Case Presentation:
A 36-year-old Caucasian male, a construction worker, presented with three weeks of high-spiking daily fevers, myalgias and fatigue. He endorsed a water-skiing trip, and tick and dog bites within recent weeks. He was discharged two days prior from an outside hospital (OH), where he was treated for possible pneumonia or a tick-borne illness with multiple antibiotics (not limited to vancomycin, doxycycline) without improvement. OH work up was non-revealing (negative for HIV, hepatitis profile, influenza, serologies for Lyme, EBV and Ehrlichia, cryptococcal antigen, ANA, RF, CPK and ESR) except for abnormal CRP, LDH and mild transaminitis. Bone marrow (BM) biopsy was performed. Empiric steroids helped symptomatically, and he was discharged on steroid taper. On presentation at our ED, vitals were T: 38.3C; BP: 130/85; HR: 110/min, RR: 22; Sp02:95% on RA. He had mild hepatosplenomegaly with otherwise normal skin and cardiopulmonary examination. Labs were unremarkable except ALT 182 IU/mL; AST 77 IU/mL; WBC 32,600/µL with 92% neutrophils; CRP:183 U/ml; ESR:80 mm/hr. CXR showed pleural effusions and perihilar opacities; CT revealed small bilateral effusions and mediastinal lymphadenopathy. Initial differential included infectious illnesses (viral, bacterial, fungal or tick-borne), connective tissue diseases, hematologic malignancy, and rare disorders like FMF. We decided to observe him closely without antibiotics or steroids as he was hemodynamically stable. On day 2, patient developed a high-grade fever at 40°C, and simultaneously developed a macular erythematous rash on his chest and abdomen. A salmon-colored evanescent rash with fever in a young male along with arthralgias, hepatosplenomegaly, elevated LFTs and negative ANA among others (meeting all Yamaguchi criteria) established diagnosis of Adult-Onset Still’s disease (AOSD). Later, ferritin resulted at 15,120 ng/mL while BM biopsy BAL cultures and cytology were negative. Patient initially responded to high-dose steroids and NSAIDs, but transaminitis and fever recurred within 48 hours requiring Anakinra (IL-1 inhibitor) resulting in significant improvement. He was discharged home on oral steroids and SC Anakinra.
Discussion:
Adult Onset Still’s Disease is a rare mixed connective tissue disease with a median time to diagnosis of four months. A diagnosis of exclusion, it is best assessed based on the Yamaguchi Criteria (as described below; diagnosis requires at least five features including 2 major), which has the highest sensitivity compared to other diagnostic criteria.
Major criteria:
– Fever >39ºC
– Arthralgia/Arthritis
– Evanescent febrile rash
– Leukocytosis > 10,000/µL
Minor criteria
– Sore throat
– Lymphadenopathy
– Hepatosplenomegaly
– Abnormal LFTs
– Negative ANA, RF
63% of AOSD patients respond to steroid monotherapy Our patient presented a relatively uncommon case of steroid-resistant AOSD, when biologic agents such as IL-1 inhibitors (Anakinra, response rate 96% amongst steroid resistant patients), TNF-alpha inhibitors (Etanercept), or IL-6 inhibitors (Tocilizumab) are needed.
Conclusions:
AOSD is a rare condition with often vague symptoms, including fever of unknown origin, and difficult-to-capture physical findings. Thorough, serial physical examinations supported with careful, targeted diagnostic workup are key to expediting diagnosis and treatment.