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$Title{Scleroderma}
$Subject{Scleroderma PSS Systemic Sclerosis Progressive Systemic Sclerosis
Sclerosis, Familial Progressive Systemic Morphea Linear Scleroderma CREST
Syndrome Mixed Connective Tissue Disease Lupus (Systemic Lupus Erythematosus)
Polymyositis Dermatomyositis Raynaud's Disease and Phenomenon }
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Copyright (C) 1986, 1987, 1988, 1990, 1992, 1993 National Organization
for Rare Disorders, Inc.

69:
Scleroderma

** IMPORTANT **
It is possible that the main title of the article (Scleroderma) is not
the name you expected.  Please check the SYNONYMS listing to find the
alternate name and disorder subdivisions covered by this article.

Synonyms

     PSS
     Systemic Sclerosis
     Progressive Systemic Sclerosis
     Sclerosis, Familial Progressive Systemic

Disorder Subdivisions:

     Morphea
     Linear Scleroderma
     CREST Syndrome

Information on the following diseases can be found in the Related
Disorders section of this report:

     Mixed Connective Tissue Disease
     Lupus (Systemic Lupus Erythematosus)
     Polymyositis
     Dermatomyositis
     Raynaud's Disease and Phenomenon

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.


Scleroderma is a rare connective tissue disorder characterized by
abnormal thickening of the skin.  Connective tissue is composed of collagen
which supports and binds other body tissues.  There are several types of
Scleroderma.  Some types effect certain parts of the body, and other types
can effect the whole body and internal organs (systemic).

Symptoms

The early symptoms of Scleroderma vary considerably.  Distinctive
abnormalities on the skin (cutaneous lesions) usually appear later in the
course of the disease.  Common symptoms of Scleroderma may include painful
joints (arthralgia), morning stiffness, fatigue, and/or weight loss.  The
intermittent loss (triggered by cold temperatures) of blood supply to the
fingers, toes, nose, and/or ears (Raynaud's Phenomenon) is an early and
frequent complaint of people with Scleroderma.

People with Scleroderma have areas of skin that become hard and leathery
(indurated).  These areas of hardness are widespread and typically appear on
both sides of the body.  Eventually tissue loss (atrophy) occurs and the skin
becomes more highly colored (hyperpigmentation).

Morphea, or localized Scleroderma, usually begins between the ages of 20
to 50 years as patches of yellowish or ivory-colored rigid, dry skin
(inflammatory stage).  These are followed by the appearance of firm, hard,
oval-shaped plaques with ivory centers that are encircled by a violet ring.
These spots generally appear on the trunk, face, and/or extremities.  Many
patients with localized Morphea improve spontaneously (without treatment).
Generalized Morphea is more rare and serious, and involves the skin (dermis)
but not the internal organs.

Linear Scleroderma appears as a band-like thickening of skin on the arms
or legs.  This type of Scleroderma is most likely to be on one side of the
body (unilateral) but may be on both sides (bilateral).  Linear Scleroderma
generally appears in young children and is characterized by the failure of
one limb (i.e., arm or leg) to grow as rapidly as its counterpart.  The band
of thick skin may extend from the hip to the heel or from the shoulder to the
hand.  Deep tissue loss may occur along this band.

Systemic Scleroderma includes a wide range of symptoms including
inflammatory diseases of the muscles (i.e., Polymyositis or Dermatomyositis),
swelling (edema) of the fingers and/or hands, microvascular abnormalities,
lung disease (i.e., progressive interstitial fibrotic pulmonary disease),
kidney dysfunction (i.e., rapidly progressive renal failure), cardiovascular
problems (i.e., myocardial accelerated hypertension), gastrointestinal
malfunction (i.e., lack of mobility of the esophagus and colon), and/or
abnormalities of the immune system.  (For more information, choose
"Polymyositis" and "Dermatomyositis" as your search terms in the Rare Disease
Database.)

