|
|
Types Of Scleroderma:
PROGRESSIVE SYSTEMIC SCLEROSIS (PSS)
(Scleroderma)
A chronic disease of unknown cause, characterized by diffuse fibrosis;degenerative
changes; and vascular abnormalities in the skin
(scleroderma), articular structures, and internal organs (especially
the esophagus, intestinal tract, lung, heart, and
kidney). PSS is about4 times more common in women than men and is comparatively
rare in children.
DIFFUSE CONNECTIVE TISSUE DISEASE PROGRESSIVE SYSTEMIC SCLEROSIS (PSS)
Symptoms, Signs, and Diagnosis
The disease varies
in severity and progression, ranging from generalized
cutaneous thickening (PSS with diffuse scleroderma) with rapidly
progressive & often fatal visceral involvement,to a form distinguished
by restricted skin involvement(often just
the fingers & face) and prolonged passage
of time, often several decades,before full manifestation of characteristic
internal manifestations (CREST syndrome
: Calcinosis,Raynaud's phenomenon, Esophageal
dysfunction, Sclerodactyly,Telangiectasia). In
addition, overlap syndromes exist; eg,
sclerodermatomyositis
(tight skin and muscle weakness indistinguishable
from polymyositis); mixed connective tissue disease(MCTD --discussed briefly
here and in a separate subchapter below);and a musculoskeletal syndrome chemically
induced by contaminated oil (the toxic oil syndrome
[TOS]), which occurred in Madrid in 1981 and
affected about 20,000 people. Recently, a syndrome of incapacitatingmyalgias
and eosinophilia was associated with the ingestion of
L-tryptophan, although the exact etiology is unknown.
Initial complaints:
The most common
are Raynaud's phenomenon and insidious swelling
of the acral portions of the extremities with gradualthickening of the skin
of the fingers. Polyarthralgia also is an earlysymptom. GI disturbances (eg,
heartburn and dysphagia) or respiratory complaints
(eg, dyspnea) occasionally are the first manifestations of thedisease.
The skin:
Induration is
symmetric and may be confined to the fingers
(sclerodactyly) and distal portions of the upper extremities, or it may
affect most or all of the body.As the disease progresses,the
skin becomestaut, shiny, and hyperpigmented; the facebecomes masklike;telangiectasesappear
on the fingers, chest, face, lips, and tongue. Subcutaneous calcifications
develop (calcinosis circumscripta), usually on the fingertips
and over bony eminences. Biopsy of indurated skin shows an increase incompact
collagen fibers in the reticular dermis, epidermal thinning, loss of
rete pegs, and atrophy of dermal appendages.
There may be variably largeaccumulations of T-dependent lymphocytes in the
dermis and subcutis (which also may be the seat
of extensive fibrosis).
Musculoskeletal
system:
Friction rubs
develop over the joints (particularly the knees),
tendon sheaths (tendinitis), and large bursae
because of fibrin deposition on synovial surfaces. Flexion contractures ofthe
fingers, wrists, and elbows result from fibrosis of the synovium andperiarticular
structures. Trophic ulcers are common, especially on the
fingertips and overlying the finger joints.
GI tract:
Esophageal dysfunction
is the most frequent visceral disturbance and
eventually occurs in most patients. Dysphagia, acid reflux due to loweresophageal
sphincter incompetence, and peptic esophagitis with possibleulceration and
stricture are common. Barrett's metaplasia of the
esophagus occurs in 1/3 of all patients with scleroderma; these patientshave
an increased risk of complications such as stricture or
adenocarcinoma. Hypomotility of the small intestine may be associated
with malabsorption resulting from anaerobic bacterial
overgrowth.Pneumatosis cystoides intestinalis may occur following degeneration
of the muscularis mucosa and entry of air into
the submucosa of the intestinal wall. Characteristic large-mouthed sacculations
develop in the colon andileum because of atrophy of the smooth muscle of
these segments. Biliary cirrhosis has
occurred in persons with the CREST syndrome.
