[Show abstract][Hide abstract] ABSTRACT: Objective:
Existing criteria for the classification of gout have suboptimal sensitivity and/or specificity, and were developed at a time when advanced imaging was not available. The current effort was undertaken to develop new classification criteria for gout.
An international group of investigators, supported by the American College of Rheumatology and the European League Against Rheumatism, conducted a systematic review of the literature on advanced imaging of gout, a diagnostic study in which the presence of monosodium urate monohydrate (MSU) crystals in synovial fluid or tophus was the gold standard, a ranking exercise of paper patient cases, and a multicriterion decision analysis exercise. These data formed the basis for developing the classification criteria, which were tested in an independent data set.
The entry criterion for the new classification criteria requires the occurrence of at least 1 episode of peripheral joint or bursal swelling, pain, or tenderness. The presence of MSU crystals in a symptomatic joint/bursa (i.e., synovial fluid) or in a tophus is a sufficient criterion for classification of the subject as having gout, and does not require further scoring. The domains of the new classification criteria include clinical (pattern of joint/bursa involvement, characteristics and time course of symptomatic episodes), laboratory (serum urate, MSU-negative synovial fluid aspirate), and imaging (double-contour sign on ultrasound or urate on dual-energy computed tomography, radiographic gout-related erosion). The sensitivity and specificity of the criteria are high (92% and 89%, respectively).
The new classification criteria, developed using a data-driven and decision analytic approach, have excellent performance characteristics and incorporate current state-of-the-art evidence regarding gout.
Arthritis and Rheumatology 09/2015; 67(10):2557-2568. DOI:10.1002/art.39254
[Show abstract][Hide abstract] ABSTRACT: Background Arthrocentesis is a common procedure in rheumatology clinical practice, usually to obtain synovial fluid for diagnostic purposes or as a therapeutic procedure for glucocorticoid intra-articular injection. There is a generally held belief amongst rheumatologists that needle arthrocentesis is a safe and well-tolerated procedure. Previous reports of the safety of needle arthrocentesis have been in the context of glucocorticoid injection (1). The safety of diagnostic arthrocentesis has not been previously studied systematically.
Objectives To determine the frequency of adverse events of diagnostic arthrocentesis in patients suspected to have gout.
Methods Consecutive patients with recent joint swelling or possible tophus underwent arthrocentesis or nodule tissue aspiration as part of a cross-sectional diagnostic study for gout. All patients were evaluated at 6 weeks by telephone or in the clinic to determine any adverse events (AE) following the arthrocentesis. The 95% confidence intervals for the percentage frequency of AE were obtained by bootstrapping.
Results Arthrocentesis was performed in 910 patients and 887 of these patients (97.5%) were evaluated for AE. Any adverse event was observed in 12 participants (1.4%, 95%CI 0.6 to 2.1). The commonest AE was pain (5 events), nearly all of which were rated as mild. Other non-serious AE reported were bruising (2 events), and joint swelling (4 events). There was 1 case (0.1%, 95% CI 0 to 0.34) of septic arthritis subsequent to the arthrocentesis who required hospitalization and antibiotics.
Conclusions Diagnostic arthrocentesis is safe and associated with a very low frequency of adverse events, which are generally mild. However, septic arthritis rarely occurs with an estimated (bootstrapped 95% CI) frequency of between 0 and 3.4 per 1000 patient-procedures.
Acknowledgements This study was supported by the American College of Rheumatology, European League against Rheumatism, Arthritis New Zealand, Association Rhumatisme et Travail, and Asociaciόn de Reumatόlogos del Hospital de Cruces.
Disclosure of Interest None declared
Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):1266.3-1267. DOI:10.1136/annrheumdis-2015-eular.2179 · 10.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the risk of hepatitis B virus (HBV) reactivation in rheumatoid arthritis (RA) patients with HBV carrier state during treatment of disease-modifying antirheumatic drugs (DMARDs) and the use of antiviral prophylaxis in real-world clinical practice.
