Scleroderma

Scleroderma, also known as systemic sclerosis, is a rare connective tissue disease. It has an annual incidence in the United States of 19 cases per one million and a prevalence of 24 people per 100,000-up to nine times the prevalence seen in other countries.1-3 Scleroderma affects both men and women of all races, but the disease typically occurs in people between the ages of 30 to 65, with a female predominance of 4:1.1,6 More frequent and severe cases have been noted in African American women as well as Choctaw Native Americans.3,7 By having a working knowledge of this disease, the nurse practitioner (NP) can detect scleroderma early in the primary care setting and intervene and refer accordingly in order to maximize the patient's quality of life.

Scleroderma is characterized by uncontrolled fibrosis and degenerative changes in the skin, blood vessels, synovium, and skeletal muscle.2,4 A variety of organ systems can be affected, including the heart, lungs, gastrointestinal tract, and kidneys.2 The spectrum of systemic sclerosis ranges from limited cutaneous involvement, in which the thickening of the skin is typically limited to the face, to diffuse cutaneous involvement characterized by rapidly developing and progressing skin thickening. There are also localized types of scleroderma that affect the skin only.4

* Scleroderma Subtypes

The first scleroderma subtype, limited cutaneous scleroderma, is also known as CREST syndrome, which stands for calcinosis, Raynaud's phenomenon, esophageal motility disorders, sclerodactyly, and telangiectasia. Two of five of these symptoms must be present to make a diagnosis of CREST.5 These patients often exhibit a slow disease progression.5 However, there is a 30% to 40% risk of developing pulmonary hypertension and a 10% risk of developing interstitial lung disease.5

The second scleroderma subtype, diffuse cutaneous scleroderma, usually progresses more rapidly and has a 30% to 40% risk of interstitial lung disease, a 30% risk of serious renal disease, and increased risk of myocardial fibrosis.5 The proximal limbs, neck, upper chest, back, and abdomen are affected.12 As thickening worsens, loss of hand function and decreased range of motion occurs secondary to skin tightness as opposed to joint involvement.12 Pulmonary complications occur in two-thirds of patients with scleroderma, making this the leading cause of scleroderma-related deaths.3

Patients may present with joint pain, swelling, and puffiness of the hands, which may occur a year prior to the development of Raynaud's phenomenon.12 Within 5 years of diffuse cutaneous scleroderma onset, fatigue, weight loss, malaise, and rapidly tightening skin, especially on the fingers, may occur.13 Patients may not recognize the digit thickening initially but may notice facial changes such as a mask-like appearance, a beak-like nose, and tightening and wrinkling of the skin around the mouth with increased difficulty opening it, also known as microstomia.13,14 With skin thickening and adherence to the subcutaneous tissue, the skin appears shiny and taut.12 Fibrosis of the dermis leads to hair loss, dryness, and loss of sweat glands.12 In addition, the affected person is susceptible to injury, ulceration, and decreased healing.12

* Localized Scleroderma

Localized scleroderma is associated with little or no internal disease.8 The three types are localized morphea, generalized morphea, and linear scleroderma. Localized morphea appears more commonly on the trunk than the extremities.8,9 It appears as circumscribed plaques with induration that become smooth and hard, often with hypopigmented centers.8,9 One or more lesions are present that soften and leave residual patches.8 Edema may occur prior to induration by weeks and may or may not be associated with pain and erythema.8 In contrast, generalized morphea involves multiple, large plaques with induration.8 In linear scleroderma, which is more common in children, the skin becomes firm, smooth, and rigid with hypopigmentation and an approximated line with lesions in a unilateral distribution along the arm, leg, or the frontal scalp.8 These lesions can impair the person's mobility and can affect underlying bones, muscles, and structures, causing contractures and difficulty with activities of daily living.8

