Prediction of postpartum onset of rheumatoid arthritis

OBJECTIVE—To investigate the prediction of the postpartum onset of rheumatoid arthritis (RA).
METHODS—Two thousand five hundred and forty seven healthy pregnant subjects were examined prospectively and the relation between serum rheumatoid factors (RF) and postpartum onset of RA was observed. Rheumatoid factors were measured in early pregnancy by the antihuman IgG latex agglutination test (Latex test) and antirabbit IgG haemagglutination test (RAHA test).
RESULTS—Latex test and RAHA test were positive in 26 (1.0%) and 64 (2.5%) pregnant subjects, respectively. Four hundred and ten subjects of 2547 pregnant women could be followed up for one year after delivery. None of 401 subjects without RF, or with only one RF on either Latex test or RAHA test, developed RA after delivery. Two (22.2%) of nine subjects with both RFs developed RA at one and three months postpartum, respectively. Transient arthralgia was found within 12 months postpartum in three of nine (33.3%) subjects with both RFs and this prevalence was significantly higher than that in RF negative subjects (8.1%).
CONCLUSION—Postpartum onset of RA was found in at least 2 of 2547 healthy subjects (0.08%) and onset was predicted by positive test for rheumatoid factors.

Keywords: rheumatoid arthritis; pregnancy; postpartum onset; rheumatoid factor     

Antiperinuclear factors are present in polyarthritis before ACR criteria for rheumatoid arthritis are fulfilled

OBJECTIVE—To show that antiperinuclear factor (APF) may be useful for the diagnosis of rheumatoid arthritis at a time when the American College of Rheumatology (ACR) criteria are not yet fulfilled.
METHODS—Testing for APF-IgG (1:100 threshold) and rheumatoid factors (RF) was done in 60 patients with polyarthritis of recent onset during a three year follow up.
RESULTS—At the end of the study, 21/40 rheumatoid arthritis were positive for RF and 31/40 for APF, including 18/40 cases (45%) in which ACR criteria were not yet fulfilled.
CONCLUSIONS—APF are useful in the diagnosis of early rheumatoid arthritis.

     

The functional affinity of IgM rheumatoid factor is related to the disease duration in patients with rheumatoid arthritis

OBJECTIVE—To determine the relevance of the functional affinity of IgM rheumatoid factor (RF) to the clinical and serological characteristics of patients with rheumatoid arthritis.
METHODS—The functional affinity of IgM RF of 57 seropositive rheumatoid arthritis patients was evaluated by an enzyme linked immunosorbent assay based on the use of a chaotropic agent. The inhibition index was taken as an estimate of functional affinity. The patient group was divided into high functional affinity subgroup 1 (functional affinity < 0.5, n = 37) and low functional affinity subgroup 2 (functional affinity > 0.5, n = 20). The medical records of all patients were reviewed with a particular note of the disease activity and the articular damage score.
RESULTS—The disease duration was shorter (P < 0.01) in subgroup 1 patients [7.9 (SD 6.4) years] than in subgroup 2 patients [13.4 (11.29) years], so that Ritchie's, Lee's, and Steinbrocker's indices were lower in the former than in the latter (P < 0.01, 0.001, and 0.01, respectively). In contrast, erythrocyte sedimentation rates, C reactive protein concentrations, antinuclear antibody, and HLA DR4 prevalences were similar in the two subgroups.
CONCLUSIONS—Different forms of RF are present during progression of the disease.

