Hyper-IgE Syndrome

Reference work entry

Hyper-IgE syndrome (HIES) is a rare, hereditary multisystem disorder characterized clinically by hyperimmunoglobulinemia E, recurrent infections, and eczematoid dermatitis. In 1966, Job reported two patients with eczematous dermatitis, recurrent staphylococcal boils, hyperextensible joints, and distinctive coarse facies. In 1972, Buckley et al. expanded the clinical picture by adding elevated immunoglobulin E (IgE).

Synonyms and Related Disorders

Job syndrome

Genetics/Basic Defects

  1. 1.
    Inheritance (Erlewyn-Lajeunnesse 2000)
    1. a.

      Autosomal dominant with variable penetrance and expressivity

    2. b.

      Linkage to a region on chromosome 4q21demonstrated in several affected families

    3. c.

      An upregulating mutation in the interleukin-4 receptor gene on chromosome 16, demonstrated in some patients with hyper-IgE syndrome

    4. d.

      Autosomal recessive hyper-IgE syndrome: a similar but distinct syndrome reported by Renner et al. (2004)

  2. 2.
    Autosomal dominant hyper-IgE syndrome (AD-HIES): caused by...


Preimplantation Genetic Diagnosis Root Resorption Otitis Externa Molluscum Contagiosum Coarse Facies 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Buckley, R. H. (2001). The hyper-IgE syndrome. Clinical Reviews in Allergy & Immunology, 20, 139–154.CrossRefGoogle Scholar
  2. Buckley, R. H., Wray, B. B., & Belmaker, E. Z. (1972). Extreme hyperimmunoglobulin E and undue susceptibility to infection. Pediatrics, 49, 59–70.PubMedGoogle Scholar
  3. Chamlin, S. L., McCalmont, T. H., Cunningham, B. B., et al. (2002). Cutaneous manifestations of hyper-IgE syndrome in infants and children. Journal of Pediatrics, 141, 572–575.PubMedCrossRefGoogle Scholar
  4. Chehimi, J., Elder, M., Greene, J., et al. (2001). Cytokine and chemokine dysregulation in hyper-IgE syndrome. Clinical Immunology, 100, 49–56.PubMedCrossRefGoogle Scholar
  5. Dahl, M. V. (2002). Hyper-IgE syndrome revisited. International Journal of Dermatology, 41, 618–619.PubMedCrossRefGoogle Scholar
  6. Dau, P. C. (1988). Remission of hyper-IgE treated with plasmapheresis and cytotoxic immunosuppression. Journal of Clinical Apheresis, 4, 8–12.PubMedCrossRefGoogle Scholar
  7. Davis, S. D., Schaller, J., & Wedgwood, R. J. (1966). Job’s syndrome: Recurrent, “cold,” staphylococcal abscesses. Lancet, 1, 1013–1015.PubMedCrossRefGoogle Scholar
  8. Donabedian, H., & Gallin, J. I. (1983). The hyperimmunoglobulin E recurrent –infection (Job’s) syndrome: a review of the NIH experience and the literature. Medicine, 62, 195–208.PubMedCrossRefGoogle Scholar
  9. Engelhardt, K. R., McGhee, S., Winkler, S., et al. (2009). Large deletions and point mutations involving the dedicator of cytokinesis 8 (DOCK8) in the autosomal-recessive form of hyper-IgE syndrome. The Journal of Allergy and Clinical Immunology, 124, 1289–1302.PubMedCrossRefGoogle Scholar
  10. Erlewyn-Lajeunesse, M. D. S. (2000). Hyperimmunoglobulin-E syndrome with recurrent infection: A review of current opinion and treatment. Pediatric Allergy and Immunology, 11, 133–141.PubMedCrossRefGoogle Scholar
  11. Freeman, A. F., Collura-burke, C. J., Patronas, N. J., et al. (2007). Brain abnormalities in patients with hyperimmunoglobulin E syndrome. Pediatrics, 119, e1121–e1125.PubMedCrossRefGoogle Scholar
  12. Freeman, A.F., Davis, J., Hsu, A.P., et al (2010). Autosomal dominant IgE syndrome. GeneReviews. Initial posting February 23, 2010. Available at:
  13. Freeman, A., & Holland, S. M. (2009). Clinical manifestations, etiology, and pathogenesis of the hyper-IgE syndrome. Pediatric Research, 65, 32R–37R.PubMedCrossRefGoogle Scholar
  14. Gatz, S. A., Benninghoff, U., & Schütz, C. (2010). Curative treatment of autosomal-recessive hyper-IgE syndrome by hematopoietic cell transplantation. Bone Marrow Transplantation, 46, 552–554.Google Scholar
  15. Gennery, A. R., Flood, T. J., Abinun, M., et al. (2000). Bone marrow transplantation does not correct the hyper IgE syndrome. Bone Marrow Transplantation, 25, 1303–1305.PubMedCrossRefGoogle Scholar
  16. Grimbacher, B., Holland, S. M., Gallin, J. I., et al. (1999a). Hyper-IgE syndrome with recurrent infections–an autosomal dominant multisystem disorder. The New England Journal of Medicine, 340, 692–702.PubMedCrossRefGoogle Scholar
  17. Grimbacher, B., Schaffer, A. A., Holland, S. M., et al. (1999b). Genetic linkage of hyper-IgE syndrome to chromosome 4. The American Journal of Human Genetics, 65, 735–744.CrossRefGoogle Scholar
  18. Holland, S. M., DeLeo, F. R., Elloumi, H. Z., et al. (2007). STAT3 mutations in the hyper-IgE syndrome. The New England Journal of Medicine, 357, 1608–1619.PubMedCrossRefGoogle Scholar