Consecutive RA patients with HBV carrier state were included. Clinical data including liver evaluation, HBV infection evaluation and the use of antiviral prophylaxis were recorded.
Fifty-three RA patients with HBV carrier state were screened and 36 patients were qualified for analysis. Thirty-six percentage of patients developed HBV reactivation and 17% developed HBV hepatitis together with reactivation, one of which developed decompensate cirrhosis. Only 50% of patients accepted lamivudine although all patients were recommended antiviral prophylaxis with entecavir or tenofovir and only 31% continued during DMARDs therapy. Seventy-one percentage of patients who discontinued antiviral prophylaxis developed HBV reactivation 3 ~ 21 months after discontinuation. Logistic regression analyses showed discontinuation of antiviral prophylaxis (OR: 66, p = 0.027), leflunomide (OR: 64, p = 0.011) and past history of hepatitis (OR: 56, p = 0.013) were risk factors of HBV reactivation. Past history of hepatitis (OR: 10, p = 0.021) was also risk factor of HBV hepatitis together with reactivation.
Our results suggest poor patient acceptance and discontinuation of antiviral prophylaxis should not be ignored for Chinese RA patients with HBV carrier state in real-world clinical practice. Discontinuation of antiviral prophylaxis, past history of hepatitis and LEF might increase risk of HBV reactivation for RA patients with HBV carrier state during DMARDs therapy.
[Show abstract][Hide abstract] ABSTRACT: Objectives To compare the sensitivity and specificity of different classification criteria for gout in early and established disease.
Methods This was a cross-sectional study of consecutive rheumatology clinic patients with joint swelling in which gout was defined by presence or absence of monosodium urate crystals as observed by a certified examiner at presentation. Early disease was defined as patient-reported onset of symptoms of 2 years or less.
Results Data from 983 patients were collected and gout was present in 509 (52%). Early disease was present in 144 gout cases and 228 non-cases. Sensitivity across criteria was better in established disease (95.3% vs 84.1%, p<0.001) and specificity was better in early disease (79.9% vs 52.5%, p<0.001). The overall best performing clinical criteria were the Rome criteria with sensitivity/specificity in early and established disease of 60.3%/84.4% and 86.4%/63.6%. Criteria not requiring synovial fluid analysis had sensitivity and specificity of less than 80% in early and established disease.
Conclusions Existing classification criteria for gout have sensitivity of over 80% in early and established disease but currently available criteria that do not require synovial fluid analysis have inadequate specificity especially later in the disease. Classification criteria for gout with better specificity are required, although the findings should be cautiously applied to non-rheumatology clinic populations.
Annals of the rheumatic diseases 10/2014; DOI:10.1136/annrheumdis-2014-206364 · 10.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Identifying persons with early rheumatoid arthritis (RA) is a major challenge. The role of the Internet in making decisions about seeking care has not been studied. We developed a method for early diagnosis and referral using the Arthritis Foundation's website. A person with less than 3 months of joint pain symptom who has not yet sought medical attention was screened. Prescreened persons are linked to a self-scoring questionnaire and get a "likelihood" of RA statement. If "likely," the person is offered a free evaluation and biomarker testing performed by Quest Diagnostics. The system available only to Massachusetts's residents yielded a small steady flow of screen-positive individuals. Over 21 months, 43,244 persons took the Arthritis Foundation website prescreening questionnaire; 196 were from Massachusetts and 60 took the self-scoring algorithm. Of the 48 who screened positive, 29 set up an appointment for a free evaluation, but six never came in. Twenty-four subjects were evaluated and diagnosed independently by three rheumatologists. One met the 1987 American College of Rheumatology (ACR) criteria for RA and two met the 2010 ACR/EULAR RA criteria. The 24 examined individuals were contacted at a minimum of 1 year and asked to redo the case-finding questionnaire and asked about their health resource utilization during the interval. Seventeen of the 24 subjects responded, and 10 had seen a health professional. Three of the 17 had a diagnosis of RA; all were on at least methotrexate. Internet case finding was useful in identifying new potential RA cases. The system's performance characteristics are theoretically limited only by the number of study sites available. However, the major barrier may be that seeing a health professional is not a priority for many individuals with early symptoms.
