Case Presentation: A 45-year-old Hispanic female presented with four weeks of high-grade fever and polyarthralgias, and one week of sore throat and night sweats. She visited an urgent care center and laboratory evaluation revealed white blood cell count 4.6K/uL with 48% bands and lactate dehydrogenase 953 U/L. Serum and urine protein electrophoresis revealed no monoclonal bands, and flow cytometry immunophenotypes were normal. Five days prior to presentation, she developed a pruritic rash on her arms and chest. Her condition failed to improve leading to this hospitalization.

Her physical exam revealed a non-blanching erythematous maculopapular rash on her extremities, and pain in her knees, ankles, elbows and wrists without effusion. Laboratory testing showed white blood cell count 9.0K/uL with 6% bands, hemoglobin 11.2g/dL, platelet count 436K/uL, lactate dehydrogenase 1064 U/L, erythrocyte sedimentation rate 67mm/hr, c-reactive protein 217mg/L and ferritin 4972ng/mL. Respiratory viral panel, quantiferon gold assay, HIV, parvovirus B19 IgM, CMV/EBV, antinuclear antibody and rheumatoid factor were unremarkable. Peripheral blood smears were negative for Plasmodium, Babesia, Trypanosoma and Microfilaria, as were serologies for Anaplasma, Ehrlichiosis, and Lyme diseases. Whole body computed tomography scan was unrevealing. Skin biopsy showed neutrophilic urticarial dermatosis, and bone marrow aspirate revealed hypercellularity with trilineage hematopoiesis without evidence of lymphoma or leukemia. Given these findings, she was diagnosed with Adult Onset Still’s Disease.

Discussion: Adult Onset Still’s Disease (AOSD) is rare, with an estimated prevalence of 0.16-1 per 100,000 persons. Lacking a definitive diagnostic test, it is instead characterized by clinical and laboratory findings including fevers, arthralgias, rash and elevated ferritin[1].                                                             

Corticosteroids have been the mainstay of treatment, with 76-95% of patients achieving symptom improvement and resolution of laboratory abnormalities. However, given complications of chronic steroid use, focus has shifted toward interventions on the cytokine cascade, including tumor necrosis factor-α (TNF- α), interleukin (IL)-1 and 6, thought to be a driver in AOSD.

Research has shown that while serum TNF-α is increased in AOSD, TNF-α inhibitors offer little clinical benefit, thus shifting focus toward the interleukin response. In one study, the IL-1 receptor antagonist Anakinra resulted in defervescence and resolution of leukocytosis in 79% of subjects, compared to a 36% response with other biologics. IL-6 has also been studied as a treatment target, with Toclizumab showing improvement in arthritic symptoms[2].

Conclusions: Our patient was diagnosed with Adult Onset Still’s Disease and initiated on intravenous corticosteroids. Immunotherapy was considered, however she reported symptom improvement at follow-up.

References:

1. Efthimiou P1, Georgy S. Pathogenesis and management of adult-onset Still’s disease. Semin Arthritis Rheum. 2006 Dec;36(3):144-52.

2. Maria ATJ, Quellec AL, Jorgensen C, Touitou I, Rivière S, Guilpain P. Adult onset Still’s disease (AOSD) in the era of biologic therapies: Dichotomous view for cytokine and clinical expressions. Autoimmunity Reviews. 2014;13(11):1149-1159. doi:10.1016/j.autrev.2014.08.032.