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ID PMID Title PublicationDate abstract
11035123 HLA association with autoimmune disease: a failure to protect? 2000 Oct That certain HLA specificities are associated with predisposition to autoimmune disease does not necessarily imply that self-reactive T cells restricted to particular HLA alleles are eliciting the disease. In the present essay, we argue that HLA can be a major genetic factor in the development of autoimmune diseases without T cells being primarily involved in its initiation or perpetuation. There is now ample evidence that self-reactive, regulatory T cells can protect against pernicious autoimmunity. Hereafter, we propose that extended HLA haplotypes, such as DQ3-DR4, DQ3-DR9, DQ5-DR1 and DQ5-DR10 in the case of rheumatoid arthritis, predispose to impaired T-cell-mediated immune regulation. The haplotypes associated with impaired regulation are the combination of certain class II alleles and a yet unknown 'amplifier'. In this model, products of the HLA class II region are not involved in the presentation of particular organ-specific autoantigens. Therefore, HLA does not predispose to autoimmune disease per se, but rather fails to provide efficient protection.
10556258 Immunohistological analysis of synovial tissue for differential diagnosis in early arthrit 1999 Nov OBJECTIVE: An early diagnosis in patients presenting with arthritis is important to provide information about prognosis and to initiate treatment. The objective of this study was to determine which markers applied in immunohistological analysis of synovial tissue (ST) specimens could be used to differentiate rheumatoid arthritis (RA) from other forms of arthritis. METHODS: Synovial biopsies were obtained by blind needle techniques from 95 patients with early arthritis. After follow-up of at least 2 yr to verify the diagnosis, the patients could be classified as follows: RA (n=36), undifferentiated arthritis (UA; n=21), osteoarthritis (OA; n=17), reactive arthritis (ReA; n=10), ankylosing spondylitis (AS; n=3), psoriatic arthritis (PsA; n=2) and crystal-induced arthritis (CA; n=6). ST sections were analysed by immunohistochemistry using monoclonal antibodies against CD3, CD4, CD8, CD22 (B cells), CD38 (plasma cells), CD68 (macrophages) and CD55 (fibroblast-like synoviocytes). RESULTS: Logistic regression analysis revealed that the higher scores for the numbers of CD38+ plasma cells and CD22+ B cells in RA were the best discriminating markers comparing RA to non-RA patients (CD38: P=0.0001; CD22: P<0.05). Polychotomous regression analysis comparing three diagnostic categories (1: RA; 2: UA, ReA, AS and PsA; 3: OA and CA) also identified the score for the number of CD38+ plasma cells (P<0.0001) as well as the numbers of CD68+ macrophages in the synovial sublining (P=0.05) as discriminating markers. CONCLUSION: The results suggest that immunohistochemical analysis of ST specimens from early arthritis patients can be used to differentiate RA from non-RA patients. The numbers of plasma cells, B cells and macrophages are especially increased in ST of patients with RA. Future studies in early arthritis patients with clinical features which do not allow an immediate confident diagnosis may clarify the role of this test system in differential diagnosis.
10963503 Tumor necrosis factor inactivation in the management of rheumatoid arthritis. 2000 Aug Biologic agents that target molecules and cells involved in chronic inflammation are coming into clinical use for the treatment of rheumatoid arthritis (RA). New agents block the action of cytokines, which play a key role in the pathogenesis of RA. Among the many cytokines involved in RA, tumor necrosis factor (TNF) is believed to be dominant. Two agents for neutralizing TNF are now available. One is a recombinant molecule, etanercept, which is derived from a naturally occurring TNF antagonist, one of the soluble human TNF receptors. The other, infliximab, is a chimeric (human-mouse) monoclonal antibody against human TNF. These biologic agents have been shown to relieve symptoms in patients with refractory RA. If tolerance of these and other anticipated anticytokine agents continues over the long term, treatment for patients with RA will become safer and more effective.
