A rare case of post COVID-19 hemophagocytic lymphohistiocytosis in a pediatric patient

Abstract

Introduction/Objective Hemophagocytic Syndromes are a cluster of disorders related to cytotoxic dysfunction of T/NK-cells and are mainly subdivided into Primary (familial) and Secondary (acquired) forms, with the latter usually linked to patients with viral infections; including EBV, CMV among many others. A myriad of other causes have been associated with hemophagocytic lymphohistiocytosis (HLH), most notably systemic inflammatory conditions; especially Juvenile Rheumatoid Arthritis and hematolymphoid malignancies particularly T/NK-cell lymphomas. Methods/Case Report A previously healthy 7-year-old boy, presented to the ER with fever and a skin rash over both lower limbs of 1 week duration. Two weeks prior he was tested for COVID-19 and was found to be positive. Physical examination further revealed slightly palpable liver and spleen. CBC was done and exhibited pancytopenia, further testing showed elevated LDH, hyperferritinemia and hypertriglyceridemia. However, serological testing for rheumatological conditions was unremarkable. Imaging studies were done and were noncontributory. Subsequently, a bone marrow aspirate and biopsy were done. The bone marrow aspirate showed afew histiocytes engulfing red blood cells and nuclear debris (hemophagocytic cells), complete trilineage maturation and normal M:E ratio of 3:1. Trephine biopsy was hypocellular for age and estimated at about 70%, composed of myeloid and erythroid precursors with various degrees of maturation. Megakaryocytes were adequate in number and showed normal morphology. Extensive histiocytic infiltration as highlighted by CD68 immunostain and focal phagocytosis were identified. CD34 highlighted <5% blasts, PAS special stain showed no fungal elements and no fibrosis was evident by Reticulin special stain. The background was devoid of lymphoid aggregates or granulomas. Stainable iron stores were depleted. No sideroblasts were identified. The patient was treated with corticosteroid and showed marked improvement and was discharged after 3 days. Results (if a Case Study enter NA) NA Conclusion Hemophagocytic lymphohistiocytosis can be a critical sequela of COVID-19 infection. Suggested mechanisms include impaired/delayed T-cell response and elevated levels of several inflammatory cytokines. Clinical suspesion is important in the diagnosis of these cases. Further study of this correlation is needed as we explore clinical sequelae of COVID-19 infection.

Hemophagocytic Lymphohistiocytosis in A Post Covid-19 Patient with Mds: A Case Report

“…Αs an entity, it may affect patients of all age groups and a causal relationship between a number of factors and HLH has been reported, including viral infections (Herpes simplex virus (HSV), EBV, CMV, HIV, Influenza A and parvovirus B19), bacterial and fungal infection (Candida, Aspergillus), hematological malignancies and solid tumors, connective tissue disorders, immunodeficiency syndromes, and cellular therapies [12][13][14]. 8,13,[21][22][23]. The main characteristics, treatment and outcome of the aforementioned cases are presented in Supplementary Table 1.…”

“…Immune-mediated macrophage activation is the hallmark of sHLH. Both Sars-Cov-2 infection [8,13,[21][22][23]25] and MDS are associated with dysregulation of the immune system. In MDS, the association between cytotoxic T-lymphocytes and apoptosis has been implicated in the pathogenesis of refractory cytopenias.…”