Scleroderma is an autoimmune disease of the connective tissue featuring skin thickening, spontaneous scarring, blood vessel disease, varying degrees of inflammation, associated with an overactive immune system. Autoimmune diseasess are illnesses which occur when the body’s tissues are attacked by its own immune system. Scleroderma is characterized by the formation of scar tissue (fibrosis) in the skin and organs of the body. This leads to thickness and firmness of involved areas. Scleroderma, when it’s diffuse or widespread over the body, is also referred to as systemic sclerosis.
The cause of scleroderma is not known. Researchers have found some evidence that certain genes are important factors, but the environment seems to also play a role. The result is activation of the immune system in a susceptible individual, causing injury to tissues that result in injury similar to scar-tissue formation. The fact that genes seem to cause a predisposition to developing scleroderma means that inheritance at least plays a partial role. It is not unusual to find other autoimmune diseases in families of scleroderma patients. Some evidence for the role genes may play in leading to the development of scleroderma comes from the study of Choctaw Native Americans who are the group with the highest reported prevalence of the disease. The disease is more frequent in females than in males. Systemic sclerosis can have many different presentations. It involves the skin and many internal organs. Therefore, the presenting symptoms may differ among patients. Note the following history findings:
€ Cutaneous pruritus is common.
€ Raynaud phenomenon, or whitening of the hands on exposure to cold, is a common finding. Pain in the affected digits, blanching, cyanosis, and hyperemia can follow.
€ Difficulty in swallowing solid foods can be followed by difficulty with swallowing liquids and subsequent nausea, vomiting, weight loss, abdominal cramps, blotting diarrhea, and fecal incontinence.
€ The patient can have shortness of breath on exertion and, subsequently, at rest.
€ Palpitations may occur without characteristic pain in thoracic cavity.
€ The patient may have a nonproductive cough.
€ Atypical chest pain, fatigue, dyspnea, and hypertension may be present.
€ Joint pain, limitation of movement, joint swelling, and muscle pain may be present. Systemic sclerosis begins as joint pain in 15% of patients. It begins as inflammatory myopathy in 10% of patients.
€ Weakness is present in 80% of patients.
Diagnosis is by clinical suspicion, presence of autoantibodies (specifically anti-centromere and anti-scl70/anti-topoisomerase antibodies) and occasionally by biopsy. Of the antibodies, 90% have a detectable anti-nuclear antibody. Anti-centromere antibody is more common in the limited form (80-90%) than in the diffuse form (10%), and anti-scl70 is more common in the diffuse form (30-40%) and in African-American patients (who are more susceptible to the systemic form).
In 1980 the American College of Rheumatology agreed upon diagnostic criteria for scleroderma.
Other conditions may mimic systemic sclerosis by causing hardening of the skin. Diagnostic hints that another disorder is responsible include the absence of Raynaud’s phenomenon, a lack of abnormalities in the skin on the hands, a lack of internal organ involvement, and a normal antinuclear antibodies test result.
There is no cure for systemic sclerosis and treatment is aimed at controlling symptoms and preventing complications. Because the symptoms of systemic sclerosis are so diverse a team of medical specialists is usually necessary.
Medical and surgical treatments:
Currently, there is no proven drug treatment to slow the progress of the disease process, although cyclophosphamide, penicillamine and mycophenolate mofetil have been used. Generally, treatment is aimed at relieving symptoms and early treatment of complications.
Management of skin and musculoskeletal symptoms
Raynauds symptoms and ulcers:
€ Calcium channel blockers (e.g. nifedipine) or AR2 blockers (e.g. losartan)
€ There are some reports that fluoxetine may help
€ Sympathectomy may relieve symptoms
€ For ischaemic ulcers:
o Simple protective dressings
o Antibiotics if infected
o Vasodilators may help in some situations, e.g. bosentan may reduce the occurence of new ulcers
o New treatments for Raynaud’s are nitroglycerin (ointment) or sildenafil (currently recommended only if other treatments not sufficient)
Skin dryness or itching:
€ Topical steroids (short course) or antihistamines
€ For patients with rapidly progressing diffuse scleroderma, consider a trial of immunosuppressant treatment, e.g. mycophenolate or cyclophosphamide
Surgical procedures for specific indications such as:
€ Release of contractures
€ Removal of troublesome calcinosis
Myalgia, arthralgia and painful oedema:
€ NSAIDs if tolerated
€ Simple analgesics
Gastrointestinal (GI) symptom management
For upper GI symptoms:
€ Upright posture after meals, raise head of bed; limit alcohol
€ Proton pump inhibitors
€ May also need H2-receptor blockers and pro-motility agents (metoclopramide or domperidone)
€ Dilatation of oesophageal strictures if required
For intestinal bacterial overgrowth and malabsorption:
€ Cyclical antibiotics
€ Nutritional advice and nutritional supplements; rarely, parenteral nutrition is required
€ Dietary fibre and good fluid intake
€ Softening laxatives (such as lactulose) and/or soluble fibre (such as ispaghula)
Complications (internal organ involvement) and their treatment
See also specific GI sections under Clinical features (symptoms) and Management headings.
€ “Watermelon stomach” (gastric antral vascular ectasia):
o May cause anaemia and GI bleeding
o May need endoscopic laser coagulation to prevent bleeding
Obstruction and pseudo-obstruction:
€ Can occur due to reduced motility and bacterial overgrowth
€ Can be complicated by perforation and peritonitis
€ Pseudo-obstruction is treated initially by bowel rest and antibiotics
€ Laparotomy may be needed
€ In some cases, the rectum and anus are involved, causing faecal incontinence
€ This may require surgery
Scleroderma renal crisis
€ A serious complication with features of accelerated hypertension
€ Can lead to renal failure if not treated promptly
€ Occurs in up to 20% of patients with diffuse scleroderma, usually in the first 4 years of the disease
€ Occurs in about 5% of patients with limited scleroderma
o Usually presents as accelerated hypertension with oliguria, headache, fatigue, oedema, rapidly rising serum creatinine levels, proteinuria and microscopic haematuria
o 10% of scleroderma renal crises occur with apparently normal blood pressure, but the BP is higher than baseline values – hence the importance of regular BP monitoring
€ Treatment is with ACE inhibitors , plus dialysis if necessary
Pulmonary fibrosis (interstitial lung disease):
€ Occurs in about 30% of scleroderma patients
€ Causes restrictive lung disease
€ Symptoms and signs: exertional dyspnoea, cough, coarse basal crackles
o Some trials suggest benefit from cyclophosphamide, which may be followed by azathioprine and prednisolone; benefits must be weighted against side-effects
o Supportive treatment: prompt treatment of chest infections, oxygen if needed
Pulmonary arterial hypertension (PAH):
€ Occurs in about 15% of patients with diffuse scleroderma and 5% with limited scleroderma
€ Symptoms and signs: exertional dyspnoea, syncope, right ventricular strain features