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A few studies have reported the safety profile of interleukin (IL)-1 blockers from real life. The aim of this study is to describe anakinra (ANA) and canakinumab (CAN) safety profile in children and adults, based on data from a real-life setting. Demographic, clinical, and therapeutic data from patients treated with ANA and CAN were retrospectively collected and analyzed. Four hundred and seventy five patients were enrolled; ANA and CAN were prescribed in 421 and 105 treatment courses, respectively. During a mean follow-up of 24.39 ± 27.04 months, 89 adverse events (AE) were recorded; 13 (14.61%) were classified as serious AE (sAE). The overall estimated rate of AE and sAE was 8.4 per 100 patients/year. Safety concerns were more frequent among patients aged ≥ 65 years compared with patients < 16 years (p = 0.002). No differences were detected in the frequency of safety concerns between monotherapy and combination therapy with immunosuppressants (p = 0.055), but a significant difference was observed when injection site reactions were excluded from AE (p = 0.01). No differences were identified in relation to gender (p = 0.462), different lines of biologic therapy (p = 0.775), and different dosages (p = 0.70 ANA; p = 0.39 CAN). The overall drug retention rate was significantly different according to the occurrence of safety concerns (p value < 0.0001); distinguishing between ANA and CAN, significance was maintained only for ANA (p < 0.0001 ANA; p > 0.05 CAN). Treatment duration was the only variable associated with onset of AE (OR = 0.399 [C.I. 0.250–0.638], p = 0.0001). ANA and CAN have shown an excellent safety profile; the risk for AE and sAE tends to decrease over time from the start of IL-1 inhibition.

The "Euro-Lupus Cohort" is composed by 1000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium-the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors. © 2005 Elsevier B.V. All rights reserved.

The "Euro-Lupus Cohort" is composed by 1,000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium - the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors.

The study investigated the differences in pain perception in highly (Highs) and low (Lows) hypnotizable patients with chronic benign pain undergoing hypnotic suggestions of analgesia. Self reports of pain intensity were collected in different groups of fibromyalgic patients: (1) Highs and Lows during pre-hypnosis, neutral hypnosis, suggestions for analgesia, posthypnotic conditions; (2) Lows during suggestions for analgesia administered after a mental stress instead of neutral hypnosis; (3) healthy Lows receiving nociceptive stimulation during hypnotic relaxation and suggestions of analgesia. The results showed that Highs and Lows differed in their response to suggestions, but significant analgesia was reported also by Lows. These individuals did not report any difference in pain perception between the sessions including mental stress and hypnotic relaxation. No change in pain perception was observed in healthy Lows during nociceptive stimulation associated with relaxation and suggestions for analgesia. In conclusion, the presence of chronic pain seems to be responsible for the paradoxical response of non hypnotizable patients to hypnotic suggestions.

To verify whether synthetic cannabinoids (CP55,940 and WIN55,212-2) are able to exert an anti-inflammatory effect on rheumatoid fibroblast-like synoviocytes (FLS) by down-regulating cytokine production, and determine whether this effect could be mediated by CB1/CB2 cannabinoid receptors.Interleukin-6 (IL-6) and interleukin-8 (IL-8) were assayed in the supernatant from cultured FLS by ELISA method before and after 3 hours of incubation with CP55,940 (10 microM) and WIN55,212-2 (10 microM). Co-stimulation of cells with the cannabinoid receptor antagonists was performed to evaluate receptor involvement in cytokine modulation. All the experiments were conducted in basal conditions and after 1 hour pre-incubation with 0.1 ng/ml IL-1beta. FLS expression of CB1 and CB2 receptor was studied by Western Blot analyses.Both CP55,940 and WIN55,212-2 induced a potent and significant reduction in IL-6 and IL-8 secretion from IL-1beta. stimulated FLS. Although FLS express CB1 and CB2 receptor, cannabinoid receptor antagonists did not significantly modify the inhibition of cytokines secretion induced by CP55,940 and WIN55,212-2.In vitro, CP55,940 and WIN55,212-2 exert a potent anti-inflammatory effect on rheumatoid FLS via a non-CB1/CB2 receptor mediated mechanism.

