Introduction
Hyper-Immunoglobulin E syndrome is a rare disorder characterized by a clinical triad of atopic dermatitis, recurrent skin staphylococcal infections, and recurrent pulmonary infections. As the name says, it has elevated immunoglobulin E levels in primary childhood. This article will elaborate on the various facts about this syndrome.
What Are Immunoglobulins?
Immunoglobulins are glycoproteins produced by plasma cells. They are also called antibodies. They help in humoral-mediated immune responses and act against bacteria, viruses, fungi, parasites, chemicals, and other foreign substances.
What Are the Types of Immunoglobulins?
There are five types of immunoglobulins.
They are:
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IgM.
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IgG.
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IgA.
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IgE.
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IgD.
What Is the Clinical Use of Immunoglobulins?
Immunoglobulins are used for immunotherapy. They are prepared in the laboratories from blood collected from donors. They are processed by fractionation, separating the protein part from the cellular components. This purified immunoglobulin treats immunological problems such as systemic lupus erythematosus, myasthenia gravis, multiple sclerosis, and organ transplantations.
What Happens When Immunoglobulins Are in Excess?
As we know, immunoglobulins are glycoproteins produced to combat any foreign substance entering the body. Therefore, if a laboratory test shows high levels of immunoglobulins, it means that:
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The individual has allergies.
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The individual is suffering from chronic infections.
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The individual has an autoimmune disorder.
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The individual has a liver disorder.
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The individual has cancer, such as leukemia and multiple myeloma.
What Is Immunoglobulin E?
Immunoglobulin E is an antibody produced by the B lymphocytes to act against pathogens, cancer cells, and other foreign substances. In addition, they are found to mediate type 1 hypersensitivity reactions in response to stimuli such as asthma, hay fever, eczema, and food allergies. Thus immunoglobulin E is produced in an allergic person to combat the allergen. The first contact between the antibody and antigen is called sensitization. Then, the antibodies bind to immune cells allowing them to recognize the allergen next time.
What Are the Two Types of Hyper-Immunoglobulin E Syndrome?
There are two types of Job syndrome such as:
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Type 1: It is an autosomal dominant type where the individual has abnormalities in different systems, such as the skeletal system, immune system, connective tissue, and vascular system.
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Type 2: It is an autosomal recessive type where the immune system is affected, leading to high immunoglobulin E, recurrent skin and lung infections, and central nervous system involvement without musculoskeletal involvement.
What Is the Cause of Job Syndrome?
Job syndrome or Hyper-immunoglobulin E syndrome is due to a mutation in the STAT 3 (signal transducer and activator of transcription) gene, and the transmission is autosomal dominant. However, in some cases, the etiology is still unknown.
What Are the Clinical Characteristics of Job Syndrome?
Immunological and non-immunological features characterize Job syndrome.
The immunological features include:
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Chronic eczematous eruptions on the skin.
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Recurrent skin infections.
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Recurrent pulmonary bacterial infections.
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Mucocutaneous candidiasis.
The eczematous rashes affecting the skin appear a few weeks after birth on the scalp and face. They may turn weeping, crusty, and follicular lesions when superinfected with Staphylococcus aureus. Candidal infections most commonly affect the skin, nails, and mucous membranes. Recurrent pneumonia can get complicated with abscesses and bronchiectasis.
The non-immunologic features include:
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Facial asymmetry.
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Prominent forehead.
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Deep-set eyes.
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Broad nasal bridge.
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Fleshy nasal tip.
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Rough skin.
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Prognathism.
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High-arched palate.
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Musculoskeletal abnormalities include scoliosis (sideways curvature of the spine), hyperextensibility of joints, and osteopenia (loss of bone mineral density). As bone density is decreased, it can lead to multiple pathologic fractures.
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Dental abnormalities include prolonged retention of deciduous teeth due to decreased resorption of roots of deciduous teeth. They are eventually preventing the eruption of permanent teeth.
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Vascular anomalies include aortic aneurysms and congenital coronary artery abnormalities.
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Ocular abnormalities include strabismus (crossed eyes) and retinal detachment.
How Is Job Syndrome Diagnosed?
The significant diagnostic feature of Job syndrome is the elevation of serum immunoglobulin E levels above 2000 units per milliliter. In addition, an autosomal dominant type of Job syndrome shows a defect in the STAT 3 (signal transducer and activator of transcription) gene. As a result, there may be an increased eosinophil count, and the white blood cell count can be normal, elevated, or reduced.
How to Manage Job Syndrome?
The effective treatment for Job’s syndrome is using antibiotics such as penicillinase-resistant penicillins, cephalosporins, and antifungal agents. A surgical procedure can also be adopted if an abscess is developed. However, the non-immunological features must be managed with an interprofessional team since it involves various body parts. In addition, orthopedic surgeries can be recommended to correct defects such as scoliosis, bone fractures, and joint diseases. Dental professionals can further treat dental abnormalities. And a specialized environment is required to manage cardiac manifestations. Studies have shown that interferon-gamma and bone marrow transplantation have helped to treat the condition.
What Are the Differential Diagnoses for Job Syndrome?
With the clinical presentations of Job syndrome, it is difficult to arrive at a diagnosis. It has to be differentiated from other disorders like chronic granulomatous diseases, acquired immunodeficiency syndrome, cystic fibrosis, and atopic dermatitis.
How Is the Prognosis?
An improved prognosis can be noted in an autosomal dominant type of Job syndrome with high morbidity and mortality rate if the patient is closely monitored and depends on the patient’s compliance.
What Are the Complications of Job Syndrome?
The complications of hyper-immunoglobulin E syndrome are:
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Hypertension with vascular abnormalities.
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Myocardial infarction.
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Non-Hodgkin's lymphoma, Hodgkin’s lymphoma, and cancers of the lung and vulva.
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Autoimmune diseases such as systemic lupus erythematosus (SLE), vasculitis (inflammation of the vessels), glomerulonephritis (inflammation of the filters in the kidney), and dermatomyositis (an inflammatory disease characterized by muscle weakness and skin rash).
Conclusion
Job syndrome is a rare immunological disorder showing recurrent infections. A hematologist manages it since it shows elevated levels of immunoglobulin E in the blood and then an infectious disease expert also accompanies him. And the follow-up is done by primary healthcare professionals. Hence Job syndrome is a rare condition that requires a professional team to investigate, diagnose and treat.
