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Therapeutic Evolution: A Professor’s View

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Scleroderma

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Abstract

My first encounter with systemic sclerosis (SSc) in medical school was the demonstration for our class by the professor at Malmö Jan Waldenström of a case of what he presented as Thibierge-Weissenbach’s syndrome. Dr. Waldenström had a strong interest in connective tissue diseases and urged us to buy the then new textbook by Talbott and Ferrandis (Talbott JH, Ferrandis RM. Collagen diseases. New York: Grune and Stratton; 1956. p. 137–80). Some lessons were “systemic scleroderma is not a rare malady,” the overlap with polymyositis, and of course the unknown cause. Much of the pathology was well described, including “scattered foci lymphocytic infiltration distributed perivascularly.” All organ manifestations were described; including the GI tract “starvation…is a serious threat.”

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References

  1. Talbott JH, Ferrandis RM. Collagen diseases. New York: Grune & Stratton; 1956. p. 137–80.

    Google Scholar 

  2. Franck-Larsson K, Graf W, Rönnblom A. Lower gastrointestinal symptoms and quality of life in patients with systemic sclerosis: a population-based study. Eur J Gastroenterol Hepatol. 2009;21(2):176–82.

    Article  PubMed  Google Scholar 

  3. Hargraves MM, Richmond H, Morton R. Presentation of two bone marrow elements; the “tart” cell and the “L.E.” cell. Proc Staff Meet Mayo Clin. 1948;23:25–8. Braun-Moscovici Y, Furst DE, Markovits D, Rozin A, Clements PJ, Nahir AM.

    CAS  Google Scholar 

  4. Balbir-Gurman A, Vitamin D. Parathyroid hormone, and acroosteolysis in systemic sclerosis. J Rheumatol. 2008;35(11):2201–5.

    Article  PubMed  Google Scholar 

  5. Vacca A, Cormier C, Piras M, Mathieu A, Kahan A, Allanore Y. Vitamin D deficiency and insufficiency in 2 independent cohorts of patients with systemic sclerosis. J Rheumatol. 2009;36(9):1924–9.

    Article  PubMed  CAS  Google Scholar 

  6. Lopez-Ovejero JA, Saal SD, D’Angelo WA, Cheigh JS, Stenzel KH, Laragh JH. Reversal of vascular and renal crises of scleroderma by oral angiotensin-converting-enzyme blockade. N Engl J Med. 1979;300(25):1417–9.

    Article  PubMed  CAS  Google Scholar 

  7. Steen VD, Medsger Jr TA. Long-term outcomes of scleroderma renal crisis. Ann Intern Med. 2000;133(8):600–3.

    PubMed  CAS  Google Scholar 

  8. Penn H, Howie AJ, Kingdon EJ, Bunn CC, Stratton RJ, Black CM, Burns A, Denton CP. Scleroderma renal crisis: patient characteristics and long-term outcomes. QJM. 2007;100(8):485–94.

    Article  PubMed  CAS  Google Scholar 

  9. Teixeira L, Mouthon L, Mahr A, Berezné A, Agard C, Mehrenberger M, Noël LH, Trolliet P, Frances C, Cabane J, Guillevin L. Group Français de Recherche sur le Sclérodermie (GFRS). Mortality and risk factors of scleroderma renal crisis: a french retrospective study of 50 patients. Ann Rheum Dis. 2008;67(1):110–6.

    Article  PubMed  CAS  Google Scholar 

  10. Herbert CM, Lindberg KA, Jayson MI, Bailey AJ. Biosynthesis and maturation of skin collagen in scleroderma, and effect of D-penicillamine. Lancet. 1974;1(7850):187–92.

    Article  PubMed  CAS  Google Scholar 

  11. Alarcón-Segovia D, Ibáñez G, Kershenobich D, Rojkind M. Letter: treatment of scleroderma. Lancet. 1974;1(7865):1054–5.

