Job syndrome, also known as the hyper-IgE syndrome is an immune system deficiency that makes the affected individual susceptible to severe infections of the skin and other organs. The symptoms appear during early infancy or childhood. This very rare condition is estimated to affect around 1 per million people.
Causes
This syndrome develops as the result of a mutation in the gene STAT3 in most of the cases. The STAT3 protein plays several important roles such as controlling certain genes, production of cells that break down bone tissue and the maturation of the immune cells which are essential to help the body fight off against harmful invaders. The genetic mutation disrupts the structure and the function of this protein affecting its ability to control the activity of certain genes and blocking the maturation of immune cells. Hence, the affected individuals are susceptible to develop various infections and the skeletal abnormalities. This syndrome is inherited in an autosomal dominant pattern meaning only one copy of the defective gene is sufficient to cause this condition. In most of the cases, the genetic mutation is inherited from an affected parent although it can also appear with no history of its prevalence in the family.
Symptoms
The severity of the symptoms varies on the different cases. They can exhibit rashes that are similar to eczema which may appear after 3 months of age. The recurrent skin infections can cause blisters, abscesses, scaling and open sores. They are prone to have the frequent onset of pneumonia caused by the lungs infection and inflammation that can result in the development of air-filled cavities known as pneumatoceles. The affected individuals also have a high level of IgE, bony abnormalities such as fractures and twisted spine (scoliosis), unusual facial appearance, dental problems such as double rows of teeth and pitted scarring of the face.
Diagnosis
The diagnosis of this syndrome is based on the evaluation of the individual’s history and in the identification of the features characteristic of this condition. The blood tests can detect the high levels of IgE and increased level of certain white blood cells called eosinophils. As the IgE level may become normal in adulthood, this should not rule out the diagnosis of Job syndrome. CT scans can detect the lung infections and pneumatoceles within the lungs. The genetic tests can confirm the diagnosis with the identification of the STAT3 mutation.
Treatment
There is no cure for Job syndrome. The treatment is based on the various symptoms that are evident in each case. This may require the coordinated efforts of various specialists such as pediatricians, dermatologists, dentist, orthopedists and immunologist to devise effective treatment options. This includes the antibiotics for the bacterial infections or anti-fungal medications for conditions such as mucocutaneous candidiasis. The skin problems may require a surgical drainage of the lesions, moisturizing creams and topical steroids. If the chronic lung infections result in the development of the air cavities (pneumatoceles), this may require a surgery to open the chest for the removal of the pneumatoceles.
References
https://rarediseases.org/rare-diseases/autosomal-dominant-hyper-ige-syndrome/
https://ghr.nlm.nih.gov/condition/autosomal-dominant-hyper-ige-syndrome#inheritance
