Scleroderma
Fact Sheet
The information on this fact sheet has mostly been found on the internet. This means that there is a bias towards treatment initiatives in America, and little information about whether treatments are available in the UK. It also means that the information may not be comprehensive. Patients should talk to their consultants about treatment options available in the UK.
New treatments for Scleroderma are extremely difficult to research well. Scleroderma affects individuals in different ways, which makes it very difficult to form homogenous groups on which to run trials, yet small samples have no statistical power, making it very difficult to predict the course of the disease. Also, some of the worst effects of the disease can be life threatening, making it unethical to have a control group that receives no treatment. 'Double blind' studies (where neither the patient, nor the researcher, know who is being treated) are therefore very difficult, and sometimes impossible, to run. The Analysis of results not from a double-blind study is then open to unconscious bias and their value can be limited.
What is Scleroderma?
Scleroderma (hard skin) is a little-known disease of the connective tissue, immune system and blood vessels, which primarily affects women in the childbearing years, though it can affect anyone of any age. It results in taut, hard, discoloured skin and may also affect the internal organs.
Scleroderma is divided into localised forms (morphoea, linear scleroderma) and generalised scleroderma (systemic sclerosis, SSc). SSc has a severe and a mild form. The severe form, diffuse cutaneous SSc, affects 40% of sufferers; the mild form, limited cutaneous SSC, 60%. In the severe form, wide areas of the skin are affected and internal organ involvement occurs early. Scleroderma can be fatal, with lung disease as the chief cause of death. Survivors have a greatly reduced quality of life with breathlessness, kidney disease, heart disease, digestive problems and reduced function in joints, muscles and hands. In the mild form, there is limited skin involvement with the later development of gut disease (and thus difficulty in swallowing and eating) and lung problems. Additionally there may be calcinosis (deposits of calcium which mass under the skin and protrude), dry eyes and mouth, ulceration and a very poor circulation.
Juvenile scleroderma differs from the adult disease in that localised forms predominate. The juvenile disease attacks particularly the skin, muscles, joints, tendons and bones, with internal organ involvement a rarity. Childhood morphoea may last 3-4 years then resolve spontaneously, but the linear form may lead to growth defects.
Treatments
Currently there is no treatment to cure scleroderma, although there are many treatments to deal with the symptoms. There are also a number of initiatives, some of which are detailed below (in alphabetic order).
Antibiotic treatment
There is increasing evidence that scleroderma and other rheumatic diseases are caused by hypersensitivity (allergic-type) reaction due to infection of mycoplasmas or bacterial L-form variants. If this is so then it is thought that antibiotics would be effective in addressing the cause of the illness. Treatment is tailored to individual patients and could be life long in some instances. Results are gradual but the following symptoms are among those reported to be improved: pain, stiffness, restricted range of motion, dry or cracked or tight skin, skin ulcers, swallowing difficulties and heartburn.
Trails have been done on Minocyclin - a member of the tetracycline group of antibiotics -, which is most commonly used to treat acne. David Trentham, MD (Harvard Medical School, Beth Israel, Deaconess Medical Centre, Boston, Massachusetts), has carried out a small open study on 11 patients with scleroderma, sponsored by The Road Back Foundation and the NIH. Results have to be treated with caution as the sample was very small and the mechanism by which mynocycline might work is not understood. However four of the patients had complete remissions. The most frequent side effects are vomiting and diarrhoea. Minocyclin also interferes with the balance mechanism of the inner ear with resulting dizziness, nausea and unsteadiness. It is not prescribed to people who have problems with their kidneys.
Brown seaweed or kelp - a wound dressing made from calcium alginates, derived from kelp, has recently been found to be useful in the treatment of sclerodermal ulcers.
Bone Marrow Transplant / stem cell transfusion.
Currently being studied in America, the procedure is for patients whose skin is extensively affected and whose internal organs have been mild to moderately affected before their disease has continued for three years. Blood cells and bone marrow are removed from the patient who is then given immunotherapy with drugs and x-ray radiation. The process of immunotherapy destroys blood cells and bone marrow, so the stored cells are then put back into the patient afterwards allowing the bone marrow to grow back. In some cases bone marrow from a matched relative (brother or sister) can be used. The process has the potential to reverse the disease.
To be eligible for the process patients must be between 18 and 60 with a diagnosis of diffuse systemic sclerosis.
For more information about clinical trials contact:
Arthritis Clinical Research Unit
Virginia Mason Research Center R1-RC
1000 Seneca Street
Seattle, WA 98101
http://www.vmresearch.org/ar_1999_clinical.htm
Corticosteroid drugs (steroids)
They are derived from, or are synthetic variants of, the natural corticosteroid hormones formed in the outer part (cortex) of the adrenal glands situated on top of each kidney. Their presence in large amounts in the body helps to reduce inflammation and suppress allergic reactions and immune system activity. (Not to be confused with anabolic steroids which build muscle.) They relieve symptoms and may also temporarily halt the disease.