Rheumatoid arthritis (RA) is a chronic inflammatory disease which involves the synovial membrane of multiple diarthroidal joints causing damage to cartilage and bones. The damage process seems to be related to an overproduction of oxygen reactive species inducing an oxidative perturbation. Since sulfhydryl groups are primary antioxidant factors, we were interested in investigating the balance of plasma sulfhydryl/disulfides in patients with active RA compared to healthy control subjects.Twenty-one patients with RA and 15 age-matched controls were studied. Plasmatic sulfhydryl groups and their disulfide form concentrations were measured by spectrophotometry or HPLC.RA patients showed significantly lower levels of plasma protein sulfhydryls and cysteinyl-glycine compared to healthy controls (p0.001). Conversely, cystine and homocystine, and protein-bound cysteine and homocysteine were significantly increased (p0.005 in disulfides forms and p0.05 in protein mixed disulfides forms). There was a significant correlation between some clinical data (ESR, number of tender/swollen joints) and some of the parameters studied.The results of this study indicate a biochemical disturbance of plasma sulfhydryl/disulfides balance in patients with RA compared to controls with an increase in some oxidised forms (disulfides and protein mixed disulfides) and a decrease in free thiols. The increase in total homocysteine, correlated to the higher risk of cardiovascular diseases in RA patients, is associated with higher levels of the oxidised forms, disulfides and protein-thiol mixed disulfides.

This study investigated the effect of hydrostatic cyclical pressure on the cell ultrastructure and cytoskeleton of normal and osteoarthritis (OA) human cultivated chondrocytes in vitro.The different effects of pressurization with sinusoidal waves at a minimum pressure of 1 MPa, a maximum pressure of 5 MPa and a frequency of 0.25 Hz for 3 hrs on normal and OA chondrocytes were assessed by transmission electron microscopy (TEM), scanning electron microscopy (SEM) and immunoflurescence microscopy (IF).Structural differences exist between normal and OA chondrocytes at the nuclear, cytoplasmic and cytoskeletal level. Pressurization did not alter the normal chondrocytes, but had a beneficial effect on OA chondrocytes, by increasing the number of cell organelles responsible for synthesis activities. IF examination has shown that the distribution of actin protein in normal chondrocytes is polarized on the apical sides of the cellular cytoplasm. However, in OA chondrocytes the signal of the actin protein is not as well defined. Similarly, the localization of the tubulin protein in normal and OA cells also appears to be different. Hydrostatic pressure did not cause any modification in the cytoskeletal organization of the OA chondrocytes.This study confirms the different morphology, structure and cytoskeletal aspect of normal and OA chondrocytes and the important role played by pressure on cell morphology. The recovery of OA chondrocytes observed by an increase of cytoplasmic organelles does not seem to involve the cytoskeleton.

We evaluated the occurrence of spontaneous chromosome damage in cultured peripheral lymphocytes of subjects with idiopathic and pre-scleroderma Raynaud's phenomenon, by means of molecular cytogenetic analysis. Using the micronucleus assay as a marker of chromosome alteration, we studied 30 patients with pre-scleroderma Raynaud's phenomenon, 30 patients with idiopathic Raynaud's phenomenon and 30 healthy subjects. All subjects were classified as ANA-, ACA+ or Scl 70+. To identify the mechanism of micronucleus formation, fluorescence in situ hybridisation analysis was also performed. Pre-scleroderma Raynaud's phenomenon subjects showed significantly higher micronucleus frequencies than idiopathic Raynaud's phenomenon subjects and controls (37.0 +/- 11.5 vs. 11.1 +/- 3.2 and 10.7 +/- 2.7 respectively p0.0001). Interestingly, subjects with idiopathic Raynaud's phenomenon displayed micronucleus frequency comparable to that of healthy controls. Furthermore, ACA+ subjects showed the highest micronucleus frequencies (41.0 +/- 7.6) as compared to subjects with Scl 70+ antibody (25.0 +/- 3.5). Our results show that circulating lymphocytes of only pre-scleroderma Raynaud's phenomenon subjects undergo chromosomal damage, as detected by the micronucleus assay, at a higher rate than expected. No prevalence of aneuploidogenic or clastogenic events in micronucleus formation is revealed by fluorescence in situ hybridisation analysis.