[Show abstract][Hide abstract] ABSTRACT: Objective:
American College of Rheumatology and European League Against Rheumatism guidelines recommend colchicine to prevent gout flares in patients initiating and increasing uric acid–lowering therapy until serum uric acid is maintained at ≤6 mg/dl. We aimed to evaluate how well colchicine prescribing practices adhere to these guidelines and to examine factors associated with improved prescribing.
Electronic medical records were reviewed for 126 patients with active colchicine prescriptions for prophylaxis of gout flares. Colchicine prescribing was defined as inappropriate if 1) no concurrent urate-lowering therapy was prescribed, 2) uric acid was not at goal and urate-lowering therapy had not been increased in the past 3 months, or 3) uric acid goals were met for >1 year and flares had resolved in the absence of tophi.
Colchicine use was considered inappropriate in 93 patients (73.8%). Thirty-four were prescribed no urate-lowering therapy, 50 were above the uric acid goal without urate-lowering therapy increase in the prior 3 months, and 9 were at the uric acid goal for >1 year without flares or tophi. Patients appropriately prescribed colchicine were younger and were more likely to have been seen by a rheumatologist. Allopurinol dose and allergy, uric acid level, and renal function were similar in the 2 groups.
We found a high prevalence of what we considered inappropriate prophylactic colchicine use, driven largely by failure to prescribe concurrent urate-lowering therapies or adequately increase these medications. Rheumatology consultation was associated with improved colchicine prescribing.
[Show abstract][Hide abstract] ABSTRACT: Objective:
To evaluate the safety and efficacy of once-weekly subcutaneous rilonacept 160 mg for prevention of gout flares in patients initiating or continuing urate-lowering therapy (ULT).
This phase III study was conducted in the United States, South Africa, Europe, and Asia. Adults (n = 1315, 18-80 yrs) with gout, who were initiating or continuing ULT, were randomized to treatment with weekly subcutaneous injections of rilonacept 160 mg or placebo for 16 weeks followed by a 4-week safety followup. The primary endpoint was safety, assessed by adverse events (AE) and laboratory values. Efficacy was a secondary endpoint.
Demographic and clinical characteristics were similar between treatments; predominantly male (87.8%), mean age 52.7 ± 11.3 years. Patients with ≥ 1 AE were 66.6% with rilonacept versus 59.1% placebo, with slightly more AE-related withdrawals with rilonacept (4.7% vs 3.0%) because of the greater incidence of injection site reactions (15.2% rilonacept, 3.3% placebo). Serious AE were similar in both groups, as were serious infections (0.9% placebo, 0.5% rilonacept); no tuberculosis or opportunistic infections occurred. Most common AE were headache, arthralgia, injection site erythema, accidental overdose, and pain in extremity. Of the 6 deaths, only 1 in the placebo group was considered treatment-related. At Week 16, rilonacept resulted in 70.3% fewer gout flares per patient (p < 0.0001), fewer patients with ≥ 1 and ≥ 2 gout flares (p < 0.0001), and 64.9% fewer gout flare days (p < 0.0001) relative to placebo.
Weekly subcutaneous administration of rilonacept 160 mg showed no new safety signals. The safety profile was consistent with previous studies. Rilonacept also significantly reduced the risk of gout flares. Clinicaltrials.gov identifier NCT00856206; EudraCT No. 2008-007784-16.
The Journal of Rheumatology 07/2014; 41(8). DOI:10.3899/jrheum.131226 · 3.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background There is a medical need for effective alternate treatments for acute gouty arthritis (GA) patients (pts) with frequent GA attacks in whom NSAIDs and/or colchicine are contraindicated, not tolerated or ineffective.1 Canakinumab (CAN), a selective, fully human anti-interleukin-1β antibody, is the only biologic approved in EU for the treatment of pts with difficult-to-treat GA. Here, we present the results of pooled analyses from long-term extensions of two phase III studies with a cumulative duration of 18 months.
