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ID PMID Title PublicationDate abstract
9523211 Inheritance of the shared epitope and long-term outcomes of rheumatoid arthritis among com 1998 Multiple HLA-DRB1 alleles encoding a shared epitope (SE) at amino acid positions 70-74 are associated with susceptibility and severity of rheumatoid arthritis (RA). We examined the relationship between the number and DRB1 genotype of SE alleles inherited and long-term outcomes of 180 community-based, Caucasian female RA patients followed annually for up to 12 years. Outcomes examined were physician assessment of RA course; annual measures of pain, function, and number of painful joint groups; history of joint surgery; and resource utilization. Models accounted for correlation among serial observations for the same patient and adjusted for patient age and disease stage. We examined two genetic models: a SE model in which patients were classified according to the number of SE copies inherited and a genotype model in which patients were categorized into one of six groups based on the inherited DRB1 genotype. We used likelihood ratio tests to compare these genetic models and to compare alternative model specifications. Our results demonstrate strong associations between inheritance of the SE and long-term outcomes of community-based Caucasian females with RA. However, the pattern of results is not consistent across the outcomes. An additive model of risk is apparent for history of joint surgery and RA hospitalization. In contrast, a near reversal of this pattern is apparent for function, joint pain, pain rating, and RA physician visits. Finally, although the genotype model did not appear to be a better predictive model for RA outcomes overall, it did reveal some striking heterogeneity of SE alleles that was masked by the more parsimonious SE model. For example, the odds ratio (OR) for joint surgery for patients with 2 SE copies (OR = 3.16) reflects an average of 2 very different ORs when patients are further categorized according to genotype groups 4 and 5 (OR = 1.3 and 11.9, respectively).
9375866 Importance of psychological well being and disease activity in termination of an initial D 1997 Nov OBJECTIVE: To estimate the frequency of and to identify possible risk factors involved with terminating an initial disease modifying antirheumatic drug (DMARD) therapy. We hypothesized that treatment termination depends not only on side effects and inefficacy but also on the therapeutic setting and the health beliefs of the patient. METHODS: We observed an inception cohort of 302 patients with early rheumatoid arthritis (< 2 years) and first prescription of DMARD for 3 years. Survival analysis was used to estimate treatment continuation under rheumatological care. The study group comprised 4 rheumatological outpatient clinics and 7 private practices in Berlin. RESULTS: Of the initial cohort 80% continued the same drug or were in remission after one year, 70% after 2 years. Within the first 2 years, methotrexate therapy was terminated in 15% of the cases and sulfasalazine therapy in 40%, respectively. In both forms of therapy, the discontinuation rate was dependent on initial disease activity. However, the influence of the patient's psychological status at baseline was equally strong. DMARD treatment was terminated earlier and more frequently in patients with poor psychological well being. These findings hold true after controlling for disease activity or severity. CONCLUSION: Patient psychological well being and disease activity at start of initial DMARD therapy are important predictors of early drug discontinuation. By influencing psychological well being (e.g., by patient education programs), continuation of DMARD therapy might be further improved.
10648052 Using the Larsen index to assess radiographic progression in rheumatoid arthritis. 2000 Jan To describe the Larsen index and its strengths and weaknesses. I reviewed the original publication, a number of published modifications, tests of reproducibility, and some clinical studies that have used the index. The Larsen index is essentially a grading of erosion severity that has satisfactory reproducibility for use in groups of patients. The Larsen index can clearly distinguish different rates of erosive progression in groups of patients with different characteristics or treatments. Recent studies using the Larsen index have identified clear treatment effects. Difficulty in measuring the success of previous treatments designed to hold back the progression of erosions relates to the inefficacy of those treatments, not insensitivity of the Larsen index.
