Case Report: Eosinophilic Esophagitis in a Patient With a Novel STAT1 Gain-of-Function Pathogenic Variant

Scott, Ori; Sharfe, Nigel; Dadi, Harjit; Vong, Linda; Garkaby, Jenny; Fuentes, Laura Abrego; Pachul, Jessica Willett; Nelles, Sandra; Nahum, Amit; Roifman, Chaim M.

doi:10.3389/fimmu.2022.801832

Cited by 6 publications

(4 citation statements)

References 41 publications

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“…Scott et al reported the case of a 39-year-old woman with EoE refractory on a six-food elimination diet, fluticasone, montelukast, and proton pump inhibitor, but responsive to subsequent therapy with slurry budesonide [ 28 ]. She probably developed the first GI symptoms in late adolescence, but she was not formally investigated until she was 31.…”

Section: Resultsmentioning

confidence: 99%

Eosinophilic Gastrointestinal Diseases in Inborn Errors of Immunity

Votto

Naso

Brambilla

et al. 2023

JCM

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Inborn errors of immunity (IEI) are disorders mostly caused by mutations in genes involved in host defense and immune regulation. Different degrees of gastrointestinal (GI) involvement have been described in IEI, and for some IEI the GI manifestations represent the main and characteristic clinical feature. IEI also carry an increased risk for atopic manifestations. Eosinophilic gastrointestinal diseases (EGIDs) are emerging disorders characterized by a chronic/remittent and prevalent eosinophilic inflammation affecting the GI tract from the esophagus to the anus in the absence of secondary causes of intestinal eosinophilia. Data from the U.S. Immunodeficiency Network (USIDNET) reported that EGIDs are more commonly found in patients with IEI. Considering this element, it is reasonable to highlight the importance of an accurate differential diagnosis in patients with IEI associated with mucosal eosinophilia to avoid potential misdiagnosis. For this reason, we provide a potential algorithm to suspect an EGID in patients with IEI or an IEI in individuals with a diagnosis of primary EGID. The early diagnosis and detection of suspicious symptoms of both conditions are fundamental to prevent clinically relevant complications.

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Section: Resultsmentioning

confidence: 99%

Eosinophilic Gastrointestinal Diseases in Inborn Errors of Immunity

Votto

Naso

Brambilla

et al. 2023

JCM

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“…In addition, eosinophils upregulated the expression of siglec-8 + and CD9 + , which indicate activation followed by subsequent apoptosis [ 63 ]. A case report of treatment refractory eosinophilic esophagitis associated with a STAT1 GOF alteration was recently published [ 64 ]. This report indicates an even wider phenotype than previously described, including involvement of eosinophils in the pathogenesis of STAT1 GOF mutations.…”

Section: Discussionmentioning

confidence: 99%

Three Adult Cases of STAT1 Gain-of-Function with Chronic Mucocutaneous Candidiasis Treated with JAK Inhibitors

et al. 2022

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Purpose The aim of this study was to characterize clinical effects and biomarkers in three patients with chronic mucocutaneous candidiasis (CMC) caused by gain-of-function (GOF) mutations in the STAT1 gene during treatment with Janus kinase (JAK) inhibitors. Methods Mass cytometry (CyTOF) was used to characterize mononuclear leukocyte populations and Olink assay to quantify 265 plasma proteins. Flow-cytometric Assay for Specific Cell-mediated Immune-response in Activated whole blood (FASCIA) was used to quantify the reactivity against Candida albicans. Results Overall, JAK inhibitors improved clinical symptoms of CMC, but caused side effects in two patients. Absolute numbers of neutrophils, T cells, B cells, and NK cells were sustained during baricitinib treatment. Detailed analysis of cellular subsets, using CyTOF, revealed increased expression of CD45, CD52, and CD99 in NK cells, reflecting a more functional phenotype. Conversely, monocytes and eosinophils downregulated CD16, consistent with reduced inflammation. Moreover, T and B cells showed increased expression of activation markers during treatment. In one patient with a remarkable clinical effect of baricitinib treatment, the immune response to C. albicans increased after 7 weeks of treatment. Alterations in plasma biomarkers involved downregulation of cellular markers CXCL10, annexin A1, granzyme B, granzyme H, and oncostatin M, whereas FGF21 was the only upregulated marker after 7 weeks. After 3 months, IFN-ɣ and CXCL10 were downregulated. Conclusions The clinical effect of JAK inhibitor treatment of CMC is promising. Several biological variables were altered during baricitinib treatment demonstrating that lymphocytes, NK cells, monocytes, and eosinophils were affected. In parallel, cellular reactivity against C. albicans was enhanced.