9358757 Tissue cytokine patterns distinguish variants of rheumatoid synovitis. 1997 Nov Rheumatoid arthritis (RA) is a chronic inflammatory disease with primary manifestations in the synovial membrane. Tissue infiltrates are composed of T cells, B cells, and macrophages, but histopathological appearances vary widely and are rarely pathognomonic. Mechanisms underlying the phenotypic heterogeneity of rheumatoid synovitis are not known. To explore whether a correlation exists between the microscopic patterns of rheumatoid synovitis and in situ production of cytokines, tissue samples from 21 consecutive patients with clinically active RA were examined. Based upon the organization of the lymphocyte infiltrate, the synovial biopsies were categorized into three distinct subsets. Ten samples were characterized by diffuse lymphoid infiltrates without further microarrangement. In seven samples, lymphoid follicles with germinal center formation were detected, and in four specimens, granuloma formation was identified. In all specimens, cytokine transcription of interferon (IFN)-gamma, interleukin (IL)-4, IL-1 beta, tumor necrosis factor (TNF)-alpha, IL-10, and transforming growth factor-beta 1 was semiquantified with polymerase chain reaction and liquid phase hybridization. Each of the morphologically defined variants of synovitis displayed a unique cytokine profile. Low-level transcription of IFN-gamma, IL-4, IL-1 beta, and TNF-alpha was typical of diffuse synovitis. In follicular synovitis, IFN-gamma was the dominant cytokine, IL-4 was virtually undetectable, and IL-10 was abundant. Granulomatous synovitis demonstrated high transcription of IFN-gamma, IL-4, IL-1 beta, and TNF-alpha and could be clearly distinguished from the other phenotypes. To investigate whether differences in the synovial lesions were related to host factors, patients were compared for clinical parameters. Diffuse synovitis was seen in most of the patients with seronegative RA, the mildest form of the disease. In contrast, extra-articular spreading of RA with nodule formation was typically associated with granulomatous synovitis. In summary, RA patients display reproducible patterns in the organization and activity of synovial infiltrates. The correlation of microanatomy with tissue cytokine production suggests that several pathomechanisms can modulate the expression of the immune response in the synovial membrane.
11563581 Long-term results of ankle and triple arthrodeses fixed with self-reinforced polylevolacti 2001 Aug Self-reinforcing polylevolactic acid (SR-PLLA) implants have been used in arthrodeses of patients with rheumatoid arthritis. No long-term evaluation has been published so far. Two patients (three ankles) with destruction of the ankle joint and seven with destruction of the subtalar joint received ten arthrodeses. One out of three ankle arthrodeses healed and nonunion developed in two. Five out of seven triple arthrodeses attained bony union. Two patients with malunion of the subtalar and talonavicular joints are free of symptoms and need no reoperation. One superficial wound infection healed by oral antibiotics. In one patient, an ankle arthrodesis was performed 6 years after the triple arthrodesis of the left foot. SR-PLLA implants can be used in triple arthrodesis in rheumatoid arthritic patients with good results comparable to those of other studies. The problems with nonunion of ankle arthrodeses noticed in former studies are also attributable to this fixation method.
11833242 Balance assessment in patients with peripheral arthritis: applicability and reliability of 2001 BACKGROUND AND PURPOSE: Many individuals with peripheral arthritis blame decreased balance as a reason for limiting their physical activity. It is therefore important to assess and improve their balance. The purpose of the present study was to evaluate the applicability and the reliability of some clinical balance assessment methods for people with arthritis and various degrees of disability. METHOD: To examine the applicability and reliability of balance tests, 65, 19 and 22 patients, respectively, with peripheral arthritis participated in sub-studies investigating the applicability, inter-rater reliability and test-retest stability of the following methods: walking on a soft surface, walking backwards, walking in a figure-of-eight, the balance sub-scale of the Index of Muscle Function (IMF), the Timed Up and Go (TUG) test and the Berg balance scale. RESULTS: For patients with moderate disability walking in a figure-of-eight was found to be the most discriminative test, whereas ceiling effects were found for the Berg balance scale. Patients with severe disability were generally able to perform the TUG test and the Berg Balance Scale without ceiling effects. Inter-rater reliability was moderate to high and test-retest stability was satisfactory for all methods assessed. CONCLUSIONS: Applicable and reliable assessment methods of clinical balance were identified for individuals with moderate and severe disability, whereas more discriminative tests need to be developed for those with limited disability.
