Serum autoantibodies that bind citrullinated fibrinogen are frequently found in patients with rheumatoid arthritis

OBJECTIVE: Autoantibodies that bind citrullinated antigens are a sensitive and specific marker for rheumatoid arthritis (RA). While synthetic cyclic citrullinated peptides (CCP) are typically used to identify these antibodies, little is known about antibody reactivity to the predominant citrullinated protein found in the inflamed synovium, citrullinated fibrinogen (CitFib). We assessed the prevalence of anti-CitFib antibodies in patients with various rheumatic diseases. METHODS: In total, 65 patients with established RA and 63 patients with other rheumatic diseases were tested for serum IgM rheumatoid factor (RF), IgG anti-CCP2, and IgG anti-CitFib antibodies. This cohort was used to determine optimal positive cutoff values for antibody reactivity to CitFib through receiver operating characteristic curve analysis. The specificity of these assays was confirmed with sera from 49 patients with psoriatic arthritis. RESULTS: Antibodies to both citrullinated antigens were identified in the majority of RA patients tested. The overall sensitivity and specificity of the assays were: CCP 82%, 96%, CitFib 75%, 98%, and IgM RF 80%, 64%, respectively. All but one patient that was positive for CitFib was also positive for CCP2, and close to half the RF-negative RA patients were positive for CitFib and CCP2. CONCLUSION: These results suggest that autoimmunity to CitFib is common in patients with RA and may play a role in disease pathogenesis.     

Ethnic variation in disease patterns and health outcomes in systemic lupus erythematosus

OBJECTIVE: In a single-center multiethnic lupus cohort, to investigate the influence of ethnicity on the prevalence of cumulative renal and central nervous system (CNS) lupus disease and damage, overall end-organ damage, and mortality. METHODS: Clinical features, end-organ damage, and mortality were compared by ethnic origin among patients at a lupus clinic followed prospectively in a longitudinal design over a 32-year period. Statistical analysis to compare demographic features, cumulative disease manifestations, and damage included chi-square test as well as linear, logistic, and Poisson regressions adjusting for disease duration, age at diagnosis, and presence of dialysis and hypertension. Kaplan-Meier and proportional hazard analyses were performed to compare survival. RESULTS: There were a total of 1017 patients: 853 Caucasian, 88 African-Canadian, and 76 Chinese-Canadian. Age at diagnosis was younger and disease duration was shorter for Chinese-Canadians compared to Caucasians, but similar between African-Canadians and Caucasians. There was no significant difference in CNS disease, comparing Caucasians to Chinese-Canadians. However, CNS disease was greater in African-Canadians than Chinese-Canadians. There was no significant difference between ethnic groups in CNS damage. Renal disease was more common in African-Canadians than Caucasians, with no significant difference between Caucasian and Chinese-Canadian patients. Renal damage was more common in African-Canadians and Chinese-Canadians than Caucasians. There was no significant difference in mortality among the 3 ethnic groups. CONCLUSION: In this single referral center cohort study, there was no significant difference in CNS damage or mortality among the 3 ethnic groups. African-Canadians had a higher prevalence of renal disease and damage. Further investigation into other determinants such as genetic predisposition, treatment, and cultural perceptions is needed.     

Barrett's oesophagus: an audit of surveillance over a 17-year period

OBJECTIVE: To audit whether our patients with Barrett's oesophagus (BO) enter into our endoscopic surveillance programme and whether they continue with it after entry. We have determined the incidence of oesophageal adenocarcinoma among our surveyed patients. DESIGN: We retrospectively audited prospectively collected data from our BO surveillance programme over the years 1987-2003. SETTING: An inner city teaching hospital. RESULTS: During these years, 466 patients with BO were diagnosed (392 long segment, >or=3 cm), 29 had oesophageal adenocarcinoma at diagnosis, 232 [195 with intestinal metaplasia (IM) on biopsy] had at least one follow-up endoscopy, and 205 have not been re-endoscoped. In 27 out of 205 no IM was present. Of the remaining 178 out of 205 with IM, 30 were within 2 years of diagnosis and 148 have not been re-endoscoped for the following reasons: age (51), non-attendance (35), not referred back by general practitioner (30), non-oesophageal cancer (14), severe concurrent illness (12), death (three), refused follow-up (two), left the area (one). The 195 patients with IM who entered endoscopic surveillance consisted of 108 men and 87 women (aged 62.9 years, range 31-96), were followed for a total of 1068 patient-years (average 5.5 years), and had 556 endoscopies (average 2.9 per patient). Ninety-seven out of 195 patients remain under active endoscopic surveillance but 98 discontinued for the following reasons: age (31), non attendance (21), death (21 including one from oesophageal adenocarcinoma), refused follow up (seven), concurrent illness (six), left the area (four), no IM on repeat biopsies (three). Of the 195 patients with IM, four developed low-grade dysplasia, two high-grade dysplasia and four adenocarcinoma (incidence 0.37%); 178 out of 195 have been maintained on proton pump inhibitor (PPI) therapy. CONCLUSIONS: The majority of patients with BO either do not enter or do not continue in an endoscopic surveillance programme. This needs to be acknowledged when the workload and cost of BO surveillance programmes are considered. The incidence of adenocarcinoma was low compared with many published series, and we speculate whether this is the result of maintenance PPI therapy.     