    Article  PubMed  Google Scholar 

  12. Clements PJ, Furst DE, Wong WK, Mayes M, White B, Wigley F, Weisman MH, Barr W, Moreland LW, Medsger Jr TA, Steen V, Martin RW, Collier D, Weinstein A, Lally E, Varga J, Weiner S, Andrews B, Abeles M, Seibold JR. High-dose versus low-dose D-penicillamine in early diffuse systemic sclerosis: analysis of a two-year, double-blind, randomized, controlled clinical trial. Arthritis Rheum. 1999;42(6):1194–203.

    Article  PubMed  CAS  Google Scholar 

  13. Medsger Jr TA, Lucas M, Wildy KS, Baker C. D-penicillamine in systemicsclerosis? Yes! Scand J Rheumatol. 2001;30(4):192–4.

    Article  PubMed  Google Scholar 

  14. Derk CT, Huaman G, Jimenez SA. A retrospective randomly selected cohort study of D-penicillamine treatment in rapidly progressive diffuse cutaneous systemic sclerosis of recent onset. Br J Dermatol. 2008;158(5):1063–8.

    Article  PubMed  CAS  Google Scholar 

  15. Herbai G. Treatment of progressive systemic sclerosis with a synthetic weak estrogen: cyclofenil (Sexovid) report of a case. Acta Med Scand. 1974;196(6):537–40.

    Article  PubMed  CAS  Google Scholar 

  16. Mason RM, Lineham JD, Phillipson MA, Black CM. Selective inhibition of proteoglycan and hyaluronate synthesis in chondrocyte cultures by cyclofenil diphenol, a non-steroidal weak oestrogen. Biochem J. 1984;223(2):401–12.

    PubMed  CAS  Google Scholar 

  17. Herbai G, Blom B, Boström H. Treatment of progressive systemic sclerosis (scleroderma, PSS) with a new drug influencing connective tissue. Acta Med Scand. 1977;201(3):203–6.

    PubMed  CAS  Google Scholar 

  18. Blom-Bülow B, Oberg K, Wollheim FA, Persson B, Jonson B, Malmberg P, Boström H, Herbai G. Cyclofenil versus placebo in progressive systemic sclerosis. A one-year double-blind crossover study of 27 patients. Acta Med Scand. 1981;210(5):419–28.

    PubMed  Google Scholar 

  19. Åkesson A, Blom-Bülow B, Scheja A, Wollmer P, Valind S, Wollheim FA. Long-term evaluation of penicillamine or cyclofenil in systemic sclerosis. Results from a two-year randomized study. Scand J Rheumatol. 1992;21(5):238–44.

    Article  PubMed  Google Scholar 

  20. Casten GG, Boucek RJ. Use of relaxin in the treatment of scleroderma. J Am Med Assoc. 1958;166(4):319–24.

    Article  PubMed  CAS  Google Scholar 

  21. Unemori EN, Amento EP. Relaxin modulates synthesis and secretion of procollagenase and collagen by human dermal fibroblasts. J Biol Chem. 1990;265(18):10681–5.

    PubMed  CAS  Google Scholar 

  22. Samuel CS, Zhao C, Bathgate RA, Bond CP, Burton MD, Parry LJ, Summers RJ, Tang ML, Amento EP, Tregear GW. Relaxin deficiency in mice is associated with an age-related progression of pulmonary fibrosis. FASEB J. 2003;17(1):121–3.

    PubMed  CAS  Google Scholar 

  23. Unemori EN, Pickford LB, Salles AL, Piercy CE, Grove BH, Erikson ME, Amento EP. Relaxin induces an extracellular matrix-degrading phenotype in human lung fibroblasts in vitro and inhibits lung fibrosis in a murine model in vivo. J Clin Invest. 1996;98(12):2739–45.

