Assessing the quality, reliability and readability of online health information regarding systemic lupus erythematosus.

Introduction Systemic lupus erythematosus (SLE) has complex pathophysiology and treatments, and patients often use the internet to better understand their condition. This report systematically assesses the quality, reliability and readability of online information. Methods The search term 'systemic lupus erythematosus' was used with Google™, Bing™ and Yahoo™ search engines sequentially. The first 25 websites returned ('hits') for each search engine (total 75 websites) were compiled. The search terms 'SLE' and 'lupus' were used in separate Google searches to assess for commonality. After removal of excluded hits, websites were assessed using the DISCERN instrument, Journal of the American Medical Association benchmarks and Gunning Fog Index for quality, reliability and readability and presence of 'Health on the Net Code' (HoN) standardisation recorded. Results There was a large degree of commonality among hits from the three different search engines using the search term 'systemic lupus erythematosus', as well as hits returned for the three different search terms using Google. The mean DISCERN score was 47.7 (SD 13.2) for 'systemic lupus erythematosus', 46.4 (SD 14.2) for 'SLE' and 45.2 (SD 10.1) for 'lupus', with no statistically significant difference. The mean number of JAMA benchmarks (maximum four) present for the 'systemic lupus erythematosus', 'SLE' and 'lupus' searches was 1.3 (SD 1.2), 1.4 (SD 1.3) and 1.2 (SD 1.0), respectively, with no statistically significance difference. The average readability of hits for the three different search terms was 9.3 (SD 3.4), 10.0 (SD 3.1) and 11.1 (SD 2.7), with no statistically significant difference. Conclusion There was a large degree of commonality of hits among the different search engines and the utilised search terms but they are not synonymous. Regardless of search term, the overall quality of websites was fair, whilst reliability was poor. Websites appearing higher in searches did not score better. Presence of the HoN did not represent better quality. Readability was higher than recommended for near-universal understanding. There was no difference in quality, reliability or readability of websites using the search terms 'systemic lupus erythematosus', 'SLE' or 'lupus', with some high-scoring websites appearing in only one search term result. This study reminds clinicians to direct patients to high-quality websites rather than rely on search engines.

Immunotherapeutic strategies in antiphospholipid syndrome.

Antiphospholipid syndrome is an autoimmune condition, characterised by the persistent presence of antiphospholipid antibodies and either thrombosis or obstetric morbidity. The cornerstone of therapy is long-term anticoagulation to reduce morbidity and mortality; however, better understanding of the immunological pathways may direct us to develop future therapeutic strategies. We provide an overview of the current understanding of the immunopathogenesis of this perplexing condition and its associated morbidities and current evidence for some of the immunotherapeutic strategies.

Recent advances in polymyalgia rheumatica.

Polymyalgia rheumatica (PMR) is a chronic inflammatory disorder of unknown cause characterised by the subacute onset of shoulder and pelvic girdle pain, and early morning stiffness in men and women over the age of 50 years. Due to the lack of a gold standard investigation, diagnosis is based on a clinical construct and laboratory evidence of inflammation. Heterogeneity in the clinical presentation and disease course of PMR has long been recognised. Aside from the evolution of alternative diagnoses, such as late-onset rheumatoid arthritis, concomitant giant cell arteritis is also recognised in 16-21% of cases. In 2012, revised classification criteria were released by the European League Against Rheumatism and American College of Rheumatology in order to identify a more homogeneous population upon which future studies could be based. In this article, we aim to provide an updated perspective on the pathogenesis and diagnosis of PMR, with particular focus on imaging modalities, such as ultrasound and whole body positron emission tomography/computed tomography, which have advanced our current understanding of this disease. Future treatment directions, based on recognition of the key cytokines involved in PMR, will also be explored.

Intravascular large B cell lymphoma: an elusive cause of pyrexia of unknown origin diagnosed postmortem.

Intravascular large B cell lymphoma (IVLBCL) is a rare cause of pyrexia of unknown origin. Because of its protean clinical manifestations, diagnosis is elusive and is often made postmortem. We report here a case of IVLBCL that evaded diagnosis despite multiple investigations in vivo for pyrexia of unknown origin over a 5‐month period.

Ankylosing spondylitis: an Australian experience.

