Case Presentation: A 24 year-old woman presented to the emergency room for a sore throat and diffuse body aches, with weakness in her shoulders and hips to the point that she required assistance with ambulation over the past week. She was afebrile and normotensive at admission but initial labs were significant for a WBC of 22.5 k/µL, an ESR of 96 mm/h, and a CRP of 24.9 mg/dL. She was started on antibiotics on hospital day 3 (HOD 3) and was noted to have a ferritin of 9,777 µg/L. Despite treatment, on HOD 4 she began spiking fevers and her ferritin increased to 96,964 µg/L. Her fevers and elevated ferritin aroused suspicion for adult onset Still’s disease (AOSD). After she developed a macular rash across her extremities on HOD 9, her clinical picture became consistent with AOSD by the Yamaguchi criteria (fever of ≥ 39˚C, arthralgias lasting > 2 weeks, leukocytosis > 10,000 µmol, and a maculopapular rash). Her course was further marked by anemia, thrombocytopenia, and hypotension requiring midodrine. Subsequent labs tests revealed that she had macrophage activation syndrome or MAS (fever > 38.5˚ C, elevated ferritin, pancytopenia, hypofibrinonemia, and elevated CD25). The patient was started on prednisone and Anakinra on HOD 13. Soon after, she defervesced and was weaned off midodrine. Her rash resolved and she felt subjectively stronger. She was ultimately discharged to a rehabilitation facility.
Discussion: AOSD is a difficult to diagnose illness that can progress to MAS, a life threatening condition with up to a 41% mortality rate. AOSD is a systemic inflammatory condition characterized by daily fevers, arthritis, and an evanescent rash. Less common symptoms include splenomegaly, pleuritis, and pericarditis. Lab values show elevated ESR, CRP, and ferritin and neutrophilic leukocytosis. The etiology of AOSD is still poorly understood but is thought to an autoinflammatory condition triggered by exposure to an infectious agent in genetically susceptible individuals. Prognosis is variable; in patients with systemic disease, their course may be monocyclic, lasting two months to a year with sustained remission, or polycyclic with repeat flares. Patients with a chronic articular pattern have symptoms lasting beyond one year and tend to have a worse prognosis, developing disabling and destructive articular disease.MAS is considered to be a subclass of hemophagocytic lymphohistocytosis (HLH), induced by infections, medications, or disease flares. It is marked by over-activation of macrophages with phagocytosis of hematopoetic cells within the bone marrow, liver, spleen, and/or lymph nodes. MAS occurs in up to 15% of patients affected by AOSD. Given the overlapping features, it is thought to be the most severe form of AOSD. Patients with MAS have high fevers and lymphadenopathy with ferritin levels often > 5000 µg/L as well as elevated triglycerides and liver enzymes. Other subtle laboratory changes include falling platelet and leukocyte counts, hypofibrinogenemia, and a downtrending ESR due to low fibrinogen. The diagnosis is established by hemophagocytosis demonstrated on bone marrow biopsy. However, lack of this finding does not exclude the MAS diagnosis.
Conclusions: Treatment consists of corticosteroids and therapy for the triggering disease. In AOSD, therapy includes IVIG, cyclosporine, and/or agents against IL-1, IL-6, and cytokines. AOSD and MAS are both challenging conditions to detect given their nonspecific symptoms but early identification and treatment is of upmost importance for optimizing patient outcome.