https://doi.org/10.4081/reumatismo.2026.2395
Anifrolumab as a therapeutic option in mixed connective tissue disease with autoimmune cytopenia: a case report and narrative review of the literature
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Published: 26 August 2026
Mixed connective tissue disease (MCTD) represents a complex autoimmune condition characterized by vasculopathy, fibrosis, and immune dysregulation. Autoimmune cytopenias are rare but clinically significant complications that increase morbidity and complicate management of these diseases. Current therapies, including glucocorticoids and conventional immunosuppressants, may be limited by intolerance or inadequate hematologic response. Type I interferon (IFN) signaling has emerged as a key pathogenic pathway, and its blockade represents a novel therapeutic approach. We describe a 39-year-old woman with MCTD and clinical features of systemic sclerosis, presenting with Raynaud’s phenomenon, digital ischemic ulcers, esophageal involvement, and pulmonary arterial hypertension. Her disease course was complicated by progressive cytopenia, including leukopenia, severe lymphopenia, mild anemia, and thrombocytopenia. Azathioprine therapy led to worsening pancytopenia, necessitating discontinuation, while glucocorticoids provided only partial hematologic recovery. Subsequent treatment with mycophenolate was ineffective. Introduction of anifrolumab (300 mg IV every 4 weeks) resulted in hematologic improvement, with normalization of hemoglobin and stabilization of leukocyte and platelet counts, without infusion-related adverse events. The findings support type I IFN blockade as a promising therapeutic avenue in refractory hematologic manifestations of connective tissue disease, warranting further investigation in larger studies.
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Resende ABL, Monteiro GP, Ramos CC, Lopes GS, Broekman LA, De Souza JM. Integrating the autoimmune connective tissue diseases for the medical student: a classification proposal based on pathogenesis and clinical phenotype. Heliyon 2023; 9: e16462. DOI: https://doi.org/10.1016/j.heliyon.2023.e16935
Ortega-Hernandez OD, Shoenfeld Y. Mixed connective tissue disease: an overview of clinical manifestations, diagnosis and treatment. Best Pract Res Clin Rheumatol 2012; 26: 61-72. DOI: https://doi.org/10.1016/j.berh.2012.01.009
Tanaka Y. Is mixed connective tissue disease (MCTD) a subtype of systemic sclerosis? Semin Arthritis Rheum 2025; 72: 152678. DOI: https://doi.org/10.1016/j.semarthrit.2025.152678
Fairley JL, Hansen D, Proudman S, Sahhar J, Ngian GS, Walker J, et al. Clinical features of systemic sclerosis-mixed connective tissue disease and systemic sclerosis overlap syndromes. Arthritis Care Res 2021; 73: 732-41. DOI: https://doi.org/10.1002/acr.24167
Zhang W, Wang F, Wang H, Hua B, Feng X, Sun L. Severe thrombocytopenia in connective tissue diseases: a single-center review of 131 cases. Clin Rheumatol 2018; 37: 3337-44. DOI: https://doi.org/10.1007/s10067-018-4312-y
Wu M, Assassi S. Dysregulation of type I interferon signaling in systemic sclerosis: a promising therapeutic target? Curr Treatm Opt Rheumatol 2021; 7: 349-60. DOI: https://doi.org/10.1007/s40674-021-00188-9
Jones SA, Morand EF. Targeting interferon signalling in systemic lupus erythematosus: lessons learned. Drugs 2024; 84: 625-35. DOI: https://doi.org/10.1007/s40265-024-02043-2
Seidel MG. Autoimmune and other cytopenias in primary immunodeficiencies: pathomechanisms, novel differential diagnoses, and treatment. Blood 2014; 124: 2337-44. DOI: https://doi.org/10.1182/blood-2014-06-583260
Panda BK, Umarje S, Diwan A. Azathioprine-induced pancytopenia and septic complications: a probable cause of death. J Pharm Pract 2018; 31: 510-3. DOI: https://doi.org/10.1177/0897190017729521
Ciechomska M, Skalska U. Targeting interferons as a strategy for systemic sclerosis treatment. Immunol Lett 2018; 195: 45-54. DOI: https://doi.org/10.1016/j.imlet.2017.10.011
Khanna D, Denton CP, Assassi S, Kuwana M, Allanore Y, Domsic RT, et al. A randomised, parallel-group, double-blind, placebo-controlled phase 3 study to determine the effectiveness of the type I interferon receptor antibody, anifrolumab, in systemic sclerosis: DAISY study design and rationale. Clin Exp Rheumatol 2024; 42: 1635-44. DOI: https://doi.org/10.55563/clinexprheumatol/s8qcyu
Katsman Y. Improved mouse models for the study of treatment modalities using sulfur-containing small-molecular-weight molecules for passive immune-mediated thrombocytopenia. 2009. Available from: https://www.collectionscanada.ca/obj/thesescanada/vol2/OTU/TC-OTU-18786.pdf.
Budhram B, Weatherald J, Humbert M. Pulmonary hypertension in connective tissue diseases other than systemic sclerosis. Semin Respir Crit Care Med 2024; 45: 419-34. DOI: https://doi.org/10.1055/s-0044-1782217
O’Reilly S. Emerging therapeutic targets in systemic sclerosis. J Mol Med 2024; 102: 465-78. DOI: https://doi.org/10.1007/s00109-024-02424-w
Ceccarelli F, Piga M, Bortoluzzi A, Coladonato L, Fredi M, Mauro D, et al. The role of anifrolumab in reshaping the treatment landscape of extra-renal systemic lupus erythematosus. Reumatismo. 2025 Nov 24;77(4). doi: 10.4081/reumatismo.2025.1830. Epub 2025 Jul 23. PMID: 40704391. DOI: https://doi.org/10.4081/reumatismo.2025.1830
CRediT authorship contribution
Noemi Italiano: conceptualization, validation and formal analysis, investigation, data acquisition and curation; writing-original draft preparation; writing review and editing; visualization, supervision. Fabio Massimo Perrotta, Mauro Fatica, Ennio Lubrano: conceptualization, validation and formal analysis, investigation data curation; writing-original draft preparation; writing review and editing; visualization, supervision. All authors have read and agreed to the published version of the manuscript.
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