Clinical Rheumatology

Published by Springer Verlag
Online ISSN: 1434-9949
Print ISSN: 0770-3198
A strong association between the human leucocyte antigen (HLA)-B*58:01 allele and allopurinol-associated severe cutaneous adverse reactions (SCAR) has been reported. A screening for HLA-B*58:01 before allopurinol has been suggested in guidelines for management of gout. HLA-B*58:01 screening is generally based on molecular biology methods that may be not suitable for wide application. We have retrospectively evaluated the performance on a rapid flow cytometry (FCM) test, based on the use of a monoclonal antibody specific for HLA-B17, an antigen that can be split into HLA-B*57 and -B*58 alleles by molecular biology testing, which is used to screen for HLA-B*57:01 before prescription of the antiretroviral agent abacavir in HIV-positive patients. Among 475 samples that were analysed by FCM and by molecular biology test as gold standard, 2 out of 89 false negative tests for HLA-B*58:01 were found. The sensitivity was 97.8 % and the negative predictive value was 98.9 %. We have shown that a FCM test can identify almost all HLA-B*58:01 positive individuals. As FCM laboratories are more widely available than molecular biology ones, this approach could be used to reduce the risk for allopurinol-induced SCAR. Where both facilities are available, a two-step strategy (FCM as screening, molecular biology for confirmation) may reduce the cost of the screening.
This study was intended to evaluate HLA-DRB1 alleles and antibodies against anti-cyclic citrullinated peptides (anti-CCP Abs) for their value in predicting patient responses to treatment with disease-modifying antirheumatic drugs (DMARDs) in early rheumatoid arthritis (RA). The subjects were 124 Japanese patients who had received their first treatment with DMARDs, usually methotrexate, within 1 year of disease onset and who had been followed-up for 2 years subsequently. Approximately 40% of patients developed DMARD resistance and accordingly required anti-tumor necrosis factor α (TNFα) therapy during the 2-year period. DMARD resistance was strongly associated with the carriage of SE-positive HLA-DRB1*04 alleles, especially the *0405 allele (OR, 3.92; 95%CI, 1.83-8.41; p = 0.0003). In contrast, the SE-positive allele HLA-DRB1*0101 was less potent in contributing to DMARD resistance. The rate of anti-CCP Ab-positive patients was significantly higher in the DMARD-resistant group (OR, 6.62; 95%CI, 1.45-30.24; p = 0.008). Multivariate logistic regression analysis confirmed the strong association of DMARD resistance with the presence of SE-positive *04 alleles (OR, 2.89; 95%CI, 1.28-6.53; p = 0.011) and anti-CCP Abs (OR, 6.31; 95%CI, 1.23-32.34; p = 0.027), yielding an area under the receiver operating characteristic curve of 0.76 (95% CI, 0.68-0.84; p = 0.000). After stratification, the highest rate of DMARD resistance was observed in patients having both SE-positive *04 alleles and anti-CCP Abs. These observations show that the presence of SE-positive *04 alleles in combination with anti-CCP Abs is the strongest predictor for development of DMARD resistance and eventual need of anti-TNFα agents in patients with early RA.
To determine the prognostic factors for knee and/or hip joint destruction in rheumatoid arthritis (RA) patients, we typed 379 RA patients for HLA-DRB alleles and analysed the antigen frequencies. The DRB1*0405 antigen frequency in RA patients who underwent total knee replacement and/or total hip replacement was significantly higher than in those who did not have replacements, which meant that DRB1*0405 was associated with knee and/or hip joint destruction. This finding may be of value for predicting knee and/or hip joint destruction in RA.
The effects of vitamin C on 1,25(OH)2D3 synthesis in humans were evaluated; the study included 20 females. They were divided into 2 groups. The first of the 10 subjects (age range 55-71) received ascorbic acid at a dose of 150 mg/die i.v. for 10 days; the second 10 subjects (age range 55-69) received a placebo i.v. for 10 days. In a later study (after a 30-day washout) the same two groups were tested for the second time with ascorbic acid at a dose of 1,000 mg/die i.v. for 10 days and placebo i.v. for 10 days. Serum calcium and phosphorus, serum Ca++, serum proteins, blood and urinary pH, serum 25(OH)D3 and 1,25(OH)2D3, serum PTH, urinary hydroxyprolin were tested before and after the treatments. In the first study a significant increase in serum 1,25(OH)2D3 was observed after ascorbic acid while no significant variation was observed for the other parameters. In the second study, a significant increase in serum Ca++ and a significant decrease in serum 1,25(OH)2D3 were observed after ascorbic acid while no significant variation was observed for the other parameters. The authors conclude that ascorbic acid promotes 1,25(OH)2D3 synthesis at a paraphysiologic dose (150 mg/die) in humans but this synthesis is inhibited at higher doses (1,000 mg/die). The latter effect by Ca++ or by an effect of ascorbate on 1 alpha-hydroxylase enzyme could be mediated.
We report two patients with non-Hodgkin's lymphoma in whom hypercalcemia and elevated 1,25 dihydroxyvitamin D (1,25-(OH)2D3) levels developed in the absence of any lytic bone lesions. Hypercalcemia responded only transiently to glucocorticoids which were ill tolerated. Intravenous APD administration was needed to circumvene hypercalcemia. Humoral hypercalcemia of malignancy is discussed. Our cases confirm that hypercalcemia associated with elevated 1,25-(OH)2D3 may occur in malignant lymphoma.
With the aim of evaluating the role of 1,25 dihydroxyvitamin D in the pathogenesis of osteoporosis, this hormone was studied in 90 subjects. They were divided into three groups: the first group consisted of 30 normal female subjects (aged 30 to 45); the second group comprised 30 elderly female subjects (aged 67 to 90) the third group consisted of female patients (aged 65 to 87) with clinical and radiological evidence of osteoporosis. Variations of serum 1,25 dihydroxyvitamin D, after stimulation with oral P04 (1,000 mg/day for 10 days) and stimulation with oral Ca (1,000 mg/day for 10 days), were studied in 16 osteoporotic females (10 of them received P04) and six Ca (Controls). This second study was performed to evaluate the renal 1-alpha-hydroxylation. No significant variation between serum 1,25 dihydroxyvitamin D of elderly and osteoporotic females was observed when compared with normal young healthy subjects. Moreover, a significant increase in serum 1,25(OH)2D after oral P04 was found in accordance with a significant increase in serum parathormone. These data demonstrate that changes in serum 1,25(OH)2D levels did not seem to play a significant part in the pathogenesis of osteoporosis in our population neither could a deficit of renal 1-alpha-hydroxylation be demonstrated.
Back pain is a significant health service issue in Australia and internationally. Back pain sufferers can draw upon a range of health care providers including complementary and alternative medicine (CAM) practitioners. Women are higher users of health services than men and tend to use CAM frequently for musculoskeletal conditions. However, there remain important gaps in our understanding of women's consultation patterns with CAM practitioners for back pain. The objective of this study is to examine the prevalence of use and characteristics of women who use CAM practitioners for back pain. The method used was a survey of a nationally representative sample of women aged 60-65 years from the Australian Longitudinal Study on Women's Health. Women consulted a massage therapist (44.1 %, n = 578) and a chiropractor (37.3 %, n = 488) more than other CAM practitioners for their back pain. Consultations with a chiropractor for back pain were lower for women who consulted a General Practitioner (GP) (OR, 0.56; 95 % CI 0.41, 0.76) or a physiotherapist (OR, 0.53; 95 % CI 0.39, 0.72) than for those who did not consult a GP or a physiotherapist. CAM practitioner consultations for back pain were greater for women who visited a pharmacist (OR, 1.99; 95 % CI 1.23, 3.32) than for women who did not visit a pharmacist. There is substantial use of CAM practitioners alongside conventional practitioners amongst women for back pain, and there is a need to provide detailed examination of the communication between patients and their providers as well as across the diverse range of health professionals involved in back pain care.