11128664 Androgen deficiency and bone mineral density in men with rheumatoid arthritis. 2000 Dec OBJECTIVE: To investigate the prevalence of osteopenia/osteoporosis in a group of men with rheumatoid arthritis (RA); and to analyze the relationship between sex hormone status and bone mineral density (BMD), taking into account disease activity, disease duration, and corticosteroid intake. METHODS: Clinical and demographic details were collected on 50 consecutive men with RA. BMD at the lumbar spine and femoral neck were measured, together with plasma concentrations of testosterone, sex hormone binding globulin, and luteinizing hormone. RESULTS: The median age of patients was 67 years, with median disease duration 20 years. Fourteen patients had never been treated with oral corticosteroids, the remaining 36 received a range of prednisone doses over prolonged periods. Plasma testosterone concentration was moderately reduced in 40% (< 10 nmol/l) and severely reduced in 6% of men (< 8 nmol/l), but androgen deficiency was not related to bone density or fractures. Spinal and femoral neck BMD was reduced in 38 and 71% of the men, respectively. Femoral neck BMD was related to age, weight, disability status, and specific disease activity scores. The only predictors of spinal BMD were pack-years of smoking and physician global assessment. CONCLUSION: Reduced BMD is common among men with RA. The predictors for spine and femoral neck BMD bear little direct relationship to blood testosterone concentrations despite the relatively high prevalence of low testosterone concentrations in this population. These findings are more consistent with the possibility that low testosterone concentrations in men with RA are a bystander effect of systemic inflammatory disease.
10685791 Association between IgM response to IgG damaged by glyoxidation and disease activity in rh 2000 Feb OBJECTIVE: To determine the association of serum IgG advanced glycation endproducts (AGE) and IgM anti-IgG-AGE antibodies with clinical measurements of rheumatoid arthritis (RA) disease activity. METHODS: The study group consisted of 62 patients with RA and 16 control patients with osteoarthritis. Patient derived variables included perceived disease activity (10 cm visual analog scale, VAS) and Health Assessment Questionnaire (HAQ) results. Clinical measures of RA activity consisted of tender and swollen joint counts and a physician evaluation of disease activity (by VAS) as well as history of nodules, bone erosions, Sjogren's syndrome, and vasculitis documented by chart review. Patient sera were evaluated for glucose, glycosylated hemoglobin, and presence of RF, IgG-AGE and IgM anti-IgG-AGE. The nitroblue tetrazolium colorimetric and aminophenyl boronic acid methods were used for measurement of IgG-AGE, along with an ELISA for measurement of IgM anti-IgG-AGE. RESULTS: Significant correlations were found between the presence of IgM anti-IgG-AGE and clinical measurements of swollen joint count and physician VAS. CONCLUSION: IgM anti-IgG-AGE appears to be associated with clinical measurements of RA activity and represents a new marker of more active disease in RA.
9603460 CD28 co-stimulation is intact and contributes to prolonged ex vivo survival of hyporespons 1998 May In rheumatoid arthritis (RA), T cells in the inflamed joint are considered to play a crucial role in the pathogenesis. However, despite the fact that synovial T cells have an activated memory phenotype, they are functionally suppressed upon combined CD3 and CD28 stimulation. Here, we analyzed the contribution of both CD3 and CD28 to the hyporesponsiveness of synovial T cells in RA. In contrast to the low CD3 responsiveness of synovial fluid (SF) T cells compared to peripheral blood (PB) T cells, the CD28 co-stimulatory response was observed to be unaffected. Hyporesponsiveness of SF T cells has previously been associated with decreased levels of intracellular glutathione (GSH), an antioxidant and regulator of the intracellular redox state. Treatment of SF T cells with N-acetylcysteine, an antioxidant and replenisher of GSH, selectively improved CD3-induced responses, while leaving CD28 responsiveness unaffected. These data show that the CD3 pathway is highly sensitive to intracellular GSH alterations, whereas CD28 responsiveness is relatively refractory. Furthermore, in support for a functional role of CD28 co-stimulation, it was demonstrated that CD28 ligation acted in synergy with the IL-2 receptor gamma chain signaling cytokine IL-15 in the enhancement of the ex vivo survival of SF T cells. These data indicate that CD28 co-stimulatory capacity of SF T cells, in contrast to CD3 stimulation, remains intact despite an altered intracellular redox state. Thereby, CD28 stimulation may contribute to the persistence of T cells at the site of inflammation, which might be of relevance in the pathogenesis of RA.
