Hyper IgE (Job) Syndrome

Hyper IgE syndrome (HIES) is a term for several rare genetic conditions that cause high levels of IgE antibodies, skin rashes and frequent infections. People with HIES also often have bone, connective tissue and blood vessel irregularities that can lead to serious complications, like stroke.

Talking about hyper IgE syndrome can get a bit confusing. Healthcare providers once diagnosed HIES in people who had high levels of IgE (an antibody that can cause allergies and rashes), frequent infections, eczema, distinctive facial features and bone and connective tissue issues. But not everyone diagnosed with HIES had all these symptoms, and some had additional health issues. Now, we know that many different gene changes can lead to similar symptoms.

Today, when providers talk about HIES, they often mean autosomal dominant hyper IgE syndrome (AD-HIES), or Job syndrome — it causes the original symptoms diagnosed as HIES. But they may also mean:

• Autosomal-recessive hyper IgE syndrome (AR-HIES): AR-HIES is caused by different gene changes from AD-HIES. It can share some of the same symptoms as AD-HIES, but can lead to many different symptoms, too.
• Other conditions: High levels of IgE can also be found in people with eczema and certain rare genetic conditions, like Wiskott-Aldrich syndrome.

If your child is diagnosed with hyper IgE, the important thing is that you and their provider understand their specific symptoms and risks.

Types

Hyper IgE syndrome can be autosomal dominant or autosomal recessive. They’re caused by different gene changes and can have different symptoms.

Autosomal-dominant hyper IgE syndrome (AD-HIES, Job syndrome)

AD-HIES fits the original definition of hyper-IgE syndrome. People with AD-HIES have frequent lung and skin infections. Specifically, they’re more likely to get bacterial and fungal infections, like Staphylococcus aureus (staph infections) and Candida (yeast infection). AD-HIES also causes bone and connective tissue changes that can alter your appearance as you grow, and blood vessel abnormalities. A change in the STAT3 gene causes AD-HIES.

Autosomal-recessive hyper IgE syndrome (AR-HIES)

While AR-HIES shares some similarities with AD-HIES, there are significant differences in symptoms. Compared to people with AD-HIES, people with AR-HIES:

• Don’t have bone changes and facial differences
• Have more severe and persistent eczema
• Get frequent and widespread viral infections in their skin (in addition to bacterial and fungal infections), which include molluscum contagiosum, herpes simplex and varicella-zoster
• Get frequent digestive tract infections
• Are more likely to have neurological complications, like facial paralysis and stroke
• Are more likely to get certain cancers, like lymphoma and squamous cell carcinoma (skin cancer), at an early age

A number of gene changes can cause AR-HIES. Changes in the DOCK8 gene are the most common. Many providers consider AR-HIES and AD-HIES to be separate conditions.

What are the symptoms of hyper IgE syndrome?

Signs and symptoms of hyper IgE syndrome include:

• Eczema or skin rashes
• Frequent bacterial or fungal skin infections (boils or ulcers)
• Frequent and widespread viral skin infections (warts)
• Frequent lung infections (pneumonia)
• Frequent digestive tract infections
• Air-filled pockets in your lungs (pneumatocele)
• Easily broken bones
• Distinctive facial features, like a broad nose or deep-set eyes
• Scoliosis
• Delayed loss of primary (“baby”) teeth
• High palate (roof of your mouth)
• Osteoporosis
• Joint hypermobility

The symptoms you have depend on the gene change that’s causing hyper IgE syndrome. Even in the same family, some people may experience different or milder symptoms than others.

Hyper IgE syndrome causes

A gene change (variation) causes hyper IgE syndrome. This means a difference in your DNA is giving your body the wrong instructions or preventing it from working as it should. In hyper-IgE syndrome, the gene change prevents your immune system from working properly. This means you can get infections more easily than other people. But experts aren’t sure why people with HIES have high levels of IgE.

Many gene changes can cause different forms of HIES. A change in the STAT3 gene causes AD-HIES (Job syndrome). STAT3 variants affect both your immune system and your bones. A change in DOCK8, TYK2, PGM3 or other genes can cause AR- HIES.

Most of the time, the change that causes HIES happens randomly (sporadic) — meaning you didn’t inherit it from a biological parent. But if you have HIES, you can pass it on to your biological children.

Risk factors

HIES can run in families. But the symptoms can vary, even in the same family. Having a relative with a form of HIES puts you at a higher risk. If you have AD-HIES, your biological children have a 50% chance of inheriting it.

