Nihal A. Fathi

Work disability remains a major problem in rheumatoid arthritis in the 2000s: Data from 32 countries in the QUEST-RA Study

IntroductionWork disability is a major consequence of rheumatoid arthritis (RA), associated not only with traditional disease activity variables, but also more significantly with demographic, functional, occupational, and societal variables. Recent reports suggest that the use of biologic agents offers potential for reduced work disability rates, but the conclusions are based on surrogate disease activity measures derived from studies primarily from Western countries.MethodsThe Quantitative Standard Monitoring of Patients with RA (QUEST-RA) multinational database of 8,039 patients in 86 sites in 32 countries, 16 with high gross domestic product (GDP) (>24K US dollars (USD) per capita) and 16 low-GDP countries (<11K USD), was analyzed for work and disability status at onset and over the course of RA and clinical status of patients who continued working or had stopped working in high-GDP versus low-GDP countries according to all RA Core Data Set measures. Associations of work disability status with RA Core Data Set variables and indices were analyzed using descriptive statistics and regression analyses.ResultsAt the time of first symptoms, 86% of men (range 57%-100% among countries) and 64% (19%-87%) of women <65 years were working. More than one third (37%) of these patients reported subsequent work disability because of RA. Among 1,756 patients whose symptoms had begun during the 2000s, the probabilities of continuing to work were 80% (95% confidence interval (CI) 78%-82%) at 2 years and 68% (95% CI 65%-71%) at 5 years, with similar patterns in high-GDP and low-GDP countries. Patients who continued working versus stopped working had significantly better clinical status for all clinical status measures and patient self-report scores, with similar patterns in high-GDP and low-GDP countries. However, patients who had stopped working in high-GDP countries had better clinical status than patients who continued working in low-GDP countries. The most significant identifier of work disability in all subgroups was Health Assessment Questionnaire (HAQ) functional disability score.ConclusionsWork disability rates remain high among people with RA during this millennium. In low-GDP countries, people remain working with high levels of disability and disease activity. Cultural and economic differences between societies affect work disability as an outcome measure for RA.

Reliability and Validity of the University of California, Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument

OBJECTIVE To refine the previously developed scleroderma (systemic sclerosis [SSc]) gastrointestinal tract (GIT) instrument (SSC-GIT 1.0). METHODS We administered the SSC-GIT 1.0 and the Short Form 36 to 152 patients with SSc; 1 item was added to the SSC-GIT 1.0 to assess rectal incontinence. In addition, subjects completed a rating of the severity of their GIT involvement (from very mild to very severe). Evaluation of psychometric properties included internal consistency reliability, test-retest reliability (mean time interval 1.1 weeks), and multitrait scaling analysis. RESULTS Study participants were mostly women (84%) and white (81%); 55% had diffuse SSc. Self-rated severity of GIT involvement ranged from no symptoms to very mild (39%), mild (21%), moderate (31%), and severe/very severe (9%). Of an initial 53 items in the SSC-GIT 1.0, 19 items were excluded, leaving a 34-item revised instrument (the University of California, Los Angeles Scleroderma Clinical Trial Consortium GIT 2.0 [UCLA SCTC GIT 2.0]). Analyses supported 7 multi-item scales: reflux, distention/bloating, diarrhea, fecal soilage, constipation, emotional well-being, and social functioning. Test-retest reliability estimates were >/=0.68 and coefficient alphas were >/=0.67. Participants who rated their GIT disease as mild had lower scores on a 0-3 scale on all 7 scales. Symptom scales were also able to discriminate subjects with corresponding clinical GIT diagnoses. The Total GIT Score, developed by averaging 6 of 7 scales (excluding constipation), was reliable and provided greater discrimination between mild, moderate, and severe self-rated GIT involvement than individual scales. CONCLUSION This study provides support for the reliability and validity of the UCLA SCTC GIT 2.0, an improvement over the SSC-GIT 1.0, and supports a Total GIT Score in SSc patients with GIT.

