Dupuytren's Contractures Associated With the BRAF Inhibitor Vemurafenib: A Case Report

Sze Wai Chan; Daniel Alberto Vorobiof

Disclosures

J Med Case Reports. 2015;9(158) 

In This Article

Abstract and Introduction

Abstract

Introduction: Two previous cases of the development of Dupuytren's contractures were reported in association with BRAF inhibitor treatment for BRAF V600E mutation-positive metastatic melanoma and metastatic papillary thyroid carcinoma. We reported on a third case with a slower onset of presentation.

Case presentation: A 66-year-old white man was diagnosed with a BRAF V600E mutated metastatic cutaneous melanoma. He was commenced on oral vemurafenib 960mg twice daily. A marked response was achieved for his metastatic disease. He noticed a change of his hair characteristics and a feeling of "lumps" in both palms by 6 months. By 9 months, classical Dupuytren's contracture was apparent.

Conclusions: Dupuytren's contracture is not a known side effect of BRAF inhibitor treatment. The timeline for the development of Dupuytren's contracture on BRAF inhibitor treatment is not well defined. Although the etiology of Dupuytren's contracture is unknown, an increase in tumor necrosis factor has been demonstrated to be a possible mechanism. BRAF inhibition has been shown to increase immune reaction in the tumor microenvironment and is associated with high serum tumor necrosis factor level. We propose that an increased level of tumor necrosis factor associated with BRAF inhibition may increase the risk of the development of Dupuytren's contractures.

Introduction

Vemurafenib, an oral anti-BRAF V600 kinase inhibitor, is indicated for the treatment of advanced malignant melanoma for patients whose tumors harbor the BRAF V600 mutation. Vemurafenib inhibits the MAP kinase pathway by binding to the kinase domain in mutant BRAF and has been shown to prolong both progression free and overall survival.[1]

Toxicity from vemurafenib is common and includes many cutaneous side effects (skin rash, photosensitivity, hyperkeratosis, cutaneous squamous cell carcinoma, keratoacanthoma, and skin papilloma), alopecia, arthralgia, headache, fatigue, diarrhea and nausea.[2–4]

Recently two cases of Dupuytren's contractures have been reported in the medical literature in patients receiving a BRAF inhibitor.[5,6] We report on an additional case, different in development when compared to the cases previously published.

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