Remission of eczema and recovery of Th1 polarization following treatment with Dupilumab in STAT3 hyper IgE syndrome

Matucci-Cerinic, Caterina; Viglizzo, Gianmaria; Pastorino, Carlotta; Corcione, Anna; Prigione, Ignazia; Bocca, Paola; Bustaffa, Marta; Cecconi, Massimiliano; Gattorno, Marco; Volpi, Stefano

doi:10.1111/pai.13770

Cited by 10 publications

(8 citation statements)

References 10 publications

(28 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…240 It may also improve AD related to IL4/4R, IL13, DOCK8, CARD11, STAT3, SPINK5, ERBB2IP, and ZNF341 dysregulation. [241][242][243][244][245][246][247][248] Tralokinumab targets IL13 and is approved for moderate to severe AD in adults. 77 Topical ruxolitinib and oral upadacitinib, abrocitinib, and baricitinib (approved in Europe and Japan) are JAK inhibitors indicated for AD.…”

Section: Discussionmentioning

confidence: 99%

Genetic/Environmental Contributions and Immune Dysregulation in Children with Atopic Dermatitis

Chong¹,

Visitsunthorn²,

Ong³

2022

JAA

View full text Add to dashboard Cite

Atopic dermatitis (AD) is one of the most common skin conditions in humans. AD affects up to 20% of children worldwide and results in morbidity for both patients and their caregivers. The basis of AD is an interplay between genetics and the environment characterized by immune dysregulation. A myriad of mutations that compromise the skin barrier and/or immune function have been linked to AD. Of these, filaggrin gene ( FLG ) mutations are the most evidenced. Many other mutations have been implicated in isolated studies that are often unreplicated, creating an archive of genes with potential but unconfirmed relevance to AD. Harnessing big data, polygenic risk scores (PRSs) and genome-wide association studies (GWAS) may provide a more practical strategy for identifying the genetic signatures of AD. Epigenetics may also play a role. Staphylococcus aureus is the most evidenced microbial contributor to AD. Cutaneous dysbiosis may result in over-colonization by pathogenic strains and aberrant skin immunity and inflammation. Aeroallergens, air pollution, and climate are other key environmental contributors to AD. The right climate and/or commensals may improve AD for some patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Genetic/Environmental Contributions and Immune Dysregulation in Children with Atopic Dermatitis

Chong¹,

Visitsunthorn²,

Ong³

2022

JAA

View full text Add to dashboard Cite

show abstract

“…In the context of IEIs-A, dupilumab has been used in many models with a Th2-skewed immune response with successful results ( 128 ). An increasing number of severe eczema treated with dupilumab IEIs-A patients are being reported in the literature ( 120 , 159 – 161 ) and a recovery of Th1 polarization after its use is described in many cases ( 120 ).…”

Section: Discussionmentioning

confidence: 99%

“…Given the increased IL-4 expression observed in patients with dominant negative STAT3 mutations, it was supposed that dupilumab might treat some clinical manifestations (118). Many reports confirmed the success of the treatment with substantial improvement of the cutaneous lesions, pruritus and IgE levels (118)(119)(120)(121).…”

Section: Stat3mentioning

confidence: 99%

Tailored treatments in inborn errors of immunity associated with atopy (IEIs-A) with skin involvement

et al. 2023

View full text Add to dashboard Cite

Inborn errors of immunity associated with atopy (IEIs-A) are a group of inherited monogenic disorders that occur with immune dysregulation and frequent skin involvement. Several pathways are involved in the pathogenesis of these conditions, including immune system defects, alterations of skin barrier and metabolism perturbations. Current technological improvements and the higher accessibility to genetic testing, recently allowed the identification of novel molecular pathways involved in IEIs-A, also informing on potential tailored therapeutic strategies. Compared to other systemic therapy for skin diseases, biologics have the less toxic and the best tolerated profile in the setting of immune dysregulation. Here, we review IEIs-A with skin involvement focusing on the tailored therapeutic approach according to their pathogenetic mechanism.

show abstract

“…However, the effect of dupilumab on the Th1-mediated response and secreted cytokines was not evaluated in our study. Nevertheless, Th1 enhancement following dupilumab treatment has been demonstrated in AD-HIES ( 14 ).…”

Section: Discussionmentioning

confidence: 99%

Dominant-negative signal transducer and activator of transcription (STAT)3 variants in adult patients: A single center experience

et al. 2022

View full text Add to dashboard Cite

BackgroundAutosomal dominant hyper-IgE syndrome (AD-HIES) caused by dominant negative (DN) variants in the signal transducer and activator of transcription 3 gene (STAT3) is characterized by recurrent Staphylococcal abscesses, severe eczema, chronic mucocutaneous candidiasis (CMC), and non-immunological facial and skeletal features.ObjectivesTo describe our experience with the diagnosis and treatment of adult patients with AD-HIES induced by DN-STAT3 variants.MethodsThe medical records of adult patients (>18 years) treated at the Allergy and Clinical Immunology Clinic of Hadassah Medical Center, Jerusalem, Israel, were retrospectively analyzed. Immune and genetic workups were used to confirm diagnosis.ResultsThree adult patients (2 males; age 29-41 years) were diagnosed with DN-STAT3 variants. All patients had non-immunological features, including coarse faces and osteopenia. Serious bacterial infections were noted in all patients, including recurrent abscesses, recurrent pneumonia, and bronchiectasis. CMC and diffuse dermatophytosis were noted in two patients. Two patients had severe atopic dermatitis refractory to topical steroids and phototherapy. Immune workup revealed elevated IgE in three patients and eosinophilia in two patients. Whole exome sequencing revealed DN-STAT3 variants (c.1166C>T; p.Thr389Ile in two patients and c.1268G>A; p. Arg423Gln in one patient). Variants were located in DNA-binding domain (DBD) and did not hamper STAT3 phosphorylation Treatment included antimicrobial prophylaxis with trimethoprim/sulfamethoxazole (n=2) and amoxycillin-clavulanic acid (n=1), and anti-fungal treatment with fluconazole (n=2) and voriconazole (n=1). Two patients who had severe atopic dermatitis, were treated with dupilumab with complete resolution of their rash. No adverse responses were noted in the dupilumab-treated patients.DiscussionDupilumab can be used safely as a biotherapy for atopic dermatitis in these patients as it can effectively alleviate eczema-related symptoms. Immunologists and dermatologists treating AD-HIES adult patients should be aware of demodicosis as a possible manifestation. DN-STAT3 variants in DBD do not hamper STAT3 phosphorylation.

show abstract

Remission of eczema and recovery of Th1 polarization following treatment with Dupilumab in STAT3 hyper IgE syndrome

Cited by 10 publications

References 10 publications

Genetic/Environmental Contributions and Immune Dysregulation in Children with Atopic Dermatitis

Genetic/Environmental Contributions and Immune Dysregulation in Children with Atopic Dermatitis

Tailored treatments in inborn errors of immunity associated with atopy (IEIs-A) with skin involvement

Dominant-negative signal transducer and activator of transcription (STAT)3 variants in adult patients: A single center experience

Contact Info

Product

Resources

About