     

Analysis of LMP and TAP polymorphisms by polymerase chain reaction-restriction fragment length polymorphism in rheumatoid arthritis

OBJECTIVE—The aim of this study was to investigate the relation between the polymorphism of large molecular weight proteasome (LMP) (LMP2-LMP7) and transporter associated with antigen processing (TAP) (TAP1-TAP2) genes and rheumatoid arthritis (RA).
METHODS—Sixty RA patients and 102 ethnically matched unrelated healthy subjects were typed for LMP, TAP, and disease associated HLA-DRB1 alleles by using a new strategy based on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) with amplification created restriction sites.
RESULTS—The polymorphism of LMP (LMP2-LMP7) and TAP (TAP1-TAP2) genes was examined in shared epitope positive and negative RA patients and controls. No significant differences in the LMP or TAP allele frequencies were observed between the total patient and control groups or the patients and controls positive or negative for the shared epitope.
CONCLUSION—The data suggest that the polymorphisms of LMP and TAP genes do not have an important influence in the pathogenesis of RA, although larger studies will be needed to provide more conclusive evidence on the role of these genes in RA. A new, highly reliable strategy for typing LMP alleles is also described.

Keywords: large molecular weight proteasome; transporter assoicated with antigen processing; rheumatoid arthritis     

Serum immunoglobulins and the risk of rheumatoid arthritis

OBJECTIVE—Rheumatoid arthritis (RA) is associated with several autoantibodies that can precede the clinical disease. The immunoglobulin concentrations in serum samples before illness were studied to learn more about the immunological process before RA.
METHODS—A case-control study was nested within a Finnish cohort of 19 072 adults who had neither arthritis nor a history of it at the baseline examination during 1973-1977. By late 1989, 124 had developed RA, of which 89 were positive for rheumatoid factor (RF). Three controls per each incident case were individually matched for sex, age, and municipality. The concentrations of IgG, IgA, and IgM were measured from stored serum samples.
RESULTS—Serum IgG before illness was found to be directly proportional to the risk of RF positive RA, and a non-linear association was present between serum IgA and the risk of RF positive RA. These associations were constant between men and women and other subgroups of the study population and not confounded by serum orosomucoid concentration, level of education, smoking, alcohol intake or body mass index. As adjusted for these factors, the odds ratios (95% confidence intervals) of RF positive RA in the lowest, mid, and highest tertiles of IgG distribution were 1.00, 1.55 (0.81, 2.97), and 2.22 (1.16, 4.26), and in the tertiles of IgA 1.00, 2.23 (1.14, 4.36), and 1.78 (0.89, 3.57), respectively. The associations persisted throughout the entire observation period but were most distinct when the period to the onset of clinical RA was ≥ 10 years. IgM carried no predictive significance. None of the serum immunoglobulins predicted the development of RF negative RA.
CONCLUSIONS—Increased IgG levels may reflect some, at present unknown process in the early events leading to the development of RA, typically occurring ≥ 10 years before the onset of clinical disease.

     

Fasting enhances mucosal antigen specific B cell responses in rheumatoid arthritis

OBJECTIVE—To evaluate the influence of fasting on the antigen specific immune responsiveness in patients with rheumatoid arthritis and healthy volunteers.
METHODS—Seven rheumatoid arthritis patients and 17 healthy volunteers were immunised perorally or parenterally with influenza virus vaccine after a three to six day long period of total energy deprivation (water fast). The subsequent antigen specific antibody mediated immune response was recorded in the blood at the single cell level by the ELISPOT method.
RESULTS—Short term starvation induced an enhanced antigen specific mucosa derived B lymphocyte response in rheumatoid arthritis patients and healthy volunteers. In contrast, the systemic B cell responses were not significantly altered by a total energy deprivation.
CONCLUSIONS—Short term starvation increases the mucosa derived B cell responsiveness, while systemic responsiveness is largely unaffected. The similar pattern of response in rheumatoid arthritis patients and healthy volunteers indicates that fasting alters the mucosal immune response independently of medical treatment.

