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International audience; Hemophagocytic lymphohistiocytosis (HLH) has been only rarely reported in patients with BRAF-mutated advanced melanoma treated with targeted therapies and never with first-line dabrafenib/trametinib combination thus far. Two patients treated with first-line dabrafenib and trametinib combination therapy for metastatic melanoma presented with sudden occurrence of fever, cytopenia, rhabdomyolysis, hepatic cytolysis, hypertriglyceridemia and very high ferritin levels after few weeks of treatment, associated with concomitant epstein-barr virus (EBV) reactivation in one patient. In both cases, drug-induced HLH was primarily considered owing to a high H-score and the absence of other etiology. Patients rapidly improved after treatment discontinuation associated with oral steroids in one patient and did not relapse after subsequent treatment resumption with a concurrent anti-BRAF/anti-MEK combination. In metastatic melanoma HLH may occur either spontaneously in the absence of any treatment as a paraneoplastic condition, related to an intercurrent infection or drug-induced mainly with various immunotherapy or with dabrafenib and trametinib following immunotherapy. However, such observations are scarce and these are the first cases of HLH occurring during first-line treatment with dabrafenib and trametinib in advanced melanoma to our knowledge. Pathomechanisms remain to be elucidated since triggering factors may encompass the treatment itself but also other significant actors including viral reactivation along with the underlying disease. The liability of treatment should be considered in cases of HLH occurring in patients with advanced melanoma successfully treated with a combined targeted therapy. A rechallenge with a concurrent anti-BRAF/anti-MEK can be proposed in this setting.

International audience; Le risque de cancers cutanés induits par des médicaments photosensibilisants est connu. Le rôle de l’hydrochlorothiazide a été soulevé par plusieurs études épidémiologiques récentes. Une revue systématique des études cas-témoins ou de cohortes prospectives montre qu’il existe un surrisque de carcinomes épidermoïdes dans la majorité des études même si certains facteurs de confusion comme le tabac n’ont pas été pris en compte. Les données sont plus contradictoires pour les carcinomes basocellulaires et les mélanomes. Ces résultats ne remettent pas en cause le rapport bénéfice/risque de cette molécule, mais peuvent inciter à des mesures de prévention renforcées chez les malades pour lesquels une prescription d’hydrochlorothiazide est proposée : identifier les patients à risque de carcinomes cutanés, éviter si possible de prescrire cette molécule chez les patients immunodéprimés ou ayant un carcinome, effectuer un examen cutané régulier chez les malades recevant ce traitement au long cours.

International audience