Dear Editors,

A 50-year-old Japanese woman presented with a 3-month history of itching, pain, swelling, and raised yellowish lesions on her eyebrows. She had a history of permanent makeup (PMU) placement on her eyebrows 9 years prior. Initial examination revealed distinct, slightly elevated yellow-brown plaques and significant hair loss in the affected area (Figure 1A). Histological examination of a skin biopsy from the right eyebrow showed epithelioid granulomas with dark-brown pigments and lymphocytic infiltration, along with multinucleated giant cells without necrosis (Figures 1B, C). Given the frequent use of iron oxide in PMU inks, we performed supplementary staining using Berlin blue, which was positive around the deposited material (Figure 1D).

Physical examination, including a chest radiograph, and laboratory tests such as angiotensin-converting enzyme and soluble interleukin-2 receptor, revealed no abnormal findings. Based on clinical and histopathological findings, the patient was diagnosed with a sarcoidal foreign body reaction to PMU tattoo ink. Various treatments for sarcoidal foreign body reactions to PMU ink are effective, including topical, oral, and intralesional steroids, tacrolimus, minocycline, doxycycline, and methotrexate [1]. The patient had already been applying a topical steroid, with no obvious improvements. Therefore, we administered monthly steroid injections in the eyebrows using a solution (10 mg/mL) comprised of triamcinolone acetonide and 1% lidocaine hydrochloride. Itching improved within 2 weeks of the first steroid injection. After the fourth injection, the flat yellowbrown raised lesion partially flattened, and some hair regrowth was observed (Figure 1E). After six injections, the lesions had almost completely flattened, hair loss had improved, and the patient expressed satisfaction with the aesthetic outcome (Figure 1F). However, itching recurred after the injections were stopped. Therefore, injections were continued every 2–3 months to prevent relapse of itching.

Although several cases of granulomatous reactions due to PMU placement in the eyebrows have been reported, distinguishing between the initial manifestation of sarcoidosis and a sarcoidal foreign body reaction is difficult. Even patients who exhibit localized sarcoidal reactions, as in the present case, are thought to have a predisposition to sarcoidosis. Therefore, this patient should be closely followed for the development of sarcoidosis [2].

In the present case, the patient developed a sarcoid-like foreign body reaction 9 years after a PMU procedure using blonde ink. While the composition of the ink is unknown, positive results on Berlin blue staining suggest that the ink contained iron oxides. The mechanism for this long latency period is thought to involve the gradual degradation of ink components. Chronic sun exposure may cause the ink components to break down slowly, generating highly reactive byproducts, which may function as new antigens, potentially triggering a granulomatous reaction. It is important to note that the eyebrow area is difficult to protect with sunscreen. In this case, the difficulty in applying sunscreen to the eyebrow area supports the hypothesis that sun exposure played a significant role in the development of the reaction [1].

Recent studies have identified the roles of M1 and M2 macrophages in inflammation promotion and tissue repair/inflammation suppression, respectively. Previous studies have associated sarcoidosis with a significant increase in M2 macrophages [3]. In the present case, we performed ionized calcium-binding adapter molecule 1 (Iba1) immunostaining to identify both M1 and M2 macrophages, along with immunostaining for inducible nitric oxide synthase (iNOS) and CD163 as M1 and M2 macrophage markers, respectively [4]. We observed a higher density of CD163-positive cells compared to iNOS-positive cells, indicating an increase in M2 macrophages (Figures 1G–I). It is hypothesized that in granuloma formation, an initial Type 1 T helper immune response involving M1 macrophages occurs, with a transition from M1 to M2 macrophages [5]. Given the predominance of M2 macrophages in the present case, the transition to the resolution phase of inflammation might have been underway.

In summary, we successfully treated sarcoidal foreign body reactions due to PMU with local steroid injections. We identified the involvement of M2 macrophages in the observed reaction to PMU, and this contribution has not been previously reported. Thus, our findings provide new insights into the mechanisms underlying PMU-associated sarcoidal reactions.