    Article  PubMed  CAS  Google Scholar 

  24. Samuel CS, Zhao C, Bathgate RA DUXJ, Summers RJ, Amento EP, Walker LL, McBurnie M, Zhao L, Tregear GW. The relaxin gene- knockout mouse: a model of progressive fibrosis. Ann N Y Acad Sci. 2005;1041:173–81.

    Article  PubMed  CAS  Google Scholar 

  25. Seibold JR, Clements PJ, Furst DE, Mayes MD, McCloskey DA, Moreland LW, White B, Wigley FM, Rocco S, Erikson M, Hannigan JF, Sanders ME, Amento EP. Safety and pharmacokinetics of recombinant human relaxin in systemic sclerosis. J Rheumatol. 1998;25(2):302–7.

    PubMed  CAS  Google Scholar 

  26. Seibold JR, Korn JH, Simms R, Clements PJ, Moreland LW, Mayes MD, Furst DE, Rothfield N, Steen V, Weisman M, Collier D, Wigley FM, Merkel PA, Csuka ME, Hsu V, Rocco S, Erikson M, Hannigan J, Harkonen WS, Sanders ME. Recombinant human relaxin in the treatment of scleroderma. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2000;132(11):87–9.

    Google Scholar 

  27. Khanna D, Clements PJ, Furst DE, Korn JH, Ellman M, Rothfield N, Wigley FM, Moreland LW, Silver R, Kim YH, Steen VD, Firestein GS, Kavanaugh AF, Weisman M, Mayes MD, Collier D, Csuka ME, Simms R, Merkel PA, Medsger Jr TA, Sanders ME, Maranian P, Seibold JR, Relaxin Investigators and the Scleroderma Clinical Trials Consortium. Recombinant human relaxin in the treatment of systemic sclerosis with diffuse cutaneous involvement: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2009;60(4):1102–11.

    Article  PubMed  CAS  Google Scholar 

  28. Giordano N, Papakostas P, Lucani B, Amendola A, Cipolli F, Agate VM, Battisti E, Martini G, Nuti R. Serum relaxin in systemic sclerosis. J Rheumatol. 2005;32(11):2164–6.

    PubMed  CAS  Google Scholar 

  29. van den Hoogen FH, Boerbooms AM, Swaak AJ, Rasker JJ, van Lier HJ, van de Putte LB. Comparison of methotrexate with placebo in the treatment of systemic sclerosis: a 24 week randomized double-blind trial, followed by a 24 week observational trial. Br J Rheumatol. 1996;35(4):364–72.

    Article  PubMed  Google Scholar 

  30. Pope JE, Bellamy N, Seibold JR, Baron M, Ellman M, Carette S, Smith CD, Chalmers IM, Hong P, O’Hanlon D, Kaminska E, Markland J, Sibley J, Catoggio L, Furst DE. A randomized, controlled trial of methotrexate versus placebo in early diffuse scleroderma. Arthritis Rheum. 2001;44(6):1351–8.

    Article  PubMed  CAS  Google Scholar 

  31. Åkesson A, Scheja A, Lundin A, Wollheim FA. Improved pulmonary function in systemic sclerosis after treatment with cyclophosphamide. Arthritis Rheum. 1994;37(5):729–35; 1981;24(9):1128–36.

    Google Scholar 

  32. Tashkin DP, Elashoff R, Clements PJ, Goldin J, Roth MD, Furst DE, Arriola E, Silver R, Strange C, Bolster M, Seibold JR, Riley DJ, Hsu VM, Varga J, Schraufnagel DE, Theodore A, Simms R, Wise R, Wigley F, White B, Steen V, Read C, Mayes M, Parsley E, Mubarak K, Connolly MK, Golden J, Olman M, Fessler B, Rothfield N, Metersky M, Scleroderma Lung Study Research Group. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med. 2006;354(25):2655–66.