     

Analysis of T cell receptor V alpha polymorphisms in rheumatoid arthritis

OBJECTIVE—To test for association of T cell receptor (TCR) V alpha polymorphisms and rheumatoid arthritis (RA) in British and Swiss white populations.
METHODS—TCRAV polymorphisms were analysed in RA patients and controls by single strand conformational polymorphism (SSCP) analysis. Associations were sought between defined genotypes and RA, and the effect of HLA-DR4 status analysed. Putative associations were then retested further in new groups of patients and controls. Overall, 360 RA patients and 197 controls were studied.
RESULTS—No association between TCRAV5S1, V6S1, V8S1, V17S1 or V21S1 polymorphisms and RA were observed in the initial population screened. Stratification for DR4 status showed an increase of V5S1*01/*01 in DR4 positive versus DR4 negative patients (χ² = 7.19, p=0.028 (2df), p=0.14 after correction for multiple comparisons). This putative association was tested in three further patient groups, none of which showed significant increase of V5S1*01/*01 in DR4 positive patients, although an overall trend towards an increase in V5S1*01/*01 was observed.
CONCLUSION—No evidence was found for a strong association of TCRAV genes and RA in a white population. However, these results suggest a weak association of V5S1*01/*01 with DR4 positive RA, although this requires confirmation using larger groups of patients and controls.

Keywords: rheumatoid arthritis; immunogenetics; T cell receptor     

Use of monoclonal antibodies to detect disease associated HLA-DRB1 alleles and the shared epitope in rheumatoid arthritis

OBJECTIVE—To use a panel of monoclonal antibodies (Mab) which recognise HLA class II alleles associated with rheumatoid arthritis for fluorescence activated cell sorter (FACS) analysis of peripheral blood mononuclear cells (PBMNC) from patients with early and established rheumatoid arthritis and to compare these results against DNA oligotyping of HLA class II molecules in the same patients.
METHODS—27 patients (18 from an early arthritis clinic, nine with established rheumatoid arthritis) were studied using both techniques. PBMNC were stained with Mab which recognise the shared epitope, the HLA-DRB1*04 molecule and its *0401, *0404 subtypes in the presence of bound peptide. Mab stained cells were analysed by FACS. Genomic DNA was prepared from PBMNC and used for DNA oligotyping and sequencing by standard methods.
RESULTS—FACS analysis of Mab stained PBMNC gave identical results to those obtained by DNA oligotyping in 26/27 patients. The antibodies identified the shared epitope in 14/14 cases and the presence of an HLA-DRB1*04 molecule in 12/12 cases. HLA-DRB1*0404 was identified in 4/4 cases. HLA-DRB1*0401 was identified in 5/6 cases. One patient oligotyped as HLA-DRB1*0401, but consistently failed to react with the *0401 Mab. DNA sequencing of the second exon of the HLA-DRB1*0401 allele in this patient confirmed a normal HLA-DRB1*0401 genotype.
CONCLUSIONS—FACS analysis of PBMNC stained with Mab recognising the shared epitope and rheumatoid arthritis associated HLA susceptibility molecules provides a rapid, reliable, and more accessible alternative to DNA oligotyping. The apparent discordance between phenotypic and genetic analysis of HLA-DRB1*0401 in one patient, may reflect variability in HLA-DRB1*0401 gene expression or in class II peptide presentation.

     

Inactivation of antithrombin III in synovial fluid from patients with rheumatoid arthritis

OBJECTIVE—To investigate the thrombin inhibitory capacity of antithrombin III in the inflamed human joint.
METHODS—Thrombin inhibitory capacity was measured, using a kinetic spectophotometric method, in matched plasma and synovial fluid samples of patients with rheumatoid arthritis (n=22) and osteoarthritis (n=16), together with normal control plasma samples (n=13). In the same samples, the concentration of antithrombin III was also determined by the method of radial immunodiffusion. The combination of these measurements allowed the calculation of the specific thrombin inhibitory capacity of these samples.
RESULTS—An increased concentration of antithrombin III in rheumatoid compared with osteoarthritic synovial fluid was noted (p<0.05). However, there was a significant depression in the specific activity of antithrombin III in rheumatoid synovial fluid when compared with matched plasma samples (p<0.001) or with osteoarthritic synovial fluid (p<0.05).
CONCLUSION—In rheumatoid synovial fluid the thrombin inhibitory capacity of antithrombin III is disproportionately depressed relative to the concentration of antithrombin III, indicating the inactivation of antithrombin III in the rheumatoid joint.