Cardiorespiratory
system:
Lung fibrosis,
with exertional dyspnea its most prominent symptom,
is associated early with an impairment in gas
exchange. Pleurisy and pericarditis with effusion may occur. Recent studiesindicate
generally indolent progression of lung involvement, with substantial
individual variability. Pulmonary hypertension
may develop as a result of long-standing interstitial
and peribronchial fibrosis or intimal hyperplasia of
small pulmonary arteries; the latter is associated with the CRESTsyndrome.
Cardiac arrhythmias, conduction disturbances, and other ECG
abnormalities are common. Ambulatory electrocardiography in patients
with cardiac or pulmonary involvement revealed ventricular
ectopy in 67%that was strongly correlated with sudden death. Cardiac failure
may develop either because of pulmonary hypertension and secondary cor
pulmonale or because of diffuse fibrous replacement
of cardiac muscle.The cardiac failure tends to be chronic and to respond
poorly to digitalis.
The kidneys:
Severe renal disease
may occur as a consequence of intimal hyperplasia
of interlobular and arcuate arteries, and usually is heralded bythe abrupt
onset of accelerated or malignant hypertension. If untreated, thisis soon
followed by rapidly progressive and irreversible renal insufficiencythat is
lethal within a few months. However, modern aggressive
antihypertensive therapy has made survival of >=2 yr common, although
not all patients respond, and some progress to renal failure despite goodBP
control.
Laboratory
findings:
Rheumatoid factor
tests are positive in 1/3 of PSS patients;
serum antinuclear and/or antinucleolar antibodies are present in>=90%
of cases. An antibody that reacts with centromeric protein(anticentromere
antibody) is found in the serum of a high proportion of
patients with the CREST syndrome. SCL-70 antigen (topoisomerase I) isa DNA-binding
protein sensitive to nucleases. A recent study of
scleroderma patients revealed that 26% had anti-SCL-70 antibodies
(ASCL-70A) and 22% had anticentromere antibodies
(ACA); no patient had both. Two thirds of patients
with ASCL-70A had diffuse scleroderma,but only 33% of all patients with diffuse
scleroderma had this antibody.ASCL-70A was associated with peripheral vascular
disease and pulmonary interstitial fibrosis
but was not predictive of cardiac or renal
involvement or survival. ACA was found almost exclusively (92%) in
patients with limited cutaneous scleroderma
or the CREST syndrome, but57% of patients with limited scleroderma did not
have this antibody.Analysis of various HLA types and scleroderma shows a
significant correlation only between PSS and
HLA-DR5, and an increased frequency of HLA-DR1
in patients with the CREST syndrome.
Localized
forms of scleroderma
occur as circumscribed
patches (morphea) or linear sclerosis
of the integument and immediately subjacenttissues without systemic involvement;
antinuclear antibodies often are found in the
latter condition. Overlap syndromes: The most distinct is MCTD
(see below), in which scleroderma and other evidence of PSS such asRaynaud's
phenomenon and esophageal dysfunction occur in associationwith clinical and
serologic features of SLE, polymyositis, and/or RA.Patients with MCTD have
extremely high titers of a serum antibody that
reacts with nuclear ribonucleoprotein.
PROGRESSIVE SYSTEMIC SCLEROSIS (PSS)
Prognosis
The course is
variable and unpredictable. It is often only slowly
progressive. Most patients eventually show evidence of visceralinvolvement.
Prognosis is poor if cardiac, pulmonary, or renal
manifestations are present early. However, the disease may remain limitedand
nonprogressive for long periods in patients with the CREST syndrome;other
visceral changes (including pulmonary hypertension due to vascular
disease of the lung, and a peculiar form of biliary
cirrhosis) eventuallydevelop, but the course of this form of PSS often is
remarkably benign.
PROGRESSIVE SYSTEMIC SCLEROSIS (PSS)
Treatment
No drug has significantly
influenced the natural history of PSS, but numerous
agents are of value in treating specific symptoms or organsystems. Corticosteroids
may be helpful for disabling myositis or MCTD.
