Scleroderma

Scleroderma is a connective-tissue disease that causes a progressive build up of tough scar-like tissue in the skin and internal organs. The term scleroderma is derived from the Greek words, skleros, meaning "hard," and derma meaning "skin." An individual with scleroderma may develop either a localized or systemic form of the disease. Localized scleroderma usually affects only the skin on the hands and face. Systemic scleroderma, however, affects the connective tissue in many parts of the body, including the skin, the esophagus, gastrointestinal tract, lungs, kidneys, heart, and other internal organs. It is unusual for localized scleroderma to progress to the systemic form. According to the Scleroderma Foundation, an estimated 300,000 people in the United States have the condition.

Signs and Symptoms

Symptoms of scleroderma may include one or more of the following:

• Raynaud's phenomenon (abnormal sensitivity to cold in the hands or feet)
• Swelling of the fingers, hands, forearms, feet, lower legs, and face
• Thickening, hardening, and discoloration of the skin
• Ulcers or lesions on fingers, face, tongue, and inner lining of the cheek
• Joint pain, swelling, and stiffness (especially in the fingers and knees)
• Carpal tunnel syndrome
• Shortness of breath, cough
• Dry eyes
• Sexual dysfunction
• Digestive and gastrointestinal problems including difficulty swallowing, bloating, and abdominal pain

Five particular symptoms occasionally occur together and are clinically recognized as a variation of scleroderma called CREST syndrome. The term CREST stands for Calcinosis (painful calcium deposits under the skin), Raynaud's phenomenon (abnormal sensitivity to cold in the hands and feet), Esophageal dysfunction (problems with swallowing caused by internal scarring), Sclerodactyly (tightening of the skin on the fingers or toes) and Telangiectasia (lesions on the hands, palms, forearms, face, and lips).

Causes

Scleroderma results from an overproduction of collagen, the primary connective tissue protein in the body. Scientists believe that the immune system mistakenly attacks the patient's own cells (an autoimmune response), producing too many white blood cells and other factors that cause a damaging inflammatory response and an overproduction of collagen, primarily in the skin. Researchers are not clear why this autoimmune response occurs, but they suggest that both genetic and environmental factors play a role in the development of the disease. For example, scleroderma has been associated with a number of industrial and pharmaceutical chemicals including:

• Silica dust
• Some plastic materials, such as epoxy resins and vinyl chloride
• Aromatic hydrocarbons
• L-tryptophan (synthetic supplement)
• Rapeseed oil

Risk Factors

The following factors may increase a person's risk for scleroderma:

• Gender – approximately 3 times more women than men develop the disease
• Age – scleroderma is most common among individuals between the ages of 20 and 50; it is relatively rare in children
• Race/Ethnicity – young women of African ancestry and native Americans of the Choctaw tribe of Oklahoma have a high prevalence of the disease

Diagnosis

An individual with symptoms of scleroderma will most likely require consultations with both a rheumatologist (arthritis specialist) and a dermatologist (skin specialist). The physician will conduct a physical examination in which he or she may feel the skin, checking for thickened and hardened areas and may also press affected tendons and joints. The physician may also conduct the following procedures to diagnose the disease:

• Blood tests – may detect elevated levels of antibodies found in the majority of individuals with scleroderma
• Skin biopsy – samples of skin may be taken to identify abnormalities suggestive of scleroderma
• Chest X ray and/or pulmonary function test – may detect lung damage or altered lung capacity
• MRI and/or CT scan – often detect early signs of damage to the muscles and internal organs

Diagnosing scleroderma may be difficult, particularly in the early stages of the disease. This is because many individuals with scleroderma experience symptoms of other connective-tissue diseases, such as rheumatoid arthritis, lupus, and polymyositis. When these conditions overlap, it is called mixed connective-tissue disease.