Keywords: antithrombin III; thrombin; rheumatoid arthritis; synovial fluid     

ICAM-1, E-selectin, and TNF α expression in labial salivary glands of patients with rheumatoid vasculitis

OBJECTIVE—To assess the expression of ICAM1, VCAM1, E-selectin, CD44, and TNF α in labial salivary glands of patients with rheumatoid vasculitis.
METHODS—Labial salivary glands from six patients with rheumatoid vasculitis before and after treatment, six aged matched rheumatoid arthritis patients without clinical evidence of rheumatoid vasculitis, 10 patients with primary Sjögren syndrome, 10 patients with rheumatoid arthritis and proven secondary Sjögren syndrome, and six controls were tested with specific antibodies.
RESULTS—ICAM1, E-selectin, and TNF α were significantly expressed in endothelial cells and perivascular cellular infiltrate only in rheumatoid vasculitis before treatment.
CONCLUSIONS—The expression of ICAM1, E-selectin, and TNF α allows an assessment of the activity of the vasculitic process in rheumatoid vasculitis. Labial salivary gland biopsy findings in patients with rheumatoid arthritis and visceral vasculitis without purpura or neuropathy (that is, mesenteric, coronary, or cerebral vasculitis) would be of interest and are examples where labial salivary gland tissue is more accessible than the affected tissue.

     

Enhanced jejunal production of antibodies to Klebsiella and other Enterobacteria in patients with ankylosing spondylitis and rheumatoid arthritis

OBJECTIVE—To measure gut immunity directly in jejunal fluid in patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA).
METHODS—Antibodies against three different Enterobacterias were measured in jejunal perfusion fluids (collected by a double balloon perfusion device) of 19 patients with AS, 14 patients with RA, and 22 healthy controls using enzyme linked immunosorbent assay.
RESULTS—The AS patients had significantly increased jejunal fluid concentrations of IgM, IgG, and IgA class antibodies against Klebsiella pneumoniae, and IgM and IgA class antibodies against Escherichia coli and Proteus mirabilis compared with healthy controls. When compared with the patients with RA, the AS patients had higher concentrations of IgA and IgG class antibodies only against K pneumoniae. The RA patients had higher IgM class antibody concentrations against all three studied Enterobacterias, when compared with the healthy controls, suggesting an enhanced mucosal immune response in these patients. A three month treatment with sulphasalazine did not decrease enterobacterial antibody concentrations in the 10 patients with AS.
CONCLUSION—There is strong direct evidence for an abnormal mucosal humoral immune response particularly to K pneumoniae in patients with AS.

     

Influence of non-inherited maternal HLA-DR antigens on susceptibility to rheumatoid arthritis

OBJECTIVE—It has recently been observed that non-inherited maternal DR4 antigens (NIMAs) of DR4 negative rheumatoid arthritis (RA) patients were increased compared with non-inherited paternal DR4 antigens (NIPAs). The aim of this study was to determine the prevalence of non-inherited DR4 antigens and DRB1 alleles in parents of RA patients.
METHODS—HLA-DR serology and DRB1 typing was performed in 97 RA patients and their parents. NIMA and NIPA frequencies were compared, stratified according to the presence of DR4 and/or the shared epitope (SE).
RESULTS—In DR4 negative patients, NIMA DR4 was increased compared with NIPA DR4 (OR 3.10, 95% CI 0.76, 12.70). When combined with results from a previous study this increase was significant (OR 3.65, 95% CI 1.29, 10.31). The NIMA effect of SE positive DR4 subtypes in this study (OR 4.73, 95% CI 0.94, 23.8) was stronger than the NIMA effect of combined SE positive DRB1 alleles (OR 2.19 95% CI 0.36, 13.22).
CONCLUSIONS—The association between non-inherited maternal HLA-DR4 alleles and the susceptibility to RA was observed in two independent populations.

