COVID‐19‐associated secondary hemophagocytic lymphohistiocytosis requiring hematopoietic cell transplant

Greenmyer, Jacob R.; Wyatt, Kirk D; Milanovich, Sam; Kohorst, Mira A.; Ferdjallah, Asmaa

doi:10.1002/jha2.456

Cited by 6 publications

(13 citation statements)

References 15 publications

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“…The detailed characteristics of the included studies are shown in Additional file 2 : Table S3. There were 73 case report [ 4 – 6 , 8 , 9 , 25 – 32 , 37 – 39 , 44 , 45 , 49 , 51 , 53 – 60 , 67 – 69 , 72 , 76 – 79 , 82 – 84 , 86 – 88 , 90 , 91 , 93 , 94 , 96 , 99 – 107 , 109 – 114 , 116 , 119 – 123 , 126 , 127 , 129 – 131 ], 38 cohort [ 7 , 10 , 19 , 33 – 36 , 40 – 43 , 46 – 48 , 50 , 52 , 61 – 66 , 70 , 71 , 73 , 74 , 80 , 81 , 92 , 95 , 97 , 98 , 108 , 117 , 118 , 124 , 125 , 132 ], 4...…”

Section: Resultsmentioning

confidence: 99%

“…Immune dysregulatory diseases were the fourth most-common IEIs in children who experienced COVID-19 (n = 95, 13.4%) [ 6 , 9 , 19 , 29 , 32 , 35 , 38 , 40 , 43 , 44 , 46 , 48 , 50 , 52 , 54 , 57 , 58 , 62 , 63 , 65 , 67 , 72 – 74 , 79 , 81 , 82 , 84 , 86 , 88 , 93 – 97 , 99 , 100 , 102 , 109 , 110 , 113 , 115 , 118 , 121 , 125 , 130 ] (see Additional file 2 : Table S3). Among them, 25 have familial hemophagocytic lymphohistiocytosis (26.3% of all immune dysregulatory diseases) [ 6 , 19 , 29 , 48 , 62 , 65 , 67 , 72 , 73 , 79 , 81 , 82 , 84 , 88 , 99 , 110 , 125 ], 19 have autoimmune polyendocrine syndromes type-1 (APS-1) (20%) [ 35 , 38 , 73 , 86 , 94 , …”

Section: Resultsmentioning

confidence: 99%

“…In those immune dysregulatory diseases patients, few studies reported on specific allele changes (n = 15, 15.8%) [ 32 , 35 , 38 , 58 , 62 , 84 , 86 , 94 , 96 , 99 , 100 , 109 , 113 , 121 , 125 ]. Reported modes of inheritance for the immune dysregulatory diseases in children were autosomal recessive (n = 64, 67.4%) [ 6 , 19 , 29 , 35 , 38 , 48 , 57 , 58 , 62 , 65 , 67 , 72 – 74 , 79 , 81 , 82 , 84 , 86 , 88 , 94 , 95 , 99 , 102 , 110 , 113 , 115 , 118 , 121 , 125 ], X-linked (n = 10, 10.5%) [ 43 , 44 , 54 , 65 , 81 , 93 , 95 , 99 , 100 , 109 ], or autosomal dominant (n = 7, 7.4%) [ 9 , 19 , 32 , 35 , 95 , 96 ], however, mode of inheritance in these immune dysregulatory diseases cases was unknown in a high percentage of patients (n = 14, 14.7%) [ 40 , 46 , 50 , …”