Criteria for patient selection and analysis 
Demographic information about enrolled patients
The curves represent survival for all the patients in the study (176) and survival for patients from groups A, B, and C. In the group of patients with a concordance of three (in which 4, 5 or 6 orthopedists agreed on the suitability of the surgery) survival is 66.5 % at 48 months 
Survival curves plotted and divided according to Lequesne index ( A ); age ( B ); pain VAS ( C ) 
Concordance score of the six orthopedists
Hip osteoarthritis is very common and costly. The European League Against Rheumatology Committee agenda asks for research to investigate treatments able to slow down the progression of hip osteoarthritis (OA), to delay joint replacement, and to determine the comparative effectiveness and cost-effectiveness of non-surgical and surgical treatment modalities as well as criteria relating to the indications for and timing of total hip replacement (THR). After publishing the results of a randomized controlled trial and a cohort study on the efficacy of Intra-articular sodium hyaluronate (MW 1,500-2,000 kDa) on symptomatic hip OA, we performed this retrospective study in patients suffering from hip OA treated with ultrasound-guided intra-articular injections of HyalOne (Hyalubrix 60 Italian brand name) involving a group of THR expert orthopedic surgeons to appraise whether or not considered eligible for THR and the frequency and timing of THR. Six orthopedists, not routinely performing hip intra-articular injections, each independently assessed whether 176 patients suffering from hip OA and treated with ultrasound-guided intra-articular injections of sodium hyaluronate (MW 1,500-2,000 kDa) were candidates for THR according to the clinical data (age, body mass index, Pain Visual Analog Scale, Lequesne Algofunctional Index, global patient assessment, global physician assessment, nonsteroidal anti-inflammatory drug intake, and hip X-ray) collected at the first intra-articular sodium hyaluronate injection visit and provided as anonymous electronic data. At 24 months, 159 out of 76 (90 %) patients did not undergo to THR. At 48 months, 82 % (N = 144) of the study population treated with intra-articular hyaluronic acid avoided THR. In the group of 93 patients considered candidates for THR (that is, in which 4, 5, or 6 orthopedic surgeons agreed that the patient was a suitable candidate for THR), only 17 had undergone THR, with survival results of 82 % at 24 months. At 48 months, this percentage reduced to 66 % in this group. In the other groups of patients (in which respectively 3, 2, 1 or no surgeons were in agreement that the patient was a candidate for THR) arthroplasty is not recorded. Sodium hyaluronate (MW 1,500-2,000 kDa) given by ultrasound-guided injection seems to delay THR in the real context of actual overall management of symptomatic hip OA patients. Although further studies are necessary to confirm these data and to identify outcome predictors, hip viscosupplementation should be considered as conservative treatment to perform before proposing patients for THR.
We compared, in a double blind, randomized, 3-center study, a pulse of 1000 mg methylprednisolone with a pulse of 250 mg methylprednisolone, in patients with active rheumatoid arthritis. Improvement of patients was similar in both groups and lasted up to 3 weeks. Side effects were minor.
The aim of the study was to investigate the pulmonary parenchymal abnormalities by high resolution computed tomography (HRCT) in patients with various forms of scleroderma. Three scans were performed sequentially in all cases: one at the level of aortic arch, one at the tracheal carina and one 1-2 cm above the diaphragm. Seventy cases with limited, 21 patients with diffuse cutaneous systemic sclerosis and 10 cases with circumscribed scleroderma were investigated. The 21 patients with diffuse scleroderma included three normal HRCT scan (14%), three with ground glass attenuation (14%), one with ground glass attenuation with fibrosis, three with fibrosis (14%), six with subpleural and five with diffuse honeycombing. The majority of cases with extensive honeycombing of the lungs had anti-Sc! 70 autoantibody which was the characteristic antibody of the diffuse scleroderma subset. The 70 cases with limited cutaneous systemic sclerosis were characterized by normal HRCT (43%), ground glass opacity with or without fibrosis (18.6%), whereas fibrosis was detected in 22.9%, subpleural or diffuse honeycombing in 15.7% of the patients. Six of the ten cases with circumscribed scleroderma also showed a fibrosis. Cases with diffuse scleroderma are characterized by the presence of advanced fibrosis, whereas the extent of fibrosis is far less pronounced in limited scleroderma. Mild fibrosis may also be present in circumscribed scleroderma forms.
Serum levels and 24-hour urinary excretion of beta 2-Microglobulin (beta 2-M) was investigated in a group of 101 patients with rheumatoid arthritis (RA), without any other signs of renal disease in past or present, and in a comparable control group. Elevated 24-hour urinary beta 2-M excretion, due to renal proximal tubules dysfunction, was observed in 19% of the patients and not in the control group. There was a significant correlation with clinical signs of extra-articular RA. It is postulated that the observed increase may be an early symptom of renal involvement in RA. Elevated serum beta 2 levels, corrected for glomerular filtration rate, were observed in 44% of the RA patients and only in 3% of the control group and correlated with clinical signs of a more severe RA, as well as with increased 24-hour urinary beta 2-M excretion.
Methotrexate (MTX) is an effective anti-psoriatic agent but there are major concerns about its long-term toxicity, in particular to the liver. Reported frequencies and recommendations for monitoring patients on MTX vary considerably. The aim of this study was to analyse the frequency and severity of MTX-associated adverse drug reactions (ADR) in patients with psoriasis and psoriatic arthritis. A retrospective analysis was performed of 104 psoriasis and psoriatic arthritis patients (60 male, 44 female) treated with MTX between October 1968 and October 1998. The severity of ADR was classified according to Common Toxicity Criteria (CTC). Acute ADR was defined as adverse effects within the first 90 days of MTX therapy. ADR seen later were classified as chronic. In 83 patients 165 ADR were noted within the beginning of MTX therapy. In five patients treatment was terminated because of ADR. During long-term therapy 23 patients received < or = 2000 mg MTX (group A); 81 received a cumulative dose greater than 2000 mg (group B). The total frequency of ADR in group B and the frequency of ADR CTC grade 3 or 4 in general was not significantly increased in group B (chi2 test; P = 0.468). Group B was characterised as follows: CTC grade 3 or 4 blood count changes led significantly more often to the termination of MTX (Fisher's exact test; P = 0.048), CNS side-effects (P = 0.016) and infections were more frequent (chi test; P<0.001). Liver changes and serum enzyme level increases were not significantly more frequent in group B. ADR are common in psoriasis patients on MTX therapy independent of the cumulative dose. In most cases they are temporary by nature and mild. Liver changes and serum enzyme level increases were not a major problem in our patients.
The objective of this study is to evaluate the clinical features and prognosis of adult-onset Still's disease (AOSD). One hundred and four AOSD patients who were analyzed retrospectively were enrolled in this study. Medical charts were systematically reviewed for: demographic data, clinical features, laboratory findings, treatments, and outcomes. The major clinical features were: spiking fever 100%, evanescent maculopapular rash 95%, polyarthralgia 90%, sore throat 78%, lymphadenopathy 66%, hepatosplenomegaly 57%, hydrohymenitis 30%, neutrophilia 98%, liver disfunction 62%, increased erythrocyte sedimentation rate (ESR) 96%, and hyperferritinaemia 99%. Reactive hyperplasia was shown in all patients who underwent lymph node biopsy. Ninety-five percent and 63% of the patients were treated with glucocorticoid and immune suppressant, respectively. Those with prednisone or its equivalent dosage of > or =0.8 mg/kg/d achieved quicker remission and less relapse. Persistent fever, evanescent rash, arthritis, and sore throat were the most prevalent symptoms in patients with AOSD, with laboratory findings of leukocytosis, elevated liver enzymes, elevated ESR and serum ferritin. Glucocorticoid and immune suppressive drugs are effective for AOSD; however, the relapsing rate is relatively high. High levels of white blood cells, serum ferritin and ESR, as well as glucocorticoid dosage were related to relapse.
