BRAF inhibition and the spectrum of granulomatous reactions

James P Pham; Phoebe Star; Kevin Phan; Yanni Loh; Anthony M Joshua; Annika Smith

doi:10.1016/j.jaad.2021.10.030

BRAF inhibition and the spectrum of granulomatous reactions

J Am Acad Dermatol. 2022 Sep;87(3):605-613. doi: 10.1016/j.jaad.2021.10.030. Epub 2021 Oct 29.

Authors

James P Pham¹, Phoebe Star², Kevin Phan³, Yanni Loh⁴, Anthony M Joshua⁵, Annika Smith⁶

Affiliations

¹ St. Vincent's Hospital, Sydney, Australia; St. Vincent's Clinical School, University of New South Wales, Sydney, Australia. Electronic address: j.Pham0011@gmail.com.
² St. Vincent's Hospital, Sydney, Australia.
³ Department of Dermatology, Liverpool Hospital, Sydney, Australia.
⁴ St. Vincent's Hospital, Sydney, Australia; St. Vincent's Clinical School, University of New South Wales, Sydney, Australia.
⁵ St. Vincent's Hospital, Sydney, Australia; St. Vincent's Clinical School, University of New South Wales, Sydney, Australia; Melanoma Institute of Australia, Sydney, Australia; Medical Oncology, The Kinghorn Cancer Centre, Sydney, Australia.
⁶ St. Vincent's Hospital, Sydney, Australia; Faculty of Medicine, University of Sydney, Sydney, Australia; Medical Oncology, The Kinghorn Cancer Centre, Sydney, Australia; The Mater Hospital, North Sydney, Australia.

PMID: 34715287
DOI: 10.1016/j.jaad.2021.10.030

Abstract

V-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitors have emerged as a promising targeted therapy for malignancies with BRAF mutations, particularly metastatic melanoma. However, granulomatous reactions (GRs), including sarcoidosis and sarcoid-like reactions, have been reported as a consequence of BRAF inhibition. It is important to adequately characterize these GRs, including cutaneous manifestations and systemic involvement, in order to guide investigations and management. A literature review was conducted to characterize the spectrum of GRs associated with BRAF inhibitors, identifying 55 reactions affecting 51 patients, with 37 reactions limited to cutaneous involvement. Further, a possible correlation with cancer response, mechanisms of granuloma formation, and a proposed workup and management approach for these GRs are presented.

Keywords: BRAF inhibitor; dabrafenib; encorafenib; granuloma; granulomatous reaction; melanoma treatment; sarcoidosis; vemurafenib.

Publication types

Review

MeSH terms

Animals
Humans
Melanoma* / drug therapy
Melanoma* / genetics
Melanoma* / pathology
Mice
Mutation
Protein Kinase Inhibitors / adverse effects
Proto-Oncogene Proteins B-raf / genetics
Skin Neoplasms* / chemically induced
Skin Neoplasms* / drug therapy
Skin Neoplasms* / genetics

Substances

Protein Kinase Inhibitors
BRAF protein, human
Proto-Oncogene Proteins B-raf