The lag time between onset of symptoms and diagnosis of rheumatoid arthritis

OBJECTIVE: Rheumatoid arthritis (RA) may be biologically reversible if treated in the first several months, yet it is unknown whether patients are diagnosed that early. We investigated the lag time between symptom onset and diagnosis of RA in a population with excellent access to rheumatology care. METHODS: Using review of medical records, we evaluated all patients newly diagnosed as having RA from 1987 through 1990, at a health maintenance organization in central Massachusetts. Total lag time from symptom onset to first definite diagnosis was divided into medical encounter lag time (from symptom onset to first medical encounter) and diagnosis lag time (from first medical encounter to diagnosis). RESULTS: The median total lag time was 36 weeks (range 4 weeks to > 10 years). The median medical encounter lag time was 4 weeks (not all patients included in the analysis). The median diagnosis lag time was 18 weeks. Diagnosis lag time was shorter for patients with progressive disease and positive rheumatoid factor on the initial test. Of 25 patients with symmetric arthritis and positive rheumatoid factor, only 5 (20%) were diagnosed within 2 months, and 10 (40%) were diagnosed more than 6 months after symptom onset. CONCLUSION: RA diagnosis is usually delayed for several months after symptoms begin, in large part because of delay in diagnosis by the physician. Thus, the goal of initiating treatment extremely early may be unrealistic for most patients.     

Nitric oxide as S-nitrosoproteins in rheumatoid arthritis

OBJECTIVE: Nitric oxide (NO) is a free radical involved in inflammation and immune reactions. The presence of NO is usually assessed by assaying its degradation products, nitrite and nitrate. NO binds to thiol-containing proteins to form S-nitrosoproteins (S-NP). The aim of this study was to investigate the presence of S-NP, together with nitrite and nitrate, in patients with rheumatoid arthritis (RA). METHODS: Forty patients with RA were studied and compared with 24 patients with osteoarthritis (OA) and 21 control subjects. Fourteen patients were treated with 3 consecutive pulses of methylprednisolone for flares of RA. Nitrite was measured by the Griess reaction, and nitrate by a spectrophotometric assay using nitrate reductase. Spectrofluorometry coupled with the inner filter effect was used for the measurement of S-NP. RESULTS: S-NP was detected in all RA samples, both in serum and synovial fluid (SF). Serum and articular S-NP concentrations were correlated (P < 0.03). In RA, nitrite and S-NP levels were higher in SF than in serum; higher SF levels of the 3 compounds were observed in RA than in OA. S-NP levels in RA patients decreased significantly (P < 0.03) after pulse methylprednisolone treatment, in parallel with the clinical improvement. CONCLUSION: S-NP, a biologically active form of NO, was consistently present in RA, with higher concentrations within the arthritic joint. S-NP assays should be added to nitrite and nitrate assays for the evaluation of NO metabolism. S-NP could be a stable storage form of active NO in RA, and its measurement could be useful in evaluating pharmacologic interventions that modulate NO generation.     

Dose escalation with repeated intrathecal injections of 131I-labelled MAbs for the treatment of central nervous system malignancies

OBJECTIVE: The 1987 American Rheumatism Association (ARA) criteria for rheumatoid arthritis (RA) were developed to discriminate between patients with established RA and those with another rheumatological disorder. Their ability to determine which patients presenting with early synovitis have "true" RA is not known. We evaluated whether the 1987 ARA classification criteria for RA in patients newly presenting with inflammatory polyarthritis (IP) predict persistent, disabling, or erosive arthritis. METHODS: We studied 486 patients with early IP referred to the Norfolk Arthritis Register. The 1987 ARA criteria were applied at baseline, and assessed for their ability to identify (1) patients referred to hospital for whom the diagnosis of RA was recorded by the hospital physician; (2) patients at 3 years with (a) persistent synovitis; (b) moderate or greater disability; and (c) erosions. RESULTS: At baseline, 323 (67%) patients satisfied the ARA criteria in the classification tree format. Exactly 50% of those referred to hospital were given a diagnosis of RA. By 3 years, 76% of the 486 patients had persistent disease, 36% had a Health Assessment Questionnaire score > or = 1, and 40% had erosions. The sensitivity of the criteria was good, ranging from 77 to 87% depending on the outcome. The specificities were poor, and thus the overall discriminatory ability showed little improvement over random probability. CONCLUSION:. Among patients newly presenting with IP, the 1987 ARA criteria for RA had a low ability to discriminate between patients who developed persistent, disabling, or erosive disease and those who did not. Alternative criteria are required for studies investigating early RA.     

