Tattoo Reactions Associated with Targeted Therapies and Immune Checkpoint Inhibitors for Advanced Cancers: A Brief Review

Abstract

To the best of our knowledge, 10 cases (6 men, 4 women; mean age 44.5 years, range 22-59) have been reported since 2012. The main characteristics are summarized in Table 1. Six patients received a combination of BRAF inhibitor (BRAFi) associated with a MEK inhibitor (MEKi), 2 patients a PD-1/PD-L1 inhibitor (PD-1i/ PD-L1i) and 2 patients a CTLA-4 inhibitor (CTLA-4i), including one in combination with a PD-1i. We found that the clinical presentation was different according to culprit drugs. Tattoo eruption associated with BRAFi + MEKi presented mostly as a complete infiltration/induration of dark-colored tattoos with striking inflammatory borders in 5 out of 6 cases [10-13, 16]. Tattoo reactions with CTLA-4i or PD-1i/PD-L1i were reminiscent of what is usually observed with sarcoidosis or granulomatous tattoo reactions in general, e.g. papules and nodules scattered within black tattoos [8, 9, 14, 15]. Tattoos were dark/black in 86% (6/7) of the cases. In case of multicolored tattoos, other colors were spared. Delays of onset after the first cycle were as follows from the earliest to the latest: CTLA-4i + PD-1i (2 months) > BRAFi + MEKi (2-6 months) > PD-1i/PD-L1i (9-15 months). Only 1 patient had additional cutaneous sarcoids on plain skin and erythema nodosum [9]. Biopsies showed noncaseating granulomas in 67% (6/9), including all the cases with CTLA-4i and/or PD-1i/PD-L1i. In the 3 remaining cases, there was only a lymphocytic infiltration without any granulomas [10, 12, 13]. Angiotensin-converting enzyme was elevated in 2 cases of granulomatous reactions [9, 15]. Lung involvement and lymph nodes were reported in 60% (6/10). Management was highly variable according to authors. It included local corticosteroids, combination of local and systemic corticosteroids, abstention with either maintenance or discontinuation of the treatment, and switch to PD-1i or surgery. One patient experienced relapses with BRAFi + MEKi cycles [10]. Overall, outcome was always favorable. Discussion Granulomatous eruptions under ICPIs are an uncommon immune-related adverse event that can become more and more frequently encountered with the increased use of this therapeutic class [7]. All the patients under PD-1i/PD-L1i/CTLA-4i developed sarcoid-like reactions on tattoos. Delays of onset and outcomes were here in line with what is known from the literature [7]. On the other hand, cutaneous granulomatous reactions and sarcoidosis are rather infrequent with BRAFi [17]. Out of the 5 patients under BRAFi + MEKi with available biopsies, 3 displayed a lymphocytic infiltration in the dermis without granulomas. Besides, the clinical presentation was rather different with a marked erythema around the tattoos which is totally unusual compared to the usual tattoo granulomatous reactions we often see in practice [4, 18, 19]. Only 1 patient did not present such an inflammatory reaction around the affected tattoos [16]. To date, there is no case report of tattoo reaction with BRAFi alone. In 1 patient [11], the reaction developed 3 months after MEKi in...

Rheumatic Manifestations in Patients Treated with Immune Checkpoint Inhibitors

“…The onset of sarcoid-like reactions varies, usually occurring between three weeks and two years following ICI initiation [95], and the most commonly affected organs are the lungs and skin. Interestingly, 10 cases have been reported where sarcoid-like reactions on permanent tattoos were induced by ICI therapy [96]. Sarcoid-like granulomatosis and lymphadenopathy of the thorax has been reported in 5%-7% of ipilimumab-treated melanoma patients [97,98].…”

Cutaneous Malignancies in Tattoos, a Case Series of Six Patients

“…We examined palpable small papules in the area of the tattooed skin with emphasis on the black color. We suspected an immunological reaction in this area triggered by the black color ink, most likely a granulomatous skin reaction as seen in another study [88]. The patient presented himself to regular follow-up examinations and has had no recurrence of the SSMM to date.…”

Complications of tattoos and permanent makeup: overview and analysis of 308 cases

“…The long delay of onset of symptoms implies the potential role of an additional triggering factor such as an infection or certain systemic medication. Several triggers for these CIBTR are reported, including targeted therapies and immune checkpoint inhibitors 25 …”

“…Several triggers for these CIBTR are reported, including targeted therapies and immune checkpoint inhibitors. 25 Tattoo-associated uveitis is an entity that has been recently described and is not completely understood. It is characterized by the simultaneous occurrence of granulomatous elevation of one or several tattoos together with recurrent uveitis, all in the absence of other signs of sarcoidosis.…”