Objectives To evaluate the long term safety and efficacy (time to first attack) of CAN (subcutaneous) compared with triamcinolone acetonide (TA [intramuscular]) in GA pts with frequent attacks.
Methods GA pts who completed two multicentre randomised phase III core and respective randomised extensions (E1) of the same design, were rolled over into open-label extension studies (E2). All pts (irrespective of assigned treatment in core and E1) were treated with CAN 150 mg on demand upon new attack in E2. Safety was measured as exposure-adjusted incidence rate (IR) of adverse events (AEs). Time to first new attack was analysed using the Cox proportional hazard regression model.
Results Of 456 pts randomised in core studies, 335 entered the two E1 extensions. Of these 335 pts, 272 entered and 249 completed the E2 studies. Baseline characteristics of both treatment groups were similar. Mean number of doses per pt over cumulative duration of 18 months in pts randomized to CAN was 2.08. The overall IR of AEs in pts randomised to CAN was 330.8/100 pt-years (pyr). Incidence of AEs following CAN re-treatment was lower than the incidence prior to re-treatment (286.8/100 vs 385.0/100 pyr). A slightly lower IR of AEs was reported by pts who switched from TA to CAN (264.7/100 vs 229.9/100 pyr). Upper respiratory infections (7.8/100 pyr) were the most commonly reported infections with CAN while nasopharyngitis (6.6/100 pyr) was the most common infection with TA. Observed IR for serious AEs for CAN was 20.1/100 pyr and 16.4/100 pyr for TA. Over the cumulative duration of 18 months, 4 deaths, not suspected to be related to study drug, were observed: 1 intracranial haemorrhage (pt not re-treated with CAN); 1 pneumonia (pt re-treated with CAN), 1 sudden cardiovascular death and 1 pneumococcal sepsis (TA pts never receiving CAN). Over the cumulative duration of 18 months, the median time to first new attack was 242 days for CAN (inter-quartile range (IQR)=130–337, n=225) compared with 131 days for TA (IQR=49–376, n=229; p=0.0012, hazard ratio=0.68).
Conclusions The results of this pooled analyses support the long-term safety and efficacy of canakinumab treatment in pts with frequent GA attacks. The safety profile was consistent with the one observed in the core and E1 studies. Canakinumab significantly delayed the time to first new attack by more than 100 days, compared with TA, a long acting corticosteroid.
Disclosure of Interest R. Alten: None declared, N. Schlesinger Grant/research support: Novartis, Consultant for: Novartis, SOBI; Advisory boards: Novartis, Takeda, Savient, Enzyme Rx, URL Pharma, SOBI, Speakers bureau: Novartis, Takeda, Savient, A. So Consultant for: Received honoraria for being member of the canakinumab advisory board, H. R. Schumacher Consultant for: Novartis, Regeneron, Abbvie, M. Bloch Grant/research support: payments to my institue for the conduct of clinical research, U. Machein Employee of: Novartis, D. Richard Shareholder of: Novartis, Employee of: Novartis, K. Lheritier Shareholder of: Novartis, Employee of: Novartis, T. Bardin Consultant for: Novartis, SOBI, Speakers bureau: Novartis
Annals of the Rheumatic Diseases 06/2014; 73(Suppl 2):785-785. DOI:10.1136/annrheumdis-2014-eular.1807 · 10.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background Although there has been major progress in gout imaging, no gout classification criteria currently include advanced imaging techniques.
Objective To examine the usefulness of imaging modalities in the classification of gout when compared to monosodium urate (MSU) crystal confirmation as the gold standard, in order to inform development of new gout classification criteria.
Methods We systematically reviewed the published literature concerning the diagnostic performance of plain film radiography, MRI, ultrasound (US), conventional CT and dual energy CT (DECT). Only studies with MSU crystal confirmation as the gold standard were included. When more than one study examined the same imaging feature, the data were pooled and summary test characteristics were calculated.