Clinician's comment on the management of pain in arthritis.

The arthritic diseases are major sources of pain or disability, although they differ in etiology and treatment approach. For diseases such as RA, inflammation is the predominant mechanism that leads to systemic complaints such as pain as well as local destruction of cartilage and bone. In contrast, OA is primarily a degenerative process and, although inflammation may occur, it differs in quality and extent from that in the systemic inflammatory arthritidies. For both conditions, psychosocial interventions have significant positive benefits, but their application involves careful consideration of a variety of factors. These factors include the following: diagnosis, disease activity, damage, disease stage, patient age and demographics, presence of comorbidities, and availability of alternative or adjunctive approaches. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lactoferrin and lysozyme in arthritic exudates

Lactoferrin (LF) has been assayed by radioimmunoassay in plasma and arthritic exudates and compared with lysozyme (LZ) levels and leukocyte counts. The mean LF concentration in 38 rheumatoid arthritis (RA) exudates was 9.1 mg/l (range 0.02-39.2). In 30 non-RA exudates LF was 3.3 mg/l (range 0.01-14.6). The corresponding LZ levels were 7.4 mg/l (range 2.5-18.5) in RA and 4.7 (range 1.0-12.5) in non-RA fluids. Exudate/plasma ratios were much higher for LF than for LZ and higher in RA than in non-RA exudates, whereas leukocyte counts did not differ. The LF/leukocyte count ratio was significantly higher in RA than in the non-RA group. The data suggest a more prominent release of neutrophilic granulocyte components in RA than in non-RA arthritis.     

Diagnosis and course of early-onset arthritis: results of a special early arthritis clinic compared to routine patient care

OBJECTIVE: Early arthritis patients referred to an Early Arthritis Clinic (EAC) (n = 233) were compared to 241 patients from the routine out-patient clinic with respect to lag time between the onset of symptoms and the visit to the rheumatologist, clinical presentation and the consistency of the diagnosis after 1 yr. RESULTS: The reduction in median lag time for the EAC patients was at least 3 months. An insidious onset of symptoms was found more often in the rheumatoid arthritis (RA) patients in the routine clinic. In 70% of all cases, a diagnosis could be made after 2 weeks and, if the clinical diagnosis was definite RA, this hardly changed during the following year. Early erosions were seen in 25% of RA patients and were associated with a positive rheumatoid factor (OR 2.08, 95% CI 0.95 4.59). CONCLUSION: An early diagnosis of RA at the EAC is possible and reliable; the high frequency of erosions illustrates the need for early treatment.     

Making the most of aid

The synovial fluid (SF) of rheumatoid arthritis (RA) patients contains a mixture of inflammatory mediators. In order to determine whether certain cytokine patterns locally in the joint are specifically related to the chronic inflammation in RA, the concentrations of interleukin (IL)-1alpha, IL-1beta, IL-6, IL-10, transforming growth factor-beta (TGF-beta), tumour necrosis factor-alpha (TNF-alpha) and IgG2b-inducing factor (IgG2bIF) were measured in SF from 22 patients with RA and 22 patients with other types of arthritic lesions. High levels of IL-10, latent and active TGF-beta and the presence of IgG2bIF are significantly correlated with RA when corrected for age. As these factors have the capacity to promote antibody production, they might contribute to the maintenance of local antibody production in RA synovial tissues. All RA-SF samples contained detectable levels of IL-10 and all except one contained IL-1beta, while concentrations in several non-RA-SF samples were below detection limits. IL-6 and TGF-beta were present in all SF samples from both RA and non-RA patients. The presence of IgG2bIF was strongly correlated with high levels of IL-10 and IL-1beta in SF. However, no distinct cytokine profile specific for the chronic inflammation characteristic of RA was found.     

