Intravenous Cyclophosphamide Pulse Therapy in the Treatment of Systemic Sclerosis-Related Interstitial Lung Disease: A Long Term Study

Interstitial lung disease (ILD) frequently complicates systemic sclerosis (SSc). Cyclophosphamide (CYC) is a promising immunosuppressive therapy for SSc-related ILD. Our objective was to investigate the effectiveness of an intravenous CYC (iv CYC) pulse regime in SSc-related ILD during treatment and thereafter. In a prospective observational study ten consecutive patients with SSc-related ILD were treated with iv CYC in a pulse regime lasting from 6 to 24 months. Clinical status, pulmonary functional testing (PFT) and high resolution computed tomography (HRCT) of the chest were evaluated at enrolment and 6, 12 and 24 months thereafter. After treatment withdrawal, patients were followed up every 6 months with PFT and chest HRCT to monitor lung disease. Clinical improvement was apparent in 8 out of 10 patients. The median values of forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and diffusion lung capacity for carbon monoxide (DLCO) as well as ground-glass pattern on HRCT did not change significantly after 6, 12 and 24 months of therapy. The follow-up continued in 8 out of 10 patients after treatment withdrawal for a median of 26.5 months (range: 12-48 months). The final median FVC was 54.5% of predicted value (interquartile range, IQR= 31.6%-94%). Only one patient suffered a FVC deterioration greater than 10%, even though less than 160 ml. The final median DLCO was 68% of predicted value (IQR=38.3-83.6%). Only 2 patients who developed pulmonary arterial hypertension deteriorated their DLCO values of more than 15%. An iv CYC pulse regimen over 24 months may stabilize pulmonary activity in patients with SSc-related ILD during the course of treatment and for a median of 26.5 months thereafter

Registry of the Spanish network for systemic sclerosis: survival, prognostic factors, and causes of death

Systemic sclerosis (SSc) is a rare, multisystem disease showing a large individual variability in disease progression and prognosis. In the present study, we assess survival, causes of death, and risk factors of mortality in a large series of Spanish SSc patients. Consecutive SSc patients fulfilling criteria of the classification by LeRoy were recruited in the survey. Kaplan-Meier and Cox proportional-hazards models were used to analyze survival and to identify predictors of mortality. Among 879 consecutive patients, 138 (15.7%) deaths were registered. Seventy-six out of 138 (55%) deceased patients were due to causes attributed to SSc, and pulmonary hypertension (PH) was the leading cause in 23 (16.6%) patients. Survival rates were 96%, 93%, 83%, and 73% at 5, 10, 20, and 30 years after the first symptom, respectively. Survival rates for diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc were 91%, 86%, 64%, and 39%; and 97%, 95%, 85%, and 81% at 5, 10, 20, and 30 years, respectively (log-rank: 67.63, P < 0.0001). The dcSSc subset, male sex, age at disease onset older than 65 years, digital ulcers, interstitial lung disease (ILD), PH, heart involvement, scleroderma renal crisis (SRC), presence of antitopoisomerase I and absence of anticentromere antibodies, and active capillaroscopic pattern showed reduced survival rate. In a multivariate analysis, older age at disease onset, dcSSc, ILD, PH, and SRC were independent risk factors for mortality. In the present study involving a large cohort of SSc patients, a high prevalence of disease-related causes of death was demonstrated. Older age at disease onset, dcSSc, ILD, PH, and SRC were identified as independent prognostic factors

Occupational exposure in patients with the antisynthetase syndrome.

Interstitial lung disease (ILD) is common in patients with myositis and is related with the presence of antisynthetase autoantibodies (aSA). Together with other manifestations, the resulting condition is known as the antisynthetase syndrome (ASS). Contact with certain environmental and occupational agents is also associated with the development of ILD. The objective of this study was to analyze occupational exposure and associated clinical manifestations in a cohort of patients with ASS. aSA had been identified by line immunoassay and confirmed by immunoprecipitation. Serial pulmonary function tests had been carried out to assess lung function. Thirty-two ASS patients and a control group of 32 myositis patients without aSA underwent a specific questionnaire interview to evaluate their cumulative exposure to biological dust, mineral dust, and gases/fumes up to disease onset. Comparisons were done with the Fisher exact test and Mann–Whitney test. Out from 32 ASS patients (median age, 42.7 yeras; IQR 32.2–52.5), twenty-six patients had anti-Jo-1, three anti-PL-12, and three anti-PL-7. Nine had polymyositis, 15 dermatomyositis, one amyopathic dermatomyositis, and seven pure ILD without myositis. Sixteen ASS patients (50 %) and seven (22 %) myositis patients without aSA had ever been highly exposed to dust, gases, or fumes (p < 0.05). A more than 10 % improvement in forced vital capacity occurred in 61 % of highly exposed patients and 23 % of those with low/no exposure (p = 0.06) over the observation period. In conclusion, a high percentage of patients with ASS had been exposed to dusts, gases, or fumes. (aut.ref.