Background Therapeutic options for progressive systemic sclerosis (SSc) are extremely restricted. Up to date, high doses of glucocorticoids have a limited role in SSc skin and lung disease severity treatment because of their possible implication in precipitating renal crisis.
Objectives To evaluate the efficacy and safety of high doses of glucocorticoid pulse therapy combined with cyclophosphamide, in the treatment of skin and lung involvement in early progressive SSc.
Methods Among the 200 SSc patients referred to our center between 2008 and 2013, 27 patients with early diffuse skin disease were treated with high dose steroid pulse therapy and cyclophosphamide for a progressive cutaneous involvement. The mean age was 46.4±14.1. Three out of 27 patients (11%) were male, two (7.4%) had a limited cutaneous involvement, 24 (88.8%) were anti-topoisomerase I positive, 3 (11%) were ANA positive.
All patients were treated with six consecutive steroid pulses (250 mg of 6-Methylprednisolone for three days, then tapered to 125 mg for other three days), in association with oral cyclophosphamide (6 or 9 gr of cumulative dose). Clinical features of disease, modified Rodnan skin score (mRSS), FVC and DLCO were evaluated at baseline and after treatment. A further follow-up of at least one year was available for each patient. A decrease of more than 25% of mRSS, of more than 10% for FVC and of more than 15% of DLCO was considered clinically significant.
Results Skin score significantly decreased after treatment (15.1±8.6) compared to baseline (20.4±7.7), (p=0.003). In 14 patients (51.9%) mRSS improved more than 25%, with a median improvement of 47.0% (range: 25.0 to 86.0%). In 4 (14.8%) mRSS remained stable and in 9 (33.3%) worsened. During further follow-up, in 11 (78,6%) of 14 responder patients the mRSS remained stable without any additional therapy.
Considering the 15 patients with lung involvement and available PFTs after steroids and cyclophosphamide therapy, the FVC values significantly increased after treatment (97.0±12.1%) compared with baseline (91.0±12.0%, p=0.02), while DLCO remained stable. In particular 5 patients (33.3%) presented a FVC increase higher than 10%. In the remaining 10 (66.7%) patients the FVC values remained stable. Neither demographic nor clinical parameters demonstrated correlation with a good response.
Five adverse events were observed: 1 patient presented an increase of liver function tests, 2 patients developed a transient cytopenia, 1 an haemorragic cystitis and 2 patients a renal crisis. In our cohort 2 patients were older than 70 years and both developed a renal crisis, while none of the patients younger than 70 years presented kidney complications (p=0,003).
Conclusions in the early inflammatory phase of cutaneous scleroderma disease steroid pulse therapy and cyclophosphamide can represent a chance to control persistently the progression of the disease in a subgroup of patients. Steroids seem to precipitate the renal crisis overall in patients with older age.
Disclosure of Interest None declared