$Unique_ID{BRK03787} $Pretitle{} $Title{Granulomatous Disease, Chronic} $Subject{Granulomatous Disease, Chronic CGD Chronic Dysphagacytosis Granulomatosis, Chronic, Familial Granulomatosis, Septic, Progressive Wegener's Granulomatosis Sarcoidosis Churg-Strauss Syndrome Polyarteritis Nodosa} $Volume{} $Log{} Copyright (C) 1989, 1991, 1992 National Organization for Rare Disorders, Inc. 682: Granulomatous Disease, Chronic ** IMPORTANT ** It is possible that the main title of the article (Chronic Granulomatous Disease) is not the name you expected. Please check the SYNONYM listing to find the alternate names and disorder subdivisions covered by this article. Synonyms CGD Chronic Dysphagacytosis Granulomatosis, Chronic, Familial Granulomatosis, Septic, Progressive Information on the following diseases can be found in the Related Disorders section of this report: Wegener's Granulomatosis Sarcoidosis Churg-Strauss Syndrome Polyarteritis Nodosa 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. Chronic Granulomatous Disease is a very rare blood disorder which primarily affects certain white blood corpuscles (lymphocytes). It is characterized by widespread granulomatous tumor-like lesions, and an inability to resist infections. Symptoms Chronic Granulomatous Disease is characterized by the widespread development of granulomatous (tumor-like mass) lesions of the skin, lungs, and lymph nodes. Excess gammaglobulin in the blood (hypergammaglobulinemia), anemia, an increase in white blood cells (leukocytosis), and a susceptibility to infections occurs. Evidence of chronic infections may be seen in the liver, gastrointestinal tract, brain and eyes. There is usually a history of repeated infections, including inflammation of the lymph glands (suppurative lymphadenitis), enlargement of the liver and spleen (hepatosplenomegaly) and pneumonia. Blood studies often show evidence of chronic infection. There may also be a persistent runny nose (rhinitis), inflammation of the skin (dermatitis), diarrhea, perianal abscesses, and an inflammation of the mucous membranes of the mouth (stomatitis). Osteomyelitis, (infection of the bones), brain abscesses, obstruction of the genitourinary tract due to the formation of granulomatous tissue, and delayed growth are also symptomatic of Chronic Granulomatous Disease. Causes The exact cause of Chronic Granulomatous Disease is unknown. There is a genetic form (X-linked recessive) that primarily affects males. Human traits including the classic genetic diseases, are the product of the interaction of two genes for that condition, 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 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 show no 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. The location for the chronic Granulomatous Disease gene has been located in the middle of the short arm of the X-chromosome. However, there are variants of the disorder that may involve other genes in females. Affected Population Chronic Granulomatous affects males more often than females. It usually occurs during childhood but symptoms may be delayed into early teens. In a few, symptoms have been known to occur in adulthood. The disorder is very rare, with only one in a million persons being affected. Related Disorders Symptoms of the following disorders can be similar to those of Chronic Granulomatous Disease. Comparisons may be useful for a differential diagnosis: Wegener's Granulomatosis is an uncommon collagen vascular disorder affecting the blood vessels. It begins as a localized inflammation of the upper and lower respiratory tract mucous membranes, and usually progresses into generalized inflammation of the blood vessels (vasculitis) and kidney (glomerulonephritis). Initial symptoms usually appear as a severe cold progressing to sinusitis, ulcerations of the mucous membranes in the nose with secondary bacterial infection, middle ear infection (otitis media), cough, expectoration of blood (hemoptysis) and pleuritis. The nasal mucous membrane appears red with a raised granular appearance. There may also be fever, loss of appetite and generalized discomfort. (For more information on this disorder, choose "Wegener" as your search term in the Rare Disease Database). Sarcoidosis is a disorder which affects many body systems. It is characterized by small lesions (tubercles) of granulation tissue. Symptoms depend on the site of involvement and may be absent, slight or severe. Fever, weight loss, and joint pain may be initial manifestations. Persistent fever is especially common with liver (hepatic) involvement. Peripheral