CREST Syndrome is an acronym for calcinosis, Raynaud's phenomenon,
esophageal dysfunction, sclerodactyly and telangiectasia.  Calcinosis is the
abnormal accumulation of calcium salts under the skin and in many other
organs.  Raynaud's Phenomenon is a vascular disorder characterized by the
intermittent loss of blood to various parts of the body particularly the
fingers, toes, nose, and/or ears.  This typically occurs after exposure to
cold and causes tingling sensations, numbness, and/or pain.  Dysfunction of
the lower esophagus results in heartburn (acid reflux into the throat and
mouth) and possible scarring.  The esophagus may eventually have areas that
are narrowed (strictures), and swallowing may become difficult.  The small
intestine may also lose the ability to push food through to the large
intestine (peristalsis) leading to malabsorption and increased bacterial
growth in the small intestine.  Sclerodactyly, a condition in which the skin
becomes thin, shiny, and bright, results in decreased function of the fingers
and toes.  Telangiectasia, the appearance of small blood vessels near the
surface of the skin, is unsightly but not debilitating.  Patients with the
CREST Syndrome are at increased risk of developing pulmonary hypertension.
(For more information, choose "Raynaud" and "Pulmonary Hypertension" as your
search term in the Rare Disease Database.)

Causes

The exact cause of Scleroderma is unknown.  The immune system and vascular
system, and connective tissue metabolism are known to play some part in the
disease process.

Affected Population

Scleroderma is a rare disorder that affects approximately 50,000 to 100,000
people in the United States.  The disease is 3 to 4 times more common in women
than men.  Scleroderma may occur at any age, but the symptoms most frequently
begin in midlife.

Related Disorders

Symptoms of the following disorders can be similar to those of Scleroderma.
Comparisons may be useful for a differential diagnosis:

Mixed Connective Tissue Disease (MCTD) is a rare inflammatory disorder of
the connective tissue.  The symptoms of this disorder overlap with those of
Lupus (Systemic Lupus Erythematosus), Scleroderma and
Polymyositis/Dermatomyositis.  Early symptoms may include a fever of unknown
origin, painfully cold fingers in response to cold (Raynaud's Phenomenon),
swollen hands, fatigue, and/or non-deforming arthritis.  Arthritis occurs in
almost every case of Mixed Connective Tissue Disease, but rarely results in
deformities similar to those seen in Rheumatoid Arthritis.  People with Mixed
Connective Tissue Disease commonly experience muscle pain and skin rashes.
(For more information on this disorder, choose "Mixed Connective Tissue
Disease" as your search term in the Rare Disease Database.)

Lupus (Systemic Lupus Erythematosus or SLE) is a rare inflammatory
connective tissue disease.  The initial symptom of this disease is usually
excessive fatigue.  Most people with Lupus experience inflammation and
swelling of the joints (arthritis), joint pain (arthralgia), and generalized
muscle pain (myalgia).  Skin rashes are common in people with Lupus.  About
50 percent of people with Lupus get a classic red "butterfly" rash across the
bridge of the nose and cheeks.  Other early symptoms may include fever,
swollen glands, loss of appetite, weight loss, headaches, loss of hair, and
swelling due to fluid retention.  (For more information on this disorder,
choose "Lupus" as your search term in the Rare Disease Database.)

Polymyositis is a rare inflammatory disorder characterized by the
inflammation and degeneration of muscle and the supporting collagen
connective tissue.  The cause of this disorder is not known.  The major early
symptom of this disorder is muscle weakness usually in the neck, trunk and
shoulders.  Eventually it may become difficult to rise from a sitting
position, climb stairs, lift objects and/or reach overhead.  Occasionally,
joint pain and tenderness also occur.  Other symptoms may also include
inflammation of the lungs (interstitial pneumonitis), difficulty breathing,
coughing, painfully cold fingers in response to cold (Raynaud's phenomenon),
digestive problems, heart irregularities, and kidney failure.  (For more
information on this disorder, choose "Polymyositis" as your search term in
the Rare Disease Database).

Dermatomyositis is a rare inflammatory connective tissue disease.  The
cause is unknown.  Dermatomyositis is identical to Polymyositis but with the
addition of a characteristic red skin rash.  These red rashes generally occur
before the muscle weakness occurs and usually appear on the face, knees,
shoulders and hands.  In some patients the skin changes caused by
Dermatomyositis are similar to those of Scleroderma.  The skin may become
dry, hard and have a brownish color.  (For more information on this disorder,
choose "Dermatomyositis" as your search term in the Rare Disease Database).

