Hyper-IgE Syndrome (HIES)

Hyper-IgE syndrome (HIES) is a rare, inherited immune system disease where the body makes very high levels of the antibody IgE and cannot fight germs in a normal way. People usually have severe eczema, repeated skin and lung infections, and often bone, teeth, and connective-tissue problems. [1] In many patients, HIES is caused by a change (mutation) in genes such as STAT3 or DOCK8. These genes help white blood cells signal to each other. When they do not work properly, important cells called Th17 cells are reduced, neutrophils do not work well, and inflammation is weak. This makes it easy for bacteria, fungi, and viruses to cause deep infections. [2]

Hyper-IgE syndrome is a rare, long-term problem of the immune system. In this condition, the body makes very high levels of a blood protein called immunoglobulin E (IgE). IgE is one of the antibodies that helps the body fight germs and parasites. In hyper-IgE syndrome, the immune system does not work in a normal, balanced way, so people get many skin and lung infections, bad eczema (a dry, itchy skin rash), and other body changes. 1

Hyper-IgE syndrome belongs to a group of illnesses called primary immunodeficiency disorders. “Primary” means the problem is usually present from birth and is caused mainly by changes in genes, not by another disease later in life. The illness can affect many parts of the body at the same time, such as the skin, lungs, bones, teeth, and blood vessels, because the same immune pathways help to protect and repair all of these tissues. 2

Over time, repeated infections can damage the lungs (bronchiectasis, pneumatoceles), sinuses, ears, skin, and sometimes bones. People may have fractures after minor injuries, scoliosis, typical facial features, and problems with baby teeth falling out. Because of these wide-ranging effects, treatment combines infection control, skin care, supportive care, and sometimes stem-cell transplantation. [3]

HIES is lifelong, but early diagnosis, strict infection prevention, and modern therapies (like prophylactic antibiotics, antifungals, biologic drugs, and selected hematopoietic stem-cell transplantation) can greatly improve quality of life and long-term outcomes. [4]

People with hyper-IgE syndrome often have normal lives between infections, but the repeated infections and tissue damage over years can slowly harm the lungs, bones, and overall health if not treated early and carefully. Early diagnosis and regular care with immune specialists can greatly reduce infections and long-term complications. 3

Other names of hyper-IgE syndrome

Doctors and books use several other names for hyper-IgE syndrome. One older and common name is “Job syndrome.” This comes from the story of Job, a person in a religious text who had many skin boils, similar to the boils seen in this disease. 4

A more exact name for the main form is “autosomal dominant hyper-IgE syndrome,” often shorted to “AD-HIES.” This name tells us that the condition is usually passed down in families in a dominant way and is often caused by a change in a gene called STAT3. 5

There is also an “autosomal recessive hyper-IgE syndrome,” sometimes called “DOCK8 deficiency” or “DOCK8-HIES,” when the main gene change is in the DOCK8 gene. Other gene-based names used in research and clinics include STAT3-HIES, DOCK8-HIES, PGM3-HIES, ZNF341-HIES, TYK2-HIES, CARD11-HIES, and IL6ST-related HIES. 6

Types of hyper-IgE syndrome

Hyper-IgE syndromes are now seen as a group of related diseases, not just a single illness. The main types, explained in simple list form, are: 7

• Autosomal dominant STAT3-HIES (classic Job syndrome) – The most common form. It is usually caused by a harmful change in the STAT3 gene. People often have eczema, skin abscesses, lung infections, special facial features, bone and joint problems, and very high IgE levels. 8

• Autosomal recessive DOCK8-HIES – This type is caused by changes in the DOCK8 gene. People tend to have very bad viral skin infections, severe allergies, asthma, and a higher risk of certain cancers like lymphoma and skin cancer. IgE is very high and T-cell function is strongly affected. 9

• PGM3-related HIES – Changes in the PGM3 gene disturb sugar processing in cells, which can affect immune function, brain development, and bones. People may have high IgE, recurrent infections, eczema, and sometimes problems with growth or learning. 10

• ZNF341-related HIES – In this type, the ZNF341 gene is changed, which indirectly lowers STAT3 activity. The clinical picture can be close to STAT3-HIES with eczema, infections, and skeletal problems, but details can differ. 11

• IL6ST-related HIES – Changes in the IL6ST gene affect how immune cells respond to several cytokines, including interleukin-6. People show very high IgE, severe eczema, recurrent infections, and often high eosinophil counts. 12

• Other rare or yet-unknown genetic HIES – Some families clearly have a hyper-IgE syndrome, but no gene has been found yet. These cases show that more genes involved in immune signaling remain to be discovered. 13

Causes of hyper-IgE syndrome

1. STAT3 gene mutation – The main cause of classic, autosomal dominant hyper-IgE syndrome is a harmful change (mutation) in the STAT3 gene. STAT3 controls signals that tell T cells and other immune cells how to grow and act. When STAT3 does not work, the body cannot form normal Th17 cells, which are important for fighting bacteria and fungi on skin and mucosal surfaces. This leads to infections and high IgE levels. 14

2. DOCK8 gene mutation – In autosomal recessive DOCK8-HIES, both copies of the DOCK8 gene are changed. DOCK8 helps immune cells move and make stable contact with other cells. Without normal DOCK8, T cells and NK cells cannot attack viruses well, so viral skin infections, allergies, and cancers become more common. IgE levels rise as part of the disturbed immune balance. 15

3. PGM3 gene mutation – Changes in PGM3 interfere with the way cells handle certain sugar molecules needed to build glycoproteins on the cell surface. Immune cells then have abnormal signaling and survival. This can cause high IgE, infections, and sometimes brain and bone problems. 16

4. ZNF341 gene mutation – ZNF341 acts like a master switch that helps turn on STAT3. When ZNF341 is faulty, STAT3 activity drops even if the STAT3 gene itself is normal. The result is a clinical picture similar to STAT3-HIES with recurrent infections, high IgE, and skeletal changes. 17

