Fatal Hemophagocytic Lymphohistiocytosis Associated with Epstein-Barr Virus Infection in a Patient with a Novel Mutation in the Signaling Lymphocytic Activation Molecule--Associated Protein

Halasa, Natasha; Whitlock, James A.; McCurley, Thomas L.; Smith, Jarrod A.; Zhu, Quili; Ochs, Hans D.; Dermody, Terence S.; Crow, James E.

doi:10.1086/379126

Cited by 14 publications

(11 citation statements)

References 22 publications

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“…4 EBV, a DNA (deoxyribonucleic acid) virus and member of the Herpesviridae family has been the most consistently reported virus associated with HLH. [36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52] The majority of EBV-associated HLH cases have been reported in Asia, with limited information on the incidence elsewhere in the world. A Japanese study estimated the annual incidence of HLH at 1 in 800,000 persons per year, with 90% of these cases being secondary and one-third of these secondary cases being related to EBV.…”

Section: Infectionsmentioning

confidence: 99%

Hemophagocytic lymphohistiocytosis: review of etiologies and management

George

2014

JBM

389

415

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Hemophagocytic lymphohistiocytosis (HLH) covers a wide array of related life-threatening conditions featuring ineffective immunity characterized by an uncontrolled hyperinflammatory response. HLH is often triggered by infection. Familial forms result from genetic defects in natural killer cells and cytotoxic T-cells, typically affecting perforin and intracellular vesicles. HLH is likely under-recognized, which contributes to its high morbidity and mortality. Early recognition is crucial for any reasonable attempt at curative therapy to be made. Current treatment regimens include immunosuppression, immune modulation, chemotherapy, and biological response modification, followed by hematopoietic stem-cell transplant (bone marrow transplant). A number of recent studies have contributed to the understanding of HLH pathophysiology, leading to alternate treatment options; however, much work remains to raise awareness and improve the high morbidity and mortality of these complex conditions.

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Section: Infectionsmentioning

confidence: 99%

Hemophagocytic lymphohistiocytosis: review of etiologies and management

George

2014

JBM

389

415

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“…To our knowledge only 13 well‐characterized cases of EBV‐associated HLH have been described in the United States (Supplemental Table III) [Quintanilla‐Martinez et al, 2000; Halasa et al, 2003; Lindemann and Greene, 2005; Mischler et al, 2007; Rouphael et al, 2007; Brodkin et al, 2008; Kaza et al, 2008; Belyea et al, 2010], and of these, four (30.8%) were Latino [Quintanilla‐Martinez et al, 2000; Brodkin et al, 2008], four (30.8%) white [Quintanilla‐Martinez et al, 2000; Halasa et al, 2003; Mischler et al, 2007; Rouphael et al, 2007], one (7.7%) Asian [Quintanilla‐Martinez et al, 2000], and one (7.7%) African‐American [Kaza et al, 2008]. Race/ethnicity was not reported in three (23.1%) of the cases [Lindemann and Greene, 2005; Belyea et al, 2010].…”

Section: Discussionmentioning

confidence: 99%

“…Race/ethnicity was not reported in three (23.1%) of the cases [Lindemann and Greene, 2005; Belyea et al, 2010]. In four (30.8%) of these cases another cause, such as immunodeficiency [Halasa et al, 2003; Mischler et al, 2007; Kaza et al, 2008] or malignancy [Brodkin et al, 2008] was attributed as the primary cause of HLH. A seasonal pattern has been suggested for EBV‐HLH, with cases more often occurring in the summer [Chen et al, 1991].…”

Section: Discussionmentioning

confidence: 99%

“…To our knowledge, only 13 well‐characterized cases of EBV‐associated HLH have been described in the United States. However, none of these cases described the molecular characteristics of the virus and host associated with the EBV‐HLH phenotype [Quintanilla‐Martinez et al, 2000; Halasa et al, 2003; Lindemann and Greene, 2005; Mischler et al, 2007; Rouphael et al, 2007; Brodkin et al, 2008; Kaza et al, 2008; Belyea et al, 2010]. Although EBV‐HLH is a rare disease, the incidence in adults in the United States may be underestimated.…”

Section: Introductionmentioning

confidence: 99%

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Epstein–Barr virus‐associated hemophagocytic lymphohistiocytosis in Los Angeles County

