Corticosteroids and the risk of scleroderma renal crisis: a systematic review

Scleroderma renal crisis (SRC) has been associated with the use of corticosteroids (CS) in retrospective studies. Using an evidence-based approach, we undertook a systematic review of the literature to identify prospective studies in which scleroderma patients were administered CS to ascertain the risk of SRC in those patients. A comprehensive search was conducted using Medline, EMBASE, the Cochrane Library, and Web of Science. All original prospective clinical studies were eligible if they enrolled SSc patients newly treated with CS. Selected studies were reviewed, and data extraction was systematically performed for the dose and duration of the CS intervention as well as the occurrence of SRC. Twenty-six studies with a total of 500 SSc patients commencing new CS therapy were included in the systematic review. Ten definite cases of SRC, equivalent to a rate of 2%, were identified. In the subset of early diffuse patients, the rate of SRC was 4%. All 10 definite cases of SRC occurred in patients who received medium- to high-dose CS therapy. Seven cases occurred in the setting of stem cell transplant. CS are associated with SRC, although this may be due to confounding by disease severity and/or co-intervention. Great caution must continue to be exerted when initiating such therapy, especially in high doses and in the early diffuse subset of SSc patients.

[1]  V. Steen.  Scleroderma renal crisis. , 2007, Indian journal of medical sciences.

[2]  C. Denton.  Renal manifestations of systemic sclerosis--clinical features and outcome assessment. , 2008, Rheumatology.

[3]  U. Müller-Ladner,et al.  Renal complications and scleroderma renal crisis. , 2006, Rheumatology.

[4]  T. Miyamoto,et al.  A phase I-II trial of autologous peripheral blood stem cell transplantation in the treatment of refractory autoimmune disease , 2005, Annals of the rheumatic diseases.

[5]  C. Srinivas,et al.  EFFICACY OF DEXAMETHASONE PULSE THERAPY IN PROGRESSIVE SYSTEMIC SCLEROSIS , 1995, International journal of dermatology.

[6]  C. Black,et al.  Pilot study of anti-thymocyte globulin plus mycophenolate mofetil in recent-onset diffuse scleroderma. , 2001, Rheumatology.

[7]  S. Ueda,et al.  A case of normotensive scleroderma renal crisis after high-dose methylprednisolone treatment. , 2000, Clinical nephrology.

[8]  Richard W. Martin,et al.  High-dose versus low-dose D-penicillamine in early diffuse systemic sclerosis: analysis of a two-year, double-blind, randomized, controlled clinical trial. , 1999, Arthritis and rheumatism.

[9]  G. Asboe-hansen.  Treatment of generalized scleroderma with inhibitors of connective tissue formation. , 1975, Acta dermato-venereologica.

[10]  J. Varga.  Systemic sclerosis: an update. , 2008, Bulletin of the NYU hospital for joint diseases.

[11]  E. Coche,et al.  A pilot study of mycophenolate mofetil combined to intravenous methylprednisolone pulses and oral low-dose glucocorticoids in severe early systemic sclerosis. , 2007, Clinical and experimental rheumatology.

[12]  Anita Lee,et al.  Corticosteroid‐induced scleroderma renal crisis , 2002, The Medical journal of Australia.

[13]  L. Mouthon,et al.  Mortality and risk factors of scleroderma renal crisis: a French retrospective study of 50 patients , 2007, Annals of the rheumatic diseases.

[14]  M. Mayes,et al.  High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for severe systemic sclerosis: long-term follow-up of the US multicenter pilot study. , 2007, Blood.

[15]  E. Matteson,et al.  Pilot study of antithymocyte globulin in systemic sclerosis. , 1996, Arthritis and rheumatism.

[16]  J. G. Sharnoff,et al.  Cortisone-treated scleroderma; report of a case with autopsy findings. , 1951, Journal of the American Medical Association.

[17]  A. Testori,et al.  Autologous non-myeloablative hematopoietic stem cell transplantation in patients with systemic sclerosis , 2007, Bone Marrow Transplantation.

[18]  M. Cerinic,et al.  Cyclophosphamide pulse regimen in the treatment of alveolitis in systemic sclerosis. , 2002, The Journal of rheumatology.

[19]  J. Ioannidis,et al.  Cyclophosphamide with low or high dose prednisolone for systemic sclerosis lung disease. , 2002, The Journal of rheumatology.

[20]  K. Miller,et al.  Evaluation and management of scleroderma lung disease using bronchoalveolar lavage. , 1990, The American journal of medicine.

[21]  C. Denton,et al.  Scleroderma renal crisis: patient characteristics and long-term outcomes. , 2007, QJM : monthly journal of the Association of Physicians.

[22]  P. Airó,et al.  Intravenous cyclophosphamide for interstitial lung disease associated to systemic sclerosis: results with an 18-month long protocol including a maintenance phase. , 2007, Clinical and experimental rheumatology.

