Emergence of azole resistant-Aspergillus fumigatus infections during STAT3-deficiency

Danion, François; Dureault, Amélie; Gautier, Claudie; Sénéchal, Agathe; Persat, Florence; Bougnoux, Marie‐Elisabeth; Givel, C.; Couderc, Louis‐Jean; Lortholary, Olivier; García-Hermoso, Dea

doi:10.1099/jmm.0.001200

Cited by 6 publications

(5 citation statements)

References 36 publications

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“…Antifungal therapy in STAT3 deficiency patients diagnosed with ABPA needs to be prolonged, due to poor penetration into parenchymal lung disease, 5,7 although such therapy could induce resistance and result in toxicity 6 . The increased emergence of azole‐resistant of A. fumigatus infections recently reported in patients with STAT3 deficiency is worrisome 14 . Despite the severity of lung disease in these patients, there have been few studies on its therapeutic management, and the efficacy and safety of systemic and/or inhaled corticosteroids as well as of nebulized amphotericin B needs to be evaluated 3,6 …”

Section: Discussionmentioning

confidence: 99%

“…6 The increased emergence of azole-resistant of A. fumigatus infections recently reported in patients with STAT3 deficiency is worrisome. 14 Despite the severity of lung disease in these patients, there have been few studies on its therapeutic management, and the efficacy and safety of systemic and/or inhaled corticosteroids as well as of nebulized amphotericin B needs to be evaluated. 3,6…”

Section: Why Making the Correct Diagnosis Is Challenging Yet Crucial?mentioning

confidence: 99%

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A challenging differential diagnosis in a patient with autosomal dominant STAT3 deficiency

Bravo‐Queipo‐de‐Llano

Bonet

Rosal

et al. 2022

Pediatric Pulmonology

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Autosomal dominant hyper IgE syndrome (AD-HIES) is a primary immunodeficiency caused by loss-of-function (LOF) mutations in the Signal Transducer and Activator of Transcription 3 (STAT3) gene. In these patients, performing a correct differential diagnosis of pulmonary infections is difficult and challenging, as they usually have atypical presentations. However, establishing a correct diagnostic and therapeutic approach is essential, as pulmonary complications are responsible for high morbidity and mortality rates in these patients. We report the case of a teenage girl with AD-HIES and respiratory symptoms and fever in whom performing a correct differential diagnosis was challenging.

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Section: Discussionmentioning

confidence: 99%

Section: Why Making the Correct Diagnosis Is Challenging Yet Crucial?mentioning

confidence: 99%

A challenging differential diagnosis in a patient with autosomal dominant STAT3 deficiency

Bravo‐Queipo‐de‐Llano

Bonet

Rosal

et al. 2022

Pediatric Pulmonology

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“…As a result of deficient phagocytosis by macrophages and neutrophils, patients may suffer from recurrent bacterial and fungal infection. Long-term antifungal therapy is suggested in this population, but an emergency in azole-resistant Aspergillus infections was reported [15]. Immune reconstruction via IFN-γ supplementation [14], stem cell transplantation [35], or GM-CSF therapy [36] may benefit these patients.…”

Section: Discussionmentioning

confidence: 99%

“…For example [14], patients with Jobs syndrome, also known as signal transducer and activator of transcription 3 (STAT3) deficiency, can manifest with high blood IgE levels and are more susceptible to fungal infection. Long-term antifungal treatment and resection for refractory CPA have been suggested, but emergency azole-resistant Aspergillus infection has been reported [15].…”

Section: Introductionmentioning

confidence: 99%

Chronic Pulmonary Aspergillosis: Disease Severity Using Image Analysis and Correlation with Systemic Proinflammation and Predictors of Clinical Outcome

Huang

Chou

et al. 2021

JoF

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(1) Background: The presentation of chronic pulmonary aspergillosis (CPA) ranges from single granuloma to fibrosis in the affected lung. CPA can be divided into five categories according to European Respirology Society (ERS) guidance but is usually assessed by clinical physicians. Computer-based quantitative lung parenchyma analysis in CPA and its correlation with clinical manifestations, systemic inflammation, and angiogenesis have never been investigated. (2) Method: Forty-nine patients with CPA and 36 controls were prospectively enrolled. Pulmonary function tests (forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and FEV1/FCV) and biomarkers in the peripheral blood (the chemokines interleukin (IL)-1B, IL-6, IL-10, IL-8, CRP, ESR, MMP1, MMP7, MMP8, TNF-α, calprotectin, SDF-1α, and VEGFA) were measured before antifungal treatment. The disease severity was categorized into mild, moderate, and severe based on chest computed tomography (CT) images. The oxygen demand and overall mortality until the end of the study were recorded. Quantitative parenchyma analysis was performed using the free software 3Dslicer. (3) Results: The results of quantitative parenchyma analysis concorded with the visual severity from the chest CT, oxygen demand, FVC, and FEV1 in the study subjects. The decrease in kurtosis and skewness of the lung density histograms on CT, increase in high attenuation area (HAA), and reduced lung volume were significantly correlated with increases in the PMN %, CRP, IL-1B, SDF-1α, MMP1, and Calprotectin in peripheral blood in the multivariable regression analysis. TNF-α and IL-1B at study entry and the CPA severity from either a visual method or computer-based evaluation were predictors of long-term mortality. (4) Conclusion: The computer-based parenchyma analysis in CPA agreed with the categorization on a visual basis and was associated with the clinical outcomes, chemokines, and systemic proinflammation profiles.

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“…According to an analysis of 74 STAT3 -deficient patients (HIES) in the French National Cohort, 13 of them experienced at least one episode of pulmonary aspergillosis. [ 43 ]…”

Section: R Esultsmentioning

confidence: 99%

Genetic Susceptibility to Fungal Infections

Yazdi,

Behnaminia,

Nafari

et al. 2023

Advanced Biomedical Research

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Reports of fungal infections have increased over the past decades, making them a major threat to human health. In this study, we review the effects of genetic defects on susceptibility to fungal diseases. To identify all relevant literature, we searched Google Scholar, PubMed, and Scopus and profiled studies published between 2008 and 2021. The results of several studies conducted on this subject have shown the significant effects of genetic variations such as hyper-IgE syndrome, Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy syndrome, dectin-1 deficiency, CARD9 mutations, STAT1 mutations, and IL17 mutationson the host immune system’s response, which has an important impact on susceptibility to fungal infections. The underlying immune system-related genetic profile affects the susceptibility of individuals to different fungal infections; therefore, this subject should be further studied for better treatment of fungal diseases.

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Emergence of azole resistant-Aspergillus fumigatus infections during STAT3-deficiency

Cited by 6 publications

References 36 publications

A challenging differential diagnosis in a patient with autosomal dominant STAT3 deficiency

A challenging differential diagnosis in a patient with autosomal dominant STAT3 deficiency

Chronic Pulmonary Aspergillosis: Disease Severity Using Image Analysis and Correlation with Systemic Proinflammation and Predictors of Clinical Outcome

Genetic Susceptibility to Fungal Infections

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