Keywords: rheumatoid arthritis; non-inherited maternal DR4 antigens; HLA; genetics     

Linkage of cytokine genes to rheumatoid arthritis. Evidence of genetic heterogeneity

OBJECTIVE—To investigate linkage of candidate disease susceptibility genes to rheumatoid arthritis (RA) in affected sibling pair families stratified for specific clinical features.
METHOD—Two hundred RA affected sibling pair families were genotyped for informative microsatellite markers mapping within or less than 3cM from: INFα, INFγ, INFβ, IL1α, IL1β, IL1R, IL2, IL6, IL5R, IL8R, BCL2, CD40L, NOS3, NRAMP, α₁ anti-trypsin, and α₁ anti-chymotrypsin, using fluorescence based automated technology. Linkage was examined by defining allele sharing sibling pairs. This was assessed by maximum likelihood—inheritance by descent methods.
RESULTS—An increase in allele sharing was seen for IL5R in female sibling pairs (LOD 0.91, p = 0.03), for INFγ in sibling pairs with an affected male (LOD 0.96, p = 0.03) and most significantly for IL2 in sibling pairs where one or both were persistently seronegative (LOD 1.05, p = 0.02).
CONCLUSION—Weak evidence of linkage of RA to IL5R, IFNγ, and IL2 has been detected in clinical subsets of sibling pairs suggesting that RA is a genetically heterogeneous disease.

Keywords: linkage; rheumatoid arthritis; sibling pairs; cytokine genes     

Cigarette smoking and rheumatoid arthritis severity

OBJECTIVES—Cigarette smoking may influence rheumatoid arthritis (RA) disease incidence and may have direct biological effects on the lungs and systemically. This study sought to determine if cigarette smoking is associated with RA disease severity.
METHODS—Clinical evaluations of patients seen in the University of Iowa rheumatology and orthopaedic ambulatory clinics were conducted. A letter of interest was mailed to 1701 patients who were first assigned an ICD-9-CM diagnostic code for RA in one of these clinics. A total of 857 patients expressed interest and were offered a clinical examination and 395 were evaluated over an 18 month period. Of these, 336 satisfied examiner criteria for prevalent RA and were included in the analysis. The disease characteristics and arthritis care utilisation of these patients seemed representative of prevalent cases in the general community. RA disease severity was assessed by radiographic bone erosions (graded as either present/absent and using the Larsen system), rheumatoid factor seropositivity, and presence of subcutaneous rheumatoid nodules.
RESULTS—Pack years of cigarette smoking was significantly associated with rheumatoid factor seropositivity (p = 0.0001), radiographic erosions (p = 0.024), and nodules (p = 0.051). After adjustment for potential confounders, smokers with ≥25 pack years were 3.1 times more likely to be rheumatoid factor positive (95% CI 1.7, 5.6) and 2.4 times more likely to show radiographic erosions (95% CI 1.2, 4.5) than never smokers. Less severe radiographic disease seemed to be more strongly associated with cigarette smoking than more severe disease.
CONCLUSION—Cigarette smoking may adversely influence the severity of RA in a potentially dose dependent fashion.

     

A comparative phenotypical analysis of rheumatoid nodules and rheumatoid synovium with special reference to adhesion molecules and activation markers

