Safety of intravenous methylprednisolone therapy in patients suffering from systemic sclerosis

Scleroderma renal crisis (SRC), defined as new-onset accelerated hypertension and/or rapidly progressive renal impairment, remains one of the most feared disease manifestations of systemic sclerosis (SSc). Many risk factors have been described, including black race, male gender, early disease, serum anti-RNA polymerase III positivity, diffuse cutaneous involvement, and rapid progression of skin thickening (1). Importantly, a case–control retrospective study indicated that the use of ‡ 15 mg/day of oral prednisolone or equivalent, within the previous 6months, was associated with an increased risk of SRC (2). Moreover, a few cases of SRC have been reported after intravenous (IV) methylprednisolone (MP) pulse therapy (3, 4). For these very reasons and because of the lack of demonstration of clear efficacy of corticosteroids in SSc, clinicians are reluctant to prescribe glucocorticoids to SSc patients, despite their potent anti-inflammatory and immunosuppressive effects on certain disease manifestations, such as interstitial lung disease (ILD), myositis, arthritis, tendon friction rubs, or scleroedema. We retrospectively reviewed 95 files of SSc patients. All met the American College of Rheumatology (ACR) classification criteria (5). We identified 24 patients (four males and 20 females, all Caucasians) who had ever received IV MP treatment. Their mean (SD) age at the start of pulse therapy was 45.6 (14.4) years. Most (75%) suffered from early disease (less than 3 years since the first non-Raynaud disease manifestation). Mean disease duration was 2.9 years. According to Le Roy and Medsger (6), 2, 5, and 17 of the patients were classified as limited (lSSc), limited cutaneous (lcSSc), and diffuse cutaneous systemic sclerosis (dcSSc), respectively. Two-hundred and twenty-nine IV MP pulses (always 1 g) were administered to these 24 patients and given as courses of a median of six (mean ± SD: 6 ± 4.4; range 1–24) consecutive monthly infusions. Thus, 13, 10, and one patient(s) received one, two, and four courses of IV MP pulses, respectively. In the 11 patients having received more than one course of pulses, the pulsefree interval varied from 3 to 57 months, according to the timing of the relapse. Overall, 37 (13 + 20 + 4) courses of pulses were administered, for the following reasons (alone or in combination): interstitial lung involvement (15/37 courses), extensive cutaneous disease and/or tendon friction rubs (17/37), arthritis (1/37), and myositis (5/37). All but one patient receiving the IV MP for extensive cutaneous involvement had a disease duration of less than 1 year. Oral prednisolone was prescribed concomitantly with all but one course, at a mean (SD) daily dose of 15.6 (12.5) mg. Antihypertensive treatment with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blocking agents (ARBs) was ongoing at the start of five out of the 37 courses of IVMP. Renal safety was assessed on a monthly basis by repeated blood pressure (BP) and serum creatinine measurements, always before the following MP infusion. As indicated in Table 1, the mean systolic and diastolic BP did not differ statistically before and after the IV MP courses, nor did serum creatinine levels. We observed no episode of SRC, either during the pulse therapy or during further follow-up. NewBP-lowering agents (including an ACEI) were prescribed for new-onset hypertension (150/ 80 after the sixth pulse and 175/100 after the second pulse) in two patients who had no renal impairment or any other clinical and biological signs of malignant hypertension. These two patients continued to receive IVMP and did not require an increase of ACEI dose. One additional patient suffering from pulmonary hypertension received an ACEI. Pulse IV glucocorticoid therapy has been studied previously in SSc patients. Thus, Griffiths et al (7) tested the effectiveness of a course of six IV MP and cyclophosphamide pulses in 14 SSc patients with lung involvement. No SRC was observed but all patients were prophylactically treated with low-dose lisinopril as a purported renal protectant (7). We did not apply this precautionary measure. Similarly, no SRC was observed bySharadaetal (8) in17patientsgivensixmonthly100mg