Hyper-IgE Syndrome (HIES)

Table of Contents

  1. What is Hyper-IgE Syndrome?
  2. Two Forms: AD-HIES and AR-HIES
  3. How HIES Develops: The Immunology of STAT3
  4. The Hallmark: Cold Abscesses
  5. Lung Disease and Pneumatoceles
  6. Systemic Features: Bones, Teeth, and Connective Tissue
  7. DOCK8 Deficiency: The AR-HIES Form
  8. Diagnosing HIES: Scoring, Lab Tests, and Genetics
  9. Treatment: Infection Prevention and Supportive Care
  10. Living with HIES: Daily Life and Patient Resources
  11. Key Research Papers
  12. Connections
  13. Featured Videos

What is Hyper-IgE Syndrome?

Hyper-IgE Syndrome (HIES) — also known as Job's Syndrome or Buckley Syndrome — is a rare primary immunodeficiency defined by one of the most striking laboratory findings in all of medicine: extraordinarily elevated serum IgE levels. While a healthy adult typically has IgE below 100–150 IU/mL, patients with HIES routinely have IgE levels of 2,000–100,000 IU/mL or higher. No other primary immunodeficiency produces IgE elevations of this magnitude, which is why markedly elevated IgE is the central diagnostic marker of the condition.

The disease is characterized by a classic clinical triad first described in the 1960s and 1970s:

  1. Markedly elevated serum IgE (typically exceeding 2,000 IU/mL; often 10,000 IU/mL or far higher)
  2. Recurrent "cold" skin abscesses — staphylococcal abscesses that form without the usual signs of inflammation (no local heat, redness, or tenderness), because the inflammatory response itself is defective
  3. Severe eczema — often the earliest manifestation, beginning as a neonatal rash and evolving into chronic, treatment-resistant atopic dermatitis

The name "Job's Syndrome" derives from the Biblical figure Job, who was afflicted with boils from head to foot — an apt metaphor for the recurrent abscesses these patients endure. The condition was first comprehensively described by Dr. Rebecca Buckley at Duke University in 1972, which is why it is also called Buckley Syndrome. HIES affects roughly 1 in 1,000,000 people worldwide, with no strong ethnic or sex predisposition, though the dominant form may appear slightly more often in males in some series.

Despite its rarity, HIES is an important disease to recognize because its consequences — severe recurrent infections, destructive lung disease, and skeletal complications — are largely preventable with early diagnosis and appropriate prophylactic treatment. The average time from first symptoms to diagnosis remains unfortunately long, partly because the combination of eczema, skin infections, and elevated IgE is often misattributed to severe atopic disease rather than an underlying immunodeficiency.

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Two Forms: AD-HIES and AR-HIES

HIES is not a single genetic disease but an umbrella term for at least two clinically and genetically distinct conditions that share the classic IgE triad. Recognizing which form a patient has significantly influences both prognosis and treatment decisions.

Autosomal Dominant HIES (AD-HIES) — STAT3 Mutations

The most common form, AD-HIES, is caused by dominant-negative heterozygous mutations in the STAT3 gene (Signal Transducer and Activator of Transcription 3). These mutations impair the function of the STAT3 protein — a critical transcription factor activated downstream of many cytokine receptors, including those for IL-6, IL-10, IL-17, IL-21, and IL-22. Because the mutant STAT3 protein actively interferes with normal STAT3 function (dominant-negative effect), a single mutated copy is sufficient to cause disease.

AD-HIES is distinguished by a broad clinical phenotype that extends well beyond the immune system to include distinctive connective tissue and skeletal abnormalities — retained primary teeth, scoliosis, pathological fractures, and characteristic facial features. These non-immune features arise because STAT3 signaling is important in many tissues outside the immune system. Most cases arise de novo (new mutations in the affected individual) rather than being inherited from an affected parent, though autosomal dominant inheritance from a parent does occur.

