Scleroderma is a rheumatic autoimmune condition characterized by tightening and thickening of the skin. The term scleroderma is derived from the Greek words "skleros" and "derma," literally meaning "hard skin." Scleroderma is actually not a single disease but an umbrella term describing diseases affecting the connective tissue.1
Scleroderma can be classified as localized or systemic. The localized form manifests as local patches or linear bands of tightening skin and may not affect other body systems. The systemic form, also called systemic sclerosis (SSc), involves tissue fibrosis in the skin and frequently in the gastrointestinal tract, respiratory system, cardiovascular system and genitourinary system. SSc affects women at least four times more often than men, and the risk is slightly higher in black people than in white people. The incidence of SSc in the United States is approximately 19 cases per million people, and the estimated prevalence is 240 cases per million people.2
Knowing the Condition
Systemic sclerosis, which accounts for 90% of all scleroderma cases,3 is characterized by progressive tissue fibrosis caused by excessive collagen production. Although it is most obvious in the skin, it also manifests in other organ systems. The causative mechanism is thought to be initiation of the inflammatory process due to the autoimmune nature of the disease, leading to T cell infiltration and vascular dysfunction in the small vessels of the skin and internal organs.3 Experts believe that multiple factors contribute to the disease, including genetic makeup and environmental triggers, but definitive research is lacking. Hormones may play a role due to the significantly higher incidence in women between the ages of 30 and 55.1 A recent study by Giovannetti et al found immunologic differences in patients with SSc that affect their capability to maintain T cell homeostasis.4
Recognizing the Signs
Patients with localized or systemic sclerosis may experience tightening of the skin, changes in pigmentation, or pruritus. Evidence of inflammatory processes precedes the development of SSc.5 For example, Raynaud phenomenon is the presenting complaint in 70% of SSc cases.2 Raynaud phenomenon is usually benign, but it can be an early general indicator of autoimmune disease. It is characterized by color changes in the fingers, which occur due to vasospasm after exposure to cold or stress.
Early musculoskeletal signs of Ssc may include swelling of the fingers and joint pain.6 Heartburn can be another early manifestation. Gastrointestinal involvement occurs in at least 80% of patients with SSc, including decreased esophageal peristalsis and sometimes decreased gastric motility. The patient may complain of frequent heartburn, as well as dysphagia, decreased appetite, weight loss, constipation or bloating.6 If pulmonary involvement is present, the patient may present with dyspnea, dry cough or chest pain. Physical assessment may reveal rales on auscultation. The practitioner should take caution with patients who display signs of multisystem involvement and refer to a rheumatologist promptly. Other presenting symptoms may include fatigue, weakness, hoarseness, erectile dysfunction, hypertension and headaches.2
Making the Diagnosis
Diagnosing SSc is difficult due to the variety of presenting symptoms and wide differential diagnosis. The classic manifestation of SSc is tightening and thickening of the skin. If SSc is suspected, workup should include an antinuclear antibodies (ANA) test, which is positive in 95% of patients with SSc.6 However, the ANA test is not specific to SSc and is usually positive in other rheumatic diseases. Therefore, the diagnosis is usually made based on clinical findings. Sclerodactyly (tightening and thickening of the skin around the fingers) and Raynaud phenomenon eventually occur in more than 90% of patients with SSc.6
Some research has shown that anti-topoisomerase and anticentromere antibodies are scleroderma-specific and should be included in the workup. Additionally, a complete blood count (CBC) should be done to assess for anemia, and a chemistry panel should be ordered to identify liver or kidney involvement. Brain natriuretic peptide levels are an important indicator of pulmonary artery hypertension (PAH) in patients with SSc.7
In all patients with suspected or diagnosed SSc, testing should be performed initially and then annually to assess for pulmonary and/or cardiac involvement, whether or not the patient complains of dyspnea. These tests should include a 6-minute walk test (to assess exercise capacity), pulmonary function tests, computed tomography, electrocardiogram and echocardiogram.5
Prescribing the Treatment
Treatment for SSc is generally symptomatic. Topical moisturizers or H1 and H2 blockers can be used to treat pruritus. Raynaud phenomenon may be treated with calcium channel blockers or sildenafil. Gastrointestinal symptoms are usually relieved with antacids, H2 blockers or proton pump inhibitors; however, diet modification may be necessary. This includes consuming smaller meals and using laxatives and/or prokinetic agents to promote gastric motility. Nonsteroidal anti-inflammatory drugs and acetaminophen are generally used in the management of arthralgia, but methotrexate may be used for arthritic symptoms such as joint pain and swelling.2 Supplemental oxygen, diuretics and digoxin are included in the basic treatment for PAH associated with Ssc.8 Sildenafil is also approved for the treatment of PAH. For more extensive treatment, the patient should be referred to a specialist.