[23]  Richard W. Martin,et al.  Predictors and outcomes of scleroderma renal crisis: the high-dose versus low-dose D-penicillamine in early diffuse systemic sclerosis trial. , 2002, Arthritis and rheumatism.

[24]  M. Yamakido,et al.  Development of ischemic colitis and scleroderma renal crisis following methylprednisolone pulse therapy for progressive systemic sclerosis. , 1996, Internal medicine.

[25]  T. Medsger,et al.  Long-Term Outcomes of Scleroderma Renal Crisis , 2000, Annals of Internal Medicine.

[26]  F. Breedveld,et al.  Autologous stem cell transplantation in the treatment of systemic sclerosis: report from the EBMT/EULAR Registry , 2004, Annals of the rheumatic diseases.

[27]  K. Takehara.  Treatment of early diffuse cutaneous systemic sclerosis patients in Japan by low-dose corticosteroids for skin involvement. , 2004, Clinical and experimental rheumatology.

[28]  I. Haznedaroglu,et al.  Effects of oral cyclophosphamide and prednisolone therapy on the endothelial functions and clinical findings in patients with early diffuse systemic sclerosis. , 2003, Arthritis and rheumatism.

[29]  M. Mayes,et al.  High-dose immunosuppressive therapy for severe systemic sclerosis: initial outcomes. , 2002, Blood.

[30]  S. Liossis,et al.  Mycophenolate mofetil as first-line treatment improves clinically evident early scleroderma lung disease. , 2006, Rheumatology.

[31]  J. Costantino,et al.  Outcome of renal crisis in systemic sclerosis: relation to availability of angiotensin converting enzyme (ACE) inhibitors. , 1990, Annals of internal medicine.

[32]  A. Lundin,et al.  Improved pulmonary function in systemic sclerosis after treatment with cyclophosphamide. , 1994, Arthritis and rheumatism.

[33]  R. Scorza,et al.  Oral cyclophosphamide improves pulmonary function in scleroderma patients with fibrosing alveolitis: experience in one centre , 2006, Clinical Rheumatology.

[34]  T. Medsger,et al.  Normotensive renal failure in systemic sclerosis. , 1989, Arthritis and rheumatism.

[35]  P. Emery,et al.  A multicenter, prospective, randomized, double-blind, placebo-controlled trial of corticosteroids and intravenous cyclophosphamide followed by oral azathioprine for the treatment of pulmonary fibrosis in scleroderma. , 2006, Arthritis and rheumatism.

[36]  G. Valentini,et al.  Low‐dose intravenous cyclophosphamide in systemic sclerosis: an open prospective efficacy study in patients with early diffuse disease , 2006, Scandinavian journal of rheumatology.

[37]  S. Kiraz,et al.  The efficacy of oral cyclophosphamide plus prednisolone in early diffuse systemic sclerosis , 2003, Clinical Rheumatology.

[38]  T. Medsger,et al.  Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis. , 1998, Arthritis and rheumatism.

[39]  P. Sfikakis,et al.  Glucocorticoid effects on myocardial performance in patients with systemic sclerosis. , 2001, Clinical and experimental rheumatology.

[40]  C. Peppas,et al.  Intravenous Cyclophosphamide Pulse Therapy for the Treatment of Lung Disease Associated with Scleroderma , 1999, Clinical Rheumatology.

[41]  A. Malaviya,et al.  Intravenous dexamethasone pulse therapy in diffuse systemic sclerosis , 1994, Rheumatology International.

[42]  A. Tarkowski,et al.  Use of anti-thymocyte globulin in the management of refractory systemic autoimmune diseases. , 1993, Scandinavian journal of rheumatology.

[43]  C. Vogelmeier,et al.  Bronchoalveolar lavage for evaluation and management of scleroderma disease of the lung. , 1996, American journal of respiratory and critical care medicine.

[44]  M. Fritzler,et al.  A randomized unblinded trial of cyclophosphamide versus azathioprine in the treatment of systemic sclerosis , 2006, Clinical Rheumatology.

[45]  S. Chevret,et al.  Autologous bone marrow transplantation in the treatment of refractory systemic sclerosis: early results from a French multicentre phase I–II study , 2002, British journal of haematology.

[46]  R. Silver,et al.  Cyclophosphamide and low-dose prednisone therapy in patients with systemic sclerosis (scleroderma) with interstitial lung disease. , 1993, The Journal of rheumatology.

[47]  G. Kalliolias,et al.  Combination of intravenous pulses of cyclophosphamide and methylprednizolone in patients with systemic sclerosis and interstitial lung disease , 2007, Rheumatology International.

[48]  L. Baker,et al.  Chronic scleroderma with acute exacerbation during corticotropin therapy; report of a case with autopsy observations. , 1951, A.M.A. archives of internal medicine.