lymphadenopathy (enlarged lymph glands) is common but usually causes no symptoms. Both enlarged and normal-sized lymph nodes may contain the characteristic sarcoid tubercles. (For more information on this disorder, choose "Sarcoidosis" as your search term in the Rare Disease Database.) Churg-Strauss Syndrome is a lung disorder often occuring as a complication of other disorders. Allergic blood vessel inflammation (angiitis or vasculitis) is accompanied by many inflammatory nodular lesions (granulomatosis). Small inflammatory growths (granulomas) may infiltrate any tissue in the body, causing deterioration. General discomfort (malaise), skin rash, kidney inflamation, nerve disease of the extremities (peripheral neuropathy), pain in many of the joints (asymmetric polyarthralgia), or arthritis may also occur. (For more information on this disorder, choose "Churg-Strauss" as your search term in the Rare Disease Database.) Polyarteritis Nodosa is characterized by an inflammation of the small and medium sized arteries causing narrowing of the vessels. This may result in a lack of blood supply to tissues, possible formation of blood clots (thrombosis), and weakening, ballooning (aneurysm) or possible rupture of the vessel walls. Joint, muscle, abdominal and testicular pain may occur. The patient may also have fever, weight loss and high blood pressure (hypertension). The kidney is the organ most involved. The lungs are rarely affected. Skin rash may be present and gastrointestinal symptoms such as abdominal pain, vomiting of blood (hematemesis) and tender abdomen may be present. (For more information on this disorder, choose "Polyarteritis Nodosa" as your search term in the Rare Disease Database.) Therapies: Standard Treatment of Chronic Granulomatous Disease consists of intermittent or continuous antibiotic therapy, such as Trimethoprim and Sulfamethoxazole. Corticosteroid drugs are also of benefit. The orphan drug, Actimmune (interferon gamma-1b), has received FDA approval as a treatment for Chronic Granulomatous Disease. The drug is manufactured by Genentech, Inc., 460 Point San Bruno Blvd., South San Francisco, CA, 94080. Genetic counseling may be of benefit for patients and their families. Other treatment is symptomatic and supportive. Therapies: Investigational Bone marrow transplants have proven to be successful in some patients, if the procedure is done at a young age. Clinical trials are underway to study compassionate treatment of recombinant human interferon gamma therapy in patients with Chronic Granulomatous Disease and active infection. Interested persons may wish to contact: Howard M. Lederman, M.D., Ph.D. Division of Pediatric Immunology-CMSC 1103 Johns Hopkins Hospital Baltimore, MD 21205 (301) 955-5883 to see if further patients are needed for this research. Clinical trials are underway to study the use of intraconazole as treatment for Aspergillosis in patients with Chronic Granulomatous Disease. For information contact: Dr. Eisentein, Dr. Gallini and Dr. Malech National Institutes of Health (NIAID) Bldg. 10, Rm. 11/N/250 Bethesda, MD 20892 This disease entry is based upon medical information available through October 1992. 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 For more information on Chronic Granulomatous Disease, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 Chronic Granulomatous Disease Association 2616 Monterey Road San Marino, CA 91108 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, 8th ed.: Victor A. McKusick; Johns Hopkins University Press, 1986. Pp. 973. INTERNAL MEDICINE, 2nd Ed.: Jay H. Stein, ed.-in-chief; Little, Brown and Co., 1987. Pp. 1286-1288. RESEARCH HIGHLIGHTS, J.E. Smith, Ph.D.; NIH Research Resources Reporter, (March 1989). CORTICOSTEROIDS IN TREATMENT OF OBSTRUCTIVE LESIONS OF CHRONIC GRANULOMATOUS DISEASE. T.W. Chin, et al.; J PEDIATRICS (September 1987; issue 111(3)). Pp. 512-518. CLINICAL FEATURES AND CURRENT MANAGEMENT OF CHRONIC GRANULOMATOUS DISEASE. C.B. Forrest et al.; HEMATOL ONCOL CLIN NORTH AM (June 1988; issue 2(2)). Pp. 253-266. DETECTION OF CARRIERS OF THE AUTOSOMAL FORM OF CHRONIC GRANULOMATOUS DISEASE. A.J. Verhoeven et al.; BLOOD (February 1988; issue 71(2)). Pp. 505-507. RECOMBINANT HUMAN INTERFERON-GAMMA RECONSTITUTES DEFECTIVE PHAGOCYTE FUNCTION IN PATIENTS WITH CHRONIC GRANULOMATOUS DISEASE IN CHILDHOOD. J.M. Sechler et al.; PROC NATL ACAD SCI USA (July 1988; issue 85(13)). Pp. 4874- 8. OTOLARYNGOLOGIC MANIFESTATIONS OF CHRONIC GRANULOMATOUS DISEASE. R. Miller et al.; AM J OTOLARYNGOL (March-April 1988; issue 9(2)). Pp.