The "Naiade" Project was carried out in execution of the Decree of December 1994 by the Italian Ministry of Health, with the objective of defining the therapeutic role of spa therapy in the various sectors of medicine. In this study the authors refer to the results obtained in osteoarthritis (OA).The OA study included the observation of patients for 2 consecutive years, with the compilation of a series of clinical and socio-economic data. The initial sample was of 11437 patients suffering from primary and secondary OA, and in the 2(nd) year the total number of assessable patients was 6111 (53.4%). All patients underwent 1 annual cycle of balneotherapy and mud packs therapy for 2 consecutive years. The thermal treatments were carried out in 98 Italian spas with sulphurous water, sodium chloride-bromide-iodide water, sulphate water, and bicarbonate water. Analysis of the data collected confirmed the clinical efficacy of spa treatments for OA, particularly for localisations in the cervical and lumbar spine. The benefits of these treatments and the persistence of the therapeutic effects over time were clearly demonstrated by the collection of some socio-economic indicators relative to the year before each cycle of thermal therapy.In fact, the analysis of these indicators showed a significant reduction in recourse to additional treatments (hospital admissions, physical and pharmacological therapies) and absence from work.The obtained data was particularly interesting for the number of samples examined, the follow-up over a period of 2 years, and the collection of clinical and, especially, socio-economic parameters. The results of the Naiade Project confirmed the value of spa therapies in the treatment of OA.

Little information is available concerning bone mass in patients with psoriatic arthritis (PsA): the existence of less severe periarticular osteoporosis is considered possible, but there are no data concerning the existence of systemic osteoporosis. We investigated bone mineral density (BMD) in patients with PsA.We studied 186 patients with non-axial PsA and 100 healthy subjects, equally divided into 3 groups: women of child-bearing age, women in menopause, and men. No patient had previously received steroid treatment. In all patients, evaluation was made of disease duration, inflammation indices (erythrocyte sedimentation rate, C-reactive protein), functional indices (Steinbrocker scale), and the Health Assessment Questionnaire (HAQ). BMD was measured by fan-beam x-ray densitometry of the lumbar spine, femur, and total body (evaluating the whole skeleton, as well as the spine, trunk, and upper and lower limbs). Ultrasound densitometry of the heel was also performed.BMD was significantly lower in the arthritic than in the healthy subjects regardless of sex, menopausal status, or age, as expressed in g/cm2 (lumbar spine 1.112 vs 1.326; femoral neck 0.870 vs 1.006; total body 1.125 vs 1.203) or by T and Z scores (lumbar T = -1.36, Z = -0.98; femoral neck T = -1.12, Z = -0.83; total body T = -1.09, Z = -0.65). Ultrasound densitometry of the heel was similarly altered (stiffness 96 vs 77; T -1.78; Z -1.29). Among the PsA patients, demineralization in at least one skeletal region was observed in 67% of premenopausal women (marked in 11%), 100% of postmenopausal women (marked in 47%), and 80% of the men (marked in 29%). In premenopausal women, demineralization did not correlate with the disease variables; in postmenopausal women and the men, it correlated with a decline in the functional indices and the HAQ score. This was confirmed by analysis of the relative risk of osteoporosis expressed in odds ratios (HAQ: 1.6; age: 1.4; years since menopause: 1.7).Demineralization was observed in more than 2/3 of our PsA patients without axial involvement. This demineralization was not related to the indices of inflammation or disease duration, but there is a delayed correlation with HAQ score, as well as age and the number of years since menopause.

We describe a patient with cerebrotendinous xanthomatosis (CTX) who saw a Rheumatologist because of joint and muscle pain in the lower limbs. Clinical examination did not reveal any classic joint disease; however, tendon lesions and clumsy gait were noted. The patient presented with a swollen Achilles tendon bilaterally and a parapareto-spastic gait; Babinski sign was positive on the right side, and hyperreflexia of both lower limbs could be demonstrated. As bilateral cataracts were present, we have interpreted the aforementioned signs as CTX with spinal involvement; mean plasma cholesterol was increased, thus confirming the diagnosis. The primary biochemical abnormality of this disease is a defect in the synthesis of bile acids; therefore, chenodeoxycholic acid (CDCA) has been tried, and beneficial effects following CDCA treatment, especially in the early stages of CTX, have been reported in the literature. We report this case because of the severity and the rarity of this disease, and also because of its hereditary transmission. Our aim is to underline the need of a precocious diagnosis, in order to prevent a further progression of the disease; this therapeutic goal can now be achieved, thanks to the therapeutic regimens recently developed.