Kelesidis

Humphries

Terashita

et al. 2012

Journal of Medical Virology

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Data on Epstein–Barr virus‐related hemophagocytic lymphohistiocytosis (EBV‐HLH) in adults in the United States remain very limited. A cluster of four cases of EBV‐HLH was observed in a 4‐month period at a tertiary center in Los Angeles County (LA County) and the clinical and molecular characteristics identified in these cases are being described. EBV typing, immunophenotypic and molecular genetic studies were performed. Diagnostic criteria that may be used to identify EBV as a cause of HLH in adults are also being suggested. Finally, the crude incidence rate for HLH in LA County was determined and was compared to the worldwide crude incidence rate for HLH. The cases each occurred in young male adult residents of California and were associated with evidence of EBV reactivation and ferritin levels of >20,000 µg/L. A higher rate of cases of EBV‐HLH in 2010 was found at UCLA Medical Center than for 2007–2009 (4.9/10,000 hospital discharges vs. 0.14/10,000 hospital discharges, respectively; P = 0.0017). The cases were associated with EBV type 1, and the insertion of the codon CTC (leucine) was found in numerous of the EBNA‐2 gene sequences. The annual incidence of secondary, non‐familial HLH was estimated to be 0.9 cases per million persons >15 years of age in LA County. Although EBV‐HLH is a rare disease, the incidence in adults in Western countries may be underestimated. J. Med. Virol. 84:777–785, 2012. © 2012 Wiley Periodicals, Inc.

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“…[2][3][4] Epstein-Barr virus (EBV), a DNA virus and member of the Herpesviridae family, has been consistently associated with HLH. [5][6][7][8][9][10][11][12][13][14][15] HLH in children is a rare disease with a high fatality rate. Studies have shown that most cytokines related to HLH are activated through activation of the Janus Kinase (JAK)/signal transducer and activator of transcription signaling pathway, which not only regulates the biological activity of cytokines, but also affects the differentiation of primary T cells into T helper (TH) cell families, TH1, TH2, TH17, and regulatory T cells.…”

Section: Introductionmentioning

confidence: 99%

Ruxolitinib Might Be an Effective Hormone Reduction and Replacement Drug in Children With Secondary Hemophagocytic Lymphohistiocytosis 

Chen

Liu

Zhou

et al. 2020

Preprint

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Background: To analyze the effects of ruxolitinib on children with secondary hemophagocytic lymphohistiocytosis (HLH).Methods: Eleven pediatric patients diagnosed with HLH and treated with ruxolitinib (ruxolitinib group: group R) between November 2017 and August 2018 were retrospectively analyzed. Eleven age-matched pediatric patients with HLH undergoing conventional treatment (control group: group C) were also analyzed.Results: In group R, three patients who did not respond to conventional treatment (dexamethasone and etoposide) were treated with Ruxolitinib and their temperature decreased to normal levels. Four patients had normal temperature after conventional treatment, but they had severe organ involvement, including obvious yellowing of the skin, increased liver enzyme levels and neuropsychiatric symptoms, and they were all ameliorated with ruxolitinib treatment. Four patients were relieved with ruxolitinib therapy alone. In group C, the body temperature of eleven patients all decreased to normal levels after conventional treatment. The body temperature of group R patients decreased to normal levels more rapidly than that of group C patients. The hormone dosage in group R was significantly lower than that in group C. Both groups were followed up for 2–2.5 years. No obvious adverse drug reactions of ruxolitinib were observed during treatment and follow-up.Conclusion: Ruxolitinib might be an effective drug in controlling body temperature and reducing inflammation indicators. It might be a potential replacement for hormone therapy for HLH treatment in children, thereby reducing or avoiding hormone-related adverse reactions.

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Fatal Hemophagocytic Lymphohistiocytosis Associated with Epstein-Barr Virus Infection in a Patient with a Novel Mutation in the Signaling Lymphocytic Activation Molecule--Associated Protein

Cited by 14 publications

References 22 publications

Hemophagocytic lymphohistiocytosis: review of etiologies and management

Hemophagocytic lymphohistiocytosis: review of etiologies and management

Epstein–Barr virus‐associated hemophagocytic lymphohistiocytosis in Los Angeles County

Ruxolitinib Might Be an Effective Hormone Reduction and Replacement Drug in Children With Secondary Hemophagocytic Lymphohistiocytosis

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Fatal Hemophagocytic Lymphohistiocytosis Associated with Epstein-Barr Virus Infection in a Patient with a Novel Mutation in the Signaling Lymphocytic Activation Molecule--Associated Protein

Cited by 14 publications

References 22 publications

Hemophagocytic lymphohistiocytosis: review of etiologies and management

Hemophagocytic lymphohistiocytosis: review of etiologies and management

Epstein–Barr virus‐associated hemophagocytic lymphohistiocytosis in Los Angeles County

Ruxolitinib Might Be an Effective Hormone Reduction and Replacement Drug in Children With Secondary Hemophagocytic Lymphohistiocytosis&nbsp;

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Ruxolitinib Might Be an Effective Hormone Reduction and Replacement Drug in Children With Secondary Hemophagocytic Lymphohistiocytosis