Section: Resultsmentioning

confidence: 99%

“…Reported modes of inheritance for the immune dysregulatory diseases in children were autosomal recessive (n = 64, 67.4%) [ 6 , 19 , 29 , 35 , 38 , 48 , 57 , 58 , 62 , 65 , 67 , 72 – 74 , 79 , 81 , 82 , 84 , 86 , 88 , 94 , 95 , 99 , 102 , 110 , 113 , 115 , 118 , 121 , 125 ], X-linked (n = 10, 10.5%) [ 43 , 44 , 54 , 65 , 81 , 93 , 95 , 99 , 100 , 109 ], or autosomal dominant (n = 7, 7.4%) [ 9 , 19 , 32 , 35 , 95 , 96 ], however, mode of inheritance in these immune dysregulatory diseases cases was unknown in a high percentage of patients (n = 14, 14.7%) [ 40 , 46 , 50 , 52 , 63 , 81 , 95 , 97 , 130 ]. COVID-19 in children with immune dysregulatory diseases was asymptomatic (11/95 = 11.6%) [ 32 , 38 , 58 , 63 , 65 , 73 , 74 , 81 , 95 , 99 ], mild (3...…”

Section: Resultsmentioning

confidence: 99%

“…COVID-19 in children with immune dysregulatory diseases was asymptomatic (11/95 = 11.6%) [ 32 , 38 , 58 , 63 , 65 , 73 , 74 , 81 , 95 , 99 ], mild (34/95 = 35.8%) [ 6 , 35 , 43 , 50 , 52 , 63 , 65 , 67 , 72 , 73 , 81 , 82 , 88 , 94 – 97 , 99 , 100 , 110 , 115 , 121 , 130 ], moderate (11/95 = 11.6%) [ 40 , 46 , 54 , 73 , 84 , 95 , 109 , 133 ], severe (19/95 = 20%) [ 9 , 19 , 29 , 44 , 48 , 57 , 79 , 86 , 93 , 102 , 113 , 133 ] or critical (2/95 = 2.1%) [ 19 , 65 ]. Most children with immune dysregulatory diseases did not get MIS-C due to COVID-19 (71/95, 74.7%) [ 6 , 9 , 19 , 32 , 35 , 38 , 40 , 43 , 44 , 46 , 50 , 52 , 54 , …”

Section: Resultsmentioning

confidence: 99%

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Severity of SARS-CoV-2 infection in children with inborn errors of immunity (primary immunodeficiencies): a systematic review

Alhumaid,

Al Mutared,

Al Alawi

et al. 2023

Allergy Asthma Clin Immunol

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Background Inborn errors of immunity (IEIs) are considered significant challenges for children with IEIs, their families, and their medical providers. Infections are the most common complication of IEIs and children can acquire coronavirus disease 2019 (COVID-19) even when protective measures are taken. Objectives To estimate the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children with IEIs and analyse the demographic parameters, clinical characteristics and treatment outcomes in children with IEIs with COVID-19 illness. Methods For this systematic review, we searched ProQuest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature through the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guideline for studies on the development of COVID-19 in children with IEIs, published from December 1, 2019 to February 28, 2023, with English language restriction. Results Of the 1095 papers that were identified, 116 articles were included in the systematic review (73 case report, 38 cohort 4 case-series and 1 case–control studies). Studies involving 710 children with IEIs with confirmed COVID-19 were analyzed. Among all 710 IEIs pediatric cases who acquired SARS-CoV-2, some children were documented to be admitted to the intensive care unit (ICU) (n = 119, 16.8%), intubated and placed on mechanical ventilation (n = 87, 12.2%), suffered acute respiratory distress syndrome (n = 98, 13.8%) or died (n = 60, 8.4%). Overall, COVID-19 in children with different IEIs patents resulted in no or low severity of disease in more than 76% of all included cases (COVID-19 severity: asymptomatic = 105, mild = 351, or moderate = 88). The majority of children with IEIs received treatment for COVID-19 (n = 579, 81.5%). Multisystem inflammatory syndrome in children (MIS-C) due to COVID-19 in children with IEIs occurred in 103 (14.5%). Fatality in children with IEIs with COVID-19 was reported in any of the included IEIs categories for cellular and humoral immunodeficiencies (n = 19, 18.6%), immune dysregulatory diseases (n = 17, 17.9%), innate immunodeficiencies (n = 5, 10%), bone marrow failure (n = 1, 14.3%), complement deficiencies (n = 1, 9.1%), combined immunodeficiencies with associated or syndromic features (n = 7, 5.5%), phagocytic diseases (n = 3, 5.5%), autoinflammatory diseases (n = 2, 3%) and predominantly antibody deficiencies (n = 5, 2.5%). Mortality was COVID-19-related in a considerable number of children with IEIs (29/60, 48.3%). The highest ICU admission and fatality rates were observed in cases belonging to cellular and humoral immunodeficiencies (26.5% and 18.6%) and immune dysregulatory diseases (35.8% and 17.9%) groups, especially in children infected with SARS-CoV-2 who suffered severe combined immunodeficiency (28.6% and 23.8%), combined immunodeficiency (25% and 15%), familial hemophagocytic lymphohistiocytosis (40% and 20%), X-linked lymphoproliferative diseases-1 (75% and 75%) and X-linked lymphoproliferative diseases-2 (50% and 50%) compared to the other IEIs cases. Conclusion Children with IEIs infected with SARS-CoV-2 may experience higher rates of ICU admission and mortality in comparison with the immunocompetent pediatric populations. Underlying immune defects does seem to be independent risk factors for severe SARS-CoV-2 infection in children with IEIs, a number of children with SCID and CID were reported to have prolonged infections–though the number of patients is small–but especially immune dysregulation diseases (XLP1 and XLP2) and innate immunodeficiencies impairing type I interferon signalling (IFNAR1, IFNAR2 and TBK1).

