Scleroderma Systemic Sclerosis

Systemic sclerosis is a multi-system connective tissue disorder characterized by intimal proliferation and fibrosis in small arteries and arterioles, and degenerative changes with fibrosis in the skin and certain internal organs. The 

Studies by Hawkins et al. (1985) and Nishioka et al. (1987) showed increased numbers of mast cells were present in clinically involved skin in early cutaneous systemic sclerosis but not in later disease. Seibold et al. (1990) however found increased numbers of mast cells in both involved and uninvolved skin in both early and late disease, and also provided evidence of increased mast cell degranulation in early but not late disease, suggesting that increases in mast cell numbers and degranulation precede clinically apparent dermal fibrosis. A study by Falanga and Julien (1990) found elevated H levels in the plasma of patients with systemic sclerosis, providing evidence of mast cell activation. 

Systemic sclerosis (SSc, scleroderma) is a complicated systemic disease with many pulmonary manifestations. Although ILD and pulmonary arterial hypertension are the best-smdied causes of dyspnea in SSc, these topics are covered in 

Exudative pleural effusions are uncommon in SSc, but their presence because of SSc alone has been described (45). Since SSc also can produce diastolic cardiac dysfunction, a thoracentesis is recommended to exclude a transudative effusion that would focus therapy on congestive heart failure. Pericardial effusions have been seen that are occasionally large enough to benefit from drainage with resolution of symptoms. Since effusions are prone to recur, most patients receive a pericardial window at the time of drainage. 

Controversy will remain about whether and to what extent esophageal reflux contributes to lung disease. Most cross-sectional studies have found a poor correlation between reflux severity and ILD severity (47), although no long-term prospective evaluations are available. Nevertheless, when dense-dependent consohdation is seen on a CT scan, the possibility of aspiration pneumonia should be considered. 

Obstructive lung disease has been seen in SSc (48). One of the complicating factors in defining this disorder is the frequency of cigarette smoking in most case series. Other diseases that have prominent interstitial components, such as asbestosis, also have described a mild obstmctive lung disease that is presumably from narrowing or tortuosity of some airways early in the fibrotic process (49). Treatment with bronchodilators or corticosteroids rarely produces clinical improvement. 

Bronchiolitis obliterans with organizing pneumonia (BOOP) is now called cryptogenic organizing pneumonia (COP) when the cause is idiopathic (50). When secondary to a CTD, such as RA or SSc, variable terminology is used. 

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Although there are reports of associations between exposure to organic solvents and various connective tissue diseases, such as systemic sclerosis, scleroderma, undifferentiated connective tissue disease, systemic lupus erythematosus, and rheumatoid arthritis, the evidence of a causal association is weak (44). 

Steen VD, MedsgerTA, Rodnan GP. D-penicillamine therapy in progressive systemic sclerosis (scleroderma). A retrospective analysis. Ann Intern Med 1982 97 652-659. 

Xenobiotic exposure can adversely affect bones, joints, connective tissue, and muscles. Rheumatoid arthritis, osteoporosis, osteomalacia, systemic sclerosis, scleroderma, systemic lupus erythematosus, and spina bifida are musculoskeletal diseases that have been associated with toxic chemical exposures. Most of these associations, however, have been made to single chemical exposures and not to mixtures. This chapter cites the evidence on which those associations are based and discusses the available examples of mixtures that have been implicated. 

The association between systemic sclerosis (scleroderma) and solvent exposure (primarily in occupational settings) has been investigated in more than a dozen studies to date (Table 11). These studies have fairly consistently reported a 2- to 3-fold increased risk of disease with various forms of solvent exposure. However, a clear consensus has not developed on specific exposures or classes of... 

Connective tissue diseases. Systemic autoimmune rheumatic diseases, including systemic lupus erythematosus, Sjogren syndrome, systemic sclerosis (scleroderma), autoimmune myositis (polymyositis, dermatomyositis), mixed connective tissue disease, and other overlapping syndromes. 

Arnett FC, Reveille JD, Goldstein R, Pollard KM, Leaird K, Smith EA, Leroy EC, Fritzler MJ (1996) Autoantibodies to fibrillarin in systemic sclerosis (scleroderma). An immuno-genetic, serologic, and clinical analysis. Arthritis Rheum, 39 1151-1160. 

Hochberg MC Perlmutter DL (1996) The association of augmentation mammoplasty with connective tissue disease, including systemic sclerosis (scleroderma) a metaanalysis. CurrTop Microbiol Immunol, 210 411-417. 

Hochberg MC, Perlmutter DL, Medsger TA Jr, Nguyen K, Steen V, Weisman MH, White B, Wigley FM (1996) Lack of association between augmentation mammoplasty and systemic sclerosis (scleroderma). Arthritis Rheum, 39 1125-1131. 

Ruzek MC, Jha S, Ledbetter S, Richards SM, Carman RD. A modified model of graft-versus-host-induced systemic sclerosis (scleroderma) exhibits all major aspects of the human disease. Arthritis Rheum 2004 50 1319-1331. 

Schottenfeld, D., Bums, C.J., Gillespie, B.W. et al (1995) The design of a population-based case-control study of systemic sclerosis (scleroderma) Commentary on the University of Michigan Study. /. Clin. Epidemiol. 48(4), 583-586. 

Choudat D (1994) Occupational lung diseases among dental technicians. Tuber Lung Dis 75 99-104 Christy WC, Rodnan GP (1984) Conjuged progressive systemic sclerosis (scleroderma) report of the disease in husband and wife. Arthritis Rheum 27 1180-1182 Conrad K, Mehlhorn J, Liithke K, Dorner T, Frank KH (1996) Systemic lupus erythematosus after heavy exposure to quartz dust in uranium mines clinical and serological characteristics. Lupus 5 62-69... 

Also, an increased incidence of cell-mediated and humoral immunity to various collagens has been found in systemic connective tissue disease such as rheumatoid arthritis, juvenile rheumatoid arthritis, and progressive systemic sclerosis (scleroderma). Patients with these diseases may thus have an increased susceptibility to hypersensitivity responses and/or accelerated clearance of their implants w hen injected with bovine dermal collagen preparations. Therefore, caution should be used when treating tliese patients including consideration for multiple skin lesions. 

Kuwana M, Kahuraki J, Okano Y, et al. The HLA-DR and DQ genes control the autoimmune response to DNA topoisomerase I in systemic sclerosis (scleroderma). J Clin Invest 1993 92(3) 1296-1301. 

Silver RM, Warrick JH, Kinsella MB, et al. Cyclophosphamide and low-dose prednisone therapy in patients with systemic sclerosis (scleroderma) with interstitial lung disease. J Rheumatol 1993 20 838-844. 

Preliminary criteria for the classification of systemic sclerosis (scleroderma). Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. Arthritis Rheum 1980 23 581-590. 

D Angelo WA, Fries JF, Masi AT, et al. Pathologic observations in systemic sclerosis (scleroderma). A study of fifty-eight autopsy cases and fifty-eight matched controls. Am J Med 1969 46 428-440. 

Steen VD, Owens GR, Fino GJ, et al. Pulmonary involvement in systemic sclerosis (scleroderma). Arthritis Rheum 1985 28 759-767. 

Akesson A, Forsberg L, Hederstrom E (1986) Ultrasound examination of skin thickness in patients with progressive systemic sclerosis (scleroderma). Acta Radiol Diagn... 

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