Bullöses Pemphigoid unter Pembrolizumab-Therapie eines metastasierten malignen Melanoms

Zusammenfassung

Pembrolizumab ist ein monoklonaler Antikörper, der an den PD-1-Rezeptor auf T-Zellen bindet und die Interaktion mit den Liganden PD-L1 und PD-L2 auf Krebszellen hemmt. Pembrolizumab wird zunehmend für die Behandlung von fortgeschrittenen Tumorerkrankungen, v. a. für metastasierte maligne Melanome, aber auch für nicht-kleinzelliges Lungenkarzinom, Urothelkarzinom und Nierenkarzinom angewendet. Trotz der beeindruckenden klinischen Wirkungen sind die Checkpoint-Inhibitoren mit einer Reihe von Nebenwirkungen verbunden, die als immunbezogene unerwünschte Ereignisse bekannt sind. Zu den bekannten Nebenwirkungen dieser Therapie gehören neben kutanen Nebenwirkungen wie Hautausschlag auch Müdigkeit, Schilddrüsendysfunktion, immunvermittelte Pneumonitis und Kolitis. Zu den kutanen unerwünschten Ereignissen gehören u. a. Pruritus, lichenoide Dermatitis, Psoriasis sowie blasenbildende Erkrankungen wie bullöses Pemphigoid. Die Nebenwirkungen werden durch die immunoregulatorischen Mechanismen des Medikaments erklärt. Hier berichten wir über den Fall eines 72-jährigen Patienten mit metastasiertem malignen Melanom und Prostatakarzinom als Zweittumor, der unter einer Therapie mit Pembrolizumab rasch sowohl eine stabile Erkrankung des Tumors hatte, aber auch zuerst eine immunvermittelte Pneumonitis und im Verlauf dann auch ein bullöses Pemphigoid entwickelte. Dieser Fall ergänzt die Liste möglicher kutaner Nebenwirkungen einer PD-1-Inhibitor-Therapie.

Abstract

Pembrolizumab is a monoclonal antibody that binds on the PD-1 receptor on T cells and inhibits the interaction with the PD-L1 and PD-L2 ligands on cancer cells. Pembrolizumab is indicated for the treatment of advanced tumor diseases, esp. for metastatic malignant melanoma, but also for non-small cell lung carcinoma, urothelial carcinoma, and renal carcinoma. Despite its impressive clinical benefits, checkpoint inhibition is associated with a number of inflammatory effects known as immune-related adverse events. The known side effects of this therapy include, beside skin rash, also fatigue, dysfunction of the thyroid gland, pneumonitis, and colitis. Cutaneous side effects include pruritus, lichenoid dermatitis, psoriasis and blistering disorders such as bullous pemphigoid. These are explained by the immunoregulatory mechanisms of the drug. Here we report the case of a 72-year-old male patient with metastatic malignant melanoma on therapy with pembrolizumab and consecutivly in a stable state of the disease, who developed an immune-mediated pneumonitis and additional a bullous pemphigoid. This case might extend the knowledge of possible cutaneous side effects of PD-1 inhibitor therapies.

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