Job Syndrome (Hyper-IgE Syndrome)

Overview of Job Syndrome (Hyper-IgE Syndrome)

Job Syndrome medically known as Hyper-IgE Syndrome (HIES), it is a rare primary immunodeficiency disorder characterised by extremely high levels of immunoglobulin E (IgE), recurring infections, eczema-like skin rashes and skeletal or connective tissue abnormalities. Named after the biblical figure Job, who was plagued with painful sores, this condition affects the immune system’s ability to respond effectively to infections. It can be inherited or sporadic, and early diagnosis is key for managing the complications effectively.

Types of Job Syndrome

1. Autosomal Dominant Hyper-IgE Syndrome (AD-HIES)

Caused by STAT3 gene mutations; most common type; includes skeletal and connective tissue symptoms.

2. Autosomal Recessive Hyper-IgE Syndrome (AR-HIES)

Caused by DOCK8 gene deficiency; more severe viral infections and neurologic issues observed.

3. PHOX2B-associated Hyper-IgE Syndrome

Rare and less understood; associated with autonomic nervous system abnormalities.

Symptoms of Hyper-IgE Syndrome

Recurrent staphylococcal skin abscesses

Pneumonia leading to lung cysts or pneumatocele

Severe eczema-like rash starting in infancy

Frequent sinus and ear infections

Elevated IgE levels in blood tests

Delayed shedding of baby teeth

Joint hyperextensibility and scoliosis

Fractures with minor trauma

Facial features like a broad nasal bridge or deep-set eyes

Causes of Job Syndrome (Hyper-IgE Syndrome)

Caused by genetic mutations (mainly in STAT3 or DOCK8).

Autosomal dominant or recessive inheritance.

Disruption in immune system signaling pathways.

Inherited from one or both parents or occurs as a new mutation.

Complications in Job Syndrome (Hyper-IgE Syndrome)

Lung infections leading to chronic damage or abscesses.

Fungal infections (e.g., candidiasis).

Sepsis due to weak immune defense.

Allergic reactions and anaphylaxis.

Higher risk of lymphomas and other malignancies in some forms.

Growth delays or developmental anomalies in children.

Risk Factors of Job Syndrome (Hyper-IgE Syndrome)

Family history of immunodeficiency syndromes.

Genetic predisposition (STAT3 or DOCK8 mutations).

Consanguineous parents in recessive types.

Presence of recurrent infections and eczema in early childhood.

Preventions of Job Syndrome (Hyper-IgE Syndrome)

Currently not preventable due to genetic nature.

Genetic counseling for families with a history.

Prenatal testing may be considered in some cases.

Early detection and management help minimize complications.