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What is scleroderma?

Scleroderma literally means “hard skin“. The name is derived from the Greek words

“sklerosis“, meaning hardness, and “derma“, meaning skin. In scleroderma, collagen

forms thick connective tissue that builds up around the cells of the skin and internal

organs. Actually, scleroderma is one symptom of a cluster of disorders that involve the

abnormal growth of connective tissue. In some forms, hard, tight skin is the extent of

the abnormal process. In other forms, the disease affects blood vessels and internal

organs, such as the heart, the lungs, and kidneys. Scleroderma is both a rheumatic and

a connective tissue disease. The term “rheumatic“ characterises the inflammation

and/or pain in the muscles, joints, or fibrous tissue. Connective tissue disorders affect

the matrix compounds of the skin, the tendons, and the bones.

The cause of scleroderma is not known. It is not an infectious disease. Studies of twins

suggest it is not inherited, and the disease is not passed from parents to children. So

far, scientists believe that scleroderma is caused by several factors, such as abnormal

activity of the immune system, genetic make-up, hormones and environmental influ-

ence. Research has shown that pregnancy increases a woman’s risk of scleroderma.

Other findings suggest that exposure to environmental factors may trigger the disease

in people who are genetically predisposed. Suspected triggers include viral infections,

certain adhesive and coating materials, and organic solvents.

Scleroderma can be divided into two forms: localised scleroderma and systemic scle-

roderma. The localised form is limited to the skin and related tissues. Internal organs

are not affected, and localised scleroderma does not progress to the systemic form.Often, localised conditions improve or disappear on their own over time, but the skin

changes and damages may become permanent. Thus, localised scleroderma can be

serious and disabling.

Scleroderma

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Scleroderma is a disabling

disease where thick tissue

forms around the cells

of the skin and internal

organs. Existing

treatments relieve

symptoms and limit

damage. There are many

research efforts into

finding new medicines.

There are two types of localised scleroderma: morphea, which means “form“ or “struc-

ture“ in Greek, and linear scleroderma. Morphea refers to reddish patches of skin that

thicken into firm, oval-shaped areas; most often on the chest, stomach and back. Mor-

phea generally fades out in three to five years; however, patients are left with dark-

ened skin patches and, in rare cases, muscle weakness. Linear scleroderma refers to

the single line or band of thickened and abnormally coloured skin. The line may run

down an arm or leg, but in some people it runs down the forehead. Dermatologistsuse the French term “en coup de sabre“ , or “sabre stroke,“ to describe this phenome-

non.

Systemic scleroderma involves the tissue layers surrounding the blood vessels and

major organs. Patients have all or some of the symptoms that are described by the

acronym CREST : (i) Calcinosis, which is a formation of calcium deposits in the con-

nective tissues; (ii) Raynaud’s phenomenon: a condition in which the small blood ves-

sels of the hands or feet contract in response to cold or anxiety; (iii) Esophageal dys-

function occurs when smooth muscles in the oesophagus lose normal movement; (iv)

Sclerodactyly , which refers to thick and tight skin on the fingers, because of deposits

of excess collagen within skin layers; and (v) Telangiectasias, which are small red

spots on the hands and face that are caused by the widening of very small blood ves-sels.

Who does sc leroderma af fect?

Scleroderma is more common in women, but the disease also occurs in men and chil-

dren. In the age group 30-55 years, women develop scleroderma at a rate 7-12 times

higher than men. The disease affects people of all races and ethnic groups. However,

there are some patterns by disease type. Localised forms are more common in Cau-

casians than in African Americans. Morphea usually appears between the ages of 20-

40. Linear scleroderma mostly occurs in children or teenagers. Systemic scleroderma

typically occurs in people from 30 to 50 years old. It affects more coloured women

than white women.

Because systemic scleroderma can be difficult to diagnose, epidemiologists can only

estimate how many cases there actually are. Estimates for the number of patients in

Europe range between 40 and 200 adults per million inhabitants, which is equivalent

to 16,000 to 80,000 cases. The five-year survival rate of patients with the systemic

form of the disease is approximately 80 per cent.

