CD-ROM Today 1996 January/CD-ROM Today 1996 January.iso/dp/0378/03787.txt

Text File | 1994-01-17 | 11.1 KB | 262 lines

$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
     [phone]

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
     [phone]

     Chronic Granulomatous Disease Association
     2616 Monterey Road
     San Marino, CA 91108

     Immune Deficiency Foundation
     3565 Ellicott Mill Drive, Unit B2
     Ellicott City, MD  21043
     [phone]
     [phone]

     NIH/National Institute of Allergy & Infectious Diseases (NIAID)
     9000 Rockville Pike
     Bethesda, MD  20892
     [phone]

For genetic information and genetic counseling referrals:

     March of Dimes Birth Defects Foundation
     1275 Mamaroneck Avenue
     White Plains, NY  10605
     [phone]

     Alliance of Genetic Support Groups
     35 Wisconsin Circle, Suite 440
     Chevy Chase, MD  20815
     (800) 336-GENE
     [phone]

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.