* Pathophysiology

Although the cause of scleroderma is unknown, various theories exist. One theory is that vascular injury to arteries, veins, and capillaries in the skin, heart, lungs, and gastrointestinal tract causes decreased circulation and creates an influx of inflammatory cells.3,9 The microvascular bed in the skin and these sites is diminished and results in ischemia.3 Early lesions show plasma cell lymphocytic infiltrates, capillary destruction, and endothelial cell proliferation.9

Injury to endothelial cells leads to vasoconstriction, ischemia, and decreased amounts of prostacyclin, a vasodilator and platelet aggregating inhibitor.14 Platelets release thromboxane A2, a vasoconstrictor, and the cytokines Platelet Derived Growth Factor and Transforming Growth Factor [beta] to stimulate fibroblast collagen synthesis.3 Increased fibroblast activity occurs with increased fibrosis and collagen production.9

Another theory for the development of scleroderma involves an immune response to a toxin such as silica, epoxy resin, and organic solvents, which results in persistent fibrosis secondary to impaired collagen regulation.1,14 T-cells, macrophages, endothelial cells, cytokines, and growth factors interact to stimulate fibrosis.3 Specific solvents and precise conditions surrounding the patient's situation must be further studied.16

The immunology of pregnancy has also been studied as a theory in the development of scleroderma.1 Fetal cells have been found in the mother's bloodstream in greater than 90% of first pregnancies and can be detected 2 to 3 decades after a pregnancy. This is known as microchimerism and may trigger an autoimmune response.1 Paternally inherited fetal cells in the maternal circulation cross the fetal-maternal interface and are associated with chronic immune system upregulation, resembling graft-versus-host disease.1 Human leukocyte antigen (HLA) molecules help the immune system distinguish between self and nonself.1 Fetal cells with paternally inherited HLA molecules pass into the mother's bloodstream and may be the source of the immune system's upregulation.1

Latent human cytomegalovirus (CMV) may also add to the progression of systemic sclerosis.17 A study by Lunardi et al showed that antibodies against human CMV caused the death of endothelial cells.17 This actually occurs as the initial event in the development of systemic sclerosis.17 The information reveals a previously unknown mechanism for a connection between human CMV and the autoimmune system, including systemic sclerosis.17

* Diagnosis

Because of the risk of complications of progressive organ damage and impact on the quality of life, accurate diagnosis and intervention are essential. Clinical and medical histories are the most useful diagnostic tools.18 A complete history should include characteristics of presenting symptoms, onset, frequency, duration, and symptom progression, as well as personal and family medical history, social history, medications, allergies, diet, activity, and occupational exposures.13,19

The next step involves determining if the patient has limited cutaneous or diffuse cutaneous scleroderma and the extent of organ involvement.6 The American College of Rheumatology's diagnostic criteria for scleroderma include having the major criterion of proximal or diffuse sclerosis or at least two of the minor criteria, which are sclerodactyly (sclerosis affecting the fingers or toes only), digital pitting scars, or the loss of the digital pads, and bibasilar pulmonary fibrosis (see Table: "American College of Rheumatology Diagnostic Criteria for Scleroderma").9

If there are no skin changes evident, the NP should examine the hands and nails and look for loss of digital pulp, pitting scars and ulcers, calcinosis, and telangiectasis.6 Then the NP should examine the nail folds by applying immersion oil drops on a few of the patient's cuticles and looking through an ophthalmoscope set at +20 to +40 to visualize the capillaries. Abnormalities of capillary dilatation and individual capillary loops with areas of capillary loop dropout can aid in a positive diagnosis.6

Next, examine the hands for flexion and deformity.12 Carpal tunnel syndrome may be evident as the structures become edematous and fibrotic.12 With the examination of wrists, elbows, shoulders, and ankles, a leathery rub may be palpated or heard with flexion and extension.6,12 Calcium deposits may also be palpated in the subcutaneous tissue in the fingers, forearms, elbows, and lower extremities with progressive disease and may cause patients to complain of pruritus.12

Strength may be decreased because of muscle weakness or tenderness secondary to the fibrosis and calcifications of overlying skin.12 Myopathy can also occur due to proximal muscle group involvement.12 Neuropathy may be present due to the fibrosis of the tendon sheaths.9,12 With decreased strength, range of motion, neuropathy, and increased pressure on the body, there is a risk of ulcerations and infection, so a thorough skin examination is imperative.