Preventive Care

It is important for an individual with scleroderma to avoid developing infections, so the physician will administer the following:

• Pneumococcal pneumonia vaccine
• Annual flu vaccine

Treatment Approach

Currently, there is no cure for scleroderma. While medications are often used to treat the symptoms of the disease, they are not always effective and many have significant side effects. There are, however, less toxic ways to treat the symptoms of scleroderma, which make living with the disease easier. For example, biofeedback successfully controls the temperature of the hands and feet of those with Raynaud's phenomenon. Studies also suggest that acupuncture may raise the temperature and improve circulation in the hands and feet. Finally, simple lifestyle changes may also improve an individual's quality of life.

Lifestyle

While lifestyle adjustments will not stop the progression of scleroderma, these simple measures may enhance an individual's quality of life:

• Eating small, frequent meals – may reduce gastrointestinal problems
• Maintaining an active lifestyle – may preserve muscle
• Avoiding smoke, exposure to cold, and stress – may prevent blood vessel spasms that diminish circulation
• Applying soothing skin creams to affected areas – may reduce pain, swelling, and stiffness

Medications

Localized scleroderma often is treated with topical therapies such as moisturizers or topical corticosteroids. Oral medications may also be used to halt the progression of localized scleroderma if it involves a large area of the body, such as an entire arm or leg. Systemic scleroderma may be treated with medications that improve circulation, promote gastrointestinal function, preserve kidney function, and control high blood pressure. Some medications a physician may prescribe for scleroderma include:

• Penicillamine – can reduce skin thickening and delay spread of damage to internal organs; has relatively high incidence of adverse reactions.
• Pentoxifylline – may improve circulation
• Immunosuppressant medications (such as cyclophosphamide) – often used for patients with life-threatening form of the disease; potent medications that damage cells' genetic information; may cause significant side effects
• Anti-inflammatory medications (such as aspirin, ibuprofen, and corticosteroids) – may reduce inflammation and swelling
• Calcium-channel blockers (such as nifedipine and diltiazem) – often used to treat Raynaud's phenomenon
• Antibiotics – prevent overgrowth of bacteria in the intestines and improve digestive processes
• ACE inhibitors (such as captopril) – may improve hypertension, prevent kidney damage, and dilate blood vessels

Surgery and Other Procedures

When symptoms of scleroderma become very severe, physicians may recommend the following procedures:

• Surgery to repair damage to the stomach or intestinal walls
• Amputation of severely diseased and infected fingers or toes
• Kidney, heart, and/or lung transplantation (in rare cases)

Nutrition and Dietary Supplements

Many individuals with scleroderma develop gastrointestinal problems and consequently reduce the amount of food they consume and nutrients they absorb. A recent study found that people with scleroderma tend to have deficiences in many vitamins and minerals. To prevent malnutrition, clinicians may recommend daily multivitamins that contain the following:

• Vitamin E
• Vitamin C
• Carotene
• Linoleic acid
• Selenium

Preliminary research also suggests that creams containing vitamin E may soften hard skin; however, more research is warranted in this area.

Herbs

Although herbs have not been rigorously tested for the treatment of scleroderma, some preliminary studies of particular herbs have shown promise in inhibiting actions that may be related to the development of scleroderma. These herbs include:

Danshen root (Salvia miltiorrhizae)
This herb is currently used in China to treat circulatory problems and kidney failure. One preliminary study indicates that danshen root prevents the formation of fibrous tissue, but further research is required before it can be proven effective for the treatment of scleroderma.

Keishi-bukuryo-gan
Laboratory studies indicate that this Chinese herbal mixture may inhibit collagen synthesis. The active ingredients in this herbal mixture include Ceylon cinnamon (Cinnamomum verum), Chinese cinnamon bark (Cinnamomum aromaticum) used traditionally for bloating and heartburn, and peony root (Paeonia lactiflora) used for arthritis as well as gastrointestinal, heart, and circulatory problems.

Gotu Kola (Centella asiatica)
Clinical trials suggest that low doses of gotu kola may decrease hardening of the skin associated with scleroderma, reduce joint pain and improve finger mobility. These studies involved small numbers of patients, however, so additional research in this area is warranted.

