Taming the Fire: Lung Sparing MDA-5 DM and MAS Overlap Successfully Treated with Methylprednisolone, Rituximab, IVIG, Anakinra, and Tofacitinib

Background Anti-melanoma differentiation-associated protein 5 (MDA5) Dermatomyositis (DM) can be refractory to multiple lines of immunosuppression.[1] Here, we present a case of refractory MDA-5 DM with Macrophage Activation Syndrome (MAS) overlap requiring numerous immunosuppressive courses to achieve stability.

Case Report A 30-year-old man of East Asian ancestry presents with a 2-month history of heliotrope rash, puffy eyes, periungal erythema, bilateral polyarthritis, as well as muscle weakness progressing to dysphagia and dyspnea. His Initial CK was 993 with a negative ANA, RF, CCP, and a CRP of 12. On his myositis panel, he was positive for anti-MDA-5 (51), anti-Ku positivity (42). His pulmonary function test had decreased DLCO (61%) but increased residual volume (133%), favoring neuromuscular restriction, with only a small non-specific ground glass opacity on CT Chest with no specific ILD signs. He was started on IVIg 2 g/kg as well as methylprednisolone 500 mg 3-day pulse (Figure 1 for full therapeutic course). He also received an initial Rituximab 1g dose 4 days after admission. On day 4, he was planned for discharge, however, his ferritin continued to rise from admission 3,779 ug/L to a peak of 6,412 ug/L on post-admission day 13, with increasing Triglycerides to peak of 2.62 mmol/L, a mid-100s range transaminitis, worsening weakness and therefore there was a concern for macrophage activation syndrome (MAS). Peak H-score was 146, however, no signs of primary HLH was seen on bone marrow biopsy. Soluble CD163 receptor (1467 ng/ml, cutoff was 1217) was positive as well as was sIL2 (360 ng/ml, cutoff was 666)s. He was started on Tofacitinib 11 mg daily and re-pulsed with Methylprednisolone 500 mg for 3 days again. He was also later (see Figure 1) given Anakinra 100 mg q8H and pulsed again with Methylprednisolone 500 mg for 3 days and also received a second Rituximab 1g dose and IVIG 2g/kg course. Multiple attempts to taper steroids were unsuccessful with MRI on post-admission day 31 demonstrating thigh hematoma and worsening myositis despite treatment, with the hematoma felt due to myositis which lead to a third course of IVIG (2g/kg) and he improved and MDA-5 level continued to reduce until discharge when it was 17. Ultimately, he was discharged on Anakinra, Prednisone, and Tofacitinib. He remained stable with Prednisone and Anakinra down-taper and was stable at a 6-month follow-up on only Tofacitinib 10 mg BID and Anakinra 100 mg sc on alternating days.

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Conclusion Here we present a novel case of MDA-5 overlap with MAS, in a patient without radiographic ILD, successfully treated by immunosuppression including Tofacitinib and Anakinra. This builds on past work treating MDA-5 with ILD with a triple regimen (Methylprednisolone, Rituximab, Tofacitinib) [2] and further supports the role of Tofacitinib.[3]

References [1.] Lu X. Nat Rev Rheumatol 2024;20:48-62. [2.] Manghani M. Rheumatol Autoimmun 2024;4:122-5. [3.] Yanagihara T. Eur Respir J 2025;65:2500458.