Hyperimmunoglobulin E syndrome

Hyper-IgE syndrome
Classification and external resources
Specialty
ICD-10	D82.4
ICD-9-CM	288.1
OMIM	243700 147060
DiseasesDB	29572
MedlinePlus	001311
eMedicine	derm/845 ped/1074
Patient UK	Hyperimmunoglobulin E syndrome
MeSH	D007589

Hyperimmunoglobulinemia E syndrome (HIES), of which the autosomal dominant form is called Job's syndrome or Buckley syndrome, is a heterogeneous group of immune disorders.

Presentation

It is characterized by recurrent "cold" staphylococcal infections, unusual eczema-like skin rashes, severe lung infections that result in pneumatoceles (balloon-like lesions that may be filled with air or pus or scar tissue) and very high concentrations of the serum antibody IgE. Inheritance can be autosomal dominant or autosomal recessive. Many patients with autosomal dominant STAT3 hyper-IgE syndrome have characteristic facial and dental abnormalities, fail to lose their primary teeth, and have two sets of teeth simultaneously.

History

HIES was first described by Davis et al. in 1966 in two girls with red hair, chronic dermatitis, and recurrent staphylococcal abscesses and pneumonias. They named the disease after the biblical figure Job, whose body was covered with boils by Satan. In 1972, Buckley et al. described two boys with similar symptoms as well as coarse facies, eosinophilia, and elevated serum IgE levels. These two syndromes are thought to be the same and are under the broad category of HIES.

Pathophysiology

Abnormal neutrophil chemotaxis due to decreased production of interferon gamma by T lymphocytes is thought to cause the disease.

Both autosomal dominant and recessive inheritance have been described:

Autosomal dominant:

• STAT3 may present as HIES with characteristic facial, dental, and skeletal abnormalities that has been called Job's Syndrome. A common mnemonic used to remember the symptoms is FATED: coarse or leonine facies, cold staph abscesses, retained primary teeth, increased IgE, and dermatologic problems [eczema]. The disease was linked to mutations in the STAT3 gene after cytokine profiles indicated alterations in the STAT3 pathway.

Autosomal recessive:

• DOCK8 - DOCK8 Immunodeficiency Syndrome (DIDS) presents primarily with immune effects including HEIS. Eczema is prominent, food and environmental allergies are common, and asthma and anaphylaxis has been variably reported.
• PGM3, a Congenital Disorder of Glycosylation, may present as HIES with neurocognitive impairment and hypomyelination. See PGM3 deficiency.
• SPINK5 may present as HIES with skin and hair effects such as trichorrhexis invaginata (bamboo hair). See Netherton Syndrome (NTS).
• TYK2 may present as HIES, although more often only with immunodeficiency.

Laboratory studies

Elevated IgE is the hallmark of HIES. An IgE level greater than 2,000 IU/mL is often considered diagnostic. However, patients younger than 6 months of age may have very low to non-detectable IgE levels. Eosinophilia is also a common finding with greater than 90% of patients having eosinophil elevations greater than two standard deviations above the normal mean. Genetic testing is available for STAT3 (Job's Syndrome), DOCK8 (DOCK8 Immunodeficiency or DIDS), PGM3 (PGM3 deficiency), SPINK5 (Netherton Syndrome - NTS), and TYK2 genetic defects.

Clinical characteristics

HIES often appears early in life with recurrent staphylococcal and candidal infections, pneumonias, and eczematoid skin.

Autosomal dominant Hyper-IgE Syndrome caused by STAT3 defects, called Job's Syndrome, have characteristic facial, dental, and skeletal abnormalities. Patients with STAT3 HIES may have either delay of or failure in shedding of primary teeth. The characteristic facial features are usually set by age 16. These include facial asymmetry, a prominent forehead, deep-set eyes, a broad nasal bridge, a wide, fleshy nasal tip, and mild prognathism. Additionally, facial skin is rough with prominent pores. Finally, some patients with STAT3 HIES have scoliosis, as well as bones that fracture easily.

Treatment

Most patients with hyper IgE syndrome are treated with chronic antibiotics to help protect them from staphylococcal infections. Good skin care is also important in patients with hyper IgE syndrome. High-dose intravenous gamma-globulin has also been suggested for the treatment of severe eczema in patients with HIES and atopic dermatitis.

See also

• Isolated primary immunoglobulin M deficiency
• List of cutaneous conditions
• List of dental abnormalities associated with cutaneous conditions

External links

• U.S. NIH Genetic Test Registry
• GeneDx Hyper-IgE Syndrome Panel HIES information sheet
• National Organization for Rare Disorders: Autosomal Dominant Hyper IgE Syndrome Autosomal Recessive Hyper IgE Syndrome
• U.S. National Institutes of Health (NIH): Clinical Research Studies: National Institute of Allergy and Infectious Diseases (NIAID) (observational) study number 00-I-0159: Natural History, Management, and Genetics of the hyperimmunoglobulin E Recurrent Infection syndrome (HIES) - NCT00006150