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Severity of SARS-CoV-2 infection in children with inborn errors of immunity (primary immunodeficiencies): a systematic review

Alhumaid,

Al Mutared,

Al Alawi

et al. 2023

Allergy Asthma Clin Immunol

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Dexamethasone/etoposide

2023

Reactions Weekly

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X-Linked Lymphoproliferative Disease Type 2 With Activation of Hemophagocytic Lymphohistiocytosis Secondary to Epstein-Barr Virus Infection

Alsheikh,

AlSaleh

2024

Int J Clin Pediatr

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Hemophagocytic lymphohistiocytosis (HLH) is a rare yet potentially life-threatening syndrome. It is best described as uncontrolled immune system activation leading to hemophagocytosis. Our case report aims to present a practical approach, discuss the challenges in the diagnosis and management of HLH, and to shed light on the X-linked lymphoproliferative disease type 2 (XLP-2) gene, STXBP2 gene (as a carrier), and Epstein-Barr virus (EBV) infection in relation to HLH. This is a 2-year-8-month-old Saudi boy, who presented to the emergency department with fever for more than 7 days, not associated with any other major complaints. During the first couple of days of admission, primary results showed hyperferritinemia, low fibrinogen, anemia, high inflammatory markers, high D-dimer, and increasing liver enzymes and triglycerides. The patient fulfilled the diagnostic criteria of HLH on the third day of admission. Further investigations revealed a genetic mutation in XLP-2 gene, STXBP2 gene (as a carrier) and EBV infection causing HLH. HLH-94 protocol was used for management. The patient had an excellent clinical outcome, unexpectedly, by only using dexamethasone, with complete remission and no recurrence up to date. HLH is not frequently encountered in daily practice. However, it can be fatal. This case report describes a unique case of XLP-2, STXBP2 carrier with extreme EBV infection and activation of HLH, who was successfully brought into remission by partial application of HLH-94 protocol and careful clinical and laboratory monitoring. The diagnosis and management of HLH can be challenging. However, a reasonable clinical judgment can improve the outcomes.

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COVID‐19‐associated secondary hemophagocytic lymphohistiocytosis requiring hematopoietic cell transplant

Cited by 6 publications

References 15 publications

Severity of SARS-CoV-2 infection in children with inborn errors of immunity (primary immunodeficiencies): a systematic review

Severity of SARS-CoV-2 infection in children with inborn errors of immunity (primary immunodeficiencies): a systematic review

Dexamethasone/etoposide

X-Linked Lymphoproliferative Disease Type 2 With Activation of Hemophagocytic Lymphohistiocytosis Secondary to Epstein-Barr Virus Infection

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