BACKGROUND: The purpose of this study was to characterize an Australian cohort of ankylosing spondylitis (AS) patients and examine predictors of important disease outcomes. METHODS: Cross-sectional study of first visit data among patients referred to the Austin Spondylitis Clinic from rheumatology or general practices. We obtained clinical and laboratory data and validated composite indices through self-reported questionnaire. RESULTS: Delay in AS diagnosis averaged 8.1 years and was higher among women and younger-onset disease. Cervicothoracic mobility was better in women although they showed more entheseal tender points and greater impairment of quality of life. Those with long-standing AS had similar disease activity to recent onset disease but had greater functional disability. Current smoking was associated with worse outcomes although there was no association between cumulative exposure and AS outcomes. CONCLUSION: The clinical expression of AS in this first-described Australian cohort is similar to previously described cohorts. We observed greater cervicothoracic mobility and a higher enthesitis index among women perhaps contributing to longer delay to diagnosis.

Detection of anti-phosphatidylethanolamine antibodies using flow cytometry.

BACKGROUND: The finding that lupus anticoagulant (LA) is significantly associated with anti-phosphatidylethanolamine (PE) activity has led to great interest in its relation to the clinical features of the antiphospholipid syndrome (APS). Considerable variability has, however, been reported in the prevalence of anti-PE antibodies in APS patients using enzyme-linked immunosorbent assay (ELISA) methodology. The lack of standardization and differences in technique may in part explain these discrepancies. PE binds variably to different types of microtiter wells, reflected in the consequent detection, or lack of detection, of anti-PE antibodies. This study describes the use of flow cytometry as an alternative method for the detection of anti-PE antibodies. METHODS: Six LA-positive plasma samples were used in this original study. Polystyrene beads were coated with PE overnight. These were subsequently incubated with patient plasma. Both IgG and IgM binding were detected by flow cytometry using a cocktail of fluorescently labelled anti-human Ig isotypes. RESULTS: When these results were compared with those from ELISA, flow cytometric analysis provided an apparent enhanced detection of anti-PE antibodies. It was found that 6/6 were IgM anti-PE positive by flow cytometry, whereas 5/6 were IgM by ELISA; 2/6 negative for anti-cardiolipin antibodies by ELISA were positive by flow cytometry; and 2/6 positive for antiphosphatidylcholine antibodies in cytometry were negative by ELISA. CONCLUSIONS: With appropriate quantification, this method may be more sensitive than ELISA in detecting anti-PE antibodies in plasma samples of patients with APS.

Microtitre plate and assay buffer alter detection of antiphosphatidylethanolamine antibodies in lupus anticoagulant positive plasma.

The ELISA for detection of anti-phosphatidylethanolamine antibodies in patients with lupus anticoagulant was studied. The influence of microtitre plate types, antigen concentration, antibody dilution, and buffer system was evaluated. Human albumin in the blocking buffer gave greater numbers of positive plasma samples than bovine serum. Comparison of simultaneous plasma and serum samples showed only minor variation in binding characteristics.

Phospholipid specificity of autoimmune and drug induced lupus anticoagulants; association of phosphatidylethanolamine reactivity with thrombosis in autoimmune disease.

OBJECTIVE: To assess the phospholipid specificity of lupus anticoagulants (LAC) in autoimmune and drug induced LAC positive patients, and to determine their relevance with the clinical feature thrombosis. METHODS: Thirty-five plasma samples with LAC were tested. Of these, 22 samples were from patients with autoimmune disease: 12 had systemic lupus erythematosus (SLE) and 10 primary antiphospholipid syndrome (APS). These were compared with 13 patients with drug induced LAC. Antiphospholipid (aPL) activity was tested by inhibition of LAC activity in a modified coagulation assay using the phospholipids: egg phosphatidylethanolamine (PE), 20% phosphatidylserine/80% phosphatidylcholine (PS/PC), and 15% PS/65%PC/20%PE mixture. Anticardiolipin antibodies (aCL) were measured in all samples by ELISA. RESULTS: In the autoimmune group, 95% were positive for reactivity to PE, 68% for PS/PC, 68% for PS/PC/PE, and 77% aCL. Of the drug induced group, 69% were positive for reactivity to PE, but only 23% for PS/PC, 46% PS/PC/PE, and 23% aCL positive. In the autoimmune patient group, 64% had thrombotic episodes, all of which had anti-PE activity, and 64% had associated anti-PS activity. No drug induced patient had episodes of thrombosis. CONCLUSION: Autoimmune induced LAC may contain a broader range of phospholipid specificities than those from drug induced patients. These data thus identify another potential reason why patients with drug induced LAC appear to be at less risk of developing APS than those with autoimmune LAC.