Gastrointestinal tract disease occurs in up to 80% of scleroderma patients.9 Decreased motility of the esophagus can lead to dysphagia, esophagitis, esophageal reflux, Barrett's esophagus, and strictures.9 Loss of gut innervation occurs due to vasa nervosum involvement, which disrupts peristalsis and lower esophageal sphincter function.9 This occurs prior to the atrophy and fibrosis of the smooth muscle in the gastrointestinal tract.9 Obstruction, malabsorption of nutrients from the intestinal tract, constipation, diverticula, and rectal prolapse may also be present.9

Cardiopulmonary involvement may yield bibasilar crackles with auscultation and pulmonary function tests often showing restrictive lung disease.9 Restriction, decreased tidal volume and impaired diffusion can all lead to pulmonary hypertension.9 An electrocardiogram (ECG) may show an arrhythmia and a chest x-ray may show pericardial effusion and pericarditis since fibrosis and necrosis lead to a change in the heart's conduction fibers.9

An assessment of blood pressure is very important as an elevated, uncontrolled blood pressure can be dangerous to a patient with scleroderma.6 The frequency of scleroderma renal crisis (SRC) in diffuse systemic sclerosis is reported to be 15% to 20%.20 Renal crisis is the result of activation of the renin-angiotensin system in the scleroderma patient.6 Damage to the kidney's blood vessels in the patient with scleroderma can cause a tremendous spike in blood pressure known as malignant hypertension.7 The blood pressure may be so elevated that the patient experiences headache, retina damage, seizures, and heart failure.7 The kidneys may also stop filtering blood and lead to renal failure.7 If in renal crisis, diastolic hypertension, decline in creatinine clearance, proteinuria, and/or hematuria can occur.6

Predictors of SRC in a study by DeMarco et al include an enlarged cardiac silhouette upon chest x-ray; prednisone use; joint contractures of the large joints including the knee, elbow, and wrist; and a Rodnan skin thickness score of greater than or equal to 20.20 Factors that failed to predict SRC include age, race, sex, fist closure, the spread of the hand, musculoskeletal weakness, pulmonary involvement, platelet count, and erythrocyte sedimentation rate (ESR).20 Despite the availability of ACE inhibitors and dialysis care, SRC is linked to poor survival, and in the aforementioned study, 50% of the patients with SRC died.20

Scleroderma usually evolves over several months to years.21 Disease activity in internal organs can be difficult to predict, but prognosis tends to be worse in people with diffuse skin changes than in those with limited scleroderma.21 Treatment considered beneficial for a specific organ will influence the outcome and will aid in the prevention of cardiac failure, renal failure, and pulmonary fibrosis.21,22

* Laboratory Studies

In scleroderma, antinuclear antibodies exist in greater than 90% of affected patients.9,23 These autoantibodies can be useful in diagnosing a patient and determining his or her prognosis.12 Anticentromere (ACA) and anticentriole antibodies are associated with limited systemic scleroderma where they are present 50% to 96% of the time.9,23 In diffuse scleroderma, ACA is present less than 10% of the time.23 The presence of ACA can be a precursor for limited skin involvement and the lack of lung involvement. Antitopoisomerase antibodies are present in approximately 15% of those with limited scleroderma and 40% of those with diffuse scleroderma.23 In addition, the presence of anti-Scl-70 antibodies indicates an increased risk for diffuse skin involvement and pulmonary disease.11

Other laboratory studies may aid in a scleroderma diagnosis. Additional indicators include an elevated rheumatoid factor and hypergammaglobulinemia, as well as the presence of cryoglobulins, antimitochondrial antibody, and thyroid antibodies.23 Although the ESR may be elevated in some patients with localized scleroderma, values within normal limits may be seen in an active disease state.9,23

