a 59-year-old woman with a bullous eruption whose lesional skin biopsy showed a subepidermal blister with a linear arrangement of neutrophils, mimicking linear IgA bullous dermatosis. However, direct immunofluorescence studies demonstrated IgG and C3 linear deposition along the basement membrane zone, compatible with bullous pemphigoid. We suggest that bullous pemphigoid should therefore be considered in the differential diagnosis of neutrophil-rich subepidermal bullous diseases along with dermatitis herpetiformis and linear IgA.     

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.     

Adult linear IgA bullous dermatosis: report of three cases

Linear immunoglobulin A bullous dermatosis is a rare autoimmune disease that usually has an excellent prognosis in childhood; however, its control is more difficult in adults. It presents heterogeneous clinical manifestations and is frequently confused with other bullous diseases such as bullous pemphigoid and Duhring’s dermatitis herpetiformis. Dermatologists’ awareness of this disease contributes to early diagnosis and appropriate treatment. We thus report three cases of linear immunoglobulin A dermatosis in adults.     

Polymorphic pemphigoid. Is it still worth using this terminology?

The term polymorphic pemphigoid has been used in the literature as a variant of bullous pemphigoid. But this term is imprecise and now obsolete, since patients with linear IgA dermatosis have been reported under this terminology. The patients who develop an atypical subepidermal bullous disease with clinical and histological features of both bullous pemphigoid and dermatitis herpetiformis may actually be classified into three groups: (1) vesicular variant of bullous pemphigoid; (2) linear IgA dermatosis, and (3) mixed subepidermal bullous disease.     

Chronic bullous disease of childhood and linear IgA disease of adults are IgA1-mediated diseases

Linear IgA disease is characterized by the presence of linear IgA deposits at the basement membrane zone of the skin, and in some cases by circulating basement membrane zone antibodies. The disease occurs in both adults and children, and is designated adult linear IgA disease in the former and chronic bullous disease of childhood in the latter. The subclass distribution of the circulating and bound basement membrane zone antibodies was studied in 32 children and eight adults. The results were compared with five dermatitis herpetiformis patients and five normal controls. The circulating antibodies (39 patients) and the cutaneous deposits (39 patients) were IgA1 in all 40 patients with linear IgA disease. The cutaneous deposits in dermatitis herpetiformis were also all IgA1, and no circulating antibodies were detected. The controls were all negative. This large series of children and adults with linear IgA disease demonstrates that the circulating and cutaneous basement membrane zone deposits are all IgA1, and suggests that linear IgA disease is an IgA1-mediated disease.     

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.     

BULLOUS PEMPHIGOID IN CHILDHOOD: REPORT OF THREE CASES AND A REVIEW OF LITERATURE

Three proven cases of bullous pemphigoid in childhood which responded to dapsone are reported. The clinical and immunological criteria for diagnosis were similar to those in the aged. This report emphasizes that the condition is a distinctive clinical entity and entirely different from dermatitis herpetiformis and benign chronic bullous dermatosis of childhood.     

Chronic bullous dermatosis of childhood–clinical and immunological features seen in African patients

During the period 1985-88, 30 children with a chronic blistering dermatosis were studied. Of these 25 were found to have chronic bullous dermatosis of childhood (CBDC) and five had bullous pemphigoid (BP). No case of dermatitis herpetiformis (DH) was seen in the same period. Except for the difference in immunofluorescence (IMF) there were no definite clinical, histological or therapeutic differences between the two groups. All the children were Africans with the exception of one Indian girl. Their ages ranged from 1 year to 12 years with a mean of 5 years. The females outnumbered the males in a ratio of 3:2. All children had a generalized eruption consisting of large tense blisters arising on normal skin. The blisters were more profuse on the lower trunk, pelvic region and limbs. Face and scalp were also affected. Histological features of BP and DH were seen. Direct IMF in the CBDC patients showed linear deposits of IgA at the basement membrane zone (BMZ) while linear deposits of IgG were seen in the BP group. Complement and IgM were also seen in some cases in both groups. Sixty per cent of the CBDC patients showed IgA BMZ antibodies by indirect IMF. There were no symptoms or signs of malabsorption. Serum vitamin B12 and folate levels were normal. HLA studies showed the B-8 antigen in five of the 20 patients studied. Therapy was difficult in most cases. All patients haemolysed on therapeutic doses of dapsone, sulphapyridine and/or prednisone had to be added. Follow-up was generally poor as six patients failed to return after discharge from hospital.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Adult linear IgA bullous dermatosis: a polymorphic disorder

We report on two patients with unusual forms of adult linear IgA bullous dermatosis. One was a middle-aged woman who had targetoid lesions and bullae on her trunk and extremities. This patient first presented with lesions that clinically resembled erythema multiforme, but these evolved into a widespread eruption with bulging, elongated bullae. Examination of a biopsy specimen showed changes compatible with dermatitis herpetiformis and bullous pemphigoid. Findings on immunofluorescence studies showed deposition of linear IgA at the basement membrane zone. The second patient was an elderly woman with intensely pruritic vesicles whom we classified as having vesicular pemphigoid, until the linear IgA band on direct immunofluorescent test results became the predominant immunofluorescent finding. These cases are reported because of their unusual clinical presentations. The mechanism for the targetoid lesions in the first patient is discussed.     

