Hyperimmunoglobulin E syndrome
| Hyper-IgE syndrome | |
|---|---|
| Other names | HIES |
 | |
| The structure of the Immunoglobulin E (IgE) antibody. | |
| Specialty | Immunology  |
Hyperimmunoglobulinemia E syndrome is a heterogeneous group of immune disorders. Job's is also very rare at about 300 cases currently in the literature.
Presentation
It is characterized by recurrent "
Pathophysiology
Abnormal neutrophil chemotaxis due to decreased production of interferon gamma by T lymphocytes is thought to cause the disease.[6]
Both
- 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.[10] This altered pathway directly reduces the modulation capacity of interleukins 6 and 10 which, respectively, inhibit the genesis of Th17 cells that, in tandem with CD4 cells, protect against bacterial and fungal infections, and foster the inappropriate immune responses exhibited by those with Job Syndrome.[11]
- PGM3, a Congenital Disorder of Glycosylation, may present as HIES with neurocognitive impairment and hypomyelination. See PGM3 deficiency.[14]
- 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,[15] although more often only with immunodeficiency.[16]
Diagnosis
Elevated IgE is the hallmark of HIES. An IgE level greater than 2,000 IU/mL is often considered diagnostic.
Types
HIES often appears early in life with recurrent staphylococcal and candidal infections, pneumonias, and eczematoid skin.[20]
- Autosomal dominant Hyper-IgE Syndrome caused by STAT3 defects, called Job 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.[18]
- Autosomal recessive[5]
Treatment
Most patients with hyper IgE syndrome are treated with long-term
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.[22] 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.[23]
See also
- Isolated primary immunoglobulin M deficiency
- List of cutaneous conditions
- List of dental abnormalities associated with cutaneous conditions
References
- ^ ISBN 978-1-4160-2999-1.
- ^ "hyperimmunoglobulinemia E syndrome" at Dorland's Medical Dictionary
- ^ "Hyper-IgE Syndrome". Merck Manual. Merck Sharp & Dohme Corp. Retrieved 3 August 2021.
- ^ Dermatologic Manifestations of Job Syndrome at eMedicine
- ^ PMID 18424333.
- PMID 10657822.
- ^ PMID 23283142.
- PMID 19190525.
- PMID 23283142.
- PMID 17881745.
- PMID 30247822, retrieved 2021-11-28
- PMID 19776401.
- PMID 24840882.
- S2CID 24566050.
- PMID 17088085.
- PMID 26304966.
- ISBN 9780071621519.
- ^ PMID 10053178.
- PMID 36703986.
- ^ "Hyper IgE syndrome". Immune Deficiency Foundation. August 9, 2023. Retrieved October 14, 2023.
- PMID 7897163.
- PMID 4161105.
- S2CID 245107427.
Further reading
- U.S. NIH Genetic Test Registry
- 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