Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Abstract

Objective. To determine whether the initiation of corticosteroids or other types of therapy affects the development of scleroderma renal crisis (SRC).Methods. Using a case-control study, 110 patients with systemic sclerosis who developed SRC between 1981 and 1993 were closely matched with controls on sex, race, age, disease duration, skin score, levels of creatine phosphokinase, and presence of tendon friction rubs. Corticosteroid use was determined prior to the onset of SRC in cases or prior to the first visit in controls. Cases were compared with matched controls using McNemar's matched-pair analysis and conditional logistic regression analysis. The effects of other drugs, including D-penicillamine, nonsteroidal antiinflammatory drugs (NSAIDs), calcium channel blockers, and angiotensin-converting enzyme (ACE) inhibitors, were also evaluated.Results. In the 6 months prior to SRC onset or to the first visit, high-dose corticosteroids (215 mg/day prednisone or equivalent) were administered significantly more frequently in SRC patients (36%) than in the controls (12%) (McNemar's odds ratio 4.37, 95% confidence interval 2.03-9.43, P < 0.0001). New use of low-dose steroids, continuous use of any steroid dose, NSAIDs, calcium channel blockers, and ACE inhibitors were not associated with an increased risk of SRC. Antecedent D-penicillamine therapy may have been protective against the development of SRC in controls.Conclusion. This retrospective case-control study has shown a significant association between antecedent high-dose corticosteroid therapy and the development of SRC. These results should discourage the use of highdose corticosteroids in patients with early diffuse scleroderma who are at increased risk of developing SRC.Scleroderma renal crisis (SRC) has been considered one of the most severe complications of systemic sclerosis. Although early treatment with angiotensinconverting enzyme (ACE) inhibitors has dramatically improved the outcome in patients with this complication, not all patients escape death or permanent dialysis (1). Predictors of renal crisis include early disease, diffuse cutaneous involvement, rapid progression of skin thickening (2), and possibly, anti-RNA polymerase I11 antibody (3). Anecdotal comments and a few case reports (4,5) have suggested that corticosteroids are associated with the development of renal crisis. However, patients who have early scleroderma with prorninent inflammatory features are precisely those who are most likely to receive steroids. The purpose of the present study was to determine whether corticosteroids are independently associated with renal crisis by controlling for the above-mentioned factors. It has been reported that D-penicillamine may prevent renal crisis (6) and ACE inhibitors may also be potentially prophylactic. Therefore, the effects of these drugs were also studied.

Predictors and outcomes of scleroderma renal crisis: Data from the high‐dose versus low‐dose D‐penicillamine in early diffuse systemic sclerosis trial

“…Although limited, this RCT methodology represents the best we have been able to accomplish at this time. Furthermore, the data from this protocol population are remarkably consistent with those from previously published longitudinal observational studies in patients with recent-onset diffuse disease (2)(3)(4)(5). This RCT failed to document efficacy of an accepted therapy, yet few, if any, previous RCTs in SSc have included such a large number of patients.…”

Serum KL-6 and surfactant protein-D as monitoring and predictive markers of interstitial lung disease in patients with systemic sclerosis and mixed connective tissue disease

“…In the treatment of SSc-ILD, although cyclophosphamide therapy can suppress the decline of pulmonary function over the short term, optimal treatment of SSc-ILD remains to be established (6). Corticosteroid has also been widely used to treat SSc-ILD, but given the lack of convincing benefit and the increased risk of SSc renal crisis, the indication for moderate-to high-dose corticosteroid therapy in SSc-ILD is limited (7,8). Therefore, the proper timing to begin medication for SSc-ILD is also unclear.…”

Interstitial Lung Disease in Systemic Sclerosis: Diagnosis and Management

“…In general, these drugs are avoided because of the well known risk of scleroderma renal crisis. This phenomenon has been well documented [53] and has been reported to occur at mean doses as low as 7.4 mg [54]. However, in most clinical trials, use of prednisone was permitted with the drug under investigation.…”