9598899 The effect of thalidomide and 2 analogs on collagen induced arthritis. 1998 May OBJECTIVE: Thalidomide has been described as an inhibitor of both angiogenesis (which may account for its teratogenic effects on limb bud formation) and tumor necrosis factor-alpha (TNF-alpha) production. We evaluated its therapeutic potential in collagen induced arthritis (CIA), a rat model of rheumatoid arthritis (RA). METHODS: Rats were administered orally 200 mg/kg/day thalidomide (n = 10) or either of 2 analogs, EM-12 (n = 9) or supidimide (n = 9). An additional group was given thalidomide (n = 10) at 200 mg/kg twice daily, and a control group (n = 13) was given vehicle only. At completion of the protocols, serum levels of TNF-alpha and vascular endothelial growth factor (VEGF) were measured. RESULTS: Suppression of inflammatory synovitis by clinical and radiographic criteria was significantly lower in all experimental protocols except the lower dose thalidomide group. The EM-12 analog was the most efficacious, and twice daily thalidomide was better than once daily. The incidence of arthritis onset was comparable among all groups. Strong cell mediated and humoral responses to type II collagen, measured by a radiometric delayed type hypersensitivity assay and anti-type II collagen IgG ELISA, respectively, were similar in the experimental and control groups. TNF-alpha and VEGF levels were increased in all rats immunized with collagen compared to naive controls. CONCLUSION: Thalidomide and its analogs can suppress the clinical severity of rat CIA, but the mechanism of action is not a result of TNF-alpha or VEGF downregulation.
11091284 The p53 status in juvenile chronic arthritis and rheumatoid arthritis. 2000 Nov The aim of this study was to investigate the p53 status in two autoimmune diseases; juvenile chronic arthritis (JCA) and rheumatoid arthritis (RA). In a PCR-sequencing analysis of exons 4-9 of the p53 gene, no mutation was identified, except for the case of an RA synovectomy sample with two mutations of intron 7. p53 gene polymorphisms for codons 36, 47, and 213 were not detected. Codon 72 polymorphism showed an indication of an increased occurrence of the Pro/Pro allelotype in JCA. Expression of P53 protein was comparable for JCA and RA synovectomy samples. For all RA samples P53 protein was detectable, whereas one sample of a JCA patient failed to express P53 protein.
10980564 Experimental induction of rheumatoid arthritis in temporomandibular joint of the guinea pi 2000 Sep OBJECTIVE: To correlate the clinical and radiographic changes at different stages of experimentally-induced rheumatoid arthritis (RA) of the TMJ. METHODS: Forty eight adult male guinea pigs, aged 4-6 months, were divided into two groups. Arthritis was induced in the experimental animals by intraperitoneal injection of heat-inactivated group A Streptococcus pyogenes. Four animals from each group were sacrificed and examined clinically and radiographically at intervals of 48 h and 1, 2, 4, 6 and 8 weeks. RESULTS: The main clinical findings were stiffness, crepitation and reduction in mouth opening. Radiographically, the main features were condylar erosion, flattening and sclerosis subcortical cyst formation. CONCLUSION: RA passes through stages that can be correlated clinically and radiographically. Both the clinical and radiographic manifestations in this experimental model are comparable with those previously reported in the small joints of humans.
9640130 Quantitative assessment of the rheumatoid synovial microvascular bed by gadolinium-DTPA en 1998 Mar OBJECTIVE: To examine the relation between rate of synovial membrane enhancement, intra-articular pressure (IAP), and histologically determined synovial vascularity in rheumatoid arthritis, using gadolinium-DTPA enhanced magnetic resonance imaging (MRI). METHODS: Dynamic gadolinium-DTPA enhanced MRI was performed in 31 patients with knee synovitis (10 patients IAP study, 21 patients vascular morphometry study). Rate of synovial membrane enhancement was quantified by line profile analysis using the image processing package ANALYZE. IAP was measured using an intra-compartmental pressure monitor system. Multiple synovial biopsy specimens were obtained by a blind biopsy technique. Blood vessels were identified immunohistochemically using the endothelial cell marker QBend30 and quantified (blood vessel numerical density and fractional area). RESULTS: Median blood vessel numerical density and fractional area were 77.5/mm2 (IQR; 69.3-110.7) and 5.6% (IQR; 3.4-8.5) respectively. The rate of synovial membrane enhancement (median 2.74 signal intensity units/s, IQR 2.0-3.8) correlated with both blood vessel numerical density (r = 0.46, p < 0.05) and blood vessel fractional area (r = 0.55, p < 0.02). IAP did not influence the rate of enhancement. CONCLUSIONS: Gadolinium-DTPA enhanced MRI may prove to be a valuable technique for evaluating drugs that influence angiogenesis.