Antineutrophil cytoplasmic antibodies (ANCA) are present in several vasculitides and in other immunomediated diseases. The reported prevalence of ANCA in rheumatoid arthritis (RA) is variable. In addition, the presence of such autoantibodies has been poorly investigated in synovial fluid (SF). The objectives of this study were (1) to investigate the presence of ANCA both in the serum and in SF from patients with RA and other forms of synovitis (OS); (2) to analyze the reactivity of ANCA against isolated antigens proteinase 3 (PR3), myeloperoxidase (MPO) and lactoferrin (LF); and (3) to evaluate the clinical relevance of these autoantibodies.Twenty-eight patients with RA, 13 with OS, and 17 with osteoarthritis (OA) of the knee joint were studied. No patient had clinical manifestations of vasculitis. SF and serum samples were investigated for the presence of ANCA by indirect immunofluorescence (IIF); the reactivity against PR3, MPO and LF was assessed by ELISA.ANCA were detected by IIF in SF of 39.3% patients with RA, 38.5% with OS, and 5.9% with OA. With 2 exceptions, patients who had ANCA in SF showed positivity also in serum. The presence of both anti-MPO and anti-LF antibodies was found in 3 patients with RA and 1 with OA; a patient with RA showed antibodies only against LF and another one with RA only against MPO. No reactivity was found against PR3. In patients with RA ANCA were not associated with disease activity.We found an increased incidence of ANCA both in SF and serum from patients with RA and OS. The pathogenic role and the clinical relevance of such autoantibodies in these diseases remain to be established.

We used polymerase chain reaction amplification and hybridization with specific oligonucleotides to analyze the distribution of DPB1, DQA1, DQB1, and DRB1 allelic variants in 48 patients with rheumatoid arthritis (RA) and compared our results with those from 109 randomly chosen, healthy control subjects. Our work confirms a previously reported increase in DR4 specificity in RA: in particular, we found a statistically significant positive association of the DRB1*0401 and DRB1*0404 alleles with RA. When we compared the DR4 groups, however, none of the DRB1*04 alleles were increased in the RA group. Molecular analysis of the other DRB1 polymorphic variants disclosed the trend of a positive association of DRB1*0101 (DR1) in DR4 negative patients vs DR4 negative healthy control subjects, and an increase in DRw6 (DRB1*13,*14) in the DR4 and/or DR1 negative patient group. Moreover, analysis of the association between RA and a heptapeptide motif (positions 67-74) in the third hypervariable region confirmed that this epitope confers enhanced risk for the development of RA with respect to the allele DRB1*0404 (etiologic fraction = 0.53 vs 0.12). We also observed a statistically significant increase in DQA1*0301 and DQB1*0302 accompanied by a significant decrease in DQA1*0202, DQA1*0501 and DQB1*0201 in RA patients. Analysis of DPB1 alleles disclosed no significant differences between RA patients and healthy control subjects.

Previous studies with intraarticular administration of somatostatin (SST14) in rheumatoid arthritis showed an antiinflammatory and analgesic effect. The aim of the present study was to demonstrate the efficacy and tolerability of SST14 in rheumatoid arthritis (RA) patients for a longer period of treatment than previously scheduled. Forty-one patients with RA of the knee were treated with a cycle of intraarticular injection of 750 micrograms of SST14, every 15 days. The efficacy of SST14 was evaluated by determining acute phase parameters (erythrocyte sedimentation rate, C-reactive protein [CRP]) and by clinical assessment (pain at rest and on movement, joint tenderness, morning stiffness, spontaneous pain). Additionally, telethermography was performed to evaluate the intensity of the joint inflammation. The tolerability of the treatment was also assessed both by patients and physicians. SST14 produced a reduction in all parameters; this was already statistically significant after the second injection in terms of pain at rest and on movement, and after the third injection for all other symptoms. The treatment showed an excellent tolerability, both local and systemic. Our results indicate the analgesic property of SST14 and demonstrate its capacity to reduce progressively joint inflammation confirmed by thermography and by reduction of pain, after a month of therapy.

Thirty patients presenting with painful shoulder syndrome were treated with i.m. ketoprofen 100 mg b.d. for 8 days to assess the efficacy and tolerance of the above treatment regime. The patients' condition was monitored by clinical, instrumental and laboratory examinations. Ketoprofen was found to be significantly effective in all cases of non calcific rotator cuff tendinitis while no improvement was noted in calcific tendinitis. The above data confirm the efficacy and tolerance of ketoprofen in the treatment of painful shoulder syndrome as an alternative to local steroid therapy.

Although the exact etiology of progressive systemic sclerosis (SSP) is still unknown, it is felt that immunologic disorders may be implicated in its pathogenesis. On the basis of these considerations, an open study with an immunomodulating drug, thymopentin, was performed in 20 SSP outpatients. These subjects were initially treated with thymopentin three times a week for three consecutive months (phase I); during a second study phase lasting three months, 10 patients continued to receive thymopentin and the remaining 10 placebo (phase II). A significant improvement in various clinical, laboratory and instrumental findings was seen following thymopentin treatment. During phase II, those on placebo regressed to basal conditions, while an added improvement was noted in those who continued with thymopentin.