Tendon transfer around the shoulder in obstetric brachial plexus paralysis: clinical and computed tomographic study.

Abstract: One hundred nine obstetrical palsy patients with defective shoulder abduction and external rotation had subscapularis release and transfer of teres major to infraspinatus with or without pedicle transfer of the clavicular head of pectoralis major to deltoid. The age at surgery averaged 67 months (11-192) and follow-up averaged 36 months (12-80). Thirty-nine cases had follow-up CT scan of both shoulders. Improvement of abduction averaged 64 degrees and that of external rotation 50 degrees, 100% and 290% gain, respectively. Both negatively correlated with the age at surgery (P < 0.001), and were significantly higher in patients operated younger than 4 years. On computed tomographic scans, the degree of glenoid retroversion positively correlated (P < 0.001) with the age at surgery, and was significantly higher in patients operated older than 4 years. The degree of posterior subluxation showed no significant difference between different ages. There was no significant difference between the operated and normal sides in patients operated younger than 4years with regard to glenoid retroversion and in those operated younger than 2 years with regard to posterior subluxation. The operation is useful for correction of defective shoulder abduction and external rotation in obstetric palsy. It is best performed before the age of 2 to get maximal improvement in motion and prevent secondary bone changes. Between the ages of 2 and 4, it also resulted in significant improvement in motion and prevented glenoid retroversion, but not posterior subluxation. After the age of 4, the improvement in motion was not significant and secondary bone changes were not prevented.

Glomerular expression and elevated serum Bcl-2 and Fas proteins in lupus nephritis : preliminary findings

Programmed cell death (apoptosis) is involved in glomerular injuries leading to glomerulonephritis. Bcl‐2 and Fas are proteins that promote cell survival and death, respectively. This study tests the hypothesis that lupus nephritis is associated with alterations of Bcl‐2 and Fas protein expression. Thirty‐six patients with lupus nephritis and 10 controls (normal individuals) were included in this study. Bcl‐2 and Fas positive cells were examined in kidney biopsies by immunohistochemistry. Bcl‐2 and Fas serum levels were evaluated by enzyme‐linked immunosorbent assay (ELISA). In the glomeruli of normal kidneys, Bcl‐2 and Fas proteins were completely absent. In lupus nephritis patients, glomerular expression of Bcl‐2 and Fas was seen in mesangial cells (1·3 ± 0·1 and 2·0 ± 0·1 for Bcl‐2 and Fas, respectively). Similarly, a statistically significantly higher Bcl‐2 (217·1 ± 85·9) and Fas (767·9 ± 271) serum levels were found in lupus patients compared to controls (148·6 ± 87, 550·3 ± 91 for Bcl‐2 and Fas, P < 0·05). A direct correlation between serum Bcl‐2 and Fas and chronicity index was also found. Compared to normal controls, lupus nephritis is associated with glomerular expression and elevated serum levels of Bcl‐2 and Fas proteins. These findings suggest possible roles for Bcl‐2 and Fas in glomerular injury during evolution of lupus nephritis. The diagnostic, prognostic and therapeutic ramifications of our findings are open to further investigation.

Diagnostic performance and predictive value of rheumatoid factor, anti-cyclic-citrullinated peptide antibodies and HLA-DRB1 locus genes in rheumatoid arthritis

