Gaucher Disease Type 2 Manifested as Hemophagocytic Lymphohistiocytosis in a Neonate in the COVID-19 Era

Kosmeri, Chrysoula; Rallis, Dimitrios; Baltogianni, Maria; Bouza, Helen; Lykopoulou, Lilia; Lianou, Loukia; Papadopoulou, Eleni; Tzanoudaki, Marianna; Farmaki, Evangelia; Papadakis, Vassilios; Giapros, Vasileios; Makis, Alexandros

doi:10.1097/mph.0000000000002551

Cited by 3 publications

(16 citation statements)

References 12 publications

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“…Studies were excluded if they did not discuss nHLH ( n = 280); aggregated nHLH patient data with all ages ( n = 83); provided insufficient detail and/or data describing a case of nHLH ( n = 28); and for other reasons ( n = 8). Two‐hundred‐five cases of nHLH from 142 articles were included in our analysis 12–152 …”

Section: Resultsmentioning

confidence: 99%

Neonatal hemophagocytic lymphohistiocytosis: A meta‐analysis of 205 cases

Kranz,

Hahn,

Thompson

et al. 2024

Pediatric Blood & Cancer

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BackgroundNeonatal hemophagocytic lymphohistiocytosis (nHLH), defined as HLH that presents in the first month of life, is clinically devastating. There have been few large descriptive studies of nHLH.ObjectivesThe objective of this study was to perform a meta‐analysis of published cases of nHLH.MethodsA comprehensive literature database search was performed. Cases of HLH were eligible for inclusion if clinical analysis was performed at age ≤30 days. Up to 70 variables were extracted from each case.ResultsA total of 544 studies were assessed for eligibility, and 205 cases of nHLH from 142 articles were included. The median age of symptom onset was day of life 3 (interquartile range [IQR]: 0–11, n = 141). Median age at diagnosis was day of life 15 (IQR: 6–27, n = 87). Causes of HLH included familial HLH (48%, n = 99/205), infection (26%, n = 53/205), unknown (17%, n = 35/205), macrophage activation syndrome/rheumatologic (2.9%, n = 4/205), primary immune deficiency (2.0%, n = 5/205), inborn errors of metabolism (2.4%, n = 5/205), and malignancy (2.0%, n = 4/205). Fever was absent in 19% (n = 28/147) of all neonates and 39% (n = 15/38) of preterm neonates. Bicytopenia was absent in 26% (n = 47/183) of patients. Central nervous system (CNS) manifestations were reported in 63% of cases (n = 64/102). Liver injury (68%, n = 91/134) and/or liver failure (24%, n = 32/134) were common. Flow cytometry was performed in 22% (n = 45/205) of cases. Many patients (63%, n = 121/193) died within the period of reporting. Discernable values for HLH diagnostic criteria were reported between 30% and 83% of the time.ConclusionsEvaluation of nHLH requires rapid testing for a wide range of differential diagnoses. HLH diagnostic criteria such as fever and bicytopenia may not occur as frequently in the neonatal population as in older pediatric populations. Neurologic and hepatic manifestations frequently occur in the neonatal population. Current reports of nHLH suggest a high mortality rate. Future publications containing data on nHLH should improve reporting quality by reporting all clinically relevant data.

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Section: Resultsmentioning

confidence: 99%

Neonatal hemophagocytic lymphohistiocytosis: A meta‐analysis of 205 cases

Kranz,

Hahn,

Thompson

et al. 2024

Pediatric Blood & Cancer

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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%

“…Only six studies were made within multi-countries (n = 6) [ 10 , 33 , 35 , 51 , 95 , 132 ]. The majority of the studies were single centre [ 4 – 6 , 8 , 9 , 19 , 25 – 32 , 34 , 37 – 39 , 41 , 43 – 47 , 49 , 50 , 52 – 60 , 62 , 64 , 66 – 69 , 71 , 72 , 75 – 80 , 82 – 84 , 86 – 90 , 93 , 94 , 96 , 98 – 117 , 119 – 131 ] and only 23 studies were multi-centre [ 7 , 10 , 33 , 35 , 36 , 40 , 42 , 48 , 51 , 61 , 63 , 65 , 70 , 73 , 74 , 81 , 85 , 91 , 92 , 95 , 97 , 118 , 132 ]. Among all included studies in our systematic review, only one study reported on the other potential modifiers in immunity-related pathways for all diagnosed IEIs in children who were infected with SARS-CoV-2 (n = 1, 0.9%) […”

Section: Resultsmentioning

confidence: 99%

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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“…Patients with GD type II, in particular, have severe hepatosplenomegaly and cytopenia from birth. Most cases of HLH associated with GD have neonatal onset, [89][90][91] and even if therapeutic intervention for HLH is performed, the prognosis is poor. Glycosylceramide, a GD metabolite, is found in macrophages, reticuloendothelial cells, monocytes, T cells, B cells, and dendritic cells.…”

Section: Other Iemsmentioning

confidence: 99%

“…Other IEMs associated with HLH have been reported (Table 5). 81–103 Propionic acidemia (PA) and Gaucher disease (GD) are relatively common causes of HLH. Two cases of PA and one case of methylmalonic aciduria (MMA) with HLH were reported by Gokce, et al 81 Three patients received immunochemotherapy, but the patient with MMA died as a result of multiple organ failure.…”

Section: Introductionmentioning

confidence: 99%

Rare diseases presenting with hemophagocytic lymphohistiocytosis

Kanegane

Noguchi

Yamada

et al. 2023

Pediatrics International

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Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal hyperinflammatory disorder characterized by hypercytokinemia caused by excessive activation of cytotoxic T cells and macrophages. HLH is caused by a variety of factors and is classified into primary and secondary HLH. Familial HLH (FHL) types 1–5, X‐linked lymphoproliferative syndrome types 1 and 2, and FHL syndrome with hypopigmentation are all examples of primary HLH. Secondary HLH, on the other hand, is linked to infections, malignant tumors, autoimmune diseases, and other diseases. The causes of HLH vary, and finding the underlying disease is critical for diagnosis and treatment. The majority of HLH is caused by the aforementioned conditions; however, approximately 10% of cases are caused by rare diseases such as inborn errors of immunity (IEI) and inborn errors of metabolism (IEM). Novel IEI, such as RhoG, MAP kinase activating death domain, TIM3, and ZNFX1 deficiencies, have recently been identified as causes of HLH. IEM patients are rarely associated with HLH. Surprisingly, children with lysinuric protein intolerance and lysosomal acid lipase deficiency (Wolman disease) frequently develop HLH. This review focuses on the most recent knowledge of HLH caused by rare diseases such as IEI and IEM.

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Gaucher Disease Type 2 Manifested as Hemophagocytic Lymphohistiocytosis in a Neonate in the COVID-19 Era

Cited by 3 publications

References 12 publications

Neonatal hemophagocytic lymphohistiocytosis: A meta‐analysis of 205 cases

Neonatal hemophagocytic lymphohistiocytosis: A meta‐analysis of 205 cases

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

Rare diseases presenting with hemophagocytic lymphohistiocytosis

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