This study aims to review clinical features, treatments, and prognostic factors of thrombotic thrombocytopenic purpura (TTP) associated with systemic lupus erythematosus patients (sTTP). The case reports of sTTP published in world literature from 1999 to 2011 were collected, and 105 cases were divided into death group and survival group. The epidemiologic characteristics, clinical manifestations, laboratory examinations, treatments, and prognostic factors were analyzed. We found that coexistence of renal and neurological impairments were significantly frequent in the death group (100 %) than in the survival group (56.5 %) (P = 0.002). Type IV was predominant in 57.7 % of renal pathological damage, followed by type V (11.5 %), type II (5.8 %), and thrombotic microangiopathy (TMA) (5.8 %). TMA appeared more frequently (50 %) in the death group than in the survival group (6.25 %) (P = 0.042). End-stage renal disease occurred in nine cases with type IV in five (55.6 %), type TMA in one (11.1 %), and unspecified in three cases (33.3 %). Of 32 cases, 40.6 % showed severe ADAMTS13 deficiency and returned to normal or mildly deficient after remission. The total mortality rate of sTTP was 12.4 % and the mortality rate of patients with infection (27.3 %) was significantly higher than those without infection (8.4 %) (P = 0.028). Plasma exchange and glucocorticoids were administrated in over 80 % of cases with 65.7 % remission rate, while additional cytotoxics or rituximab was mostly used in refractory sTTP and achieved over 90 % of remission rate. Above all, coexistence of renal and neurological impairments, infection, and renal damage with type IV or TMA might denote a poor prognosis of sTTP.
Interleukin-10 (IL-10) is an immunoregulatory cytokine, usually considered to mediate the downregulation of the inflammatory response in rheumatoid arthritis (RA). Some effects of IL-10 are not anti-inflammatory; for example, the activation of B cells to promote autoantibody production. Allelic polymorphisms located in the promoter region of the IL-10 gene may contribute to the regulation of autoantibodies production. To examine the putative association between the −1082 G/A polymorphism in the promoter region of the IL-10 gene and the susceptibility to disease onset and severity of RA, a total of 144 patients with RA diagnosed according to the revised criteria of the American College of Rheumatology for RA were consecutively recruited into the study. Radiographic progression of RA was scored according to the Sharp/van der Heijde method. Serum levels of rheumatoid factors (RFs) were measured by enzyme-linked immunosorbent assay. Polymerase chain reaction amplification was used for the analysis of the promoter polymorphism of the IL-10 gene. We observed significant differences in genotype distribution of the −1082 G/A polymorphism between IgM RF, IgA RF, and IgG RF positive/negative subgroups of RA patients, with higher prevalence of the GG genotype within IgM RF (P g = 0.006), IgA RF (P g = 0.05), and IgG RF (P g = 0.007) negative RA patients. Results obtained in this study provide the evidence of an association between the −1082 G/A polymorphism in the IL-10 gene promoter and the production of RFs in RA patients.
A child with polyarthritis is always a diagnostic challenge for the treating physician. Polyarthritis can be a clinical manifestation of diverse disease processes, and the differential diagnosis is understandably very broad. We present a case of polyarticular septic arthritis, which is osteomyelitis complicated, caused by Streptococcus pyogenes identified by 16S polymerase chain reaction (PCR) in a healthy child, with previous synovial fluid cultures negative. This case underlines the importance of early aggressive therapy and the role of PCR/16S ribosomal bacterial DNA amplification to detect the causative microorganisms in septic arthritis when cultures remain negative.
An understanding of the cytokine cascade in a rheumatoid joint has led to the development of new therapeutic options, including drugs targeting tumor necrosis factor-alpha (TNF-alpha). The safety profile of these agents in patients with hepatitis-induced liver disease, however, remains a concern because of risks associated with immune suppression. To examine the effect of three different TNF-alpha antagonists, infliximab, etanercept, and adalimumab, on serum transaminases and hepatitis viral load in patients with rheumatoid arthritis (RA) and concurrent hepatitis B (HBV) or hepatitis C (HCV). Medical records of 11 patients with diagnosis of RA and documented seropositivity for hepatitis B or hepatitis C were retrospectively reviewed for worsening of hepatic inflammation and viral proliferation as measured by a rise in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) and viral load while using these agents. Three patients had RA with concurrent chronic HBV and eight patients had RA with concurrent chronic HCV. Seven patients remained on a single anti-TNF-alpha agent and four patients switched to a second anti-TNF-alpha agent due to treatment failure. Two patients showed a transient elevation in AST and/or ALT from normal, but in all 11 patients, AST and ALT levels were within one time the upper range of normal at the conclusion of the study. No significant increase in viral load was seen except one patient who showed a fourfold increase from baseline. Our case series supports results obtained from previous studies examining the safety of anti-TNF-alpha agents in patients with underlying hepatic disease. Use of these agents in patients with HBV or HCV may be associated with a transient transaminitis but appears to be safe overall. In both groups, frequent monitoring of serum transaminase levels and viral load is essential.
This study aims to investigate the association between subcutaneous panniculitis-like T-cell lymphoma (SPTCL) or cutaneous gamma/delta T-cell lymphoma (CGDTCL) and a variety of manifestations that mimic autoimmune disorders. A retrospective chart review was made for 11 patients who were initially diagnosed as autoimmune diseases but finally turned out to be SPTCL or CGDTCL. Eleven patients were initially diagnosed with erythema nodosum, nodular panniculitis, lupus erythematosus profundus, systemic vasculitis, dermatomyositis, or pyoderma gangrenosum. The interval between presenting symptoms and the diagnosis of lymphoma was 17.5 (range, 3-84) months on average. Nearly all cases had multiple subcutaneous nodules or plaques that were most commonly distributed on the extremities and trunk. Fever was the primary accompanying sign (9/10), followed by lymphadenopathy (6/11), splenomegaly (5/11), and hepatomegaly (3/11). Two patients developed hemophagocytic syndrome. A total of 26 biopsies involving multiple anatomic locations were performed. Antirheumatic therapy including steroids and immunosuppressive agents administered before the identification of T-cell lymphoma revealed unsustainable therapeutic effect. In contrast, seven cases gained partial response after chemotherapy, while the remaining four cases died with disease progression and disease-associated severe infections. SPTCL and CGDTCL are rare and heterogeneous which may resemble those rheumatologic diseases that are characterized by inflammation involving the skin or subcutaneous fat tissue. The diagnosis relies on the constellation of disease-specific pathologic, immunophenotypic, and T-cell receptor gene rearrangement tests. In the context of an ambiguous clinical picture demonstrating inconsistency with the initial diagnosis of benign autoimmune diseases, repeated excisional biopsies of the subcutaneous lesions may be required to uncover the underlying lymphoma.