Immunoblotting detection of autoantibodies to human epidermis filaggrin: a new diagnostic test for rheumatoid arthritis

OBJECTIVE: We previously reported that so-called antikeratin antibodies (AKA) and antiperinuclear factor (APF) recognize epitope(s) present on human epidermal filaggrin. In the present study, we developed a new diagnostic test for rheumatoid arthritis (RA) based on detection of antifilaggrin autoantibodies (AFA) by immunoblotting. METHODS: We tested 670 serum samples, including 190 RA. AFA titers were estimated by immunoblotting on filaggrin enriched human epidermis extracts, and AKA titers by indirect immunofluorescence (IIF) on rat esophagus epithelium. Diagnostic values of the tests were compared. RESULTS: Each test resulted in diagnosis of more than 40% of RA samples, with a specificity of 0.99. Although the tests were strongly correlated, their association allowed the diagnosis of more than 60% of RA samples, with the same specificity. CONCLUSION: Immunoblot detection of AFA, a simple and standardizable test, may be an alternative or complement to conventional IIF detection of AKA.     

Diabetes care for Medicare beneficiaries. Attitudes and behaviors of primary care physicians

OBJECTIVE: To obtain information related to primary care physician (PCP) attitudes, knowledge, and practice patterns, as well as perceptions about barriers to care and the use of materials to assist in the delivery of diabetes care for elderly patients in the office setting. RESEARCH DESIGN AND METHODS: A survey was mailed to a random sample (n = 900) of PCPs (internal medicine, family practice, and general practice physicians and endocrinologists) from the states of Alabama, Iowa, and Maryland who met selection criteria and provided diabetes care to > or = 25 Medicare beneficiaries during calendar year 1993. RESULTS: Respondents provided self-reported information regarding diabetes care for elderly patients. PCP respondents (n = 370) considered blood glucose control to be the most important treatment goal. Most respondents (92%) considered acceptable GHb values to be those < 8%. Blood pressure measurement and foot inspections for the detection of ulcers and infection were the most commonly reported routine procedures performed as part of an office visit. Laboratory tests reported to be frequently ordered included GHb, serum creatinine, and proteinuria tests. Patient nonadherence to the treatment regimen was reported to be the most common barrier to care. The majority of respondents reported using two treatment aids in caring for patients with diabetes. CONCLUSIONS: The results of this study provide some evidence that PCP self-reported attitudes, knowledge, and practice patterns in delivering diabetes care for elderly patients in the office setting more closely reflect current recommended practice than reported in previous physician surveys. Opportunities for improvement still exist.     

Health status, somatization, and severity of posttraumatic stress disorder in Vietnam combat veterans with posttraumatic stress disorder

OBJECTIVE: A two-part study was conducted to examine the health status of Vietnam veterans with posttraumatic stress disorder (PTSD). In part 1, veterans with and without PTSD were compared on health behaviors and on self-reported and physician-rated health problems. Consistency of self-report with physician rating for health problems across the two groups was compared. In part 2, the association between health status and PTSD symptom severity, depression, somatization, and health behaviors in PTSD patients was evaluated. METHOD: In part 1, 276 combat veterans (225 with PTSD and 51 without PTSD) provided health status information, and medical records were reviewed. In part 2, 225 PTSD patients completed standardized PTSD severity, somatization, and depression measures. RESULTS: When analyses controlled for age, socioeconomic status, minority status, combat exposure, alcohol use, and pack-year history, veterans with PTSD reported and were rated as having a greater number of health problems than veterans without PTSD. Agreement between self-report and physician ratings for both groups ranged from low to moderate. Level of agreement between patient and physician was similar across groups. In the analysis of veterans with PTSD, somatization and PTSD symptom severity were significantly related to self-report of health problems, whereas only PTSD symptom severity was related to physician-rated health. Pack-year history was significantly related to self-reported health status in both groups. CONCLUSIONS: The presence and severity of PTSD in veterans were associated with greater physical health problems and conditions. Psychological variables (e.g., PTSD status, PTSD severity, somatization) and a behavioral variable (pack-year history) were related to health status.     

