Hemophagocytic lymphohistiocytosis (HLH): A rare & often fatal diagnosis in older adults

ABSTRACT

INTRO Hemophagocytic lymphohistiocytosis (HLH) is an uncommon type of hemophagocytic syndrome characterized by systemic inflammation and overactivation of the immune system leading to multisystem failure.1 Most common in pediatrics1, it's a rare, challenging diagnosis often missed in older adults. CASE A 67 year-old male with a PMH of COPD, CKD3a, and lung nodules presented to his PCP for dyspnea and cough. COVID19 test was negative, CXR showed irregular opacities but no consolidation, so he was treated for COPD exacerbation. One month prior, he saw Pulmonology and completed a 10 day course of Augmentin. After 3 days, family noted the patient was jaundiced with dark urine. Labs showed normocytic anemia, acute on chronic kidney injury, and elevated LFTs. His PCP had him admitted for further workup and treated for community-acquired pneumonia;dyspnea improved. But, the patient's acute kidney injury worsened, so he was transferred from an outside facility to U of M Hospital. Nephrology was consulted and urine studies were consistent with ATN. Liver function worsened and drug-induced liver injury with cholestasis was suspected, given recent Augmentin. Acute hepatitis panel, infectious and autoimmune workups were negative. The patient's hgb declined, requiring multiple transfusions despite no source for an active bleed. Abdominal ultrasound showed an enlarged liver with diffusely coarse echogenicity. Liver biopsy showed diffuse granulomatous hepatitis with necrosis and cholestasis. Finally, soluble IL-2R was ordered and was quite elevated at 35,150 U/mL (normal 137-838 U/mL). Lab findings and clinical presentation led to a diagnosis of HLH. At the end, the patient decompensated requiring transfer to ICU for multi-organ failure. Following goals of care discussions with family, he was transitioned to comfort care and passed away soon afterward. DISCUSSION: This case shows the importance of considering HLH as a diagnosis in older adults with characteristic findings. Early diagnosis is often hard due to low suspicion, limitations of diagnostic criteria in adults, and inaccessibility to specialized lab tests (like soluble IL-2 assay). Adult HLH is usually fatal with median survival of about 2 months.