Survival studies in scleroderma show diverse results, depending on the patient demographics, clinical subsets and organ system involvement, and are thus difficult to compare. Differences in the proportion of patients with limited and diffuse SSc, and in the frequency of serum autoantibodies, such as anticentromere antibodies and antiscleroderma 70 antibody, in different ethnic populations and countries are reasons why comparisons from one country to another are not easily interpreted. Differences observed in the starting time periods, such as the first symptom, first physician diagnosis or first study centre visit, have been used. Consequently, SSc survival studies from Canada, Hungary, Spain, England, Japan, Denmark, Sweden, Australia, Italy and Greece show a wide variation in outcomes.2,3,4,5,6,7
Our study compares the survival of patients with scleroderma seen at the same institution by the same investigators over a 30‐year time period. All patients were evaluated and were followed up in a similar fashion, making it possible to compare time periods. As of 2001, we had a 93% accountability of the patients first seen between 1972 and 1996. The 10‐year cumulative survival improved significantly from 53% in the 1970s to 67% in the 1990s. Although some of this difference is related to the improved outcome of renal crisis, the significant improvement still remained even when all patients with renal crisis throughout the time period studied were excluded. As the proportion of patients with diffuse scleroderma increased over time, it might be expected that survival would decrease. Instead, survival improved in both patients with limited and those with diffuse SSc. There was no difference in the disease duration at the time of the first physician diagnosis of SSc in these five time periods, which could be contributing to improved survival. It seems likely that improved physician management of patients with scleroderma, and earlier, more intensive treatment of scleroderma organ involvement has resulted in improved survival. Patients dying of scleroderma‐related causes died at an earlier age than (51 years, before 1986) than those dying of non‐scleroderma‐related causes (58 years, after 1986; p<0.001). This gives them a greater chance of dying from non‐scleroderma‐related causes.
Ferri et al
's study had similar findings in their long‐term outcome of 1012 Italian patients with scleroderma.4
These patients' 10‐year survival from the time of diagnosis was 60.6% before 1985, which improved to 76.8% in more recent years. Although our survival figures, at 52% in the earliest time period, improving to 68% in the most recent time period, are not quite as good as those in the Italian population, both studies show the same significant improvement in outcome over time. Our population had more men and more patients with diffuse cutaneous scleroderma than the Italian patients, which probably accounts for the survival difference between these two large studies.
Previous studies have focused on risk factors for poor survival that included older age, male sex, poor socioeconomic status, scleroderma subtype and specific organ involvement. Other factors such as erythrocyte sedimentation rate and anaemia have also been shown to affect survival.3,8,9
Not surprisingly, the presence of any major organ involvement is associated with decreased survival.8,10
A recent study showed that severity of disease also predicted early death.11
In patients with severe skin (modified Rodnan skin score >40), lung (vital capacity <55% predicted), GI (malabsorption, pseudo‐obstruction), heart (severe arrhythmia or congestive heart failure) or kidney involvement (renal crisis), the 9‐year cumulative survival was 38%, whereas, in patients who had mild organ involvement, the 9‐year cumulative survival was 78%.
The most significant change in survival over time occurred in those patients with SRC. Earlier diagnosis and aggressive use of ACE inhibitors can prevent or even reverse renal failure, with more than half of the cases pertaining to dialysis.12,13
The 5‐year cumulative survival for patients with SRC increased from <10% before the use of ACE inhibitors to 65% after the use of these drugs.13
During the past 10 years, patients with a good outcome from renal crisis had a 5‐year cumulative survival equivalent to that of patients with diffuse cutaneous SSc who did not have renal crisis, approximately 90% of potential. Some people question whether there is also an actual decrease in the frequency of deaths due to renal crisis because of the increased use of ACE inhibitors. However, we have not used ACE inhibitors prophylactically, and have previously demonstrated the dramatic improvement in survival in our patients.13
Patients who survive the initial renal crisis do not contribute to the increased deaths from PF. Most survivors of renal crisis who died later succumbed to non‐scleroderma‐related illnesses. Only 3% of patients who have survived SRC died of PF, and 5% died of pulmonary hypertension. This result should not be surprising, as the most common antibody found in patients with renal crisis is anti‐RNA polymerase III, an autoantibody that is associated with a low frequency of severe PF.14,15
PAH was the second most frequent cause of scleroderma‐related deaths in the 1970s. It has continued to be a leading cause of death, with close to 30% of scleroderma‐related deaths being due to PAH. There is no apparent explanation for the increase in causes of death due to PAH during the 1987–91 time period. There was no change in the frequency of direct new PAH referrals during this time. Around that time, we became more aware that PAH occurred in patients with diffuse scleroderma independent of PF. However, 11% of the patients who died of PAH in the time periods before and after that time period had diffuse SSc. The slight increase in deaths due to PAH over the 25 years is likely to be the result of our more aggressive search for this complication since treatment had become available. Over the past 5 years, there has been a significant improvement in the pharmacological treatment of pulmonary hypertension.16,17
Recent studies suggest that there has been improvement in short‐term survival in patients with PAH‐SSc treated with these new drugs,18
but it is too soon to conclude that there will be improvement in the long‐term survival.
The proportion of deaths due to PF has increased from 5% of scleroderma‐related deaths in the 1970s to >30% of scleroderma‐related deaths in the 1990s. Even considering the overall decrease in scleroderma‐related deaths over time, deaths due to PF were found to be increased from 3% of all deaths in the 1970s to 18% of all deaths in the 1990s (p<0.001). This is not related to the differences in disease duration in patients seen during these time periods. It is possible that patients who would have died of other SSc‐related causes in the 1970s are now living longer. These additional years, along with slow progression of fibrosis, ageing or infection, are likely to contribute to the increase in deaths due to PF. We considered other possible explanations, such as an increased frequency of anti‐topoisomerase I antibodies or referral bias of patients with severe interstitial lung disease, but did not find these to be important factors.
The survival of patients with scleroderma has improved over the past 30 years. Although the global mortality has not changed, fewer scleroderma‐related deaths are being reported, with patients living longer despite having the disease. The change in the distribution of scleroderma‐related deaths over the past 30 years confirms that lung disease (both pulmonary hypertension and PF) is the primary cause of scleroderma‐related deaths today. It is important that aggressive searches continue to develop better therapies for these severe pulmonary complications of SSc.