Refractory Macrophage Activation Syndrome Secondary to anti-mda5 Antibody Positive Juvenile Dermatomyositis

Introduction: Macrophage activation syndrome (MAS) is a severe and under recognized complication of systemic inflammatory disease. In pediatrics MAS is most commonly associated with systemic juvenile idiopathic arthritis (sJIA), but the true incidence is likely underestimated. We present a patient whose initial presentation of anti-MDA5 antibody juvenile dermatomyositis (JDM) was complicated by rapidly progressive MAS.

Case Description: We describe a 14-year-old female who presented with a history of daily fevers for six weeks and an unintentional twenty-six-pound weight loss. Review of systems was significant for cough, shortness of breath, chest pain, headaches, sore throat, muscle aches, nausea, and loss of appetite. Two months prior she described an episode of palmar and plantar vesicular and macular lesions diagnosed as hand foot and mouth disease. This was followed by rash and pain over her knuckles. Extensive initial work up was negative for infection and malignancy but did show findings consistent with a probable autoimmune process with elevated transaminases, CK, aldolase, GGT, ferritin, serum IgG level, anti-SS-A antibody, anti-smooth muscle antibody, and von Willebrand factor antigen. While workup continued, she had clinical decompensation with multi-organ system involvement including pancytopenias, interstitial lung disease, hepatitis, cardiac involvement, gastrointestinal distension and pain, feeding intolerance, extensive mucocutaneous candidiasis, and neuropsychiatric decline. Due to her decompensation and clinically apparent MAS with unclear underlying etiology she was started on high dose pulse steroids and mycophenolate. MRI was performed due to shoulder pain revealing significant proximal symmetric myositis, which in conjunction with her rash was consistent with JDM. Her myositis antibody panel, positive for anti-MDA5 and anti-SSA-52 antibodies, solidified this diagnosis. Despite high dose pulse steroids, mycophenolate, and adding IVIG, her disease progressed requiring escalating therapy. Mycophenolate was discontinued and she was treated with escalating doses of IV anakinra, IVIG, and cyclosporine. Her MAS continued to worsen and was complicated by posterior reversible encephalopathy syndrome (PRES), attributed to cyclosporine. Cyclosporine was discontinued and etoposide with dexamethasone was initiated. Tofacitinib was also initiated given recent successful reports of its use in JDM. She suffered additional complications of duodenal ulceration and typhlitis but ultimately she responded well to this medication combination. Treatment resulted in resolution of her MAS and feeding intolerance with significant and steady improvement in her interstitial lung disease, cardiac dysfunction, myositis, arthritis, and cutaneous findings.

Discussion: Reports of anti-MDA5 antibody positive JDM complicated by MAS in children are rare, but similar presentations have been described in adults. While MAS is recognized as a complication of rheumatologic diseases, our patient demonstrated this rare complication to her uncommon subset of JDM.

Conclusion: This case highlights the importance of recognizing clinical features and having an index of suspicion for MAS when treating JDM and that treatment may be refractory requiring multiple immunosuppressants.