title: Clinical observation of panniculitis in two patients with BRAF-mutated metastatic melanoma treated with a combination of a BRAF inhibitor and a MEK inhibitor.
abstract: BACKGROUND
  Treatment with selective BRAF or MEK inhibitors is frequently associated with cutaneous toxicities, including squamous cell carcinoma (SCC), papillomas and rash. These cutaneous adverse effects are typically observed at a lower incidence during combined BRAF and MEK inhibitor therapy.
  
  
  METHODS
  Two male patients with stage IV metastatic BRAF-mutated melanoma were treated with a combination of a selective BRAF inhibitor and a selective MEK inhibitor (dabrafenib and trametinib, or encorafenib (LGX818) and binimetinib (MEK162)) within two different clinical trials. Ten and 150 days after treatment start respectively, the patients developed painful nodules on the legs. In addition, one patient developed symmetrical articulation pain and intermittent fever episodes.
  
  
  RESULTS
  Based on the clinical and histological presentation, erythema nodosum-like panniculitis was diagnosed in both cases. No other aetiology could be found. After receiving topical or oral steroid treatment and anti-inflammatory analgesics, the painful nodular lesions disappeared several weeks later. In one case, a rebound of the painful nodules was observed when the combination treatment (dabrafenib and trametinib) was resumed after a 1-week unscheduled treatment interruption.
  
  
  CONCLUSIONS
  Panniculitis has previously been described in association with BRAF inhibitor treatment, but not MEK inhibitor treatment. Combination treatment is usually associated with a lower incidence of cutaneous adverse events (AEs), as compared to monotherapy. Panniculitis was observed in two patients during combined BRAF and MEK inhibitor treatment. These cases illustrate the need for further research in a larger patient population to identify a possible link between combined BRAF and MEK inhibitor treatment and the incidence of panniculitis.
authors: University Hospital of Zürich Department of Dermatology Gloriastrasse 31 CH-8091 Zürich Switzerland.
authors: Nadja A
authors: NA
authors: Galliker
authors: University Hospital of Zürich Department of Dermatology Gloriastrasse 31 CH-8091 Zürich Switzerland.
authors: Carla
authors: C
authors: Murer
authors: University Hospital of Zürich Department of Dermatology Gloriastrasse 31 CH-8091 Zürich Switzerland.
authors: Jivko
authors: J
authors: Kamarashev
authors: University Hospital of Zürich Department of Dermatology Gloriastrasse 31 CH-8091 Zürich Switzerland.
authors: Reinhard
authors: R
authors: Dummer
authors: University Hospital of Zürich Department of Dermatology Gloriastrasse 31 CH-8091 Zürich Switzerland.
authors: Simone M
authors: SM
authors: Goldinger
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001562:Benzimidazoles / Q000008:administration & dosage; D002219:Carbamates / Q000008:administration & dosage; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D010091:Oximes / Q000008:administration & dosage; D015434:Panniculitis / Q000139:chemically induced*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics*; D011728:Pyridones / Q000008:administration & dosage; D011744:Pyrimidinones / Q000008:administration & dosage; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D013449:Sulfonamides / Q000008:administration & dosage
chemical_list: D001562:Benzimidazoles; D002219:Carbamates; D007093:Imidazoles; D010091:Oximes; D011728:Pyridones; D011744:Pyrimidinones; D013449:Sulfonamides; C581313:binimetinib; C560077:trametinib; C000601108:encorafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020928:Mitogen-Activated Protein Kinases; C561627:dabrafenib
keywords: BRAF inhibition; MEK inhibition; adverse event; melanoma; panniculitis; targeted therapy