Side effects include increased susceptibility to infection, peptic ulcers, and the risk of diabetes/worsening of pre-existing diabetes. In children they can retard growth. Long-term use of high doses can lead to acne, mood changes, rounding of the face (moon-face), increased blood pressure and fluid retention, muscle wasting, easy bruising, a fat pad on the back and osteoporosis.
Dimethyl Sulfoxide (DMSO)
In America it has been in use since the 1940's as an industrial solvent and introduced into therapeutic practice in the 1960's as a treatment for strains, sprains, bruises and arthritis. It is currently being studied, but not approved, for use in a number of skin, nerve and autoimmune diseases. There have been some studies which seem to show better survival rates among mice who were given a 3% solution of DMSO in their drinking water.
DMSO has been in use since 1974 by the Institute of Rheumatology AMS USSR for systemic scleroderma. Affected areas are either immersed in a DMSO solution, or it can be applied topically, or administered subcutaneously. Research seems to show that patients with relatively mild disease are more likely to respond favourably than those with severe to advanced disease. DMSO seems to work on collagen leading to greater movement ability and skin pliability with dense skin swelling lessened.
D-penicillamine
An antirheumatic drug given to slow or even halt the progression of rheumatic arthritis has been used in scleroderma with variable effects.
Interferon-g
Interferons are a group of substances produced in human and animal cells that have been infected with viruses or stimulated by other substances. They are thought to promote resistance to other types of viral infection. In an open, controlled multicenter study from Germany 32 patients suffering from diffuse or limited forms of systemic sclerosis were given 50mg interferon-g three times a week for 1 year. After a year patients had stabilised where they would have been expected to worsen. Side effects were minor flu-like symptoms.
Methotrexate
This drug is capable of blocking the metabolism of cells and is therefore used in the treatment of certain diseases characterised by abnormally rapid cell growth. It has been used in the treatment of rheumatoid arthritis and psoriasis, although the reason why it is helpful is not known.
Nutritional supplements
Malabsorption can be a big problem for scleroderma sufferers due to the scarring and bacterial overgrowth of their intestines. Antibiotics are often prescribed which help with absorption and removing bad bugs, but often liquid nutritional supplements or intravenous nutrition is also required. Some deficiencies common amongst scleroderma sufferers include:
· Vitamin B12 deficiency, which can lead to fatigue, memory loss and abnormal gait.
· Vitamin D deficiency, leading to softened bones.
· Vitamin K deficiency leading to haemorrhaging.
· Vitamin E deficiency can lead to sclerodermal bowel disease.
Photopheresis
A procedure similar to dialysis in that a large-caliber IV tube is inserted into one arm, blood is removed, treated and returned to the patient. The blood is passed through a centrifuge, which separates white and red blood cells. The white blood cells - the main cells responsible for autoimmune disease - are collected in a bag, which is injected with a medicine, then exposed to ultraviolet light, then transfused back into the patient. In Seattle a study was carried out in 1991 but was deemed inconclusive by the FDA. Some patients in the test, however, showed dramatic improvement with few side effects. It is not known why it should work.
For further information on photopheresis contact:
Arthritis Clinical Research Unit
Virginia Mason Research Center, R1-RC
1000 Seneca Street
Seattle WA 98101
http://www.vmresearch.org/ar_1999_clinical.htm
Psoralen-UV-A therapy (PUVA)
Psoralen is one of a class of compounds originally used in the treatment of cutaneous diseases, initially for psoriasis, in the early 1970's by TB Fitzpatrick and JA Parrish at Harvard. When it was activated with UVA (320-400 nm radiation) it showed good results in controlling psoriasis. Research has been carried out on patients with systemic sclerosis showing some improvement of symptoms and indicated that it may be an effective treatment for patients who are undergoing skin changes.
For more information contact on this research contact:
Angelike Hofer, MD
Department of Dermatology University of Graz
Universitaetplatz3
A-8010 Graz
Austria
E-Mail: angelika.hofer@uni-graz.at
For more information on PUVA contact:
Francis P Gasparro PhD, Director
Jefferson University Photobiology Lab
Department of Dermatology and Cutaneous Biology
233 South 10th Street (Room 428)
Philadelphia
PA 19107-5541
Relaxin (brand name ConXnR)
In development, Relaxin (recombinant human relaxin H2) is a natural protein and has been shown to inhibit excessive connective tissue build-up by decreasing collagen production and enhancing collagen breakdown. This has led to improvements in, among other things, the function of the lungs, the ability to extend the hands and increased eating, gripping and reaching ability.