In this study, we evaluated the prevalence of fibromyalgia (FM) in iron deficiency anemia (IDA) and thalassemia minor (TM) patients and associated factors. In addition, we investigated the prevalence of IDA in outpatients with fibromyalgia, and its effect on clinical findings. The study included 205 IDA, 40 TM patients and 100 healthy controls. FM was diagnosed according to 1990 ACR criteria. Whole blood count, biochemical tests, and serum iron parameters were determined. Pain, fatigue, and FM Impact Questionnaire (FIQ) functional item scores were assessed in FM subjects. In addition, the prevalence of IDA in FM patients diagnosed at the Rheumatology Outpatient Clinic was determined. The prevalences of FM in IDA (17.6%) and TM (20%) groups were higher than in controls (6%; p values 0.006 and 0.025, respectively). When IDA patients with FM were compared to those without FM, it was seen that a higher percentage were females, married, and a higher percentage had history of pica (all p values < 0.05). Serum hemoglobin and iron parameters did not differ between IDA patients with and without FM. IDA was detected in 48 (24.5%) of 196 FM patients. FM patients without IDA had higher sleep disturbance scores (p = 0.012) and longer duration of FM (p = 0.045). FM was a common finding in patients with IDA and TM. FM was associated with female sex and history of pica in IDA patients, and not associated with serum hemoglobin and selected iron parameters. The presence of FM in TM had no association with any of the above-mentioned parameters.
There is no unanimity as to whether polymyalgia rheumatica (PMR) and temporal arteritis (TA) are two distinct diseases or different features of one disease. The objective of this study was to assess the value of histological findings of temporal artery biopsy and the efficacy and complications of drug therapy as well as the frequency of malignancies. It was carried out as a retrospective follow-up study. One hundred eleven patients (89 PMR, 14 TA and 8 PMR+TA) were studied. In 56 patients with PMR a temporal artery biopsy was performed; in none of these biopsies was active arteritis found. Of the 19 patients with TA or PMR+TA, where a temporal artery biopsy was performed, arteritis was found in 15 patients. Reactivation occurred in 27 patients: 4 patients using NSAIDs and 23 patients using corticosteroids. Side effects of the medication included vertebral compression in 10 patients, most of whom were using corticosteroids. Malignancies were diagnosed in 12 of the 111 patients. Most malignancies were diagnosed long before or after the diagnosis of PMR. In case of a PMR diagnosed by the clinician a biopsy of the temporal artery has no value, while the yield of this diagnostic procedure is high in TA. Reactivation was seen quite often and warrants a prolonged period of medical treatment.
The aim of this study was to determine whether the prolactin -1149 G/T polymorphism confers susceptibility to systemic lupus erythematous (SLE) and rheumatoid arthritis (RA). A meta-analysis was conducted for examining the associations between prolactin -1149 G/T polymorphism and susceptibility to SLE or RA using allele contrast, recessive and dominant models, and homozygote contrast. A total of 10 comparative studies, consisting of 4 SLE and 6 RA studies, involving 4252 patients and 4949 controls, were included in the meta-analysis. No association between the prolactin -1149 G allele and SLE was found when all study subjects were considered together (OR = 1.019, 95 % CI = 1.841-1.236, p = 0.845). Stratification by ethnicity also indicated no association between the prolactin G allele and SLE in either Caucasian or Latin American populations. In contrast, a significant association was observed between the prolactin G allele and RA in all subjects (OR = 1.123, 95 % CI = 1.052-1.198, p = 4.6 × 10(-5)). After stratification by ethnicity, the G allele was found to be significantly associated with RA in Caucasians (OR = 1.112, 95 % CI = 1.041-1.189, p = 0.002). Furthermore, the prolactin -1149 G/T polymorphism was found to be associated with RA in Caucasians under the dominant model and under homozygote contrast. This meta-analysis demonstrates that the prolactin -1149 G/T polymorphism is associated with susceptibility to RA, but not SLE, in Caucasians.
To retrospectively evaluate the efficacy and safety of combination therapy with tacrolimus (TAC) and other disease-modifying antirheumatic drugs (DMARDs). One hundred fifteen rheumatoid arthritis (RA) patients treated with tacrolimus were enrolled in this retrospective analysis. We collected clinical information, including patient background, treatment efficacy (evaluated using the DAS score), and adverse events observed. Multiple logistic regression analysis was conducted to analyze factors contributing to clinical response and adverse effects. The disease activity score of 28 joints (DAS28) improved significantly at 24 weeks, and continuation rate at 1 year was 57.9%. There was no difference in continuation rate between different DMARD combinations, and not only methotrexate (MTX) but also bucillamine (BUC) and salazosulfapyridine (SSZ) were effective combination partners with TAC. No serious adverse events were observed, and no different inefficacy or safety was observed between non-elderly (<65 years old) and elderly (≥65 years old) RA patients. By conducting multiple logistic regression analysis, combination therapy with MTX and TAC, the number of baseline DMARDs (specifically, ≥3), and old age were identified as risk factors for adverse events. Our findings indicate that TAC is a valuable DMARD for second-line combination therapy in RA.
The aim of this study was to evaluate the incidence of neurological manifestations of Behçet's disease (BD) in patients on cyclosporin A (CSA) compared with those on other medications. The records of 117 patients with BD who visited our hospital between 1990 and 2003 were reviewed with respect to symptoms and medication. All episodes of constant therapy prior to central nervous system (CNS) involvement were counted, and then the associations were analysed by the exact Fisher-Freeman-Halton test and adjusted for multiple tests by the Bonferroni-Holm method. We observed ten new cases of CNS manifestations in our patients with BD being regularly seen and treated in our tertiary care centre. The overall prevalence of neuro-BD in our patient group was 8.5%. In a retrospective analysis, the incidence of new-onset neurological disease (neuro-BD) in all patients with BD who regularly visited our hospital was significantly higher in patients on CSA than in those on other medications (6 of 21 vs 0 of 175 episodes, P<0.0001). This contrasts the obvious efficacy of CSA on extracerebral manifestations of BD, such as severe ocular disease, mucocutaneous lesions or arthritis. CSA exerts differential efficacy on various manifestations of BD. It is very effective for severe ocular and other moderate to severe manifestations of BD, but its efficacy for the prevention of neuro-BD seems to be inferior to that of other medications used in BD, such as azathioprine or interferon-alpha. The reasons for this are unclear, but the potential toxic effects of CSA on the CNS may be a predisposing factor for CNS vasculitis in BD.
To establish the prevalence of the associated secondary diseases in patients with Raynaud's phenomenon (RP) attending a rheumatology specialty centre and to determine the frequency with which a secondary illness develops in those having RP, in absence of a well-defined secondary cause. 118 consecutive patients were evaluated. Medical history, physical and laboratory investigations entered into a database. Patients with primary RP and patients with RP who did not fulfil any diagnostic criteria for inclusion in a secondary form were followed up over a three-year period. 63 RP patients were found with related conditions. 35 patients met criteria for inclusion in a primary RP group, 20 patients had 'unclassifiable' RP, of which two (10%) developed a well-defined disease. None of the primary RP patients developed a secondary disease. This study shows that less than 50% of patients with RP attending a rheumatology specialty centre have a connective tissue disease. Patients with isolated RP appear to have a benign disease, since primary RP remains as such, and only a small percentage of patients with 'unclassifiable' RP evolve into a well-defined CTD.
Amongst 149 cases of reflex sympathetic dystrophy syndrome (RSDS), 25 (16.8%) were being treated with barbiturates at the time the RSDS symptoms began. This group is unusual by the frequent absence of provocative events (32%), a high number of diseased joints, bilaterality (76%), involvement of upper limbs (76%) and Dupuytren's disease (52%). Swift and complete recovery depends mostly on barbiturate withdrawal. These data support the idea that barbiturates may be the principal initiating event in some RSDS. Since unfavorable progress is seen with persistent use of barbiturates, this medication should be recognised early in the course of the disease in order to prevent severe sequels.
