Hyper Ige Syndrome (job's Syndrome)

Beatriz Morillo-Gutiérrez
Primary Immunodeficiencies Paediatric Infectious Diseases Consultant
Translational Paediatrics and Infectious Diseases
Santiago de Compostela University Hospital
A Choupana, 15706, Santiago de Compostela, Spain

First Created: 04/02/2002  Last Updated: 09/05/2018

Patient Education

What is Hyper IgE syndrome?

Hyper IgE syndrome (HIES) is also known as Job's syndrome. It comprises a group of primary immunodeficiency where recurrent skin and lung infections, eczema, and sometimes allergies are seen.

What are the symptoms of Hyper IgE syndrome?

Symptoms of Job's syndrome include eczema, recurrent abscesses, pneumonia, and recurrent candida infections. Eczema usually occurs in the creases behind the ears, the back, buttocks, and scalp. Boils and abscesses are commonly caused by bacteria called as Staphylococcal aureus. Patients can also have recurrent sinusitis, otitis media, and ear infections. Pneumonia in patients with Hyper IgE syndrome leads to cavities in the lung (pneumatoceles) or scarring of the lower air passages (bronchiectasis).

Adolescents have a prominent forehead and chin, broad nose, and thickened facial skin with lax joints. Fractures are common due to weak bones. Scoliosis (curved spine) is common. Primary teeth are retained for a longer time which in turn prevents eruption of the permanent teeth.

Other features depending on the underlying gene defect can be increased susceptibility to cutaneous viral infections and severe manifestations of allergy.

What is the cause of Hyper IgE syndrome?

Hyper IgE syndrome is rare with less than 850 cases reported worldwide. It affects both boys and girls equally. So far, there have been 4 mutations linked to this syndrome, but in some cases, the genetic mutation has not been identified.

Does Hyper IgE syndrome run in families?

There is a type of Hyper IgE syndrome, which runs in families due to mutations in a gene on chromosome 4. This kind of Hyper IgE syndrome is acquired by autosomal dominant inheritance whereby if one of the parents is affected, then chances of passing the abnormal gene to the child is about 50%.

For the other 3 mutations, they run in an autosomal recessive manner, this is, the chances to have the condition is 25%, increasing if the parents are family between them.

How is the diagnosis of Hyper IgE syndrome made?

Measuring IgE levels is one of the laboratory tests used for the diagnosis of Hyper IgE syndrome. Usually, patients with Hyper IgE syndrome have levels above 1000-2000 IU/ml. The presence of other clinical features such as boils, pneumonia, teeth abnormalities helps to reach the diagnosis.

Elevated IgE levels may be seen in other conditions such as severe allergies and thus results must be interpreted with clinical features, and ultimately, a genetic test should be done.

What is the treatment of Hyper IgE syndrome?

Depending on the underlying condition causing the HIES, the treatment could differ. For some of these patients, skincare and prompt treatment of infections are essential. Eczema can be treated with moisturizing creams. Fungal infections can be treated with antifungals and bacterial with antibiotics, including prophylaxis or long term treatment if needed. For some conditions, hematopoietic stem cell transplant should be done in a special unit.

What are complications of Hyper IgE syndrome?

Patients with Job's syndrome are at increased risk of certain types of cancers such as lymphoma or autoimmune diseases such as systemic lupus erythematosus (SLE). They can have as well chronic problems in the lungs secondary to the scarring of pneumonia, such as bronchiectasis.

1. Grimbacher B, Schäffer AA, Holland SM, Davis J, Gallin JI, Malech HL, et al. Genetic linkage of hyper-IgE syndrome to chromosome 4. Am J Hum Genet. 1999 Sep;65(3):735–44.
2. Minegishi Y, Saito M, Morio T, Watanabe K, Agematsu K, Tsuchiya S, et al. Human Tyrosine Kinase 2 Deficiency Reveals Its Requisite Roles in Multiple Cytokine Signals Involved in Innate and Acquired Immunity. Immunity. 2006 Nov;25(5):745–55.
3. Watford WT, O’Shea JJ. Human tyk2 kinase deficiency: another primary immunodeficiency syndrome. Immunity 2006;25:695–697.
4. Freeman AF, Holland SM. Clinical Manifestations, Etiology, and Pathogenesis of the Hyper-IgE Syndromes. Pediatr Res. 2009 May;65(5 Part 2):32R–37R.
5. Woellner C, Gertz EM, Schäffer AA, Lagos M, Perro M, Glocker E-O, et al. Mutations in STAT3 and diagnostic guidelines for hyper-IgE syndrome. Journal of Allergy and Clinical Immunology. 2010 Feb;125(2):424–432.e8.
6. Su HC, Jing H, Zhang Q. DOCK8 deficiency. Ann N Y Acad Sci. 2011 Dec;1246(1):26–33.
7. Zhang Y, Yu X, Ichikawa M, et al. Autosomal recessive phosphoglucomutase 3 (PGM3) mutations link glycosylation defects to atopy, immune deficiency, autoimmunity, and neurocognitive impairment. J Allergy Clin Immunol 2014;133:1400–1409.
8. Sassi A, Lazaroski S, Wu G, et al. Hypomorphic homozygous mutations in phosphoglucomutase 3 (PGM3) impair immunity and increase serum IgE levels. J Allergy Clin Immunol 2014;133:1410–1419.
9. Mogensen TH. Primary Immunodeficiencies with Elevated IgE. Int Rev Immunol. 2015 May 13;1–18.
10. Williams KW, Milner JD, Freeman AF. Eosinophilia associated with disorders of immune deficiency or immune dysregulation. Immunol Allergy Clin North Am. 2015 Aug;35(3):523–44.
11. Shah NN, Freeman AF, Su H, Cole K, Parta M, Moutsopoulos NM, et al. Haploidentical Related Donor Hematopoietic Stem Cell Transplantation for Dedicator-of-Cytokinesis 8 Deficiency Using Post-Transplantation Cyclophosphamide. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 2017 Jun;23(6):980–90.
12. Biggs CM, Keles S, Chatila TA. DOCK8 deficiency: Insights into pathophysiology, clinical features and management. Clin Immunol. 2017 Aug;181:75–82.
13. Gennery AR, Marodi L, Ziegler JB, Español T, Grimbacher B. Other Well-Defined Immunodeficiencies. In: Primary Immunodeficiency Diseases [Internet]. Springer, Berlin, Heidelberg; 2017 [cited 2018 Jan 22]. p. 461–517. Available from: https://link.springer.com/chapter/10.1007/978-3-662-52909-6_9

Hyper Ige Syndrome (Job's Syndrome) Hyper Ige Syndrome (Job's Syndrome) https://www.pediatriconcall.com/show_article/default.aspx?main_cat=immunodeficiencies&sub_cat=hyper-ige-syndrome-jobs-syndrome&url=hyper-ige-syndrome-jobs-syndrome-patient-education 2018-09-05
Disclaimer: The information given by www.pediatriconcall.com is provided by medical and paramedical & Health providers voluntarily for display & is meant only for informational purpose. The site does not guarantee the accuracy or authenticity of the information. Use of any information is solely at the user's own risk. The appearance of advertisement or product information in the various section in the website does not constitute an endorsement or approval by Pediatric Oncall of the quality or value of the said product or of claims made by its manufacturer.
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0