Superoxide Dismutase (SOD) and Liposomal Superoxide Dismutase (LIPSOD)
Superoxide dismutase is an enzyme that in its different forms is associated with copper, zinc and manganese. Its function in the body is to keep the membranes fluid and the tissues and muscles supple. Without SOD the body would harden up and wither.
SOD is available in health stores, however, unfortunately it seems that this product has no effect, as taken orally, it is destroyed in the gut and so is unable to affect the tissues it is supposed to benefit. In order to do some good SOD must be injected or taken in liposomal forms (encapsulated in a liposome 'delivery vehicle'). It is thought to be beneficial for 'hardening' diseases and disorders. Much of the pioneering work on the use of SOD and LIPSOD has been done by A. M Michelson of the Institut de Biologie Physico-Chimique in Paris, and research is being carried out in Japan and America. In one woman with severe scleroderma who received two injections of LIPSOD weekly, a significant regression of the disease was observed.
Thalidomide
Thalidomide has been used to clear severe skin reaction associated with leprosy treatment, and more recently in chronic inflammatory skin and mucous membrane disorders. Theoretically it has the potential to have a positive effect on scleroderma. A study is planned to use thalidomide in treating scleroderma by The Rockefeller University Hospital, New York City.
UVA - 1 therapy
UVA-1 radiation penetrates the skin and has an effect on epidermal structures and midermal and deep dermal components, especially blood vessels. It is being investigated as a safer alternative to PUVA for treating long-term conditions. Much of the early work in this realm has been done in Europe where efficient sources of UVA-1 radiation are more widely available. Initial results are promising but more detailed tests need to be carried out. Pilot studies have shown that it can soften and reduce the diameter of sclerotic legions and in some instances clear plaques completely.
For further information contact:
Jefferson University Photobiology Lab
Department of Dermatology and Cutaneous Biology
233 South 10th St (Room 428)
Philadelphia
PA 19107-5541
Tel: 215 503 3327
E-mail: forondoc@AOL.com
Other
Muscle aches and pains can be helped by therapies such as physiotherapy, chiropractic, acupuncture, massage, hydrotherapy and relaxation. Heartburn can be treated with antacids. Other medications used to alleviate symptoms of the disease are aspirin, nonsteroidal anti-inflammatory drugs, and blood pressure medication.
References
- The CaF Directory (Contact a Family) of Specific Conditions and Rare Syndromes in Children with their Family Support Networks.
- The Efficacy of Long-Term Application of Dimethyl Sulfoxide in a complex therapy of Patients with Systemic Scleroderma, U.V. Murav'ev, A.P. Aliab'eva, I.A Sigidin, and N.G. Guseva.
- Hunzelmann N, Anders S, Fierlbeck G et al. Systemic Scleroderma. Multicenter trial of 1 year of treatment with recombinant interferon gamma. Arch Dermatol 1997; 133:609-613
Resources
Organisations
The Scleroderma Society
3 Caple Rd
London
NW10 8AB
Tel: 020 8961 4912
http://www.sclerodermasociety.co.uk
The Raynaud's & Scleroderma Association
112 Crewe Road
Alsager
Stoke-on-Trent
ST7 2JA
Tel: 01270 872776
http://www.raynauds.demon.co.uk/
Offers help to families of newly diagnosed children and adults, support to families of sufferers, information about the condition and names of appropriate medical consultants, a quarterly newsletter and information pack.
UK Scleroderma Group Central Register of UK Systemic Sclerosis Patients
Centre for Rheumatology
Royal Free and University College Medical School
Rowland Hill Street
London NW3 2PF
Tel: 0171 830 2360
This register aims to increase the numbers of UK patients available for research.
The Scleroderma Foundation
12 Kent Way Suite
101 Byfield,
MA 01922
Tel: (001) 978 463 5843
http://www.scleroderma.org/
Websites
- http://www.worldchat.com/public/scleroderma/greatlinks.htm - from this site you can access other relevant websites.
Further Reading
These are some of the references that have been passed to us; the list is not exhaustive. We have not necessarily read the books, and cannot say how easy it will be to get them.
- Scammell Henry The New Arthritis Breakthrough, ISBN: 0871318431
- Scammell Henry Scleroderma: The Proven Therapy That Can Save Your Life. ISBN: 0871318423
- Mayes Maureen Scleroderma Book: A Guide for Patients and Families. ISBN: 0195115074
- Melvin Jeanne Scleroderma: Caring for Your Hands & Face. ISBN: 1569000069
- Clements Philip Systemic Sclerosis. ISBN: 0683017403
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