Summary about Disease
Job's syndrome-like disorder, now often referred to as Hyperimmunoglobulin E Syndrome (HIES), is a rare primary immunodeficiency disorder characterized by a triad of symptoms: recurrent skin and lung infections, elevated levels of immunoglobulin E (IgE) in the blood, and characteristic facial and skeletal abnormalities. It results from impaired neutrophil chemotaxis, which means the body's infection-fighting white blood cells don't migrate properly to sites of infection. HIES is not a single disease but a group of related disorders with similar clinical presentations but potentially different genetic causes. Autosomal dominant (AD-HIES) and autosomal recessive (AR-HIES) forms exist, each stemming from different genetic mutations.
Symptoms
The symptoms of HIES can vary in severity and presentation. Common symptoms include:
Recurrent Skin Infections: Eczema-like rash, boils, skin abscesses (often "cold," meaning little redness, pain, or pus), and fungal infections.
Recurrent Lung Infections: Pneumonia, often leading to pneumatoceles (air-filled cavities in the lung).
High IgE Levels: Markedly elevated levels of immunoglobulin E in the blood.
Characteristic Facial Features: Broad nasal bridge, prominent forehead, deep-set eyes, coarse facial skin.
Skeletal Abnormalities: Scoliosis, joint hyperextensibility, osteoporosis, and retained primary teeth.
Other: Failure to thrive, chronic mucocutaneous candidiasis (yeast infection of the skin and mucous membranes), and increased risk of certain malignancies.
Causes
HIES can be caused by mutations in several different genes.
STAT3 mutations: Are the most common cause of autosomal dominant HIES. These mutations impair signaling by several cytokines, leading to defects in immune cell development and function.
Other Genetic Mutations: Including mutations in TYK2, DOCK8, PGM3, SPINK5, ZNF341, and *ACT1*, may cause autosomal recessive forms of HIES. These genes play roles in immune cell development, signaling, and function.
Sporadic Mutations: In some cases, the genetic mutation is not inherited but occurs spontaneously.
Medicine Used
Treatment for HIES focuses on managing infections and alleviating symptoms:
Antibiotics: Prophylactic antibiotics (given regularly to prevent infections) are used to reduce the frequency and severity of bacterial infections.
Antifungals: Used to treat fungal infections, particularly Candida.
Intravenous Immunoglobulin (IVIG): May be used in some cases to provide additional antibodies to help fight infection.
Anti-inflammatory Medications: Corticosteroids or other anti-inflammatory medications may be used to manage eczema.
Interferon Gamma: In some cases, interferon gamma can help improve neutrophil function.
Supportive Care: Good skin care, nutritional support, and physical therapy are important components of management.
Hematopoietic stem cell transplantation (HSCT): May be a curative option for some severe cases.
Is Communicable
HIES itself is not communicable. It is a genetic disorder, meaning it is caused by mutations in a person's genes and cannot be spread from person to person. However, the infections that people with HIES are susceptible to (e.g., pneumonia, skin infections) can be communicable.
Precautions
Precautions for individuals with HIES focus on minimizing exposure to infectious agents and managing existing infections:
Good Hygiene: Frequent hand washing, proper wound care, and avoidance of close contact with people who are sick are important.
Vaccinations: Vaccinations are important but should be discussed with an immunologist, as live vaccines may be contraindicated.
Avoidance of Environmental Molds: Since fungal infections are common, avoiding exposure to moldy environments is recommended.
Skin Care: Maintaining good skin hygiene and using emollients can help prevent skin infections.
Prompt Medical Attention: Seek medical attention promptly for any signs of infection.
How long does an outbreak last?
The duration of an outbreak (e.g., a skin infection or pneumonia) in HIES depends on the specific infection, its severity, and how quickly it is treated. Without treatment, infections can become chronic and persistent. With appropriate treatment, outbreaks can typically be resolved within days to weeks. Individuals with HIES are prone to recurrent infections, so they may experience multiple outbreaks over their lifetime.
How is it diagnosed?
Diagnosis of HIES typically involves a combination of clinical evaluation, laboratory testing, and genetic testing:
Clinical Evaluation: Assessing the patient's history of recurrent infections, characteristic facial features, and skeletal abnormalities.
Laboratory Testing: Measuring IgE levels (typically very high), performing complete blood counts (CBCs) to assess white blood cell function, and evaluating the patient's immune response to vaccines.
Genetic Testing: Identifying mutations in genes known to cause HIES (e.g., STAT3, TYK2, DOCK8, PGM3, SPINK5, ZNF341, ACT1).
Neutrophil Chemotaxis Testing: Assessing the ability of neutrophils to migrate towards chemoattractants (although this test is not always reliable).
Timeline of Symptoms
The onset and progression of symptoms in HIES can vary.
Infancy: Eczema-like rash, recurrent skin infections, and lung infections often begin in infancy or early childhood.
Childhood: Characteristic facial features and skeletal abnormalities may become more apparent during childhood. Retained primary teeth are also common.
Adolescence/Adulthood: Chronic lung disease and other complications, such as malignancies, can develop over time. The severity of symptoms can fluctuate throughout life.
Important Considerations
Multidisciplinary Care: Management of HIES requires a multidisciplinary approach involving immunologists, pulmonologists, dermatologists, and other specialists.
Genetic Counseling: Genetic counseling is important for families affected by HIES to understand the inheritance pattern and recurrence risk.
Early Diagnosis and Treatment: Early diagnosis and treatment are crucial to prevent or minimize long-term complications.
Research: Ongoing research is focused on better understanding the pathogenesis of HIES and developing new therapies.
Psychosocial Support: Individuals with HIES and their families may benefit from psychosocial support to cope with the challenges of living with a chronic illness.