    Article  PubMed  CAS  Google Scholar 

  33. Tashkin DP, Elashoff R, Clements PJ, Roth MD, Furst DE, Silver RM, Goldin J, Arriola E, Strange C, Bolster MB, Seibold JR, Riley DJ, Hsu VM, Varga J, Schraufnagel D, Theodore A, Simms R, Wise R, Wigley F, White B, Steen V, Read C, Mayes M, Parsley E, Mubarak K, Connolly MK, Golden J, Olman M, Fessler B, Rothfield N, Metersky M, Khanna D, Li N, Li G; Scleroderma Lung Study Research Group. Effects of 1-year treatment with cyclophosphamide on outcomes at 2 years in scleroderma lung disease. Am J Respir Crit Care Med. 2007;176(10):1026–34.

    Article  PubMed  CAS  Google Scholar 

  34. Khanna D, Yan X, Tashkin DP, Furst DE, Elashoff R, Roth MD, Silver R, Strange C, Bolster M, Seibold JR, Riley DJ, Hsu VM, Varga J, Schraufnagel DE, Theodore A, Simms R, Wise R, Wigley F, White B, Steen V, Read C, Mayes M, Parsley E, Mubarak K, Connolly MK, Golden J, Olman M, Fessler B, Rothfield N, Metersky M, Clements PJ, Scleroderma Lung Study Group. Impact of oral cyclophosphamide on health-related quality of life in patients with active scleroderma lung disease: results from the scleroderma lung study. Arthritis Rheum. 2007;56(5):1676–84.

    Article  PubMed  CAS  Google Scholar 

  35. Dau PC, Kahaleh MB, Sagebiel RW. Plasmapheresis and immunosuppressive drug therapy in scleroderma. Arthritis Rheum. 1981;24(9):1128–36.

    Article  PubMed  CAS  Google Scholar 

  36. Åkesson A, Wollheim FA, Thysell H, Gustafson T, Forsberg L, Pahlm O, Wollmer P, Akesson B. Visceral improvement following combined plasmapheresis and immunosuppressive drug therapy in progressive systemic sclerosis. Scand J Rheumatol. 1988;17(5):313–23.

    Article  PubMed  Google Scholar 

  37. Gratwohl A, Passweg J, Bocelli-Tyndall C, Fassas A, van Laar JM, Farge D, Andolina M, Arnold R, Carreras E, Finke J, Kötter I, Kozak T, Lisukov I, Löwenberg B, Marmont A, Moore J, Saccardi R, Snowden JA, van den Hoogen F, Wulffraat NM, Zhao XW, Tyndall A, Autoimmune Diseases Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Autologous hematopoietic stem cell transplantation for autoimmune diseases. Bone Marrow Transplant. 2005;35(9):869–79.

    Article  PubMed  CAS  Google Scholar 

  38. Nash RA, McSweeney PA, Crofford LJ, Abidi M, Chen CS, Godwin JD, Gooley TA, Holmberg L, Henstorf G, LeMaistre CF, Mayes MD, McDonagh KT, McLaughlin B, Molitor JA, Nelson JL, Shulman H, Storb R, Viganego F, Wener MH, Seibold JR, Sullivan KM, Furst DE. High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for severe systemic sclerosis: long-term follow-up of the US multicenter pilot study. Blood. 2007;110(4):1388–96.

    Article  PubMed  CAS  Google Scholar 

  39. Farge D, Passweg J, van Laar JM, Marjanovic Z, Besenthal C, Finke J, Peter HH, Breedveld FC, Fibbe WE, Black C, Denton C, Koetter I, Locatelli F, Martini A, Schattenberg AV, van den Hoogen F, van de Putte L, Lanza F, Arnold R, Bacon PA, Bingham S, Ciceri F, Didier B, Diez-Martin JL, Emery P, Feremans W, Hertenstein B, Hiepe F, Luosujärvi R, Leon Lara A, Marmont A, Martinez AM, Pascual Cascon H, Bocelli-Tyndall C, Gluckman E, Gratwohl A, Tyndall A, EBMT/EULAR Registry. Autologous stem cell transplantation in the treatment of systemic sclerosis: report from the EBMT/EULAR registry. Ann Rheum Dis. 2004;63(8):974–81.

