title: Panniculitis in patients treated with BRAF inhibitors: a case series.
abstract: Panniculitis is a rare complication of BRAF inhibitor therapy that is used to treat patients with BRAF-mutated metastatic melanoma. We present a clinicopathologic review of 9 patients who developed panniculitis while on BRAF inhibitor therapy. In 13% of patients on vemurafenib, 3% of patients on dabrafenib and 10% on combination of dabrafenib + trametinib, tender erythematous nodular lesions of panniculitis appeared on legs, arms and trunk. Histological evaluation of 8 biopsies from 7 patients showed predominantly neutrophilic infiltrate in 4, lymphocytic in 1, and mixed in 3. Lesions with neutrophilic infiltrate appeared in earlier stages of treatment than those with mixed or lymphocytic infiltrate. All biopsies showed lobular involvement and 5 also had a septal component. In addition, 1 biopsy had lichenoid inflammation in the epidermis and the other had evidence of vasculitis. Most patients responded to conservative medical management without the need to reduce or to stop BRAF inhibitor therapy. Panniculitis seems to be a rare class effect of BRAF inhibitors that is predominantly lobular and neutrophilic, although other patterns can be seen.
authors.affiliation: *Department of Dermatology, Westmead Hospital, Sydney, Australia; †Sydney Medical School, The University of Sydney, Sydney, Australia; and ‡Department of Tissue Pathology and Diagnostic Oncology, Pathology West, Institute of Clinical Pathology and Medical Research, Westmead, Sydney, Australia.
authors.forename: Bonita
authors.initials: B
authors.lastname: Choy
authors.forename: Shaun
authors.initials: S
authors.lastname: Chou
authors.forename: Rachael
authors.initials: R
authors.lastname: Anforth
authors.forename: Pablo
authors.initials: P
authors.lastname: Fernández-Peñas
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects; D007211:Indoles / Q000009:adverse effects; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged; D010091:Oximes / Q000009:adverse effects; D015434:Panniculitis / Q000139:chemically induced* / Q000453:epidemiology / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors*; D011728:Pyridones / Q000009:adverse effects; D011744:Pyrimidinones / Q000009:adverse effects; D012878:Skin Neoplasms / Q000188:drug therapy*; D013449:Sulfonamides / Q000009:adverse effects; D000077484:Vemurafenib
chemical_list: D007093:Imidazoles; D007211:Indoles; D010091:Oximes; D047428:Protein Kinase Inhibitors; D011728:Pyridones; D011744:Pyrimidinones; D013449:Sulfonamides; D000077484:Vemurafenib; C560077:trametinib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C561627:dabrafenib