Hyper IgE syndromes (HIES), also known as Job syndrome, are a group of rare primary immunodeficiency disorders characterized by abnormally high levels of immunoglobulin E (IgE) in the blood. IgE is an antibody involved in allergic responses, and its excessive production results in a high predisposition to allergies and recurrent infections.
The main symptoms of HIES include severe eczema (a chronic inflammatory skin condition), recurrent pulmonary infections (such as pneumonia and lung abscesses), and diverse features associated with connective tissue, bones, and teeth abnormalities. Patients with HIES often present craniofacial manifestations, including coarse facial features, a prominent forehead, and a wide nose. Other symptoms may include recurrent fractures, scoliosis, retained primary teeth, and brittle nails.
The two major forms of HIES are autosomal dominant HIES (AD-HIES) and autosomal recessive HIES (AR-HIES). AD-HIES is caused by mutations in the STAT3 gene, a protein involved in immune cell signaling pathways. AR-HIES, on the other hand, is caused by mutations in the DOCK8 gene, which is responsible for immune cell migration. Both forms result in impaired immune responses, particularly the function of T-cells and the development of natural killer cells.
Diagnosis of HIES involves a combination of clinical evaluation, a detailed medical history, specific immunological tests, and genetic testing to identify the underlying gene mutation. Management focuses on preventing and treating infections, as well as controlling the symptoms associated with allergic responses and eczema. This may involve a combination of immunomodulatory medications, antibiotics, antifungals, and personalized preventive measures to reduce the risk of infections. In severe cases, stem cell transplantation may be