Although they haven't been scientifically examined for the treatment of scleroderma specifically, certain herbs, including bromelain (Ananas comosus), hawthorn berry (Crataegus monogyna), and horse chestnut (Aesculus hippocastanum), may be beneficial in treating connective tissue disorders in general.

Acupuncture

A few studies of patients with systemic scleroderma indicate that acupuncture may improve circulation in the hands and fingers, mend fingertip ulcers, and possibly reduce the formation of fibrous tissue.

Massage and Physical Therapy

Research suggests that massage may be useful in improving circulation and preventing muscle distortion. More research is needed in this area to determine whether massage is truly an effective complementary therapy for scleroderma.

Mind/Body Medicine

Biofeedback appears to successfully control the temperature in the hands and feet of those with Raynaud's phenomenon, a symptom often found in those with scleroderma.

Other Considerations

Prognosis and Complications

Possible complications that may result from scleroderma include the following:

• Joint damage
• Damage to smooth muscles in the gastrointestinal tract
• Malnutrition
• Formation of fibrous tissue in the heart muscle; may lead to permanent damage and/or degradation
• Kidney damage and/or failure
• Formation of fibrous tissue in the thyroid gland

The prognosis for those with scleroderma is highly variable and depends primarily on the form of the disease. For example:

• The CREST syndrome tends to progress slowly and remains relatively benign for decades. The 10-year survival rate for those with CREST is 75%.
• Those with localized scleroderma also have a 10-year survival rate of 75%.
• Systemic scleroderma tends to progress faster in men and in those who are older at the onset of the disease. The 10-year survival rate for those with systemic scleroderma is 55%. If damage spreads to the heart, lung, or kidneys early in the course of the disease, prognosis is generally poor.
• Spontaneous remissions from scleroderma have also been reported, with symptoms of the disease resolving in the reverse order that they appeared.

References

ACE inhibitors. NMIHI. Accessed at http://drugs.nmihi.com/ace-inhibitors.htm on June 28, 2018.

Amento EP. Immunologic abnormalities in scleroderma. Semin Cutan Med Surg. 1998;17(1):18-21.

Anti-inflammatory drugs. NMIHI. Accessed at http://drugs.nmihi.com/anti-inflammatory.htm on June 28, 2018.

Antibiotics. NMIHI. Accessed at http://drugs.nmihi.com/antibiotics.htm on June 28, 2018.

Arlett CM et al Identification of fetal DNA and cells in skin lesions from women with systemic sclerosis. N Engl J Med. 1998;338(17):1186-91.

Barr WG. Current topics in the diagnosis and treatment of scleroderma. Compr Ther. 1991;17(6):39-45.

Beers MH, Berkow R, eds. The Merck Manual of Diagnosis and Therapy. 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999. Section 5, Chapter 50.

Behr J, Maier K, Degenkolb B, et al. Antioxidative and clinical effects of high-dose N-acetylcysteine in fibrosing alveolitis. Adjunctive therapy to maintain immunosuppression. Am J Respir Crit Care Med. 1997;156:1897-1901.

Bhalla AK, Amento EP, Serog B, et al. 1,25-dihydroxyvitamin D3 inhibits antigen-induced T cell activation. J Immunol. 1984;133(4):1748-1754.

Black CM. Prognosis and management of scleroderma and scleroderma-like disorders in children. Clin Exp Rheumatol. 1994;12(suppl 10):S75-81.

Black CM. Scleroderma in children. Adv Exp Med Biol. 1999;455:35-48.

Black CM. Scleroderma: clinical aspects. J Intern Med. 1993;234(2):115-8.

Blumenthal M, ed. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Boston, Mass: Integrative Medicine Communications; 1998:94, 121, 222, 364.

Blumenthal M, ed. Herbal Medicine. Expanded Commission E Monographs. Boston, Mass: Integrative Medicine Communications; 2000:65-71.