Takayasu's arteritis (TA) is a chronic inflammation that frequently involves the aorta and its major branches. The clinical features of TA vary in different ethnic populations. The objective of this study is to characterize the clinical features, angiographic findings, and response to treatment of patients with TA in Changhai Hospital, Shanghai, China. The hospital records of 125 patients diagnosed with TA were retrospectively evaluated. Eighty patients were followed for a median duration of 36 months. Females (86.4%) were most frequently affected. The mean age at onset was 26.9 years. Constitutional symptoms were present in only 38.4% of patients. The most common clinical finding was pulse deficit. Histological findings from 12 clinically inactive patients showed active lesions in 58.3%. Angiographic classification showed that type I was the most common, followed by type V and IV. Type I was more common in adult patients than in pediatric patients. Although immunosuppressive treatment induced remission in most patients, over 90% of those who achieved later remission relapsed. Both bypass procedures and angioplasty showed high rates of initial success, but restenosis occurred in 34.7% of bypass procedures and 77.3% of angioplasty procedures. Eight patients died during the follow-up period with the main cause of death being congestive heart failure. Constitutional symptoms were not frequent in our study. Correlation between the clinical assessment of disease activity and histologic findings is often poor in TA. Angiographic findings showed that type I was the most common in our study. Over the longer term, the outcomes of revascularization were superior to angioplasty.
The aims of this study were to find the characteristics and prevalence of nailfold capillary changes in a large series of patients with Behçet's disease (BD) and to analyze their possible relation to other clinical characteristics of the disease. We performed nailfold capillaroscopy in 128 randomly selected patients fulfilling the international classification criteria for BD. Capillaroscopy was done in eight fingers with a x3.2 microscopy. All patients were questioned for history of Raynaud's phenomenon, ischemic ulcers, smoking, and hypertension. A computerized form including demographic, clinical, and para-clinical features was used to collect data. Univariate and multivariate logistic regressions were used to analyze the relation between capillaroscopic findings and disease characteristics. Odds ratio and a confidence interval at 95% (CI) were calculated for each item. The mean age of the patients was 37 +/- 10 years, and the male to female ratio was 1.56:1. Capillaroscopy was abnormal in 51 patients (40%, CI 8.5). Enlarged capillaries were seen in 33 patients (26%, CI 7.6), hemorrhages in 21 (16%, CI 6.4), and capillary loss only in one patient. In univariate logistic regression analysis, the presence of enlarged capillaries was associated with lower age at disease onset (OR = 0.9, CI 0.9-1; p = 0.04), hypertension (OR = 4.2, CI 1.5-11.4; p = 0.006), superficial phlebitis (OR = 5.5, CI 1.2-24.4; p = 0.03), and negative pathergy test (OR = 0.4, CI 0.2-0.9; p = 0.04). The presence of hemorrhages tended to be associated with articular symptoms (p = 0.05). Multivariate analysis also confirmed the association of enlarged capillaries with lower age at disease onset (p = 0.01), hypertension (p = 0.001), and superficial phlebitis (p = 0.03). Nailfold abnormalities, mainly enlarged capillaries, are frequent in patients with BD. Our results suggest that these abnormalities may be related to other vascular features of the disease such as superficial phlebitis, but it does not seem to confer special risk for any other specific clinical symptom of the disease.
Recently, a new classification algorithm (CA) for systemic necrotizing vasculitides was proposed by Watts et al. (Annals Rheum Dis 66:222-227, 2007) by using the American College of Rheumatology (ACR), Chapel Hill Consensus Criteria (CHCC) and Sorensen surrogate markers (So). We aimed to validate CA in our patients. One hundred twenty-nine patients followed up in our vasculitis clinic were reclassified according to CA in different categories (ACR or Lanham criteria in "1" for Churg-Strauss Syndrome (CSS); ACR in "2a"; CHCC-Wegener's granulomatosis (WG) in "2b"; CHCC-microscopic polyangiitis (MPA), So-WG in "2c"; So-WG, proteinase 3 (PR3) or myeloperoxidase antineutrophil cytoplasmic antibody (MPO ANCA) serology in "2d" for WG; clinical features and histology compatible with small vessel vasculitis without So-WG in "3a"; So-MPA, PR3 or MPO ANCA serology in "3b" for MPA; CHCC-classic-polyarteritis nodosa (c-PAN) or typical angiographic features in "4" for c-PAN; unclassifiable in "5"). Kappa statistic was used to analyse the agreement of the criteria that formed the algorithm. All of 12 CSS, 91% of 69 WG, 78% of 18 MPA and 93% of 26 c-PAN patients remained in their previous diagnosis. WG patients were placed in 2a (83%), 2c (3%), 2d (14%) categories. Four WG (6%) and four MPA (22%) patients were categorized as MPA (in 3a (75%), 3b (25%)) and WG (in 2c (75%), 2d (25%)), respectively. Three of four unclassified patients could be classified as c-PAN (two) and MPA (one). Significant agreement was demonstrated only for ACR and So criteria in WG (κ = 0.62, p < 0.001). The majority of our patients stayed on their previous diagnosis in "CA". Our findings suggest that this algorithm is helpful and practical for epidemiological studies. Poor correlation of defined criteria was thought to be related to the fact that each criteria mainly consist of different characteristics of vasculitides such as clinical, histopathological and serological features.
Characteristics of the patients with Behçet's disease and malignancy 
Characteristics of the patients with Behçet's disease and malignancy in the literature 
Behçet's disease (BD) has rarely been reported in association with malignant diseases. In most cases the autoimmune nature of the disease itself or immunosuppressive drug use has been blamed for malignant transformation. We report 13 cases of BD concurrent with neoplastic disease as well as treatment-related morbidities in this particular patient group. Between 1986 and 1999, 400 patients were diagnosed as having BD in Hacettepe University Hospitals. Of these 13 patients, 3.25% developed malignant diseases within a median follow-up time of 9.8 years. Solid tumors were diagnosed in 10 patients and haematological or lymphoid malignancies in three. Surgery was performed in seven patients, whereas radiotherapy was applied in six and chemotherapy in eight. A literature review revealed 27 cases of BD associated with malignancies, mostly lymphoid or haematological. Ten of our cases were solid tumors, and to our knowledge most of these are the first reported cases of specific malignancies concurrent with BD. Treatment-related morbidities were wound infection as surgical morbidity in one patient (1/7) and radiotherapy-related morbidity in three (3/6) patients in a median follow-up time of 2 years. Solid tumors in addition to lymphoid and haematological malignancies are also seen during the course of BD. Radiation therapy may cause severe late toxicities in the presence of BD. Chemotherapy and surgery are fairly safe for the treatment of malignancies in BD patients.
The objective of this study was to evaluate the efficacy, safety and tolerability of lumiracoxib compared with placebo and celecoxib in patients with osteoarthritis (OA). Following a 3- to 7-day washout period for previous non-steroidal anti-inflammatory drugs, 1,600 patients aged >or=18 years with primary knee OA were randomized to receive lumiracoxib 200 or 400 mg once daily (o.d.), celecoxib 200 mg o.d. or placebo for 13 weeks. Primary efficacy variables were OA pain intensity in the target knee, patient's global assessment of disease activity and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale and total scores at week 13. Secondary variables included OA pain intensity in the target knee and physician's and patient's global assessments of disease activity by visit. Exploratory analysis of responder rates using the Outcomes Measures in Rheumatology Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) criteria was performed. Safety and tolerability were assessed. Lumiracoxib was superior to placebo in all primary and secondary variables and was generally similar to celecoxib. There were no statistically significant differences between the two doses of lumiracoxib. All active treatments were significantly more effective than placebo at weeks 2 and 13 in terms of response to treatment assessed using OMERACT-OARSI criteria. The incidence of adverse events was similar across the groups. Lumiracoxib 200 mg o.d. is a well-tolerated and effective treatment option for OA of the knee, providing pain relief and improved functional status with efficacy superior to placebo and similar to celecoxib. Lumiracoxib demonstrated a tolerability profile similar to placebo and celecoxib.