A case of CREST syndrome presenting with marked diffuse calcinosis and prevailing joint involvement is presented by the authors. Diffractometry revealed the presence of calcified hydroxy-apatite crystals within subcutaneous nodules. Scleroderma-like microcirculatory changes with blood flow alterations typical of Raynaud's syndrome were present on capillaroscopy. The authors feel the case to be of interest not only in view of the rare occurrence of the condition but also of the particular extent and severity of the signs and symptoms presented by this patient.

In 20 patients suffering from osteoarthritis and treated with non steroidal anti-inflammatory drugs (NSAIDs) for one month sucralfate has been added for further two months. Endoscopic examination before/after this treatment confirmed the cytoprotective property of sucralfate, with normalization of the gastric mucosa and subsidence of subjective symptomatology.

A double-blind crossover trial was carried out in 60 patients with osteoarthritis of large joints. Patients received both indoprofen 600 mg daily and diclofenac 100 mg daily for one week without any interval between treatments. The variables investigated were: pain at rest, pain on active motion under load, quality of sleep, articular flexion and patient's preference. The assessments were made before and at the end of each treatment period. Significant improvements were found for all variables with both drugs. No significant differences were detected between the two drugs. Ten patients (6 on indoprofen and 4 on diclofenac) reported adverse reactions i.e. slight gastralgia in most cases. No withdrawals of treatment were observed.

In order to study the role of excessive synovial iron sequestration in the production of anemia in rheumatoid arthritis (RA), the antianemic efficacy and anti-inflammatory effect of desferrioxamine administered in a short-term treatment (14 days), were evaluated in 10 patients suffering from classic or definite RA and hyposideremic anemia. Treatment with desferrioxamine showed an elevated urinary iron excretion, a significant increase of serum iron, UIBC and hemoglobin, and a marked progressive decrease of serum ferritin. A moderate improvement of the pain intensity, morning stiffness and Ritchie's index was also observed. The results obtained suggest that excessive reticuloendothelial iron deposits occur in RA and that the iron uptake can be an important factor in the production of anemia. Desferrioxamine seems to be useful in the treatment of patients suffering from RA and anemia, in order to release iron from synovial tissue, reduce the inflammatory process and improve anemia, changing an anemia which is typically resistant to the martial therapy into an iron-sensitive anemia.

Eighty patients with osteoarthritis of various localization completed a double-blind, parallel-group trial of 2 weeks' duration comparing the efficacy and tolerance of ketoprofen slow-release capsules (150 mg) given either as a morning or a midday or an evening dose with that of ketoprofen conventional capsules (50 mg) 3X daily. All regimens were associated with a statistically significant improvement in pain at rest, pain on active motion, quality of sleep, and spine flexion, but there was no difference between treatments. The tolerance of ketoprofen was also similar in all groups. In view of the alleged better compliance of patients with once-daily medications, the new slow-release formulation of ketoprofen appears to be a useful alternative to the conventional capsules.

The occurrence of cardiac involvement in RA is frequent but cardiac lesions are observed more frequently at necroscopy than on clinical examination. The case of a RA patient with a serious mitral valves involvement is reported in which the histological examination of the bioptic tissue obtained during surgical valves replacement showed a typical rheumatoid granulomatous inflammation of the endocardium.

The changes occurring in the fatty acid composition of the plasma lipids were studied in gout. The major changes consisted in an increase in oleic acid and a decrease in linoleic and arachidonic acids in most lipid fractions of plasma; linoleic acid is unchanged in plasma cholesteryl esters and in FFA while arachidonic acid does not vary only in FFA. These changes are not related either to diet or to the age of patients and are similar to those reported in atherosclerotic and diabetic patients, as well as those with cardiac ischemia. The variations observed are directly influenced by the ratio essential fatty acids/monoenoic acids and all factors affecting this ratio.

The authors have examined the levels of the plasma cholesterol and triglycerides, of the plasma lipoprotein (HDL, LDL, VLDL) and of their main apolipoproteins (apo-A and apo-B) in a group of 34 patients affected by gout and in a population of healthy subjects considered as a contrast group, trying to establish a plausible dislipidemic factor which could justify the major occurrence of coronary heart disease in patients suffering from gout. Statistical analysis was done with the t-test. The group of patients affected by gout had significantly higher levels of triglycerides and VLDL-C and lower levels of HDL-C than the population of healthy subjects. The change of the lipoprotein pattern observed in the patients suffering from gout may be linked to reduction of the catabolism of the triglycerides rich lipoprotein. This reduction is probably linked to a inhibition of lipoprotein lipase.