Burckdorfer KR, Hillary JB, Bunce T, et al. Increased susceptibility to oxidation of low-density lipoproteins isolated from patients with systemic sclerosis. Arthritis Rheum. 1995;38(8):1060-1067.

Calcium channel blockers. NMIHI. Accessed at http://drugs.nmihi.com/ccbs.htm on June 28, 2018.

Caca-Biljanovska NG, Vlckova-Laskoska MT, Dervendi DV, et al. Treatment of generalized morphea with oral 1,25-dihydroxyvitamin D3. Adv Exp Med Biol. 1999;455:299-304.

Casale R et al Systemic sclerosis (scleroderma): an integrated challenge in rehabilitation. Arch Phys Med Rehab. 1997;78(7):767-73.

Cunningham BB, Landells, IDR, Langman C, et al. Topical calcipotriene for morphea/linear scleroderma. J Am Acad Dermatol. 1998;39(2 Pt 1):211-215.

Elst EF, van Suijlekom-Smit LWA, Oranje AP. Treatment of linear scleroderma with oral 1,25-dihydroxyvitamin D₃ (calcitriol) in seven children. Pediatr Dermatol. 1999;16(1):53-58.

Emery H. Pediatric scleroderma. Semin Cutan Med Surg. 1998;17(1):41-7.

Esomeprazole. NMIHI. Accessed at http://www.nmihi.com/e/esomeprazole.html on June 28, 2018.

Eubanks LE et al. Linear scleroderma in children. Int J Dermatol. 1996;35(5):330-6.

Furlong JH. Acetyl-L-carnitine: metabolism and applications in clinical practice. Alternative Medicine Review. 1996;1(2):85-93.

Gelber AC, Wigley FM. Treatment of scleroderma. Curr Opin Rheumatol. 1995;7(6):551-9.

Gilliland BC. Systemic sclerosis (scleroderma). In: Fauci AS, Braunwald E, Isselbacher KJ, et al., eds. Harrison's Principles of Internal Medicine. 14th ed. New York, NY: McGraw-Hill; 1998:1888-1895.

Haustein UF, Anderegg U. Pathophysiology of scleroderma: an update. J Eur Acad Dermatol Venereol. 1998;11(1):1-8.

Hecht C. Scleroderma. In: Jonathan Adler et al., eds. Emergency Medicine: an On-line Medical Reference. http://www.emedicine.com/. Chapter version October 12, 1999.

Herrick AL, Worthington H, Rieley F, et al. Dietary intake of micronutrient antioxidants in relation to blood levels in patients with systemic sclerosis. J Rheumatol. 1996;23(4):650-653.

Herrick AL. Advances in palliative care for the patient with scleroderma. Curr Opin Rheumatol. 1996;8(6):555-60.

Herron GS, Romero LI. Vascular abnormalities in scleroderma. Semin Cutan Med Surg. 1998;17(1):12-7.

Hodler B, Evequoz V, Trechsel U, et al. Influence of vitamin D3 metabolites on the production of interleukins 1,2 and 3. Immunobiology. 1985:170(4):256-269.

Humbert P, Dupond JL, Agache P et al. Treatment of scleroderma with oral 1, 25-dihydroxyvitamin D₃: evaluation of skin involvement using non-invasive techniques. Acta Derm Venereol. 1993;73(6):449-451.

Hunzelmann N et al. Management of localized scleroderma. Semin Cutan Med Surg. 1998;17(1):34-40.

Jimenez SA et al. Pathogenesis of scleroderma. Rheum Dis Clin North Am. 1996;22(4):647-74.

Kerin K, Yost JH. Advances in the diagnosis and management of scleroderma-related vascular complications. Compr Ther. 1998;24(11-12):574-81.

Krane SM, Amento EP. Cellular interactions and control of collagenase secretion in the synovium. J Rheumatol Suppl. 1983;11:7-12.