Results 11 studies (9 manuscripts and 2 meeting abstracts) satisfied the inclusion criteria. All were set in secondary care, with mean gout disease duration of at least 7 years. Three features were examined in more than one study: the double contour sign (DCS) on US, tophus on US, and MSU crystal deposition on DECT. The pooled (95% CI) sensitivity and specificity of US DCS were 0.83 (0.72 to 0.91) and 0.76 (0.68 to 0.83), respectively; of US tophus, were 0.65 (0.34 to 0.87) and 0.80 (0.38 to 0.96), respectively; and of DECT, were 0.87 (0.79 to 0.93) and 0.84 (0.75 to 0.90), respectively.
Conclusions US and DECT show promise for gout classification but the few studies to date have mostly been in patients with longstanding, established disease. The contribution of imaging over clinical features for gout classification criteria requires further examination.
Annals of the Rheumatic Diseases 06/2014; 73(Suppl 2). DOI:10.1136/annrheumdis-2014-205431 · 10.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background The gold standard for diagnosing crystal arthritis is aspiration of synovial fluid and subsequent polarized microscopy on the punctured fluid. However, various studies have shown a lack of consistency in results of crystal analysis among different observers. We have proposed to certify dedicated colleagues by confirming skill of crystal identification and to increase our insight in general about expertise with the identification of crystals in synovial fluid. By obtaining these data concerning current microscopical performance, we aim to find areas of crystal recognition which are open for further improvement.
Objectives The primary objective is to confirm the expertise of physicians with the identification of crystals in synovial fluid/tissue. An online test prepared for the Study of Updated Gout criteria: acr/eulaR (SugaR) emphasizes the recognition of monosodium urate (MSU) crystals, plus the identification of a predefined set as non-MSU crystals; this online test also includes identification of other crystals, such as calcium pyrophosphate dihydrate (CPP), cholesterol, oxalate and apatite. Our secondary objective is to find out whether observer factors are related to microscopical performance.
Methods Diagnosticians from different countries, who are working in the rheumatology field and performing microscopic analysis were asked to participate to qualify for entrance to the SugaR Study. The first part of the test included a number of questions concerning personal/professional data. The second part contained 30 slides with images of crystals and other look-a-likes from synovial fluid: crystals shown were 8 MSU, 5 CPP, 4 cholesterol, 2 oxalate and 1 apatite. The test also included slides with potentially confusing look-a-likes.
Results Up to January 1st 2013, 56 persons performed the online test; 46% (n=43) of them identified each one of the 20 crystals correctly. With respect to MSU crystals 77% identified 8 MSU crystals, 91% identified at least 7 out of 8 MSU crystals; 68% of all attendees identified 5 CPP crystals and 91% at least 4 out of 5 CPP crystals. See table.
Ability to recognize crystals when they are there (%)
Conclusions Almost half of the attendees performed well at identifying a diversity of crystals: MSU crystals appeared easier to identify than CPP. The objective performance regarding crystal identification can be improved in all. There seems to be no clear relationship between confidence of expertise and actual expertise.
Disclosure of Interest None Declared
Annals of the Rheumatic Diseases 01/2014; 72(Suppl 3):A981-A982. DOI:10.1136/annrheumdis-2013-eular.2951 · 10.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background Our previous survey found that gout patients in south China have poor knowledge on urate-lowering therapy (ULT). Physicians are the main provider of disease knowledge for patients but few reports on physician knowledge about gout have been published.
Objectives To investigate gout knowledge level of physicians in South China.
Methods A multi-center survey in Guang Dong Province of 185 physicians from groups considered most likely to be consulted by gout patients conducted with a questionnaire adopted from Zhang et al . Such physicians included residents and fellows who in this system often see patients with little supervision. The questionnaire was composed of 10 questions concerning essential areas of knowledge of gout. Physicians were considered as well aware of gout when they correctly answered 8 or more questions.