Raynaud's Disease is a rare disorder characterized by spasms of the blood
vessels in the fingers, toes, nose, and ears (Raynaud's Phenomenon) usually
in response to cold.  Raynaud's Disease includes the symptoms of Raynaud's
Phenomenon along with other systemic disorders.  The major symptom of this
disorder is a dramatic stark white pallor of the affected fingers and toes
when exposed to cold, although a blue or red color may also be present from
time to time.  Other symptoms in the affected fingers and toes vary in
response to cold and may include a feeling of numbness, severe aching or
pain, tingling or throbbing, a sensation of tightness, "pins and needles,"
and/or a profound loss of sensation.  (For more information on this disorder,
choose "Raynaud's" as your search term in the Rare Disease Database.)

Therapies:  Standard

Treatment of Scleroderma is symptomatic and supportive.  Medications used to
control the hardening of the skin and internal organs (fibrosis) are D-
penicillamine and cholchicine.  Other skin care may include lubricating
creams or antibiotic ointments for infected ulcerations.

Captopril and enalapril, angiotensin-converting enzyme inhibitors that
inhibit the formation of angiotensin, are the drugs of choice for the
treatment of kidney disease associated with Scleroderma.  Other vasodilators
or beta-adrenergic blockers also have been used with some success.  These
agents are effective in controlling hypertension and can preserve kidney
function.

If Raynaud's Phenomenon occurs with Scleroderma, drug therapy may help
dilate blood vessels.  Vasodilators, including the drugs nifedipine
(Procardia), reserpine (Serpasil), guanethidine (Ismelin), phenoxybenzamine
(Dibenzyline), nicotinic acid, diltiazem, verapamil, and/or prazosin
(Minipress) are prescribed.

In rare cases of Scleroderma, calcinosis may require surgical
intervention.  For joint pain or arthritis, anti-inflammatory drugs are
generally prescribed including aspirin, indomethadin (Indocin), and naproxen
(Naprosyn).  Some patients may require low-doses of corticosteroid drugs to
control these symptoms.

The management of symptoms of Scleroderma related to pulmonary
hypertension involves the use of supplemental oxygen.

When abnormalities of the heart occur (myocardial perfusions) as a result
of Scleroderma, the drugs nifedipine and dipyridamole may be administered.
Nonsteroidal anti-inflammatory or corticosteroid drugs are typically used to
treat the symptoms relating to the inflammation of the membranes of the heart
(pericarditis).

When Scleroderma causes the esophagus and/or gastrointestinal tract to
become inflamed or ulcerated, the treatments of choice are drugs known as H2
blockers such as cimetidine or ranitidine; omeprazole may also be used.
Metoclopramide has been beneficial in treating the symptoms associated with
gastrointestinal dysmotility.  Acid reflux from the stomach into the
esophagus may be partially controlled by dietary regulation.  Patients are
urged to avoid certain foods such as fats, spices, tea, coffee and alcohol.
Several small and frequent meals per day lighten the work of the
gastrointestinal system.  Sitting upright for at least 2 hours after eating
aids the digestive process.

Good oral hygiene is important because gum disease is common in
Scleroderma.  Some patients suffer from excessive dryness of the mouth and
eyes.  The combination of dry mouth and dry eyes is known as Sjogren's
Syndrome.  (For more information choose "Sjogren" as your search term in the
Rare Disease Database.)

Therapies:  Investigational

Many possible causes of Scleroderma and other "sclerosis-like" connective
tissue diseases are currently being investigated.  These include a wide
variety of chemical and environmental exposures (i.e., vinyl chloride,
pentazocine, silicone, tricholorethylene, paraffin), as well as the use of
adulterated L-tryptophan and appetite suppressants.  There is some evidence
that Scleroderma seems to cluster in certain geographic areas.

Other studies have suggested that the tendency to develop Scleroderma and
other sclerosis-like diseases runs in families.  Scientists are studying the
possible inheritance of a genetic trait that would predispose a person to
this disorder.  Some studies suggest the presence of an antibody that causes
chromosomes to break (anticentromere antibody) in some people with CREST
Syndrome.  Other research suggests that a spontaneous genetic change (de
novo) may cause a genetic predisposition to Scleroderma.  A genetic
predisposition means that a person may carry a gene for a disease but it may
not be expressed unless something in the environment triggers the disease.