10025105 [Promoting patient-oriented quality management in rheumatologic management from the viewpo 1998 Dec Limited resources in our health system require fast action to maintain sufficient health care. Improvements in the quality of standards and the processes involved are overcome more easily by the industry compared to human medicine. Can the heterogenous group of rheumatic patients be compared? Can the demands of the individual groups be satisfied concerning their health care? Coordination centers for rheumatic diseases can improve the quality of health care in conjunction with the infrastructure created by the patient support groups. These projects should not fail due to the financial crisis in our social system. It is about time to think about alternative financial models, such as foundations.
9379448 Synthesis and evaluation of novel fluorinated methotrexate derivatives for application to 1997 Sep 26 An ongoing search for new antifolate drugs useful against rheumatoid arthritis (RA) led us to prepare new methotrexate (MTX) derivatives containing enantiomerically pure L-erythro- or L-threo-gamma-fluoroglutamic acid. The derivatives in which the phenyl ring was replaced by a 3'-substituted phenyl or methylthiophene ring showed potent immunosuppressive activities, including in vitro inhibition of mitogen responses to both T and B cells and in vivo inhibition of antibody production in mice. These compounds also exhibited inhibitory activity in adjuvant arthritis in rats. Their toxicity was lower than that of MTX, which was probably due to the strong electronegativity of fluorine, which increases the acidity of the gamma-carboxyl group and thereby decreases polyglutamylation in normal cells. These results revealed the potential of the fluorinated MTX derivatives as candidate drugs for the treatment of RA.
11872950 Analysis of the sequence polymorphism within class II transactivator gene promoters. 2001 The class II transactivator is a major transcriptional factor acting on the promoters of MHC class II genes. Transcription of the CIITA gene is driven by four alternative promoters, which exhibit cell-type-specific activity. The CIITA promoter III (PIII) is constitutively active in B cells, whereas promoter IV (PIV) becomes activated upon interferon-gamma activation. The aim of this study was to investigate whether these two promoters exhibit a sequence variability like the MHC class II promoters do. We isolated PIII and PIV fragments from healthy individuals and rheumatoid arthritis patients and screened them for sequence polymorphisms. Single base pair substitutions within the CIITA PIV were found in 9% of the individuals analyzed. The majority of the substitutions were located upstream of the known cis-acting elements of the promoter. PIII was non-polymorphic. To evaluate the functional relevance of the detected polymorphism we cloned variable PIV upstream of the luciferase reporter gene. Such prepared constructs were transfected into monocytes, melanoma and HeLa cells, which were subsequently stimulated with interferon-gamma. The analysis of promoter activities did not reveal significant differences in all three cell types. We conclude that the level of CIITA expression does not vary within the population. Thus the differences in the level of MHC class II expression, which are observed between individuals, stem for the polymorphisms of the MHC class II promoters themselves.
10646485 The role of current strategies in the future treatment of rheumatoid arthritis. 1999 Nov Rheumatoid arthritis (RA) is a serious, chronic, debilitating disease for which no cure is available. Therapeutic aims for patients with RA are to alleviate symptoms, slow disease progression and optimize quality of life. In recent years, measures to achieve these goals have changed, and the development of new drugs will probably result in new treatment regimens. Two drugs with an extensive record of clinical experience are methotrexate and cyclosporin. Methotrexate is widely used because of its efficacy and high therapy retention rate. Both drugs have been shown to slow the progression of RA, but not without side-effects that sometimes preclude their use. As neither drug generally induces remission, improved treatments are needed. Combination therapy using drugs with different mechanisms of action is beginning to be evaluated, as are biological response modifiers targeted to specific mediators of the immune response. The future treatment of RA should provide more effective relief with fewer side-effects.
