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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.