$Unique_ID{BRK03887} $Pretitle{} $Title{Job Syndrome} $Subject{Job Syndrome HIE Syndrome Hyper-IgE Syndrome Hyperimmunoglobulinemia E-staphylococcal Abscess Syndrome Hyperimmunoglobulin E-Recurrent Infection Syndrome Hyperimmunoglobulin E Syndrome Job-Buckley Syndrome Dermatitis Atopic Granulomatous Disease Chronic Wiskott-Aldrich Syndrome } $Volume{} $Log{} Copyright (C) 1991 National Organization for Rare Disorders, Inc. 856: Job Syndrome ** IMPORTANT ** It is possible that the main title of the article (Job Syndrome) is not the name you expected. Please check the SYNONYMS listing to find the alternate names and subdivisions covered by this article. Synonyms HIE Syndrome Hyper-IgE Syndrome Hyperimmunoglobulinemia E-staphylococcal Abscess Syndrome Hyperimmunoglobulin E-Recurrent Infection Syndrome Hyperimmunoglobulin E Syndrome Job-Buckley Syndrome Information on the following diseases can be found in the Related Disorders section of this report: Dermatitis, Atopic Granulomatous Disease, Chronic Wiskott-Aldrich Syndrome General Discussion ** REMINDER ** The Information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. Job Syndrome is a rare disorder present at birth (congenital) in which there are large bacterial infections, particularly of the skin, with some swelling and redness (cold staphylococcal abscesses); a defect in the attraction of white blood cells (leukocytes) that destroy bacteria, fungi, and viruses to chemical stimuli (granulocyte chemotactic defect); an abundance of one of the antibodies that are concentrated in the lungs, skin and cells of mucous membranes (immunoglobulinemia E); inflammation, redness, pain or itching of the skin (chronic-eczematoid dermatitis); and a mild increase in the number of leukocyte white blood cells (mild eosinophilia). Job Syndrome is often inherited as an autosomal recessive trait. Symptoms The main symptoms of Job Syndrome are: 1. Cold staphylococcal abscesses - pus filled holes caused by a bacterial infection (most often staphylococcal aureus bacteria). These abscesses are usually found on the skin, but may also be present on the bone behind the ear (mastoid), joints, gums, air passages in the lungs (bronchi), and in the lungs themselves. 2. Granulocyte chemotactic defect - The living substance of white blood cells that destroys bacteria, fungi and viruses (leukocytes) can be attracted or repelled by chemical stimuli in the body. Patients with Job Syndrome have a defect in this process allowing the bacteria to thrive. 3. Chronic eczema - swelling of the outer skin with itchy, small red blisters that become scaly, crusted and thick. 4. Hyperimmunoglobulinemia E - an unusual abundance of Immunoglobulin E is one of the five fluid antibodies produced by the human body and is concentrated in the lung, skin and cells of mucous membranes. This antibody defends against substances foreign to the body and reacts with them to release chemicals that cause reddening of the skin. 5. Mild eosinophilia - a mild increase in the number of leukocyte white blood cells (eosinophils). Eosinophils increase in number when infection and allergies are present. Some (but not all) of the following additional conditions may be present in patients with Job Syndrome: 6. Mucocutaneous Candidiasis - a rare form of candida infection characterized by chronic infection of the skin, nails, scalp and mucous membranes. This disorder usually develops in people with immune deficiencies and in particular infants with Job Syndrome. It causes red, pustular, crusted and thickened lesions. (For more information on this disorder choose "Candidiasis" as your search term in the Rare Disease Database). 7. Coarse facial features - broad nasal bridge, prominent nose, and irregularly proportioned cheeks and jaws. 8. Fair skin and reddish hair. Causes It is thought that immune complexes may impair the white blood cells (neutrophils) that destroy bacteria, cell debris and solid particles in the blood and their attraction to chemical stimuli. Some patients with Job Syndrome inherit this disorder through an autosomal recessive trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother. In recessive disorders, the condition does not appear unless a person inherits the same defective gene for the same trait from each parent. If one receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is twenty-five percent. Fifty percent of their children will be carriers, but healthy as described above. Twenty-five percent of their children will receive both normal