Results (1) 184 participants completed ≥8 questions. Among them, 17.9% were rheumatologists, 82.1% were non-rheumatologists including internal medicine physicians (38.6%), orthopedists (23.4%), traditional Chinese medical physicians (4.3%) and other specialists (15.8%). 86.7% were interested in gout. The mean number of correct answers of all participants was 8.3±1.4, with median value 9 (7-9). The mean of correct answers from rheumatologists was significantly higher than that of the non-rheumatologist group (9.6±0.53 vs 8. 0±1.4, P<0.05). (2) Both groups were well informed (correct answer rate of all participants >85%) about the cause of gout, crystals causing attacks, the characteristics of acute attacks, the most effective drugs for acute attacks and common complications of gout. For the ULT related knowledge, only 75.0% of non-rheumatologists knew that allopurinol is a kind of urate-lowering drugs, 55.3% knew optimal SUA target level and 42.8% knew that urate-lowering drugs should be taken life-long. 84.8% of rheumatologists and 74.8% of non-rheumatologists knew how to prevent attacks induced by ULT. The calculated adequate awareness rate of all participants was 73.4% and the awareness rate of the rheumatologist group was significantly higher that that of the non-rheumatologist group (100.0% vs 67.5%, P<0.05). The awareness rate of participants who were interested in gout was significantly higher than those not (76.9% VS 45.8%, P<0.05). Logistic regression showed that the number of consulted gout patients per year significantly predicated the non-rheumatologists’ awareness of gout-related knowledge.
Conclusions Chinese rheumatologists and trainees were generally very familiar with gout related knowledge. However, the non-rheumatologist had relatively poor knowledge on ULT. The further CME for Chinese non-rheumatologist should emphasize the use of urate-lowering drugs, treatment duration, optimal target SUA level and prevention of attacks on initiating ULT.
Disclosure of Interest None Declared
Annals of the Rheumatic Diseases 01/2014; 71(Suppl 3):308-309. DOI:10.1136/annrheumdis-2012-eular.2419 · 10.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the extent to which instruments that measure core outcome domains in acute gout fulfill the Outcome Measures in Rheumatology (OMERACT) filter requirements of truth, discrimination, and feasibility.
Patient-level data from 4 randomized controlled trials of agents designed to treat acute gout and 1 observational study of acute gout were analyzed. For each available measure, construct validity, test-retest reliability, within-group change using effect size, between-group change using the Kruskall-Wallis statistic, and repeated measures generalized estimating equations were assessed. Floor and ceiling effects were also assessed and minimal clinically important difference was estimated. These analyses were presented to participants at OMERACT 11 to help inform voting for possible endorsement.
There was evidence for construct validity and discriminative ability for 3 measures of pain [0 to 4 Likert, 0 to 10 numeric rating scale (NRS), 0 to 100 mm visual analog scale (VAS)]. Likewise, there appears to be sufficient evidence for a 4-point Likert scale to possess construct validity and discriminative ability for physician assessment of joint swelling and joint tenderness. There was some evidence for construct validity and within-group discriminative ability for the Health Assessment Questionnaire as a measure of activity limitations, but not for discrimination between groups allocated to different treatment.
There is sufficient evidence to support measures of pain (using Likert, NRS, or VAS), joint tenderness, and swelling (using Likert scale) as fulfilling the requirements of the OMERACT filter. Further research on a measure of activity limitations in acute gout clinical trials is required.
The Journal of Rheumatology 01/2014; 41(3). DOI:10.3899/jrheum.131245 · 3.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the extent to which participants at the Outcome Measures in Rheumatology (OMERACT) 11 meeting agree that instruments used in clinical trials to measure OMERACT core outcome domains in acute gout fulfill OMERACT filter requirements of truth, discrimination, and feasibility; and where future research efforts need to be directed.
Results of a systematic literature review and analysis of individual-level data from recent clinical studies of acute gout were presented to OMERACT participants. The information was discussed in breakout groups, and opinion was defined by subsequent voting in a plenary session. Endorsement was defined as at least 70% of participants voting in agreement with the proposition (where the denominator excluded those participants who did not vote or who voted "don't know").
