Primary immunodeficiencies associated with eosinophilia

Abstract

BackgroundEosinophilia is not an uncommon clinical finding. However, diagnosis of its cause can be a dilemma once common culprits, namely infection, allergy and reactive causes are excluded. Primary immunodeficiency disorders (PID) are among known differentials of eosinophilia. However, the list of PIDs typically reported with eosinophilia is small and the literature lacks an inclusive list of PIDs which have been reported with eosinophilia. This motivated us to review the literature for all PIDs which have been described to have elevated eosinophils as this may contribute to an earlier diagnosis of PID and further the understanding of eosinophilia.MethodsA retrospective PubMed, and Google Scholar search using the terms “eosinophilia” and “every individual PID” as classified by Expert Committee of the International Union of Immunological Societies with the limit of the English language was performed. Results were assessed to capture case(s) which reported eosinophilia in the context of PID conditions. Absolute eosinophil counts (AEC) were retrieved from manuscripts whenever reported.ResultsIn addition to the typical PID conditions described with eosinophilia, we document that MHC class II deficiency, CD3γ deficiency, STAT1 deficiency (AD form), Kostmann disease, cyclic neutropenia, TCRα deficiency, Papillon-Lefevre syndrome, CD40 deficiency, CD40L deficiency, anhidrotic ectodermal dysplasia with immune deficiency, ataxia-telangiectasia, common variable immunodeficiency disorders (CVID), Blau syndrome, CARD9 deficiency, neonatal onset multisystem inflammatory disease or chronic infantile neurologic cutaneous and articular syndrome (NOMID/CINCA), chronic granulomatous disease, MALT1 deficiency and Roifman syndrome have been noted to have elevated eosinophils. Severe eosinophilia (>5.0 × 109/L) was reported in Omenn syndrome, Wiskott Aldrich syndrome, ADA deficiency, autoimmune lymphoproliferative syndrome, immunodysregulation polyendocrinopathy enteropathy X-linked, STAT3 deficiency, DOCK8 deficiency, CD40 deficiency, MHC II deficiency, Kostmann disease, Papillon-Lefevre syndrome, and CVID.ConclusionsThis literature review shows that there is an extensive list of PIDs which have been reported with eosinophilia. This list helps clinicians to consider an extended differential diagnoses when tasked with exclusion of PID as a cause for eosinophilia.Electronic supplementary materialThe online version of this article (doi:10.1186/s13223-016-0130-4) contains supplementary material, which is available to authorized users.

Germline Genetic Risk Variants for Progressive Multifocal Leukoencephalopathy

“…A list of candidate immune function genes was curated from the following main sources: genome-wide study of rare copy number variants in 70 PML cases (Dis cohort) that impact immune function genes (data not shown), genes from the ClinVar database (43) using search terms "immune deficiency" and "immunodeficiency, " IUIS and other immunodeficiency reviews (29,30,(44)(45)(46)(47)(48)(49)(50), type I interferon pathway genes (51)(52)(53)(54)(55)(56)(57)(58), complement pathway genes (59), and JCV or PML linked biology (23,26,33,(60)(61)(62)(63)(64). The full list of 711 unique genes were cross-checked against genes that were found with DV-called variants in the Dis and/or Rep cohorts.…”

An Approach to the Evaluation of Persistent Hypereosinophilia in Pediatric Patients

“…However, the presence of severe, persistent eosinophilia (i.e., eosinophils >5,000/microL) is unlikely secondary to atopy and should prompt additional evaluation for another etiology. Importantly, several immunodeficiency syndromes (signal transducer and activator of transcription 3 [STAT3] deficiency, dedicator of cytokinesis 8 [DOCK8] deficiency, lipopolysaccharide-responsive-beige-like-anchor [LRBA] deficiency, Wiskott-Aldrich syndrome [WAS], and immune dysregulation, polyendocrinopathy, enteropathy, X-linked [IPEX] syndrome) present in childhood with atopy, elevated IgE and peripheral blood eosinophilia ( 27 ). Consequently, a thorough infection history (with focus on the frequency and etiology of infections) should be obtained in any pediatric patient with HE and atopy.…”

“…Consequently, a thorough infection history (with focus on the frequency and etiology of infections) should be obtained in any pediatric patient with HE and atopy. Other immunodeficiencies that can present with HE in the pediatric population include autoimmune lymphoproliferative syndrome (ALPS) and Omenn syndrome associated with severe combined immunodeficiency ( 27 ).…”

Genetics of eosinophilic esophagitis

“…EoE co-occurs with several Mendelian and non-Mendelian disorders (Table 2 and refs 85,86). For example, EoE is enriched in patients with hypermobility-associated connective-tissue disorders including Loeys-Dietz syndrome (also known as Marfan syndrome type II) 88 and the hypermobility variant of Ehlers-Danlos syndrome.…”