9489816 A clinical study of the relationship between silicone breast implants and connective tissu 1998 Feb OBJECTIVE: This study was a blinded, concurrent assessment of a historical cohort derived from a provincial registry (1978 to 1986) of breast implant recipients (cosmetic, not reconstructive) and controls (other cosmetic surgery) to test the hypothesis that connective tissue disease (CTD) is increased in breast implant recipients. METHODS: Women who underwent breast implant or other cosmetic surgery during the interval from 1978 to 1986 were contacted confidentially by Alberta Health and asked to participate in the study. Those willing to participate completed an extensive questionnaire and supplied a blood sample, subsequent to which all surgical records were reviewed to confirm implant type(s) or cosmetic surgery(ies). All participants with any suggestion of rheumatic disease were assessed blindly by a rheumatologist for CTD. RESULTS: One thousand five hundred seventy-six breast implant recipients were recruited, including 1112 who had received silicone gel-filled implants (> 13,500 person yrs exposure). Seven hundred twenty-six controls were recruited. Prevalence rates adjusted for sex and age for rheumatoid arthritis, systemic lupus erythematosus, scleroderma, and Sjögren's syndrome (the principal targeted conditions) were consistent with published reports for Caucasian women. While breast implant recipients self-reported significantly greater rates of symptoms than controls, post-surgical diagnoses of the principal targeted conditions did not indicate an increased incidence of typical or atypical CTD. CONCLUSION: The results of the study do not support the hypothesis that silicone gel-filled implants induce or promote CTD.
10575439 [Color Doppler-echo in rheumatoid arthritis with extra-articular location. Preliminary exp 1999 Sep INTRODUCTION: Chronic inflammation in rheumatoid arthritis usually involves articular synovia and extends to other joint components such as bursae, tendons and sheaths. Conventional US with high frequency transducers is an accurate tool for assessing abnormal changes in evolutive rheumatoid arthritis. We investigated the role of color and power Doppler imaging in staging extra-articular involvement, monitoring local inflammatory changes and drug treatment response. MATERIAL AND METHODS: We used a color Doppler unit with a 5-10 Mhz transducer and automatic power Doppler switch to examine 23 patients with tenosynovitis of the flexor (4/23) and extensor (8/23) tendons of the hand, Achilles (6/23) and posterior tibial (3/23) tendons, and long head of biceps (2/23) in acute rheumatoid arthritis. Only minimal pressure was exerted with the probe on the patients' skin to avoid compression and collapse of blood vessels. Ten normal volunteers were also examined as a control group. RESULTS: In all 23 acute rheumatoid arthritis patients, conventional US showed tendon involvement with intra-articular fluid, thickened tendons with partial tear and markedly hypoechoic thickened sheaths. Color signals were shown in all patients. Mid-caliber vessels were visualized coursing straight from the sheath deep into the tendon. Intra-articular signals were seen in 10/12 patients only. Spectral analysis showed arterial flow, with RI ranging .40-.70. Power Doppler added no important information, but improved vessel depiction relative to color Doppler thanks to its higher accuracy in detecting flow signals. There were no color signals in the tendons of the 10 healthy volunteers in the control group. No color signals were seen in both joints and tendons in 12 patients submitted to medical treatment. CONCLUSION: Color and power Doppler can be a necessary and useful integration to high resolution US for flow mapping in rheumatoid arthritis patients with tendon and extra-articular involvement. These modes depict local circulation changes related to disease stage and treatment response.
11469485 Starting a disease modifying antirheumatic drug or a biologic agent in rheumatoid arthriti 2001 Jul Our aim was to investigate the practices and standards by which disease modifying antirheumatic drugs (DMARD) and biologics are and have been prescribed. We reviewed the literature and examined data from patients with rheumatoid arthritis (RA) participating in a national cohort: the National Data Bank for Rheumatic Diseases (NDB). Four pathways for DMARD prescription were identified: (1) A time-based pyramidal approach (the RA pyramid); (2) a severity-based pyramid in which the most effective treatment is given to those with more active disease; (3) a cost-based pathway in which the primary goal is cost containment--this pathway intertwines with the severity-based pathway; and (4) a patient preference pathway where treatment is geared to patient needs and wishes regardless of severity. Data show that the time-based and severity-based pathways are not generally used in contemporary expert practice, and that patients with all degrees of severity and disease duration are receiving DMARD and biologic treatment. With the abandonment of the pyramid and the development of effective therapy, rheumatic disease care has swung away from the imperative of time and severity-based treatment to the imperative of care based on patient preference. It is the standard of practice to treat patients with mild and early disease with aggressive therapy, with the goal of limiting subsequent damage and retarding progression, and with the realistic purpose of relieving symptoms. The standard may at times be in conflict with the goals of insurers, but there is no legitimate medical reason for such limitations.
