Impact of systemic sclerosis on occupational and professional activity with attention to patients with digital ulcers.

OBJECTIVE: To evaluate the impact of systemic sclerosis (SSc; scleroderma) and digital ulcers (DUs) on daily living and professional activities. METHODS: We prospectively evaluated 189 SSc patients for employment status and disability during meetings of the French SSc patient association (n=86, 45.5%) or during hospitalization (n=103, 54.5%). RESULTS: Seventy-eight (41.2%) patients had diffuse SSc. The mean±SD age was 54±13 years, and the mean±SD disease duration was 9.3±8.4 years at the time of evaluation. Sixty (31.7%) patients had at least one DU. Assessed using the Health Assessment Questionnaire (mean±SD 1.12±0.79 versus 1.39±0.84; P=0.001), the Cochin Hand Function Scale (mean±SD 20.2±18.3 versus 27.8±19.1; P<0.0001), and the Hospital Anxiety Scale (mean±SD 9.9±5 versus 8.5±4.2; P=0.04), global disability, hand disability, and anxiety, respectively, were significantly higher in patients with DUs than in others. Most patients reported a limitation in daily activities related to SSc, as assessed by a daily activity limitation scale (mean±SD 4.4±2.9) and an increased need for help in the home. Patients reported needing mean±SD 4±13.5 hours per month of paid household help related to SSc and mean±SD 1.5±10 hours per month related to DUs, with significant differences between patients with or without DUs (P=0.004). Among the 113 patients in the workforce, 67 (59.3%) were employed, 42 (37.2%) were employed full time, 36 (31.8%) received full disability pension, and 27 (23.9%) were on sick leave, with no difference between patients with or without DUs. CONCLUSION: SSc has a significant impact on activities of daily living and work disability. The need for external home help and disability are increased for those patients with DUs.

Noninvasive assessment of systolic pulmonary artery pressure in systemic lupus erythematosus: retrospective analysis of 93 patients.

OBJECTIVES: To describe the frequency of patients with an elevated systolic pulmonary artery pressure (sPAP) estimated by Doppler echocardiography in a population of SLE patients followed in a tertiary reference centre. METHODS: A search of our Internal Medicine Department database identified 93 SLE patients followed between 1995 and 2005. Their medical records were reviewed retrospectively. The PH threshold was defined as sPAP≥35mmHg. Characteristics of PH and non-PH SLE patients were compared using Fisher's, chi-square or Wilcoxon's exact test. RESULTS: Elevated sPAP was detected in 12/93 (13%) patients. When analysing the mechanisms of PH, it was considered as secondary to specific lung involvement in 2 cases, due to severe left ventricular dysfunction in 1 patient and probably corresponding to SLE-associated PAH in the 9 remaining subjects. Univariate analyses showed that sPAP≥35mmHg was more common in Black subjects (50 vs. 20%, p=0.03), in patients with longer disease duration (14±8 vs. 9.5±8 years, p=0.049), and in patients with a history of peripheral nervous system involvement (25 vs. 4%, p=0.02), pericarditis (58 vs. 27%, p=0.04), anti-Sm (42 vs. 11%, p=0.01), and anticardiolipin antibodies (75 vs. 31% p=0.007). CONCLUSIONS: PH is a relatively common complication of SLE patients managed in tertiary care centres. Doppler echocardiography allows non-invasive detection of elevated sPAP in this population that should then benefit from gold-standard techniques including right-heart catheterisation in order to confirm the diagnosis, as well as the cause and severity of PH.

Phenotypical and functional characteristics of in vitro expanded bone marrow mesenchymal stem cells from patients with systemic sclerosis.

BACKGROUND: Mesenchymal stem cells (MSCs) have a potential immunomodulatory role in autoimmune disease; however, the qualitative properties and haematopoietic support capacity of MSCs derived from patients with autoimmune disease is unclear. OBJECTIVES: To further characterise phenotypically and functionally bone marrow (BM)-derived MSCs from patients with systemic sclerosis (SSc). METHODS: Key parameters of BM-derived MSC function and phenotype were assessed in 12 patients with SSc and compared with 13 healthy normal controls. The parameters included the ability to: form colony-forming unit fibroblasts (CFU-F), differentiate along the adipogenic and osteogenic lineages, express cell surface antigens defining the MSCs population, support normal haematopoiesis and suppress in vitro lymphocyte proliferation induced by either anti-CD3epsilon plus anti-CD28 monoclonal antibodies or the mixed lymphocyte reaction. RESULTS: SSc MSCs were shown to have a similar characteristic phenotype, capacities to form CFU-F and to differentiate along adipogenic and osteogenic lineages as those of healthy donor MSCs. The ability of SSc MSCs to support long-term haematopoiesis was also identical to that of controls. Both healthy donor and SSc BM MSCs reduced the proliferation of autologous and allogeneic peripheral blood mononuclear cells in a cell number dependent fashion. CONCLUSIONS: These results show that BM-derived MSCs from patients with SSc under the described culture conditions exhibit the same phenotypic, proliferative, differentiation potential and immunosuppressive properties as their healthy counterparts and could therefore be considered in an autologous setting. Further studies are needed to ensure the quality and safety of large-scale expansion of patient MSCs prior to their potential use in clinical trials.