Treatment
for Skin:
Studies indicate
that prolonged administration (>1½ yr) of penicillamine(0.5 to
1.0 gm/day) reduces skin thickening and may delay the rate of newvisceral
involvement. However, penicillamine is poorly tolerated by many
patients, and long-term benefits are equivocal at best. Colchicine and
various immunosuppressive agents also are under
trial in PSS, but results to date are
variable; a recent double-blind study of 65 patients revealed
that after 3 yr of immunosuppressive treatment with chlorambucil there was
no benefit.
Treatment
for Raynaud's phenomenon.
Nifedipine 20
mg tid may help control Raynaud's phenomenon.
Treatment
for digestive problems:
Reflux esophagitis
is relieved by frequent small feedings, antacids, andcimetidine (300 mg qid
--30 min before meals and at bedtime), and by
having the patient sleep with the head of the bed elevated. Esophagealstrictures
may require periodic dilation; successful correction ofgastroesophageal reflux
by gastroplasty has been reported. Tetracycline 1gm/day orally, or another
broad-spectrum antibiotic, suppresses intestinalflora and may alleviate intestinal
malabsorption symptoms.
Joint and
Muscle Treatment:
Physiotherapymay
help preserve muscle strength but is ineffective in preventing jointcontractures.
Treatment
for Kidneys:
For kidney disease,
angiotensin-converting enzyme inhibitors, which inhibitthe formation of angiotensin
(eg, captopril), are the drugs of choice. Othervasodilators (eg, minoxidil)
or beta-adrenergic blockers also have beenused with some success. All of
these agents are effective in controlling
hypertension and can preserve renal function. When end-stage renaldisease
is unpreventable, dialysis and transplantation can be used, althoughthe mortality
rate still is high.
We received the
following letter from R. M. Alford, MD
& thought it may be of interest to others. Scleroderma is the
reult of a retracted peripheral vasculature secondary to the hypothermia
of hypoththyroidism, in this case usually a deficiency of triiodothyronine
(T3), the active form of thyroid. The associated connective tissue
changes are likewise due to the same T3 deficiency with T3 being essential
in the production of cortisol that is necessary to block the causitiveautoimmune
reaction. Why T3 deficiency? This is a result of the excess production
of reverse T3 (rT3), a total inactive thryoid isomer. RT3 and T3 are
derived from the same precursor, thyroxine (T4). When there is excess
amount of rT3 being produced,it consume so much of the T4 that there is not
enough available for the production of enough T3 to insure an optimal metabolic
rate, essential for homeostasis.How does this manifest in scleroderma?
With hypothyroidism, there is a relataive cooling of the body , a result
of the slowed metabolism. Because this, there is shunting of
the warmer arterial blood directly back to the core and the vital organs,
the brain included, via peripheral glomus bodies to help ensure maximal function
of the vital organs. With this shunting, a there is a relative fall
in the blood pressure. As aging goes on, there is a continuous decline
in the metabolic rate, increased shunting and a further fall in the
blood pressure. When this fall in blood pressure reaches the point
that it compromises the renal perfusion pressure, angiotensin is released
to constrict a relative number of arterioles to in turn raise the renal perfusion
pressure to a more physiologic level. It is at this point that the
peripheral vascular disease become most obvious, and it is at this point
that hypertension also begins. It is also at this point that it become more
critical to treat the problem appropriately with T3 to raise the total body
temperature and reverse the shunting. All the present day medication
used for hypertension should be reconsidered because they interfer with angiotensin's
protective effect on the renal perfusion pressure. With continued aging,
all of the problems become progressively more severe, until such time
as ulceration and gangrene occur and amputations may have to be considered.
Sclerocerma is no different than Raynaud's and the peripheral vascular problems
of diabetes in etiology, the manifestations only being different.
