Bankstown Hospital - Grand Rounds - Further Reading

Welcome to the Grand Rounds Further Reading List, Haematology edition, brought to you by the Clinical Library, on Level 4, next to the Auditorium.

This library guide is to help support you in your professional development. Please give us feedback so we can improve this list in the future.

If you have any questions, please contact the Clinical Library on 9722 8250 or email SWSLHD-BankstownLibrary@health.nsw.gov.au or visit us Monday to Fridays, 8.30am - 5.00pm.

“Hungry Little Histiocyte”

Canna, S. W. and R. A. Marsh (2020). "Pediatric hemophagocytic lymphohistiocytosis." Blood 135(16): 1332-1343. https://doi.org/10.1182/blood.2019000936 FULL TEXT @ URL

            Hemophagocytic lymphohistiocytosis (HLH) is a syndrome describing patients with severe systemic hyperinflammation. Characteristic features include unremitting fever, cytopenias, hepatosplenomegaly, and elevation of typical HLH biomarkers. Patients can develop hepatitis, coagulopathy, liver failure, central nervous system involvement, multiorgan failure, and other manifestations. The syndrome has a high mortality rate. More and more, it is recognized that while HLH can be appropriately used as a broad summary diagnosis, many pediatric patients actually suffer from an expanding spectrum of genetic diseases that can be complicated by the syndrome of HLH. Classic genetic diseases in which HLH is a typical and common manifestation include pathogenic changes in familial HLH genes (PRF1, UNC13D, STXBP2, and STX11), several granule/pigment abnormality genes (RAB27A, LYST, and AP3B1), X-linked lymphoproliferative disease genes (SH2D1A and XIAP), and others such as NLRC4, CDC42, and the Epstein-Barr virus susceptibility diseases. There are many other genetic diseases in which HLH is an infrequent complication of the disorder as opposed to a prominent manifestation of the disease caused directly by the genetic defect, including other primary immune deficiencies and inborn errors of metabolism. HLH can also occur in patients with underlying rheumatologic or autoinflammatory disorders and is usually designated macrophage activation syndrome in those settings. Additionally, HLH can develop in patients during infections or malignancies without a known (or as-yet-identified) genetic predisposition. This article will attempt to summarize current concepts in the pediatric HLH field as well as offer a practical diagnostic and treatment overview.

Griffin, G., et al. (2020). "Hemophagocytic lymphohistiocytosis: An update on pathogenesis, diagnosis, and therapy." Best Practice & Research Clinical Rheumatology 34(4): 101515. https://pubmed.ncbi.nlm.nih.gov/32387063/  FULL TEXT @ URL

            Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening state of immune hyperactivation that arises in the setting of genetic mutations and infectious, inflammatory, or neoplastic triggers. Sustained, aberrant activation of cytotoxic CD8+ T cells and resultant inflammatory cytokine release are core pathogenic mechanisms. Key clinical features include high persistent fever, hepatosplenomegaly, blood cytopenia, elevated aminotransferase and ferritin levels, and coagulopathy. HLH is likely under-recognized, and mortality remains high, especially in adults; thus, prompt diagnosis and treatment are essential. Familial forms of HLH are currently treated with chemotherapy as a bridge to hematopoietic stem cell transplantation. HLH occurring in rheumatic disease (macrophage activation syndrome) is treated with glucocorticoids, IL-1 blockade, or cyclosporine A. In other forms of HLH, addressing the underlying trigger is essential. There remains a pressing need for more sensitive, context-specific diagnostic tools. Safer, more effective therapies will arise with improved understanding of the cellular and molecular mechanisms of HLH.

Kim, Y. R. and D. Y. Kim (2021). "Current status of the diagnosis and treatment of hemophagocytic lymphohistiocytosis in adults." Blood Res 56(S1): S17-s25. https://pubmed.ncbi.nlm.nih.gov/33935031/ FULL TEXT/PDF @ URL

            Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of defective apoptosis, a disruption of the regulatory pathway that terminates immune and inflammatory responses. Fever, cytopenia, splenomegaly, and/or hemophagocytosis are typical findings of this syndrome. HLH can be induced by genetic disorders (familial) or secondary causes. Familial HLH is rare, while secondary causes in adults include infection, autoimmunity, and malignancy. HLH in adults tends to be confused with or misdiagnosed as sepsis, mainly due to similar clinical manifestations and laboratory findings, which make it difficult to diagnose HLH rapidly and adopt immunosuppressive agents and/or chemotherapy adequately. Treatment of pediatric HLH using HLH-2004 or multi-agent chemotherapy can be applied in adult patients, although the dose and type of drug need to be adjusted. It is highly recommended that allogenic hematopoietic stem cell transplantation should be used in patients who become reactivated or are refractory to the initial treatment as soon as possible to improve survival. Future clinical trials are warranted to determine more suitable treatments for adult patients with HLH.

Koumadoraki, E., et al. (2022). "Hemophagocytic lymphohistiocytosis and infection: a literature review." Cureus 14(2).  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8942143/  PDF @ URL

            Hemophagocytic lymphocytosis (HLH) is a life-threatening, underdiagnosed syndrome caused by the excessive release of inflammatory mediators. Primary lymphocytosis is usually seen in young children and is associated with genetic defects, while secondary lymphocytosis is presented in adults due to malignancy, rheumatic disease, or infection. The aim of this study is to describe the infectious agents that trigger HLH in the adult population and provide diagnostic and treatment guidelines for this life-threatening syndrome. We conducted a literature review using PubMed as our basic database. We collected papers from the past six years that studied infectious agents that triggered HLH and described the most recommended treatment options for this serious condition. A total of 32 studies were included for this literature review.HLH is considered a syndrome with variable symptoms, and clinicians should be familiar with its complexity and the pathologies that could contribute to its presentation. Collaboration between physicians and awareness are basic steps for the management of patients with HLH.