10822525 Antiinflammatory effect of laser therapy in rheumatoid arthritis. 1998 Jul The effect of a 940-980 nm length wave laser radiation on rheumatoid arthritis was analyzed in 60 patients: 44 adults and 16 children. Each joint was daily treated by irradiation during 7 minutes for a period of 10 days. The evolution was estimated using an analogic scale with 3 steps for 2 parameters: local pain and local inflammation for each treated joint. The evolution was favourable in both aspects, but the inflammation seemed to be better influenced than the pain. The evolution was better in children than in adults. The inflammations of the interphalangeal, carpometacarpal and shoulder's joints were a better evolution than the knee inflammation. The serological data were not influenced by laser therapy. When relapse never the treated joint was affected again. No adverse or unwanted effects were observed during the treatment excepting a sedation and an increase of night sleep duration.
11084947 Interactions of autonomic nervous, neuroendocrine, and immune systems in rheumatoid arthri 2000 Nov In general, it is assumed that the two pathways (i.e., HPA axis and sympathetic nervous system) probably act cooperatively to maintain homeostasis. The previously mentioned studies clearly point to a disturbance in the interaction between the ANS, the HPA axis, and the immune system in chronic rheumatic diseases (Fig. 2). Even early on in the course of RA, these changes can be observed. Along with the results obtained in animal models, an important role of neuroendocrine interactions in the pathogenesis of RA is proposed. Further studies are required to establish the exact contribution of the ANS in the initiation and perpetuation of RA. To date, it is quite obvious that neuropeptides play a part in the orchestration of the various molecules (e.g., cytokines) exerting modulatory effects on immune cells. One can speculate that therapeutic implications are likely to result from investigations on the ANS-immune interactions. Based on early observations that blocking catecholamine actions ameliorate symptoms of RA, it is quite promising to follow this avenue in investigating ANS-immune interactions of various time points of the disease. Conversely, further studies are required to determine the contribution of the HPA axis to the onset of RA. Results from ongoing studies are eagerly awaited so as to establish new therapeutic options. In the future,it may be possible to interfere with the inflammatory process in RA by an exactly timed neuroendocrine intervention right at or even before the onset of disease. Therapy with steroids in RA might be better planned based on the genetically determined reactivity of an individual's HPA axis. In this respect, a recent report by Masi et al is of special interest. Based on the current literature on the disturbances in the neuroendocrine, immune, and microvascular systems found in early RA, the authors hypothesize that an imbalance in the interactive homeostasis of these systems develops during a long preclinical phase and eventually leads to the outbreak of the disease in genetically predisposed individuals. This interesting hypothesis includes the perspective that individuals prone to develop RA may be identified in a preclinical phase and treated prophylactically. In any event, results from all these studies are promising in two ways: to gain more insight in the pathogenic process of RA and to establish novel therapies to help the patients bear their burden of a chronic rheumatic disease.
10895373 Serum levels of interleukin-6 and dehydroepiandrosterone sulphate in response to either fa 2000 May OBJECTIVE: To investigate the effects of either a 7-day fast or a 7-day ketogenic diet upon serum interleukin-6 (IL-6) and dehydroepiandrosterone sulphate (DHEAS) in RA patients. METHODS: We measured serum concentrations of DHEAS and IL-6 in 23 RA patients with active disease, 10 of whom followed a 7-day sub-total fast and 13 of whom consumed a ketogenic diet (isoenergetic, carbohydrate < 40 g/day) for 7 days. Clinical and laboratory variables were measured at baseline, on day 7 and after re-feeding on day 21. Correlation analyses were used to assess the associations between serum IL-6, DHEAS and disease activity variables at each timepoint. RESULTS: Fasting, but not the ketogenic diet, decreased serum IL-6 concentrations by 37% (p < 0.03) and improved disease activity at day 7. Both fasting and the ketogenic diet increased serum DHEAS levels by 34% as compared with baseline (both p < 0.006). Levels of IL-6, but not DHEAS, correlated with several disease activity variables. CONCLUSION: Both fasting and a ketogenic diet significantly increased serum DHEAS concentrations in RA patients. Only fasting significantly decreased serum IL-6 levels and improved disease activity. As the increases in serum DHEAS were similar in response to both fasting and a ketogenic diet, it is unlikely that the fall in serum IL-6 or clinical improvements after fasting were directly related to increases in serum DHEAS. The fasting-induced fall in serum IL-6 may underlie the fall in CRP and ESR observed in RA patients in response to a 7-day fast.