OBJECTIVES—(1)To analyse the in situ expression of adhesion molecules in rheumatoid nodules. (2) To compare the endothelial expression of adhesion molecules in synovial tissue and subcutaneous nodules obtained from the same patients. (3) To compare the expression of adhesion molecules and activation markers on T cell lines from nodules and synovium.
METHODS—(1) Immunohistochemical analysis by APAAP technique of E selectin, CD44, ICAM-1, PECAM-1, and VCAM-1 was performed on 10 rheumatoid nodules from seven patients with rheumatoid arthritis (RA); nodules and synovium were simultaneously analysed from three patients. (2) T cell lines were generated from RA nodules (n=7) and synovium (n=7) by interleukin 2 expansion, and subsequently characterised by flow cytometry for surface expression of αEβ7, α4β7, CD44, L selectin, LFA-1a, PECAM-1, and CD30.
RESULTS—(1) In rheumatoid nodules, the palisading layer strongly stains for ICAM-1 and PECAM-1, but less pronounced for CD44. VCAM-1 staining was usually negative. ICAM-1 is upregulated in the vessels surrounding the central zone of fibrinoid necrosis. The immunohistological picture in different nodules derived from the same patient was similar. (2) The endothelial expression of adhesion molecules is comparable in RA nodules and synovium on an individual level, except for E selectin, which is overexpressed in nodule endothelium. (3) T cell lines from nodules and synovium display similar adhesion molecule profiles. However, the expression of CD30, a T cell activation marker linked with Th2 subsets, is higher in nodules compared with synovium.
CONCLUSION—These data support a recirculation hypothesis of T cells between articular and extra-articular manifestations in RA, although the activation state of the T cells in each of these localisations may differ.

Keywords: T cells; adhesion molecules; rheumatoid nodules; rheumatoid synovium     

HLA-DRB1 typing in rheumatoid arthritis: predicting response to specific treatments

OBJECTIVE—To determine the predictive value of shared epitope alleles for response to treatment in patients with rheumatoid arthritis.
METHODS—Patients from our previously published triple DMARD study were tested for the presence of shared epitope alleles (DRB1 *0401,0404/0408, 0405,0101, 1001,and 1402). Patients who were shared epitope positive were then compared with those who were negative to see if there was a differential effect on therapeutic response.
RESULTS—Shared epitope positive patients were much more likely to achieve a 50% response if treated with methotrexate-sulphasalazine-hydroxychloroquine compared with methotrexate alone (94% responders versus 32%, p<0.0001). In contrast shared epitope negative patients did equally well regardless of treatment (88% responders for methotrexate-sulphasalazine-hydroxychloroquine versus 83% for methotrexate). Additionally, a trend toward an inverse relation of the gene dose was seen for response to methotrexate treatment (p=0.05).
CONCLUSIONS—These data suggest that determining shared epitope status may provide clinical information useful in selecting among treatment options.

Keywords: DRB1; rheumatoid arthritis; combination treatment; shared epitope     

Serum concentrations of α tocopherol, β carotene, and retinol preceding the diagnosis of rheumatoid arthritis and systemic lupus erythematosus

OBJECTIVES—Because oxidative damage has been implicated in the pathogenesis of rheumatoid arthritis and systemic lupus erythematosus, this study was designed to see if serum concentrations of α tocopherol, β carotene, and retinol, substances believed to be involved in the prevention or repair of oxidative damage, might be lower among persons who develop rheumatoid arthritis or systemic lupus erythematosus than among those who do not.
METHODS—For this prospective case-control study, persons with rheumatoid arthritis and systemic lupus erythematosus that developed two to 15 years after donating blood for a serum bank in 1974 were designated as cases. For each case, four controls were selected from the serum bank donors, matched for race, sex, and age. Stored serum samples from cases and controls were assayed for α tocopherol, β carotene, and retinol.
RESULTS—Cases of both diseases had lower serum concentrations of α tocopherol, β carotene, and retinol in 1974 than their matched controls. For rheumatoid arthritis, the difference for β carotene (−29%) was statistically significant.
CONCLUSIONS—These findings support those of a previous study that low antioxidant status is a risk factor for rheumatoid arthritis. They suggest a similar association for systemic lupus erythematosus.

