Contribution of the new 2012 EULAR/ACR classification criteria for the diagnosis of polymyalgia rheumatica.

Polymyalgia rheumatica (PMR) is one of the most common rheumatic inflammatory disorders in people aged over 50. It is characterized by aching and prolonged morning stiffness in the shoulder and pelvic girdles and neck. To date there are no specific diagnostic tests, and in clinical practice the diagnosis of PMR remains based on its characteristic clinical manifestations, laboratory evidence of systemic inflammation, rapid response to low doses of glucocorticoids and exclusion of other disorders that may present with proximal pain and stiffness. For classification purposes, several criteria have been proposed over time based on retrospective clinical series, but none have been validated and received universal acceptance. Recently, an international collaborative initiative between the EULAR and the ACR was undertaken to develop new polymyalgia rheumatica classification criteria. In this review, the provisional 2012 EULAR/ACR classification criteria will be presented and their contribution for the diagnosis of polymyalgia rheumatica will be discussed.

Serum levels of long pentraxin PTX3 in patients with polymyalgia rheumatica.

OBJECTIVES: To evaluate PTX3 feasibility to provide a prognostic tool in PMR clinical practice. METHODS: Circulating PTX3 levels were measured in 93 PMR patients at disease onset and during corticosteroid therapy and in 46 normal controls (NC) by ELISA. RESULTS: No difference in PTX3 concentrations was observed between NC and PMR either at disease onset and during follow-up or between groups of patients defined according to the presence of recurrence/relapse. CONCLUSIONS: PTX3 serum levels do not increase significantly in active PMR. Further studies on patients with giant-cell arteritis could evaluate whether large vessel involvement may be associated to increased PTX3 levels.

Safety of rituximab in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic disease that requires long-term administration of immunomodulatory drugs with a greater risk of side effects like malignancies, serious infections and cardiovascular diseases. Furthermore, patients with RA are more prone than the general population to these manifestations. Safety of rituximab has been evaluated in the short-term (6 months) and in the medium-term (up to 10 years) in patients who had been previously treated with antagonists of tumor necrosis factor (a-TNF) and/or with methotrexate (MTX) and in patients who were not. Data obtained from clinical trials demonstrated that rituximab is well tolerated either after a single course or after multiple courses. The overall rate of adverse events (AEs) was stable after the first three courses. The most frequent adverse event was infusion-related reactions (IRR). Serious infections did not increase after multiple courses. Data from "real life" confirm that treatment with rituximab is well tolerated.

Toll-like receptor 4 (TLR4) gene polymorphisms in giant cell arteritis.

OBJECTIVE: To investigate potential associations between toll-like receptor 4 (TLR4) gene polymorphisms and susceptibility to, and clinical features of giant cell arteritis (GCA). METHODS: A total of 155 patients with biopsy-proven GCA who were residents of Reggio Emilia, Italy, and 210 population-based controls from the same geographical area were genotyped for two coding single nucleotide polymorphisms of TLR4 (Asp299Gly and Thr399Ile) by molecular methods. The patients were subgrouped according to the presence or absence of polymyalgia rheumatica and severe ischemic complications (visual loss and/or cerebrovascular accidents). RESULTS: The distribution of allele and genotype frequencies did not differ significantly between GCA patients and healthy controls. Carriers of the -299 G allele (G/A+ G/G) [odds ratio (OR) 1.78, 95% confidence intervals (CI) 0.90-3.50)] were more frequent among GCA patients than among the controls, but the difference was not statistically significant. No significant associations were found when GCA patients with and without PMR or with and without severe ischemic complications were compared. CONCLUSION: Our data suggest that the TLR4 gene polymorphisms are not associated with susceptibility to, and clinical expression of, GCA in Italian patients.

Risk factors for severe cranial ischaemic events in an Italian population-based cohort of patients with giant cell arteritis.