Present treatments

Currently, there is no therapy that controls or inhibits the pathological production of

collagen in scleroderma. Thus, therapy focuses on relieving symptoms and limiting

damage. Pain-killers and non-steroidal anti-inflammatory drugs (NSAID) are used to

ease joint inflammation or muscle pain. Oil-based creams and lotions are applied to

soften the hardened skin. For the treatment of heartburn, medicines of the group of proton pump inhibitors or H2-antagonists are used.

About 10-15 per cent of patients with systemic scleroderma develop either pulmonary

fibrosis (hardening of lung tissue because of excess collagen) or pulmonary hyperten-

sion (high blood pressure in the artery that carries blood from the heart to the lungs).

Pulmonary fibrosis is treated with immunosuppressant compounds, along with low

doses of corticosteroids. Pulmonary hypertension is treated with medicines that dilate

the blood vessels such as prostacyclins or 5-phosphodiesterase (5-PDE) inhibitors. For

patients with heart problems, e.g. cardiomyopathy (scarring and weakening of the

heart), myocarditis (inflammation of the heart muscle) or arrhythmia (abnormal heart

beat), treatment options range from medicines to surgery. About 15-20 per cent of

patients develop severe kidney problems. Medicines known as angiotensin-convertingenzyme (ACE) inhibitors have made scleroderma-related kidney failure a less threat-

ening problem than it was in the past.

Localised scleroderma (skin)Courtesy of Dermatology Group Practice, Brussels,

Belgium © DGP, Brussels, Belgium

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What’s in the development pipeline?

Compounds that are capable of inhibiting fibroblast activity may be beneficial if

administered early in the course of the disease. In a phase 1/2 clinical trial, investi-

gators are assessing the effect of an endothelin-1 antagonist on disease progression.

Endothelin-1 has several distinct properties, among them profibrotic and inflammato-

ry activity, and vasoconstriction.

Researchers are studying the effect of a newly found imidazo-chi-

noline compound which induces cytokines that inhibit fibrotic

activity. The compound is applied topically as five per cent cream

in localised scleroderma. Main outcome of this phase 3 clinical

trial will be improvement of skin hardening.

Early studies suggest relaxin, a hormone that helps a woman’s

body to stretch to meet the demands of a growing pregnancy, may

soften the connective tissues of women with scleroderma. The hor-

mone is believed to work by inhibiting fibrosis.

Other research groups are investigating the effectiveness of vari-ous treatments, including: (i) combinations of immunosuppressant

compounds; (ii) collagen peptides administered orally; (iii) a med-

icine which inhibits the synthesis of type I collagen, which is the primary component

of connective tissue; (iv) ultraviolet light therapy for localised forms of scleroderma;

and (v) stem cell transfusions, which represents a form of bone marrow transplant that

uses a patient’s own cells, for early systemic scleroderma.

The longer -term future

Scientists have found a gene associated with scleroderma in Choctaw Native Ameri-

cans who develop the disease far more of ten than other people. The gene codes for a

protein called fibrillin-1, and researchers believe that it may put people at risk for the

disease.

The role of environmental factors and particularly exposure to certain compounds, has

been suggested as a cause of scleroderma. This warrants large scale prospective, case-

control studies. With financial support from the EU, the European League against

Rheumatism (EULAR) has established the EUSTAR (EULAR Scleroderma Trials and

Research Group) data bank, to lay the foundation for better cooperation between clin-

ical and research centres dealing with the pathophysiology and aetiology of the dis-

ease. The network will strive to improve both patient care, and the clinical and basic

research environment and infrastructure.

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D I S C L A I M E R

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completeness or accuracy of the information.

You must consult your doctor, or other qualified healthcare professional on any specific problem or matter covered by

the information in this PDF.

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Editing Board: Dr. Robert Geursen (Chief Editor), Peter Heer, Bill Kirkness, Philippe Loewenstein, Steve Mees,

Dr. Jean-Marie Muschart, Marie-Claire Pickaert (Coordinator).

Photocredits: ABPI, Allergan, AstraZeneca, EFPIA/Lander Loeckx, Damian Foundation, Galderma, Hilaire Pletinckx,

Roche, sanofi-aventis; Design & Production: Megaluna+Triumviraat

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