Skin gene expression correlates of severity of interstitial lung disease in systemic sclerosis.

OBJECTIVE: We undertook this hypothesis-generating study to identify skin transcripts correlating with severity of interstitial lung disease (ILD) in systemic sclerosis (SSc). METHODS: Skin biopsy samples from 59 patients enrolled in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) cohort or an open-label imatinib study (baseline visit) were examined by global gene expression analysis using Illumina HT-12 arrays. Skin transcripts correlating with concomitantly obtained forced vital capacity (FVC) values and the modified Rodnan skin thickness score (MRSS) were identified by quantitative trait analysis. Also, immunofluorescence staining for selected transcripts was performed in affected skin and lung tissue. Plasma levels of CCL2, soluble SELP, and soluble P-selectin glycoprotein ligand 1 (sPSGL-1) were examined in all patients enrolled in the GENISOS cohort (n = 266). RESULTS: Eighty-two skin transcripts correlated significantly with FVC. This gene list distinguished patients with more severe ILD (FVC <70% predicted) in unsupervised hierarchical clustering analysis (P < 0.001). These genes included SELP, CCL2, and matrix metalloproteinase 3, which are involved in extravasation and adhesion of inflammatory cells. Among the FVC correlates, 8 genes (CCL2, HAPLN3, GPR4, ADCYAP1, WARS, CDC25B, PLP1, and STXBP6) also correlated with the MRSS. Immunofluorescence staining revealed that SELP and CCL2 were also overexpressed in affected skin and lung tissue from SSc patients compared to those from controls. Plasma levels of CCL2 and sPSGL-1 correlated with concomitantly obtained FVC values (r = -0.22, P = 0.001 and r = 0.17, P = 0.015, respectively). This relationship was independent of potential confounders (age, sex, ethnicity, smoking status, anti-topoisomerase I positivity, treatment with immunosuppressive agents, MRSS, disease type, and disease duration). CONCLUSION: A limited number of skin transcripts including genes involved in extravasation and adhesion of inflammatory cells correlate with severity of ILD.

Biopsychosocial typologies of pain in a cohort of patients with systemic sclerosis.

OBJECTIVE: Despite being a common problem in systemic sclerosis (SSc; scleroderma), the extant literature on pain has primarily focused on biomedical correlates, or bivariate relationships with a few psychological characteristics. There is a need to investigate the more heuristic biopsychosocial model, which incorporates the simultaneous contributions of medical, psychological, and social variables in understanding pain. METHODS: Patients with SSc (n = 333) received clinical examinations and completed self-report surveys at enrollment in the Genetics versus Environment in Scleroderma Outcome Study. Latent profile analysis was used to derive biopsychosocial profiles of patients using skin thickening, percent predicted forced vital lung capacity, perceived physical health, health worry, mental health, and social support. The profiles were examined in relation to pain and pain medication usage. RESULTS: A 3-profile solution provided the best fit to the data. Based on the biopsychosocial indicators, the profiles were characterized as managing (n = 217), resilient (n = 86), and distressed (n = 30). Between-group differences for pain emerged, with the distressed group, whose disease was less severe than the resilient group, reporting the highest pain and the greatest utilization of pain medication. CONCLUSION: Clinicians should consider biopsychosocial characteristics as contributing factors to the experience of pain in patients with SSc. Patients who are similar to those in the distressed profile may be at an increased risk for pain and would likely benefit from a referral to a behavioral health or other ancillary service provider for pain management, rather than relying solely on pharmacologic therapies.

New population-based reference values for spinal mobility measures based on the 2009-2010 National Health and Nutrition Examination Survey.

OBJECTIVE: To report population-based percentile reference values for selected spinal mobility measures in a nationally representative sample of 5,001 US adults ages 20-69 years who were examined in the 2009-2010 US National Health and Nutrition Examination Survey (NHANES). METHODS: Occiput-to-wall distance (OWD), thoracic expansion (TE), and anterior lumbar flexion (ALF; by modified Schober test) were measured by trained examiners in a standardized manner. TE was measured at the xiphisternal level, while the lower reference point for ALF was a line marked at the level of the superior margin of the lateral iliac crests. We report reference values based on the 95th percentile for the OWD and the 5th percentile for TE and ALF, as well as other summary statistics for these measures, in the study population. RESULTS: An OWD of >0 was present in 3.8% of the participants, while 8.8% of them had out-of-range values for TE based on the commonly used threshold of 2.5 cm. The 95th percentile of the OWD measurement was 0, while the 5th percentile for TE and ALF were 1.9 cm and 2 cm, respectively. The spinal measures were significantly associated with sex, age, ethnicity, height, and body mass index (BMI). Exclusion of individuals with severe obesity (BMI >35 kg/m(2) ) changed the proposed reference values for TE and ALF to 2.2 cm and 1.9 cm, respectively. CONCLUSION: We verified a reference value of 0 for the OWD in the general population. Using the reported population-based percentile values, new reference values for TE and ALF can be derived.