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.     

Skin immunofluorescence in the diagnosis of primary bullous diseases—a review of 279 cases

Immunofluorescence (IF) findings are reviewed in 279 consecutive patients with a suspected primary bullous disorder (PBD), IF substantiated the diagnosis of PBD in 51%. The most frequent disorders were bullous pemphigoid (44%), dermatitis herpetiformis (25%) and pemphigus (13%) A diagnosis of PBD was refuted in 29% of cases with bullae; whereas 18% of cases presenting with an itchy papular eruption were shown to have a PBD. All 19 patients with intercellular epidermal IgG ± C3 on direct IF had a clinical and histological diagnosis of pemphigus. Thirty-five patients with granular sub-epidermal IgA ± C3 had dermatitis herpetiformis. Of the 72 with linear C3 ± IgG at the dermo-epidermal junction (DEJ), 62 had bullous pemphigoid, seven herpes gestationis, two cicatricial pemphigoid, and one epidermolysis bullosa acquisita. The 13 patients with linear IgA as the predominant immunoglobulin at the DEJ appeared to form a distinct clinical group, i.e. linear IgA disease. Deposition of IgA at the DEJ appeared to be a marker for mucosal disease in the series as a whole. The presence of a second immunoglobulin at the DEJ (in addition to IgG) in patients with bullous pemphigoid was associated with more severe disease. In 50%, of the biopsies IF was either negative or showed non-specific patterns of staining which did not associate with any particular clinical feature: of these, the most common were diffuse dermal IgG, dermal fibrinogen, granular C3 at the DEJ and vascular deposits. IF examination is of considerable value in the diagnosis and management of PBD provided that non-specific patterns of deposition are interpreted appropriately.     

Vancomycin-induced linear IgA bullous disease presenting as toxic epidermal necrolysis

Linear IgA bullous dermatosis (LABD) is a rare autoimmune vesiculobullous disorder characterized by variable clinical presentations that may mimic bullous pemphigoid, dermatitis herpetiformis, cicatricial pemphigoid and erythema multiforme. A few cases of drug-induced LABD that clinically resembled toxic epidermal necrolysis (TEN) have been reported. A subset of patients with LABD have been found to be drug-induced; the most common drug being vancomycin. The diagnosis of LABD is confirmed by the presence of a linear band of IgA along the basement membrane zone on direct immunofluorescence microscopy. We report a case of a 77-year-old man who presented to us with vancomycin-induced LABD that presented clinically as TEN. He had a complete recovery over a 3-week period following discontinuation of the vancomycin and the addition of oral dapsone therapy. It is important to be aware that drug-induced LABD can mimic TEN.     

Chronic bullous dermatosis of childhood.

The clinical features, laboratory studies, and therapeutic responses of two boys with chronic bullous dermatosis of childhood are described. Direct immunofluorescent preparations of sections from a lesion, skin adjacent to a lesion, and uninvolved skin demonstrated linear deposition of IgA at the dermoepidermal junction in all three biopsy specimens from one patient. Similar preparations from the second child were negative for staining. No circulating antibodies to skin components were detected in either child by means of multiple substrates. Neither child had clinical manifestations nor laboratory findings suggestive of an associated gastrointestinal lesion; therefore, small bowel biopsies were not performed. Immunologic studies failed to demonstrate any of the abnormalities frequently described in dermatitis herpetiformis. Both boys responded dramatically to sulfapyridine therapy.     

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.     

Bullous pemphigoid and dermatitis herpetiformis: mixed bullous disease or coexistence of two separate entities?

We present a 73-year-old man with a 5-year history of dermatitis herpetiformis who developed lesions with the clinical, histologic, and immunologic features of bullous pemphigoid. Direct immunofluorescence testing of a skin biopsy demonstrated both granular deposition of IgA, predominantly in the papillary bodies, and linear deposition of IgG and C3 at the basement membrane zone. This mixed direct immunofluorescence pattern, typical for dermatitis herpetiformis in the type of IgA deposits, but also typical for pemphigoid in the linear localization of IgG and C3, is unusual. This case emphasizes that even after a specific diagnosis has been established, if the clinical morphology or response to therapy changes, repeat histologic and immunofluorescence studies may be indicated in diagnosis and management of patients with bullous disease.