There is great diversity in the clinical presentation of EBA. The common denominator for patients with EBA is autoimmunity to type VII (anchoring fibrils) collagen and diminished anchoring fibrils (Woodley 1988; Woodley et al. 1988). Although the clinical spectrum of EBA is still being defined, it appears that there are at least five clinical presentations of EBA (Fig. 2):
(1) "Classical" presentation that was initially described in EBA and closely resembles the features seen in patients with inherited forms of DEB
(2) BP-like presentation
(3) CP-like presentation
(4) Brunsting-Perry Pemphigoid-like presentation
(5) Linear IgA bullous dermatosis (LABD)-like disease. Its childhood presentation can be reminiscent of Chronic Bullous Disease of Childhood.
This form of EBA presents as a mechanobullous noninflammatory disease with an acral distribution. The blisters and erosions heal with scarring and milia formation. This presentation in its mild form is reminiscent of porphyria cutanea tarda, and in its more severe forms is reminiscent of hereditary recessive DEB (Yaoita et al. 1981). Despite the similarities between EBA and porphyria cutanea tarda, patients with EBA do not present with hirsutism, photodistribution, scleroderma like changes and high levels of urinary por-phyrins (Woodley 1988; Woodley et al. 1998).
Classical EBA is a mechanobullous disease marked by skin fragility over trauma prone surfaces. Blisters, erosions and scars occur over the back of the hands, knuckles, elbows, knees, sacral area, and feet (Fig. 2A). There is often significant involvement of the oral mucosa with erosions and frank blisters. On the glabrous skin, the vesicles and bullae appear tense on non-inflamed or scarred skin. They can be hemorrhagic and can result in erosions, crusts, scales, scars, scarring alopecia, milia cysts and nail dystrophy. The lesions heal with scarring and frequently with the formation of pearl-like milia cysts within the scarred areas. In severe cases, there may be fibrosis of the hands and fingers and esophageal stenosis (Stewart et al. 1991; Harman et al. 1998). The histology shows dermal-epidermal separation at the BMZ and minimal inflammation.
These patients present with features characteristic of the autoimmune bullous disease, BP, or a mixture of features characteristic of both BP and classic EBA presentation (Gammon et al. 1982, 1984b). This form of EBA manifests as a widespread inflammatory vesiculobullous eruption involving the trunk, extremities and skin folds usually accompanied by pruritus (Fig. 2B). Tense bullae are situated on inflamed and/or urticarial skin. In contrast to classical EBA, skin fragility is not prominent and scarring and milia formation may be minimal or absent. The distribution of the lesions is not confined to traumaprone sites. The histology shows a moderate to dense polymorphic infiltrate of mononuclear cells and granulocytes. Neutrophils are often the predominant granulocyte, but occasionally eosinophils are seen.
The clinical features in these patients closely resemble those considered characteristic of CP. This form of EBA presents as a bullous disease with a predominance of mucosal involvement. The patient may present with erosions and scars of the mouth, upper esophagus, conjunctiva, anus, and vagina (Dahl 1979; Stewart et al. 1991; Harman et al. 1998) with or without similar lesions on the glabrous skin. Recently, tracheal involvement has been reported in the CP-like presentation of EBA (Wieme et al. 1999). There is also one report of predominantly mucosal involvement with no scaring (Tokuda et al. 1998). Unlike classical EBA, patients with the CP-like presentation often do not show significant skin fragility, evidence of trauma-induced lesions, or a predilection for blistering on extensor skin surfaces. The histology shows subepidermal blisters and usually a mixed inflammatory infiltrate in the upper dermis and at the BMZ and microscopic scarring.
Brunsting-Perry Pemphigoid is a chronic recurrent subepidermal scarring vesiculobullous eruption localized to the head and neck. In contrast to CP, it has minimal or no mucosal involvement (Kurzhals et al. 1991; Yancey 1998). IgG autoantibodies are deposited at the BMZ, but the autoantigenic target for these autoantibodies has not been defined. Recently, several patients have been reported to have the clinical, histological and immunological features of Brunsting-Perry Pemphigoid but their IgG autoantibodies are targeted against type VII (anchoring fibril) collagen (Kurzhals et al. 1991; Joly et al. 1993; Choi et al. 1998; Woodley et al. 1998). Therefore, we believe that Brunsting Perry Pemphigoid may actually be a clinical presentation of EBA.
This form of EBA is manifested by a subepidermal bullous eruption, a neut-rophilic infiltrate and linear IgA deposits at the BMZ when viewed by direct immunofluorescence microscopy. It may resemble Chronic Bullous Disease of Childhood and feature tense vesicles arranged in an annular fashion and involvement of mucous membranes (Callot-Mellot et al. 1997, Park et al. 1997). The autoantibodies are usually IgA, IgG or both.
The diagnostic category of these patients with IgA antibodies against type VII collagen deposited in a linear fashion along the BMZ is not clear. Some clinicians regard these patients as purely LABD (Hashimoto et al. 1996), while others regard these patients as a subset of EBA (Rusenko et al. 1989; Bauer et al. 1999). It is interesting to note that in a recent study (Lee 2000), 20 EBA patients' sera were evaluated for serum IgA anti-type VII collagen antibodies by immunoblotting. The investigators detected low titers of IgA anti-type VII collagen antibodies in 80% of the patients in addition to IgG.
Childhood EBA is a rare disease with variable presentations. In a recent study of 14 children with EBA, five of the patients presented as a LABD - like disease and five patients presented with the BP-like form of EBA. The remaining four children presented with the classical mechanobullous form of EBA (Callot-Mellot et al. 1997). Eleven out of 14 had mucosal involvement and all had IgG deposits at the BMZ by direct immunofluorescence, in addition to other immunoreactants. Indirect immunofluorescence was positive in 10 out of 14 patient sera, and the predominant serum antibody was of the IgG class. Although mucosal involvement is frequent and severe in childhood EBA, the overall prognosis and treatment is more favorable than in adult EBA (Callot-Mellot et al. 1997; Edwards et al. 1998).
The clinical presentation of the EBA patient may change during the course of the disease or can show two different presentations simultaneously. About 25% of patients with EBA may appear with the BP-like clinical appearance (unpublished observation). With time, the disease of some patients will eventually smolder into a more noninflammatory classic form of EBA. Both the classical and the BP-like forms (Stewart et al. 1991), and the CP-like and BP-like forms of the disease may coexist in the same patient (Wieme et al. 1999). The clinical phenotype of EBA that is reminiscent of pure CP is probably more rare and occurs in fewer than 10% of all EBA cases.
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