10612204 [Experiences with the GSB (Geschwend-Scheier-Bähler) III total endoprosthesis in the elbo 1999 Studies on the results with elbow prostheses published in the seventies reported on marked problems such as high loosening rates and instabilities of the joints. However, enormous progresses in elbow replacements have been made in the meantime. Therefore, we analyzed the results of the GSB III-elbow-prostheses that were implanted in our department for 9 years. Between January 1, 1987 and April 1995 at our department 34 total elbow replacements were performed in 32 patients. In this study, we reviewed 25 patients with elbow replacements both clinically and radiologically. The clinical outcome was rated according to the score of INGLIS and PELLICI. The mean follow-up time was 3.7 years. Our follow up examination revealed a total complication rate of 22%. Septic prosthesis loosening with explantation of the prostheses occurred in 3 patients resulting in a prosthesis survival-rate of 88%. However, clinical assessment revealed 80% excellent or good results. While the range of motion could only be improved to a small degree, a marked reduction of the preoperative pain could be achieved. Patients were satisfied with the outcome of the operation in 97%. Although the results of total elbow arthroplasties cannot be compared with those of hip or knee arthroplasties, in selected patients with rheumatoid arthritis and osteoathrosis the use of elbow replacements proved to be a successful procedure with satisfactory results. The implantation of elbow prostheses should mainly be considered when debilitating pain, strongly limited range of motion and instability of the joint are the main problems.
10873963 Decreased T cell precursor frequencies to Epstein-Barr virus glycoprotein Gp110 in periphe 2000 Jul OBJECTIVES: Rheumatoid arthritis (RA) is a chronic joint disease associated with certain HLA-DR alleles expressing the QK/RRAA motif or shared epitope. The Epstein-Barr virus (EBV) has been suspected to be a causative factor for RA. The EBV gp110, a glycoprotein of the replicative cycle that contains a copy of the shared epitope, constitutes an important target in the immune control of EBV replication. This study evaluated the specific T cell response to EBV gp110 in patients with RA expressing or not the shared epitope and examined whether this immune cellular response might be related to disease activity and severity. METHODS: 25 patients with RA were studied and compared with 25 healthy controls. Disease activity was assessed by biochemical markers of inflammation (erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) levels). Disease severity was defined by extra-articular disease (vasculitis, subcutaneous nodules, or other organ disease). The frequencies of peripheral blood T cells specific for EBV gp110 and a control protein (total protein extract from Escherichia coli) were determined by direct limiting dilution analysis without preliminary bulk culture. RESULTS: The gp110 precursor frequencies ranged from 0 to 20 x 10(-6) in patients with RA and controls. The mean gp110 T cell precursor frequency was lower in patients with RA (SD 3.2 (4.4) x 10(-6)) than in healthy controls (4.1 (3.8) x 10(-6)) (p = 0.02). No difference was found for the control protein (p = 0.09). Both shared epitope positive and negative patients with RA responded to gp110, without significant difference. A negative correlation between both ESR and CRP levels and the gp110 T cell response was found (r = -0.71, p<0.0001 and r = -0.42, p = 0.038, respectively). Finally, patients with extra-articular disease displayed the lowest immune cellular response to EBV gp110. CONCLUSION: These results suggest that patients with RA have a decreased T cell response to EBV gp110. Since gp110 is an important protein in the control of EBV replication, this might lead to a poor control of EBV infection, chronic exposure to other EBV antigens, and thus to a chronic inflammatory response in patients with RA.
9328785 TCRB clonotypes are present in CD4+ T cell populations prepared directly from rheumatoid s 1997 Jun The identification of clonal T cells at sites of inflammation is hampered by the large number of polyclonal T cells that nonspecifically accumulate. In this report, we combine the use of T cell sorting with spectratyping of the third complementarity determining region (CDR3) and direct sequence analysis to rapidly screen for and identify clonal expansions of T cells from synovial tissue specimens from patients with rheumatoid arthritis (RA). Initially, we used a polymerase chain reaction specific for the variable region gene of the T cell receptor beta chain (TCRBV) to compare the TCRBV repertoire expressed by CD4+ T cells from the peripheral blood and synovium of five patients with long-standing RA. Each patient had several TCRBV genes that were amplified to a greater degree from synovium. Extensive sequence analysis (n > 170) showed that each patient contained junctional sequences that occurred more than once, implying the presence of T cell clones within the starting CD4+ T cell population. To assess a more straightforward approach to identifying clones, six additional patients were recruited and CD4+, TCRBV2+ synovial T cells were positively selected and analyzed by CDR3 spectratyping. Bands deviating from a normal distribution were excised from the gel and sequenced directly. Clones were detected in half of the patients. These data are consistent with the possibility of an antigen-driven T cell response in RA that remains present in the setting of advanced disease.
11496398 [Long-term experience with renal transplantation in systemic amyloidosis: a case report]. 2001 Jun Renal transplantation was performed on a 39-year old woman with secondary amyloidosis due to rheumatoid arthritis. She remains alive and renal function has been maintained satistfactorily with the exception of proteinuria ten years after transplantation. Recent renal biopsy showed no amyloid recurrence, but the presence of chronic rejection reaction and mild cyclosporin arteriolopathy. Symptoms related to systemic amyloidosis and rheumatoid arthritis improved after transplantation. Renal transplantation is the recommended therapy for the type AA systemic amyloidosis. This is the second report of long-term experience with renal transplantation in systemic amyloidosis in Japan.
