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Advances in dermatology and venereology Acta Dermato-Venereologica
Pyoderma Gangrenosum Under Dabrafenib and Trametinib for Metastatic Melanoma
Mélanie SAINT-JEAN 1 , 2 , Marie LE MOIGNE 1 , Justine DAGUZE 1 , Céline BOSSARD 3 , Lucie PEUVREL 1 , 2 , Gaëlle QUEREUX 1 , 2 and Brigitte DRENO 1 , 2 *; on behalf of GESTIM Nantes group of cutaneous adverse events induced by anticancer drugs
1
Dermatology Department , 2 CIC1413 , CRCINA Inserm 1232 , and 3 Pathology Department , CHU Nantes , Nantes , France . * E-mail : brigitte . dreno @ wanadoo . fr Accepted Jan 23 , 2018 ; Epub ahead of print Jan 24 , 2018
In recent years a combination of BRAF and MEK inhibitors has become the first-line treatment for BRAF V600 mutated unresectable or metastatic melanoma , with a response rate of 70 % ( 1 ). Cutaneous adverse events are frequent and mostly related to BRAF inhibitor treatment . Reported toxicities can be severe , and include skin rash , photosensitivity , dry skin , and squamous cell carcinoma ( 2 ).
In addition to the numerous cases of neutrophilic BRAF inhibitor-induced panniculitis reported previously , rare cases of other neutrophilic dermatoses have been described in the literature , including 2 cases of Sweet ’ s syndrome ( 3 , 4 ) and 2 cases of neutrophilic eccrine hidradenitis ( 5 ).
To the best of our knowledge , this is the first report of pyoderma gangrenosum ( PG ) in a patient treated with combined BRAF and MEK inhibitor for metastatic melanoma .
CASE REPORT
A 74-year-old man presented with a medical history of hypertension , which was being treated with lercanidipine , candesartan and hydrochlorothiazide , and atrial fibrillation being treated with oral anticoagulant . He had had a primary melanoma on his back in 1995 , which was treated with local excision ( Breslow index 1.6 mm ) with no adjuvant treatment . Eight years later he had a relapse of melanoma , with metastasis to axillary lymph nodes and a cutaneous nodule on the back histologically
Fig . 1 . Clinical aspect of the metastasis on the patient ’ s back at the start of dabrafenib and trametinib treatment .
proven to be melanoma metastasis . As the disease was unresectable , he was given several treatments : NY-ESO1 vaccine ( NCT01213472 ), vemurafenib alone in 2014 , dabrafenib alone in 2015 , anti-PD1 nivolumab , talimogene laherparepvec ( T-VEC ) injections ( NCT02366195 ), dabrafenib combined with trametinib in Mekinist access protocol ( protocol NCT02416232 ) ( Fig . 1 ). More recently , after European Medicines Agency approval , the same combination of BRAF and MEK inhibitor was continued off protocol .
Ten weeks after introduction of dabrafenib and trametinib , the patient presented with an acute and painful ulceration overlying a subcutaneous melanoma metastasis on his back with no accompanying fever . The ulcer was necrotic with pustules on the edge ( Fig . 2 ). Laboratory evaluation revealed an inflammatory syndrome with an increase in C-reactive protein ( 146 mg / l ) and neutrophils leukocytosis ( 12,360 / mm 3 ). The first hypothesis was a tumour necrosis with superinfection . Skin cultures were performed and a methicillin-sensible Staphylococcus aureus was isolated . Based on this result , the patient received amoxicillin and clavulanic acid for 7 days with no clinical improvement . Pathological examination of a skin specimen revealed a dense infiltrate of neutrophils in the dermis with no identifiable tumour cells ( negative Melan-A staining ) or pathogenic agents ( Fig . S1 1 ), using Periodic acid – Schiff ( PAS ) and Grocott staining . This confirmed the other hypothesis ; clinical suspicion of PG . Considering the benefit / risk ratio , targeted therapy was continued and the patient received minocycline , 100 mg per day , in parallel , for the PG . Tolerance was excellent . Healing of PG was obtained after 3 months of minocy-
1 https :// www . medicaljournals . se / acta / content / abstract / 10.2340 / 00015555-2890
Fig . 2 . ( A ) Pyoderma gangrenosum of the back 10 weeks after the start of treatment . ( B ) Pustules on the edge of the ulcer . doi : 10.2340 / 00015555-2890 Acta Derm Venereol 2018 ; 98 : 530 – 531
This is an open access article under the CC BY-NC license . www . medicaljournals . se / acta Journal Compilation © 2018 Acta Dermato-Venereologica .