Because SSc can affect multiple organ systems, the associated complications are widespread. Due to vascular involvement, patients with SSc are at higher risk for coronary artery disease. In a study by Mok et al, patients with SSc were 11 times more likely to have coronary calcification compared to patients without SSc.9 The study also concluded that SSc was a risk factor independent of conventional cardiovascular risk. Patients with SSc may also develop extensive lung involvement, including PAH. Development of PAH is associated with poor prognosis in patients with diffuse SSc.5 Renal crisis is a rare but serious complication of SSc. Early recognition of hypertension and aggressive treatment with angiotensin-converting enzyme inhibitors are the most effective prevention measures.10
Some research has been published about the psychologic effects of an SSc diagnosis. Richards et al measured psychologic impact on SSc patients using the Hospital Anxiety and Depression Scale and discovered that many patients with SSc had a high probability of a mood disorder.11 A study by Hyphantis et al found that health-related quality of life in patients with SSc was significantly lower than that of healthy controls in terms of physical, psychological and social relationships.12 Another study indicated that the disease has a considerable effect on sexual function in women.13
One survey assessed the employment status of SSc patients and concluded that it is not uncommon for these patients to require full-time sick leave from work, causing a substantial socioeconomic burden.14 Sleep disturbances are also common and are generally caused by worsening respiratory and gastrointestinal symptoms, which occur more often as the disease progresses.15 A recent study evaluated the psychologic impact of facial disfigurement caused by the disease, and concluded that "facial changes were ranked as the most worrying aspect of the condition."16
The evidence indicates that the psychologic consequences of SSc are extensive. The primary care provider should be cognizant of the patient from a holistic perspective and regularly assess for anxiety or depression. Patients with SSc or suspected SSc can be referred to the Scleroderma Foundation website at www.scleroderma.org. The site provides a wealth of information on the disease, as well as links to local resources and support groups for patients.1
A study by Arakawa et al concluded that SSc may be associated with decreased serum adiponectin levels and that these levels may be beneficial in assessing the extent of fibrosis in collagen diseases.18 A preliminary study by Bassyouni et al showed that an elevated serum sCD36 level may be a useful marker for elevated pulmonary artery pressure and vascular damage in SSc.19 Another study, conducted by Moinzadeh et al, found that circulating levels of the enzyme MMP-7 correlate with the extent of pulmonary involvement in SSc.20
Recent research has examined the use of cyclophosphamide (Cytoxan), a potent immunosuppressive agent, in the treatment of SSc. Several studies found that cyclophosphamide is a potentially effective treatment for extensive SSc, including the possibility of improving pulmonary function tests in SSc with extensive lung involvement.5,21
SSc is a rare but complicated disease with a profound effect on quality of life. Early recognition by the primary care provider is an essential step in obtaining prompt evaluation by a specialist. Diagnosis is challenging due to vague symptomatology and potential multisystem involvement. Additionally, further investigation is warranted in cases of suspected SSc to identify the extent of the disease. The primary care provider can manage symptomatic treatment, but referral is recommended for the management of diffuse disease.
1. National Institute of Arthritis and Musculoskeletal and Skin Diseases. Handout on Health: Scleroderma. http://www.niams.nih.gov/Health_Info/Scleroderma/default.asp
2. Jimenez S, et al. Scleroderma. http://emedicine.medscape.com/article/331864-overview
3. Wilson H, Vincent R. Autoimmune connective tissue disease: scleroderma. Brit J Nurs. 2006;15(15):805-809.
4. Giovannetti A, et al. Analyses of T cell phenotype and function reveal an altered T cell homeostasis in systemic sclerosis. Correlations with disease severity and phenotypes. Clin Immunol. 2010;137(1):122-133.
5. van Laar J, et al. Scleroderma lung: pathogenesis, evaluation and current therapy. Drugs. 2007;67(7):985-996.
6. Khavari R, et al. Decision making in systemic sclerosis: a guide for primary care. J Musculoskel Med. 2009;26(7):247-255.
7. Hinchcliff M, Varga J. Managing systemic sclerosis and its complications. J Musculoskel Med. 2011;28(10):380-387.
8. Chatterjee S. Pulmonary hypertension in systemic sclerosis. Semin Arthritis Rheum. 2011;41(1):19-37.
9. Mok MY, et al. Systemic sclerosis is an independent risk factor for increased coronary artery calcium deposition. Arthritis Rheum. 2011;63(5):1387-1395.
10. Mouthon L, et al. Scleroderma renal crisis: a rare but severe complication of systemic sclerosis. Clin Rev All Immunol. 2011;40(2):84-91.
11. Richards H, et al. Psychological adjustment to systemic sclerosis -- exploring the association of disease factors, functional ability, body related attitudes and fear of negative evaluation. Psychology, Health & Medicine. 2004;9(1):29-39.
12. Hyphantis TN, et al. The impact of psychological functioning upon systemic sclerosis patients' quality of life. Semin Arthritis Rheum. 2007;37(2):81-92.
13. Schouffoer AJ, et al. Impaired sexual function in women with systemic sclerosis: a cross-sectional study. Arthritis Rheum. 2009;61(11):1601-1608.
14. Nguyen C, et al. Employment status and socio-economic burden in systemic sclerosis: a cross-sectional survey. Rheumatol. 2010;49(5):982-989.
15. Frech T, et al. Prevalence and correlates of sleep disturbance in systemic sclerosis-results from the UCLA scleroderma quality of life study. Rheumatology. 2011;50(7):1280-1287.
16. Amin K, et al. The psychological impact of facial changes in scleroderma. Psychol Health Med. 2011;16(3):304-312.
17. Scleroderma Foundation. http://www.scleroderma.org
18. Arakawa H, et al. Adiponectin expression is decreased in the involved skin and sera of diffuse cutaneous scleroderma patients. Exp Dermatol. 2011;20(9):764-766.
19. Bassyouni I, et al. Clinical significance of serum levels of sCD36 in patients with systemic sclerosis: preliminary data. Rheumatology. 2011;50(11):2108-2112.
20. Moinzadeh P, et al. Elevated MMP-7 levels in patients with systemic sclerosis: correlation with pulmonary involvement. Experimental Dermatology. 2011;20(9):770-773.
21. Chighizola C, et al. Cyclophosphamide as disease-modifying therapy for scleroderma: pros and cons. Int J Clin Rheumatol. 2011;6(2):219-230.
Lindsey Ray is a family nurse practitioner at St. Vincent's Primary Care in Jacksonville, Fla. She has completed a disclosure statement and reports not relationships related to this article.