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hyper-IgE syndrome (HIES) - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

hyper-IgE syndrome

MONDO:0018037

Also known as:HIEShyper-IgE recurrent infection syndromehyperimmunoglobulin E syndrome

Overview

A condition that is characterized by elevated serum IgE, dermatitis, and respiratory infections.

OnsetNEONATAL, INFANTILE, CHILDHOOD

TreatmentsNo approved treatments · 1 in pipeline

Clinical Presentation

Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.

No HPO annotations are available for this condition.

Age of onset: newborn period, infancy, childhood.

GeneReviews

Clinical Guidance

STAT3 hyper IgE syndrome (STAT3-HIES) is a primary immune deficiency syndrome characterized by elevated serum IgE, eczema, and recurrent skin and respiratory tract infections, together with several connective tissue and skeletal abnormalities.

Presentation

Diagnosis

Drawn from GeneReviews diagnostic guidelines, newborn screening panel status (RUSP), and ClinGen gene-disease validity classifications. Reflects current clinical evidence and consensus where available.

GeneReviews

Diagnostic Criteria

Suggestive Findings

STAT3 hyper IgE syndrome (STAT3-HIES) should be suspected in individuals with the following findings:

Newborn rash and typically eczematous rash at least through childhood
Recurrent skin boils (often "cold," manifesting little inflammatory reaction)
Cyst-forming pneumonias

Treatment

Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.

No approved treatments are currently available for hyper-IgE syndrome. An additional 1 compound holds orphan drug designation.

Orphan Drug Designations

While no drugs are FDA-approved specifically for hyper-IgE syndrome, some of the following designated compounds may be used off-label in clinical practice. Treatment decisions should be made in consultation with a specialist familiar with this condition.

The following drugs have received orphan drug designation from the FDA for hyper-IgE syndrome. Orphan designation reflects regulatory interest and does not indicate approval for treatment.

Brand Name	Generic Name	Sponsor

Prognosis

Based on GeneReviews surveillance recommendations, HPO phenotype frequency and severity annotations, and published prevalence estimates from Orphanet and OMIM.

GeneReviews

Surveillance Guidelines

Table 5. Recommended Surveillance for Individuals with STAT3 Hyper IgE Syndrome

System/Concern

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

No clinical trials have been registered for hyper-IgE syndrome.

119 publications have been identified in PubMed for hyper-IgE syndrome. Research spans Case Report / Case Series (39%), Basic Science / Preclinical (22%), and Review / Meta-Analysis (13%).

Research Type	Count	% of Total
Patient case studies	47	39%

Data assembled from 5 of 12 sources · Last updated Sep 18, 2026, 7:12 PM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

Orphanet

European rare disease database

Orphanet:331223

GARD

Genetic and Rare Diseases Info Center

GARD:10956

Questions for Your Care Team

→What is the current development status of Recombinant humanized immunoglobulin gamma 1 monoclonal antibody (mAb) directed against the CemX segment of human membrane-bound immunoglobulin E (mIgE), and when might it become available?
→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

← Back to All Diseases

GeneReviews

Differential Diagnosis

Table 2. Disorders with Elevated Serum Concentration of IgE to Consider in the Differential Diagnosis of STAT3 Hyper IgE Syndrome

Gene(s)	Disorder	MOI	Additional Clinical Features of Differential Disorder
Overlapping w/STAT3-HIES	Distinguishing from STAT3-HIES CARD141FLG2	Atopic dermatitis3	ADAR4
CARD11	Immunodeficiency 11B w/atopic dermatitis5 (OMIM 617638)	AD	Early-onset eczema (frequently)
RAG2	Omenn syndrome6 (OMIM 603554)	AR	Presents in newborn period w/rash typically serum IgE
DOCK8	DOCK8 deficiency (DOCK8 AR HIES7) (OMIM 243700)	AR	Eczema
IL6ST	IL6ST deficiency9 (OMIM 618523)	AR	Recurrent skin lung infections; Craniosynostosis scoliosis
PGM3	PGM3 deficiency10 (OMIM 615816)	AR	Recurrent skin sinopulmonary infections; bone defects incl scoliosis
SPINK5	Netherton syndrome (OMIM 256500)	AR	Rash
WAS	Wiskott-Aldrich syndrome (See WAS Disorders.)	XL	Eczema recurrent infections
ZNF341	ZNF341 deficiency11 (OMIM 618282)	AR	Eczema recurrent infections