9721556 [Tendon rupture of the extensor pollicis longus tendon in rheumatoid arthritis]. 1998 Jun Seven patients with subcutaneus of the extensor pollicis longus tendon (EPL) in rheumatoid arthritis were studied. There were one man and six women. The mean age of the patients was 56. 9 years, with a range of 47 to 83 years. The duration of the disease was from 0.2 to 6 years, its average 3 years. An interval between rupture of the tendon and operation was 9 days to 18 months. Tendon transfers of the extensor indicis proprius tendons were performed in 3 cases, sutures in 2 cases and free tendon graft of the palmaris longus in one case. All cases showed very active tenosynovitis around the EPLs, which were ruptured near Lister's tubercle. The histopathological findings of the ruptured EPL revealed that synovial proliferative tissue with chronic inflammatory cells infiltration were invading into the tenion tissue directly. The synovial granulatins might weaken the tendon and repetitive mechanical stress on the tendon at Lister's tubercle could result in the rupture of EPLs.
9453740 [Arthrodesis of the wrist in inflammatory arthropathy. Effects of fusion of intracarpal jo 1997 We retrospectively analysed 25 wrist arthrodeses performed in 23 patients because of inflammatory joint disease (21 rheumatoid arthritis, 1 case of Still's disease, 1 case of psoriatic arthritis) to assess: 1) the functional result, the position and the fusion rate; 2) the correlation between the radiographic features and the results on pain. The results were evaluated after an average of 56 months (12-121) by an observer not involved in surgery. 8 wrists were pain-free, 12 caused occasional pain, 4 caused frequent pain and 1 wrist was responsible for continuous pain at follow-up. The position of the arthrodesis was acceptable in the sagittal plane (mean extension 4.3 degrees), but with a slight ulnar tilt (mean ulnar tilt 12.8 degrees). Fusion was achieved in all cases after a mean of 8.2 weeks (5-16). All the intracarpal joints had united in only 8 cases, while the scaphotrapezo-trapezoid joint had not united in 17 cases, but fusion was spontaneously obtained in 8 cases. We identified 5 non-unions between lunatum and triquetrum, 5 non-unions between hamatum and capitatum and 3 non-unions between triquetrum and hamatum. Pain at follow-up was related to non-union of triquetro-lunate joints (p = 0.035). Wrist arthrodesis remains appropriate for severe lesions of the rheumatoid wrist in order to restore function and relieve pain.
10734350 Giant rheumatoid synovial cyst of the hip joint: diagnosed by MRI. 1999 Oct Synovial cysts are commonly found in the knee joint. Hip Joint is an infrequent site for formation of synovial cysts. The features of a large, synovial cyst on magnetic resonance imaging, occurring in the hip joint, are described.
11578018 Interleukin-1beta and interleukin-1 receptor antagonist gene polymorphisms in rheumatoid a 2001 The purpose of this study was to evaluate if IL-1beta (IL-1beta promoter and IL-1beta exon 5) and IL-1receptor antagonist (IL-1Ra) gene polymorphisms act as markers of susceptibility to or severity of RA. The study included 104 RA patients and 103 normal controls. No significant difference was observed in the cytokine allelic frequencies of IL-1beta promoter and IL-1beta exon 5 between patients with RA and healthy controls. In addition, there was no significant association in the cytokine carriage rates of I and II allele of IL-1Ra between RA patients and healthy controls. In contrast, the IV allele of IL-1Ra was significantly increased in RA patients with low inflammatory activity (P=0.03). This study indicated that allelic frequency and carriage rate of IL-1beta (IL-1beta promoter and IL-1beta exon 5) and IL-1Ra (I and II allele) do not differ significantly between normal controls and RA patients in Taiwan. However, the carriage rate of IV allele of IL-1Ra was high in the RA patients with low inflammatory activity.