5. IL6ST gene mutation – IL6ST encodes a receptor subunit called gp130 that sits on the surface of many cells. It is needed for several cytokine signals, including IL-6. When IL6ST is mutated, immune cells cannot respond properly, leading to severe eczema, very high IgE, eosinophilia, and recurrent infections that resemble other forms of HIES. 18

6. TYK2 gene mutation – TYK2 is part of the JAK-STAT signaling pathway. Some patients with TYK2 defects can have high IgE and recurrent infections. The exact pattern may be different from classic STAT3-HIES but shares the problem of poor responses to key cytokines that guide immunity. 19

7. CARD11 gene mutation – CARD11 helps connect the antigen receptor on B and T cells to the NF-κB pathway inside the cell. Certain CARD11 mutations can cause a HIES-like state with high IgE, eczema, and infections, because lymphocytes cannot signal and mature normally. 20

8. Other, still-unknown gene defects – Genetic tests cannot yet find every cause. Some families have typical hyper-IgE features, but no known gene change is seen. This suggests that more rare genes and pathways still need to be discovered as causes of HIES. 21

9. Autosomal dominant inheritance – In many families, one changed copy of STAT3 is enough to cause the disease. A parent with STAT3-HIES has a 50% chance of passing the mutation to each child. This pattern of inheritance explains why several generations in one family may have similar symptoms. 22

10. Autosomal recessive inheritance – In DOCK8-HIES and some other forms, both gene copies must be changed. Parents are usually healthy carriers. When two carriers have a child, there is a 25% chance the child will have the disease. This is more common in communities with close-relative marriages. 23

11. Defective Th17 cell development – Many forms of hyper-IgE syndrome share a common pathway: poor development of Th17 cells, a type of T cell that protects barriers like skin and airways. Without enough Th17 cells, people get recurrent bacterial and fungal infections in these areas. 24

12. Impaired neutrophil chemotaxis – In some patients, white blood cells called neutrophils do not move properly to infection sites. This weak “chemotaxis” response helps explain deep “cold” abscesses that do not look very red or hot but are full of bacteria. 25

13. Abnormal B-cell signaling and antibody class switching – Problems in STAT3, CARD11, and related pathways can disturb the way B cells switch from making one type of antibody to another. IgE may be overproduced, while other protective antibody types may not form properly, raising infection risk. 26

14. Chronic barrier skin damage – Eczema and scratching break the skin barrier. This is not the root genetic cause, but it is a key reason why bacteria and viruses can enter the body easily, causing repeated infections and abscesses in people who already have immune weakness. 27

15. Eosinophil overactivity – Many patients have high levels of eosinophils, another type of white cell. Eosinophils release toxic proteins and chemicals that can damage tissues if not controlled, adding to lung and skin inflammation in hyper-IgE syndrome. 28

16. Disturbed cytokine signaling (IL-6, IL-10, IL-21, IFN-γ and others) – Many of the genes linked to HIES sit in pathways that carry messages from cytokines, the “text messages” of the immune system. When these messages are weak or wrong, the immune response becomes unbalanced, leading to high IgE and poor infection control. 29

17. Consanguinity and limited gene pool – In some regions, marriage between relatives is common. This increases the chance that both parents carry the same rare recessive gene change, making recessive forms of HIES more frequent in those communities. 30

18. De novo (new) mutations – Sometimes a child is the first in the family with hyper-IgE syndrome. In these cases, the gene change happened for the first time in the egg, sperm, or early embryo. The parents do not have the disease, but the child can later pass it on. 31

19. Somatic or mosaic mutations – In rare cases, only some cells in the body carry the gene change (mosaicism). This can lead to milder or unusual forms of HIES and can make genetic testing harder, because not all cells show the mutation. 32

20. Unknown or complex combined mechanisms – Even when a gene is known, scientists still do not fully understand every step from gene change to the many clinical signs. Other genes, environment, and random factors all likely combine to shape how severe hyper-IgE syndrome becomes in each person. 33

Symptoms of hyper-IgE syndrome

1. Chronic eczema (itchy skin rash) – Many babies with hyper-IgE syndrome develop a red, itchy rash in the first weeks or months of life. The rash often looks like atopic dermatitis and may cover large areas of the body. It can flare again and again, causing broken skin and severe discomfort. 34

2. Recurrent skin abscesses and boils – People often get deep, painful lumps filled with pus, especially caused by Staphylococcus bacteria. These abscesses may look surprisingly “cold,” with less redness or pain than usual, because of the special immune defect, but they still carry many germs. 35

3. Recurrent lung infections (pneumonia) – Frequent bacterial pneumonia is common. Over time, repeated infections can damage the lung tissue and airways, leading to chronic cough, shortness of breath, and structural problems like bronchiectasis. 36

4. Pneumatoceles (air-filled lung cavities) – Some patients develop thin-walled air pockets in the lungs after severe infections. These pneumatoceles can become infected again or press on healthy lung tissue, making breathing harder and raising the risk of serious complications. 37

5. Recurrent ear, nose, and sinus infections – Chronic sinusitis, middle ear infections, and blocked nose are common because the same immune problems affect the upper airways. This can cause ear pain, runny or blocked nose, headaches, and hearing issues if infections are frequent and severe. 38

6. Fungal infections of skin, nails, and mouth – Yeast infections, especially from Candida, can affect the mouth (thrush), nails, and skin folds. These infections may last a long time or come back quickly after treatment, because the body’s defense against fungi is weak. 39

7. Coarse facial features – Over time, some people with STAT3-HIES develop a characteristic facial look, including a prominent forehead, deep-set eyes, broad nose, and sometimes a high-arched palate. These features do not hurt but are useful signs that help doctors suspect the disease. 40

8. Retained primary (baby) teeth – A classic sign is that baby teeth do not fall out on time, even when adult teeth start growing behind them. This “double row” of teeth is striking and often needs dental removal. It happens because the roots of the baby teeth do not dissolve normally. 41

9. Frequent bone fractures and joint problems – Bones may be fragile, so fractures can occur after minor injuries. Some patients also develop scoliosis (curved spine) or joint hyper-flexibility and pain. These skeletal problems are thought to be linked to the same signaling pathways that are abnormal in STAT3-HIES. 42