Autosomal Recessive HIES (AR-HIES) — DOCK8 Mutations

The second major form, AR-HIES, is caused by biallelic loss-of-function mutations in the DOCK8 gene (Dedicator of Cytokinesis 8). Both copies of the gene must be mutated for disease to occur, which is why parents of affected children are usually unaffected carriers. AR-HIES shares the elevated IgE and eczema of the dominant form but has a distinctly different infectious profile and is generally considered more severe overall.

Where AD-HIES is dominated by staphylococcal and fungal infections, AR-HIES is characterized by recurrent and severe viral infections — particularly extensive HPV warts, herpes simplex, molluscum contagiosum, and herpes zoster. Connective tissue and skeletal features typical of AD-HIES are generally absent in AR-HIES. Crucially, AR-HIES carries a significantly elevated risk of malignancy, particularly HPV-associated squamous cell carcinomas and lymphomas, and responds well to hematopoietic stem cell transplantation (HSCT), which can be curative.

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How HIES Develops: The Immunology of STAT3

Understanding why STAT3 mutations produce such a peculiar combination of very high IgE and very poor neutrophil responses requires a brief look at what STAT3 normally does in the immune system.

STAT3 is activated when cytokines — chemical messengers including IL-6, IL-10, IL-17, IL-21, and IL-22 — bind to their receptors on immune cells. This activation triggers STAT3 to enter the cell's nucleus and turn on genes needed for proper immune cell development and function. In HIES, the dominant-negative STAT3 mutation cripples this signaling cascade, with several critical downstream consequences:

Impaired Th17 Cell Differentiation

The most important immunological consequence of STAT3 loss-of-function is a dramatic reduction in Th17 helper T cells. Th17 cells are a subset of CD4+ T cells named for their production of the cytokines IL-17 and IL-22. These cytokines are essential for recruiting neutrophils to the skin and mucous membranes and for maintaining the barrier function of skin and gut epithelium against bacteria and fungi. In HIES, the block in STAT3 signaling prevents naive CD4+ T cells from differentiating into the Th17 lineage.

The consequence is a selective gap in mucosal and cutaneous immunity. Neutrophils cannot be efficiently recruited to sites of infection in the skin and lungs. Candida and Staphylococcus — organisms normally repelled by IL-17-dependent barrier defenses — establish recurrent infections. The classic "cold" abscess is the direct result: Staphylococcus accumulates in tissue, but the neutrophil recruitment that normally causes the redness, heat, and pain of inflammation fails to materialize. Pus collects, the abscess grows, but the expected inflammatory signs are largely absent.

Skewed Th2 Response and Extremely High IgE

When the Th17 pathway is blocked, the immune system's T-helper responses skew strongly toward Th2 — the other major helper T-cell lineage, which promotes allergic-type immune responses. Th2 cytokines (particularly IL-4 and IL-13) powerfully drive B cells to produce IgE rather than other antibody classes. This Th2 skew explains why HIES patients produce vastly more IgE than any other immunodeficient population. Paradoxically, however, this enormous IgE is largely non-functional — it represents a misdirected immune response, not an effective defense against infection.

Impaired Acute-Phase Response

STAT3 is also required for the liver's acute-phase response to infection — the rapid production of C-reactive protein (CRP) and other inflammatory markers. In HIES patients, CRP may fail to rise appropriately during serious infection, which can dangerously mask the severity of illness. Clinicians caring for HIES patients cannot rely on CRP elevation to gauge the seriousness of a suspected infection.

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The Hallmark: Cold Abscesses

The defining clinical feature of HIES — and the one that most dramatically illustrates the underlying immune defect — is the cold abscess. Understanding what makes these abscesses "cold" is essential for clinicians and patients alike.

In a person with a normal immune system, a Staphylococcus aureus skin abscess presents as the classic "SIRS" picture at the local level: the area becomes red, hot, swollen, and painful. This inflammatory response is driven by neutrophils flooding into the infected tissue and releasing cytokines (including IL-1, IL-6, and IL-17-driven signals) that dilate local blood vessels, increase their permeability, and recruit more immune cells. The heat, redness, and tenderness are signs that the immune system is mounting a vigorous counterattack.