Source: GeneReviews — "STAT3 Hyper IgE Syndrome"

GeneReviews

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease in an individual diagnosed with STAT3 hyper IgE syndrome (STAT3-HIES), the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with STAT3 Hyper IgE Syndrome

System/Concern	Evaluation	Comment
Skin	Dermatologic exam	Newborn rash eczema during childhood; often improves w/age
Pulmonary	Chest imaging	Detection of bronchiectasis pneumatoceles
Skeletal	Eval for scoliosis osteoporosis	Scoliosis typically progresses through adolescence.; Osteoporosis can be present in children adults; DXA screening recommended.
Dental	Dental exam for possible retention of primary teeth	—
Vascular	Screening for coronary artery cerebral artery aneurysms	Aneurysms much more common in adults than in children; Screening by brain MRA heart CTA or coronary artery MRA every 3 yrs recommended for adolescents adults
Other	Consultation w/clinical geneticist /or genetic counselor	DXA = dual-energy x-ray absorptiometry Currently, there is no complete cure or targeted treatment for STAT3-HIES. The mainstay of therapy is prevention of staphylococcal abscesses and pneumonias with prophylactic anti-staphylococcal antibiotics as well as early aggressive treatment of infections.
Treatment of Manifestations in Individuals with STAT3 Hyper IgE Syndrome Manifestation/Concern	Treatment	Considerations/Other Eczema
recurrent boils	Topical antiseptics, e.g., dilute bleach baths1 chlorhexidine; frequent swimming in chlorinated pool	Adequate skin lubrication is needed after bleach. Anti-staphylococcal prophylaxis, e.g., w/2x/day TMP/SMX
pneumonias	Antibiotic prophylaxis, typically w/2x/day TMP/SMX	Targeting Staphylococcus aureus other pyogenic bacteria to prevent the pneumonias their complications In Coccidioides endemic regions use of prophylactic antifungals (e.g., fluconazole) can be considered.
candidiasis	Antifungal prophylaxis	Consider fluconazole prophylaxis if living in a Coccidioides endemic region. Osteoporosis Minimal trauma
fractures	Optimize calcium vitamin D intake	The role of bisphosphonates for those w/this disorder w/osteoporosis is unclear; some improvement seen in bone density but unclear improvement in fractures . Arterial
aneurysms	Optimal blood pressure mgmt	Antiplatelet or anticoagulation therapies may be considered for individuals w/significant coronary artery aneurysms to prevent myocardial infarction related to clotting w/in the aneurysm.

Source: GeneReviews — "STAT3 Hyper IgE Syndrome"

Kisho

hyper-IgE syndrome

Overview

Clinical Presentation

Clinical Guidance

Presentation

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Orphan Drug Designations

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

Immunologic Characteristics

Differential Diagnosis

Management Guidelines

Therapies Under Investigation

Clinical Trials

Recent Publications

Latest News & Developments

STAT3 Dominant Negative Hyper-IgE Syndrome: A Patient Report with Actionable Genomic Findings.

hyper-IgE syndrome

Overview

Clinical Presentation

Clinical Guidance

Presentation

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Orphan Drug Designations

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

Orphanet

GARD

Subtypes

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Immunologic Characteristics

Differential Diagnosis

Management Guidelines

Therapies Under Investigation

Clinical Trials

Recent Publications

Latest News & Developments

STAT3 Dominant Negative Hyper-IgE Syndrome: A Patient Report with Actionable Genomic Findings.