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Primary Immune Deficiency Diseases (PIDDs)​

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Hyper-Immunoglobulin E Syndrome (HIES) or Job’s Syndrome

People with HIES have recurrent boils of the skin and lungs caused by bacterial infections. They also have an itchy skin rash (eczema), very high levels of a type of antibody called immunoglobulin E (IgE), and a tendency to experience bone fractures.

Causes

artwork of Job with boils
Folio 46r from the Syriac Bible of Paris depicting the biblical character Job suffering from boils. Credit: Wikimedia Commons

HIES may refer to two diseases that are caused by different genetic mutations, resulting in overlapping but distinct symptoms. Classic HIES is called autosomal dominant HIES (AD-HIES) and results from mutations in a gene that encodes a signaling molecule called STAT3. This molecule is involved in many different activities of the body, explaining why HIES affects facial appearance, bones, lungs, skin, and arteries. NIAID investigators identified the role of STAT3 in AD-HIES in 2007.

A distinct disease called DOCK8 deficiency is sometimes referred to as autosomal recessive HIES (AR-HIES). In 2009 however, NIAID researchers discovered that AR-HIES is a separate disease caused by mutations in the DOCK8 gene.

Signs and Symptoms

People with AD-HIES may have repeated bacterial abscesses, or boils, of the skin and lungs. These infections are often caused by Staphylococcus aureus but also may be caused by other bacteria and fungi. Furthermore, people with AD-HIES have recurrent bone fractures, flexible joints, and inflamed skin. Their baby teeth often do not fall out on their own. In 2008, NIAID scientists discovered that important immune cells, Th17 cells, are missing in people with AD-HIES. In 2011, NIAID researchers also identified why people with AD-HIES are more susceptible to viral infections.

People with AD-HIES often have distinctive facial characteristics, such as the following:

  • Uneven facial features
  • Prominent forehead
  • Deep-set eyes
  • Broad nasal bridge
  • Wide, fleshy nose tip
  • Protruding lower jaw

DOCK8 deficiency, like AD-HIES, also results in recurrent skin and lung infections. However, people with DOCK8 deficiency do not typically have the joint, bone, and facial changes that are seen in AD-HIES. In addition, those with DOCK8 deficiency frequently have viral skin infections, such as warts, and have a higher incidence of cancers, such as squamous cell carcinomas and lymphomas. In 2014, NIAID researchers discovered that DOCK8 is required to mobilize immune cells in the skin, accounting for the distinct skin infections seen in people with DOCK8 deficiency.

Diagnosis

A doctor will suspect AD-HIES in a person with eczema, recurrent boils, and pneumonias.

Blood tests diagnosing AD-HIES will show normal levels of IgG, IgA, and IgM antibodies but very high levels of IgE antibodies. They also may show a high number of white blood cells called eosinophils and a poor response to immunizations.

Treatment

The most effective treatment for AD-HIES is continuous antibiotics and antifungals as needed. Some receive antibody replacement therapies. Antiseptic baths or washes, such as dilute bleach baths, are often helpful to prevent skin infections and improve eczema. Watch an NIAID video on wet-wrap therapy.

Bone marrow transplantation is frequently recommended for DOCK8 deficiency.

Last Updated February 18, 2015

Last Reviewed February 18, 2015