Hyper-IgE syndrome
Encyclopedia
Hyperimmunoglobulin E syndrome (HIES), also called Job's syndrome and Buckley syndrome, is a heterogeneous group of immune disorders.

Presentation

It is characterized by recurrent "cold" staphylococcal
Staphylococcus
Staphylococcus is a genus of Gram-positive bacteria. Under the microscope they appear round , and form in grape-like clusters....

 infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...

s, unusual eczema
Eczema
Eczema is a form of dermatitis, or inflammation of the epidermis . In England, an estimated 5.7 million or about one in every nine people have been diagnosed with the disease by a clinician at some point in their lives.The term eczema is broadly applied to a range of persistent skin conditions...

-like skin rashes, severe lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...

 infections that result in pneumatocele
Pneumatocele
A pneumatocele, or pneumatocyst is a cavity in the lungs filled with air that may result from pulmonary trauma. A pneumatocele results when a lung laceration, a cut or tear in the lung tissue, fills with air. A rupture of a small airway creates the air-filled cavity. Pulmonary lacerations that...

s (balloon-like lesions that may be filled with air or pus or scar tissue) and very high concentrations of the serum antibody IgE
IGE
IGE was one of the largest services company buying and selling virtual currencies and accounts for MMORPG. During its peak time, it had offices in Los Angeles, China , and headquarters & customer service centre in Hong Kong. IGE was one of the main monopoly in virtual economy services, also known...

. Inheritance can be autosomal dominant, or recessive, and autosomal dominant form of the disease; these patients have problems with their bones including recurrent fractures and scoliosis
Scoliosis
Scoliosis is a medical condition in which a person's spine is curved from side to side. Although it is a complex three-dimensional deformity, on an X-ray, viewed from the rear, the spine of an individual with scoliosis may look more like an "S" or a "C" than a straight line...

. Many patients with autosomal dominant hyper IgE syndrome fail to lose their primary teeth and have two sets of teeth simultaneously.

A common mnemonic used to remember the symptoms is FATED: coarse facies, cold staph abscesses, retained primary teeth, increased IgE, and dermatologic problems [eczema].

History

HIES was first described by Davis et al. in 1966 in two girls with red hair, chronic dermatitis, and recurrent staphylococcal abscesses and pneumonias. They named the disease after the biblical character Job
Book of Job
The Book of Job , commonly referred to simply as Job, is one of the books of the Hebrew Bible. It relates the story of Job, his trials at the hands of Satan, his discussions with friends on the origins and nature of his suffering, his challenge to God, and finally a response from God. The book is a...

, whose body was covered with boils by Satan
Satan
Satan , "the opposer", is the title of various entities, both human and divine, who challenge the faith of humans in the Hebrew Bible...

. In 1972, Buckley et al. described two boys with similar symptoms as well as coarse facies, eosinophilia
Eosinophilia
Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds 0.45×109/L . A marked increase in non-blood tissue eosinophil count noticed upon histopathologic examination is diagnostic for tissue eosinophilia. Several causes are known, with the most common being...

, and elevated serum IgE levels. These two syndromes are thought to be the same and are under the broad category of HIES.

Pathophysiology

Abnormal neutrophil chemotaxis
Chemotaxis
Chemotaxis is the phenomenon in which somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment. This is important for bacteria to find food by swimming towards the highest concentration of food molecules,...

 due to decreased production of interferon gamma by T lymphocytes is thought to cause the disease.

Both autosomal dominant and recessive inheritance have been described:
  • autosomal dominant, STAT3
    STAT3
    Signal transducer and activator of transcription 3 also known as STAT3 is a transcription factor which in humans is encoded by the STAT3 gene.- Function :The protein encoded by this gene is a member of the STAT protein family...

    . The disease was linked to mutations in the STAT3
    STAT3
    Signal transducer and activator of transcription 3 also known as STAT3 is a transcription factor which in humans is encoded by the STAT3 gene.- Function :The protein encoded by this gene is a member of the STAT protein family...

    gene after cytokine profiles indicated alterations in the STAT3 pathway.
  • autosomal recessive, DOCK8
    DOCK8
    Dock8 , also known as Zir3, is a large protein involved in intracellular signalling networks. It is a member of the DOCK-C subfamily of the DOCK family of guanine nucleotide exchange factors which function as activators of small G proteins.-Discovery:Dock8 was identified during a yeast two hybrid...

    .

Laboratory studies

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
Eosinophilia
Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds 0.45×109/L . A marked increase in non-blood tissue eosinophil count noticed upon histopathologic examination is diagnostic for tissue eosinophilia. Several causes are known, with the most common being...

 is also a common finding with greater than 90% of patients having eosinophil elevations greater than two standard deviations above the normal mean.

Clinical characteristics

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
Prognathism
Prognathism is a term used to describe the positional relationship of the mandible and/or maxilla to the skeletal base where either of the jaws protrudes beyond a predetermined imaginary line in the coronal plane of the skull. In general dentistry, oral and maxillofacial surgery and orthodontics...

. Additionally, facial skin was rough with prominent pores. Finally, some patients have scoliosis
Scoliosis
Scoliosis is a medical condition in which a person's spine is curved from side to side. Although it is a complex three-dimensional deformity, on an X-ray, viewed from the rear, the spine of an individual with scoliosis may look more like an "S" or a "C" than a straight line...

, as well as bones that fracture easily.

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
Atopic dermatitis
Atopic dermatitis is an inflammatory, chronically relapsing, non-contagious and pruritic skin disorder...

.
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