10. Recurrent fevers and feeling unwell – During infections, people get fevers, chills, and tiredness like anyone else, but these episodes may happen more often and last longer. Repeated sickness can interfere with school, work, and normal daily activities. 43

11. Chronic cough and breathing difficulty – Even between acute infections, damaged lungs and airways may cause a long-term cough, wheeze, or shortness of breath. Exercise can become hard, and some patients may need long-term breathing support or oxygen in severe cases. 44

12. Severe allergies and asthma-like symptoms – High IgE is often linked with allergies. Many patients have food allergies, hay fever, or asthma-like wheeze. However, the pattern is not always the same as simple allergy, because the underlying cause is a primary immune defect. 45

13. Skin scarring and changes from repeated infections – Deep skin infections and chronic eczema can leave scars, areas of lighter or darker skin, and thickened skin in affected regions. These marks can affect self-image and quality of life, especially in teenagers and young adults. 46

14. Recurrent viral skin infections (especially in DOCK8-HIES) – Patients with DOCK8-HIES often have large, stubborn viral warts, molluscum contagiosum lesions, or herpes infections. These can be painful, disfiguring, and hard to treat, because the immune system cannot clear the virus well. 47

15. Increased risk of certain cancers (especially in recessive forms) – Some forms, particularly DOCK8-HIES, carry a higher risk of lymphoma and skin cancers during adolescence or young adulthood. This makes regular follow-up and early cancer screening very important in these patients. 48

Diagnostic tests for hyper-IgE syndrome

Doctors use both clinical signs and many tests to diagnose hyper-IgE syndrome. A useful clinical tool is the NIH hyper-IgE scoring system, which gives points for features like infections, IgE level, fractures, and facial changes. High scores, together with blood tests and genetic tests, strongly support the diagnosis. 49

1. Full skin and general physical exam (Physical exam) – The doctor carefully looks at the whole skin to check for eczema, scars, boils, warts, and other lesions. They also note general growth, body build, and any facial changes. This first, simple step already gives many clues that point toward hyper-IgE syndrome rather than common allergy alone. 50

2. Chest and lung examination with stethoscope (Physical exam) – By listening to the chest, the doctor can hear crackles, wheezes, or decreased breath sounds that suggest pneumonia, bronchiectasis, or pneumatoceles. Repeated abnormal findings over time support the idea of a chronic lung problem linked to immune deficiency. 51

3. Musculoskeletal and spine exam (Physical exam) – The doctor checks the spine for curves, the chest for shape changes, and the joints for flexibility or pain. Frequent fractures, scoliosis, or unusual joint movement are common in STAT3-HIES and add points in scoring systems. 52

4. Oral and dental examination (Physical exam) – The dentist or doctor looks for retained baby teeth, extra teeth rows, cavities, and gum disease. The pattern of delayed shedding of primary teeth is so typical in STAT3-HIES that it is considered one of the hallmark signs. 53

5. Growth and development review (Physical exam) – Height, weight, head size, and pubertal stage are checked and plotted on charts. Delayed growth or pubertal delay can appear in some forms of HIES, especially when infections are frequent and nutrition is poor. 54

6. Manual spine and posture check (Manual test) – The clinician uses their hands and eyes to check posture, spine curve, and shoulder level. This simple bedside test helps detect scoliosis and chest wall changes early, which are part of the connective tissue involvement in STAT3-HIES. 55

7. Joint flexibility and range-of-motion test (Manual test) – By gently moving joints, the doctor can see if they are unusually loose (hyper-mobile) or stiff and painful. Excess joint looseness is another skeletal feature often seen in STAT3-HIES. 56

8. Simple bedside balance and neurologic exam (Manual test) – Basic tests of balance, walking, and strength can show whether there are neurological problems. This is especially useful in some recessive HIES forms where infections or immune problems may affect the nervous system. 57

9. Complete blood count with differential (Lab/pathological test) – This common blood test counts all blood cells. In hyper-IgE syndrome, eosinophils are often raised, and other changes such as mild anemia or altered white cell counts may appear. The results help support the clinical suspicion and rule out other causes. 58

10. Serum total IgE level (Lab/pathological test) – A very high IgE level is a key feature. In many patients, IgE is greater than 2,000 IU/mL, far above the normal range. IgE level alone does not prove HIES, but when combined with typical infections and features, it is very important. 59

11. Other immunoglobulin levels and specific antibody tests (Lab/pathological test) – Levels of IgG, IgA, and IgM are measured, and the body’s response to vaccines may be checked. Some patients have reduced protective antibodies, which explains why they keep getting serious infections. 60

12. Lymphocyte subset analysis (Lab/pathological test) – Using flow cytometry, doctors measure numbers of T cells, B cells, and NK cells, and sometimes special subsets like Th17 cells. Abnormal patterns, such as low Th17 cells, strongly support the diagnosis of STAT3-HIES and related forms. 61

13. Cytokine and functional immune tests (Lab/pathological test) – In specialized centers, cells can be tested for their response to cytokines like IL-6 or IL-21, or for their ability to kill bacteria or fungi. These tests are complex but help to understand which signaling steps are blocked in each patient. 62

14. Microbiology cultures from skin, sputum, and other sites (Lab/pathological test) – Samples from abscesses, sputum, or sinuses are sent to the lab to grow bacteria and fungi. The results show which germs are causing infections, guiding targeted antibiotic or antifungal treatment. 63

15. Genetic testing for STAT3, DOCK8, and other HIES genes (Lab/pathological test) – DNA tests search for harmful changes in genes known to cause HIES. Finding a clear mutation in STAT3, DOCK8, PGM3, ZNF341, IL6ST, or related genes usually confirms the diagnosis and helps with family counseling. 64

16. Nerve conduction studies and electromyography (Electrodiagnostic test) – In some patients, especially with DOCK8-HIES or long-standing infections, nerve damage may occur. Nerve conduction studies and EMG measure how fast and how well nerves carry signals. Abnormal results can explain weakness or numbness and guide further care. 65