Background We evaluated the significance of the genes, defined as DRB1*04 or DRB1*01, in rheumatoid arthritis (RA) patients. We focused on the role of genetic and serologic markers to predict disease activity and destructive process of joints. Methods Sixty patients with RA were examined. Radiographic changes were evaluated by (Larsen score) and disease activity was measured by disease activity score 28 (DAS28). The markers analyzed were: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptides (anti-CCP2) and HLA-DRB1 alleles typed by PCR. Results In this study, anti-CCP antibodies, CRP, RF and AKA were detected in 83.3%, 56.7%, 71.7% and 52% of patients respectively. HLA-DRB1*01 was found in 45% of patients and 35% of them had one or two HLA-DRB1*04 alleles. According to DRB1*04 subtypes, (DRB1* 0405) was present in of 80% them. For prediction of grade of activity, the independent predictors were anti-CCP (OR 19.6), and DRB1*04 positive allele (OR 5.1). The combination of DRB1*04 + anti-CCP antibodies gave increase in the specificity and positive predictive value to 92% and 90 respectively. As regards to the prediction of radiological joint damage, the independent predictors were HLA-DRB1*04, HLA-DRB1*01, RF, and CRP > 18 (OR 5.5, 4.5, 2.5, 2.0 respectively). Conclusion Our findings suggest that anti-CCP2 is superior to RF for the detection of RA and provided predictive information on joint destruction and disease activity. The presence of RA associated antibodies (ACCP or RF) and/or the SE genes are indicative for a poorer radiological outcome and higher grade of activity.

Amyloid arthropathy associated with multiple myeloma: a systematic analysis of 101 reported cases.

OBJECTIVE Amyloid deposition in multiple myeloma (MM) may lead to an arthropathy resembling rheumatoid arthritis (RA). Since a systematic description of its natural history is lacking, we have performed a systematic analysis of all published cases. METHODS Literature review featuring backward and forward database searches and direct inspection of reference lists. Inclusion criteria were as follows: publication between 1931 and 2012, diagnosis of multiple myeloma, and demonstration of light chain amyloid (AL) in any organ or in synovial fluid, arthritis, or synovitis. RESULTS Overall, 101 cases were identified. Median age was 59 years and the male-to-female ratio was 1:1. A systemic manifestation of MM was reported in 88 cases. In 53 of these, characteristic physical findings (carpal tunnel syndrome, macroglossia, shoulder pad, and soft tissue swelling/masses) were present. Arthritis manifested before the diagnosis of MM in 63 cases, with 33 cases initially misdiagnosed as RA. There were 72 cases of poly-, 17 of oligo-, and three of monoarthritis. The shoulder joint was most commonly affected, followed by knees and small hand joints. Median synovial fluid leukocyte count was 2460 cells/mm(3), and was normal in seven cases. Synovial histopathology often featured mild synovitis without plasma cell infiltration. Imaging revealed articular or periarticular inflammation in many cases and bone lesions near 22% of affected joints. Treatments varied but led to some improvement in the majority of cases. CONCLUSIONS These results solidify previous experience that MM arthropathy tends to feature a symmetric RF-negative nonerosive polyarthritis. However, the results also highlight the diversity of its presentations and stress the importance of arthropathy as a potentially under-recognized presenting manifestation of MM.

High-resolution manometry compared with the University of California, Los Angeles Scleroderma Clinical Trials Consortium GIT 2.0 in Systemic Sclerosis

OBJECTIVES To study esophageal high resolution manometry (HRM) in systemic sclerosis (SSc) patients and the correlation of findings to The University of California, Los Angeles Scleroderma Clinical Trials Consortium gastrointestinal tract 2.0 (UCLA SCTC_GIT 2.0). METHODS Forty SSc patients were administered to the UCLA SCTC GIT 2.0. Patients underwent HRM study (Solar GI MMS). HRM data were compared with 15 healthy volunteers. RESULTS Forty patients with mean age 46 ± 7 years and disease duration 9.3 ± 7 years reported upper (85.7%), lower GI symptoms (75%), while 5% reported no symptoms. Mean ± SD scores of UCLA SCTC_GIT 2.0 items were as follows: reflux 1.2 ± 0.8, distention 1.6 ± 1.2, fecal soiling 0.3 ± 0.9, diarrhea 0.8 ± 1, social 1 ± 1, emotional 1 ± 1.1, constipation 0.5 ± 0.9, and total GIT score 0.9 ± 0.6. Lower esophageal sphincter (LES) pressure and distal esophageal amplitude were significantly lower in SSc patients than controls. Main manometric findings were decreased LES resting pressure (40%) and aperistalsis (40%). Regression analyses showed distal esophageal amplitude and LES resting pressure negatively correlated with reflux score (r = -0.64; p = 0.001 and r = -0.46; p = 0.019, respectively), and total GIT score (r = -0.54; p = 0.007 and r = -0.42; p = 0.03, respectively). LES resting pressure had negative correlations with diarrhea score (r = -0.062; p = 0.002). CONCLUSIONS Decreased distal esophageal amplitude encountered as hypoperistalsis or even aperistalsis was associated with increased reflux and GIT scores (negatively correlated) UCLA SCTC_GIT 2.0 questionnaires. The GIT2.0 is easy to use and can serve as an indicator that further testing of the GI tract, including the esophagus, is indicated.

