Adalimumab‐Induced Folliculitis‐Like Lichenoid Sarcoidosis

Tumor necrosis factor-α (TNF-α) plays a central role in granuloma maintenance; paradoxically, sarcoidosis-like reactions occur in patients receiving TNF-α inhibitors [1, 2]. We report a rare case of adalimumab-induced folliculitis-like lichenoid sarcoidosis. An 18-year-old Japanese woman presented with a 2-month history of facial eruption. She had received adalimumab for 1 year for bilateral panuveitis, with Behçet's disease or sarcoidosis suspected. Physical examination revealed multiple slightly infiltrated, pale erythematous papules diffusely involving the face (Figure 1a). Since acne vulgaris was initially suspected, oral doxycycline (200 mg/day) and topical benzoyl peroxide were initiated, and a diagnostic skin biopsy was obtained; however, no improvement was observed (Figure 1b). Treatment was continued while awaiting histopathology. Doxycycline was discontinued on day 11 because of nausea and replaced with roxithromycin (300 mg/day), but the eruption further worsened over the subsequent 2 weeks (Figure 1c). Histopathological examination revealed well-formed granulomas predominantly confined to the perifollicular region, with prominent perilesional lymphocytic infiltration, minimal fibrosis, and mild central fibrinoid necrosis (Figure 1d,e). Prior systemic evaluation excluded systemic sarcoidosis, including chest imaging, serum angiotensin-converting enzyme and calcium levels, and electrocardiography all within normal limits. Based on these findings, adalimumab-induced folliculitis-like lichenoid sarcoidosis was diagnosed. Antimicrobial therapy was discontinued, and topical benzoyl peroxide was replaced with hydrocortisone butyrate in week 3, resulting in marked improvement (Figure 1f). Tacrolimus 0.1% ointment was added in week 5, after which the lesions remained stable (Figure 1g). Adalimumab was continued because the disease was confined to the skin and adequately controlled with topical therapy. Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Several drugs, including TNF-α inhibitors, can induce sarcoidosis-like reactions termed drug-induced sarcoidosis-like reactions (DISRs) [3, 4]. TNF-α blockade disrupts signaling through TNFR1 and TNFR2, the latter being critical for regulatory T-cell expansion and suppressive function. Interference with the TNFR2-Treg axis may destabilize immune tolerance and promote immune re-polarization toward granuloma formation. In parallel, TNF-α inhibition alters cytokine networks, favoring Th1- and Th17-dominant responses and enhancing interferon-mediated antigen presentation, thereby creating a pro-granulomatous milieu. Pharmacologic differences among TNF-α inhibitors may further modulate this risk; notably, etanercept also neutralizes lymphotoxin-α, potentially amplifying immune dysregulation and accounting for its higher association with DISR. Consistent with these mechanistic distinctions, etanercept accounts for the largest proportion of reported DISR cases, followed by adalimumab and infliximab [4]. Reported cases also arise predominantly in rheumatic and psoriatic diseases, whereas inflammatory bowel disease and uveitis are less common [3, 4]. However, current evidence does not support disease-specific susceptibility; rather, these patterns likely reflect differential TNF-α inhibitor exposure across indications. The absence of reliable exposure denominators precludes estimation of incidence by underlying disease. Histopathologically, folliculitis-like lichenoid sarcoidosis is characterized by perifollicular granulomatous inflammation with a lichenoid lymphocytic infiltrate and minimal fibrosis, distinguishing it from acne vulgaris and Behçet's disease [1]. Management of TNF-α inhibitor-associated DISR should be individualized; while some cases resolve spontaneously or after drug withdrawal, topical corticosteroids may suffice for localized cutaneous disease [4]. This case highlights the importance of considering folliculitis-like lichenoid sarcoidosis in acneiform eruptions refractory to antimicrobial therapy in patients receiving TNF-α inhibitors. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.