  19. Jhaveri, K. S., Sahani, D. V., Shetty, P. G., et al. (2000). Hyperimmunoglobulinaemia E syndrome: Pulmonary imaging features. Australasian Radiology, 44, 328–330.PubMedCrossRefGoogle Scholar
  20. Jiao, H., Toth, B., Fransson, I., et al. (2008). Novel and recurrent STAT3 mutations in hyper-IgE syndrome patients from different ethnic groups. Molecular Immunology, 46, 202–206.PubMedCrossRefGoogle Scholar
  21. Khurana-Hershey, G. K., Friedrich, M. F., Esswein, L. A., et al. (1997). The association of atopy with a gain of function mutation in the alpha subunit of the interleukin-4 receptor. The New England Journal of Medicine, 337, 1720–1725.CrossRefGoogle Scholar
  22. Kikkawa, Y., Kamimura, K., Hamajima, T., et al. (1973). Thymic alymphoplasia with hyper-IgE-globulinemia. Pediatrics, 51, 690–696.PubMedGoogle Scholar
  23. Kimata, H. (1995). High-dose intravenous gamma-globulin treatment for hyperimmunoglobulin E syndrome. The Journal of Allergy and Clinical Immunology, 95, 771–774.PubMedCrossRefGoogle Scholar
  24. Mawhinney, H., Killen, M., Fleming, W. A., et al. (1980). The hyperimmunoglobulin E syndrome-a neutrophil chemotactic defect reversible by histamine H2 receptor blockade? Clinical Immunology and Immunopathology, 17, 483–491.PubMedCrossRefGoogle Scholar
  25. Minegishi, Y., Saito, M., Morio, T., et al. (2006). Human tyrosine kinase 2 deficiency reveals its requisite roles in multiple cytokine signals involved in innate and acquired immunity. Immunity, 25, 745–755.PubMedCrossRefGoogle Scholar
  26. Minegishi, Y., Saito, M., & Tsuchiya, S. (2007). Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome. Nature, 448, 1058–1062.PubMedCrossRefGoogle Scholar
  27. Nester, T. A., Wagnon, A. H., Reilly, W. F., et al. (1998). Effects of allogeneic peripheral stem cell transplantation in a patient with Job syndrome of hyperimmunoglobulinemia E and recurrent infections. The American Journal of Medicine, 105, 162–164.PubMedCrossRefGoogle Scholar
  28. Ochs, H. D., Kraemer, M. J., Lindgren, C. G., et al. (1983). Immune regulation in the hyper-IgE/Job syndrome. Birth Defects Original Article Series, 19, 57–61.PubMedGoogle Scholar
  29. Ohga, S., Nomura, A., Ihara, K., et al. (2003). Cytokine imbalance in hyper-IgE syndrome: Reduced expression of transforming growth factor beta and interferon gamma genes in circulating activated T cells. British Journal of Haematology, 121, 324–331.PubMedCrossRefGoogle Scholar
  30. Paganelli, R., Quinti, I., Carbonari, M., et al. (1986). IgG anti-IgE in circulating immune complexes in the hyper-IgE syndrome. Clinical Allergy, 16, 513–521.PubMedCrossRefGoogle Scholar
  31. Renner, E. D., Puck, J. M., Holland, S. M., et al. (2004). Autosomal recessive hyperimmunoglobulin E syndrome: A distinct disease entity. Journal of Pediatrics, 144, 93–99.PubMedCrossRefGoogle Scholar
  32. Renner, E. D., Ryalaarsdam, S., Anover-Sombke, S., et al. (2008). Novel signal transducer and activator of transcription 3 (STAT3) mutations, reduced T(H)17 cell numbers, and STAT3 phosphorylation in hyper-IgE syndrome. The Journal of Allergy and Clinical Immunology, 122, 181–187.PubMedCrossRefGoogle Scholar
  33. Ring, J., & Landthaler, M. (1989). Hyper-IgE syndromes. Current Problems in Dermatology, 18, 79–88.PubMedGoogle Scholar
  34. Shemer, A., Weiss, G., Confino, Y., et al. (2001). The hyper-IgE syndrome. Two cases and review of the literature. International Journal of Dermatology, 40, 622–628.PubMedCrossRefGoogle Scholar
  35. Thompson, R. A., & Kumararatne, D. S. (1989). Hyper-IgE syndrome and H2-recptor blockade. Lancet, 2, 630.PubMedCrossRefGoogle Scholar
  36. Vercelli, D., Jabara, H. H., Cunningham-Rundles, C., et al. (1990). Regulation of immunoglobulin (Ig)E synthesis in the hyper-IgE syndrome. The Journal of Clinical Investigation, 85, 1666–1671.PubMedCrossRefGoogle Scholar
  37. Wakim, M., Alazard, M., Yajima, A., et al. (1998). High dose intravenous immunoglobulin in atopic dermatitis and hyper-IgE syndrome. Annals of Allergy, Asthma & Immunology, 81, 153–158.CrossRefGoogle Scholar
  38. Woellner, C., Schaffer, A. A., Puck, J. M., et al. (2007). The hyper IgE syndrome and mutations in Tyk2. Immunity, 26, 535.PubMedCrossRefGoogle Scholar
  39. Yavuz, H., & Chee, R. (2009). A review on the vascular features of the hyperimmunoglobulin E syndrome. Clinical and Experimental Immunology, 159, 238–244.PubMedCrossRefGoogle Scholar
  40. Yokota, S., Mitsuda, T., Shimizu, H., et al. (1990). Cromoglycate treatment of a patient with Hyperimmunoglobulin E syndrome. Lancet, 335, 857–858.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Personalised recommendations