It has been suggested that Scleroderma is actually a group of distinct
disorders each of which has its own characteristic genetic or environmental
predisposing risk factors.

Several experimental treatments are currently being evaluated for use in
treating people with Scleroderma.  The orphan drug etretinate (Tigason) is
now under study in the United States for the treatment of certain types of
Scleroderma.  The early steps of the production of excess collagen by cells
may be blocked by Vitamin A components (retinoids) in etretinate.  Excess
collagen production is a primary abnormality of Scleroderma.  It should be
remembered that although this orphan drug is available experimentally in the
United States, it is still under study and conclusive results are not yet
available.

The Arthritis Unit of Massachusetts General Hospital and the New England
Deaconess Hospital are evaluating the effects of recombinant gamma-interferon
in individuals with Scleroderma.  More testing is necessary to determine the
safety and effectiveness of this treatment.  Interferon is a potential
therapy for Scleroderma because of its inhibition of excessive synthesis of
collagen, but side effects are common.

The drug ketanserin, a serotonin antagonist, is being tested for
treatment of the abnormal blood flow in the fingers caused by Raynaud's
Phenomenon associated with Scleroderma.  More research is needed before these
types of drugs will be available for more general use.

Cyclosporine (Sandimmune) may be of potential benefit for treating a
number of skin diseases, including those seen in collagen vascular diseases.
These include Pemphigus, Bullous Pemphigoid, Posterior Uveitis, Bechet's
Disease, and collagen vascular disorders such as Scleroderma, severe
Dermatomyositis, Sjogren's Syndrome, Mycosis Fungoides, and Alopecia Areata.
Certain types of skin grafts have sometimes improved after cyclosporine
treatment.  However, cyclosporine is toxic and it reduces the function of the
immune system; therefore, it is not ordinarily used to treat Scleroderma.
Relapses can occur when the drug is stopped.  More research is needed before
cyclosporine can be recommended as a treatment for all but the most severe
cases of Scleroderma.  (For more information choose "Pemphigus," "Bechet,"
"Dermatomyositis," "Sjogren," "Mycosis Fungoides," and "Alopecia Areata" as
your search term in the Rare Disease Database.)

A treatment known as photochemotherapy is under investigation for people
with Scleroderma.  During this procedure, blood in removed from the body (as
in dialysis) and certain blood cells (monocytes) are "washed" with a drug (8-
methoxypsoralen).  The blood is then exposed to ultraviolet light (type A).
This process is known as photopheresis.  It is hoped that this treatment
might suppress collagen production and increase the levels of an enzyme that
breaks down collagen (collagenase).  More study is needed to determine the
long-term safety and effectiveness of this treatment.

Scleroderma has been treated experimentally with the local anesthetic and
anti-inflammatory drug, dimethyl sulfoxide (DMSO), as part of the Arthritis
research program of the National Institute of Arthritis, Musculoskeletal and
Skin Diseases.  These investigational studies are being performed to
determine the long-term effect of this drug on patients suffering from
Scleroderma.

Octreotide Acetate (Sandostatin), manufactured by Sandoz, is being
studied as a treatment for the intestinal motility problems of people with
Scleroderma.  In a study of patients with Scleroderma and control patients,
octreotide acetate was given to increase motility and relieve abdominal
symptoms.  More study is indicated to determine the long-term safety and
effectiveness of this drug for Scleroderma.

Clinical trials are underway to test the orphan drug chlorambucil as a
treatment for Scleroderma.  For more information, patients may have their
physicians contact:

     Daniel Furtst, M.D.
     University of Iowa
     Iowa City, IA  52240

Scientists are studying a new orphan drug, Iloprost, for treatment of
Raynaud's Phenomenon when it occurs along with Scleroderma.  The drug is
manufactured by Berlex Laboratories.  More research is needed to determine
the safety and effectiveness of this experimental treatment.

