Systemic sclerosis treatment

Kaye SA, Lim SG, Taylor M, Patel S, Gillespie S, Black CM Small bowel bacterial overgrowth in systemic sclerosis Detection using direct and indirect methods and treatment outcome. BrJ Rheumatol 1995 34 265-269. 

It has been shown that lung macrophages from patients with systemic sclerosis (SS) produced the elevated levels of nitric oxide, superoxide, and peroxynitrite and expressed the enhanced level of iNOS [281], NAC administration reduced peroxynitrite production and might be possibly recommended for the treatment SS patients. Solans et al. [282] found the significant enhancement of lipid peroxidation in erythrocytes from SS patients. Cracowski et al. [283] showed that in vivo lipid peroxidation was enhanced in scleroderma spectrum disorders including SS and undifferentiated connective tissue disease. 

Ntoso, K.A., Tomaszewski, J.E., Jimenez, S.A. and Neilson, E.G. (1986). Penicillamine-induced rapidly progressive glomerulonephritis in patients with progressive systemic sclerosis successful treatment of two patients and a review of the literature. Amer. J. Kidney Dis. 8 159-163. 

The use of iloprost has been proposed in patients with systemic sclerosis, a disease that is often characterized by pulmonary hypertension and Raynaud s phenomenon. Three patients with systemic sclerosis who were treated with iloprost developed acute thrombotic events (3). In one case, intestinal infarction occurred 1 day after infusion of iloprost. In another patient the left kidney was not perfused 22 days after the last infusion of iloprost because of thrombosis of the left renal artery. The last patient, 9 months after the start of treatment with iloprost, and 5 days after the last infusion, had an anterolateral myocardial infarction. The authors commented that their observations did not allow them to conclude that there is a direct relation between infusion of iloprost and thrombotic events. However, they said that this possibility should be considered, and they suggested that risk factors for thromboembolism should be carefully evaluated in each patient with systemic sclerosis who is receiving iloprost. 

There are reports of correlations of defective or deficient NKT cells in a number of autoimmune diseases in mice and humans (Sumida et al., 1995 Baxter et al., 1997, Wilson et al., 1998 Hies et al., 2000 Mieza et al., 1996 Zeng et al., 2000 Shi et al., 2001 Nagane et al., 2001). In humans, diabetes, systemic sclerosis, myasthenia gravis, and multiple sclerosis and in mice, a lupus model, are associated with NKT cell deficiencies. It was demonstrated that the adoptive transfer of NKT cells prevented diabetes in NOD mice. However, it is not clear whether the effectiveness of this treatment was actually due to the establishment of immune deviation of Tr cell-mediated aedve tolerance. 

In a comparison of high doses (750-1000 mg/day) and low doses (125 mg every other day) of penicillamine in the treatment of early diffuse systemic sclerosis, seven of the 34 patients in the high-dose group had proteinuria (over 1 g/day) compared with only one of the 32 in the low-dose group (45). Rheumatoid arthritis is a risk factor for renal disease, and the distinction from adverse drug reactions can be difficult in these patients (SED-14, 729). 

Jimenez SA, Sigal SH. A 15-year prospective study of treatment of rapidly progressive systemic sclerosis with D-penicUlamine. J Rheumatol 1991 18(10) 1496-503. 

Rook AH, Freundlich B, Jegasothy BV, Perez Ml, Barr WG, Jimenez SA, Rietschel RL, Wintroub B, Kahaleh MB, Varga J, Heald PW, Steen V, Massa MC, Murphy GF, Perniciaro C, Istfan M, Balias SK, Edelson RL. Treatment of systemic sclerosis with extracorporeal photochemotherapy. Results of a multicenter trial. Arch Dermatol 1992 128(3) 337 6. 

Wigley FM, Korn JH, Csuka ME, Medsger TA Jr, Rothfield NF, Ellman M, Martin R, Collier DH, Weinstein A, Furst DE, Jimenez SA, Mayes MD, Merkel PA, Gruber B, Kaufman L, Varga J, Bell P, Kern J, Marrott P, White B, Simms RW, PhilUps AC, Seibold JR. Oral iloprost treatment in patients with Raynaud s phenomenon secondary to systemic sclerosis a multicenter, placebo-controlled, double-blind study. Arthritis Rheum 1998 41(4) 670-7. 

Although CSA has been used for treatment of other autoimmune diseases such as atopic dermatitis, myasthenia gravis, systemic sclerosis and primary biliary cirrhosis, data about chronic structural injury in these situations are scarce. There are occasional reports of end stage renal failure or development of interstitial fibrosis in kidney biopsies in demyelinat-... 

Lin ATH, Clements PJ, Furst DE. Update on disease-modifying antirheumatic drugs in the treatment of systemic sclerosis. Rheum Dis Clin North Am 2003 29 409 26. 

Ahmadi-Simab K, Lamprecht P, Hellmisch B, Gross WL. Treatment of pulmonary arterial hypertension (PAH) with oral endothelin-receptor antagonist bosentan in systemic sclerosis BREATHE-1 trial and clinical experience. Z Rheumatol 2004 63(6) 495-7. [Article in German]... 

Photophoresis is a variant of PUVA treatment (Edelson et al., 1987 Horio, 2000). Leukocytes from patients with cutaneous T-cell lymphoma or autoimmune disorders (rheumatoid arthritis and systemic sclerosis) are exposed to UVA radiation in the presence of a psoralen and given back to the patients. It is believed that PUVA changes some surface markers of T-cells and thus triggers the immune system. Thus, this treatment can be regarded as a beneficial application of a photoallergic reaction. 

D-penicillamine is so named because it was first isolated as an amine, from the degradation products of penicillin by Abraham et al [87]. Later studies showed the characteristic chemical behavior of D-penicillamine which involve three types of reactions, formation of disulphide links, formation of thiazolidine rings, and formation of metal complexes and chelates [67]. It was first used in 1956 in the treatment of Wilson s disease [88]. D-penicillamine has since been used in the treatment of many diseases, such as cystinuria [89], rheumatoid arthritis [90-92], systemic sclerosis [93], primary bdiary cirrhosis [94], heavy metal poisoning due to lead [95], cadmium [%], and mercury [97], and hyperviscosity syndrome [99]. In rheumatoid arthritis, D-peni-cdlamine has been widely accepted as an effective second line treatment. Despite of its effectiveness, it causes many adverse effects, such as skin rashes [99,100], taste abnormalities [100,101], hepatic dysfunction [102-104], gastrointestinal toxiciiy [99,105], proteinuria [100,106], hematuria [107, 108], thrombocytopenia [92, 109], aplastic anemia [110], lupus-like syndrome [111, 112], Goodpasture s-tike pulmonary renal syndrome [113-115], vasculitis [116,117], myasthenia gravis [118-122], polymyositis [123, 124], and dermatomyositis [125]. 

Nifedipine also has a use in the treatment of Raynaud s disease. In Raynaud s disease, there is inappropriate vasoconstriction in the fingers and toes, usually in response to cold. The condition can be mild or severe leading to ulceration and possibly gangrene of the digits. Raynaud s disease can occur on its own, or as a consequence of systemic sclerosis or systemic lupus erythematosus, both chronic inflammatory diseases (see Chapter 7). 

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