Decreased hemoglobin may be seen and can be characteristic of anemia of chronic disease.23 Chronic disease, malignancy, and inflammation can impair the delivery of iron to developing red blood cells.23 Anemia of chronic disease resolves when the underlying disease is treated.23 Microangiopathic hemolytic anemia, however, can also be a sign of a scleroderma renal crisis.23 Thus, a urinalysis with microscopic study should be performed to look for protein and microscopic blood in the urine22 (see Table: "Scleroderma Laboratory Features").

* Mimicking Scleroderma

Several differential diagnoses may mimic scleroderma. A thorough patient history, physical examination, and laboratory evaluation to rule out other disease processes are important. Differential diagnoses include systemic lupus erythrematosus (SLE), sicca syndrome (Sjögren's syndrome), dermatomyositis, polymyositis, eosinophilia myalgia, and collagen disease.3 In addition, a person with type 1 diabetes may have sclerotic digits and contractures of the hands.3 People with amyloidosis and multiple myeloma may also have diffuse effects on the skin of their limbs and face, giving them a scleroderma-like presentation.3

Many autoimmune disorders have overlapping features that may present a challenge to specific disease classification.3 With mixed connective tissue disease, features of the diseases overlap SLE, scleroderma, polymyositis, rheumatoid arthritis, eosinophilic fasciitis, and eosinophilia-myalgia syndrome.3 In addition, there are the possible causes of drug- and toxin-induced scleroderma.3 Exposures to silica dust, epoxy resin, and organic solvents may trigger macrophage activation and increase the production of the inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor (TNF).1 Medications such as ethosuximide, pentazocine, vitamin K, carbidopa, and D-penicillamine can cause sclerodermalike skin changes, including dyspigmentation, Raynaud's phenomenon, morphea-like plaques, and the development of antibodies.8 Chemotherapeutic agents and beta-blockers can also produce diffuse scleroderma.8 Symptoms all improve with cessation of treatment with the medication.

* Managing Scleroderma

Because a diagnosis of scleroderma will affect a patient's physical and psychological well-being, a holistic approach to care should be taken. An evaluation of organ involvement, patient education regarding clinical course, patient and family support, and treatment dependent on disease severity and organ involvement are necessary.6 Referral to a rheumatologist is highly advised. Organ-specific treatment will influence outcomes, including mortality, disease progression, and quality of life issues (see Table: "Organ-Based Treatment of Patients with Scleroderma").21

With Raynaud's phenomenon, encouraging patients to keep warm, avoid the cold, wear gloves, and dress in layers is very important.6,8 The NP must also emphasize smoking cessation, as cigarette smoking is vasoconstricting.8 Beta-agonists and cocaine are also potent vasoconstrictors.8 The use of calcium channel blockers such as verapamil (Calan) or angiotensin II receptor antagonists such as irbesartan (Avapro) and nitroglycerin ointment or patches can assist with vasodilatation.6

Dry skin should be cared for daily using thick, emollient creams and routinely examined by the patient at home and during visits with the NP for the development of ulcerations.7 If lesions appear inflamed, a class I or class II topical corticosteroid can be applied until the inflammation resolves. The topical corticosteroid should be tapered down to the lowest possible dose that will control the patient's symptoms.8 Since 80% to 90% of diffuse scleroderma patients and 95% of patients with limited scleroderma have Raynaud's phenomenon, microvascular involvement, and vasoconstriction, ulcers are common.8 If the patient develops digital ulcers, local wound cleansing and the use of bacteriostatic creams can be helpful.6