Frequency and determinants of flare and persistently active disease in systemic lupus erythematosus

Objective

Selection of flare as the primary outcome variable in systemic lupus erythematosus (SLE) clinical trials fails to capture patients with persistently active disease (PAD). We sought to elucidate the frequency and determinants of flare and PAD.

Methods

Prospectively collected data from the Toronto Lupus Cohort were used to determine the incidence of flare and PAD in 2004 and 2005. Flare was defined as an increase in SLE Disease Activity Index 2000 update (SLEDAI‐2K) score of ≥4 from the previous visit. PAD was defined as a SLEDAI‐2K score of ≥4, excluding serology alone, on ≥2 consecutive visits. Data from 1, 2, and 3 years prior were used to model flare and PAD in 2004. Model properties were tested for prediction of flare and PAD in 2005.

Results

One‐third of the patients had ≥1 flare, whereas nearly half experienced PAD in a given year. Nearly 60% of the patients had episodes of flare or PAD per year. At least 25% of patients had PAD without achieving the definition of flare. In the best‐fitting model, predictors of PAD in 2004 were SLEDAI‐2K score at the start of the outcome interval and prior cutaneous or musculoskeletal disease activity. This model gave 79% correct prediction of PAD in 2005. In contrast, flare prediction models performed poorly.

Conclusion

Persistent activity is a common disease state in SLE and should be an outcome variable in SLE clinical trials. Our PAD prediction model may aid prognostication and selection of patients for inclusion in clinical trials.     

Abdominal malignancy masquerading as gastro-oesophageal reflux

Gastro-oesophageal reflux disease is a common condition, and the typical symptoms of postprandial heartburn and upper abdominal pain usually respond well to acid-suppressive medication. Occasionally, the gastro-oesophageal reflux is secondary to gastric outlet obstruction, and rarely, it is due to more distal intestinal obstruction. Two patients are described who seemed to have a primary diagnosis of gastro-oesophageal reflux but who were subsequently found to have disseminated intra-abdominal malignancy. Further investigation beyond the endoscopic confirmation of oesophagitis should be considered in patients who have typical gastro-oesophageal reflux symptoms but who also have any associated worrying clinical features.     

Undergraduate Teaching in Geriatric Medicine: The Role of National Curricula

There has been recent international concern that the teaching of geriatrics may be in decline. Research has suggested that support for geriatrics in national undergraduate curricula is the key to effective delivery of teaching in the specialty. We set out to determine the geriatric medicine content in the U.K. generic curriculum, reviewing this in the context of the international guidance available on undergraduate teaching in geriatric medicine. Ten learning outcomes from the U.K. generic curriculum were identified as being relevant to geriatric medicine. The domains of learning and actual learning outcomes were similar among the specialty curricula from different countries. Expert-judge consultation revealed general satisfaction that these outcomes were adequate in depth and scope. Our findings show the U.K. generic curriculum supports the learning outcomes suggested in the specialty undergraduate curricula in geriatrics providing additional weight to calls for a comprehensive review of undergraduate teaching in geriatrics. This process of validating specialty curricula against national guidelines might be usefully replicated in other countries.     

Cardiovascular comorbidities in psoriasis and psoriatic arthritis: pathogenesis, consequences for patient management, and future research agenda: a report from the GRAPPA 2009 annual meeting

Psoriasis is often associated with other diseases, substantially adding to the patient's burden of disease. Recent epidemiologic studies have demonstrated an increased cardiovascular morbidity among patients with psoriasis and psoriatic arthritis (PsA), which contributes to their reduced life expectancy. At the meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) adjacent to the International Federation of Psoriasis Associations (IFPA) congress, members discussed the pathogenetic aspects of this association and resulting consequences for the management of patients with psoriasis and PsA. A future research agenda was considered.