The authors have examined the incidence of the rheumatoid factor in the serum of a group of 100 patients, 95 males and 5 females, suffering from gout, of whom only 6 suffered from chronic gout. The rheumatoid factor in the serum was measured by RA-test (1:40) and by Waaler-Rose test (1:32). The rheumatoid factor was not present in the examined subjects and so we can state that such serum parameter does not represent, for its negativity, a laboratory index of any evidence in the gout and it doesn't represent a reason for diagnostic doubts with other forms with the rheumatoid factor in the serum.

To investigate by high frequency grey-scale ultrasonography (US) and power Doppler sonography (PDS) the modality and frequency of involvement of the Achilles tendon and plantar fascia in chondrocalcinosis (CC), and to correlate these findings with clinical complaints and radiographic evidence.The heels of 57 consecutive patients with CC were evaluated by US, PDS, and radiography. One control group of 50 consecutive patients with osteoarthritis (OA) without signs of CC was studied in the same way. A second control group of 50 healthy subjects underwent only US/PDS examination. All subjects also underwent clinical assessment.US revealed Achilles tendon calcifications in 57.9% of those with CC, but none in the control groups. Plantar fascia calcifications were observed in 15.8% of CC and in 2% of OA cases, but not in healthy controls. US showed no significant difference in postero-inferior and inferior calcaneal enthesophytosis between subjects with CC (59.6% and 61.4%, respectively) and those with OA (46% and 44%, respectively). Such alterations were also present, in lower percentages, in the healthy controls. Posterior and inferior calcaneal erosions were absent in all groups. Achilles enthesopathy was found in 22.8% of patients with CC (14.9% of heels, with vascular signals in 11.4% of heels on PDS). Deep retrocalcaneal bursitis was found in 10.5% of patients with CC (7% of heels, with vascular signals in 5.2% of heels on PDS). Plantar fasciitis was found in 40.3% of patients with CC (36% of heels, with vascular signals in 2.6% of heels on PDS) and in 14% of OA patients, but not in healthy controls. No significant correlation was found between talalgia or sex of patients and presence of calcifications. A significant correlation was observed between talalgia and Achilles enthesopathy (r = 0.78, p0.0001), deep retrocalcaneal bursitis (r = 0.7, p0.0001), and plantar fasciitis (r = 0.31, p0.001). A significant correlation between talalgia and vascular signals on PDS was observed in Achilles enthesopathy (r = 0.91, p0.0001) and deep retrocalcaneal bursitis (r = 0.65, p0.0001). The presence of vascular signals on PDS was significantly associated with the presence of tendinous and bursal grey-scale US alterations. Achilles tendon calcifications were 39% sensitive, 100% specific, and 77% accurate for the presence of CC, whereas plantar fascia calcifications were 15% sensitive, 98% specific, and 54% accurate. Excellent agreement was found between US and radiography in detecting Achilles tendon calcifications (k = 0.86), plantar fascia calcifications (k = 0.77), postero-inferior enthesophytosis (k = 0.90), and inferior enthesophytosis (k = 0.83).Calcaneal tendon calcifications are frequent and asymptomatic findings in patients with CC, and they have a high specificity for this disease. US shows high agreement with radiography in depicting calcifications and enthesophytosis. Inflammatory changes of the calcaneal soft tissues are frequently observed by US and PDS in patients with chondrocalcinosis.

To identify the time point of the greatest degree of improvement in daily living activities, pain and depression in patients with osteoarthritis (OA) of the knee during 6 months of treatment with NSAIDs, in order to define compliance and drop-out rate.107 patients were recruited into a multicentre, prospective, randomized, controlled trial comparing two treatments, piroxicam-beta-cyclodextrin (PBCD) and slow release diclofenac (DCL).The greatest improvement in quality of life occurred in both groups after 3 months, with a slight further gain observed by the end of treatment. The Stanford Health Assessment Questionnaire score improved (p0.05 vs baseline) at 3 and 6 months with PBCD and at 6 months with DCL. The Arthritis Impact Measurement Scale score improved (p0.05 vs baseline) after 6 months in both groups. Significant (p0.05 vs baseline) improvement in other psychological and pain scores were recorded in both groups after 3 and 6 months. Compliance with treatment at 3 months was 73% for PBCD and 72% for DCL, and was 60% in both groups at 6 months.The results of this study indicate that the optimal length of time for an NSAID trial in OA patients is 3 months, when assessment of daily living activities is considered as the main outcome criterion.