The aim of this study was to investigate whether interleukin-13 (IL-13) serum levels correlate to different nailfold capillaroscopy (NC) findings in patients with systemic sclerosis (SSc). IL-13 serum levels were measured using an ELISA method. The following NC abnormalities were considered: the presence of giant loops, haemorrhages, loss of capillaries, disorganisation of the vascular array, ramified/bushy capillaries and sludging of blood. A semiquantitative rating scale was adopted to score these changes, as well as a rating system for avascular areas and three morphological NC patterns ('early', 'active' and 'late'). Mean capillary density was determined by counting the total number of capillaries in a 1 mm length, and the arterial and venous diameters of the capillary as well as the total loop diameter were measured. In SSc patients IL-13 serum levels were significantly higher than in controls ( P < 00.1), whereas in patients with ( n=8) and without ( n=24) abnormal IL-13 serum levels (>17 pg/ml) the comparison of the NC features showed significantly relevant differences concerning a more frequent 'active' NC pattern ( P < 0.02), the presence of haemorrhages ( P < 0.0037) and sludging of blood ( P < 0.038), as well as larger total loop ( P < 0.036) and arterial ( P < 0.03) diameters, in those patients with elevated IL-13 serum levels. The study confirmed that IL-13 serum levels are higher in the sera of patients with SSc, and shows for the first time the significant correlations between this serological finding and some of the main relevant SSc capillaroscopic features, leading us to believe that this cytokine not only seems to sustain the immunological and fibrotic process of SSc, but might have a role in determining the more severe microvascular lesions in this disease.
Histopathologic examination of a small intestine, H & E ×40, b mesenteric lymph node, H & E ×40, c spleen, H & E ×200, and d mesenteric blood vessel, H & E ×40. Necrotizing vasculitis with extensive thrombosis and extravascular granuloma. Dense inflammatory reaction rich in eosinophils. H Hemorrhage, TH thrombosis, NM normal intestinal mucosa. Arrows point to necrotizing thrombosed blood vessels
There are no generally accepted diagnostic criteria for primary systemic vasculitis, and the application of classification as diagnostic criteria is not feasible and may even be misleading. We report a case of a 13-year-old boy with acute abdomen who was found to have isolated eosinophilic mesenteric vasculitis with extensive thrombosis and splenic infarction. All serological tests were negative, including antineutrophil cytoplasmic antibody. The vasculitis had been successfully controlled with surgical intervention, steroid, and cyclophosphamide therapy. This may be an atypical presentation of Churg-Strauss syndrome.
a Chest radiograph. b CT scan of the thorax
Churg-Strauss syndrome (CSS) is a rare systemic vasculitis of the small- and medium-size vessels. It is mostly seen in elderly patients presenting as de novo asthma, eosinophilia, and vasculitic organ involvement. In childhood, CSS is extremely rare. The course of pediatric CSS is usually severe and often lethal. We present a case of a 13-year-old girl with a short history of asthma, marked eosinophilia, and multiorgan involvement. The extremely high level of blood eosinophilic granulocytes (51.6 x 10(9)/L) prompted a workup for eosinophilic leukemia before the diagnosis CSS could be made. Subsequently, the disease was successfully treated. This case report shows a classical case of childhood CSS, remarkable because of the presence of extreme hypereosinophilia. It underlines the importance of CSS as a life-threatening cause of hypereosinophilia in children.
The aim of this 13-week, multicenter, randomized, double-blind, double-dummy, placebo- and positive-internal (celecoxib)-controlled, parallel-group study was to demonstrate the efficacy, safety, and tolerability of lumiracoxib in primary hip osteoarthritis (OA) patients. Eligible patients (n = 1,262; ACR criteria) were randomized (1:1:1) to receive lumiracoxib 100 mg once daily (o.d.) (n = 427), celecoxib 200 mg o.d. (n = 419), or matching placebo o.d. (n = 416) administered orally. The primary objective was to compare lumiracoxib 100 mg o.d. and placebo with respect to three co-primary efficacy variables: the pain subscale of the Western Ontario and McMaster Universities Osteoarthritis Index Likert version 3.1 (WOMAC™ LK 3.1) questionnaire, the function subscale of the WOMAC™ LK 3.1 questionnaire, and patient's global assessment of disease activity (100-mm visual analog scale (VAS)) after 13 weeks of treatment. Of the 1,262 randomized patients, 951 completed the study. All randomized patients were included in the intention-to-treat and safety populations. Lumiracoxib was superior to the placebo (p < 0.001) after 13 weeks for all three co-primary endpoints. By week 13, the patient's global assessment of disease activity (100-mm VAS) improved by 23.3 mm (±SD, 27.83 mm) with lumiracoxib and 13.3 mm (±26.71 mm) with placebo. The WOMAC™ function score decreased by 10.4 (±13.56) with lumiracoxib and 6.8 (±12.55) with placebo. The WOMAC™ pain scores decreased by 3.4 (±4.16) with lumiracoxib and 2.2 (±3.94) with placebo at week 13. Similar results were observed for secondary endpoints: OA pain intensity and WOMAC™ total score. Lumiracoxib was similar to celecoxib for all three co-primary endpoints. All treatments were well tolerated. In conclusion, lumiracoxib is effective in reducing pain and improving function in hip OA patients.
The aim of the study was to evaluate whether the imbalance between IL-12 and IL-13 serum levels, reflecting Th1/Th2 activity, is related to class-specific circulating rheumatoid factors (RF) and anticardiolipin (aCL) antibodies in SLE. Using ELISA we measured serum IL-12, IL-13, RF and aCL antibodies in 73 SLE patients and 20 healthy controls. The determination of IL-12/IL-13 ratio showed that IL-12 levels were above (group A), equal to (group B) or below (group C) IL-13 levels in 71.2%, 15.1% and 13.7% of SLE patients, respectively. IgM-RF levels were significantly higher in group C than in groups A ( P < 0.002) and B ( P < 0.019). Group C had also higher IgM-aCL levels than group A ( P < 0.04). No relationship between IL-12/IL-13 ratio and clinical or other laboratory parameters was found. It was concluded that the increased levels of both IgM-RF and IgM-aCL in patients with prevalent Th2 activity suggest that the predominance of Th2 over Th1 could drive autoantibody production in SLE patients.
This is a cross-sectional study that analyzed the pattern and frequency of articular and ophthalmologic manifestations in patients with Crohn's disease (CD) and ulcerative colitis (UC), with or without signs of active bowel inflammation. One hundred and thirty consecutive patients with CD (n = 71) and UC (n = 59) were examined. Simple X-rays of lumbar spine, sacroiliac joints, and calcaneal bone were performed and human leukocyte antigen (HLA)-B27 was typed. Joint manifestations occurred in 41 (31.5%) patients, 27 (38%) with CD and 14 (23.7%) with UC. Peripheral involvement occurred in 22 patients, axial involvement in five, and mixed involvement in 14. The most frequently involved joints were knees (56.1%), ankles (29.3%), and hips (29.3%), while the predominant pattern was oligoarticular (84.6%) and asymmetrical (65.6%). Enthesitis was identified in seven (5.4%) patients and inflammatory lumbar pain in 13 (10%). Eight of these patients fulfilled the diagnostic criteria for ankylosing spondylitis (6.2%). Radiographic sacroiliitis occurred in 12 patients (9.2%). Ocular abnormalities were present in six patients (6.2%), and HLA-B27 was positive in five (5.8%). In conclusion, the articular manifestations in the present study were predominantly oligoarticular and asymmetric, with a low frequency of ophthalmologic involvement and positive HLA-B27.