17. Electroencephalogram (EEG) or other targeted electro tests (Electrodiagnostic test) – If a patient has seizures or episodes suggesting brain involvement, an EEG or similar tests may be done. These do not diagnose HIES directly but help to assess complications linked to infections or immune problems in the nervous system. 66

18. Chest X-ray (Imaging test) – A basic chest X-ray can show pneumonia, areas of collapsed lung, or large air pockets (pneumatoceles). Because chest X-rays are easy to repeat, they are often used to follow lung changes over time in HIES patients. 67

19. High-resolution CT scan of the chest (Imaging test) – CT scans give a detailed view of the lungs and airways, showing bronchiectasis, pneumatoceles, and small cavities that might be missed on X-ray. This helps doctors plan treatment and monitor long-term lung damage. 68

20. Sinus imaging and dental or skeletal X-rays (Imaging tests) – CT or MRI scans of the sinuses show chronic sinus infections and structural problems. Dental panoramic X-rays reveal retained baby teeth and jaw structure. Skeletal surveys can show fractures, scoliosis, or other bone changes linked to hyper-IgE syndrome. 69

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Non-pharmacological treatments (therapies and others)

1. Structured eczema skin-care routine
A gentle, daily routine with lukewarm baths, fragrance-free cleansers, and thick emollients helps repair the damaged skin barrier. Moist skin cracks less, so bacteria and fungi enter less easily. Reducing scratching also lowers the risk of skin abscesses and scarring. This routine is usually the foundation of care for all patients with HIES and severe eczema. [1]

2. Regular use of emollients and barrier creams
Thick moisturising ointments or creams are applied at least twice per day to seal water into the skin. Barrier creams with ceramides or petrolatum reduce dryness and micro-cracks in the skin surface. By improving the barrier, they lower itch and reduce the number of infections, which is crucial in HIES where the skin is a major portal of entry for germs. [1]

3. Antiseptic or dilute bleach baths
Short baths using very dilute household bleach or other antiseptic solutions (only under medical guidance) reduce the number of Staphylococcus aureus and other bacteria on the skin. This can lower the frequency of skin infections and abscesses in HIES. The solution must be carefully prepared so that it is safe for the skin and eyes. [2]

4. Gentle clothing and environment for skin
Soft cotton clothes, mild detergents, and avoiding wool or rough fabrics help decrease friction and irritation. Keeping the home cool and avoiding heavy sweating can reduce itching and eczema flares. In HIES, any scratch can become infected, so minimising irritation is a simple but powerful supportive therapy. [3]

5. Intensive hand and nail hygiene
Short, clean nails reduce skin damage from scratching. Regular hand-washing with mild soap and careful drying reduces the movement of bacteria from the hands to broken skin or mucous membranes. For people with HIES, this routine lowers the risk of spreading skin and respiratory infections within the household. [4]

6. Chest physiotherapy and airway-clearance techniques
Because HIES patients often develop chronic lung disease and thick mucus, chest physiotherapy, postural drainage, and devices that vibrate the airways help clear secretions. This reduces the risk of pneumonia and bronchiectasis worsening. Respiratory therapists can teach families simple daily routines tailored to age and lung condition. [5]

7. Nasal saline irrigation and sinus care
Daily or frequent rinses with isotonic saline wash out mucus, crusts, and allergens from the nose and sinuses. This decreases bacterial load and improves drainage, helping prevent chronic sinusitis and facial pain. In HIES, where sinus infections can be recurrent and severe, this non-drug measure supports antibiotic treatment and lowers flare frequency. [6]

8. Dental and oral hygiene program
HIES can cause problems with baby teeth not falling out, deep caries, and gum infections. Regular brushing with fluoride toothpaste, flossing, antiseptic mouth rinses, and scheduled visits to a dentist familiar with HIES reduce tooth infections and abscesses. Early dental extraction of retained teeth may be needed as part of preventive care. [7]

9. Physiotherapy and orthopaedic rehabilitation
Because of bone fragility and joint problems, guided physiotherapy builds muscle strength and improves posture and balance. This may lower fracture risk and help patients recover after bone or joint infections. Simple home exercises, taught by a physiotherapist, can be adapted for children and adults with different levels of mobility. [8]

10. Hearing and vestibular rehabilitation
Chronic ear and sinus infections in HIES can lead to hearing loss and balance problems. Hearing tests, hearing aids when needed, and vestibular exercises can improve communication and reduce falls. Early recognition of hearing issues is important for child development and school performance. [9]

11. Infection-control measures at home
Simple infection-control steps—frequent hand-washing, cleaning often-touched surfaces, not sharing towels or razors, and good kitchen hygiene—reduce exposure to germs. Avoiding crowded places during outbreaks and keeping sick household members separate when possible can help prevent serious infections in a person with HIES. [10]

12. Vaccination planning with specialists
Vaccination is a key non-drug prevention tool. In HIES, doctors carefully choose which vaccines are safe (often inactivated vaccines) and which live vaccines to avoid, based on the exact genetic defect and immune status. A personalised schedule helps reduce risk from pneumococcus, influenza, and other pathogens. [11]

13. Nutrition counselling and growth monitoring
Dietitians can design calorie- and protein-adequate diets to support growth, wound healing, and immune function. In children with HIES, monitoring weight and height helps detect malnutrition early. Good nutrition improves the body’s resilience against infections and helps skin and bone repair. [12]

14. Psychological support and counselling
Chronic disease, visible skin lesions, and repeated hospital visits can cause anxiety, low mood, and social isolation. Talking therapies, support groups, and school-based counselling help patients and families cope emotionally. Good mental health improves adherence to treatment and overall quality of life. [13]

15. Patient and family education programs
Teaching families to recognise early signs of infection, how to give preventive medicines, and how to manage skin flare-ups makes day-to-day care safer. Written “action plans” for fever or breathing problems guide decisions about when to call the doctor or go to hospital, which is vital in HIES. [14]

