Abstract Introduction Hemophagocytic lymphohistiocytosis (HLH) is a severe, often fatal syndrome of immune dysregulation. While primary HLH is typically inherited and occurs in children, secondary HLH is acquired and has been increasingly recognized in adults. Secondary HLH is commonly triggered by infection, predominantly viral. Early identification of disease is essential as timely intervention is associated with improved outcomes. Early signs of HLH include fever, cytopenias, organomegaly, and lab abnormalities such as elevated ferritin, increased liver enzymes, hypertriglyceridemia, and marrow hemophagocytosis. The “H-score,” a validated tool that predicts the likelihood of HLH using these signs, is commonly used by clinicians. Additional biomarkers associated with HLH include soluble interleukin-2 receptor (sCD25) and cytokines such as chemokine ligand 9 (CXCL9) and interleukin-18 (IL-18). Description A 59-year-old man was admitted to the ICU with Streptococcal pneumonia and bacteremia resulting in acute respiratory distress syndrome and septic shock. Despite appropriate treatment, he remained ventilator-dependent with progressive multiorgan failure. At week two, fevers persisted and he developed anemia and thrombocytopenia. Cytopenias were initially attributed to myelosuppression and fevers to dexmedetomidine. HLH was considered but thought unlikely due to factors including an initial low H-score (101, 1-3% probability of disease) and low historical association of HLH with pneumococcal infection. Over the next few days, he became profoundly pancytopenic with ongoing high fevers while off dexmedetomidine. The H-score rose to 166 indicating 40-54% risk of disease. sCD25 levels collected at time of initial HLH consideration resulted as elevated (3076 U/mL). Empiric treatment for HLH was initiated with high dose steroids and intravenous immunoglobulins. Despite treatment, cell counts continued to decline and mental status worsened with development of seizures. Computed tomography imaging revealed new intracranial hemorrhage with midline shift, and the patient soon expired secondary to cerebral herniation. Results that became available postmortem included elevated CXCL9 (20943 pg/mL) and IL-18 (1816 pg/mL) levels, and bone marrow biopsy which revealed histiocytes with hemophagocytosis. Discussion While HLH is increasingly recognized in adults, it is often diagnosed late. This case describes an atypical presentation triggered by Streptococcus infection with a low initial H-score given lack of traditional laboratory abnormalities at disease onset. Supporting markers including sCD25, CXCL9, and IL-18 were elevated, but were not available for diagnostic consideration in a timely manner. Increased availability of cytokine markers and their incorporation into predictive scoring models may lead to improved HLH detection. Earlier HLH detection and treatment might have improved the outcome for this patient. This abstract is funded by: None
McNamara et al. (Fri,) studied this question.