In HIES, the neutrophil recruitment step is defective because IL-17 — the key chemokine signal that calls neutrophils to the skin — is not being produced in adequate amounts due to the Th17 deficit. As a result, Staphylococcus proliferates in the dermis and subcutaneous tissue, forming a collection of pus, but without triggering the normal inflammatory cascade. The abscess is "cold": it is a fluctuant, pus-filled collection of infected tissue, but it lacks redness, warmth, and tenderness. Patients and parents may not even realize a large abscess is forming because it is not painful.

What Cold Abscesses Look Like in Practice

Cold abscesses in HIES most commonly affect the face, neck, and trunk. They can reach considerable size — golf ball-sized or larger — before being noticed. The overlying skin may appear relatively normal in color and texture, with only a soft, fluctuant swelling beneath the surface. Because they are not painful and lack the signs that would normally prompt urgent medical attention, these abscesses are sometimes present for weeks or months before treatment is sought.

Staphylococcus aureus is the causative organism in the vast majority of cases, though other bacteria including Streptococcus can occasionally be involved. Surgical incision and drainage is required in addition to antibiotics, because the pus collection must be physically evacuated. HIES patients may require dozens of incision and drainage procedures over their lifetime without prophylactic antibiotic treatment.

Eczema: The Earliest Manifestation

Before the skin abscesses typically appear, the first sign of HIES in most patients is eczema, beginning in the neonatal period — often within the first weeks of life. The initial presentation is frequently a pustular or papular rash on the face and scalp that resembles neonatal acne or seborrheic dermatitis. Over the first months of life, this evolves into chronic, pruritic eczematous plaques, particularly affecting the face, scalp, and flexural surfaces. The eczema in HIES is often severe and treatment-resistant, resembling atopic dermatitis but typically more extensive and responding poorly to standard topical therapies.

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Lung Disease and Pneumatoceles

The most serious and potentially life-threatening complication of AD-HIES is progressive structural lung disease, culminating in the formation of pneumatoceles — air-filled cysts in the lung parenchyma. Lung disease is the primary driver of morbidity and mortality in HIES, and its prevention is the central goal of treatment.

Recurrent Pulmonary Infections

HIES patients experience recurrent pneumonias beginning in childhood. The causative organisms reflect the underlying Th17 deficiency: Staphylococcus aureus and Haemophilus influenzae are the most common bacterial pathogens, while Aspergillus fumigatus and other molds become important opportunistic pathogens over time. These pneumonias can be severe and difficult to clear despite appropriate antibiotic therapy, because the neutrophil response in the lung — just as in the skin — is deficient.

Pneumatoceles: The Pathognomonic Complication

After one or more severe pneumonias, the lung parenchyma is damaged and small cysts begin to form. As these cysts enlarge, they are called pneumatoceles — thin-walled, air-filled cavities where normal lung tissue used to be. Pneumatoceles are a hallmark of HIES and are among the most pathognomonic imaging findings in all of primary immunodeficiency. They are visualized on chest CT scan and may range in size from centimeters to occupying large portions of the lung lobe.

Pneumatoceles are dangerous for two reasons. First, they represent irreversible destruction of functioning lung tissue. Second, they are at high risk of becoming colonized and infected by opportunistic organisms — particularly Aspergillus fumigatus and Pseudomonas aeruginosa — which are extremely difficult to eradicate once established within a cavity. The image that immunologists sometimes use is "Swiss cheese lungs": lungs riddled with holes of varying sizes, each representing a site of previous tissue destruction.

Secondary Infections of Pneumatoceles

Aspergillus colonization of pre-existing pneumatoceles (forming an aspergilloma — a "fungal ball") is a dreaded complication that may require surgical resection of the affected lobe. Pseudomonas aeruginosa can also colonize pneumatoceles and establish a chronic infection similar to what is seen in cystic fibrosis, requiring prolonged courses of anti-pseudomonal antibiotics. These secondary infections often accelerate the structural decline of lung function.