16. Genetic counselling for families
Because HIES is often inherited (autosomal dominant STAT3 variants or autosomal recessive DOCK8 and other genes), genetic counselling explains recurrence risks, options for testing relatives, and family-planning choices. Early diagnosis in relatives can lead to earlier preventive care and better outcomes. [15]

17. School and workplace accommodations
Flexible school attendance, infection-control measures at school, and understanding employers help patients keep up with education and work despite hospital visits. Allowing rest breaks, avoiding very dusty tasks, and supporting remote work when ill can reduce stress and infection exposure for people with HIES. [16]

18. Sun-protection and skin-trauma avoidance
Using sunscreen, protective clothing, and avoiding sunburn protects fragile skin and reduces inflammation. Avoiding contact sports or taking extra precautions in high-risk activities reduces injury-related fractures in those with bone fragility. This is important as fractures can complicate already weakened bones in HIES. [17]

19. Long-term multidisciplinary follow-up
Care from an immunologist, dermatologist, pulmonologist, ENT specialist, dentist, and sometimes orthopaedic and transplant teams ensures all complications are monitored. Regular check-ups catch problems early—for example, lung changes or hearing loss—when they are easier to treat. [18]

20. Safe travel and emergency planning
Before travel, patients arrange extra medicines, medical letters, and emergency contact plans. Knowing where the nearest hospital with immunology or intensive care is located can be life-saving. This planning reduces anxiety and allows safer travel for people with HIES. [19]

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Drug treatments (medical management)

(Doses below are general educational examples for adults; real dosing must be adjusted by specialists using official prescribing information, often from FDA labels.)

1. Trimethoprim–sulfamethoxazole (TMP-SMX / Bactrim)
TMP-SMX is a combination antibiotic often used continuously in low doses to prevent skin and lung infections, especially Staphylococcus and Pneumocystis jirovecii. Typical adult prophylaxis uses one double-strength tablet once daily or three times per week, adjusted for kidney function. Common side effects include rash, nausea, and rarely severe allergic reactions or low blood counts. [1]

2. Fluconazole
Fluconazole is an oral antifungal used to prevent or treat candida infections of the mouth, oesophagus, or bloodstream, which can be more common in immunodeficiency. Dosing varies (for example 100–400 mg once daily in adults), guided by infection site and kidney function. Side effects include liver enzyme elevation, stomach upset, and interactions with other drugs that use liver enzyme CYP3A4. [2]

3. Itraconazole or posaconazole
These azole antifungals can be used when there is risk of more resistant mould infections, such as Aspergillus, especially in patients with lung damage. They are usually given orally with food; doses depend on formulation. Drug–drug interactions and liver toxicity must be monitored carefully, so regular blood tests and level monitoring are often needed. [3]

4. Amoxicillin–clavulanate
This broad-spectrum oral antibiotic (a penicillin plus β-lactamase inhibitor) is useful for acute sinus, ear, and chest infections caused by common bacteria. Typical adult doses (for example 875/125 mg twice daily) depend on severity and kidney function. Side effects include diarrhoea, allergic reactions, and, rarely, liver inflammation. [4]

5. Clindamycin
Clindamycin is used for serious skin, soft-tissue, and bone infections, especially when Staphylococcus aureus is suspected, including some MRSA strains. It can be given orally or intravenously. Usual adult doses range from 300–450 mg orally three or four times daily. It may cause diarrhoea and increases the risk of Clostridioides difficile colitis, so careful monitoring is needed. [5]

6. Azithromycin
Azithromycin is a macrolide antibiotic used for respiratory infections and sometimes as long-term prophylaxis in chronic lung disease. It is often given once daily or three times weekly because of its long half-life. Side effects include stomach upset, changes in heart rhythm in at-risk patients, and promotion of antibiotic resistance if overused. [6]

7. Ceftriaxone or other third-generation cephalosporins
For severe bacterial infections requiring hospital treatment, intravenous ceftriaxone is commonly used. It covers many gram-negative and some gram-positive organisms. Adult doses are often 1–2 g once daily, adjusted for infection type. Side effects include allergic reactions, biliary sludging, and diarrhoea. [7]

8. Vancomycin or linezolid
These antibiotics target resistant gram-positive bacteria (e.g., MRSA) and may be necessary in complicated skin or lung infections. Vancomycin is given intravenously with dose monitoring by blood levels; linezolid can be oral or IV. Important side effects include kidney injury (vancomycin) and bone-marrow suppression or neuropathy (linezolid). [8]

9. Acyclovir or valacyclovir
Reactivation of herpes simplex or varicella-zoster viruses can be more serious in immunodeficiency. Acyclovir-type antivirals, given orally or intravenously, shorten disease and may be used preventively in high-risk patients. Dose depends on kidney function. Side effects include nausea, kidney issues at high IV doses, and headache. [9]

10. Topical corticosteroids
Mild to potent steroid creams or ointments (for example hydrocortisone, triamcinolone, mometasone) reduce eczema inflammation, itch, and redness. Thin layers are applied to inflamed areas for limited periods, then tapered. Overuse can cause skin thinning, stretch marks, and increased infection risk, so treatment plans must be supervised by dermatologists. [10]

11. Topical calcineurin inhibitors (tacrolimus, pimecrolimus)
These non-steroid creams reduce skin inflammation by blocking calcineurin-dependent T-cell activation. They are useful on delicate areas like face and folds to avoid steroid side effects. Burning or stinging at application sites is common at first. Long-term cancer risk appears low when used correctly, but they should follow specialist advice. [11]

12. Oral antihistamines (e.g., cetirizine, loratadine)
Non-sedating antihistamines help control itching and allergy-type symptoms. They do not treat the underlying immune defect but improve comfort and reduce scratching, which lowers infection risk. Usual adult doses are once daily. Side effects are usually mild, such as drowsiness or dry mouth in some patients. [12]

13. Inhaled corticosteroids and bronchodilators
In patients with asthma or chronic lung disease, inhaled steroids and bronchodilators (such as salbutamol and formoterol combinations) reduce airway inflammation and improve breathing. They are delivered by inhaler or nebuliser. Incorrect technique is common, so teaching and regular review are important. Potential side effects include oral thrush and, rarely, systemic steroid effects at high doses. [13]

