A 43–year–old man with recently diagnosed HIV/AIDS on HAART presented for further evaluation of worsening jaundice, abdominal pain and weight loss. He developed immune reconstitution syndrome following the initiation of HAART, and had concurrent disseminated MAI, CMV and HIV–related Cholangiopathy. Prior care included cholecystectomy, ERCP, Stent placement and hepatobiliary workup for reported irregular intrahepatic ducts with beaded appearance. On examination, he appeared chronically ill with scleral icterus and mild hepatomegaly. A complete blood count showed Anemia, Thrombocytopenia, hyponatremia, and transaminitis with marked hyperbilirubunemia (combined conjugated and unconjugated bilirubin). Ferritin level was markedly elevated, 4914, with an associated hypofibrinogenemia. Abdominal ultrasound showed marked intrahepatic billiary dilatation, and a liver biopsy demonstrated proliferation of bile ducts and small non caseating granulomas. Bone marrow stained with Wright stain showed increased histiocytic activity with 50% of histocytes showing hemophagocytosis. A diagnosis of the Hemophagocytic Syndrome was made.
Hemophagocytic Syndrome (Hemophagocytic lymphohistiocytosis, HLH) is a disorder related to cytokine dysfunction resulting in uncontrolled accumulation of activated T–Lymphocytes and activated histocytes. It can be precipitated by a variety of infections, malignancies and autoimmune disorders; it is a relatively rare complication of HIV infection but can be aggressive and potentially fatal. The management of HLH requires treatment of the underlying disease plus a regimen including steroids and etoposide. In this patient, treatment for concurrent infections including HIV, CMV and MAI were continued, and dexamethasone was started. However, the patient’s clinical status deteriorated with the development of severe sepsis, multiorgan failure, acute kidney injury, GI bleeding, central nervous system depression and respiratory failure that required ventilatory support. The patient succumbed a few days after transfer to the intensive care unit.
Internists, especially Hospitalists, should consider the hemophagocytic syndrome in the differential diagnosis for patients presenting with AIDS/ Immune reconstitution syndrome and/or multiple opportunistic infections. Proper diagnosis requires a high index of suspicion as its presentation can mimic common infections, and it should be in the forefront of differential diagnosis when these patients present with fever, splenomegaly, cytopenia and elevated ferritin and triglycerides. Early tissue biopsy with demonstration of hemophagocytosis in bone marrow, spleen or lymph nodes is essential in guiding aggressive early treatment with steroids and etoposide.