The combination therapy of dabrafenib and trametinib is now standard of care in the management of metastatic melanoma for patients with activating mutations of the oncogenic BRAF serine-threonine kinase enzyme. Cutaneous toxicities are commonly seen with BRAF inhibitors as seen in the pivotal BREAK-3 trial, where 39% of patients treated with dabrafenib developed hyperkeratosis and 10% developed keratocanthoma and SCC. Other toxicities include maculopapular rash, pruritus, dry skin and keratosis. Cutaneous toxicities usually occur within a few weeks of initiation of therapy.

We illustrate a much unexpected diagnosis of extensive bilateral pedal Kaposi sarcoma (KS) in a patient being treated for both metastatic melanoma with dabrafenib and trametinib, and a concurrent severe autoimmune disease.  Of particular note, in its early stages, Kaposi sarcoma of the feet may be confused with the frequently painful plantar hyperkeratotic change seen as a well-described adverse effect of BRAF inhibitor therapy.

This case highlights the need to have broad differentials of unusual presentations particularly in the current era of targeted therapies and immunotherapies, where more frequently patients with complex medical backgrounds are being treated with these agents. Close multidisciplinary surveillance and early intervention especially in cases that do not respond to therapy should be recommended.