Although no medication exists for treatment of spontaneous skin thickening, many drugs are being investigated.6 The use of D-penicillamine has been used, but remains controversial.6 Other trials include the use of recombinant human relaxin, oral bovine collagen, and autologous bone marrow transplantation.6 Current clinical trials include the use of tissue growth factor - [beta] which inhibits collagen breakdown and fights against fibroblast cell death.24 Endothelin 1 (ET 1), a vasoconstrictor, is elevated in scleroderma patients, and the ET 1 receptor antagonist bosentan has been effective in treating pulmonary hypertension, the primary cause for death in scleroderma patients.24 Other studies include the use of thalidomide and inhibitors in cell pathways.24 Interferon alpha, photophoresis, and antithymocyte globulin have been rendered ineffective.6

Treating gastrointestinal symptoms and providing patient education is crucial, as dysphagia, esophageal reflux, bloating, diarrhea, constipation, and weight loss can be concerns.22 The patient should be instructed to eat small, frequent meals, softer foods, and avoid triggers such as spicy foods, peppermint, and caffeine.7 Proton pump inhibitors such as omeprazole (Prilosec) and lansoprazole (Prevacid) can prevent erosions of the esophagus, and metoclopramide may help with dysphagia.6 Low-dose erythromycin or the somatostatin analog, octreotide, can help with intestinal dysmotility and feelings of bloating, fullness, and abdominal cramps.6 A referral to a dietitian and a gastroenterologist may be warranted.25

Again, cigarette smoking should be discouraged and environmental triggers such as dust, pollen, and animal dander eliminated. Interstitial fibrosis leads to restrictive lung disease, and although trials suggest that daily oral cyclophosphamide therapy for 12 to 18 months may improve lung function and patient survival, no treatment has been conclusive.6 Pulmonary fibrosis leading to pulmonary hypertension may be treated with calcium channel blockers, although a lung transplant may be needed in a patient with end-stage lung disease.6 Treating the scleroderma patient with cardiac manifestations such as arrhythmias, cardiomyopathy, and congestive heart failure will not differ from treating any other cardiac patient.6

The goal of treatment is to prevent scleroderma renal crisis.5,6 Patients should be advised to invest in a home blood pressure monitoring kit as well as dipstick tests to check urine.5,6 Not all patients with scleroderma develop hypertension before a renal crisis, but many do.5,6 Home monitoring of blood pressure and urine can be an easy way to assess for and prevent early disease as well as actively involve the patient in her care.5,6 The latest research shows that angiotensin-converting enzyme (ACE) inhibitors play a role in the management of scleroderma renal crisis.26 Serum creatinine and blood pressure increased and worsened with the use of angiotensin II receptor blockers (ARB), but then improved when a patient was returned to an ACE inhibitor.26

Musculoskeletal manifestations and arthralgias can be one of the first complaints of a patient with scleroderma.26 Although methotrexate can decrease symptoms, non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Advil) and naproxen (Aleve), especially cyclo-oxygenase-2 (Cox-2) inhibitors such as celecoxib (Celebrex) and rofecoxib (Vioxx), can be effective for muscle and joint pain.6 Pharmacologic and nonpharmacologic pain management options should be discussed with the patient to decrease pain and fatigue, and to maximize the patient's quality of life.

The NP should assess and recognize the need for home health care as well as in-home or outpatient physical therapy. Exercise, massage, and appropriate assistive devices are important in preventing joint immobility, contractures, and disability.7,8,25 Occupational therapy can be beneficial for hand exercises, assisting with joint protection, splints, relaxation, ergonomics, and teaching energy conservation.25 A safety assessment with inquiry about the patient's home environment and ADLs will help the NP make recommendations regarding areas of concern such as dysphagia, decreased mobility, living arrangements, family support, and presence of an emergency plan. The NP can then provide the patient with recommendations and referral to appropriate resources in the community.

