A three-year-old previously healthy, fully vaccinated female presented to the emergency department for the third time after a two-week history of recurrent fevers of unknown origin with associated back and abdominal pain (Table 1). Her exposure history was notable for attending daycare and living with her family on a rural farm with livestock on a well water system. She had initially presented to the emergency department (ED) twice in the preceding two weeks for the same complaints, thought secondary to a viral illness. At this third presentation, she was found to have significantly elevated inflammatory markers. An abdominal ultrasound revealed a small left sided pleural effusion. Patient was admitted for further workup. EKG showed diffuse ST elevations consistent with acute pericarditis, and echocardiogram showed significant circumferential pericardial effusion without tamponade. Cardiology and Rheumatology services were consulted. Computerized tomography (CT) scan of the chest showed small bilateral pleural effusions. Blood cultures were negative. Urine cultures grew 40,000 col/mL Actinomyces turicensis and 2000 col/mL of Staphylococcus simulans, thought secondary to contamination, thus no antibiotics were initiated. Coxsackie B antibody titers were positive at 1:80. She was treated with ibuprofen and furosemide, and repeat echocardiogram showed interval improvement in the size of her pericardial effusion. She defervesced and was discharged home on ibuprofen and furosemide. One week after discharge, repeat echocardiogram demonstrated trivial residual effusion, thus ibuprofen and furosemide were discontinued.
Ten days after follow-up, patient presented to the ED for the fourth time with recurrent fevers and was found to have worsening inflammatory markers. Repeat echocardiogram had significantly increased pericardial effusion. She was re-admitted, colchicine was initiated and both ibuprofen and furosemide were restarted. Additional tests were obtained, including ANA, ANCA, anti-ds DNA, Invitae auto-inflammatory panel, Coccidiomycosis screen, and QuantiFERON TB Gold. She showed no symptom progression and was discharged home the day after. She was kept on colchicine, furosemide, and ibuprofen.
At follow-up three days later, she was still noted to have recurrent daily fevers. Given concern for an evolving systemic autoimmune process, she was started on a five-day course of prednisone (1 mg/kg daily) in addition to continuing ibuprofen and colchicine. A repeat echocardiogram two days later was normal. Coccidiomycosis screen, ANA, ANCA, and anti-ds DNA results were negative. QuantiFERON TB Gold was indeterminate, thus a T-spot was advised but not obtained at that time.(Table 2).
Two days after the completion of her steroids, patient presented to the ED for the fifth time still with persistent fevers and now in acute respiratory distress. Initial labs at presentation were notable for a leukocytosis of 35,300/mm^3, elevated procalcitonin of 0.65 ug/L, and elevated C-reactive protein (CRP) of 23.7 mg/dL; however, erythrocyte sedimentation rate (ESR) was decreased at 47 mm/h, as was her B-type natriuretic peptide (BNP) at 121 pg/mL compared to 326.1 pg/mL previously. Complete metabolic panel (CMP) was grossly normal except for an elevated alanine aminotransferase (ALT) of 110 U/L. EKG was only notable for sinus tachycardia, hence echocardiogram was not repeated given low concern for recurrent pericardial effusion with interval improvement in BNP. Given persistence of fevers on this fifth visit, Infectious Disease was eventually consulted.
Blood cultures were obtained, and she was started on vancomycin and cefepime. Chest x-ray (CXR) demonstrated a large opacity throughout the right hemithorax with cavitary lesion, which was not seen on previous CXRs. Further characterization on chest ultrasound showed a homogenous hypoechoic pleural effusion without septations and new complete atelectasis of the right lung. She was subsequently admitted to the PICU.
Chest tube was inserted and 500 mL of malodorous, purulent output was drained. Pleural fluid cultures were obtained. Findings on follow-up CT chest were suggestive of empyema with moderate right sided hydropneumothorax. Final autoimmune workup was negative (Table 3). Blood cultures grew S. epidermidis in 1/2 bottles, thought to be a contaminant as repeat blood cultures were negative. Preliminary pleural fluid showed many white blood cells, gram positive cocci, gram negative cocci, gram negative rods, and gram positive rods, some of which appeared to be branching. Vancomycin and cefepime were discontinued, and she was narrowed to ampicillin and sulbactam. Her home dose of colchicine was also continued.
Initial immunologic work up (Table 4) were within normal limits. CXR supported pneumatocele versus pneumothorax. Given possible pneumatocele, hyper-IgE syndrome was considered, however IgE levels were also normal. Patient improved and by day 3 she was transferred to the acute care floor.
Approximately one week following admission, her pleural fluid cultures were finalized as growing pan-sensitive A. meyeri, and antibiotics was further narrowed to ampicillin alone. Other infectious workup were largely negative. Due to concerns for underlying immunodeficiency, T-spot test with a Candida control was done. Both PPD and Candida control were negative, prompting further immunologic workup. Oxidative burst was within normal limits, however CH50 activity was absent and AH50 activity was low (Table 4). Because of concern the colchicine may be causing some degree of immunosuppression, it was discontinued after a normal repeat echocardiogram.
Her hospital course was complicated by development of normocytic anemia likely secondary to chronic disease. Fevers resolved by week two of admission, and she was discharged by week three on IV ceftriaxone to complete a total 6 week course of IV antibiotics, followed by 6-12 months of oral antibiotics. Following discharge, she was referred to Immunology. A repeat CH50 activity performed two months after was subsequently normal. The remainder of her immune work up was also within normal.