The following measures were endorsed for use in clinical trials of acute gout: (1) 5-point Likert scale and/or visual analog scale (0 to 100 mm) to measure pain; (2) 4-point Likert scale for joint swelling; (3) 4-point Likert scale for joint tenderness; and (4) 5-point Likert scale for patient global assessment of response to treatment. Measures for the activity limitations domain were not endorsed.
Measures of pain, joint swelling, joint tenderness, and patient global assessment in acute gout were endorsed at OMERACT 11. These measures should now be used in clinical trials of acute gout.
The Journal of Rheumatology 12/2013; 41(3). DOI:10.3899/jrheum.131246 · 3.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives
To describe histological, immunohistochemical and ultrastructural features of synovial biopsies of amyloid arthropathy associated with multiple myeloma (MM).
Synovial biopsies from affected joints of two patients with MM and amyloid arthropathy were examined with light and electron microscopy, and immunohistochemically for expression of CD3, CD8, CD20, CD38, CD68, Ki-67 and vWF. Results were compared to values from osteoarthritis (OA, n = 26), rheumatoid arthritis (RA, n = 24) and normal (n = 15) synovial membranes.
There was no or only mild lining hyperplasia. Vascular density was not elevated, and there were few Ki-67+ proliferating cells in the stroma. The Krenn synovitis score classified one specimen as “low-grade” and one as “high-grade” synovitis. CD68+ and CD3+ cells were the predominant mononuclear inflammatory cells, whereas CD20+ and CD38+ cells were absent from both synovial membrane and synovial fluid sediment. Electron microscopy demonstrated amyloid phagocytosis by synovial macrophages. In hierarchical clustering the two amyloid arthropathy specimens were more closely related to OA than to RA or normal synovium.
This first detailed immunohistological analysis of MM-associated amyloid arthropathy suggests that it is a chronic synovitis that evolves despite the loss of humoral immunity seen in advanced MM. Instead, amyloid phagocytosis by synovial macrophages likely triggers and perpetuates local disease.
Amyloid: the international journal of experimental and clinical investigation: the official journal of the International Society of Amyloidosis 11/2013; 21(1). DOI:10.3109/13506129.2013.862229 · 2.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Amyloid deposition in multiple myeloma (MM) may lead to an arthropathy resembling rheumatoid arthritis (RA). Since a systematic description of its natural history is lacking, we have performed a systematic analysis of all published cases.
Literature review featuring backward and forward database searches and direct inspection of reference lists. Inclusion criteria were as follows: publication between 1931 and 2012, diagnosis of multiple myeloma, and demonstration of light chain amyloid (AL) in any organ or in synovial fluid, arthritis, or synovitis.
Overall, 101 cases were identified. Median age was 59 years and the male-to-female ratio was 1:1. A systemic manifestation of MM was reported in 88 cases. In 53 of these, characteristic physical findings (carpal tunnel syndrome, macroglossia, shoulder pad, and soft tissue swelling/masses) were present. Arthritis manifested before the diagnosis of MM in 63 cases, with 33 cases initially misdiagnosed as RA. There were 72 cases of poly-, 17 of oligo-, and three of monoarthritis. The shoulder joint was most commonly affected, followed by small hand joints. Median synovial fluid leukocyte count was 2460 cells/mm(3), and was normal in seven cases. Synovial histopathology often featured mild synovitis without plasma cell infiltration. Imaging revealed articular or periarticular inflammation in many cases and bone lesions near 22% of affected joints. Treatments varied but led to some improvement in the majority of cases.
These results solidify previous experience that MM arthropathy tends to feature a symmetric RF-negative nonerosive polyarthritis. However, the results also highlight the diversity of its presentations and stress the importance of arthropathy as a potentially under-recognized presenting manifestation of MM.
Seminars in arthritis and rheumatism 08/2013; 43(3). DOI:10.1016/j.semarthrit.2013.07.004 · 3.93 Impact Factor