Cyclic nucleotide phosphodiesterase 4 subtypes are differentially expressed by primary keratinocytes and human epidermoid cell lines

The monoclonal antibody 5B5 reacts with the beta subunit of proline-4-hydroxylase, the enzyme which catalyses the formation of 4-hydroxyl proline in collagen and other proteins with collagen-like amino acid sequences. This study aims to assess the production and tissue distribution of this enzyme in normal and diseased synovia from patients with various joint diseases, on the basis that it is a putative marker of collagen-producing cells and, therefore, in this context, of fibroblasts. Sections from five normal, 10 osteoarthritic (OA) and 26 rheumatoid arthritic (RA) synovia were labelled with a mouse monoclonal antibody to proline-4-hydroxylase. The enzyme was found to be expressed by a proportion of synovial intimal cells and by fibroblasts in the underlying connective tissue in normal, OA and RA synovia. Labelling was more pronounced in OA and RA cases. The intimal cells labelling positively showed type B synoviocyte morphology, which was confirmed by subsequent double immunolabelling with 5B5 and antibody against type IV collagen using immunocytochemistry and immunoelectron microscopy.     

Deaths caused by venomous snakes in the State of S?o Paulo: evaluation of 43 cases from 1988 to 1993]

PURPOSE: To examine rheumatology subspecialty practice patterns, determinants of referral to rheumatologists, and utilization of aspiration and injection procedures in a population-based sample of elderly individuals. SUBJECTS AND METHODS: We obtained Medicare physician claims for all visits to rheumatologists among beneficiaries aged 65 years and older in Colorado, Massachusetts, and Virginia in 1993, and for visits to all providers by patients with coded diagnoses of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We examined variations in visit frequency and aspiration/injection procedures, and we analyzed determinants of referral to a rheumatologist for RA or SLE. RESULTS: In 1 year, 144,797 visits were made to rheumatologists by 38,443 patients in the three states. An inflammatory disorder was coded in 45% of visits and a noninflammatory disorder in 50%. Half of patients with RA were seen three or fewer times in the year. For RA and SLE, African Americans were about 60% as likely to be seen by a rheumatologist as whites. Utilization of rheumatologist services for rheumatoid arthritis and systemic lupus erythematosus was highest in the state (Virginia) with the lowest per capita supply of rheumatologists. Among patients with bursitis, tendinitis, and osteoarthritis, African-American women were more likely to receive an injection or aspiration procedure than whites or African-American men. CONCLUSION: Elderly patients with rheumatologic disorders were seen by specialists less frequently than recommended by a recent rheumatology manpower survey. African-Americans with RA and SLE had fewer rheumatology visits than whites.     

Elevated levels of hyaluronic acid in the sera of women with fibromyalgia

OBJECTIVE: To evaluate serum levels of hyaluronic acid (HA) in patients with fibromyalgia (FM). METHODS: HA serum levels were evaluated by a radiometric assay in 42 women with FM (ACR criteria), 27 female patients with rheumatoid arthritis (RA) and 36 healthy female controls matched for age. RESULTS: HA serum levels (mean microg/l +/- SEM) were 41 +/- 8.7 in healthy controls; 113 +/- 15.9 in RA: and 420 +/- 26 in FM. CONCLUSION: HA serum levels in women with FM were significantly elevated compared to healthy controls and patients with RA. This observation suggests that FM is associated with a biochemical abnormality and that serum HA could be a laboratory marker for its diagnosis.     