Lemire J. 1,25-Dihydroxyvitamin D3 — a hormone with immunomodulatory

Lundberg A-C, Åkesson A, Åkesson B. Dietary intake and nutritional status in patients with systemic sclerosis. Ann Rheum Dis. 1992;51(10):1143-1148.

Maeda M, Kachi H, Ichihashi N et al. The effect of electrical acupuncture-stimulation therapy using thermography and plasma endothelin (ET-1) levels in patients with progressive system sclerosis (PSS). J Dermatol Sci. 1998;17(2):151-155.

Mayes MD. Scleroderma epidemiology. Rheum Dis Clin North Am. 1996;22(4):751-64.

McGee BA et al. Current options for the treatment of systemic scleroderma. Clin Pharm. 1991;10(1):14-25.

Miller M. Scleroderma. Aust Fam Physician. 1993;22(12):2112-9.

Mitchell H, et al. Scleroderma and related conditions. Med Clin North Am. 1997;81(1):129-49.

Muller-Ladner U, et al. Current therapy of systemic sclerosis (scleroderma). Clin Investig. 1993;71(4):257-63.

Murray MT. The Healing Power of Herbs: The Enlightened Person's Guide to the Wonders of Medicinal Plants. Rocklin, Calif: Prima Publishing; 1991:209.

Olsen NJ, et al. Muscle abnormalities in scleroderma. Rheum Dis Clin North Am. 1996;22(4):783-96.

Pang BK, Munro V, Kossard S. Pseudoscleroderma secondary to phytomenadione (vitamin K₁) injections: Texier's disease. Australas J Dermatol.1996;37(1):44-47.

Proton pump inhibitors. NMIHI. Accessed at http://drugs.nmihi.com/ppis.htm on June 28, 2018.

Rose S, et al. Gastrointestinal manifestations of scleroderma. Gastroenterol Clin North Am. 1998;27(3):563-94.

Schachter RK. Localized scleroderma. Curr Opin Rheumatol. 1990;2(6):947-55.

Sheng FY, Ohta A, Yamaguchi M. Inhibition of collagen production by traditional Chinese herbal medicine in scleroderma fibroblast cultures. Intern Med. 1994;33(8):466-471.

Shigematsu T, Tajima S, Nishikawa T, et al. Inhibition of collagen hydroxylation by lithospermic acid magnesium salt, a novel compound isolated from Salviae miltiorrhizae Radix. Biochem Biophys Acta. 1994:1200(1):79-83.

Silman AJ. Scleroderma. Baillieres Clin Rheumatol. 1995;9(3):471-82.

Silver RM. Scleroderma: clinical problems: the lungs. Rheum Dis Clin North Am. 1996;22(4):825-40.

Scleroderma. NMIHI. Accessed at http://www.nmihi.com/s/scleroderma.htm on June 28, 2018.

Scleroderma. MedlinePlus. Accessed at https://medlineplus.gov/scleroderma.html on June 28, 2018.

Scleroderma. Symptoms and causes. MFMER. Accessed at https://www.mayoclinic.org/ on June 28, 2018.

Sjogren RW. Gastrointestinal features of scleroderma. Curr Opin Rheumatol. 1996;8(6):569-75.

Sjogren RW. Gastrointestinal motility disorders in scleroderma. Arthritis Rheum. 1994;37(9):1265-82.

Tuffanelli DL. Localized scleroderma. Semin Cutan Med Surg. 1998;17(1):27-33.

Uziel Y et al. Scleroderma in children. Pediatr Clin North Am. 1995;42(5):1171-203.

Van den Hoogen FH, de Jong EM. Clinical aspects of systemic and localized scleroderma. Curr Opin Rheumatol. 1995;7(6):546-50.

What is scleroderma? American Academy of Family Physicians Accessed at https://familydoctor.org/ on June 28, 2018.

White B. Immunologic aspects of scleroderma. Curr Opin Rheumatol. 1995;7(6):541-5.