A methodological appraisal of the impact of different classification procedures used in three different phases of the australian rheumatoid arthritis twin survey.

AIMS: To compare methodological aspects of the impact of different classification procedures used in three phases of a twin study examining genetic factors in the aetiopathogenesis of rheumatoid arthritis (RA). METHODS: We have previously reported the results of a study of the aetiopathogenesis of RA based on the Australian Twin Registry (ATR). In the original 258 pairs self-reporting a diagnosis of RA in twin, co-twin or both, a very high false positive self-reporting rate for RA was noted (Phase 1). Subsequent diagnostic information obtained by a disease-specific questionnaire, followed by telephone interviews with subjects and review of information obtained by mail and telephone interview from the patient's general practitioner or musculoskeletal specialist, identified 23 'true' RA pairs (Phase 2). Pairwise concordance percentages for RA based on those 20 discordant and 3 concordant pairs were as follows: monozygotic (MZ) 21% (95% confidence interval (CI)=6-44%), dizygotic (DZ) 0% (95% CI=0-25%) (probandwise concordance MZ 35% (8.9-67.3), DZ 0% (0-50.3)). Given the potential effects of misclassification on data interpretation, we have further pursued the accuracy of diagnosis by a systematic clinical, serological and radiographical evaluation of the 23 RA pairs (Phase 3). RESULTS: In only one instance did more intense diagnostic investigation of the 23 pairs result in recategorization. The probandwise concordance percentages were recalculated: MZ=37.5%, DZ=0%. CONCLUSIONS: Our original contention that genetic factors play some part in the aetiopathogenesis of RA, but do not account entirely for its determination, has been substantiated at a higher level of confidence and at almost identical levels of concordance.

Autoantibodies and target antigens in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides.

In this study of antineutrophil cytoplasmic antibody (ANCA)-associated diseases, we determined the prevalence of other autoantibodies and the antigen specificities of ANCA. ANA were common, occurring in 7 of 36 (19%) patients with Wegener's granulomatosis, in 16 of 34 (47%) patients with microscopic polyarteritis, in 6 of 11 (55%) patients with segmental necrotising glomerulonephritis and in 8 of 18 (44%) of those with ANCA-associated systemic vasculitis without renal involvement. ANA were associated more often with pANCA and microscopic polyarteritis than with cANCA (P < 0.05). Patterns were speckled (n = 23), homogeneous (n = 10) or nucleolar (n = 4). Anticardiolipin antibodies were also common, occurring in 10 of 25 (40%) patients with Wegener's granulomatosis, in 8 of 14 (57%) patients with microscopic polyarteritis and in 6 of 18 (33%) of those with a systemic vasculitis. However, anticardiolipin antibodies did not correlate with the presence of ANCA in any of the disease groups. Anti-GBM antibodies were demonstrated in only 2 of 25 (8%) patients with Wegener's granulomatosis, in 1 patient with microscopic polyarteritis (1/14, 7%) and in 1 with segmental necrotising glomerulonephritis (1/11, 9%). All four patients with anti-GBM antibodies had either cANCA or pANCA. In the second part of the study, the target antigens of ANCA were determined in Wegener's granulomatosis, microscopic polyarteritis, systemic vasculitis, inflammatory bowel disease, rheumatoid arthritis and systemic lupus erythematosus (SLE). Of the 19 sera with cANCA, 13 (68%) were directed against proteinase 3; other antigens were myeloperoxidase (1/19, 5%), elastase and lactoferrin together (1/19, 5%), lysozyme (1/19, 5%) or unknown (3/19, 16%). Of the 12 (58%) sera from patients with Wegener's granulomatosis who had cANCA, 7 bound to proteinase 3. Antimyeloperoxidase antibodies were present in 14 of 45 (31%) sera with pANCA; other antigens were proteinase 3 (5/45, 11%), elastase (3/45, 78%), lactoferrin (1/45, 2%), cathepsin G (5/45, 11%) or unknown (17/45, 38%). Antimyeloperoxidase antibodies were common in microscopic polyarteritis (6/14, 43%) and systemic vasculitis (5/16, 31%). However, the majority of target antigens in systemic vasculitis and rheumatoid arthritis with pANCA were not determined. "Atypical" ANCA were present in four patients, one with inflammatory bowel disease (1/8, 13%) and three with SLE (3/15, 20%). The specificities were cathepsin G, cathepsin G plus lactoferrin, or unknown in two sera. A recent report has suggested that bactericidal/permeability-increasing protein may be the target in patients with inflammatory bowel disease.