9714359 Sacral insufficiency fractures: an unsuspected cause of low back pain. 1998 Jul We describe 10 cases of sacral fractures diagnosed within the rheumatology department at Southend Hospital over the last 5 yr. All presented with sudden-onset low back pain. The majority were elderly, frail, with chronic inflammatory disease (six with rheumatoid arthritis, one with polymyalgia rheumatica, one with vasculitis) and had received steroids. Diagnosis was delayed by the inability of plain radiographs to show these fractures and was ultimately demonstrated by technetium scintigraphy/computed tomography scan. We feel that this diagnosis should be considered in elderly patients with rheumatoid arthritis or other risk factors for osteoporosis who present with low back pain and sacral tenderness. Further clues may be parasymphyseal tenderness (suggesting associated pubic ramus fracture), elevated alkaline phosphatase and plain radiograph showing pubic ramus fractures or parasymphyseal sclerosis. Patients with this complication generally have a poor prognosis and two of our patients have died. Seven required in-patient stay (mean 20 days; range 14-41). The mortality, morbidity and costs incurred in management may be comparable to those of femoral neck fractures.
10513508 Rheumatologist-patient communication about exercise and physical therapy in the management 1999 Jun OBJECTIVE: Little is known about the features and role of exercise discussions between rheumatologists and patients. The goals of this study were to: 1) describe rheumatologists' and patients' attitudes and beliefs regarding exercise and physical therapy for rheumatoid arthritis (RA); 2) describe frequency and length of exercise discussions; 3) determine the accuracy of recall for exercise discussions; and 4) assess the influence of attitudes regarding exercise on communication about exercise. METHODS: Goals 1-3 were addressed with analysis of baseline questionnaires and audiotaped encounters. The influence of attitudes and beliefs regarding exercise on the frequency and length of exercise discussions was assessed prospectively. Patients and rheumatologists were enrolled from a large tertiary care institution. Clinical encounters were audiotaped, transcribed, coded, and analyzed to identify specific characteristics of the exercise discussions. RESULTS: One hundred thirty-two patients and 25 rheumatologists participated in the study. Rheumatologists and patients discussed exercise in 53% of the encounters. Rheumatologists' beliefs regarding the usefulness of exercise for RA varied, with the least positive beliefs being reported for aerobic exercise. Exercise discussions were more likely to occur if the patient was currently exercising, odds ratio (OR) = 2.4; 95% confidence interval (CI) (1.2-4.9), and when the rheumatologist believed aerobic exercises were useful in managing RA, OR = 1.4; 95% CI (1.1-1.9). Current exercise behavior was associated with patients' positive attitude toward exercise (chi 2 1 = 8.4; P = 0.004) and perceived social support for exercise (chi 2 1 = 4.5; P = 0.04). When rheumatologists initiated exercise discussions, there was nearly twice as much discussion (beta = -8.4; P = 0.001). CONCLUSIONS: Exercise talk was influenced by patients' and rheumatologists' beliefs and attitudes regarding the effectiveness of exercise and physical therapy in managing RA, patient experience with exercise, and by characteristics of the rheumatologist.
11764340 Total hip arthroplasty using two different cementless tapered stems. 2001 Dec The authors report their 15-year experience with primary total hip arthroplasty using collarless, tapered, porous-coated femoral stems (Trilock and Taperloc) in patients with osteoarthritis, rheumatoid arthritis, and in octogenarians. Excellent clinical results were achieved in all groups at latest followup. For the patients with Trilock stems, Taperloc stems, and patients who were octogenarians and patients with rheumatoid arthritis, Charnley pain scores were 5.6, 5.5, 5.7, and 5.7; Charnley function scores were 5.2, 5.1, 4.2, and 5.3; Harris hip scores were 92, 92, 82, and 93 points, respectively. There was a 2% rate of thigh pain with the Trilock, 4% with Taperloc, 4% in octogenarians, and 2% in patients with rheumatoid arthritis. In 96% of the patients in the Trilock group, in 100% of the patients in the Taperloc group, in 100% of the patients who were octogenarians, and in 100% of the patients with rheumatoid arthritis, femoral components showed radiographic evidence of bone ingrowth. There were six (12%) femoral component revisions in the Trilock group (all secondary to nonmodularity of the component at the time of acetabular revision), one femoral component revision in the Taperloc group and no femoral component revisions in the patients who were octogenarians or who had rheumatoid arthritis. Design features (collarless tapered wedge fit, circumferentially porous-coated) virtually ensure bone ingrowth and are thought to be responsible for the excellent clinical results and longevity.
