Job's syndrome

Job's Syndrome, also known as Hyperimmunoglobulin E Syndrome (HIES), is a rare, primary immunodeficiency disorder characterized by high levels of serum immunoglobulin E (IgE), eczema, and recurrent skin and lung infections. The syndrome is named after the biblical figure Job, who was afflicted with severe boils. It is a multisystem disorder that affects several parts of the body, including the skin, lungs, and bones.

Etiology and Pathogenesis

Job's Syndrome is primarily caused by mutations in the STAT3 gene, which plays a crucial role in the body's immune response and development. The STAT3 gene mutations lead to impaired signaling pathways that are essential for the functioning of the immune system, resulting in the hallmark features of the syndrome. In some cases, mutations in the DOCK8 gene have also been associated with a similar clinical phenotype, although this form of the disease may present with slightly different clinical features.

Clinical Manifestations

The clinical manifestations of Job's Syndrome can vary widely among affected individuals but typically include:

• Recurrent Skin Infections: Patients often suffer from recurrent skin infections, including boils and abscesses, which are usually caused by Staphylococcus aureus.
• Eczema: Eczema is a common feature, characterized by itchy, inflamed skin.
• Lung Infections: Recurrent lung infections, which can lead to the development of pneumatoceles and other chronic pulmonary complications.
• Elevated IgE Levels: Significantly elevated levels of immunoglobulin E (IgE) in the serum.
• Skeletal Abnormalities: Patients may exhibit skeletal abnormalities such as scoliosis, fractures with minimal trauma, and hyperextensibility of the joints.

Diagnosis

The diagnosis of Job's Syndrome is based on a combination of clinical features, laboratory findings, and genetic testing. Elevated serum IgE levels, in conjunction with the clinical history of recurrent skin and lung infections, are suggestive of the diagnosis. Genetic testing for mutations in the STAT3 or DOCK8 genes can confirm the diagnosis.

Treatment

There is no cure for Job's Syndrome, and treatment is aimed at managing symptoms and preventing complications. Management strategies include:

• Antibiotic Therapy: Prophylactic and therapeutic antibiotics to manage and prevent bacterial infections.
• Immunomodulatory Therapy: Treatment with immunomodulatory agents such as interferon gamma may be beneficial in some cases.
• IgE Management: Omalizumab, an anti-IgE antibody, has been used in some cases to help control symptoms.
• Supportive Care: Management of eczema with topical corticosteroids and emollients, and care for pulmonary complications.

Prognosis

The prognosis for individuals with Job's Syndrome varies. With appropriate management, many patients can lead relatively normal lives. However, the risk of severe infections and potential complications from lung and skeletal involvement can affect overall life expectancy and quality of life.

See Also

• Immunodeficiency
• Eczema
• Staphylococcus aureus
• Pneumatocele