Clinical trials are underway to study bronchoalveolar lavage in
Interstitial Lung Disease that can be associated with Scleroderma.  For more
information, patients may have their physicians contact:

     Gary W. Hunninghake, M.D.
     Pulmonary Disease Division, C33, GH
     Dept. of Internal Medicine
     University of Iowa Hospitals and Clinics
     Iowa City, IA  52242
     [phone]

Clinical trials are underway to study the safety and efficacy of Xomazyme
COS.  For more information, patients may have their physicians contact:

     Dr. Thomas D. Geppart
     University of Texas Southwestern Medical Center
     5323 Harry Hines Blvd.
     Dallas, TX  75235
     [phone]

This disease entry is based upon medical information available through
April 1993.  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 Scleroderma, please contact:

     National Organization for Rare Disorders (NORD)
     P.O. Box 8923
     New Fairfield, CT  06812-1783
     [phone]

     Scleroderma Society/Federation
     1182 Teaneck Rd., Suite 104
     Teaneck, NJ  107666
     [phone]

     Scleroderma Federation
     One Newbury St.
     Peabody, MA  01960
     [phone]

     Scleroderma Research Foundation
     Pueblo Medical Commons
     2320 Bath St., Suite 307
     Santa Barbara, CA  93105
     [phone]
     (800) 441-CURE

     United Scleroderma Foundation, Inc.
     P.O. Box 350
     Watsonville, CA  94077-0350
     [phone]

     Scleroderma International Foundation
     704 Gardner Center Road
     New Castle, PA  16101

     The National Arthritis and Musculoskeletal and Skin Diseases Information
Clearinghouse
     Box AMS
     Bethesda, MD  20892
     [phone]

References

MENDELIAN INHERITANCE IN MAN, 10th Ed.:  Victor A. McKusick, Editor:  Johns
Hopkins University Press, 1992.  Pp. 1006.

CECIL TEXTBOOK OF MEDICINE, 19th Ed.:  James B. Wyngaarden, and Lloyd H.
Smith, Jr., Editors; W.B. Saunders Co., 1990.  Pp. 1530-35.

THE MERCK MANUAL, 16th Ed.:  Robert Berkow Ed.; Merck Research
Laboratories, 1992.  Pp. 1321-1323.

BIRTH DEFECTS ENCYCLOPEDIA, Mary Louise Buyse, M.D., Editor-In-Chief;
Blackwell Scientific Publications, 1990.  Pp. 1515-1516.

THE MANY FACES OF SCLERODERMA.  J.D. Smiley; Am J Med Sci (Nov 1992;
304(5)).  Pp. 319-33.

TREATMENT OF SYSTEMIC SCLEROSIS.  T.A. Medsger; Ann Rheum Dis (Nov 1991;
50(4)).  Pp. 877-886.

USE OF ANGIOTENSIN-CONVERTING-ENZYME INHIBITORS IN THE MANAGEMENT OF
RENAL DISEASE.  J.P. Asher; Clin Pharm (Jan 1991; 10(10)).  Pp. 25-31.

TREATMENT OF SYSTEMIC SCLEROSIS.  V. Steen; Curr Opin Rheumatol (Dec 1991;
3(6)).  Pp. 979-85.

EPIDEMIOLOGY OF SCLERODERMA.  A.J. Silman; Curr Opin Rheumatol (Dec 1991;
3(6)).  Pp. 967-72.

TREATMENT OF SYSTEMIC SCLEROSIS.  F.M. Wigley; Curr Opin Rheumatol (Dec.
1992; 4(6)).  Pp. 878-886.

GENETIC AND ENVIRONMENTAL FACTORS IN SYSTEMIC SCLEROSIS.  R.I. Fox; Curr
Opin Rheumatol (Dec 1992 4(6)).  Pp. 857-61.

EXTRACORPOREAL PHOTOCHEMOTHERAPY INDUCES THE PRODUCTION OF TUMOR NECROSIS
FACTOR-ALPHA BY MONOCYTES:  IMPLICATIONS FOR THE TREATMENT OF CUTANEOUS T-CELL
LYMPHOMAS AND SYSTEMIC SCLEROSIS.  B.R. Vowels; J Invest Dermatol (May 1992;
98(5)).  Pp. 686-692.

TREATMENT OF AUTOIMMUNE DISEASE WITH EXTRACORPOREAL PHOTOCHEMOTHERAPY:
PROGRESSIVE SYSTEMIC SCLEROSIS.  A.H. Rook; Yale J Biol Med (Nov-Dec 1989;
62(6)).  Pp. 639-645.