OBJECTIVE: To evaluate the impact of traditional cardiovascular risk factors, carotid atherosclerosis and the effect of anti-platelet/anti-coagulant therapy on the occurrence of severe cranial ischaemic events (CIEs) in GCA. METHODS: We identified 180 Reggio Emilia (Italy) residents with biopsy-proven GCA diagnosed between 1986 and 2005. We evaluated data on demographics, clinical features, laboratory investigations, cardiovascular risk factors, anti-platelet/anti-coagulant use and carotid atherosclerosis. RESULTS: Systemic signs/symptoms were significantly less frequent (P = 0.004) and ESR and C-reactive protein (CRP) values at diagnosis were significantly lower (P = 0.03 and P = 0.04, respectively) in patients with CIEs. The prevalence of hypertension and ischaemic heart disease was significantly higher in patients with CIEs than in those without (P = 0.01 and P = 0.006, respectively). Patients treated with anti-platelet/anti-coagulant therapy were significantly more likely to suffer CIEs than those without (P = 0.03), while CIEs were significantly associated with ischaemic heart disease in this subset of patients (P = 0.02). By multivariate logistic regression, we found that the best predictors for the development of severe CIEs included the absence of high (>5.38 mg/dl) CRP levels at diagnosis (OR = 0.31, 95% CI 0.08, 1.20), the absence of systemic manifestations (OR = 0.30, 95% CI 0.08, 1.08), the presence of hypertension (OR = 7.77, 95% CI 0.83, 72.76), and a past history of ischaemic heart disease (OR = 8.65, 95% CI 0.92, 80.95). CONCLUSIONS: In GCA, hypertension, a past history of ischaemic heart disease and a low inflammatory response are associated with a higher risk of developing severe CIEs.

Long-term follow-up of polymyalgia rheumatica patients treated with methotrexate and steroids.

OBJECTIVE: A series of patients with polymyalgia rheumatica (PMR) who received the steroid-sparing combination therapy, prednisone and methotrexate (MTX), underwent a long-term follow-up study at five years to investigate possible reductions of steroid-related side effects. Additional end-points were the number of patients still in need of steroid treatment, the cumulative steroid dose, and the number of flare-ups of PMR. PATIENTS AND METHODS: Fifty-seven PMR patients who were enrolled in a double-blind placebo-controlled randomised trial on the efficacy of MTX added to standard steroid treatment were reviewed after 5 years. Information was collected on the patients' previous health conditions or causes of death through a standardized questionnaire by direct visit, chart review, or interviews with relatives. RESULTS: After 6 years from initiation of therapy, MTX-treated patients had lower ESR (17.1+/-9.7 mm/h vs. 26.8+/-22.9 mm/h, p=0.08) and CRP (2.7+/-2.3 mg/L vs. 10.2+/-16.4 mg/L, p=0.04). 31% MTX-treated patients were still on steroids in comparison with 39.3% controls. The mean cumulative dosage of prednisone in MTX-treated patients was 2.6+/-3.8 g in comparison with 3.2+/-4.1 g for controls (p=0.6). PMR flare-ups were seen in 30.8% of MTX-treated patients and in 44.4% of controls (p=0.39). During the follow-up, 58 and 55 side effects were observed in MTX-treated patients and in controls, respectively. CONCLUSIONS: MTX-treated patients showed slightly less residual inflammation than controls, with the same incidence of steroid-related side effects. PMR is not a benign condition, as often reported, since one third of patients need steroid treatment for more than 6 years.

Cervical interspinous bursitis in active polymyalgia rheumatica.

OBJECTIVE: To evaluate the inflammatory involvement of cervical interspinous bursae in patients with polymyalgia rheumatica (PMR) using MRI. METHODS: In all, 12 consecutive, untreated new patients with PMR were investigated. Five patients with fibromyalgia, two patients with cervical osteoarthritis and six patients with spondyloarthritis with neck pain served as controls. MRI of the cervical spine was performed in all 12 PMR case patients and in 13 control patients. Two of the four patients with PMR with pelvic girdle pain also had MRI of the lumbar spine. RESULTS: MRI evidence of interspinous cervical bursitis was found in all patients with PMR, and in three patients with fibromyalgia, in two with psoriatic spondylitis and one with cervical osteoarthritis. A moderate to marked (grade >or=2 on a semiquantitative 0-3 scale) cervical bursitis occurred significantly more frequently in patients with PMR than in control patients (83.3% compared with 30.7%, p = 0.015). In all patients and controls with cervical bursitis the involvement was found at the C5-C7 cervical interspaces. MRI of the lumbar spine showed lumbar interspinous bursitis at the L3-L5 lumbar interspaces in the two patients with PMR and pelvic girdle pain examined. CONCLUSIONS: Cervical interspinous bursitis is a likely basis for discomfort in the neck of patients with PMR. The prominent inflammatory involvement of cervical bursae supports the hypothesis that PMR is a disorder of prominent involvement of extra-articular synovial structures.

-463 G/A myeloperoxidase promoter polymorphism in giant cell arteritis.

