Hyper-IgE syndrome (Job syndrome) !

A rare inherited immune disorder with eczema, skin boils, repeated pneumonias that leave lung cysts, very high IgE and baby teeth that do not fall out.

Updated 2026-11-01

Structures involved

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Why it happens

What it is

A primary immunodeficiency, classically autosomal dominant and caused by STAT3 variants, characterised by the triad of recurrent staphylococcal skin abscesses, recurrent pneumonia with pneumatoceles, and very high serum IgE, together with eczema, chronic mucocutaneous candidiasis and connective tissue, skeletal and dental abnormalities.

Who gets it

Very rare, fewer than 1 per million people, with no sex or ethnic predilection. Symptoms start in the newborn period or infancy with a rash, followed by infections in childhood. Most STAT3 cases are new (de novo) variants.

Causes

Dominant-negative variants in STAT3 (autosomal dominant hyper-IgE syndrome, Job syndrome)
Similar recessive syndromes: ZNF341 and DOCK8 deficiency (DOCK8 adds severe viral skin infections, allergy and cancer)

Risk factors

Parent with a STAT3 variant (50% transmission risk)
Consanguinity for the recessive forms

Pathophysiology

STAT3 transmits signals from several cytokines, including IL-6 and IL-23. Without it, T helper 17 (Th17) cells do not develop, so IL-17 and IL-22 are lacking and keratinocytes and airway epithelium cannot recruit neutrophils or make antimicrobial peptides against Staphylococcus aureus and Candida. Infections cause little warmth, redness or systemic inflammation (cold abscesses). Lung tissue heals abnormally after pneumonia, forming pneumatoceles and bronchiectasis that become colonised by Aspergillus and Pseudomonas. Altered STAT3 signalling in bone, teeth and vessels causes osteopenia, retained primary teeth and arterial aneurysms. IgE rises for reasons not fully understood.

Classification

Autosomal dominant (STAT3) hyper-IgE syndrome: classic Job syndrome
Autosomal recessive forms: ZNF341 deficiency (similar to STAT3) and DOCK8 deficiency (combined immunodeficiency)

Symptoms and signs

Eczematous rash starting in the newborn period or early infancy
Recurrent staphylococcal skin boils and abscesses with little redness, warmth or pain (cold abscesses)
Recurrent bacterial pneumonia with few systemic symptoms, leaving pneumatoceles
Chronic mucocutaneous candidiasis of the mouth and nails
Characteristic face that becomes coarse with age: broad nose, prominent forehead, deep-set eyes
Retained primary teeth, joint hypermobility, scoliosis and fractures after minor trauma

Diagnosis

Clinical: Suspect it in a child with newborn eczema, recurrent skin abscesses and pneumonias with pneumatoceles. Scoring systems that weigh IgE level, infections, facial and dental features help estimate probability.
Tests: Very high serum IgE (often over 2,000 IU/mL) with eosinophilia; cultures of abscesses (Staphylococcus aureus); reduced Th17 cells by flow cytometry; genetic testing for STAT3 (and DOCK8 or ZNF341 if recessive features).
Imaging: Chest CT for pneumatoceles, bronchiectasis and fungal infection; spine imaging for scoliosis; bone density testing; dental assessment of retained primary teeth.

Differential diagnosis

Severe atopic dermatitis (also high IgE, but no pneumatoceles or cold abscesses)
Chronic granulomatous disease
DOCK8 deficiency
Wiskott-Aldrich syndrome
Cystic fibrosis

Goal of treatment

Prevent and treat staphylococcal and fungal infections, protect the lungs, control eczema and manage skeletal and dental problems.

Treatment

Medical: Long-term antistaphylococcal antibiotic prophylaxis, often trimethoprim-sulfamethoxazole; antifungal prophylaxis when lung cysts are present or candidiasis recurs.
Medical: Early treatment of infections even when the patient looks well, because signs of inflammation are blunted.
Conservative: Skin care for eczema: emollients, topical anti-inflammatories and antiseptic measures such as dilute bleach baths.
Surgical: Drainage of abscesses; lung surgery for persistent pneumatoceles is avoided when possible because healing is poor.
Procedure: Dental extraction of retained primary teeth; immunoglobulin replacement in some patients with poor antibody responses; stem cell transplantation for DOCK8 deficiency and selected STAT3 cases.
Follow-up: Monitoring: lung imaging, scoliosis and bone health, and surveillance for aneurysms and lymphoma.

Complications

Pneumatoceles and bronchiectasis colonised by Aspergillus or Pseudomonas
Haemoptysis
Scoliosis, osteopenia and minimal-trauma fractures
Coronary and cerebral artery aneurysms
Non-Hodgkin lymphoma
Chronic candidiasis

Prognosis

With prophylactic antimicrobials and close lung care, many patients survive into adulthood. Chronic lung disease with fungal infection is the main cause of illness and death.

Prevention

Genetic counselling for affected families
Antimicrobial prophylaxis to prevent recurrent infections

Test yourself

Think of the answer, then tap the question to see it.

Which gene is mutated in autosomal dominant hyper-IgE (Job) syndrome?

STAT3.

What is the classic triad?

Recurrent staphylococcal (cold) skin abscesses, recurrent pneumonia with pneumatoceles and very high serum IgE.

Why are the abscesses 'cold'?

Th17 cells are lacking, so neutrophil recruitment and inflammation are weak.

What dental finding is typical?

Retained primary (baby) teeth because they fail to shed.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: Autosomal dominant hyper-IgE syndrome (MedlinePlus Genetics (U.S. National Library of Medicine), 2019).

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