The Chaos of the Hematology-Rheumatology Border: Adult Onset Still Disease-Associated Macrophage Activation Syndrome
Authors: Oo Yadana , Srisawitri Liana , Thein Min Zaw 
Published: December 2024

Introduction

Macrophage Activation Syndrome (MAS) is an under-recognized hematologic disorder associated with rheumatological diseases, including Adult Onset Still's Disease (AOSD). AOSD is a rare inflammatory disorder primarily affecting adults and characterized by immune dysfunction which can exacerbates MAS. If MAS is not promptly treated, it can lead to critical illness and lethal. The following is a clinical case presenting severe AOSD-associated MAS.

Case Report

A 37-year-old Caucasian female with a past medical history of mesiotemporal lobe epilepsy and uterine fibroids was initially admitted with the principal diagnosis of severe sepsis secondary to pneumonia and pelvic abscess from a recent hysterectomy. The hospital course was complicated with acute hypoxic respiratory failure that required intubation, cardiac arrest, and anuric acute kidney injury that needed renal replacement therapy. From the hematology and rheumatology standpoint, the history was significant in that she had diffuse severe arthralgia and pruritic generalized maculopapular rash for seven months before admission. She has a family history of lupus in her father and brother. Her labs showed WBC of 14.5 K, hemoglobin of 6.2, platelet of 191, and reticulocyte count of 3.2%. PT/INR, PTT, Fibrinogen, and complements were normal. Haptoglobin was less than 6 mg/dL, and Coombs was negative. D-dimer of 29,700 ng/ml, LDH of 1092 units/L, and ferritin of 42,800 ng/mL. AST of 233 U/L, ALT of 66 U/L, alkaline phosphatase of 289 U/L, total bilirubin of 2.0 mg/dL, and triglycerides of 312 mg/dL. Autoimmune panels, including ANA, anti-dsDNA, and rheumatoid factor, were negative. Infections workup including HIV, respiratory viral panel, EBV, Lyme disease, toxoplasma, Fungitell, Histoplasma, and blood culture were negative. CT abdomen was negative for hepatosplenomegaly. The skin biopsy showed neutrophil margination, endothelial swelling, perivascular monocyte-like cells, no hemophagocytosis, and most consistent with AOSD. The liver biopsy showed nonspecific acute hepatitis. The patient was started on IV methylprednisolone as there was concern for MAS in the setting of possible AOSD. Anakinra was started, followed by etoposide and cyclosporin in later days. With the starting of these medications, the D-dimer and ferritin trended down significantly. She was clinically improved and extubated successfully. The patient was discharged on day 27. She was prescribed mycophenolate 500 mg twice daily with a plan of discontinuing cyclosporine after 5 days of being on mycophenolate and tapered dose of steroids. She is currently following up with the hemato-oncologist team and has been stable since discharge.

Discussion

MAS is a potentially life-threatening complication of rheumatic diseases like systemic juvenile idiopathic arthritis, AOSD, and SLE. MAS is also considered a type of secondary hemophagocytic lymphohistiocytosis (HLH). AOSD has dysregulated immune responses and can trigger MAS. The over-activation of T lymphocytes and macrophages leads to a cytokine storm which can lead to multiorgan failure. MAS can present as persistent fever, lymphadenopathy, hepatosplenomegaly, cytopenias, increased inflammatory markers, hypofibrinogenemia, transaminitis, hypertriglyceridemia, and extreme hyperferritinemia. The poor prognostic factors in AOSD-associated MAS are thrombocytopenia, high serum ferritin levels, reduced fibrinogen levels, splenomegaly, and liver dysfunction. MAS is a significant cause of death in AOSD patients per the multi-center retrospective analysis conducted in China. The first-line medications crucial in MAS treatment are high-dose intravenous corticosteroids, cyclosporin, intravenous immunoglobulin (IVIg), and anakinra, a recombinant IL-1 receptor antagonist. Recognizing the MAS, initiating the first-line treatment, and conducting a multidisciplinary approach are crucial to reducing mortality in AOSD-assisted MAS.