Publications

Up to 80% of patients with scleroderma have lung disease, with interstitial lung disease (ILD) being the most common manifestation. Currently, there is no definitive therapy for this condition. The objective of the study is to investigate the use of mycophenolate mofetil (MMF) to treat scleroderma interstitial ILD. We report a retrospective chart review of 17 patients with scleroderma ILD treated with MMF (2g/day) for at least 12 months. Demographics, bronchoalveolar lavage (BAL) findings, pulmonary physiology and high-resolution computed tomography were recorded at baseline and after 12 and 24 months of therapy. Baseline BAL (n=12) showed alveolitis (median of 18% neutrophils). Ninety-four percent of subjects had either improved or stable lung function after 12 months of treatment: four improved, 12 were stable and only one worsened. All patients had radiographic abnormalities consistent with ILD. After 12 months of therapy, radiological findings (n=15) were stable in 11 patients, worse in three, and improved in one. There were no side effects attributable to MMF therapy recorded. Treatment of patients with scleroderma ILD for up to 24 months with MMF was generally associated with stable pulmonary function. These data argue for a prospective trial using MMF to treat scleroderma ILD.

OBJECTIVE

The short allele of a functional polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) has been shown to interact with stressful life events to predict depression in otherwise healthy individuals. Whether the short allele increases risk for depression associated with the stress of a chronic illness has not been established.

METHOD

In a cross-sectional genetic association study, the authors examined the association of 5-HTTLPR with current depression (measured by the Computerized Diagnostic Interview Schedule), perceived stress (measured by the Perceived Stress Scale), and 24-hour urinary norepinephrine excretion in 557 outpatients with chronic coronary disease.

RESULTS

Among individuals carrying an s allele, 25% (97 of 383) had current depression, compared with 17% (29 of 174) of l/l homozygotes. The unadjusted odds ratio was 1.6, with a 95% confidence interval (CI) of 1.0-2.6; the age- and gender-adjusted odds ratio was also 1.6 (95% CI=1.0-2.5). Participants carrying an s allele had a higher mean score for perceived stress than l/l homozygotes (5.4 versus 4.7) and a higher rate of moderate or high perceived stress (adjusted odds ratio=1.6, 95% CI=1.1-2.3). Mean 24-hour norepinephrine excretion was higher in s allele carriers (55.6 versus 50.2 mg/day), who were more likely to have norepinephrine values in the highest quartile (adjusted odds ratio=1.7, 95% CI=1.0-3.0).

CONCLUSIONS

Among patients with chronic illness, carriers of the s allele of 5-HTTLPR are more vulnerable to depression, perceived stress, and high norepinephrine secretion. These factors may contribute to worse cardiovascular outcomes in these patients.