BRAF Inhibitor–Associated Granulomatous Dermatitis: A Report of 3 Cases

Abstract

Cutaneous toxicities associated with BRAF inhibitor treatment in patients with metastatic melanoma have been well described. We present a rare association of granulomatous dermatitis in association with the BRAF inhibitor vemurafenib. Three patients with metastatic melanoma all presented with asymptomatic papular eruptions 8–21 months into vemurafenib therapy. Skin biopsies confirmed the diagnosis of granulomatous dermatitis. Other causes of granulomatous dermatitis including infectious agents and sarcoid were excluded. Treatment with potent topical and oral steroids improved the eruptions, but only after the cessation of vemurafenib did all 3 cases of granulomatous dermatitis completely resolve within 2 weeks. It is important to recognize that this association, unlike most other BRAF inhibitor–related skin toxicities, can occur many months after commencement of therapy and that vemurafenib treatment can be continued without clinically significant adverse effects.

The diagnosis and management of sarcoid-like reactions in patients with melanoma treated with BRAF and MEK inhibitors. A case series and review of the literature

“…30 Skin SLR presents more commonly with papules and plaques, but can also appear as subcutaneous nodules on the arms or legs, both early and late after treatment initiation. 4,6,9,11 –14,31,32 Finally, Korman et al 33 reported a case of granulomatous dermatitis within a benign blue nevus. Granulomatous infiltration of tattoos has also been reported.…”

“…Several cases have been reported as granulomatous involvement of specific organs, e.g., granulomatous myocarditis, 8 hepatitis, 9 nephritis, 10 uveitis, 11 and dermatitis. 12 –16 Cases of systemic sarcoid-like granulomatosis have also been reported. 17 Finally, Dando et al 3 reviewed all the above reported cases using the term ‘drug- induced SLR’.…”

Dermatologic toxicities of targeted antineoplastic agents and immune checkpoint inhibitor therapy in pediatric patients: A systematic review

“…Bland emollients, topical keratolytics, and tretinoin cream have been used to treat KP. Like in adults, granulomatous dermatitis can occur many months after the onset of vemurafenib therapy 96 . Interestingly, there is only one reported case of squamous cell carcinoma arising in a child treated with a BRAF inhibitor 15 .…”

“…Like in adults, granulomatous dermatitis can occur many months after the onset of vemurafenib therapy. 96 Interestingly, there is only one reported case of squamous cell carcinoma arising in a child treated with a BRAF inhibitor. 15 The rarity in childhood suggests that chronic actinic damage may play a role in the eruptive squamoproliferative lesions, which is seen in 20%-30% of adults, on BRAF inhibitor therapy.…”

Cutaneous Side Effects of Modern Targeted Therapy and Immunotherapy in Patients with Dermatological Malignancies

“…Acneiform eruption [123,124] Alopecia (telogen effluvium) [136] Basal cell carcinoma [137] Cheilitis [9] Granulomatous eruption [138][139][140] Grover's disease [141] Hand-foot skin reaction [142] Milia [9] Panniculitis [143,144] Pruritus [10,14] Vitiligo [145,146] Xerosis [9] 5. MEK-Inhibitors…”