New treatments for Scleroderma
Minocycline
This comes from
CNN
http://cnn.com/HEALTH/9805/08/disease.breakthrough/index.html
BOSTON (CNN)
-- Researchers say a common antibiotic that has been in usefor more than
20 years has proven effective against a potentially fatal skindisease from
which thousands of Americans suffer. People in
the early stages of scleroderma can get total relief from the debilitating
autoimmune disease by taking the antibiotic
minocycline twice a day,
according to the findings of a year-long pilot study. "The results are highly
significant," said study leader Dr. David Trentham, a rheumatologist at Beth
Israel Deaconess Medical Center in Boston.Minocycline is ordinarily used
to treat acne, but Trentham gave it to six patients
with scleroderma and it effectively cured four of them. "Wethought the drug
would lead to improvement, but to have total clearing of the skin was quite
a surprise," he said. Scleroderma affects about 150,000 Americans, and may
be familiar to those who have seen the TV movie "For Hope." Scleroderma had
been untreatable The disease causes degeneration of the connective tissue
of the skin, lungs and internal organs, especially the esophagus, digestive
tract and kidneys. Patients with scleroderma experience a stiffening and
thickening of the skin, which makes it difficult to move certain parts of
the body. In some cases, there is difficulty swallowing and breathing, and
the person dies. "Patients may live three to five to 10 years," Trentham
said, "but they increasingly become more and more disabled. It becomes
more difficult to move hands; limbs become rigid. "Trentham thought minocycline
might work with scleroderma because it had been found to help those with
rheumatoid arthritis. Both are autoimmune diseases, meaning the body's immune
system attacks its own tissue. He had no idea, however, that it would work
as well as it did. "I must admit we were pleasantly surprised," he said.
"Heretofore, scleroderma has never been treatable in any real form or fashion."
Cynthia Dale, one of Trentham's patients, said she had no energy and was
in great pain before she began taking minocyline. "Brushing my teeth became
a chore, because I wasn't able to open my mouth wide enough, and I couldn't
grip the toothbrush," she said. "It was too small to grip."Dale added, "I
couldn't braid my little girl's hair. Every morning she wanted me to do it,
and I couldn't." 'You feel like you're a 12-year-old'After taking minocycline
for a year, almost all of her symptoms are gone. "You feel like you're a
12-year-old and you can do anything," she said."You can climb Mt. Everest,
and you have energy and you're happy and you're past it."Trentham warns that
his study was small and only worked on patients whose disease was in the
early stages. But he said it offers hope to people who once had very little.
Indeed, the researchers are soencouraged that they say they will also try
it on those who suffer from other autoimmune diseases such as arthritis and
lupus.
Correspondent
Elizabeth Cohen contributed to this report.
For more info on TREATMENT OF INFLAMMATORY RHEUMATIC DISEASE WITH LOW DOSE
ANTIBIOTIC THERAPY:
Please visit http://www.rheumatic.org/
Thanks to Chris and Chas Adlard
For sending us this info.
This is another
article on new treatments:
This comes from
http://detnews.com/1998/nation/9803/07/03070033.htm
Relaxin
Hormone-based drug may reverse
scarring & crippling of scleroderma
By Linda A. Johnson
/ AP Business Writer
TRENTON, N.J.