Specificity of antiperinuclear factor for rheumatoid arthritis in rheumatoid factor-positive sera

Although antiperinuclear factor (APF) has the same specificity for rheumatoid arthritis (RA) as rheumatoid factor (RF), there is no evidence that this specificity is maintained in patients with positive RF-agglutination tests. Thus, we evaluated the specificity and usefulness of APF for RA diagnosis, regardless of RF titre. APF was tested (1:100 threshold) on 214 sera sent for RF evaluation over a 9-month period. These sera were previously determined to have latex or Rose-Waaler (RW) titres > or = 12 or 4 IU, respectively, but not necessarily above the threshold values of 100 and 32 IU. The APF test was performed blindly, and physicians were not advised of the results. In the patient population (119 RA and 95 non-RA) APF still demonstrated good specificity (0.82) for RA. As expected, APF proved useful for RA diagnosis in 28/33 (85%) RA cases with an RF level below 1:100 for latex and 1:32 for RW, thus reducing the number of 'seronegative' RA from 33/119 to 5/119. However, it also improved the serological positive predictive value for RA, even in cases when RW results were > or = 32 IU. Indeed, the positive predictive value for RA when both tests were positive was 0.94 (68/72), whereas concordant results (either positive or negative) for both APF and RW tests allowed correct classification (RA or non-RA) in 94% of cases.     

Increase in adhesion molecules on CD4+ cells and CD4+ cell subsets in synovial fluid from patients with rheumatoid arthritis

OBJECTIVE: To elucidate the role of adhesion molecules in the pathogenesis of rheumatoid arthritis (RA). METHODS: We evaluated their expression and that of an activation marker on CD4+ cell populations and CD4+ cell subsets in specimens of peripheral blood (PB) and synovial fluid (SF) obtained from 10 patients with RA and 7 with osteoarthritis (OA). A 2 or 3-color immunofluorescent method was used for analysis. RESULTS: The SF from both groups of patients showed a greater density of adhesion molecules including LFA-1 alpha, LFA-1 beta, CD2, VLA-4 alpha and VLA-5 alpha on CD4+ cells, and a higher percentage of CD4+HLA-DR+ cells compared with their PB. IN PB-CD4+ cell subsets from the arthritic and healthy subjects, the CD4+CD45RO+ cell population showed an increased expression of adhesion molecules compared with CD4+CD45RA+ cell population. The expression of adhesion molecules on circulating CD4+ cell population and CD4+ cell subsets from the patients with RA and OA was comparable to that from healthy subjects. SF from both groups of patients showed a higher percentage of CD4+CD45RO+ cells and a lower percentage of CD4+CD45RA+ cells. In SF-CD4+ cell subsets from patients with RA, the CD4+CD45RO+ cell population had an increased expression of VLA-4 alpha compared to the CD4+CD45RA+ cell population; however, there was no significant difference in other adhesion molecule expression and the percentage of HLA-DR+ cells between the 2 cell subsets. Furthermore, the expression of VLA-4 alpha on the CD4+CD45RO+ cell population in SF from patients with RA was significantly higher than that in matched PB. In CD4+CD45RA+ cell population from both groups of patients, SF showed an enhanced expression of adhesion molecules and an increased percentage of HLA-DR+ cells compared with matched PB. CONCLUSION: Our results suggest that increased expression of adhesion molecules and increased percentage of HLA-DR+ cells on CD4+ cells in SF may be responsible for cellular interactions between these cells and synovial cells or extracellular matrix.     