Complications

HIES causes issues with your immune system, bones and blood vessels that can lead to additional health conditions. Some are life-threatening. Complications include:

• Aneurysm
• Arthritis
• Autoimmune diseases
• Facial paralysis
• Hemiplegia
• Lymphoma
• Squamous cell carcinoma
• Stroke

People with HIES are also at a higher risk of surgical complications — like poor wound healing, abnormal tissue healing and remodeling and increased risk of infection.

How is hyper IgE syndrome diagnosed?

Healthcare providers diagnose hyper IgE syndrome based on your symptoms and the results of blood tests. These may include:

• Tests to check your immune system, including IgE levels
• Imaging tests, like X-rays or CT scans, to look for changes in your bones or lungs
• Genetic testing for further evaluation (if you’re diagnosed with hyper IgE)

It’s important to note that high levels of IgE alone don’t mean you have hyper IgE syndrome. Many conditions, including eczema and allergies, can lead to high IgE levels in your blood.

How is hyper IgE syndrome treated?

Most treatments for HIES focus on symptom management and preventing infections. Depending on your symptoms and the type of HIES you have, treatments could include:

• Antibiotics and antifungal medications to help prevent and treat infections
• Antiviral medications to treat certain viral infections, like herpes simplex
• Immunoglobulin replacement therapy to help fight bacterial infections
• Topical corticosteroids to treat eczema
• Bisphosphonates to treat bone thinning
• Stem cell transplant

When should I see my healthcare provider?

Hyper IgE syndrome is rare. But it’s important to diagnose it as early as possible. If your child has frequent skin rashes, ulcers or boils, or if they get sick frequently, talk to their healthcare provider.

If you or your child has a hyper IgE diagnosis, talk to your provider if you have questions about any treatments you’re receiving, how to prevent infections and when to seek care.

It might be helpful to ask them:

• What type of HIES do I have/does my child have?
• What are my treatment options?
• What can I do to prevent infections?
• What should I do if I have signs of infection?

When should I go to the ER?

Go to the emergency room if you have symptoms of a severe infection, including:

• High fever (over 103 degrees Fahrenheit/40 degrees Celsius)
• Difficulty breathing
• Chest pain
• Coughing up blood
• A wound that’s very painful, not healing or getting larger
• Large bubbles or blisters that are red, brown, dark green or black
• Ulcers or sores filled with foul-smelling fluid

Having a weakened immune system means you might need to seek emergency care sooner than other people would. Ask your provider when you should go to the ER based on your specific situation.

What can I expect if I have hyper IgE syndrome?

If you or your child has hyper IgE syndrome, you’ll likely always have to be on the lookout for signs of infection. Your provider may prescribe antibiotics or antifungals to try to prevent infections and the complications that come with them.

Kids with HIES can sometimes be cured with a stem cell transplant. But there aren’t any large studies to track its effectiveness.

Depending on other health conditions — like bone or blood vessel issues — you may also need to take special precautions to prevent or recognize the signs of medical emergencies, like a stroke or aneurysm.

Since there are many conditions that can cause elevated IgE levels, people’s experiences can vary. Your team of healthcare providers can help you navigate your specific symptoms and health concerns. This team could include a:

• Primary care provider or your child’s pediatrician
• Immunologist (also called an allergist/immunologist)
• Vascular doctor or cardiologist
• Orthopedic surgeon
• Rheumatologist

What’s the life expectancy of someone with hyper IgE syndrome?

Since it’s so rare, we don’t know a lot about the life expectancy of people with hyper IgE syndrome. But thanks to a better understanding of HIES and ways to prevent and treat infections, many people with HIES live into adulthood if they get an early diagnosis.

How do I take care of myself with hyper IgE syndrome?

People with HIES have a weakened immune system and are more likely to get skin and lung infections. You can reduce your risk with these strategies:

• Clean cuts and scrapes well with soap and water. Cover them with a bandage.
• Don’t share personal items — like towels or cups — with other people.
• Wash your hands frequently, especially before meals and after going to the bathroom.
• Avoid being around people who are sick with contagious diseases.
• Avoid areas with lots of dust or mold, like construction sites.
• Avoid activities that disturb soil and create dust, such as gardening or lawn mowing. If you might be exposed to airborne dust or mold, wear an N95 face mask.
• Talk to your provider about what recommended vaccinations you should get.

Can hyper IgE syndrome be prevented?

You can’t prevent sporadic cases of hyper IgE syndrome. If you have hyper IgE syndrome, you can talk to a genetic counselor about the risk of a child inheriting it.