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

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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. 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.

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	-	-	-	↑	-	+

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 and boils.
• 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.

Diagnosis

Physical Examination

HIES often appears early in life with recurrent staphylococcal and candidal infections, pneumonias, and eczematoid skin. Characteristic facial, dental, and skeletal abnormalities have also been described. Patients with HIES have either delay of or failure in shedding of primary teeth. The characteristic facial features are usually set by age 16. These include facial asymmetry, a prominent forehead, deep-set eyes, a broad nasal bridge, a wide, fleshy nasal tip, and mild prognathism. Additionally, facial skin was rough with prominent pores. Finally, some patients have scoliosis, as well as bones that fracture easily.

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.

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.

References

[[Category:Immunology]

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