Preventive Approach

The goal of prophylactic antibiotic therapy is to prevent the bacterial pneumonias that initiate pneumatocele formation in the first place. Once established, pneumatoceles cannot be reversed — they can only be prevented from becoming infected. Patients with significant symptomatic or infected pneumatoceles may require surgical resection, which can be technically challenging due to the surrounding tissue inflammation. Regular chest CT surveillance is recommended to monitor pneumatocele burden and detect early signs of colonization.

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Systemic Features: Bones, Teeth, and Connective Tissue

One of the features that distinguishes AD-HIES from virtually every other primary immunodeficiency is its involvement of non-immune tissues — the skeleton, connective tissue, dentition, and facial structure. These features reflect STAT3's broad role in tissue development and homeostasis beyond the immune system. Because these findings are so characteristic, clinicians who recognize them can often suspect the diagnosis on clinical examination alone.

Retained Primary Teeth: A Pathognomonic Sign

Perhaps the most striking and diagnostically specific dental feature of HIES is failure of primary (baby) teeth to shed normally. In healthy children, primary teeth loosen and fall out as the permanent teeth erupt underneath them, physically resorbing the primary root. In HIES, this root resorption process fails — the primary teeth remain firmly anchored even as the permanent teeth attempt to erupt, sometimes resulting in a child having two nearly complete sets of teeth simultaneously. Without intervention (extraction of retained primary teeth), permanent teeth may erupt in abnormal positions or fail to erupt at all. Early and proactive dental care — with extraction of retained primary teeth to allow proper permanent eruption — is an important but often overlooked part of HIES management.

Characteristic Facial Features

Adults and older children with HIES often develop distinctive facial features that become more pronounced with age: coarse facial features with a prominent, broad forehead; deep-set eyes; a broad, fleshy nasal bridge and tip; and mild facial asymmetry. These features may not be obvious in early childhood but become recognizable over time and are part of the NIH clinical scoring system for HIES. A high-arched palate and macroglossia (large tongue) are also described.

Scoliosis and Spinal Abnormalities

Scoliosis — lateral curvature of the spine — develops in a large proportion of AD-HIES patients, often in adolescence. It may be progressive and occasionally requires bracing or surgical correction. The mechanism likely reflects impaired STAT3 signaling in skeletal development and connective tissue maintenance. Accompanying this, some patients develop cervical spine instability (particularly at C2-C3) and Chiari I malformation (downward displacement of the cerebellar tonsils through the foramen magnum), which occasionally causes headaches or neurological symptoms.

Osteoporosis and Pathological Fractures

Bone mineral density is reduced in many HIES patients, and pathological fractures — fractures occurring with minimal or no trauma — are well documented. Rib fractures and minor long-bone fractures may occur spontaneously or with activities that would not normally cause injury. Bisphosphonate therapy and calcium/vitamin D supplementation may be beneficial, though data specifically in HIES are limited. Dual-energy X-ray absorptiometry (DEXA) scanning to assess bone density is recommended as part of routine monitoring.

Connective Tissue and Vascular Abnormalities

Hyperextensibility of joints is common in HIES, reflecting systemic connective tissue laxity. In a minority of patients, more serious vascular complications have been reported, including coronary artery aneurysms and aortic aneurysms. These are rare but potentially life-threatening, and periodic cardiac and vascular imaging may be warranted in adult HIES patients. The connective tissue phenotype overlaps superficially with Marfan syndrome and Ehlers-Danlos syndrome, which should be considered in the differential diagnosis when immunodeficiency features are absent.

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DOCK8 Deficiency: The AR-HIES Form

DOCK8 deficiency — the autosomal recessive form of HIES — shares the elevated IgE and eczema of STAT3-deficient HIES but has a fundamentally different immunological profile and clinical course. Understanding the distinction is critical because the treatment implications differ significantly.

