Hyper-IgE syndrome
| Hyper-IgE syndrome | |
| ICD-10 | D82.4 |
|---|---|
| ICD-9 | 288.1 |
| OMIM | 29572 147060 |
| DiseasesDB | 29572 |
| eMedicine | derm/845 ped/1074 |
| MeSH | D007589 |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]
Synonyms and keywords: Job-Buckley syndrome; Job syndrome; Buckley syndrome.
Overview
Hyper IgE syndrome (HIES) is a heterogeneous group of disorders characterized by recurrent staphylococcal infections, unusual eczema-like skin rashes, severe lung infections that result in pneumatoceles (balloon-like lesions that may be filled with air or pus or scar tissue) and very high concentrations of serum IgE. Some patients have an autosomal dominant form of the disease; these patients have problems with their bones including recurrent fractures and scoliosis. Many patients with autosomal dominant hyper IgE syndrome fail to lose their baby teeth and have two sets of teeth simultaneously.
Historical Perspective
- HIES was first described by Davis et al in 1966 and it was named as Job's syndrome.
- The criterai included triad of eczema, recurrent skin and lung infections and high serum IgE .
Classification
Hyper IgE syndrome is classified into 2 types:
- Autosomal dominant.
- Autosomal recessive.
Pathophysiology
Abnormal neutrophil chemotaxis due to decreased production of interferon gamma is thought to cause the disease.[1] But both autosomal dominant and recessive inheritance have been described. The disease was linked to mutations in the STAT3 gene after cytokine profiles indicated alterations in the STAT3 pathway.[2]
Causes
- Hyper igE syndrome is caused due to mutations in the signal transducer and activator of transcription 3 (STAT3) and tyrosine kinase 2 (TYK2) gene.
- STAT 3 gene is essential for the differentiation of helper T cells, mutation causes autosomal dominant type.
- Tyrosine kinase 2 (TYK2) gene mutation causes autosomal recessive type.
Differentiating Hyper-IgE syndrome from Other Diseases
Hyper IgE syndrome can be differentiated from other diseases of the same kind by measuring the serum IgE levels.
| Disease | IgM levels | IgG levels | IgA levels | IgE levels | B cell defect | T cell defect |
|---|---|---|---|---|---|---|
| IgM deficiency | ↓ | - | - | - | - | - |
| IgA deficiency | - | - | ↓ | - | - | - |
| IgG deficiency | - | ↓ | - | - | - | - |
| IgE deficiency | - | - | - | ↓ | - | - |
| Hypoproteinemia/Proteinuria | ↓ | ↓ | ↓ | ↓ | - | - |
| Comined Immunodeficiency | ↓ | ↓ | ↓ | ↓ | + | + |
| X linked agammaglobulinemia | ↓ | ↓ | ↓ | ↓ | + | - |
| Hyperimmunoglobulin M syndrome | ↑ | ↓ | ↓ | ↓ | + | - |
| Common variable immunodeficiency | ↓ | ↓ | ↓ | ↓ | + | - |
| Wiskott-Aldrich syndrome | ↓ | ↓ | ↑ | ↑ | - | + |
| Hyper IgE syndrome | - | - | - | ↑ | - | + |
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications, and Prognosis
Natural History
- Patients of hyper IgE syndrome are born with pustular or eczematoid rashes, or they may appear in first month of life.
- Recurrent eczema, boils and skin abscesses.
- Recurrent infections such as chronic otitis media, sinusitis, pneumonias, mucocutaneous infections, neurological and systemic.
- Hyperextensible joints/recurrent bone fractures, and distinctive coarse faces( prominent forehead, deep-set eyes, broad nasal bridge, and wide interalar distance) in early childhood.
- Eczema complicated by mucocutaneous candidiasis involving the mouth and diaper areas.
- Skeletal abnormalities include scoliosis, osteopenia, minimal trauma fractures, hyperextensibility, and degenerative joint disease.
- Retained primary teeth past the age of normal dental exfoliation.
Complications
- Pustular and eczematoid rashes usually begin within the first month of life, usually affecting the face and scalp.
- Recurrent pneumonias start in childhood.
- Recurrent lung infections cause bronchiectasis and formation of pneumatocoeles that lead to secondary infections such as fungal and gram negative bacterial infections resulting in pulmonary vessels rupture and haemoptysis.
- Mucocutaneous candidiasis is common, manifesting typically as oral thrush, vaginal candidiasis or onychomycosis.
- Skeletal abnormalities include scoliosis, osteopenia, minimal trauma fractures, hyperextensibility, and degenerative joint disease.
- Chiari 1 malformations are common.
- Arterial aneurysms are fairly common. Aneurysms can be present in brain circulation or Aorta. It can lead to myocardial infarction or stroke.
- Malignancies such as squamous cell carcinoma, cutaneous T-cell lymphoma/leukemia, Burkitt lymphoma, Hodgkin's and non-Hodgkin's lymphoma .
- Systemic vasculitis.
Prognosis
Diagnosis
Diagnostic Criteria
Diagnosis requires clinical interepretation of symptoms alongwith laboratory findings..
- Serum IgE levels above 2,000 IU/ml(100 times greater than normal).