10753945 Wild type and mutant p53 differentially regulate the gene expression of human collagenase- 2000 Apr 14 Matrix metalloproteinases (MMPs) are a family of secreted or transmembrane proteins that can degrade all the proteins of the extracellular matrix and have been implicated in many abnormal physiological conditions including arthritis and cancer metastasis. Recently we have shown for the first time that the human MMP-1 gene is a p53 target gene subject to repression by wild type p53 (Sun, Y., Sun, Y. I., Wenger, L., Rutter, J. L., Brinckerhoff, C. E., and Cheung, H. S. (1999) J. Biol. Chem. 274, 11535-11540). Here, we report that cotransfection of fibroblast-like synoviocytes with p53 expression and hMMP13CAT reporter plasmids revealed that (i) hMMP13, another member of the human MMP family, was down-regulated by wild type p53, whereas all six of the p53 mutants tested lost the wild type p53 repressor activity in fibroblast-like synoviocytes; (ii) this repression of hMMP-13 gene expression by wild type p53 could be reversed by overexpression of p53 mutants p53-143A, p53-248W, p53-273H, and p53-281G; (iii) the dominant effect of p53 mutants over wild type p53 appears to be a promoter- and mutant-specific effect. An intriguing finding was that p53 mutant p53-281G could conversely stimulate the promoter activity of hMMP13 up to 2-4-fold and that it was dominant over wild type p53. Northern analysis confirmed these findings. Although the significance of these findings is currently unknown, they suggest that in addition to the effect of cytokines activation, the gene expression of hMMP13 could be dysregulated during the disease progression of rheumatoid arthritis (or cancer) associated with p53 inactivation. Since hMMP13 is 5-10 times as active as hMMP1 in its ability to digest type II collagen, the dysregulation or up-modulation of MMP13 gene expression due to the inactivation of p53 may contribute to the joint degeneration in rheumatoid arthritis.
11072115 Gene therapy of chronic inflammatory disease. 2000 Nov 15 Immune mediated inflammation that culminates in severe tissue necrosis is the hallmark of diseases that result from an inappropriate response to antigen. The inflammatory response becomes chronic when antigen is non-limiting and persists until the reactive tissue is destroyed, or the environment is changed and exposure to antigen is eliminated. The purpose of this review is to: (1) briefly outline common features of immune related inflammatory diseases such as rheumatoid arthritis (RA), multiple sclerosis (MS), inflammatory bowel disease (IBD), and allergic asthma; (2) provide a rationale for the development of gene based drugs for these indications; and (3) describe current experimental results that support the usefulness of this approach for creating novel DNA based therapeutics.
11361226 Which HAQ is best? A comparison of the HAQ, MHAQ and RA-HAQ, a difficult 8 item HAQ (DHAQ) 2001 May OBJECTIVE: To determine whether the full Health Assessment Questionnaire (HAQ), the shortened modified HAQ (MHAQ), or the new shortened RA-HAQ, developed on the basis of Rasch item response theory (IRT), performs best in terms of distributional characteristics, detection of functional loss, and identification of change in functional status in patients with active rheumatoid arthritis (RA). METHODS: A total of 2,491 clinic patients with RA with active disease from the practices of 519 US rheumatologists were assessed by questionnaire at the time leflunomide was started and at subsequent followup when there had been sufficient time for response. RESULTS: The HAQ scores were almost normally distributed along the 0-3 scale, but 95% of MHAQ and RA-HAQ values were clustered between 0 and 1.5. Normal or minimally abnormal scores (0 or 0.125) were noted in 6.6% of HAQ but in 21-22% of MHAQ/RA-HAQ. Mild functional loss (< or =0.375) was found in 12.7, 39.1, and 36.1% of patients by the HAQ, MHAQ, and RA-HAQ, respectively. This indicates that the MHAQ and RA-HAQ generally fail to identify appropriately the extent of functional loss in RA. The HAQ was significantly better at detecting changes than the MHAQ or RA-HAQ, with relative efficiencies of 1.28 and 1.37 compared to the MHAQ and RA-HAQ, respectively. This results in roughly a 20-26% reduction in sample size requirements. Two additional HAQ were identified that performed better than the HAQ itself, a 20 item HAQ without the use of aids and devices and an 8 item HAQ composed of the most difficult item in each of the 8 HAQ subscale categories. CONCLUSION: The HAQ is better (more efficient) than the MHAQ or RA-HAQ at detecting treatment change, and identifies the extent of functional disability better than the shortened questionnaires. The 3 questionnaires have different means, sensitivities, and distributional properties and cannot be thought of as simply different versions of the same questionnaire. The benefits of the MHAQ and RA-HAQ are that they are short and easier to score. But these benefits come at the price of loss of sensitivity and loss of sensitivity to change. The 20 item HAQ and the difficult 8 item HAQ are intriguing additional choices that are worthy of further study.