Hyperimmunoglobulin E syndrome

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

Hyperimmunoglobulin E syndrome[1] (HIES), also called Job's syndrome[1] and Buckley syndrome,[1] is a heterogeneous group of immune disorders.


It is characterized by recurrent "cold" staphylococcal infections,[2] 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.[3] Many patients with autosomal dominant hyper IgE syndrome fail to lose their primary teeth and have two sets of teeth simultaneously.

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].


HIES was first described by Davis et al. in 1966 in two girls with red hair, chronic dermatitis, and recurrent staphylococcal abscesses and pneumonias.[4] They named the disease after the biblical character 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.[5]


Abnormal neutrophil chemotaxis due to decreased production of interferon gamma by T lymphocytes is thought to cause the disease.[6]

Both autosomal dominant and recessive inheritance have been described:

  • autosomal dominant, STAT3. The disease was linked to mutations in the STAT3 gene after cytokine profiles indicated alterations in the STAT3 pathway.[7]
  • autosomal recessive, DOCK8.[8]

Laboratory studies[edit]

Elevated IgE is the hallmark of HIES. An IgE level greater than 2,000 IU/mL is often considered diagnostic.[9] 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.[10]

Clinical characteristics[edit]

HIES often appears early in life with recurrent staphylococcal and candidal infections, pneumonias, and eczematoid skin. Characteristic facial, dental, and skeletal abnormalities have also been described. Patients with HIES 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 was rough with prominent pores. Finally, some patients have scoliosis, as well as bones that fracture easily.[10]


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.[11]

See also[edit]


  1. ^ a b c Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 1-4160-2999-0. 
  2. ^ "hyperimmunoglobulinemia E syndrome" at Dorland's Medical Dictionary
  3. ^ http://emedicine.medscape.com/article/1050852-overview
  4. ^ Davis S, Schaller J, Wedgwood R; Schaller; Wedgwood (1966). "Job's Syndrome. Recurrent, "cold", staphylococcal abscesses". Lancet 1 (7445): 1013–5. doi:10.1016/S0140-6736(66)90119-X. PMID 4161105. 
  5. ^ Buckley R, Wray B, Belmaker E; Wray; Belmaker (1972). "Extreme hyperimmunoglobulinemia E and undue susceptibility to infection". Pediatrics 49 (1): 59–70. PMID 5059313. 
  6. ^ Borges W, Augustine N, Hill H; Augustine; Hill (2000). "Defective interleukin-12/interferon-gamma pathway in patients with hyperimmunoglobulinemia E syndrome". J Pediatr 136 (2): 176–80. doi:10.1016/S0022-3476(00)70098-9. PMID 10657822. 
  7. ^ Holland SM, DeLeo FR, Elloumi HZ et al. (2007). STAT3 Mutations in the Hyper-IgE Syndrome. N. Engl. J. Med. published online, 2007-09-19. doi:10.1056/NEJMoa073687.
  8. ^ Zhang Q, Davis JC, Lamborn IT et al. (November 2009). "Combined immunodeficiency associated with DOCK8 mutations". N. Engl. J. Med. 361 (21): 2046–55. doi:10.1056/NEJMoa0905506. PMC 2965730. PMID 19776401. 
  9. ^ Ochs, HD; Notarangelo, LD (2010). Williams Hematology: Chapter 82. Immunodeficiency Diseases (8th ed.). New York: McGraw-Hill Medical. ISBN 9780071621519. 
  10. ^ a b Grimbacher B, Holland S, Gallin J, Greenberg F, Hill S, Malech H, Miller J, O'Connell A, Puck J; Holland; Gallin; Greenberg; Hill; Malech; Miller; O'Connell; Puck (1999). "Hyper-IgE syndrome with recurrent infections--an autosomal dominant multisystem disorder". N Engl J Med 340 (9): 692–702. doi:10.1056/NEJM199903043400904. PMID 10053178. 
  11. ^ Kimata H (1995). "High-dose intravenous gamma-globulin treatment for hyperimmunoglobulinemia E syndrome". J Allergy Clin Immunol 95 (3): 771–4. doi:10.1016/S0091-6749(95)70185-0. PMID 7897163.