Hemophagocytic Lymphohistiocytosis Secondary to Unknown Underlying Hodgkin Lymphoma Presenting with a Cholestatic Pattern of Liver Injury

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is an uncommon disease that often presents with nonspecific findings. A high index of suspicion is necessary to make a prompt diagnosis and prevent fatal disease. A 45-year-old man presented with fever, hypotension, abdominal pain, nausea, and vomiting. Imaging showed hepatosplenomegaly and laboratory tests revealed pancytopenia, increased ferritin, and a cholestatic pattern of injury with elevated alkaline phosphatase and total bilirubin. Due to a history of Crohn disease, systemic lupus erythematous, and rheumatoid arthritis, the patient was on immunosuppressants, including infliximab. After multiple negative cultures, persistent fever, and days of empiric broad spectrum antibiotics, our differential shifted to fever of unknown origin. A liver wedge biopsy revealed areas of sinusoidal dilatation with enlarged, activated macrophages containing erythrocytes and intracytoplasmic iron, consistent with hemophagocytosis due to HLH. The portal tracts showed mixed lymphoplasmacytic inflammation, a prominent bile ductular reaction, periportal fibrosis, and scattered large cells with occasional binucleation and prominent nucleoli. These cells stained positive for Epstein-Barr virus encoding region in situ hybridization, PAX5, CD15, and CD30, and hepatic involvement by classic Hodgkin lymphoma was diagnosed and determined to be the cause of the HLH and cholestatic pattern of injury. Simultaneously, a bone marrow biopsy showed diffuse involvement by Hodgkin lymphoma with a similar staining pattern. Aggressive treatment failed and the patient succumbed to multiorgan failure. HLH is a rare, potentially fatal disease, with nonspecific signs and symptoms, and should be considered in any patient presenting with fever and pancytopenia, especially if they are immune compromised.

Pseudo-monoclonal gammopathy due to autoimmune disease: a case report

“…Fortunately, we did not find any abnormal tracer concentrations. For this young patient, we consider that AID caused liver injury, as previously reported, 11 and then cirrhosis and hypersplenism occurred after a long time. Portal vein thrombosis and splenic vein thrombosis are common complications in cirrhosis mainly because of portal hypertension and dysfunction of blood coagulation.…”

Hepatic haemophagocytosis in haematology patients with hepatic dysfunction: prognostic impact and contribution of liver biopsy combined with the haemophagocytic syndrome diagnostic score (HScore)

“…At D0, 35% were critically ill and required ICU management. The median SOFA score was 6 4–9 . Clinically, almost one‐third of patients presented with hepatomegaly, weight gain, hepatodynia, ascites, fever, or sepsis, and 65% received antimicrobial therapy.…”

“…Many situations can lead to HD. At diagnosis or relapse, patients can present with hepatic tumour infiltration, 6 tumour lysis syndrome 7 or haemophagocytic syndrome (HS) 8 . During treatment, HD is mainly caused by infections, sepsis, chemotherapy‐induced hepatotoxicity, 9,10 targeted therapies, 11 immunotherapy, 12,13 allo‐HSCT conditioning regimens, 2 immunosuppressive drugs 14 and prolonged parenteral nutrition.…”

“…At diagnosis or relapse, patients can present with hepatic tumour infiltration, 6 tumour lysis syndrome 7 or haemophagocytic syndrome (HS). 8 During treatment, HD is mainly caused by infections, sepsis, chemotherapy‐induced hepatotoxicity, 9 , 10 targeted therapies, 11 immunotherapy, 12 , 13 allo‐HSCT conditioning regimens, 2 immunosuppressive drugs 14 and prolonged parenteral nutrition. Allo‐HSCT patients can develop specific toxicities such as graft‐versus‐host disease (GVHD) of the liver, 15 sinusoidal obstruction syndrome (SOS) 16 and transfusional iron overload, 17 , 18 as well as decompensation of underlying chronic liver disease.…”

Hemophagocytic Lymphohistiocytosis as the Presenting Manifestation of Relapsed Classic Hodgkin’s Lymphoma in the Presence of Concurrent Human Immunodeficiency Virus, Genital Herpes, Epstein-Barr Virus and Mycobacterium Avium Complex Infection

“…The most common inciting factor for secondary HLH in adults is infection followed by malignancy and autoimmune conditions. Many patients with secondary HLH have multiple risk factors [2][3][4][5][6]. It is important to diagnose not only HLH but also the inciting event as the treatment considerations and prognosis greatly depends on the underlying cause [7].…”