Subacute Cutaneous Lupus Erythematosus and Dermatomyositis-Like Eruptions During Anti-TNF-Alpha Therapy

Dear Editor, Anti-tumour necrosis factor-α (TNF-α) therapies paradoxically induce autoimmune phenomena, including dermatomyositis (DM)-like eruptions.[1,2] This mechanism may involve the promotion of type I interferon production, which stimulates autoimmunity. While DM and polymyositis (PM) cases are documented, our case represents the world’s first report of clinically amyopathic dermatomyositis (CADM) manageable without discontinuing the causative agent, particularly given the diverse and complex skin lesions observed. A 56-year-old Japanese woman was diagnosed 22 years ago with limited cutaneous systemic sclerosis (lcSSc), with sclerotic finger lesions and Raynaud’s. Twelve years ago, she started 20 mg prednisolone (PSL) for interstitial lung disease (ILD) of a non-specific interstitial pneumonia (NSIP) pattern. Eleven years ago, she developed rheumatoid arthritis (RA) and was started on etanercept. Nine years ago, she presented Gottron’s sign and nail fold changes [Figure 1a and b]. Serum creatine kinase (CK) and aldolase were normal. Anti-SS-A/Ro antibody was elevated, but other autoantibodies were negative. She opted to continue etanercept, managing skin lesions with topical corticosteroids. Over the next several years, she developed mechanic’s hands-like erythema [Figure 1c] and SCLE-like scaly erythema [Figure 1d]. Histopathological examinations consistently revealed perivascular lymphocytic infiltrates with mucin deposition, consistent with a DM-like eruption. Erythema developed on her auricular and posterior neck 8 years ago [Figure 1e], and on her shoulder and upper back 6 years ago [Figure 1f].Figure 1: (a and b) Nine years ago, Gottron’s sign on the dorsum of the hands (a), and onychoscopy showed enlarged capillaries and haemorrhages (b). (c) Nine years ago, mechanics hands-like erythema occurred. (d-f) Various eruption not corresponding to dermatomyositis, including scaly erythema on her left upper arm 8 years ago (d), erythema on her auricular and posterior neck area 6 years ago (e), and erythema on her shoulder and upper back 4 years ago (f). (g and h) Two years ago, Gottron’s sign on the dorsum of the hands (g), and onychoscopy showed enlarged capillaries and haemorrhages (h). (i) Histopathology of erythema on the dorsum of her hand showed hyperkeratosis, vacuolar degeneration, and perivascular lymphocytic infiltration in the dermis (haematoxylin and eosin staining, original magnification ×100)Two years ago, her ILD worsened, and PSL was increased to 10 mg. Following clinical improvement, similar lesions on her hands and nail fold reappeared [Figure 1g, 1h]. A biopsy from the dorsal hand showed hyperkeratosis, perivascular lymphocytic infiltration of the dermis, and mucin deposition on Alcian blue staining consistent with the DM-like eruption [Figure 1i]. CK was transiently elevated but normalised without muscular symptoms. Autoantibodies to MDA5, TIF1-γ, and other DM-specific markers remained negative. Malignant RA and Sjögren’s syndrome were excluded. Despite repeated cutaneous relapses, her ILD remained stable. Finger swelling due to SSc persisted. The patient strongly wished to continue etanercept. Due to worsening joint symptoms, etanercept was eventually switched to upadacitinib. The multiple skin lesions did not recur at the 6-month follow-up. We finally diagnosed her with SCLE[3,4] and DM-like eruptions[1,5] associated with anti-TNF-α [Figure 2].Figure 2: Timeline summarising the main events of this caseCausality was assessed using the Naranjo/WHO Causality Assessment Scale. The patient’s adverse reaction scored 11, indicating a definite causal relationship. Skin lesions appeared after initiating etanercept, recurred during long-term use, and resolved after switching therapy. While anti-TNF-α therapy has been linked to DM or PM in about 20 reported cases, most required discontinuation. In contrast, our patient is a rare instance where CADM-like skin involvement emerged during etanercept therapy but was manageable without stopping treatment. Importantly, her ILD did not progress throughout the course. This case emphasises the need to consider paradoxical autoimmune events during long-term anti-TNF-α therapy. Recognising cutaneous markers of DM, even without myopathy, is essential for timely intervention. Our experience highlights that individualised management − including continuing biologics when systemic disease remains stable − can be considered part of shared decision-making with patients. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.