Su1098 Esophageal High Resolution Manometry (HRM) in Systemic Sclerosis: Correlation With University of California Los Angeles Scleroderma Clinical Trial Consortium GIT 2.0 (UCLA SSc_GIT 2.0) Questionnaire

Esophageal HRM is a new method to assess esophageal pressure characteristics. The UCLA SSc_GIT 2.0 is a validated disease-specific HRQOL instrument for evaluation of GIT-related activity and severity in systemic sclerosis (SSc). Aim: We studied HRM in SSc patients and the correlation of findings to the UCLA SSc_GIT 2.0 scores. Methods: Forty SSc patients administered UCLA SSc GIT 2.0 that includes multi-item scales: reflux, distention, diarrhea, fecal soiling, constipation, emotional well-being, social functioning, and total GIT score. Twenty out of 40 patients underwent esophageal HRM study (Solar GI MMS). HRM studies were analyzed for LES resting and residual pressures, esophageal amplitude and peristalsis integrity, duration and velocity of distal esophageal contraction, and UES resting and residual pressures. HRM data were compared with 15 healthy volunteers. Stepwise multiple linear regression analysis was done to test if HRM parameters could predict UCLA SSc_GIT 2.0 variables. Results: Forty patients (32 females), mean age 46 +/7 years, mean disease duration 9.3 +/7 years, reported upper (85.7%) and lower GI symptoms (75%), while 5% reported no symptoms. 31 patients had diffuse cutaneous systemic sclerosis (dcSSc), and 9 had limited cutaneous systemic sclerosis (LcSSc). Mean (SD) score of UCLA SSc_GIT 2.0 items for those who underwent HRM were as follow: reflux 1.2 +/0.8, distention 1.6 +/1.2, fecal soiling 0.3 +/0.9, diarrhea 0.8 +/1, social 1 +/1, emotional 1 +/1.1, constipation 0.5 +/0.9, and total GIT score 0.9 +/0.6. LES resting pressure and distal esophageal amplitude were significantly lower in SSc patients than control (table 1). Main manometric findings were decrease LES resting pressure (40%), aperistalsis (40%), small and large peristaltic breaks in mid and distal esophagus (55%), and low amplitude of proximal esophagus (25%) of patients. While, normal manometric findings were found in (15%) of SSc patients. Regression analyses showed distal esophageal amplitude and LES resting pressure negatively correlated with reflux score (r= -0.64; p= 0.001 and r= -0.46; p= 0.019 respectively), and total GIT score (r= -0.54; p= 0.007 and r=-0.42; p=0.03 respectively). While LES resting pressure only had negative correlation with diarrhea score (r= -0.062 p=0.002). No correlation was found between other HRM parameters and symptoms score. Conclusion: LES resting pressure and distal esophageal amplitude correlate with the UCLA SSc_GIT 2.0 questionnaire, and can be a predictor of the GIT affection in SSc. HRM parameters among SSc patients and control.