-- An experimental drug for scleroderma appears to reverse the crippling,
disfiguring tissue disease that afflicts about 400,000 Americans and can kill
quickly in severe cases.Relaxin,
made by Connectics Corp., has promise both for controlling little-understood
scleroderma and helping researchers battling other autoimmune diseases, principal
investigator Dr.James R. Seibold of the University of Medicine and Dentistry
of New Jersey-Robert Wood Johnson Medical School said Friday."I think the
way the scientific community looks at it is, if we make a breakthrough in
scleroderma, it will open the doors in many other diseases," such as rheumatoid
arthritis and lupus, said Seibold, director of the New Brunswick medical
school's Scleroderma Research Center.The school is one of 13 U.S. sites where
120 patients have received Relaxin, also called ConXn, according to John
L.Higgins,chief financial officer at Connectics, a 5-year-old biotechnology
company developing rheumatology and dermatology medications. It is based in
Palo Alto, Calif. Scleroderma primarily strikes women. It causes certain cells
to produce excess collagen, making scar tissue build up and thickening and
hardening the skin. That makes fingers clumsy and joints so tight and sore
patients increasingly have trouble feeding, bathing and dressing themselves,
let alone working. In about 70,000 Americans, it spreads through the
body, hardening vital organs and often killing within five years.Diane Drolet,
48, who was diagnosed with scleroderma in 1991,said that Relaxin has "helped
quite a bit," unlike previous drugs."It's definitely changed my life for
the better."The former administrative assistant, of Queens, N.Y.,has been
unable to work for the past 3-1/2 years and couldn't cook, dress or brush
her hair unassisted. She received Relaxin for two six-month periods during
the drug's testing and noticed much of her skin softening up, letting her
function without help.Relaxin, administered via a stomach pump worn on a
belt, decreases collagen production and accelerates breakdown of the structural
protein.While existing medications ease pain and control complications of
scleroderma, Relaxin is the only drug being developed
to reverse the
disease, according to Karl Kastrof, executive director of the Scleroderma
Foundation, which is "quietly optimistic"about the drug. In the most recent
research phase, 70 percent of patients getting a low dose saw a significant
decrease in skin scarring and increase in ability to function -- as did about
half as many patients getting a dummy pill.Independent researchers said the
drug, a genetically engineered version of a hormone prevalent in pregnant
women, shows promise but further research is needed."This drug has a very
good safety profile. I think it's promising, and it's an exciting option
when you look at some of the toxic drugs that we've been using," said Dr.
Fredrick Wigley, professor of medicine and co-director
of the scleroderma center at Johns Hopkins University School of Medicine
in Baltimore.Higgins said Connectics plans to start the final research phase
this summer and seek approval in 2000 from the Food and Drug Administration.
For further information,
contact the Scleroderma Foundation
at www.scleroderma.com
or Call 1-800-722-HOPE
,or the medical school scleroderma program at
1-732-235-7520.
Scleroderma Links
The Scleroderma Research Foundation
Photo of Scleroderma
United Scleroderma Foundation
Scleroderma Federation
American Medical Association
Children with Scleroderma
Yahoo Scleroderma
Yahoo Scleroderma Organization
Surving Scleraderma
Medicine Net
DMSO--Scleraderma
Scleroderma Organization Addresses
British Coalition of Heritable Disorders of Connective Tissue
6 Queens
Road, Fairborough Hants GU14 6DH, United Kingdom
NIH/National
Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse,
One AMS Circle,
Bethesda, MD 20892-3675
Scleroderma
Federation
Peabody Office
Building, 1 Newbury Street, Peabody, MA 01960
Scleroderma
Info Exchange, Inc.
150 Hines Farm
Road, Cranston, RI 02921
Scleroderma
Research Foundation
2320 Bath Street,
Suite 307, Santa Barbara, CA 93105
United Scleroderma
Foundation, Inc.
P.O. Box 399
Watsonville, CA95076
Scleroderma NewsGroups
Usenet - alt.support.scleroderma
My name is Rose Goode
I have had Linear Scleraderma since the age of 6 (1973)-
I wasn't Diagnosed until the age of 11(1978).
I have been in Remission for the last 20 years.
I have the Linear form.
I also have Juvenile Rheumatoid Arthritis,
and have been wheel-chair bound since 1983.
In 2001, I
was diagnosed with Hemolytic Anemia which was a result of the
Juvenile Rheumatoid Arthritis.
Took having my spleen removed to help me.
Doctor's tell me I am a miracle.
PRAISE THE
LORD!!!
|
NOTE:
This page is not meant to give medical advice,
But to help you have a better understanding of
Scleroderma/Scleraderma
Always Check with your own Medical Professional. |
October 15,1997
Date Last Modified
|