- Increased levels of eosinophills with normal levels of neutrophils and lymphocytes.
- A scoring system devised by NIH for the diagnosis of hyper IgE syndrome, score >30 suggests the presence of the disease.
| Clinical findings | Points* | |||||||||
| 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 10 | |
| Highest serum-IgE level (international units/mL)¶ | <200 | 200 to 500 | 501 to 1000 | 1001 to 2000 | >2000 | |||||
| Skin abscesses | None | 1 to 2 | 3 to 4 | >4 | ||||||
| Pneumonia (episodes over lifetime) | None | 1 | 2 | 3 | >3 | |||||
| Parenchymal lung anomalies | Absent | Bronchiectasis | Pneumatocele | |||||||
| Retained primary teeth | None | 1 | 2 | 3 | >3 | |||||
| Scoliosis, maximum curvature | <10° | 10 to 14° | 15 to 20° | >20° | ||||||
| Fractures with minor trauma | None | 1 to 2 | >2 | |||||||
| Highest eosinophil count (cells/microL)Δ | <700 | 700 to 800 | >800 | |||||||
| Characteristic face | Absent | Mildly present | Present | |||||||
| Midline anomaly◊ | Absent | Present | ||||||||
| Newborn rash | Absent | Present | ||||||||
| Eczema (worst stage) | Absent | Mild | Moderate | Severe | ||||||
| Upper respiratory infections per year | 1 to 2 | 3 | 4 to 6 | >6 | ||||||
| Candidiasis | None | Oral | Fingernails | Systemic | ||||||
| Other serious infections | None | Severe | ||||||||
| Fatal infection | Absent | Present | ||||||||
| Hyperextensibility | Absent | Present | ||||||||
| Lymphoma | Absent | Present | ||||||||
| Increased nasal width§ | <1 SD | 1 to 2 SD | >2 SD | |||||||
| High palate | Absent | Present | ||||||||
| Young-age correction | >5 years | 2 to 5 years | 1 to 2 years | ≤1 year | ||||||
History and Symptoms
- Patients of hyper IgE syndrome are born with pustular or eczematoid rashes, or they may appear in first month of life.
- Recurrent eczema, boils and skin abscesses.
- Recurrent infections such as chronic otitis media, sinusitis, pneumonias, mucocutaneous infections, neurological and systemic.
- Hyperextensible joints/recurrent bone fractures, and distinctive coarse faces( prominent forehead, deep-set eyes, broad nasal bridge, and wide interalar distance) in early childhood.
- Eczema complicated by mucocutaneous candidiasis involving the mouth and diaper areas.
- Skeletal abnormalities include scoliosis, osteopenia, minimal trauma fractures, hyperextensibility, and degenerative joint disease.
- Retained primary teeth past the age of normal dental exfoliation.
Physical Examination
- Coarse facial features( prominent forehead, deep-set eyes, broad nasal bridge, and wide interalar distance).
- Dental abnormalities- retained primary teeth.
- Facial pain(sinusitis), ear pain and discharge(otitis media).
- Purulent sputum producing cough or dry cough due to recurrent pneumonias.
- Eczematous dermatitis and lichenification affect the face, trunk, and extremities.
- Boils and multiple skin abscesses.
- Purpural rash.
- Skeletal abnormalities include scoliosis, osteopenia, minimal trauma fractures, hyperextensibility, and degenerative joint disease.
Laboratory Findings
Elevated IgE is the hallmark of HIES, usually > 10 times normal. However, patients younger than 6 months of age may have very low to non-detectable IgE levels. Eosinophilia is also a common finding with greater than 90% of patients having eosinophil elevations greater than two standard deviations above the normal mean.[3]
Imaging Findings
Other Diagnostic Studies
Treatment
Most patients with hyper IgE syndrome are treated with chronic antibiotics to help protect them from staphylococcal infections. Good skin care is also important in patients with hyper IgE syndrome. High-dose intravenous gamma-globulin has also been suggested for the treatment of severe eczema in patients with HIES and atopic dermatitis.[4]
Surgery
Primary Prevention
Secondary Prevention
References
- ↑ Borges W, Augustine N, Hill H (2000). "Defective interleukin-12/interferon-gamma pathway in patients with hyperimmunoglobulinemia E syndrome". J Pediatr. 136 (2): 176–80. PMID 10657822.
- ↑ Holland SM, DeLeo FR, Elloumi HZ et al. (2007). STAT3 Mutations in the Hyper-IgE Syndrome. N. Engl. J. Med. published online, 2007-09-19. doi:10.1056/NEJMoa073687.
- ↑ Grimbacher B, Holland S, Gallin J, Greenberg F, Hill S, Malech H, Miller J, O'Connell A, Puck J (1999). "Hyper-IgE syndrome with recurrent infections--an autosomal dominant multisystem disorder". N Engl J Med. 340 (9): 692–702. PMID 10053178.
- ↑ Kimata H (1995). "High-dose intravenous gamma-globulin treatment for hyperimmunoglobulinemia E syndrome". J Allergy Clin Immunol. 95 (3): 771–4. PMID 7897163.
[[Category:Immunology]