We analyzed the association between single nucleotide polymorphisms in IL-12 and IL-18 genes in disease susceptibility and severity of SLE in Thais. A weak association was observed between A allele of the IL-12 gene at the 3' untranslated region in SLE patients with proteinuria (OR = 1.89, 95% CI = 1.05-3.40, P = 0.02, Pc = 0.06). In addition, we found a significant association between C allele of IL-18 (-137) with arthritis (OR = 6.88, 95% CI = 1.54-42.93, P = 0.003, Pc = 0.009). The presence of one C allele (C/C+C/G) was associated with significant OR of 8.72 (95% CI = 1.83-56.71, P = 0.001, Pc = 0.003). Interestingly, we found the combined effect between the G/C genotype of IL-18 (-137) and the A/A genotype of IFNG (+874) gene causing susceptibility of arthritis in SLE patients (OR = 13.22, 95% CI = 1.56-291.66, P = 0.004).
Out of a cohort of 64 patients with seronegative oligoarthritis (SO), 8 patients with HLA-B13, 5 with Bw16 and 3 with HLA-B17 were invited to participate in a 14-year check-up. Thirteen patients showed some features of psoriatic arthritis, including 5 with suspected skin or nail disease, 5 with a family history of psoriasis, 3 with DIP joint affliction, and 2 with aortic valve insufficiency. It is concluded that a quarter of the patients with SO may have hidden psoriatic arthritis.
We studied the clinical profile, laboratory parameters, disease course, and outcomes of patients with adult onset Still's disease (AOSD). A retrospective analysis of adult patients with Still's disease diagnosed from 2000 to 2004 was carried out. Their clinical features and laboratory findings at presentation, disease course, and outcomes were analyzed. Data of 14 patients with Still's disease were analyzed. The age at disease onset ranged from 16 to 59 years with a mean of 29.85, the male to female ratio being 9:5. The mean duration of illness from onset of symptoms to presentation was 14.5 months (range). The most common clinical manifestations were fever (n = 14), articular symptoms (n = 14), rash (n = 8), weight loss (n = 12), and sore throat (n = 5). Elevated ESR was present in all patients with a mean of 98.3 mm at 1 h. Hepatic enzymes were elevated in seven patients at disease onset. The mean duration of follow up was 19.14 months (range). Three patients progressed to chronic arthropathy. Cyclosporine led to dramatic recovery in five patients. Macrophage activation syndrome (MAS) was present in two patients, one after sulfasalazine therapy. One patient with MAS died. Still's disease, although uncommon, has characteristic constellation of clinical and laboratory features and should be considered in the differential diagnosis of fever of unknown origin. Nonsteroidal anti-inflammatory drugs, steroids, and methotrexate may not be always effective, and cyclosporine is an effective drug in resistant cases. Sulfasalazine should be avoided in cases of AOSD.
Bone biopsy is a diagnostic procedure restricted to untypical, unclear and complicated cases in evidence-based guidelines on diagnosis and treatment of osteoporosis. Its relevance has been a topic of recent controversial discussion. This study was performed to evaluate its role and relevance in routine use. A total of 99 horizontal transiliac bone biopsies performed over a time period of 14 years because of an osteological indication in one single centre were analysed, which reflects that bone biopsy followed about 0.003% of patients' consultations. Bone biopsies were indicated for osteoporotic males (n = 63) and premenopausal osteoporotic females (n = 18) without endocrine abnormality and normal immunofixation (serum and urine), suspected systemic/malignant disease such as mastocytosis, osteogenesis imperfecta, non-secreting plasmocytoma, metastatic infiltration (n = 16) and decreasing bone mineral density under anti-osteoporotic treatment (n = 2). The most frequent diagnoses besides osteoporosis were normal histology, borderline finding towards mild osteoporosis, and osteoporomalacia with relevant osteoidosis. In some cases, pathological findings in bone marrow were detected. In most cases (82/99), bone biopsy led to consequences in medical treatment. Following histopathological diagnosis, 16 patients did not receive any anti-osteoporotic treatment. In six patients, further diagnostic procedures were initiated because of bone histology. Bone biopsy was well tolerated and complications were rare and mild. In conclusion, despite all progress in non-invasive diagnostic procedures for metabolic bone diseases such as osteoporosis, there remains a small but significant subset of patients who may benefit from inclusion of bone biopsy into the diagnostic procedure.
We studied the levels of miR-146a and miR-155 in the urine sediment of SLE patients. The levels of miR-146a and miR-155 in the urine sediment of 40 SLE patients who were receiving calcitriol treatment and 13 healthy controls were determined with real-time quantitative polymerase chain reaction. The levels of urinary miR-146a and miR-155 in patients with SLE were significantly higher than that in healthy controls. Calcitriol treatment reduced the levels of urinary miR-155 in patients with SLE. The level of urinary miR-146a significantly correlated with estimated glomerular filtration rate (r = 0.242, P = 0.008). The level of urinary miR-155 significantly correlated with proteinuria (r = 0.407, P < 0.001) and systemic lupus erythematosus disease activity index (r = 0.278, P = 0.002). The level of urinary miR-146a reversely correlated with the urinary expression of TNF-α (r = -0.247, P = 0.012). Our results suggested that miR-146a and miR-155 might play important roles in the pathophysiology of SLE and the levels of urinary miR-146a and miR-155 could be used as potential markers for diagnosis, disease activity, and therapeutic response.
The present paper is a description of 148 patients with circulating antinuclear antibodies and multisystemic disease filed during 18 years by one of the authors and followed up to date in 1981-83. Seventy-eight per cent of the patients satisfied the 1971 ARA criteria for the classification of systemic lupus erythematosus and 92 per cent fulfilled the 1982 ARA criteria. Eighty-five per cent were women, the mean age at onset of SLE was 32 years. Malar rash and arthritis were early manifestations in 80 per cent of the patients whereas the onset of nephropathy, CNS manifestations, serositis, and peripheral cytopenia was delayed in about half of the patients. Nephropathy and thrombocytopenia were observed particularly in the youngest patients. The mean duration of the observation period was 8 years. The 10-year-survival was 80 per cent. Half of the deaths were presumably unrelated to SLE. The mean ages at entry of patients who died of SLE and of unrelated causes were 30 and 52 years respectively. Eighteen per cent of the deaths were caused by uremia and 18 per cent by infections. The total and the SLE related mortalities were evenly distributed throughout the observation period. The morbidity (incidence of new ARA criteria and other findings indicating active disease) decreased during the first year of observation but rarely subsided completely during the following years. All patients observed for more than 10 years showed evidence of active disease during the rest of the observation period and most showed evidence of renal disease.
The predictive value of a number of clinical and laboratory variables for the mortality of 148 patients with systemic lupus erythematosus (SLE) with a mean observation period of 8 years and a 10-year-survival of 80 per cent was calculated by means of differentiated survival rate analyses and stepwise regression analyses. The predictive power of several variables increased if the calculations were based on deaths caused by SLE rather than on the total mortality rate. The survival rate decreased after 1973 because a diagnosis of SLE was made in some patients with terminal disease who would have remained without a diagnosis before that time. The causes of death and the treatment were identical before and after 1973. The presence of a high number of diagnostic ARA criteria within the first year of observation was a predictor of decreased survival. Severe but non-fatal infections (meningitis, septicemia, pneumonia) significantly reduced the survival rate. Patients with proteinuria and azotemia, within the first 2 years of observation, had a 10-year-survival of 70 per cent. The survival of patients with CNS manifestations was not significantly reduced. The butterfly rash and the presence of lymphopenia were predictors of decreased survival, whereas the presence of DNA antibodies had no predictive value for survival.
