A 49 year old male with unknown history is brought in by EMS for three days of a productive cough, fever, chills and increasing somnolence  at home. He is found to have a temp of 102.3° F, BP 88/40, RR 26 and SpO2 86% on BiPAP. His CXR shows bilateral infiltrates and he is intubated for respiratory failure and admitted to the MICU with a diagnosis of sepsis secondary to pneumonia. Initial labs are notable for WBC 1.2, Hgb 7.4, platelets 86, lactate 6.7, Cr 1.9. He is aggressively treated over the course of the next few days for septic shock and continues to decline. On Hospital day three he is encephalopathic, has developed ARDS, and his shock is worse requiring multiple vasopressors. CRRT is initiated for ARF, and AST/ALT are both >3,000. During rounds the nurse is concerned that his CVC dressing is bloody. Your attending asks if there is anything on the differential that this could mimic sepsis.

Hemophagocytic lymphohistiocytosis (HLH)  

HLH is a disorder of excessive immune activation. It is life threatening and it’s etiology can be difficult to determine in the critically ill patient. It was originally described as immune dysregulation due to genetic predisposition but now it is also thought to be triggered by infection, malignancy, and autoimmune disease.  The patient in this case has both sepsis secondary to pneumonia and HLH diagnosed after bone marrow biopsy. Keep HLH in mind when you have a critically ill patient in septic shock with the below diagnostic criteria 

Diagnosis requires at least of the following 

•  Fever > 38.5°C
• Splenomegaly
• Cytopenia in at least two cell lines
• Hemoglobin < 9 mg/dL
• Platelets < 100 billion/L
• Neutrophils < 1,000 / microliter
• Hypertriglyceridemia and/or hypofibrinogenemia
• Triglycerides >265 mg/dL
• Fibrinogen < 150 mg/dL
• Hemophagocytosis in bone marrow, spleen, or lymph node biopsy 
• Ferritin >500 ng/ml
• Low natural killer-cell activity 
• Soluble CD25 (i.e. soluble IL-2 receptor) > 2,400 U/ml

Macrophage phagocytosing other cells (Public Domain Image, Wikimedia)  

References:

Bergsten E, Horne A, Aricó M, et al. Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-term results of the cooperative HLH-2004 study. Blood. 2017;130(25):2728–2738. doi:10.1182/blood-2017-06-788349 

Raschke, R., & Garcia-Orr, R. (2011). Hemophagocytic lymphohistiocytosis: a potentially underrecognized association with systemic inflammatory response syndrome, severe sepsis, and septic shock in adults. Chest., 140(4), 933–938. https://doi.org/10.1378/chest.11-0619

Ramos-Casals, M., Brito-Zerón, P., López-Guillermo, A., Khamashta, M., & Bosch, X. (n.d.). Adult haemophagocytic syndrome. The Lancet., 383(9927), 1503–1516. https://doi.org/10.1016/S0140-6736(13)61048-X