Hyper IgE syndromes: A clinical approach

Gharehzadehshirazi, Azadeh; Amini, Abbas; Rezaei, Nima

doi:10.1016/j.clim.2022.108988

Cited by 11 publications

(11 citation statements)

References 73 publications

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“…Supportive therapy of AD-HIES consists of antibiotics and anti-fungal treatments, either as prophylaxis or upon signs of infections. Other therapies consist of immunoglobulin replacement treatments, by intravenous (IVIG) or subcutaneous (SCIG) routes ( 28 ). Use of hematopoietic stem cell transplantations (HSCT) in AD-HIES patients is currently increasing.…”

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

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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.

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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

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“…It can cause high mortality and high susceptibility to the development of infections in patients. The major difficulty in this disease remains the lack of specific treatment [ 90 ].…”

Section: Oral Manifestations In Selected Diseasesmentioning

confidence: 99%

“…Oral lesions may be developmental, reactive changes resulting from chronic infections associated with the syndrome, or reflect the role of the HIES gene, STAT3, in epithelial development [ 87 , 88 , 89 ]. About 64% of patients with HIES show no exfoliation of the primary teeth, often preventing eruption of the permanent teeth [ 88 , 89 , 90 , 91 ]. This retention of the deciduous teeth may predispose to malocclusion.…”

Section: Oral Manifestations In Selected Diseasesmentioning

confidence: 99%

Immunoglobulin Disorders and the Oral Cavity: A Narrative Review

Ptasiewicz

Bębnowska

Małkowska

et al. 2022

JCM

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The oral mucosa is a mechanical barrier against the penetration and colonization of microorganisms. Oral homeostasis is maintained by congenital and adaptive systems in conjunction with normal oral flora and an intact oral mucosa. Components contributing to the defense of the oral cavity include the salivary glands, innate antimicrobial proteins of saliva, plasma proteins, circulating white blood cells, keratinocyte products of the oral mucosa, and gingival crevicular fluid. General disturbances in the level of immunoglobulins in the human body may be manifested as pathological lesions in the oral mucosa. Symptoms of immunoglobulin-related general diseases such as mucous membrane pemphigoid (MMP), pemphigus vulgaris (PV), linear IgA bullous dermatosis (LABD), Epidermolysis Bullosa Aquisita (EBA), and Hyper-IgE syndrome (HIES) may appear in the oral cavity. In this review, authors present selected diseases associated with immunoglobulins in which the lesions appear in the oral cavity. Early detection and treatment of autoimmune diseases, sometimes showing a severe evolution (e.g., PV), allow the control of their dissemination and involvement of skin or other body organs. Immunoglobulin disorders with oral manifestations are not common, but knowledge, differentiation and diagnosis are essential for proper treatment.

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“…For example, in the presence of elastomas, an X‐ray of the long bones or wrists can reveal osteopoikilosis and confirm the diagnosis of Buschke–Ollendorff syndrome 12 . The association of hypereosinophilia and hyper‐IgE in a patient with severe eczema may guide the clinician toward several genodermatoses, such as Omenn, Wiskott–Aldrich, Netherton, or Job's syndromes 39,40 …”

Section: Diagnostic Strategies In Genodermatosesmentioning

confidence: 99%

“…12 The association of hypereosinophilia and hyper-IgE in a patient with severe eczema may guide the clinician toward several genodermatoses, such as Omenn, Wiskott-Aldrich, Netherton, or Job's syndromes. 39,40 The order of in-depth genetic or clinical phases can vary; sometimes, it is useful to work classically (in-depth clinical investigations before the genetic tests, or 'phenotype first'), whereas in other instances, performing genetic tests first may be preferable, followed by target clinical investigations according to the genetic variants identified in the patient DNA or RNA (an approach called 'genotype first' which allow deciphering atypical or rare clinical presentations, observing phenotypic expansion, or performing reverse phenotyping). 12,41 More frequently, both processes are performed in parallel when monogenic genodermatosis is suspected.…”

Section: Agnostic Str Ategie S I N Ge Node R M Atose Smentioning

confidence: 99%

Clinical and molecular diagnosis of genodermatoses: Review and perspectives

Salik

Richert

Smits

2022

Acad Dermatol Venereol

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Genodermatoses are a complex and heterogeneous group of genetic skin disorders characterized by variable expression and clinical and genetic heterogeneity, rendering their diagnosis challenging. DNA‐based techniques, like whole‐exome sequencing, can establish a diagnosis in 50% of cases. RNA‐sequencing is emerging as an attractive tool that can obtain information regarding gene expression while integrating functional genomic data with regard to the interpretation of variants. This increases the diagnostic rate by an additional 10–15%. In the present review, we detail the clinical steps involved in the diagnosis of genodermatoses, as well as the current DNA‐based technologies available to clinicians. Herein, the intention is to facilitate a better understanding of the possibilities and limitations of these diagnostic technologies. In addition, this review could guide dermatologists through new emerging techniques, such as RNA‐sequencing and its applications to familiarizing them with future techniques. Currently, this multi‐omics approach is likely the best strategy designed to promote the diagnosis of patients with genodermatoses and discover new skin disease genes that could result in novel targeted therapies.

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Hyper IgE syndromes: A clinical approach

Cited by 11 publications

References 73 publications

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

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

Immunoglobulin Disorders and the Oral Cavity: A Narrative Review

Clinical and molecular diagnosis of genodermatoses: Review and perspectives

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