Microbial contamination of BM products before and after processing: a report of incidence and immediate adverse events in 257 grafts.

BACKGROUND: The incidence and potential clinical consequences of bacterial contamination of autologous and allogeneic BM products remains open to question. We report our experience of bacterial contamination of BM grafts and adverse events that occurred after transplantation. METHODS: From January 2003 to February 2006, 257 BM harvests were processed and infused at our institution. Analysis of microbial contamination incidence before and after processing, sensitivity spectra of isolated bacteria and adverse events after graft infusion were analyzed. RESULTS: Nineteen of 257 BM (7.4%) were contaminated. Coagulase-negative Staphylococcus (n=9) and Propionibacterium acnes (n=6) were the most frequently isolated microorganisms. Two of nine coagulase-negative staphylococci were found to be resistant to erythromycin and two of six P. acnes to fosfomycin and gentamycin. The frequency and severity of immediate adverse events reported in patients receiving a contaminated graft were similar to those observed in patients receiving a non-contaminated product. No major adverse sequelae occurred after infusion of contaminated grafts. Finally, none of the patients transplanted with a contaminated graft developed bacteriemia that could have been related to the isolated microorganism. DISCUSSION: Microbial contamination of BM progenitor cell grafts does not induce severe clinical complications or infectious diseases after infusion. The vast majority of isolated pathogens were skin contaminants.

Recovery, viability and clinical toxicity of thawed and washed haematopoietic progenitor cells: analysis of 952 autologous peripheral blood stem cell transplantations.

Cryopreservation and thawing of haematopoietic stem cells are associated with cell loss and infusion-related toxicities. We analysed viability, total nucleated cell (TNC) and CD34+ cell recovery, and infusion-related toxicities of 952 thawed and washed products. Mean TNC and CD34+ viable cells recoveries were 55.9+/-18.6 and 98.0+/-36.5%, respectively. Mean cell viability was 68.25+/-18.9%. TNC recovery was correlated with viability but independent of the initial nucleated cell concentration. No difference in TNC recovery or viability was observed according to underlying diseases, except for myeloma, for which these variables were significantly lower (P<0.05). CD34+ cell recovery was not correlated with viability or CD34+ initial count and was similar for all diseases. Cryostorage duration was not associated with cell loss. Immediate adverse events occurred in 169 patients (19%) and were moderate (grade I or II) for the majority of patients. Clinical toxicity was associated with a higher infused cell number and the presence of clumps in infused bags. The washing procedure of cell products lead to a low rate of adverse events, but patients transplanted with high cell numbers or bags in which clumps were identified are predisposed to such complications.

Development and validation of a scale for mouth handicap in systemic sclerosis: the Mouth Handicap in Systemic Sclerosis scale.

OBJECTIVE: To develop and assess the reliability and construct validity of a scale assessing disability involving the mouth in systemic sclerosis (SSc). METHODS: We generated a 34-item provisional scale from mailed responses of patients (n = 74), expert consensus (n = 10) and literature analysis. A total of 71 other SSc patients were recruited. The test-retest reliability was assessed using the intraclass coefficient correlation and divergent validity using the Spearman correlation coefficient. Factor analysis followed by varimax rotation was performed to assess the factorial structure of the scale. RESULTS: The item reduction process retained 12 items with 5 levels of answers (total score range 0-48). The mean total score of the scale was 20.3 (SD 9.7). The test-retest reliability was 0.96. Divergent validity was confirmed for global disability (Health Assessment Questionnaire (HAQ), r = 0.33), hand function (Cochin Hand Function Scale, r = 0.37), inter-incisor distance (r = -0.34), handicap (McMaster-Toronto Arthritis questionnaire (MACTAR), r = 0.24), depression (Hospital Anxiety and Depression (HAD); HADd, r = 0.26) and anxiety (HADa, r = 0.17). Factor analysis extracted 3 factors with eigenvalues of 4.26, 1.76 and 1.47, explaining 63% of the variance. These 3 factors could be clinically characterised. The first factor (5 items) represents handicap induced by the reduction in mouth opening, the second (5 items) handicap induced by sicca syndrome and the third (2 items) aesthetic concerns. CONCLUSION: We propose a new scale, the Mouth Handicap in Systemic Sclerosis (MHISS) scale, which has excellent reliability and good construct validity, and assesses specifically disability involving the mouth in patients with SSc.