What DOCK8 Does

DOCK8 (Dedicator of Cytokinesis 8) is a guanine nucleotide exchange factor that regulates the cytoskeleton of lymphocytes — the internal scaffolding that allows immune cells to move efficiently, form stable contacts with target cells, and survive in peripheral tissues. Without functional DOCK8, lymphocytes — particularly CD8+ cytotoxic T cells and NK cells — cannot navigate through tight extracellular spaces (like the dermis) and undergo a phenomenon called "cytoskeletal collapse," leading to premature cell death when they attempt to migrate through tissue.

Viral Susceptibility: The Dominant Clinical Problem

Because DOCK8 deficiency impairs cytotoxic T-cell and NK-cell function rather than neutrophil recruitment, the infectious phenotype of AR-HIES is dominated by viral rather than bacterial pathogens. Patients develop:

Malignancy Risk

A critically important feature of AR-HIES is its significantly elevated risk of malignancy. HPV-associated cancers — squamous cell carcinoma of the skin, anus, cervix, and oropharynx — develop at higher rates and younger ages than in the general population, reflecting the inability to control HPV viral load. Lymphomas, both Hodgkin and non-Hodgkin, also occur at elevated rates. Regular cancer surveillance is an essential component of AR-HIES management.

Hematopoietic Stem Cell Transplantation for AR-HIES

Unlike AD-HIES (where the benefit of HSCT is still being established), HSCT has emerged as a potentially curative treatment for AR-HIES. Successful transplantation reconstitutes the DOCK8-expressing lymphocyte population, restores cytotoxic T-cell and NK-cell function, reduces infection frequency, and may reduce malignancy risk. Results from case series are encouraging, with most transplanted patients experiencing dramatic improvement in viral infection burden and quality of life. HSCT should be considered for AR-HIES patients with severe phenotypes, particularly those with recurrent malignancies or life-threatening infections.

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Diagnosing HIES: Scoring, Lab Tests, and Genetics

HIES diagnosis rests on combining clinical features with laboratory results and, increasingly, molecular genetic testing. No single finding is diagnostic in isolation — the pattern must be recognized.

The NIH Clinical Scoring System

The most widely used diagnostic tool is the NIH HIES scoring system (also called the Woods scoring system), which assigns points to clinical and laboratory features. Points are assigned for:

A score above 40 suggests a high probability of HIES; a score above 60 is considered consistent with a definitive clinical diagnosis. This scoring tool is particularly valuable in cases where genetic testing is unavailable or inconclusive.

Laboratory Testing

Key laboratory evaluations in suspected HIES include:

Genetic Testing

STAT3 gene sequencing confirms the diagnosis of AD-HIES. Mutations are typically heterozygous and cluster in the SH2 domain and DNA-binding domain of the STAT3 protein — the functional regions responsible for cytokine signaling and transcriptional activation, respectively. The dominant-negative mechanism means that these mutations must impair the function of the normal STAT3 allele as well, which is why they are particularly severe. If STAT3 sequencing is negative and clinical features more closely resemble AR-HIES (viral predominance, no connective tissue features), DOCK8 gene sequencing and copy number analysis (looking for deletions of one or both copies) should be performed.

Chest CT Scanning

Chest CT is essential at diagnosis and for ongoing surveillance. Key findings include air trapping, bronchial wall thickening, tree-in-bud opacity during active infection, parenchymal consolidation, and — the pathognomonic finding — pneumatoceles of varying sizes. CT allows assessment of the structural lung disease burden and guides decisions about prophylactic antifungal therapy and surgical intervention.

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Treatment: Infection Prevention and Supportive Care

There is no cure for AD-HIES (STAT3 deficiency) in the way that transplantation can cure AR-HIES. Management is therefore centered on preventing infections before they cause irreversible damage, particularly the pneumonias that lead to pneumatocele formation and lung destruction. Early, consistent prophylaxis dramatically reduces morbidity.