OBJECTIVE: To investigate potential associations between-463 G/A myeloperoxidase (MPO) promoter polymorphism and susceptibility to, and clinical features of giant cell arteritis (GCA). METHODS: A total of 156 patients with biopsy-proven GCA who were residents of Reggio Emilia, Italy, and 235 population-based controls from the same geographic area were genotyped for-463 G/A promoter polymorphism of the MPO gene by molecular methods. The patients were subgrouped according to the presence or absence of polymyalgia rheumatica and severe ischaemic complications (visual loss and/or cerebrovascular accidents). RESULTS: The distribution of the MPO-G/A genotype differed significantly between patients with GCA and the controls (p(corr) = 0.003). Allele G was significantly more frequent in patients with GCA than in the controls (p(corr) = 0.0002, OR 2.0, 95% CI 1.4 to 2.9). Homozygosity for the G allele was significantly more frequent in patients with GCA than in controls (p(corr) = 0.0002, OR 2.2, 95% CI 1.4 to 3.4). No significant associations were found when patients with GCA with and without polymyalgia rheumatica or with and without severe ischaemic complications were compared. CONCLUSIONS: Our findings show that the-463 G/A promoter polymorphism of the MPO gene is associated with GCA susceptibility and support a role for MPO in the pathophysiology of GCA.

Circulating RANKL/OPG in polymyalgia rheumatica.

OBJECTIVE: To evaluate whether RANKL/OPG balance is modified in PMR patients, either in the active phase of the disease or during corticosteroid treatment. METHODS: Circulating levels of RANKL and OPG were assayed by enzyme-linked immunosorbent assay in PMR patients with active untreated disease and in patients treated by corticosteroids over a 12-month follow-up period. RESULTS: We found no statistically significant differences in circulating levels of OPG between PMR patients either in the active phase of the disease or during all follow-up period compared to normal controls. On the other hand, systemic production of sRANKL is increased and is not modulated by corticosteroid treatment. CONCLUSION: In PMR increased levels of sRANKL may be related to bone osteoporosis. Further investigations are necessary to evaluate the relationship between the RANK/RANKL/OPG system and bone turnover in PMR patients.

The codon 72 polymorphic variants of p53 in Italian rheumatoid arthritis patients.

OBJECTIVE: The p53 tumor suppressor protein plays an important role in cell apoptosis. The wild type p53 protein presents a common polymorphism at position 72 resulting in either a proline or an arginine residue at this position, leading to differences between the two variants in the induction of apoptosis. We examined the possible associations of this polymorphism with the occurrence of rheumatoid arthritis (RA) and its severity in a series of RA patients of Italian origin. METHODS: 170 consecutive RA patients fulfilling the 1997 ACR criteria and seen over a 4-month period in our rheumatology centre were studied. The medical records of the patients were reviewed for demographic and clinical parameters. Radiographs of the hands and feet taken at disease onset and after 5 years were available for 122 of the patients and were used to determine the presence and number of erosions, which were scored according to the modified Sharp/van der Heijde method (S/vdH). All of the RA patients and controls were genotyped by the polymerase chain reaction and allele-specific oligonucleotide techniques for p53 gene polymorphism Arg/Pro at codon 72. RESULTS: The distribution of the polymorphism of Arg/Pro 72 did not differ significantly between patients and healthy controls (Arg/Arg 47.1 vs 48.5%, Arg/Pro 43.5% vs 42%, Pro/Pro 9.8 vs 9.5% respectively, p=ns). Patients carrying the Pro/Pro genotype had a significantly higher percentage of erosive disease at year 5 compared with patients carrying the Arg/Arg genotype (Pro/Pro 93%, Arg/Arg 52%, p=0.0001). The mean number of eroded joints per patient at 5 years was higher in the Pro/Pro subgroup and significantly lower in the Arg/Arg subgroup (Pro/Pro 13.2, Arg/Arg 3.6, p=0.0001). The mean S/vdH erosive score, joint space narrowing score and total damage score were significantly higher in the Pro/Pro subgroup compared with the Arg/Arg and Arg/Pro subgroups. CONCLUSION: In the Italian population there is no association between codon 72-p53 gene polymorphism and the occurrence of RA. However, this polymorphism is associated with the structural damage of the disease.

Influence of dietary conjugated linoleic acids and vitamin E on meat quality, and adipose tissue in rabbits.

Eighty New Zealand White rabbits, age 55 days, half male and half female, were randomly assigned to one of four diets in a 2×2×2 factorial arrangement. The diets contained 0% or 0.5% CLA, and 60 or 240mg/kg α-Tocopheryl acetate. Forty-eight rabbits were slaughtered at age 92 days. Growth performances and carcass weight were higher (P<0.05) in 240mg/kg of α-tocopheryl acetate-fed rabbits. Fat and CLA isomers content of Longissimus Lumborum (LL) muscle was higher (P<0.05) in CLA-fed rabbits than control. Fatty acid composition of LL muscle was modified (P<0.05) and oxidative stability was increased (P<0.001) by both dietary treatments. CLA increased (P<0.05) triglyceride, total cholesterol and glucose levels in plasma. Adipocytes in interscapular and perirenal fat in the 240mg/kg α-tocopheryl acetate and 0.5% CLA groups were larger in size but lesser in number than in 60mg/kg α-tocopheryl acetate and no CLA rabbit (P<0.01).