A cross sectional assessment of health status instruments in patients with rheumatoid arthritis participating in a clinical trial. Minocycline in Rheumatoid Arthritis Trial Group

OBJECTIVE: To (1) validate the Short-Form Health Survey (SF-36) as a generic functional health status measure in patients with rheumatoid arthritis (RA); and (2) assess correlations between the SF-36 and other outcome measures used in the Minocycline in Rheumatoid Arthritis (MIRA) Trial. METHODS: We conducted a cross sectional analysis of the final visit outcome measures from the 48 week, multicenter, placebo controlled, double blind MIRA trial. Multitrait scaling analyses assessed convergent and discriminant validity and internal consistency reliability of the SF-36 in the study patients. Responses to comparable items on the SF-36 and modified Health Assessment Questionnaire (M-HAQ) regarding physical functioning were compared and questions from both instruments were also compared to other RA outcome measures. RESULTS: In patients with RA, the SF-36 had high internal consistency and reliability, high discriminant and high convergent validity. Moderate correlations were observed (r = -0.46 to -0.61, p < 0.01 in each case) for comparable items on the SF-36 and M-HAQ regarding dressing, walking, and bending. Joint tenderness score correlations with items on the M-HAQ and SF-36, and joint tenderness score correlations with the SF-36 scales were higher than for joint swelling scores. Physician and patient global assessments were most highly correlated (r = 0.58 and 0.66; p < 0.01, respectively) with the SF-36 bodily pain item. CONCLUSION: The SF-36 is a valid instrument for this RA population. The SF-36 correlates with the M-HAQ and the physician and patient global assessments. The usefulness of the SF-36 in measuring change in RA clinical trials requires testing in longitudinal studies.     

Information about the diagnosis: a subjective experience of patients with multiple sclerosis and rheumatoid arthritis

INTRODUCTION: It may be difficult to determine the adequate mement, the information content and the most convenient person to inform patients with chronic, incurable disorders with uncertain prognosis as sclerosis multiple (MS). MATERIAL AND METHODS: To gain information on how these aspects had been carried-out and the extent to which patients felt satisfied, we studied 60 definite MS ambulatory patients by means of a semistructured questionnaire attending a hospital-based MS unit. The results were compared with those from 40 patients with rheumatoid arthritis (RA), a chronic disabling disorder of the locomotor system with variable course, examined in a similar way. RESULTS: In the vast majority of patients (81.7 and 82.9%, respectively) in both groups the diagnosis had been delivered by a specialist, a point on which most patients agreed upon as convenient. However, most MS patients (78.4%) and nearly all of those with RA (97.6%) should have desired to receive information on their diagnosis as soon as this might had been firmly established. Though more than half the patients (61.7 of MS and 56.1% of RA) admitted to have developed depressive symptoms following information on their diagnosis, a majority expressed their desire to have been informed early about 'all the truth' regarding their prognosis (78.4 and 87.8%, respectively). CONCLUSIONS: Though data from this study should be taken with caution when applied to MS patients shortly after experiencing their first symptoms, and it is therefore unwise to give rigid rules, the vast majority of MS patients express the desire to receive early, accurate, and individualized information on their diagnosis provided by a competent specialist.     

Memory complaint and memory performance in the depressed elderly.

Compared depressed and nondepressed elderly Ss recruited in the context of a large epidemiological study of health on measures of self-reported memory disturbance and an objective index of memory performance (free recall). Three groups were studied: (a) 26 Ss (mean age 71.56 yrs) meeting Research Diagnostic Criteria (RDC) for major depression, (b) 25 Ss (mean age 72.16 yrs) with high levels of self-reported depressive symptoms who did not meet RDC for major depression, and (c) 26 Ss (mean age 71.81 yrs) with low levels of self-reported depressive symptoms. Ss with high depression symptom levels reported significantly higher levels of memory complaint than did Ss with low symptom levels, but there were no differences in self-reported memory disturbance as a function of depression diagnosis. There were no significant differences between groups on the free-recall measure, either as a function of symptom level or diagnosis. It is argued that symptom severity rather than diagnosis of depression is important in determining impairment in depressed elderly people. (34 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Diagnosis and therapy of chronic polyarthritis

