Pemphigoid (Herpes) gestationis: Neue Aspekte zur Pathogenese und Diagnostik

Zusammenfassung

Das Pemphigoid gestationis (PG), früher als Herpes gestationis bezeichnet, ist eine Autoimmundermatose der Schwangerschaft, die typischerweise durch vesikulo-bullöse Hautveränderungen gekennzeichnet ist. Die Blasenbildung kann jedoch häufig fehlen; in diesen Fällen äußert sich die Erkrankung in Form juckender makulo-papulöser, urtikarieller oder ekzematöser Veränderungen. In der direkten immunfluoreszenzmikroskopischen Untersuchung der Haut der Patientinnen finden sich lineare Ablagerungen des Komplementfaktors C3 an der dermo-epidermalen Junktionszone. Proteinchemische und molekularbiologische Untersuchungen führten in den letzten Jahren zu einer Reihe neuer Erkenntnisse zur Pathogenese des PG. So konnte gezeigt werden, dass die Autoantikörper dieser Erkrankung gegen das 180 kDa schwere bullöse Pemphigoid Antigen (BP180) gerichtet sind. BP180 wird auch als Kollagen Typ XVII bezeichnet und stellt einen wichtigen Bestandteil epidermaler Hemidesmosomen dar, die für die Verankerung basaler Keratinozyten auf der kutanen Basalmembran von Bedeutung sind. Die Reaktivität gegen BP180 wird vor allem durch Antikörper der IgG1- und IgG3-Subklasse vermittelt. Deren Bindung führt zur Komplementaktivierung, zur Einwanderung von Entzündungszellen und schließlich zur subepidermalen Blasenbildung. Unter Verwendung rekombinanter Formen des BP180-Autoantigens können die zirkulierenden Autoantikörper im Serum der PG-Patienten mittels Immunoblot oder ELISA nachgewiesen werden. Beide Verfahren haben eine hohe Sensitivität und Spezifität und ermöglichen in den meisten Fällen die Abgrenzung des PG von anderen Schwangerschaftsdermatosen auch ohne Entnahme einer Hautbiopsie.

Summary

Pemphigoid gestationis (PG) is an autoimmune subepidermal blistering disease associated with pregnancy. Patients can present with blisters or with itchy macular, papular, urticarial or eczematous lesions. Direct immunofluorescence microscopy of perilesional skin biopsies shows linear deposits of C3 along the basement membrane. Recent biochemical and molecular biologic studies have shed light on the pathogenesis of PG. Antibodies are directed against the 180-kDa bullous pemphigoid antigen (BP180), also referred to as type XVII collagen. BP180 is an important component of epidermal hemidesmosomes, epithelial structures essential for adhesion of basal keratinocytes to the cutaneous basement membrane. Circulating anti-BP180 autoantibodies predominantly belong to the IgG1 and IgG3 subclasses. Binding of the antibodies leads to complement activation, infiltration of inflammatory cells into the skin, and, finally, to subepidermal blister formation. These autoantibodies can be demonstrated by immunoblotting and ELISA techniques using recombinant BP180 as the target antigen. Both tests are sensitive and specific and in most cases make it easier to distinguish between PG and other pregnancy-associated skin diseases without resorting to skin biopsy.

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