This study aims to investigate the disease-related knowledge of gout patients and doctors in south China and to identify the important targets of education for patients and doctors. A cross-section survey of 154 primary gout patients and 185 doctors who may see gout patients was conducted with a modified questionnaire with ten items of gout-related knowledge. The participants were considered to have gout-related knowledge if he or she correctly answered seven or more items. One hundred and forty-nine valid questionnaires from patients, 33 from rheumatology physicians, and 151 from non-rheumatology doctors were collected for statistical analysis. The mean correctly answered items of three groups were 6.6 ± 2.2, 9.6 ± 0.53, and 8.0 ± 1.4, with rate of being considered to have knowledge about gout 51.7, 100, and 90.1 %, respectively (P < 0.05). The correct answer rate for each particular item was over 80 % in the rheumatology physician group. Patients or non-rheumatology doctors knew the optimal serum uric acid (sUA) level (48.3 vs 55.6 %), the need to take lifelong urate-lowering drugs (29.5 vs 43.6 %), that allopurinol is a urate-lowering drug (55.7 vs 76.0 %), and how to prevent attacks induced by urate-lowering therapy (ULT) (60.4 vs 74.0 %). Logistic regression showed that higher education predicted which patients had gout-related knowledge. Both the gout patients and non-rheumatology doctors in south China had poor knowledge on ULT. Since many gout patients do not see rheumatologists, our data suggest that further education should focus on patients and non-rheumatologists and emphasize the use of urate-lowering drugs, treatment duration, the target sUA level, and prophylaxis against acute attacks.
Needle arthroscopy is an office-based technique allowing direct visualisation of the knee cavity and selective sampling of the synovial membrane. We performed needle arthroscopy in 150 patients with synovitis of the knee (1) to evaluate the diagnostic potential in early arthritis, (2) to perform therapeutic lavage in persistent inflammatory synovitis and (3) to assess the balance between technical feasibility, safety and patient comfort on the one hand, and the relevance of the obtained macro- and microscopic information for diagnosis and research purposes on the other. After disinfection of the leg and local anaesthesia of the skin and joint, a 1.8-2.7 mm needle arthroscope was introduced into the knee. Synovial fluid was aspirated and lavage of the joint cavity was performed to allow macroscopic evaluation of hyperaemia and hypertrophy of the synovial membrane. Biopsies were taken at inflamed sites, followed by another lavage to remove blood and debris. Needle arthroscopy of the knee is a simple and easy to perform technique made particularly attractive by the local anaesthesia and the ambulatory setting. It allows good macroscopic evaluation of synovial inflammation and selective sampling of the synovial membrane. Biopsies are suitable for RNA and DNA extraction, bacterial or lymphocyte culture, and cell isolation. Because samples were sometimes too small for representative histology, we switched from a 1.8 mm to a 2.7 mm biopsy forceps with good results. In nearly all cases the arthroscopy was well tolerated. Moreover, some patients reported relief of symptoms and even improvement of mobility after lavage of the inflamed joint. No major complications were noted. It was concluded that needle arthroscopy of the knee is a simple, safe and well-tolerated technique, with promising perspectives as a diagnostic, scientific and possibly therapeutic tool in rheumatic diseases.
We performed a longitudinal follow-up study of clinical findings in 151 patients with high-titer antibodies against U1 ribonucleoprotein (U1RNP) as measured by haemagglutination. Formal connective tissue disease (CTD) diagnoses were assigned and diagnostic transitions analysed. One-hundred eighteen females and 33 males entered the study; the mean duration of follow-up was 7.1 years. Mean age at entry was 34.7 years; 73% of the patients had early disease (duration <2 years). Fifty-six patients (37%) presented with a definite diagnosis, most often mixed connective tissue disease (MCTD, n=40), followed by systemic lupus erythematosus (SLE, n=11) and systemic sclerosis (SSc, n=5). Of 84 patients (56%) presenting with nonspecific symptoms of possible, “undifferentiated” CTD, 58 developed MCTD, 4 SSc and 2 SLE. By the end of the follow-up period, 127 patients had developed a well-defined CTD; final diagnoses were: MCTD (n=97), SLE (n=18), SSc (n=12). We conclude that CTD in the context of high-titer anti-U1RNP antibodies may be transitive and sequential in nature, although the diagnostic criteria for MCTD previously proposed by our group seem to delimit a clinically stable condition in most patients in this subgroup.
Characteristics of the sample at baseline 
-Assessment of clinical parameters 
-Knee function according to the Lequesne and HAQ questionnaires
-Distribution of the types of adverse effects and events between groups 
The aim of the present study was to investigate the long-term effectiveness of and tolerance to Yttrium-90 and Samarium-153-particulate hydroxyapatite radiation synovectomy in patients with rheumatoid arthritis (RA) and chronic knee synovitis. Eight-four patients (90 knees) with chronic knee synovitis and RA (according to the American College of Rheumatology criteria) participated in a controlled, double-blinded trial. Patients were randomized to receive an intra-articular injection with either 5 mCi Yttrium-90 plus 40 mg of triamcinolone hexacetonide (Y/TH Group), 15 mCi Samarium-153 hydroxyapatite plus 40 mg of triamcinolone hexacetonide (Sm/TH Group), or 40 mg triamcinolone hexacetonide alone (Control Group). Blinded examination at baseline, 1, 4, 12, 32, and 48 weeks post-intervention included a visual analog scale for joint pain and swelling, morning stiffness, range of motion, knee circumference, Likert scale, percentage of improvement, Stanford Health Assessment Questionnaire, Lequesne index, use of non-steroidal anti-inflammatory drugs and corticosteroids, events and adverse effects, calls to the physician, and hospital visits. There were three withdrawals prior to the injections. Regarding the pain, there was a significantly better response in the Y/TH Group versus the Sm/TH Group at T1 (p = 0.025) and versus TH alone at T48 (p = 0.026). The Sm/TH group had more adverse effects (p = 0.042), but these were mild and transitory. For the pain parameter alone, Yttrium-90 radiosynovectomy associated to TH proved superior to Samarium-153 hydroxyapatite radiosynovectomy associated to TH at T1 and to synovectomy with TH at T48. No other statistically significant inter-group differences were detected.
The authors investigated changes in the ratio of CD4+ to CD8+ T cells (CD4/CD8 ratio) and T-cell activation, indicated by human leukocyte antigen (HLA)-DR expression, in patients with systemic lupus erythematosus (SLE) following treatment. An increase was observed in the CD4/CD8 ratio as well as a decrease in the expression of HLA-DR on T cells with the improvement of clinical manifestations on treatment with steroids or cyclosporine (CSA). In addition, steroid treatment suppressed whereas CSA treatment exerted no perceptible influence on the serum interleukin (IL)-16 level, concurrent with changes in T-cell phenotypes. This indicated that the mechanism of the change in the CD4/CD8 ratio differed depending on the drug, and CD8+ T cells could play an important role in reducing this ratio. The CD4/CD8 ratio and HLA-DR expression may be good indicators of therapeutic efficacy in some SLE patients.
Top-cited authors
Luca Cantarini
  • Università degli Studi di Siena
Francesco Caso
  • University of Naples Federico II
Jo Nijs
  • Vrije Universiteit Brussel
Luisa Costa
  • University of Naples Federico II
Mauro Galeazzi
  • Università degli Studi di Siena