What is the utility of routine ANA testing in predicting development of biological DMARD-induced lupus and vasculitis in patients with rheumatoid arthritis? Data from a single-centre cohort.

OBJECTIVE: To determine whether serial ANA testing predicts biological disease modifying antirheumatic drugs (bDMARD)-associated ANA/dsDNA production in patients with rheumatoid arthritis (RA). METHODS: Serial autoantibody profiles, bDMARD treatment sequences and clinical data were collected from patients identified from our database that since 2005 received (i) a first bDMARD (tumour necrosis factor inhibitor (TNFi)) and (ii) tocilizumab and/or abatacept. RESULTS: Of over 1000 patients, 454 RA patients received a first TNFi. Infliximab group demonstrated higher ANA seroconversion rates (31.2%) compared with etanercept (11.8%) and adalimumab (16.1%) (p<0.001). Median (range) treatment duration prior to ANA seroconversion was 10.9 (1.3-80.0) months. Positive anti-dsDNA titres of IgG class (median (range) of 77 IU/mL (65-109)) were noted in six (7.2%) patients, within a median (range) of 2.0 (0.8-4.2) years. Three patients developed classifiable lupus. 4 of 74 (5.4%) primary non-responders and 24 of 111 (21.6%) secondary non-responders developed positive ANA antibodies after TNFi initiation (p=0.003). Seven (9.5%) tocilizumab-treated patients changed to positive ANA; five (8.6%) abatacept-treated patients changed to positive ANA status. CONCLUSIONS: This study demonstrates no utility of serial ANA/dsDNA testing that could be used to predict onset of seroconversion and therefore the development of lupus/vasculitis. An association however between seroconversion and the development of a secondary non-response to bDMARD therapy is suggested.

Established rheumatoid arthritis: rationale for best practice: physicians' perspective of how to realise tight control in clinical practice.

Developments in the understanding of the pathogenesis of rheumatoid arthritis (RA) and the introduction of targeted biologic therapies have greatly advanced the management of RA in clinical practice. The management of RA is now aimed at achieving remission, to prevent joint damage and disability. In particular, a critical period early in disease is recognised, in which early aggressive treatment with disease-modifying therapy is advocated. Although a state of remission is the ideal, this chapter discusses the difficulties which may arise in achieving this goal in patients with established disease. The evidence for best management, aimed at achieving clinical remission in established disease, is reviewed. The consequences of incomplete control of chronic inflammation in established disease, including pain, disability and co-morbidities (such as cardiovascular disease and osteoporosis), also pose a significant clinical challenge. The rationale for a multidisciplinary team approach in reducing the associated morbidity and mortality of the disease are examined.

Direct effects of tillage on the activity density of ground beetle (Coleoptera: Carabidae) weed seed predators.

Ground beetles are well known as beneficial organisms in agroecosystems, contributing to the predation of a wide range of animal pests and weed seeds. Tillage has generally been shown to have a negative effect on ground beetles, but it is not known whether this is because of direct mortality or the result of indirect losses resulting from dispersal caused by habitat deterioration. In 2005, field experiments measured direct, tillage-induced mortality, of four carabid weed seed predators, Harpalus rufipes DeGeer, Agonum muelleri Herbst, Anisodactylus merula Germar, and Amara cupreolata Putzeys, and one arthropod predator, Pterostichus melanarius Illiger, common to agroecosystems in the northeastern United States. Three tillage treatments (moldboard plow, chisel plow, and rotary tillage) were compared with undisturbed controls at two sites (Stillwater and Presque Isle) and at two dates (July and August) in Maine. Carabid activity density after disturbance was measured using fenced pitfall traps installed immediately after tillage to remove any effects of dispersal. Rotary tillage and moldboard plowing reduced weed seed predator activity density 52 and 54%, respectively. Carabid activity density after chisel plowing was similar to the undisturbed control. This trend was true for each of the weed seed predator species studied. However, activity density of the arthropod predator P. melanarius was reduced by all tillage types, indicating a greater sensitivity to tillage than the four weed seed predator species. These results confirm the need to consider both direct and indirect effects of management in studies of invertebrate seed predators.

Postchallenge plasma lipoprotein retinoids: chylomicron remnants in endogenous hypertriglyceridemia.

This study was conducted to determine whether chylomicron remnants accumulate in the plasma of patients with "endogenous" hypertriglyceridemia. Retinyl esters were used as markers of chylomicrons and chylomicron remnants since they are carried mainly if not exclusively by lipoproteins of intestinal origin. Seventy-six fasting normotriglyceridemic and hypertriglyceridemic patients were studied 12 to 15 hours after ingesting 25,000 IU of vitamin A. Plasma retinol and retinyl esters were measured by reversed-phase high-performance liquid chromatography. Chylomicronemia was assessed by flotation at unit gravity and by chylomicron flocculation in 3% polyvinylpyrrolidone. Plasma lipids, retinoids, lipoprotein cholesterol, and the electrophoretic mobility of very-low density lipoproteins were determined in a subset of 36 subjects. Progressively elevated plasma retinyl ester concentrations were observed among patients with mild, moderate, and severe hypertriglyceridemia. All subjects with fasting chylomicronemia had retinyl ester retention. The majority of subjects with mild or moderate hypertriglyceridemia (predominantly type IV hyperlipoproteinemia) also had elevated plasma concentrations of retinyl esters. Total plasma retinyl ester and plasma triglyceride concentrations correlated significantly (rs = 0.721, P less than 0.001) in nonchylomicronemic subjects. In addition, total plasma retinol concentrations were mildly elevated among hypertriglyceridemic subjects because retinol, as well as retinyl esters, is transported by triglyceride-rich lipoproteins. If lipoprotein remnants are atherogenic in man, then chylomicron remnant retention may accelerate atherogenesis in hypertriglyceridemic individuals.

Eucaloric substitution of medium chain triglycerides for dietary long chain fatty acids in acquired total lipodystrophy: effects on hyperlipoproteinemia and endogenous insulin resistance.

Previous studies have suggested that reduction of dietary fat intake, with or without caloric restriction, may lead to improvement in certain of the characteristic abnormalities that accompany total lipodystrophy (TLD). We have studied the effects of eucaloric medium chain triglyceride (MCT) substitution for dietary long chain fatty acids in a patient with acquired total lipodystrophy and unusual somatic and visceral anomalies. The patient exhibited insulin resistance, carbohydrate intolerance, striking fasting- and glucose-stimulated hyperinsulinemia, hyperglucagonemia, type V hyperlipoproteinemia, and lipoprotein lipase deficiency on a normal diet. Improvement in chylomicronemia, hypertriglyceridemia, and xanthomatosis occurred during eucaloric MCT substitution. Carbohydrate intolerance decreased and fasting immunoreactive glucagon and insulin concentrations fell 37% and 83%, respectively. Plasma triglyceride polyunsaturated fatty acid concentrations decreased to very low levels. With long term MCT feeding supplemented by polyunsaturated fatty acids, hepatomegaly has gradually decreased, while body weight has remained stable. The patient has not yet required insulin therapy. These observations suggest that the abnormalities in carbohydrate metabolism are closely linked to, and perhaps dependent on, the abnormalities in lipoprotein transport in TLD. Long chain triglyceride restriction and MCT supplementation should be attempted in additional patients with the features of TLD to determine whether this is a generally effective therapeutic approach.