CPC06 The proof is in the ink: granulomatous tattoo reaction secondary to BRAF and MEK inhibition
Authors: Porter Emma , Gould Aaron , Hopkins Ilona , Talbot Toby , Mogawer Rania 
Published: June 2024

Abstract
A 61-year-old man presented with a 2-week history of a rash affecting tattooed skin. Following an initial 48-h period of fevers, a papular eruption developed within tattoos. Within 1 week it significantly progressed and was associated with itch and skin hyperalgesia. He had a background of BRAF-mutant resected stage III malignant melanoma, for which he was taking dabrafenib and trametinib daily starting 5 months earlier. He had an excellent performance status and no evidence of disseminated metastatic disease on updated imaging. His only other medication was perindopril. He had no history of dermatological issues or any relevant dermatoses in his family history. Review of systems was noncontributory. On examination, there were erythematous papules and plaques confined to the black ink of tattoos, with slight extension beyond the tattoo boundaries and secondary desquamation. Coloured ink was unaffected. There was no mucosal involvement, blistering, skin fragility, ulceration or evidence of infection. Skin biopsy demonstrated granulomatous inflammation surrounding black pigmented material. Laboratory tests including full blood count, inflammatory markers, and renal and liver profiles were normal. Antinuclear antibodies were negative. Serum angiotensin-converting enzyme was low, and no pulmonary findings were noted on imaging. Dabrafenib and trametinib were paused after the initial fever. Clobetasol propionate ointment was initiated to treat affected areas topically. BRAF and MEK inhibitor therapy (BRAF/MEKi) was recommenced at a reduced dose 4 weeks later when the rash had resolved. Subtle dermal thickening within black tattoo ink was noted within 1 week of restarting therapy, although this subsided, and the patient has continued on BRAF/MEKi without symptoms since. Few cases of cutaneous tattoo reactions to BRAF/MEKi have been reported. They have been recognized in those on immunotherapy, as a manifestation of immune restoration syndrome in the context of antiretroviral therapy for HIV, and in sarcoidosis (Kluger N. Tattoo reactions associated with targeted therapies and immune checkpoint inhibitors for advanced cancers: a brief review. Dermatology 2019; 235: 522–4). In previously reported cases of tattoo reactions due to BRAF/MEKi, like in this case, it was particularly black ink affected, and most patients tolerated treatment recommencement. The pathophysiology is not fully understood, although it may represent innate immune ­system activation, T-cell dysfunction, or BRAK/MEKi-induced paradoxical granuloma formation through activation of the AKT/mTOR pathway (Kluger). Distinguishing sarcoidosis-associated tattoo reactions from other granulomatous tattoo reactions can be challenging, although it has been reported that the extension of erythema beyond tattoo borders is less frequently seen in sarcoidosis (Kluger). In summary, this case illustrates a rare manifestation of reaction to targeted therapy for melanoma, which may be more frequently encountered as therapeutic indications expand for neoadjuvant use and in earlier stages of disease.