* Patient Support

Patients with scleroderma may have significant physical disability and can feel isolated since they may never meet someone else battling the disease.26 A careful assessment for depression should be part of the patient's examination, including assessment of coping, work and family relationships, and energy conservation for leisure time.25 Screening with a tool such as the Beck Depression Index can be helpful.27 Patients with systemic sclerosis often suffer from mild to severe depression due to a variety of factors, including increased pain levels, decreased ability to work, decreased socialization and increased isolation, low resilience, and an impending sense of helplessness.27 Taking the time to discuss and counsel patients regarding sexual health is also very important because the patient with scleroderma may experience dyspareunia or erectile dysfunction.7

A study by Richards et al examined scleroderma patients' beliefs about their illness and explored the relationship among beliefs, symptoms, and demographic variables.28 The Revised Illness Perception Questionnaire revealed that the patients' symptoms of stiff joints, pain, fatigue, and their subsequent disease process were caused by increased stress levels, decreased immunity, and simply by chance.28 Individuals with diffuse cutaneous scleroderma reported more significant consequences than those with limited cutaneous disease.28 All in all, their beliefs about their disease process were associated with the meaning that they attributed to their condition rather than the severity of their symptoms.28 Thus, a thorough psychosocial history must be explored with a focus on the patients' beliefs about their illness, coping mechanisms and options discussed, and appropriate referrals made for counseling as indicated.

Patient education is paramount in managing patients with rheumatic disease or any disease. Among studies of patients with arthritis, educational intervention was 25% as effective as NSAID treatment for pain relief and 30% to 40% as effective as NSAID therapy for improving functional disability.25 Holistic patient care, including lengthy education with family and caregivers about the disease process and psychosocial aspects of scleroderma, is an integral part of maximizing the wellness of patients with scleroderma. Internet resources and support groups are available for patients to make contact with others with the disease (see Table: "Resources for Patients with Scleroderma").

The fundamental goals of treating the patient with scleroderma are to determine organ involvement, intervene early, treat the patient based on the extent of organ involvement, and educate the patient regarding the disease process and clinical course.6 With an early patient presentation in the primary care setting and thorough assessment, diagnosis, and intervention by the NP, end-organ damage can be decreased and morbidity associated with vascular, gastrointestinal, and musculoskeletal manifestations reduced.6 Referral to and collaboration with a rheumatologist can assist in decreasing morbidity and mortality.6 The patient must be a partner with the practitioner in this process and the treatment plan should be holistic in nature with the ultimate goal of maximizing patient satisfaction and quality of life.

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Early Identification Key to Scleroderma Treatment

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REFERENCES

1. Buyon JP, Giesser BS, Nelson JL: Deciphering autoimmune disease in women. Contemporary OB/GYN 2000;8:76-86.

2. Nietert PJ, Silverstein MD, Silver RM: Hospital admissions, length of stay, charges, and in-hospital death among patients with systemic sclerosis. J Rheumatol 2001; 28(9):2031-2037.

3. Gilliland BC: Systemic sclerosis (scleroderma). Braunwald E, Fauci A, Kasper D, et al., eds. In: Harrison's Internal Medicine, 15th edition. New York, NY: McGraw-Hill, 2001;1937-1947.

4. Gunduz OH, Fertig N, Lucas M, et al: Systemic sclerosis with renal crisis and pulmonary hypertension. Arthritis Rheum 2001;44 (7): 1663-1666.

5. Jancic B: Advances make scleroderma manageable, (skin, renal, GI manifestations). Skin & Allergy News 2002;33(3):4.

6. Rus V, White B: Systemic sclerosis: multiple therapies control morbidity; early assessment of internal organ involvement is needed for timely treatment. The J Musculo Med 2002;19(3):110-121.

7. Carson-DeWitt R: Scleroderma. Olendorf D, Jeryan C, and Boyden K, eds. In: The Gale Encyclopedia of Medicine. Farmington Hills, Mich.: Gale research, 1999.

8. Sabir SM, Werth VP: Cutaneous manifestations of sclerosing conditions. J Musculo Med 2000;17(4):207-219.

9. Brown CW Jr., Marschall SF: Connective tissue update: focus on scleroderma. Consultant 1999; 39(7):2071-2074, 2077-2078, 2081-2082.