    Article  PubMed  CAS  Google Scholar 

  40. Thompson AE, Shea B, Welch V, Fenlon D, Pope JE. Calcium-channel blockers for Raynaud’s phenomenon in systemic sclerosis. Arthritis Rheum. 2001;44(8):1841–7.

    Article  PubMed  CAS  Google Scholar 

  41. Bartosik I, Eskilsson J, Scheja A, Akesson A. Intermittent iloprost infusion therapy of pulmonary hypertension in scleroderma–a pilot study. Br J Rheumatol. 1996;35(11):1187–8.

    Article  PubMed  CAS  Google Scholar 

  42. Channick RN, Simonneau G, Sitbon O, Robbins IM, Frost A, Tapson VF, Badesch DB, Roux S, Rainisio M, Bodin F, Rubin LJ. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study. Lancet. 2001;358(9288):1119–23.

    Article  PubMed  CAS  Google Scholar 

  43. Rosenkranz S, Diet F, Karasch T, Weihrauch J, Wassermann K, Erdmann E. Sildenafil improved pulmonary hypertension and peripheral blood flow in a patient with scleroderma-associated lung fibrosis and the raynaud phenomenon. Ann Intern Med. 2003;139(10):871–3.

    PubMed  Google Scholar 

  44. Wollheim FA, Åkesson A. Management of intestinal involvement in systemic sclerosis. J Clin Rheumatol. 2007;13(3):116–8.

    Article  PubMed  Google Scholar 

  45. Dumitrascu DL, Weinbeck M. Domperidone versus metoclopramide in the treatment of diabetic gastroparesis. Am J Gastroenterol. 2000;95(1):316–7.

    Article  PubMed  CAS  Google Scholar 

  46. Kenefick NJ, Vaizey CJ, Nicholls RJ, Cohen R, Kamm MA. Sacral nerve stimulation for faecal incontinence due to systemic sclerosis. Gut. 2002;51(6):881–3.

    Article  PubMed  CAS  Google Scholar 

  47. van Laar JM, Farge D, Tyndall A. Stem cell transplantation: a treatment option for severe systemic sclerosis? Ann Rheum Dis. 2008;67(Suppl 3):35–8.

    Google Scholar 

  48. Hesselstrand R, Wildt M, Ekmehag B, Wuttge D, Scheja A. Survival in patients with pulmonary arterial hypertension associated with systemic sclerosis from a Swedish single centre: prognosis still poor and prediction difficult. Scand J Rheumatol. 2010;40(2):127–32.

    PubMed  Google Scholar 

  49. Hughes GRV. Connective tissue diseases. 2nd ed. London: Blackwell Scientific Publications; 1979. p. 154.

    Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Rheumatology, Lund University Hospital, Lund, Sweden

    Frank Wollheim MD, PhD, FRCP

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  1. Frank Wollheim MD, PhD, FRCP
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Correspondence to Frank Wollheim MD, PhD, FRCP .

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Editors and Affiliations

  1. Feinberg School of Medicine, Northwestern University, E. Huron Street 240, Chicago, 60611-2909, Illinois, USA

    John Varga

  2. Royal Free and University College, Medical School, University College London, Rowland Street, London, NW3 2PF, United Kingdom

    Christopher P. Denton

  3. School of Medicine, Div. Rheumatology, Johns Hopkins University, Eastern Avenue 5200, Baltimore, 21224, Maryland, USA

    Fredrick M. Wigley

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Wollheim, F. (2012). Therapeutic Evolution: A Professor’s View. In: Varga, J., Denton, C., Wigley, F. (eds) Scleroderma. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-5774-0_2

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