DELAYED HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS (HLH) DIAGNOSIS IN A PATIENT WITH PULMONARY SARCOIDOSIS AND NEWLY DIAGNOSED T-CELL LYMPHOMA: A CASE REPORT

Abstract

SESSION TITLE: Challenging Cases of Hemophagocytic LymphohistiocytosisSESSION TYPE: Rapid Fire Case ReportsPRESENTED ON: 10/19/2022 12:45 pm - 1:45 pmINTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a rare and often fatal disorder caused by histiocyte proliferation and profound systemic inflammation. HLH can mimic many conditions, often leading to delayed diagnosis and increased morbidity. We present a fatal case of HLH that was misdiagnosed over the span of several months.CASE PRESENTATION: A 65-year-old African American male with history of obstructive sleep apnea, pulmonary sarcoidosis on 5mg prednisone/day, hypertension, chronic kidney disease, prostate cancer status post prostatectomy, elevated right ventricular systolic pressure (64 mmHg) was admitted for acute hypoxic respiratory failure. Symptoms included chills and fatigue. Physical exam revealed that he was afebrile and normotensive with decreased breath sounds bilaterally and tachycardia.This was his fourth hospitalization in six weeks for similar presentations, previously presumed to be due to sarcoidosis flares. He required heated high flow nasal cannula (HHFNC) oxygen supplementation and was started on intravenous: steroids, antibiotics, and diuresis. A chest radiograph showed extensive pulmonary infiltrates appearing stable from previous discharge. His hypoxia was attributed to pulmonary sarcoidosis and presumed pulmonary hypertension after a negative infectious workup. Although he initially improved, the subsequent days featured worsening mentation, tachycardia, and profound hypoxemia. A ferritin of >21,000ng/mL prompted HLH workup. Bone marrow biopsy revealed CD30+ T-cell lymphoma and marrow histiocytes with hemophagocytosis. Flow cytometry revealed an abnormal T-cell population and natural killer (NK) cells lacking CD5 and CD7. Abnormal findings that confirmed the diagnosis of HLH included: triglycerides (TG) at 419mg/dL, platelets at 83,000K/uL, fibrinogen at 142mg/dL, lactate dehydrogenase at 3325IU/L, splenomegaly, elevated soluble CD-25. Despite receiving etoposide, the patient was intubated for worsening respiratory failure and succumbed to cardiac arrest shortly after.DISCUSSION: Secondary HLH is triggered by infection, malignancy, rheumatologic conditions or immunodeficiency. The HLH-2004 diagnostic criteria are widely accepted and require 5 of the following 8 items: cytopenia (platelets, hemoglobin, leukocytes); organomegaly (spleen, liver); TG or fibrinogen elevations; fever; hemophagocytosis; low/absent NK activity; ferritin >500ug/L; soluble CD25 elevation. While treatment almost always includes glucocorticoids initially, studies have shown improved survival with etoposide and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) therapies. HLH due to lymphoma has been correlated with significantly higher mortality.CONCLUSIONS: HLH provides a diagnostic dilemma as the presenting symptoms may resemble multiple conditions and affect various organs. The prompt consideration of HLH is imperative as early management leads to improved patient survival.Reference #1: Henter JI, Horne A, Aricó M, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48(2):124-131. doi:10.1002/pbc.21039Reference #2: La Rosée P, Horne A, Hines M, et al. Recommendations for the management of hemophagocytic lymphohistiocytosis in adults. Blood. 2019;133(23):2465-2477. doi:10.1182/blood.2018894618Reference #3: Hayden A, Park S, Giustini D, Lee AY, Chen LY. Hemophagocytic syndromes (HPSs) including hemophagocytic lymphohistiocytosis (HLH) in adults: A systematic scoping review. Blood Rev. 2016;30(6):411-420. doi:10.1016/j.blre.2016.05.001DISCLOSURES: No relevant relationships by Michelle JonesNo relevant relationships by Yianni ProtopapadakisNo relevant relationships by Matthew Wilson SESSION TITLE: Challenging Cases of Hemophagocytic Lymphohistiocytosis SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a rare and often fatal disorder caused by histiocyte proliferation and profound systemic inflammation. HLH can mimic many conditions, often leading to delayed diagnosis and increased morbidity. We present a fatal case of HLH that was misdiagnosed over the span of several months. CASE PRESENTATION: A 65-year-old African American male with history of obstructive sleep apnea, pulmonary sarcoidosis on 5mg prednisone/day, hypertension, chronic kidney disease, prostate cancer status post prostatectomy, elevated right ventricular systolic pressure (64 mmHg) was admitted for acute hypoxic respiratory failure. Symptoms included chills and fatigue. Physical exam revealed that he was afebrile and normotensive with decreased breath sounds bilaterally and tachycardia. This was his fourth hospitalization in six weeks for similar presentations, previously presumed to be due to sarcoidosis flares. He required heated high flow nasal cannula (HHFNC) oxygen supplementation and was started on intravenous: steroids, antibiotics, and diuresis. A chest radiograph showed extensive pulmonary infiltrates appearing stable from previous discharge. His hypoxia was attributed to pulmonary sarcoidosis and presumed pulmonary hypertension after a negative infectious workup. Although he initially improved, the subsequent days featured worsening mentation, tachycardia, and profound hypoxemia. A ferritin of >21,000ng/mL prompted HLH workup. Bone marrow biopsy revealed CD30+ T-cell lymphoma and marrow histiocytes with hemophagocytosis. Flow cytometry revealed an abnormal T-cell population and natural killer (NK) cells lacking CD5 and CD7. Abnormal findings that confirmed the diagnosis of HLH included: triglycerides (TG) at 419mg/dL, platelets at 83,000K/uL, fibrinogen at 142mg/dL, lactate dehydrogenase at 3325IU/L, splenomegaly, elevated soluble CD-25. Despite receiving etoposide, the patient was intubated for worsening respiratory failure and succumbed to cardiac arrest shortly after. DISCUSSION: Secondary HLH is triggered by infection, malignancy, rheumatologic conditions or immunodeficiency. The HLH-2004 diagnostic criteria are widely accepted and require 5 of the following 8 items: cytopenia (platelets, hemoglobin, leukocytes); organomegaly (spleen, liver); TG or fibrinogen elevations; fever; hemophagocytosis; low/absent NK activity; ferritin >500ug/L; soluble CD25 elevation. While treatment almost always includes glucocorticoids initially, studies have shown improved survival with etoposide and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) therapies. HLH due to lymphoma has been correlated with significantly higher mortality. CONCLUSIONS: HLH provides a diagnostic dilemma as the presenting symptoms may resemble multiple conditions and affect various organs. The prompt consideration of HLH is imperative as early management leads to improved patient survival. Reference #1: Henter JI, Horne A, Aricó M, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48(2):124-131. doi:10.1002/pbc.21039 Reference #2: La Rosée P, Horne A, Hines M, et al. Recommendations for the management of hemophagocytic lymphohistiocytosis in adults. Blood. 2019;133(23):2465-2477. doi:10.1182/blood.2018894618 Reference #3: Hayden A, Park S, Giustini D, Lee AY, Chen LY. Hemophagocytic syndromes (HPSs) including hemophagocytic lymphohistiocytosis (HLH) in adults: A systematic scoping review. Blood Rev. 2016;30(6):411-420. doi:10.1016/j.blre.2016.05.001 DISCLOSURES: No relevant relationships by Michelle Jones No relevant relationships by Yianni Protopapadakis No relevant relationships by Matthew Wilson