10. Medsger TA Jr., Silman AJ, Steen VD, et al: A disease severity scale for systemic sclerosis: development and testing. J Rheumatol 1999;26(10):2159-2167.

11. Khanh TH, Reveille JD: The clinical relevance of autoantibodies in scleroderma. Arthritis Res Ther 2003;5(2):80-93.

12. Gulin J, Korn JH: Systemic sclerosis: challenges in diagnosis and management. J Musculo Med 1999;16(5):288-300.

13. Isenberg DA, Black C: Raynaud's phenomenon, scleroderma, and overlap syndromes. B Med J 1995;310:795.

14. Huether SE, McCance KL: Structure, function, and disorders of the integument. Schrefer S, Brower G, eds. In: Pathophysiology the Biologic Basis for Disease in Adults and Children, 3rd edition. St. Louis, Mo.: Mosby, Inc., 1998;1542.

15. American College of Rheumatology: Complete Clinical Slide Collection on the Rheumatic Diseases, 2nd CD-Rom edition. Novartis, 1998.

16. Garabrant DH, Dumas C: Epidemiology of organic solvents and connective tissue disease. Arthritis Res Ther 2000;2(1):5-15.

17. Lunardi C, Bason C, et al: Systemic sclerosis immunoglobulin G autoantibodies bind the human cytomegaloviruslate protein UL 94 and induce apoptosis in human endothelial cells. Nat Med 2000;6(10):1183-1186.

18. Robinson D, Kidd P, Rogers KM: Primary care across the lifespan. St. Louis, Mo.: Mosby 2000;475-481.

19. Seidel HM, Ball JW, Dains JE, et al: The history and interviewing process. Thompson J, Brower G, eds. In: Mosby's Guide to Physical Examination, 4th edition. St. Louis, Mo.: Mosby 1999;16-46.

20. DeMarco PJ, Weisman MH, et ah Predictors and outcomes of scleroderma renal crisis: the high-dose versus low-dose D-penicillamine in early diffuse systemic sclerosis trial. Arthritis Rheum 2002;46 (11):2836-2837.

21. Gelber A, Wigley FM: Disease seventy as a predictor of outcome in scleroderma. The Lancet 2002;359:277.

22. Medline Plus Heath information: Systemic sclerosis (scleroderma). 2001. Retrieved November 7, 2002, from http://www.nlm.nih.gov/medlineplus/ency/article/000429.htm

23. Desai SP, Isa-Pratt S. Clinician's guide to laboratory medicine. Hudson, OH: Lexi-Comp Inc., 2000;606.

24. Jancin B: Rich pipeline seen for scleroderma. Skin & Allergy News 2002;33(3):1.

25. Samuelson UK, Ahlmen EM: Development and evaluation of a patient education program for persons with systemic sclerosis (scleroderma). Arthritis Care Res 2000;13(3):141-148.

26. Boschert S: Angiotensin receptor blockers: a note of caution. (scleroderma renal crisis). Skin and Allergy News 2002;33(2):21.

27. Matsuura E, Ohta A et al.: Frequency and analysis of factors closely associated with the development of depressive symptoms in patients with scleroderma. Journal Rheumatol 2003;30(8):1782-1787.

28. Junko T, Masatoshi N, et al: Increased frequency of interleukin 4 producing CD4+ and CD8+ cells in peripheral blood from patients with systemic sclerosis. J Rheumatol 2001;28:1252-1258.

Nicole Joslin, MS, APRN, NP-C

AUTHOR DISCLOSURE

The author has disclosed she has no significant relationship or financial interest in any commercial companies that pertain to this education activity.

ABOUT THE AUTHOR

Nicole M. Joslin is an Adult Primary Care nurse practitioner at Vernon Internal Medicine, Vernon, Conn., and a clinical faculty member at the University of Connecticut School of Nursing.

Copyright Springhouse Corporation Jul 2004
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