Familial hemophagocytic lymphohistiocytosis induced by SARS-CoV-2

Alhumaidan, Wejdan; Al-Otaibi, Abdulnasir; Elyamany, Ghaleb; Alabbas, Fahad; Ali, Tahani Bin

doi:10.1080/08880018.2020.1867267

Cited by 4 publications

(13 citation statements)

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“…Alhumaidan et al . first reported the case of an infant who developed fatal HLH in the setting of an acute SARS‐CoV‐2 infection and was subsequently diagnosed with autosomal recessive familial HLH type 3 9 . Given the massive immune response elicited by SARS‐CoV‐2, it is conceivable that SARS‐CoV‐2 might be a potent trigger for primary HLH.…”

Section: Figurementioning

confidence: 99%

“…Alhumaidan et al first reported the case of an infant who developed fatal HLH in the setting of an acute SARS-CoV-2 infection and was subsequently diagnosed with autosomal recessive familial HLH type 3. 9 Given the massive immune response elicited by SARS-CoV-2, it is conceivable that SARS-CoV-2 might be a potent trigger for primary HLH. Therefore, the diagnosis of primary HLH should be considered in children and adolescents presenting with signs of hyperinflammation in the setting of SARS-CoV-2 infection, especially early in the course of the disease, i.e., during the 'active' phase of infection and viral replication, and weeks before one might typically diagnose a MIS-C related cytokine storm.…”

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confidence: 99%

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Primary haemophagocytic lymphohistiocytosis (Chédiak‐Higashi Syndrome) triggered by acute SARS‐CoV‐2 infection in a six‐week‐old infant

et al. 2021

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Section: Figurementioning

confidence: 99%

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confidence: 99%

Primary haemophagocytic lymphohistiocytosis (Chédiak‐Higashi Syndrome) triggered by acute SARS‐CoV‐2 infection in a six‐week‐old infant

et al. 2021

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“…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%

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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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Anakinra/dexamethasone/etoposide

2021

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Anakinra/dexamethasone/etoposideLack of efficacy: case report A 7-week-old girl exhibited lack of efficacy during treatment with anakinra, dexamethasone and etoposide for familial haemophagocytic lymphohistiocytosis (FHLH).The girl was brought to hospital in Saudi Arabia in a state of respiratory distress, with fever and reduced activity for 4 days. She started receiving unspecified empirical antibacterials [antibiotics] for sepsis. Meanwhile, investigations led to the diagnosis of SARS-CoV-2 infection; further analyses raised suspicions for COVID-19-associated HLH or cytokine release syndrome. Therefore, she started receiving immune globin and dexamethasone. Tocilizumab was subsequently added to her ongoing regimen. However, tests revealed a worsening hyperinflammatory condition, indicative of possible FHLH. Therefore, she switched to HLH-directed therapy, comprising anakinra, dexamethasone and etoposide [routes and dosages not stated]. However, in spite of these interventions, her clinical status progressively deteriorated, with elevated ferritin levels. She eventually succumbed to the refractory HLH and sepsis. Whole-exome sequencing identified a homozygous variant in the UNC13D gene, compatible with the diagnosis of autosomal recessive FHLH type-3.

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Familial hemophagocytic lymphohistiocytosis induced by SARS-CoV-2

Cited by 4 publications

References 14 publications

Primary haemophagocytic lymphohistiocytosis (Chédiak‐Higashi Syndrome) triggered by acute SARS‐CoV‐2 infection in a six‐week‐old infant

Primary haemophagocytic lymphohistiocytosis (Chédiak‐Higashi Syndrome) triggered by acute SARS‐CoV‐2 infection in a six‐week‐old infant

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

Anakinra/dexamethasone/etoposide

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