Braun, Chris

Abstract Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of aggressive inflammation and immune system activation. Its diagnosis is often hindered by its clinical overlap with sepsis, multiorgan failure, and other severe diseases common in the intensive care unit. We present a case of HLH diagnosed in the setting of multiple confounding conditions. Case Presentation: 24-year-old Caucasian male with common variable immunodeficiency presented to local hospital after a week of diffuse swelling and shortness of breath, initially found to be hypoxemic, hypoglycemic, hypovolemic, and febrile to 105°F. He was treated for septic shock, requiring norepinephrine, vasopressin, angiotensin, and stress dose hydrocortisone to maintain perfusion pressures. For work of breathing, he failed noninvasive ventilation and was intubated. Initial labs showed shock liver, acute kidney injury with severe metabolic acidosis, and MSSA bacteremia without endocarditis on transesophageal echocardiogram. He met HLH diagnostic criteria with high fever and ferritin 44,838 ng/mL; other inflammatory markers were not tested. Over two weeks the patient developed significant left lower extremity soft tissue infection concerning for Staphylococcus toxic shock syndrome, cholecystitis with cholecystostomy tube placement, hemorrhagic bullae on all limbs, left thigh hematoma, and new liver lesion that underwent biopsy complicated by significant bleeding requiring interventional radiology embolization. After transfer to our institution, he remained on fluctuating doses of norepinephrine with recurring fevers despite broad spectrum antibiotic and antifungal coverage. Repeat blood cultures were negative, MRI negative for osteomyelitis, pan-CT negative for other occult sources of infection, broad laboratory workup negative for atypical infections or antibodies related to rheumatologic diseases. At this point, he fulfilled HLH criteria given high fever, anemia and thrombocytopenia, splenomegaly, triglyceride 417 mg/dL, ferritin 1,953 ng/mL, and soluble IL-2 receptor >4,000 pg/mL. A multidisciplinary decision was made to start methylprednisone. Patient's fever and hemodynamic instability quickly resolved. He was then transitioned to anakinra with downtrend in his inflammatory markers. Discussion: HLH syndrome is often a delayed diagnosis as clinical manifestations mimic infections, can be triggered by such infections, or mimic other diseases in which a robust inflammatory response occurs. HLH laboratory findings are nonspecific or can have long turnaround time. Even its namesake of “hemophagocytosis” is not pathognomic for the disease. It is only in the case of excessive pathologic immune system activation, i.e. HLH syndrome, that immunosuppression is beneficial. Diagnosing HLH requires a curious clinical mind while treating concomitant urgent conditions, to avoid the “tunnel vision” of the often-cited occam's razor.