14. Bisphosphonates (e.g., alendronate)
These drugs slow bone resorption and may be used when HIES patients develop osteoporosis or repeated low-impact fractures. They are usually taken weekly or monthly with strict instructions (fasting, upright posture after swallowing) to protect the oesophagus. Side effects include stomach irritation, bone or joint pain, and very rarely osteonecrosis of the jaw. [14]

15. Intravenous immunoglobulin (IVIG)
IVIG is pooled IgG from donors, given by infusion every 3–4 weeks to support antibody function in patients with recurrent bacterial infections or low specific antibodies. Dose is calculated by weight (for example 400–600 mg/kg per cycle). Side effects include headache, chills, and rarely thrombosis or kidney injury, so monitoring during infusion is needed. [15]

16. Omalizumab (anti-IgE monoclonal antibody)
Omalizumab binds free IgE and reduces allergic inflammation. Case reports show that in selected adults and children with HIES, it can improve eczema, asthma, and infection frequency, though use is off-label. Doses are based on weight and baseline IgE. Side effects include injection-site reactions and rare anaphylaxis, so injections are supervised. [16]

17. Dupilumab (anti-IL-4Rα monoclonal antibody)
Dupilumab blocks IL-4 and IL-13 signalling, dampening type-2 inflammation that drives eczema and allergies. Case reports and small series in STAT3-HIES and DOCK8-HIES show better skin control and fewer infections. It is given as subcutaneous injections every 2–4 weeks. Side effects include eye irritation, injection-site reactions, and transient eosinophilia. [17]

18. Systemic corticosteroids (short courses)
Oral or intravenous steroids (such as prednisolone) may be used short-term for severe inflammation, e.g., serious lung flare-ups or allergic reactions. Because they also suppress immunity, they must be used carefully and for as short a time as possible. Side effects include weight gain, high blood sugar, mood changes, and higher infection risk. [18]

19. Growth factors (G-CSF / filgrastim)
If HIES coexists with low neutrophil counts, granulocyte-colony-stimulating factor (G-CSF) can temporarily boost neutrophil numbers and help fight infections. It is injected under the skin at doses based on weight and blood counts. Bone pain and high white counts are common side effects, so dosing is individualised. [19]

20. Analgesics and antipyretics (e.g., paracetamol)
These medicines do not treat HIES itself but ease pain and fever, improving comfort and allowing better breathing and sleep. Paracetamol is often preferred because it has fewer stomach and bleeding side effects than NSAIDs when used at correct doses. Overdose can damage the liver, so maximum daily doses must never be exceeded. [20]

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Dietary molecular supplements

(All supplements should be checked with the treating doctor to avoid interactions or excess doses.)

1. Vitamin D
Vitamin D supports bone strength and helps immune cells recognise and respond to germs. Many patients with chronic illness are deficient. Doctors may use doses such as 800–2000 IU/day in adults, adjusted by blood levels. Too much vitamin D can cause high calcium and kidney stones, so monitoring is essential. [1]

2. Vitamin C
Vitamin C is an antioxidant that supports collagen formation, skin repair, and white blood cell function. In HIES, it may help wound healing and gum health when taken in usual dietary-supplement doses (for example 200–500 mg/day). Very high doses can cause diarrhoea and kidney stones in predisposed people, so balance is important. [2]

3. Zinc
Zinc is crucial for skin integrity and immune cell signalling. Low zinc levels worsen eczema and infection risk. Supplement doses (e.g., 10–25 mg/day of elemental zinc for limited periods) are chosen based on diet and labs. Too much zinc can upset the stomach and disturb copper balance, so long-term high doses are avoided. [3]

4. Omega-3 fatty acids (EPA/DHA)
Fish-oil-derived omega-3 fats may soften inflammation in skin and lungs and support cardiovascular health. Typical doses range from 500–1000 mg/day of combined EPA/DHA, taken with food. Side effects include mild stomach upset and, rarely, increased bleeding tendency at very high doses or when combined with anticoagulants. [4]

5. Probiotics
Selected probiotic strains may support gut barrier function and immune regulation, potentially reducing antibiotic-associated diarrhoea. Their role in HIES is not fully studied, so they should be used cautiously, especially in severely immunocompromised patients. Doses follow product instructions, and doctors should be informed about any probiotic use. [5]

6. Selenium
Selenium is a trace mineral that supports antioxidant enzymes and thyroid function. Adequate selenium may help immune responses and protect tissues from oxidative stress. Small supplement doses (e.g., 50–100 micrograms/day) may be considered when dietary intake is low. Very high doses are toxic and can cause hair loss and nail changes, so lab-guided dosing is important. [6]

7. Vitamin A (carefully dosed)
Vitamin A is needed for skin and mucosal health and for certain immune functions. Mild supplementation may help if there is true deficiency, but high doses are dangerous and can cause liver and bone problems. Therefore, vitamin A should only be given when deficiency is proven and under specialist guidance. [7]

8. B-complex vitamins (including folate and B12)
B vitamins support energy metabolism and blood-cell production. In children or adults with poor appetite, chronic illness, or malabsorption, modest B-complex supplements can correct deficiencies and support overall health. Doses are usually those found in standard multivitamins. Very high doses of some B vitamins can cause nerve or liver problems, so “mega-doses” are avoided. [8]

9. High-quality protein and amino acids
While not a pill, adequate intake of complete proteins (from eggs, dairy, legumes, meat, or specialised formulas) supplies amino acids needed for immune proteins, enzymes, and tissue repair. In HIES, where healing after infections and surgeries is important, dietitians may recommend protein-enriched diets or supplements, tailored to kidney and liver function. [9]

10. Prebiotic fibre (e.g., inulin, resistant starch)
Prebiotic fibres feed beneficial gut bacteria and help maintain a healthy microbiome, which interacts with the immune system. They can be obtained from foods (oats, bananas, chicory) or as supplements. Sudden large doses may cause gas and bloating, so amounts should be increased slowly and adjusted if bowel disease is present. [10]

