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

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder of uncontrolled immune activation which is usually divided into two main types. Primary, which is associated with genetic mutation and familial predisposition and secondary, which is usually associated with infections, malignancies and autoimmune conditions. More often multiple risk factors are present at the time of initial presentation. We report a case where HLH was the presenting manifestation of relapsed Classic Hodgkin's Lymphoma in the presence of multiple risk factors of secondary HLH such as human immunodeficiency virus (HIV), active genital herpes, Epstein-Barr virus (EBV) viremia, Mycobacterium avium complex (MAC) infection and prior chemotherapy. A 38-year-old male to female transgender woman presented with one-week history of fever, nausea, vomiting and generalized weakness. The past medical history was significant for HIV and previously treated and positron emission tomography (PET) scan confirmed complete remission of Classic Hodgkin's Lymphoma. Physical examination showed BP 92/40 mmHg, fever of 102.6 F, heart rate of 114 beats per minutes, diffuse abdominal tenderness and male genitalia with multiple small ulcerative lesions. Labs showed pancytopenia, hyponatremia, mildly elevated total and direct bilirubin, transaminitis, CD-4 count 96/mcL, HIV viral load undetectable and COVID-19 polymerase chain reaction (PCR) negative. Imaging showed right middle lung lobe consolidation and hepatosplenomegaly with multiple hypodense lesions. Lymphadenopathy was reported in mediastinum and retroperitoneum. The patient was initially treated with broad spectrum antibiotics, IV fluids, vasopressors and stress dose steroids. After initial improvement, vasopressors and steroids were stopped. The patient again started spiking fever on day 9 despite being on antibiotics. Workup showed EBV viremia, genital herpes and evidence of MAC infection on sputum culture. No improvement noted despite appropriate treatment for genital herpes and MAC. Additional lab work showed hyperferritinemia and elevated soluble Interleukin-2 receptors. The patient was diagnosed with HLH as per HLH-2004 criteria and treated with dexamethasone and etoposide. Bone marrow biopsy confirmed hemophagocytosis and immunoperoxidase staining established the diagnosis of relapsed Classic Hodgkin's Lymphoma. We can conclude that in patients with a history of hematological malignancy presenting with HLH, a high degree of suspicion for relapse should be maintained even in the presence of other risk factors.

Haemophagocytic syndrome caused by disseminated nontuberculous mycobacterial infection

“…We conducted a review of the PubMed and EMBASE databases of previously reported cases of haemophagocytic syndrome associated with non-tuberculous mycobacterial infection. We found only 12 specific cases of infection by M. avium complex10–21 (Table S1 in the online supplemental appendix 1) and nine cases of infection by other non-tuberculous mycobacteria, including Mycobacterium Kansasii in three cases, Mycobacterium leprae in two cases, and Mycobacterium xenopi , Mycobacterium abscessus , Mycobacterium lentiflavum and Mycobacterium iranicum in one case each22–30 (Table S2 in the online supplemental appendix 1). As in the case of our patient, most of the reported cases correspond to disseminated infections where the lack of localised symptoms delayed the correct diagnosis, and the detection of granulomas in bone marrow biopsy served as an early indicator of infection by non-tuberculous mycobacteria.…”

Prediction Model of Bone Marrow Infiltration in Patients with Malignant Lymphoma Based on Logistic Regression and XGBoost Algorithm

“…Malignant tumor cells use 5-10 times more glucose than cells in normal tissue and convert most of the glucose into lactic acid. Increased LDH ensures an extensive glycolysis metabolism, thus storing energy for tumor growth [ 26 ]. Serum ALP mainly comes from the liver and bone, while the BMI of ML patients will lead to the release of ALP in the bone, which will lead to the elevation of serum ALP level.…”

Secondary Hemophagocytic Lymphohistiocytosis and Autoimmune Cytopenias: Case Description and Review of the Literature

“…Infections are the most frequent underlying cause, accounting for a half of all HLH cases, with nearly 70% being secondary to viruses, mainly Herpes virus [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. In a review of nearly 2200 cases of adult HLH and several case reports, infections are associated with a worse outcome in the presence of underlying immunodeficiency or cancer, and requirement of intensive care unit admission [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. Consistently, hematological and solid cancers are the second most frequent cause of secondary HLH [ 12 , 16 , 19 , 20 , 24 ].…”

“…In a review of nearly 2200 cases of adult HLH and several case reports, infections are associated with a worse outcome in the presence of underlying immunodeficiency or cancer, and requirement of intensive care unit admission [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. Consistently, hematological and solid cancers are the second most frequent cause of secondary HLH [ 12 , 16 , 19 , 20 , 24 ]. The main association is lymphoma, particularly T-cell and aggressive NHL, which also carry the highest mortality [ 2 , 12 ].…”

“…Infections, particularly EBV and CMV, are the main precipitating factors in HLH secondary to NHL. Other hematologic conditions include Hodgkin lymphoma, Castleman disease, acute myeloid leukemia, and myelodysplastic syndromes [ 12 , 16 , 20 ]. Lastly, HLH is a rare complication of solid tumors too (pancreas, liver, pituitary cancer and neuroblastoma, etc.)…”