SECONDARY HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS IN A PATIENT WITH COVID-19 AND HERPES SIMPLEX VIRUS (HSV): A CASE REPORT

Abstract

SESSION TITLE: Unique Inflammatory and Autoimmune Complications of COVID-19 InfectionsSESSION TYPE: Rapid Fire Case ReportsPRESENTED ON: 10/19/2022 12:45 pm - 1:45 pmINTRODUCTION: Hemophagocytic Lymphohistiocytosis (HLH) is a rare, life-threatening hyperinflammatory syndrome caused by severe, dysregulated hypercytokinemia. This can be associated with genetic defects or immunologic triggers such as infection, malignancy or autoimmune disorder. The clinical picture consists of multi-organ failure including fever, hepatosplenomegaly, cytopenia,hypertriglyceridemia, hemophagocytosis, high ferritin and IL-2 levels, neurological and liver dysfunction. We present a case of a patient with HLH in the setting of Herpes Simplex Virus (HSV) and SARS-CoV-2 co-infection.CASE PRESENTATION: A 39-year-old male presented to the ER with dyspnea and was found to have COVID-19 pneumonia. He had worsening hypoxemia and was admitted to ICU. He rapidly developed multi-system organ failure (MSOF)including severe hepatitis with AST 13,950 U/L and ALT 10,000 U/L, pancytopenia (Hb 12.9 g/dL, WBC 1.7 K/uL, platelet 15,000 K/uL), acute kidney injury (Cr 6.61 mg/dL), and severe ARDS requiring mechanical ventilation. Abdominal ultrasonography showed splenomegaly. Blood HSV1 DNA PCR was positive with liver biopsy revealing viral inclusions consistent with HSV hepatitis. He had elevated ferritin > 100,000 ug/L and LDH > 2500 U/L. Bone marrow biopsy demonstrated hemophagocytosis and trilineage hematopoiesis. He met 6 of 8 diagnostic criteria for HLH per the HLH-2004 protocol. He received dexamethasone. Risks and benefits of HLH-specific therapy were considered in the setting of liver dysfunction and the decision was made to withhold etoposide and administer anakinra. He died of refractory septic shock and disseminated intravascular coagulopathy.DISCUSSION: Diagnosis of HLH can be challenging due to its rarity and the clinical picture may be initially attributed to sepsis in the presence of infection, as in our patient who had COVID-19 infection and HSV hepatitis. However, a ferritin level >10,000 ng/mL is 90% sensitive and 96 % specific for HLH, with very minimal overlap with sepsis, infections, and liver failure. Additionally, infection is a known trigger of HLH. Despite high mortality without therapy, survival can be significantly increased with HLH-specific therapy, such as etoposide. Treatment with etoposide in the setting of severe liver disease can raise concern because it is metabolized by the liver but it is an essential component of optimal therapy and can be considered in patients with hepatic dysfunction with dose reduction.CONCLUSIONS: Our case highlights the importance of maintaining a high index of suspicion for HLH in critically ill patients with MSOF and liver failure, despite an apparent infectious etiology. This may allow timely diagnosis, early referral to a specialist center and consideration of HLH-specific therapy such as etoposide despite liver dysfunction, to prevent high morbidity and mortality in this potentially fatal disease.Reference #1: Filipovich AH. Hemophagocytic lymphohistiocytosis (HLH) and related disorders. Hematology Am Soc Hematol Educ Program 2009; :127.DISCLOSURES: No relevant relationships by Abdul KhanNo relevant relationships by Nehan SherNo relevant relationships by yuttiwat vorakunthada SESSION TITLE: Unique Inflammatory and Autoimmune Complications of COVID-19 Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Hemophagocytic Lymphohistiocytosis (HLH) is a rare, life-threatening hyperinflammatory syndrome caused by severe, dysregulated hypercytokinemia. This can be associated with genetic defects or immunologic triggers such as infection, malignancy or autoimmune disorder. The clinical picture consists of multi-organ failure including fever, hepatosplenomegaly, cytopenia,hypertriglyceridemia, hemophagocytosis, high ferritin and IL-2 levels, neurological and liver dysfunction. We present a case of a patient with HLH in the setting of Herpes Simplex Virus (HSV) and SARS-CoV-2 co-infection. CASE PRESENTATION: A 39-year-old male presented to the ER with dyspnea and was found to have COVID-19 pneumonia. He had worsening hypoxemia and was admitted to ICU. He rapidly developed multi-system organ failure (MSOF)including severe hepatitis with AST 13,950 U/L and ALT 10,000 U/L, pancytopenia (Hb 12.9 g/dL, WBC 1.7 K/uL, platelet 15,000 K/uL), acute kidney injury (Cr 6.61 mg/dL), and severe ARDS requiring mechanical ventilation. Abdominal ultrasonography showed splenomegaly. Blood HSV1 DNA PCR was positive with liver biopsy revealing viral inclusions consistent with HSV hepatitis. He had elevated ferritin > 100,000 ug/L and LDH > 2500 U/L. Bone marrow biopsy demonstrated hemophagocytosis and trilineage hematopoiesis. He met 6 of 8 diagnostic criteria for HLH per the HLH-2004 protocol. He received dexamethasone. Risks and benefits of HLH-specific therapy were considered in the setting of liver dysfunction and the decision was made to withhold etoposide and administer anakinra. He died of refractory septic shock and disseminated intravascular coagulopathy. DISCUSSION: Diagnosis of HLH can be challenging due to its rarity and the clinical picture may be initially attributed to sepsis in the presence of infection, as in our patient who had COVID-19 infection and HSV hepatitis. However, a ferritin level >10,000 ng/mL is 90% sensitive and 96 % specific for HLH, with very minimal overlap with sepsis, infections, and liver failure. Additionally, infection is a known trigger of HLH. Despite high mortality without therapy, survival can be significantly increased with HLH-specific therapy, such as etoposide. Treatment with etoposide in the setting of severe liver disease can raise concern because it is metabolized by the liver but it is an essential component of optimal therapy and can be considered in patients with hepatic dysfunction with dose reduction. CONCLUSIONS: Our case highlights the importance of maintaining a high index of suspicion for HLH in critically ill patients with MSOF and liver failure, despite an apparent infectious etiology. This may allow timely diagnosis, early referral to a specialist center and consideration of HLH-specific therapy such as etoposide despite liver dysfunction, to prevent high morbidity and mortality in this potentially fatal disease. Reference #1: Filipovich AH. Hemophagocytic lymphohistiocytosis (HLH) and related disorders. Hematology Am Soc Hematol Educ Program 2009; :127. DISCLOSURES: No relevant relationships by Abdul Khan No relevant relationships by Nehan Sher No relevant relationships by yuttiwat vorakunthada