THERAPEUTIC CHALLENGES IN POLYAUTOIMMUNITY: ANIFROLUMAB FOR LUPUS ERYTHEMATODES IN OVERLAPPING AUTOIMMUNE SYNDROMES

PV303 / #378 Case Report Poster Topic: AS24 - SLE-Treatment Introduction Polyautoimmunity is defined as the presence of 2 autoimmune diseases in a single individual, while Multiple Autoimmune Syndrome (MAS) involves 3 or more coexisting autoimmune conditions.[1] Diagnosing specific diseases in patients with multiple autoimmune conditions can be challenging and treatment regimens are often complex. Here we present 2 patients with polyautoimmunity and refractory lupus erythematosus who showed significant symptom improvement after adding anifrolumab, a monoclonal antibody targeting the interferon alpha receptor 1 (IFNAR1), to their treatment regimen. Case Presentation With Investigation Case 1: A 57-year-old woman with a history of multiple sclerosis (MS), treated with glatiramer acetate, presented with recurrent facial and periungual erythema, fatigue, weight loss, fever episodes, and finger pain. Diagnostic workup, including elevated ANA titer of 1:320, positive anti-dsDNA antibodies (42 U/mL), strongly positive anti-MDA5 and anti-RO-52 antibodies, led to an overlap syndrome of amyopathic dermatomyositis and lupus erythematosus. To address her full spectrum of autoimmune diseases, her MS treatment was switched to azathioprine and prednisolone, resulting in improved general condition and reduced facial erythema. However, painful periungual lesions with fissures persisted, greatly impairing her quality of life. Due to fine motor skill loss and significantly elevated Siglec-1 expression (16,347 antigens/monocyte), anifrolumab was added to her treatment regimen. This led to a rapid and marked improvement in the previously resistant periungual lesions, allowing corticosteroid tapering while maintaining MS stability. Case 2: A 60-year-old male patient with a history of psoriasis vulgaris and previous thromboembolic events presented with painful, scarring lesions on the fingers, nose, and scalp. Histology confirmed discoid lupus, and laboratory tests revealed a high ANA titer (1:1280), anti-dsDNA antibodies, and positive antiphospholipid antibodies, resulting in diagnoses of systemic lupus erythematosus (SLE) and antiphospholipid syndrome. Hydroxychloroquine was avoided due to concerns about exacerbating psoriasis. Alternative therapies with methotrexate and mycophenolate mofetil provided limited benefit. Although apremilast effectively controlled psoriasis, lupus lesions continued to progress. The initiation of anifrolumab therapy led to a rapid improvement in cutaneous lupus symptoms within weeks, while psoriasis remained stable and was well-controlled with topical treatments. Phenprocoumon was added for thromboembolic prevention, with no further thromboembolic events reported. Literature Review Anifrolumab is an effective treatment for refractory SLE, particularly cutaneous manifestations. Evidence shows that blocking type I interferon pathways, central in lupus pathology, can effectively reduce inflammatory responses. Clinical trials (eg, TULIP-1 and TULIP-2) have demonstrated anifrolumab’s efficacy in decreasing both systemic and cutaneous disease activity.[2] While the use of anifrolumab in polyautoimmunity and MAS requires further research, its targeted mechanism of action and favorable safety profile already make it a promising option for patients with overlapping connective tissue diseases.[3] Discussion Both cases illustrate the potential of anifrolumab as an effective add-on therapy for targeting refractory cutaneous symptoms in patients with connective tissue diseases. Although anifrolumab is currently approved only for SLE, its positive effects may extend to other connective tissue diseases characterized by elevated interferon alpha activity. The successful and safe use in patients with polyautoimmunity underscores anifrolumab’s suitability for patients with overlapping autoimmune diseases. References: [1.] Matusiewicz A. Int J Rheum Dis 2019;22:386-91. [2.] Morand EF. Lancet Rheumatol 2022;4:282-92. [3.] Shaw KS. J Am Acad Dermatol 2024;91(6):1217-9.