     

Serum androgen-anabolic hormones and the risk of rheumatoid arthritis

OBJECTIVE—It has been hypothesised, mainly on the basis of indirect evidence, that low serum concentrations of androgen-anabolic hormones would play a causal part in the aetiology of rheumatoid arthritis (RA).
METHODS—A case-control study was nested with a Finnish cohort of 19 072 adults who had neither arthritis nor a history of it at the baseline examination during 1973-1977. Pre-illness serum specimens for the assay of testosterone and dehydroepiandrosterone sulphate (DHEAS) were available from 116 cases who had developed RA by late 1989. Three controls per each incident case were individually matched for sex, age, and municipality.
RESULTS—The mean testosterone concentration was 1.4 nmol/l in those 84 women who developed RA and 1.4 nmol/l in their controls; the corresponding figures for DHEAS were 5.2 µmol/l and 5.5 µmol/l, respectively. Mean testosterone concentration in the 32 male cases was 26.1 nmol/l and 26.4 nmol/l in their controls; the corresponding figures for DHEAS were 11.2 µmol/l and 10.1 µmol/l, respectively. Analysis by subgroups (rheumatoid factor positive and negative disease, premenopausal and postmenopausal women) and by hormone distributions showed no differences.
CONCLUSION—The findings are not in line with the contention that low concentrations of testosterone and DHEAS play a part in the aetiology of RA.

Keywords: rheumatoid arthritis; epidemiology; testosterone; dehydroepiandrosterone sulphate     

The timing of glucocorticoid administration in rheumatoid arthritis

OBJECTIVE—To test the hypothesis that the timing of prednisolone administration might be critical in determining its effect on the diurnal rheumatoid inflammatory process.
METHODS—26 patients with rheumatoid arthritis were randomly divided into two equal groups and allocated to low doses of prednisolone at either 2.00 am or 7.30 am. Because of the diurnal variation in disease activity in rheumatoid arthritis, assessments of the two study groups were performed at 7.30 am both at the start of the study (day 1) and after four doses of prednisolone (day 5). The study protocol differences in the time period from the last dose of prednisolone to assessment were 5.5 hours in the 2.00 am group and 24 hours in the 7.30 am group.
RESULTS—Administration of low doses of prednisolone (5 or 7.5 mg daily) at 2.00 am had favourable effects on the duration of morning stiffness (P << 0.001), joint pain (P < 0.001), Lansbury index (P << 0.001), Ritchie index (P << 0.001), and morning serum concentrations of IL-6 (P < 0.01). The other study group showed minor but significant effects on morning stiffness (P < 0.05) and circulating concentrations of IL-6 (P < 0.05). Modest and similar improvements of C reactive protein, serum amyloid protein A, and erythrocyte sedimentation rate were seen in both study groups.
CONCLUSIONS—Administration of low doses of glucocorticoids with a rather short biological half life seems to improve acute rheumatoid arthritis symptoms if it precedes the period of circadian flare in inflammatory activity, as defined by enhanced IL-6 synthesis. Further studies are needed to test the relative merits of different timing protocols of glucocorticoid administration in rheumatoid arthritis.

     

Effect of social deprivation on disease severity and outcome in patients with rheumatoid arthritis

OBJECTIVE—Social deprivation is now recognised to have an important impact on morbidity and mortality. This study sought to ascertain the effect of deprivation, if any, on disease severity, functional disability, and outcome in rheumatoid patients in Glasgow.
METHODS—814 patients with rheumatoid arthritis (RA) were assessed for clinical, functional, and laboratory indices of disease activity. Deprivation categories for individual patients were determined using the Carstairs index. Five year follow up is available for 440 patients.
RESULTS—The study population of RA patients live largely in the most deprived areas. Patients from deprived areas have significantly poorer function at outset and at five years as defined by the Health Assessment Questionnaire (HAQ) score. This is not attributable to differences in disease duration in patients from the most deprived regions or compliance with treatment. Furthermore, these patients do not achieve over five years the initial functional level of those living in the most advantaged localities.
CONCLUSION—RA patients from deprived areas have poorer function, which is associated with greater need—medical, social, and paramedical. Strategies and resources for healthcare need to be adjusted according to this variation.