The authors investigated the possible correlation between blood concentrations and clinical outcome in 38 auranofin-treated patients with rheumatoid arthritis, diagnosed according to ARA criteria. The results showed that the whole blood gold concentrations did not correlate with the clinical parameters investigated and some laboratory findings. The authors discuss this lack of correlation, suggesting that a clear genetic disposition can interfere with the clinical response, affecting the metabolism and kinetics of the drug.

A qualitative and semi-quantitative evaluation of synovial iron deposits in 20 patients with rheumatoid arthritis (RA) and in 12 patients presenting with degenerative and traumatic joint disease was carried out. Ferric iron deposits, abundant and preferentially distributed in the superficial and deeper connective tissue layers in the RA patients, were more limited and prevalently sited in the synovial lining layer in the controls. These results further underline the increase in synovial iron stores found in active RA and the role played by iron deposits in sustaining inflammation, as has been reported in the literature.

The authors studied sixty patients affected by classical or definite rheumatoid arthritis (RA), to evaluate the possible existence of retinal vasculitis, by employing fluorescein angiography. Retinal vasculitis was found in 18% of the examined patients, even if no clinical and ophthalmoscopic signs of retinal vessel inflammation were present. The authors suggest that the retina should be examined in RA patients, since retinal vasculitis may be asymptomatic at the beginning, but can represent one of the possible extra-articular manifestations of the disease.

The aim of this study was to evaluate bone mass and bone ultrasonometry in patients affected with systemic sclerosis (SSc).Fifty-five patients (mean age 54.1 +/- 14.1 years; 25 premenopausal, and 30 postmenopausal women) affected with SSc (in a limited, intermediate or diffused form) and 60 age-matched healthy controls (30 premenopausal, and 30 postmenopausal women) were studied for Bone Mineral Density (BMD) measured by fan-beam x-ray densitometry, Stiffness Index (SI) measured by ultrasonometry of the heel, inflammation indices (erithrocyte sedimentation rate, C-reactive protein), and autoantibodies (ANA, ENA). Examinations were also carried out in order to determine any internal organ involvement. None of the patients had previously received steroid treatment.BMD was significantly lower in the SSc group than in the control group, whether it was expressed in g/cm2 (lumbar spine: 0.980 vs 1.241, p0.01; femoral neck: 0.832 vs 0.955, p0.05; total body 1.050 vs 1.168, p0.01) or by T- and Z-score (lumbar spine: T = -2.48; Z = -1.10; femoral neck: T = -1.69; Z = -0.55; total body: T = -1.11; Z = -0.48). SI was also altered (75.8 vs 96.2, p0.01; T = -2.10, Z = -1.12). BMD and SI were lower in women with the diffuse form of skin involvement. BMD and SI were lower in women in whom one or more internal organs were involved.SSc patients had reduced BMD and SI that was more marked in the diffuse form and in those with internal organ involvement and that became more marked with age and estrogen deficiency. This demineralisation was not related to the inflammation indices, disease duration, or to the immunological pattern.

Objectives: This study sought to investigate the effects of immunosuppression on arrhythmic myocarditis. Background: The effects of immunosuppressive therapy (IST) on ventricular arrhythmia (VA) have not been reported in patients with immune-mediated biopsy-proven myocarditis. Furthermore, myocarditis arrhythmic risk is still unpredictable. Methods: We enrolled 255 patients with biopsy-proven virus-negative myocarditis and VA (major: ventricular fibrillation, ventricular tachycardia; minor: nonsustained ventricular tachycardia, Lown grade ≥2 premature ventral complexes) at presentation. Serum cardiac autoantibodies (antiheart antibodies, anti–intercalated disk autoantibodies [AIDA]) were detected by a standardized indirect immunofluorescence technique. Whenever accepted and noncontraindicated, IST was started. Control individuals (IST−) were chosen after 1:1 matching to IST+ patients by age, sex, ethnicity, left ventricular ejection fraction, VA type, and treatment. Results: A total of 58 matched patient couples (age 42 ± 13 years; 67% male) were analyzed in the main study cohort. IST duration was 12 ± 1 months. By the 24-month prospective follow-up, major VA occurred in 6 IST+ versus 10 IST− patients (p = 0.42), with no episodes following IST termination. As compared to IST− patients, IST+ patients showed a significant reduction in minor VA burden, as well as improvement in clinical, laboratory, and imaging findings (all p < 0.05). Major VA onset and positive AIDA status were independently associated with major VA at follow-up (hazard ratio [HR]: 14.2; 95% confidence interval [CI]: 2.9 to 68.7 and HR: 8.0; 95% CI: 2.6 to 25.2, respectively; both p < 0.001). Furthermore, in the whole study population (N = 255), IST was independently associated with protection from major VA (HR: 0.3; 95% CI: 0.2 to 0.7; p = 0.01) at 38 ± 21 months of follow-up. Conclusions: In patients with immune-mediated virus-negative myocarditis presenting with VA, IST is associated with positive effects on minor VA and nonarrhythmic endpoints. Short-term effects are limited on major VA, which were independently associated with major VA onset and positive AIDA.

