Septic shock is one of the most common reasons that patients require intensive care unit (ICU) admission. We present a patient that had all the markings of septic shock, but a careful review of the data revealed a rare alternate diagnosis.
A 20-year-old female was admitted to the hospital with a complaint of right knee swelling, pain, and erythema. Her past medical history was significant for an occasional arthritic condition. The patient underwent aspiration of the right knee and was given vancomycin and ceftriaxone for suspected septic arthritis. Labs on admission were significant for a white blood cell (WBC) count of 19.4 x 109/L with 56% neutrophils and 32% bands, and C-reactive protein 196 mg/dl. Renal and liver function were essentially normal. All joint aspirate cultures and blood cultures were negative, and no crystals were observed. WBC count of the knee aspirate was 90,000 x 109/L (neutrophils 91%). Anti-nuclear antibody, double stranded DNA, rheumatoid factor, and HIV testing were all negative. The hospital course was marked by recurrent fevers, development of cervical and inguinal lymphadenopathy, increasing bandemia, anemia, elevation of liver function tests (LFTs), coagulopathy, and worsening renal failure. On the 11th day of hospitalization the patient had a generalized tonic clonic seizure. She became hypotensive, was transferred to the ICU and intubated. The physical exam upon arrival to the ICU showed cervical and inguinal lymphadenopathy. Her WBC count 6.9 x 109/L (bands 88%), hemoglobin 6.9 g/dl, platelets 115 x 109/L, internationalized normalized ratio 2.77, aspartate aminotransferase (AST) 2653 U/L, total bilirubin 2.9 mg/dl, direct bilirubin 1.7 mg/dl, albumin 1.8 g/dl, creatinine 3.5 mg/dl, CRP 24 mg/dl, and ferritin level 152,197 ng/ml. Peripheral blood smear showed no evidence of hemolysis. The initial ICU course was remarkable for hypotension requiring support with norepinephrine, continued mechanical ventilation, worsening liver and renal function, and institution of hemodialysis, and initiation of broad-spectrum antibiotic coverage. The history of a poorly categorized arthritis with the above presentation and laboratory data, combined with persistently negative cultures led to a diagnosis of juvenile idiopathic arthritis complicated by macrophage activation syndrome (MAS). This diagnosis was confirmed by bone marrow aspirate and biopsy that displayed macrophages actively phagocytosing hematopoietic cells (see figure). Methylprednisolone 1 gm IV daily and cyclosporine A 4 mg/kg/day were administered. By hospital day 20, the patient had been extubated. She no longer required blood products or hemodialysis; both her coagulopathy and LFTs improved and she was transferred to the general medical floor.
MAS is a rare complication of childhood systemic inflammatory disorders, such as juvenile idiopathic arthritis (JIA), that can present acutely and dramatically. Clinical features include high fever, elevated serum liver enzymes, coagulopathy, pancytopenia, and lymphadenopathy. As in our patient, neurologic, renal, and pulmonary involvement has been reported. The patient may show a paradoxical improvement in the signs and symptoms of the underlying inflammatory disease at the onset of MAS. The pathognomonic feature is a bone marrow biopsy showing hematophagocytosing macrophages. The primary modality of treatment is high dose parenteral corticosteroids, but cyclosporine has been shown to be helpful in steroid resistant cases. Other agents such as intravenous immunoglobulins, cyclophosphamide, plasma exchange, and TNF-alpha inhibitors have had variable success.
MAS is one of the many diseases that can present with a systemic inflammatory response that mirrors the signs of sepsis. This case emphasizes the importance of maintaining a healthy suspicion for other unusual disorders in the intensive care unit.
A.J. Blaivas, None.