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Drugs for immunity boosting, regenerative and stem-cell related therapy

1. Intravenous immunoglobulin (IVIG)
IVIG gives ready-made antibodies from many donors to patients who cannot make effective antibodies themselves. In HIES, IVIG may reduce bacterial infections in those with specific antibody defects. It is infused every 3–4 weeks in hospital or clinic. This is a “passive immunisation” that boosts immunity temporarily but can greatly improve quality of life in selected patients. [1]

2. Granulocyte-colony-stimulating factor (G-CSF / filgrastim)
G-CSF acts on the bone marrow to increase production and release of neutrophils. In HIES patients with overlapping neutropenia or during severe infections, short courses of G-CSF injections may help the body control infections better. It is not used in everyone, because it can cause bone pain and very high white cell counts if over-dosed. [2]

3. Allogeneic hematopoietic stem-cell transplantation (HSCT)
HSCT replaces the patient’s defective immune system with stem cells from a healthy donor. It is the most “regenerative” option and can correct the immune defect, especially in DOCK8-deficient HIES and some STAT3-HIES cases. However, it carries serious risks (graft-versus-host disease, infections, organ toxicity) and is reserved for carefully selected patients in expert centres. [3]

4. Emerging gene-therapy approaches
Experimental gene-therapy strategies aim to correct the underlying genetic defect in the patient’s own stem cells, then re-infuse them. This is still under research for primary immune deficiencies and has not yet become standard care for HIES. In the future, gene therapy may offer a more targeted and potentially curative option with fewer long-term complications than allogeneic HSCT. [4]

5. Biologic modulators (omalizumab)
As mentioned above, omalizumab indirectly “boosts” immune balance by lowering extreme IgE-driven allergic inflammation. In some HIES patients, this appears to reduce eczema severity, asthma symptoms, and possibly infection frequency, giving the immune system a more stable baseline. Because data come mainly from small case reports, its use is restricted to specialist centres. [5]

6. Biologic modulators (dupilumab)
Dupilumab changes the cytokine environment by blocking IL-4/IL-13 signals, shifting the immune response away from uncontrolled type-2 activity. Case series show improved skin, fewer infections, and better lung function in some HIES patients. It is not a classic “immune booster,” but by correcting imbalance it may allow more effective host defence. Again, it is off-label and requires expert oversight. [6]

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Surgeries and procedures

1. Incision and drainage of skin abscesses
Large or deep skin abscesses often require minor surgery to open, drain pus, and remove dead tissue. This reduces the amount of bacteria, helps antibiotics work better, and prevents spread to the bloodstream. In HIES, prompt drainage is important to avoid chronic sinus tracts and scarring. [1]

2. Functional endoscopic sinus surgery (FESS)
When chronic sinusitis does not respond to medical therapy, ENT surgeons may perform FESS to widen sinus openings and remove inflamed tissue or polyps. This improves drainage and makes future infections easier to treat with nasal rinses and antibiotics. HIES patients with persistent sinus disease and facial pain may benefit from this procedure. [2]

3. Lung surgery for pneumatoceles or localised bronchiectasis
Severely damaged parts of the lung, such as large air-filled pneumatoceles or localised areas of bronchiectasis, can become chronic infection sites. Surgical removal of these areas may reduce repeated pneumonias and risk of life-threatening complications like rupture or bleeding. This is major surgery and is only considered after careful imaging and multidisciplinary discussion. [3]

4. Dental extractions and corrective oral surgery
Because baby teeth often fail to fall out normally in STAT3-HIES, dental surgeons may need to remove retained teeth to allow permanent teeth to erupt. Surgical drainage of oral abscesses and treatment of severe gum disease are also common. These procedures prevent chronic pain, infections, and nutrition problems. [4]

5. Central venous catheter placement for HSCT or long-term therapy
Patients undergoing HSCT or frequent IV antibiotics may need central venous lines or ports surgically inserted. These allow reliable access for infusions and blood tests. Strict line care is essential to prevent catheter-related infections, which can be very serious in immunodeficient patients. [5]

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Prevention and lifestyle measures

1. Daily skin care and rapid treatment of breaks: Keeping skin moisturised and treating small cuts quickly with cleaning and dressings reduces infection risk. [1]

2. Prompt treatment of any fever: In HIES, fever can signal serious deep infections. Families are usually advised to contact a doctor early for evaluation and cultures. [2]

3. Structured vaccination plan: Keeping up-to-date with recommended inactivated vaccines (e.g., influenza, pneumococcal) under specialist guidance reduces preventable infections. [3]

4. Avoidance of smoking and second-hand smoke: Tobacco smoke damages airways and worsens lung infections and bronchiectasis, so patients and household members should avoid smoking. [4]

5. Healthy sleep and stress management: Regular sleep and stress-reduction strategies support immune function and coping with chronic illness. [5]

6. Regular monitoring with specialists: Scheduled visits allow early detection of complications such as lung changes, hearing loss, or early cancers, leading to timely interventions. [6]

7. Safe use of antibiotics: Using prophylactic antibiotics as prescribed and avoiding unnecessary extra courses reduce resistance and side effects, while still protecting against key pathogens. [7]

8. Household infection-control habits: Hand hygiene, staying away from people with active infections, and cleaning shared objects help prevent serious illnesses. [8]

9. Sun and injury protection: Protecting skin and bones from excessive sun and trauma prevents avoidable damage in already fragile tissues. [9]

10. Emergency plan for severe symptoms: Families should know when to call emergency services or go directly to hospital (e.g., sudden breathing difficulty, confusion, very high fever), which can save lives. [10]

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When to see doctors

People with hyper-IgE syndrome should have regular, planned visits with an immunologist and other specialists even when they feel well. At these visits, doctors review infections, medicines, lung function, hearing, dental status, and growth in children, adjusting the care plan as needed. [1]

Urgent medical review is needed if there is fever, worsening cough, chest pain, shortness of breath, severe headache, confusion, new rash with blisters, rapidly spreading skin redness, or any signs of sepsis such as fast heart rate, low blood pressure, or extreme fatigue. In HIES, infections can become serious quickly, so low threshold for hospital evaluation is recommended. [2]