Rheumatoid arthritis (RA) is the most frequent inflammatory joint disease, and it affects about 1% of the population. The onset of arthritis is rarely acute; it is subacute and usually progresses slowly. The clinical picture of RA is variable: mild to very aggressive and destructive courses, sometimes accompanied by organ involvement, leading to severe functional impairment and early disability can be observed. RA is diagnosed according to the ACR criteria published in 1958 and modified in 1988. The appearance of a palpable joint swelling or effusion is obligatory for the clinical diagnosis of arthritis. In RA, typically involvement of the joint of the hands and feet can be seen. Laboratory parameters play an important role as both diagnostic and prognostic tools. Besides clinical features and laboratory parameters, imaging techniques provide another cornerstone in the diagnosis of RA. Until now plain X-rays, which primarily visualize osseous changes, are the most important technique in daily practice, whereas magnetic resonance imaging and ultrasound may provide information about soft tissue changes in an earlier stage of disease. The main differential diagnoses of RA to be considered are the seronegative spondylarthropathies (psoriatic arthritis, arthritides accompanying inflammatory bowel diseases, Reiter's syndrome, and spondylitis ankylosans with peripheral arthritis), Parvovirus-induced arthritis, crystal-induced arthritides and septic arthritis. Early diagnosis and therapeutic intervention seem to be of great prognostic importance. In several independently performed investigations a higher mortality was found in RA patients than in the normal population. Drug therapy of RA consists of nonsteroidal antirheumatic drugs (NSAIDs), corticosteroids and disease-modifying drugs (DMARDs). When the functional and radiological parameters were assessed, the DMARDs were found to have a disease modifying and in rare cases a remission-inducing property. Moreover, tolerance these to drugs is limited. Newer therapeutic trials have employed substances like Tenidap, Leflunomid, bacterial extracts, antibiotics and biological subcomes (e.g., monoclonal antibodies against cytokines, fusion proteins for soluble cytokinereceptors). Some promising results of these investigations need confirmation in larger patient populations, but some new perspectives for a more efficacious treatment of RA can be expected.     

Nonsteroidal anti-inflammatory drug-associated upper gastrointestinal lesions in rheumatoid arthritis patients. Relationships to gastric histology, Helicobacter pylori infection, and other risk factors for peptic ulcer

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are risk factors for peptic ulcer in rheumatoid arthritis (RA) patients, but the contribution of reactive gastritis, concomitant Helicobacter pylori infection, or RA activity to NSAID ulcer pathogenesis is unknown. METHODS: Ninety-six RA patients taking NSAIDs and dyspeptic sex- and age-matched control patients without NSAID use or an RA diagnosis were enrolled in the study. RESULTS: Gastric ulcer (GU) was detected in 29 (30%) RA patients and 3 control patients (P < 0.001). Sixteen RA patients and no control patient had an H. pylori-negative GU. The GUs of the RA patients were mainly located in the prepyloric region (28%) and antrum (62%). Nine of the 29 RA patients (31%) with GU had more than 1 ulcer. Erosive gastropathy was detected in 34 (71% H. pylori-negative) RA patients and in 13 (62% H. pylori-negative) control subjects (P < 0.001). Chronic gastritis was observed in 65 RA patients (48% H. pylori-negative) and in 58 control subjects (43% H. pylori-negative) (NS). whereas reactive gastritis was found in only 2 RA patients and in none of the controls. Corticosteroid use was the only independent risk factor for GU: odds ratio was 6.8 (95% confidence interval, 1.3-36.0). The prevalences of duodenal ulcer or esophagitis were not increased in RA patients. CONCLUSIONS: RA patients using NSAIDs continuously are at a greatly increased risk of developing both H. pylori-negative and -positive GUs, and corticosteroid use is an independent risk factor for ulcer development. Most RA patients have chronic gastritis, whereas reactive gastritis is rarely associated with continuous NSAID use in RA patients.