Osteoporosis in rheumatoid arthritis. A monozygotic co-twin control study.

OBJECTIVE: To quantify the magnitude and distribution of osteoporosis in rheumatoid arthritis (RA). METHODS: Bone mineral density (BMD) was measured by dual x-ray absorptiometry, in a monozygotic co-twin control study. RESULTS: BMD was reduced at most skeletal sites in the twin with RA compared with the co-twin (lumbar spine 4.6%, femoral neck 9.7%, total body 5.7%). Differences in lean soft tissue (5.6% for total body) correlated with differences in BMD between twins at multiple sites. CONCLUSION: Osteoporosis in RA is generalized and may be related to loss of mobility or muscle mass associated with the disease.

Lupus anticoagulant in the elderly may be associated with both quinine and quinidine usage.

Thirty-one patients aged over 60 yrs and with lupus anticoagulant (LA) were reviewed for their drug intake. Twenty-three (73%) were taking cinchona alkaloids, 10 (32%) quinine for night cramps, 11 (35%) quinidine for cardiac arrhythmia and 2 (6%) were taking both. These frequencies of drugs usage differed significantly from age and sex matched controls (p < 0.001). Five patients had features suggestive of the antiphospholipid syndrome. Repeat testing showed persistent LA activity in all but 2 of 5 patients in whom the relevant drug had been ceased. This is the first description of a possible causal association between LA and quinine therapy.

Familial CREST syndrome.

The familial occurrence of scleroderma is uncommon particularly the limited (CREST) form. We describe 2 families in which such an association occurred. Family pedigree 1 consists of 2 of 3 sisters with CREST scleroderma. Both affected sisters shared HLA types and C4 allotypes including DR5, found more frequently in patients with scleroderma. The unaffected sister did not share this MHC allele. Family pedigree 2 includes a grandmother and grandson with CREST scleroderma as well as a family member with Raynaud's phenomena alone. We conclude that familial occurrence of scleroderma may be associated with shared class II MHC antigens.

Efficacy of 12 months' misoprostol as prophylaxis against NSAID-induced gastric ulcers. A placebo-controlled trial.

We performed a 12-month, double-blind, randomised, placebo-controlled study to determine the long term effect of misoprostol (600-800 micrograms/d) in the prevention of gastric ulcers and gastroduodenal erosions in 83 arthritis patients on chronic NSAID therapy. Patients underwent endoscopy at 0, 3, 6 and 12 months. At the initial endoscopy, 12 patients had an ulcer (11 gastric), which was healed prior to randomization. Seventy eligible patients reached the 3 month endoscopy. Four (12.5%) of the 32 patients given misoprostol developed a gastric ulcer compared with 11 (28.9%) of the 38 on placebo (p < 0.05, life-table analysis). Six of the 11 patients with an initial gastric ulcer developed a further gastric ulcer, compared to 9 of 58 patients without an initial ulcer (p < 0.05). We conclude that misoprostol decreases the cumulative development of NSAID-induced gastric ulcers. Patients with a previous NSAID-ulcer have a higher risk of further ulceration.

The lupus anticoagulant, anticardiolipin antibodies, and recurrent miscarriage.

The presence of antibodies to cardiolipin and the lupus anticoagulant were investigated in 189 couples with recurrent abortion. Abnormal coagulation results as measured by an elevation of the APTT or KCT were found in 6% and 7% of patients, respectively; however, the lupus anticoagulant was detected in only 3% of patients. Anticardiolipin antibody levels higher than normal were found in 15% of patients. There was no significant difference between parameters in primary as compared to secondary recurrent aborters or subfertile compared to fertile recurrent aborters. The success of the next pregnancy could not be predicted by any of the laboratory tests.

Hyperviscosity syndrome secondary to rheumatoid arthritis.

A women with longstanding seropositive rheumatoid arthritis presented with the insidious onset of a hyperviscosity syndrome. This responded to plasma exchange and corticosteroids. Plasma exchange was complicated by severe bleeding which was associated with disturbances of coagulation and of platelet function related to the marked increase in plasma immunoglobulins.