Anti-Staphylococcal Prophylaxis: The Cornerstone

Continuous prophylactic antibiotics targeting Staphylococcus aureus form the foundation of HIES management. Options include:

Prophylaxis is given continuously, year-round, and indefinitely. Clinical series consistently show that patients on continuous anti-staphylococcal prophylaxis have dramatically fewer skin abscesses, fewer pneumonias, and better long-term lung function than untreated patients. The decision to start prophylaxis should not be delayed waiting for genetic confirmation — if the clinical picture strongly suggests HIES, prophylaxis should begin immediately.

Antifungal Prophylaxis

Fluconazole (or itraconazole) is given to prevent and treat mucocutaneous candidiasis and to reduce the risk of Aspergillus pneumonia. Fluconazole prophylaxis significantly reduces the burden of oral and vaginal candidiasis, improving quality of life considerably. In patients with established pneumatoceles at risk for Aspergillus colonization, extended antifungal prophylaxis with voriconazole or posaconazole may be appropriate, though this requires balancing efficacy against drug toxicity.

Managing Skin Abscesses

When cold abscesses form despite prophylaxis, they require incision and drainage in addition to systemic antibiotic treatment. The pus must be physically removed — antibiotics alone are often insufficient to clear a large abscess cavity. Because abscesses may not be painful or warm, patients and families should perform regular skin surveillance to detect new collections early. Culture of abscess contents helps guide antibiotic selection, particularly to detect methicillin-resistant S. aureus (MRSA).

Skin Care for Eczema

Management of the chronic eczema in HIES follows principles similar to atopic dermatitis treatment but requires additional attention to infection:

Intravenous Immunoglobulin (IVIG)

IVIG is used in HIES patients with recurrent infections despite maximal prophylaxis, particularly those who also have functional antibody deficiency or abnormally low IgG despite elevated IgE. IVIG provides passive antibody protection similar to its role in CVID. It does not correct the Th17 defect or the underlying STAT3 dysfunction, but it can reduce the frequency of breakthrough bacterial infections. Dosing follows similar principles to CVID treatment — trough IgG levels guide dose adjustment.

Dental Management

Proactive dental care is an often underappreciated but important aspect of HIES management. Retained primary teeth should be extracted by a dentist familiar with the condition, as this allows permanent teeth to erupt in their correct positions. Without extraction, permanent teeth may erupt ectopically (in abnormal positions), become impacted, or fail to erupt at all, creating long-term dental and jaw structural problems. Regular dental surveillance beginning in early childhood is recommended for all AD-HIES patients.

HSCT for AD-HIES

Hematopoietic stem cell transplantation for AD-HIES (STAT3 deficiency) is more controversial than for AR-HIES. STAT3 is expressed in virtually all nucleated cells, not just hematopoietic cells, so replacing the bone marrow does not correct the connective tissue and skeletal manifestations. However, growing case series suggest that HSCT can substantially improve the immunological features — reducing infection frequency, improving Th17 cell numbers, and potentially halting pneumatocele progression. HSCT is increasingly being considered for AD-HIES patients with severe phenotypes, particularly those with life-threatening or rapidly progressive lung disease despite maximum prophylaxis. The decision should be made at a specialized center with expertise in both HIES and transplantation immunology.

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Living with HIES: Daily Life and Patient Resources

Living with Hyper-IgE Syndrome requires ongoing vigilance, but with appropriate medical management, many patients lead full and active lives. The key is building habits and knowledge that reduce infection risk while supporting overall health and wellbeing.

Infection Surveillance at Home

Because cold abscesses are neither painful nor inflamed in the usual way, patients and families must learn to perform regular skin checks — running hands over the skin to feel for fluctuant (soft, fluid-filled) swellings that may not be visible or tender. Any suspicious swelling should be evaluated promptly by a clinician. Similarly, respiratory symptoms — even mild cough or increased shortness of breath — should be taken seriously and evaluated early, because pneumonia can progress without the fever and leukocytosis that would normally signal severity.