Aims Novel therapies are needed for recurrent pericarditis, particularly when corticosteroid dependent and colchicine resistant. Based on limited data, interleukin-1 blockade with anakinra may be beneficial. The aim of this multicentre registry was to evaluate the broader effectiveness and safety of anakinra in a ‘real world’ population. Methods and results This registry enrolled consecutive patients with recurrent pericarditis who were corticosteroid dependent and colchicine resistant and treated with anakinra. The primary outcome was the pericarditis recurrence rate after treatment. Secondary outcomes included emergency department visits, hospitalisations, corticosteroid use and adverse events. Among 224 patients (46 ± 14 years old, 63% women, 75% idiopathic), the median duration of disease was 17 months (interquartile range 9–33). Most patients had elevated C-reactive protein (91%) and pericardial effusion (88%). After a median treatment of 6 months (3–12), pericarditis recurrences were reduced six-fold (2.33–0.39 per patient per year), emergency department admissions were reduced 11-fold (1.08–0.10 per patient per year), hospitalisations were reduced seven-fold (0.99–0.13 per patient per year). Corticosteroid use was decreased by anakinra (respectively from 80% to 27%; P Conclusion In patients with recurrent pericarditis, anakinra appears efficacious and safe in reducing recurrences, emergency department admissions and hospitalisations.

OBJECTIVE: To assess the clinical characteristics and determinants of pain observed by general practitioners (GPs) in Italian patients with osteoarthritis (OA) of the hand, hip, and knee. METHODS: The 2764 GPs participating in the study were asked to enroll 10 consecutive patients with OA diagnosed according to the American College of Rheumatology (ACR) clinical criteria. To standardize the diagnosis, the GPs received ad hoc training from musculoskeletal system specialists. A questionnaire evaluating demographic data, the clinical characteristics of OA, and previous diagnostic and therapeutic interventions was administered by the GPs. RESULTS: 25,589 evaluable patients were enrolled during a mean period of 2.8 weeks by the GPs: 17,567 women (69%) and 7878 men (31%). The most painful OA joints were the knee in 12,827 patients (54%), the hip in 5645 patients (24%), and the hand in 5467 patients (23%)--percentages calculated on the 23,939 patients for whom this information was available. The weekly incidence of referrals to GPs for OA was higher for women and for knee OA. The median age of the patients was 70 years (range 50 to 104 years) and disease duration was 8.3 +/- 7.10 years. The most frequent comorbidities were hypertension (53%), obesity (22%), osteoporosis (21%), type II diabetes mellitus (15%), and chronic obstructive pulmonary disease (13%). The median pain visual analog scale (VAS) score was higher for women than for men, for hip OA, and for generalized OA (GOA) than for knee and hand OA (P < 0.0001). Intense pain, defined as VAS readings of >60 mm, was increased in women only in the knee (OR = 1.24; 95% CI 1.15 to 1.34) and in GOA (OR = 1.17; 95% CI 1.03 to 1.33). It was also significantly increased in patients older than 70 years (OR = 1.46; 95% CI 1.39 to 1.54), those with a low educational level (OR = 1.44; 95% CI 1.36 to 1.5), a BMI of > or =30 (OR = 1.52; 95% CI 1.42 to 1.61), a disease duration of more than 7 years (OR = 1.60; 95% CI 1.52 to 1.68), comorbidities (OR = 1.61; 95% CI 1.5 to 1.73), and GOA (OR = 2.05; 95% CI 1.91 to 2.19). Manual occupations were associated with highly intense pain only in men. CONCLUSIONS: The results of this study underscore the major impact of OA on care in general practice, the high frequency of OA-associated comorbidities, and the role of different risk factors in OA pain.