genes, one from each parent, and will be genetically normal. Affected Population Job Syndrome is a very rare disorder that affects males and females in equal numbers. Symptoms of this disorder are present at birth or early childhood. Related Disorders Symptoms of the following disorders can be similar to those of Job Syndrome. Comparisons may be useful for a differential diagnosis: Atopic Dermatitis, is a common chronic form of eczema. Eczema is a skin condition characterized by redness, swelling, oozing, crusting, scaling, burning pain, and itching. The causes of eczema fall into two classifications: 1) constitutional eczema (Atopic dermatitis), and 2) external eczema which is caused by allergies, irritations, or chemical reactions. (For more information on this disorder choose "Atopic Dermatitis" as your search term in the Rare Disease Database). Chronic Granulomatous Disease is a very rare blood disorder which primarily affects certain white blood cells (lymphocytes). It is characterized by widespread granulomatous tumor-like lesions, and an inability to resist infections. The exact cause of this disorder is not known but there is a genetic form that primarily affects males and is thought to be inherited as an X-linked recessive trait. (For more information on this disorder choose "Granulomatous Disease, Chronic" as your search term in the Rare Disease Database). Wiskott-Aldrich Syndrome is a hereditary disorder characterized by a partial immune deficiency, eczema, and a deficiency of platelets and structures in the blood involved in clotting (thrombocytopenia). This disorder affects only males. An early sign of Wiscott-Aldrich Syndrome is excessive bleeding from the site of circumcision or from other wounds. This disorder is transmitted to males by an X-linked recessive trait. (For more information on this disorder choose "Wiskott-Aldrich Syndrome" as your search term in the Rare Disease Database). Therapies: Standard Job Syndrome is treated with antibiotics. Trimethoprim/sulfamethoxazole is given continuously or intermittently depending on the longevity of the infections. These antibiotics are usually effective, but patients often experience repeated infections. For treatment of Chronic Mucocutaneous Candidiasis, amphotericin B, nystatin, clotrimazole, miconizole or 5-fluorocytosine are useful drugs. Antifungal and immune system-stimulating substances (such as the molecule that can transfer immunity from a sensitized to a non-sensitized individual) called transfer factor, thymosin, thymus epithelial cell transplantation, and levamisol, are also used in treatment. Genetic counseling may be of benefit for patients and their families. Other treatment is symptomatic and supportive. Therapies: Investigational The effects of interferon gamma on excessive immunoglobulin E production in patients with Job Syndrome (HIE-hyperimmunoglobulinemia E) are being studied at this time. Long-term safety and effectiveness of this treatment is still under investigation. This disease entry is based upon medical information available through June 1991. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 203-746-6518 Immune Deficiency Foundation 3565 Ellicott Mill Drive, Unit B2 Ellicott City, MD 21043 (800) 296-4433 (410) 461-3127 NIH/National Institute of Allergy & Infectious Diseases (NIAID) 9000 Rockville Pike Bethesda, MD 20892 301-496-5717 For Genetic Information and Genetic Counseling Referrals: March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue White Plains, NY 10605 914-428-7100 Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 (800) 336-GENE (301) 652-5553 References MENDELIAN INHERITANCE IN MAN, 9th Ed.: Victor A. McKusick, Editor: Johns Hopkins University Press, 1990. Pp. 1281-82. HEMATOLOGY, 4th Ed,: William J. Williams, et al,; Editors; McGraw-Hill, Inc., 1990. Pp. 823, 826. CLINICAL DERMATOLOGY, 2nd Ed.; Thomas P. Habif, M.D., Editor: The C.V. Mosby Company, 1990. Pp. 200-1. USE OF RECOMBINANT HUMAN INTERFERON GAMMA TO ENHANCE NEUTROPHIL CHEMOTACTIC RESPONSES IN JOB SYNDROME OF HYPERIMMUNOGLOBULINEMIA E AND RECURRENT INFECTIONS: J.D. Jeppson et al.; J Pediatr (March, 1991; issue 118(3)). Pp. 383-7. THE HYPERIMMUNOGLOBULINEMIA E AND RECURRENT INFECTIONS SYNDROME IN THE ADULT: J.P. L'Huillier et al,; Thorax (September, 1990; issue 45(9)). Pp. 707-8. REGULATION OF IMMUNOGLOBULIN PRODUCTION IN HYPERIMMUNOGLOBULIN E RECURRENT INFECTION SYNDROME BY INTERFERON GAMMA: C.L. King et al.; Proc Natl Acad Sci (December, 1989; issue 86(24)). Pp. 10085-9.