Anifrolumab for refractory chilblain lupus erythematosus

Dear Editors, Pernio, also known as chilblains, is a rare inflammatory condition that presents with erythematous papules on acral surfaces, such as the fingers, toes, and ears, often triggered by cold exposure.1 Pernio can occur as a primary disorder or as a secondary manifestation of an underlying condition. When associated with systemic lupus erythematosus (SLE), it is referred to as chilblain lupus erythematosus, a subtype of cutaneous lupus erythematosus (CLE).2 The pathogenesis of lupus-related conditions, including SLE, discoid lupus erythematosus, subacute cutaneous lupus erythematosus, and chilblain lupus erythematosus, is largely driven by cytokine dysregulation, with interferon (IFN)-1 playing a key role in the inflammatory process.3,4 Anifrolumab, a monoclonal antibody that blocks the IFN-1 receptor, was approved by the Food and Drug Administration in 2021 for the treatment of moderate-to-severe SLE following clinical trials demonstrating its efficacy. These trials also demonstrated significant reductions in skin disease activity.5 Despite its success in CLE, there is limited data on its use specifically in chilblain lupus erythematosus. We present a case of treatment-resistant chilblain lupus erythematosus that showed marked improvement following anifrolumab therapy. An 85-year-old female with myelodysplastic syndrome was referred for an annular photodistributed eruption on the trunk and extremities as well as significant pain, erythema, and swelling in her fingertips, which worsened with cold exposure (Fig. 1A). Antinuclear antibody was positive (1:320). Lupus anticoagulant, anti-β2-glycoprotein antibodies, anticardiolipin antibodies, antineutrophil cytoplasmic antibody, anti-PR3, antimyeloperoxidase, and a myositis panel were all negative. C3, C4, creatine kinase, and urine testing were normal. A biopsy of the annular eruption on her chest demonstrated interface dermatitis with dyskeratosis of basaloid keratinocytes and a mild superficial perivascular lymphocytic infiltrate, consistent with a connective tissue disorder. A biopsy of the right fourth fingertip showed marked capillary ectasia with minimal nonspecific inflammation and no evidence of vasculitis. She was diagnosed with subacute cutaneous lupus erythematosus and chilblain lupus erythematosus but did not meet the criteria for SLE. Annular plaques persisted despite topical steroids. She was sequentially treated with hydroxychloroquine, methotrexate, and mycophenolate mofetil, but was unable to achieve remission. Moreover, her pernio was refractory to the aforementioned agents as well as nifedipine, amlodipine, and sildenafil.Fig. 1.: (A) Clinical image of the patient’s hands showing erythema, swelling, and onycholysis in multiple digits. (B) Follow-up image 6 months after initiating therapy, demonstrating significant resolution of swelling, erythema, and nail abnormalities.Her chilblain lupus erythematosus was complicated by acute on chronic paronychia in multiple fingernails, with the right 4th finger developing onycholysis and bacterial infection necessitating nail avulsion and antibiotics. She also developed ulceration adjacent to the nail. Due to persistent symptoms and functional impairment after multiple failed treatments, anifrolumab was initiated. Within 1 week of the first infusion, the patient reported marked improvement, with a substantial reduction in pain, swelling, and erythema in her fingers. At her 6-month follow-up, the patient demonstrated a sustained response (Fig. 1B), complete resolution of annular plaques, and reported improved use of her hands and the ability to resume activities previously limited by her disease. This case highlights the potential role of anifrolumab in addressing treatment-resistant chilblain lupus erythematosus. While the drug is Food and Drug Administration-approved for SLE and has demonstrated benefits in CLE, its role in managing chilblain lupus erythematosus remains underexplored. The significant and sustained response observed in this patient underscores the potential of targeting the IFN-1 pathway for refractory pernio, including cases unrelated to SLE. Further research is necessary to evaluate its efficacy in larger cohorts and expand its therapeutic potential. Conflicts of interest None. Funding None. Study approval N/A Author contributions HB: Drafted the manuscript and contributed to revisions. AK: Provided patient care and contributed to manuscript editing and revisions. JT: Provided patient care and contributed to manuscript editing and revisions. ALC: Conceived the case report, provided patient care, reviewed the manuscript, and provided final approval. Patient consent Informed, written consent was received from all patients for whom photographs are present in the manuscript.