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“…EoE is increasingly recognized to co-occur with inflammatory bowel disease (38)(39)(40), and in some cohorts, the patients are more likely to be male, present at a younger age, and be associated with comorbid atopic disorders (41). It is important to note that mucocutaneous candidiasis can cause secondary gastrointestinal eosinophilia (13,27,28). Patients with some forms of IEI, like HIES or combined immunodeficiency, are more susceptible to candidal infections.…”

Section: Discussionmentioning

confidence: 99%

“…The association of EGID and EoE in IEI patients has not been thoroughly investigated. However, there are reports of EoE in patients with IEI, including CVID, chronic granulomatous disease (CGD), and STAT1 gain of function (11)(12)(13)(14). EGID, including esophageal, gastric, and colonic involvement, has been reported in patients with STAT 3 deficiency [autosomal dominant hyper immunoglobulin E syndrome (AD-HIES)] and PTEN hamartoma syndrome (15,16).…”

Section: Introductionmentioning

confidence: 99%

Eosinophilic gastrointestinal disorders in patients with inborn errors of immunity: Data from the USIDNET registry

Tran

Gober²,

Garabedian³

et al. 2022

Front. Immunol.

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RationaleEosinophilic gastrointestinal disorders (EGID), including eosinophilic esophagitis (EoE), are inflammatory disorders of the gastrointestinal mucosa mediated by complex immune mechanisms. Although there have been initial reports of EGID in patients with inborn errors of immunity (IEI), little is known about the presentation of EGID in immunodeficient individuals.MethodsWe queried the U.S. Immunodeficiency Network (USIDNET) for patient records including the terms eosinophilic esophagitis, gastritis, enteritis, or colitis. We analyzed 74 patient records from the database, including diagnoses, demographics, infectious history, laboratory findings, genetic studies, therapeutic interventions, and clinical outcomes.ResultsWe examined 74 patient records. A total of 61 patients had isolated EoE, and 13 had distal gastrointestinal involvement consistent with EGID. The most common IEI were common variable immunodeficiency (43.2%), some form of combined immunodeficiency (21.6%), chronic granulomatous disease (8.1%), hyper-IgE syndrome (6.8%), and autoimmune lymphoproliferative syndrome (6.8%). The median age at presentation with IEI was 0.5 years (IQR 1.725, max 39 years) and 56.76% were male. Approximately 20% of the patients in the cohort received a hematopoietic stem cell transplantation for treatment of IEI, but the timing of the HSCT in relationship to the EGID diagnosis was unknown.ConclusionsHere, we report EGID in a diverse cohort of IEI patients, suggesting that both non-EoE EGID and EoE can be seen as comorbid conditions with a variety of IEI. Our data suggests that EGID may be more common in patients with IEI than would be expected based on estimates of EGID in the general population.

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Case Report: Eosinophilic Esophagitis in a Patient With a Novel STAT1 Gain-of-Function Pathogenic Variant

Cited by 6 publications

References 41 publications

Eosinophilic Gastrointestinal Diseases in Inborn Errors of Immunity

Eosinophilic Gastrointestinal Diseases in Inborn Errors of Immunity

Three Adult Cases of STAT1 Gain-of-Function with Chronic Mucocutaneous Candidiasis Treated with JAK Inhibitors

Eosinophilic gastrointestinal disorders in patients with inborn errors of immunity: Data from the USIDNET registry

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