Macrophage Activation Syndrome in Mixed Connective Tissue Disease: A Case of Multisystem Crisis and Recovery

Background To describe a life-threatening presentation of macrophage activation syndrome (MAS) in a young adult with mixed connective tissue disease (MCTD) with predominant features of SLE, highlighting diagnostic challenges, therapeutic escalation, and the multidisciplinary coordination required for recovery.

Case Report Methods: A 28-year-old female with MCTD and Systemic Lupus Erythematosus (SLE) features (managed by Rheumatology in the community), presented to the ER with 3 days of febrile illness, headache and diplopia, chest pain, diarrhea, and profound myalgias. She had been off treatment for several months due to intolerance to Azathioprine and self-discontinuation of Hydroxychloroquine and was recently started on Rinvoq by Dermatology for her only active symptom of inflammatory dermatosis. In the hospital, initial labs revealed bi cytopenia (hemoglobin 111, platelets 128), elevated ferritin (10,827 μg/L), CK (490 U/L), troponin (75 ng/L), and BNP (2497 ng/L). Imaging confirmed myocarditis and MRI brain showed cytotoxic lesion of the corpus callosum (CLOCC). MAS was suspected based on fever, cytopenia’s, hyperferritinemia, and systemic inflammation. Initial treatment included pulse IV methylprednisolone (1 gm daily for 3 days), Anakinra 100 mg SC BID, and continuation of Rinvoq. The patient initially improved but suffered a pulseless electrical activity (PEA) arrest on day 4, requiring 10 minutes of CPR and ICU transfer. Anakinra was escalated, and Emapalumab access was urgently pursued. Results: Following Emapalumab initiation and intensified immunosuppression, the patient stabilized. She was extubated on day 5 post-arrest and transitioned back to the medical unit. Rituximab was added, and hydroxychloroquine was reintroduced. Laboratory markers improved: ferritin decreased to 982 μg/L over 2 weeks, CK and liver enzymes improved, and inflammatory markers resolved. Post ICU stay was complicated by ongoing diplopia and headache, digital gangrene, new proteinuria, and persistent oral ulcerations. Multispecialty involvement included Cardiology, Neurology, Nephrology, Dermatology, and Hematology.

Conclusion MAS in MCTD can present subtly before rapid deterioration. Early recognition of hyperferritinemia and cytopenia’s is critical. This case underscores the importance of clinical suspicion, therapeutic escalation, including biologics like anakinra and Emapalumab, and highlights the logistical challenges of accessing rare therapies. Multisystem involvement demands coordinated care, and even with clinical improvement, vigilance is essential due to the risk of delayed complications. We recognize the importance of reporting this case and advocating for the use of these limited access medications that are pivotal for this life-threatening condition.