Parents should seek immediate care for children with HIES who show poor feeding, reduced urine output, persistent vomiting, or drowsiness. Any concern about bone pain after minor trauma, sudden hearing loss, or new neurological symptoms (weakness, seizures) should also prompt urgent assessment. [3]

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What to eat and what to avoid

1. Eat: protein-rich foods such as eggs, dairy, beans, fish, and lean meats to support immune cell production and tissue repair. [1]

2. Eat: colourful fruits and vegetables (berries, oranges, leafy greens) for vitamins, minerals, and antioxidants that help skin healing and general immunity. [2]

3. Eat: whole grains and fibre from oats, brown rice, and whole-grain bread to support gut health and steady energy levels. [3]

4. Eat: healthy fats from sources like olive oil, nuts, seeds, and oily fish, which provide omega-3 fatty acids and support cell membranes and anti-inflammatory pathways. [4]

5. Eat: fermented foods (if safe) such as yoghurt with live cultures, kefir, or traditional fermented foods, after discussing with the doctor, to gently support a healthy gut microbiome. [5]

6. Avoid: very high-sugar drinks and snacks that cause rapid blood-sugar swings and may worsen inflammation and dental problems. [6]

7. Avoid: heavily processed fast foods rich in trans fats and salt, which can promote inflammation and do not provide the nutrients needed for healing. [7]

8. Avoid: foods that clearly trigger eczema or allergy in that individual (for example certain nuts, eggs, milk), but only after proper allergy testing so that the diet does not become unnecessarily restricted. [8]

9. Avoid: alcohol and unnecessary herbal products in older teens/adults, as they can interact with important medicines and stress the liver, especially when many drugs (like azoles or antibiotics) are being used. [9]

10. Avoid: unpasteurised or high-risk raw foods (e.g., raw eggs, undercooked meat, unpasteurised milk) that can carry dangerous bacteria and cause severe infections in immunocompromised people. [10]

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Frequently asked questions (FAQs)

1. Is hyper-IgE syndrome the same as severe eczema?
No. Many people have eczema with high IgE, but HIES is a specific primary immune deficiency with genetic causes, very high IgE, and characteristic infections and skeletal features. Specialist testing is needed to make the diagnosis. [1]

2. Can hyper-IgE syndrome be cured?
At present, there is no simple cure for most forms of HIES, but careful long-term management can control symptoms very well. For some genetic forms, allogeneic stem-cell transplantation may correct the immune defect and offer a potential cure, but it carries significant risks. [2]

3. Why is IgE so high in this disease?
Mutations in genes like STAT3 and DOCK8 change how T cells and other immune cells communicate. This shifts the immune system towards type-2 responses, leading to excessive IgE production and eosinophilia, while weakening protective Th17-mediated responses against bacteria and fungi. [3]

4. Do all patients have the same problems?
No. Some have mainly skin disease, others have severe lung or brain complications. The exact gene involved, environment, and treatment quality all influence how severe the disease becomes. This is why personalised management and genetic characterisation are important. [4]

5. What is the life expectancy with HIES?
With modern care—prophylactic antibiotics, targeted biologics, and better infection treatment—many patients reach adulthood and middle age. However, severe lung damage, malignancies, or complications of HSCT can shorten life in some forms. Prognosis is best with early diagnosis and expert management. [5]

6. Is pregnancy possible for someone with HIES?
Many women with milder HIES can become pregnant, but pregnancy requires high-risk obstetric and immunology care. Infection prevention, lung function, and drug safety (for the fetus) must be carefully planned. Genetic counselling is important to discuss inheritance risk. [6]

7. Are biologics like omalizumab and dupilumab standard treatment?
They are not yet standard, but growing case reports and series show benefit for severe eczema and recurrent infections in selected HIES patients. Their use is off-label and limited to centres with experience, after careful risk–benefit discussions. [7]

8. How early should children be screened if a parent has HIES?
If a parent has a known pathogenic variant, children can often be offered testing soon after birth or in early childhood. This allows early monitoring and infection prevention, which may protect lungs and other organs from long-term damage. [8]

9. Can lifestyle alone control hyper-IgE syndrome?
No. Lifestyle and non-pharmacological strategies are very helpful, but because the core problem is an inherited immune defect, most patients need long-term medical treatments such as prophylactic antibiotics and specialist care. [9]

10. Is it safe to give live vaccines?
In some genetic forms of HIES, live vaccines may be risky, while in others they may be acceptable. The decision must be made by an immunologist for each patient, based on detailed immune testing and genetic diagnosis. [10]

11. Why do some patients get fractures from minor injuries?
STAT3-HIES is associated with abnormal connective tissue and reduced bone density. This makes bones more fragile, so even small falls can cause fractures. Vitamin D, calcium, physiotherapy, and, in some cases, bisphosphonates help protect bones. [11]

12. Are cancers more common in HIES?
Certain forms, particularly DOCK8-deficient HIES, are associated with higher risks of lymphomas and virus-related cancers. Regular monitoring, early treatment of chronic viral infections, and consideration of HSCT in high-risk genotypes are important strategies. [12]

13. Can people with HIES travel or attend school?
Yes, with careful planning. They should keep up with preventive medicines, avoid travel during major outbreaks, and ensure good infection control at school. Written plans for emergencies and communication with teachers make participation safer and more inclusive. [13]

14. How often are follow-up visits needed?
In stable patients, visits every 3–6 months may be enough, but after serious infections, HSCT, or when starting new therapies like biologics, visits may be more frequent. The schedule is tailored to the individual’s disease severity and treatment plan. [14]

15. What is the most important message for families?
Hyper-IgE syndrome is complex but manageable. Early diagnosis, strict infection prevention, good skin and lung care, and close work with an experienced specialist team can greatly improve life quality and long-term outlook. Families are not alone—support groups and expert centres can guide them through each stage. [15]

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.

The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members

Last Updated: February 13, 2025.