Hyper IgE syndrome is an immunodeficiency disorder that causes high IgE levels, recurring infections, and severe eczema. It’s caused by genetic changes that affect the way the immune system functions.

Your immune system makes proteins called immunoglobulins in order to protect you from potentially harmful foreign substances. There are five different types of immunoglobulins, or antibodies.

Immunoglobulin E (IgE) is a type of antibody that’s mainly involved in allergic conditions like asthma, eczema, and food allergies. It also helps your body respond to parasitic infections.

Having too many or too few immunoglobulins can cause problems throughout the body. One example is hyper IgE syndrome, a group of rare conditions associated with too much IgE, recurring infections, and eczema.

Hyper IgE syndrome (HIES) has three key features.

High IgE levels

People with HIES have very high levels of IgE, often measured at 2,000 IU/ml. For reference, the typical range of IgE for an adult is below 140 IU/ml.

It’s also common for people with HIES to have high levels of eosinophils, a type of white blood cell that’s also involved in allergic conditions.

Recurring infections

HIES is associated with recurring infections. These infections are often caused by Staphylococcus aureus bacteria and include recurrent pneumonia and skin abscesses.

Examples of other infections that can happen frequently in HIES include:

Eczema

The last key feature of HIES is severe eczema, a skin condition characterized by patches of dry, itchy, and inflamed skin. In many cases, eczema related to HIES appears very early — just a few weeks after birth.

What are other signs and symptoms of HIES?

Individuals with HIES can have other health issues as well. These can vary based on the type of HIES, but may include:

  • lung abnormalities like a widening of the bronchi (bronchiectasis) or air-filled cysts (pneumatocele)
  • bones that break easily

HIES is a primary immunodeficiency disorder. That means that the issues with the immune system in HIES are present from birth.

HIES is caused by genetic changes that may occur randomly during development or be inherited. When HIES is inherited, it’s either in an autosomal dominant or autosomal recessive manner, depending on the type of genetic change.

Examples of genes that may be associated with HIES include:

  • STAT3
  • ZNF341
  • IL6ST
  • IL6R
  • PGM3

On a basic level, these genes are involved in various aspects of immune system development, signaling, or regulation. As such, harmful changes in these genes can lead to the immune issues seen in HIES.

Overall, HIES is rare. It’s estimated to impact only 1 in 100,000 to 1,000,000 people worldwide.

Diagnosing HIES can be difficult, both due to its rarity and the wide spectrum of signs and symptoms it can cause. Many of the symptoms of HIES overlap with those of other immunodeficiency disorders.

A doctor will make a diagnosis based on the observed signs and symptoms as well as test results. For example, they’ll be looking for the three key features of HIES:

  • high IgE levels, measured using a blood test
  • recurring infections that impact the lungs and skin
  • severe eczema

Additional tests that may be done to help diagnose HIES include:

  • complete blood count to check for high eosinophil levels
  • genetic testing
  • imaging to check for lung and bone abnormalities

Some diagnostic criteria for HIES due to mutations in STAT3 have been proposed. This includes a scoring system where a higher score correlates with the presence of HIES.

There’s currently no cure for HIES. Treatment involves long-term management of its different symptoms.

HIES is typically managed with medications. Additionally, certain lifestyle changes may also help people with HIES.

Medications to treat hyper IgE syndrome

Individuals with HIES often take antibiotics to help reduce the risk of infections or to limit their severity, should an infection occur. A type of antibiotic commonly used is trimethoprim‐sulfamethoxazole.

Antifungal treatments may be used to treat fungal infections like thrush. Intravenous immunoglobulin (IVIG) treatments can also help to manage infections in people with HIES.

Some biologic medications, such as omalizumab (Xolair) and dupilumab (Dupixent), have shown effectiveness at managing aspects of HIES like eczema and inflammation.

Bone marrow transplants may also be used for people with certain types of HIES, such as those with genetic changes in STAT3. However, results have been mixed.

Lifestyle changes that can help with hyper IgE syndrome

A variety of lifestyle changes can help to ease some of the skin symptoms of HIES and prevent infections. These include:

  • applying a topical moisturizing cream to eczema patches
  • using disinfectant baths containing diluted bleach or chlorohexidine
  • avoiding scratching at eczema patches

General infection control measures are also important. These include things like:

  • frequent handwashing
  • not sharing personal items like cups, eating utensils, or towels
  • avoiding people who are currently sick

Some types of HIES can also cause bone abnormalities, such as bones that break easily. Ensuring adequate intake of vitamin D and calcium can help boost bone health.

HIES is an immunodeficiency disorder that’s present from birth. It has three key features: high IgE levels, recurring infections, and severe eczema.

HIES is caused by genetic changes in a variety of genes that affect immune system function. These changes can occur randomly during development or be inherited.

HIES is a long term condition with no cure currently. However, treatment focuses on managing its various symptoms and preventing complications. Lifestyle changes can also help to prevent infections in people with HIES.