School and Work Considerations

Children with HIES can generally attend school, though they may miss more days than average due to infections and procedures. Informing teachers and school nurses about the diagnosis — particularly explaining that infections can be serious even when the child does not appear severely ill — is important. Adolescents and adults with HIES may need flexible work arrangements during periods of frequent infections or during recovery from procedures. Career choices that minimize exposure to highly infectious environments (crowded settings, certain healthcare roles) may be worth considering, though this is a personal decision.

Dental Care as a Priority

Regular, proactive dental care is not optional for HIES patients — it is a medical priority. Dentists should be informed of the diagnosis, as retained primary teeth require planned extraction rather than waiting for natural shedding. A pediatric dentist experienced with immunodeficient patients is ideal. Good oral hygiene reduces the risk of dental infections, which could potentially seed systemic infections in an immunocompromised patient.

Physical Activity and Bone Health

While HIES patients have osteoporosis and a risk of pathological fractures, this should not lead to excessive restriction of physical activity — quite the opposite. Weight-bearing exercise is important for maintaining bone density. However, high-impact contact sports or activities with significant fall risk may need modification, particularly for patients with documented osteoporosis or prior fractures. A bone health specialist (endocrinologist or rheumatologist) can provide individualized guidance.

Psychological Wellbeing

The burden of managing a rare disease — with its cycles of infections, procedures, hospital admissions, and medical uncertainty — takes a real psychological toll on patients and families. The rarity of HIES means that most clinicians, schools, employers, and even family members have never heard of it, which adds an additional layer of isolation. Connecting with patient advocacy organizations can be transformative:

Tracking and Monitoring Your Own Health

Keeping a personal health log — tracking infection episodes, abscess locations and sizes, pulmonary symptoms, antibiotic courses, and clinical scoring parameters — can help both patients and clinicians recognize patterns and adjust management. Patients who understand their own NIH HIES score and its components are better positioned to communicate the severity of their condition to new providers and to recognize when new features warrant evaluation.

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Key Research Papers

  1. Minegishi Y et al. Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome. Nature. 2007. PMID 17881745
  2. Holland SM et al. STAT3 mutations in the hyper-IgE syndrome. N Engl J Med. 2007. PMID 17881744
  3. Engelhardt KR et al. Large deletions and point mutations involving the dedicator of cytokinesis 8 (DOCK8) in the autosomal-recessive form of hyper-IgE syndrome. J Allergy Clin Immunol. 2009. PMID 18948956
  4. Zhang Q et al. Combined immunodeficiency associated with DOCK8 mutations. N Engl J Med. 2009. PMID 19494218
  5. Freeman AF, Holland SM. The hyper-IgE syndromes. Immunol Allergy Clin North Am. 2008. PMID 18282554
  6. Woellner C et al. Mutations in STAT3 and diagnostic guidelines for hyper-IgE syndrome. J Allergy Clin Immunol. 2010. PMID 20159255
  7. Grimbacher B et al. Hyper-IgE syndrome with recurrent infections — an autosomal dominant multisystem disorder. N Engl J Med. 1999. PMID 10080849
  8. Sowerwine KJ et al. Hyper-IgE syndrome update. Ann N Y Acad Sci. 2012. PMID 22853347
  9. Milner JD et al. Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature. 2008. PMID 18337720
  10. Gernez Y et al. Blood basophil activation is a reliable biomarker of allergic asthma evaluated with multiple allergens and for monitoring the treatment with omalizumab. Clin Exp Allergy. 2016. Alternate citation: Maillard MH et al. J Allergy Clin Immunol. 2014. PMID 24856987
  11. Hsu AP et al. Intermediate phenotypes in patients with autosomal dominant hyper-IgE syndrome caused by somatic mosaicism. J Allergy Clin Immunol. 2013. PMID 23684070
  12. Dimitrova D et al. Outcomes of hematopoietic stem cell transplantation for autosomal dominant and autosomal recessive hyper-IgE syndrome. J Allergy Clin Immunol Pract. 2021. PMID 33180439

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Connections

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