Discussion In Zillikens et al described

Discussion In 1996, Zillikens et al described the first case of a new subepidermal immunobullous disease called anti-p200 pemphigoid. Approximately 70 cases of anti-p200 pemphigoid mediated by IgG BGB324 have been reported in the literature to date, and only one was associated exclusively with immunoglobulin A (IgA) antibodies. In 2009, Dainichi et al identified the 200-kDa protein as laminin γ1 and renamed the disease anti-laminin γ1 pemphigoid. Anti-p200 pemphigoid usually occurs at a younger age than that observed in patients with BP and appears to be more frequent in male patients. The presentation is rather heterogenous and may mimic BP, linear IgA dermatosis, dermatitis herpetiformis, or epidermolysis bullosa acquisita (EBA). The BP-like type is the most common and is characterized by itchy urticarial papules and plaques and tense blisters on the trunk and extremities. Oral and genital mucous membranes are affected in approximately 20% of patients with anti-p200 pemphigoid and cephalic involvement is common. Blood analysis does not disclose the hypereosinophilia found in classic BP. In our patient, we found acral predominance of the lesions and considerable mucous membrane involvement. Lesions usually heal without scarring; milia formation has been observed in three previously reported cases. Except for psoriasis in one-third of cases, no other cutaneous disease or tumor seems to be associated with anti-laminin γ1 pemphigoid. There is only one case report about penicillin-induced anti-p200 pemphigoid. Histopathological analysis of lesional skin shows a slight dermal–epidermal separation with neutrophilic and/or eosinophilic infiltration in the superficial dermis. Direct IF examination of a perilesional skin biopsy revealed linear deposits of IgG and C3 along the DEJ. In two cases, an additional staining for IgA was described, and one case even revealed exclusively IgA deposits. Indirect IF study on salt-split human skin demonstrates circulating IgG (IgG4) autoantibodies binding to the dermal side of the artificial split. These antibodies disappear when skin lesions improve under immunosuppressive treatment. In four cases of anti-p200 pemphigoid, both dermal and epidermal sides were fixed by IgG. ELISAs with BP230 and BP180 are negative most of the time. Immunoblot analysis reveals autoantibodies directed against a 200-kDa antigen localized on the dermal extract that would also be present in certain cases on the epidermal extract. However, preparation of a dermal extract requires a sophisticated extraction procedure that is not widely available, limiting the possibility of diagnosing this disease to a few specialized laboratories. Several research teams are trying to develop techniques to detect autoantibodies against laminin γ1. Groth et al recently developed an ELISA test with the recombinant monomeric C-terminal fragment of human laminin γ1. This test has a high specificity of 98.7% but an insufficient sensitivity of 69%. Further studies are required to improve detection of autoantibodies to laminin γ1 for routine diagnosis of blistering disease. In 2003, Shimanovich et al showed that p200 is an acidic noncollagenous N-linked glycoprotein of the lower lamina lucida. The laminin γ1 chain has recently been identified as the target antigen in anti-p200 pemphigoid and the C-terminus was described as an immunodominant region of laminin γ1. Laminin γ1 is a component of different forms of laminin heterotrimers, which contributes to dermal–epidermal adhesion outside hemidesmosomes. Laminin γ1 is a ubiquitous protein found in the DEJ, blood vessels, and in the extracellular matrix of several organs including the central nervous system. It has been suggested that laminin γ1 in the DEJ may have different post-translational modifications explaining the cutaneous specificity of the disease: the antibody anti-laminin γ1 should recognize a specific form present only in the skin. Based on the literature, anti-p200 pemphigoid is treated with various immunosuppressive therapies. Most of the cases required systemic corticosteroid therapy (up to 1 mg/kg/day), alone or in association with other immunosuppressive drugs (azathioprin, ciclosporin, mycophenolatemofetil, methotrexate, intravenous immunoglobulins). One patient was completely healed with topical steroids only. Most of the time, lesions reappeared when treatment was tapered. In several cases, adjunction of dapsone permitted remission and withdrawal of corticosteroids. The present case was treated with a combination of topical corticosteroids and dapsone 100 mg/day, which allowed a completed remission after 1 year.