Synovial expression of vasoactive intestinal peptide in polymyalgia rheumatica.

OBJECTIVE: Polymyalgia rheumatica (PMR) is an inflammatory disease that typically affects elderly people. Its clinical hallmark is the severity of pain in the shoulder and pelvic girdle. Mild to moderate synovitis and/or bursitis of the joints involved has been described. Neuropeptides are involved in nociception and modulation of inflammatory reaction. To evaluate whether neuropeptides have a role in PMR pathophysiology, we studied the expression of substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and somatostatin (SOM) in shoulder synovial tissues of PMR patients. METHODS: Synovial expression of neuropeptides was investigated by immunohistochemical analysis, in two groups of PMR patients: the first one at the onset of disease and the second one after corticosteroid treatment, and in other joint diseases, rheumatoid arthritis (RA) and osteoarthritis (OA). RESULTS: The only significant expression of VIP was found in PMR and, to a lesser extent, in RA synovial tissue. In PMR, we observed VIP immunostaining both in the lining layer and in the sublining area. In patients on corticosteroid treatment VIP lining layer expression was not significantly different while VIP positive cells in the sublining area were almost absent. CONCLUSION: Local VIP production in PMR synovial tissue might contribute to the typical musculoskeletal discomfort and it may have a role in the immunomodulation of synovial inflammation.

Frequency of musculoskeletal conditions among patients referred to Italian tertiary rheumatological centers.

OBJECTIVE: To describe the occurrence of different rheumatic diseases and to examine the characteristics of patients referred to six Italian rheumatological units. To compare these data with those from other countries. METHODS: Six Italian rheumatological tertiary referral centers participated in the study. Diagnoses of in- and outpatients aged over 16 years were classified according to the International Classification of Diseases, ninth revision. RESULTS: Three thousand, five hundred and thirty-seven patients with mean age 56 +/- 14.8 years, of which 2604 (73.6%) were women, were studied. Inflammatory joint and spine diseases were diagnosed in 40.4%, connective tissue diseases in 14.4%, degenerative joint and spine diseases in 21.4%, soft tissue rheumatisms in 18.5%, and metabolic bone diseases in 5.3%. There was a significant difference among centers in the frequency of most diagnoses: non-academic centers cared for more patients with arthritis and connective tissue diseases and for less patients with degenerative diseases, soft tissue rheumatisms and metabolic bone diseases. Connective tissue diseases were constantly seen more often in Italian centers, whereas soft tissue rheumatisms were seen more often abroad. CONCLUSION: Our data emphasize the great variability of the diagnostic case-mix in different centers from the same country, an observation that raises some concerns of the results of descriptive multicenter studies. Studies on the breakdown of diagnoses made in rheumatological centers could be helpful to determine the burden of rheumatic diseases on the health system, and for the planning of health interventions by both the national rheumatological societies and health authorities.

Influence of genetic type, live weight at slaughter and carcass fatness on fatty acid composition of subcutaneous adipose tissue of raw ham in the heavy pig.

The study aimed to assess some quality traits of the subcutaneous adipose tissue of raw ham for Parma production, obtained from 56 "traditional" Landrace×Large White (L×LW) and 56 Cotswold commercial hybrid (CH) pigs reared in the same conditions and slaughtered at an average live weight (l.w.) of about 165 kg. Further, the relationships between lipid composition, l.w. and carcass fatness were studied. Compared to the CH, the fatty tissue of L×LW pigs showed a lower water (6.33% vs. 7.35%, P<0.01) and a higher lipid (91.18% vs. 90.18%, P<0.01) content. CH lipids had higher polyunsaturated fatty acids (16.53% vs. 13.75%, P<0.01), and smaller saturated fatty acids (38.20% vs. 40.26%, P<0.01) content and a higher iodine value (69.69 vs. 65.22, P<0.01). An increased slaughter weight was associated with a lower degree of lipid unsaturation, but only the lowest weight class (<160 kg) showed a significant difference compared to the other two classes (⩾160<170 and ⩾170 kg). Regardless of genetic type or l.w. class, an increase in backfat thickness is associated with an increase in saturated and monounsaturated fatty acids and a remarkable reduction in polyunsaturated content.

The effect of dietary supplementation of vitamins C and E on the α-tocopherol content of muscles, liver and kidney, on the stability of lipids, and on certain meat quality parameters of the longissimus dorsi of rabbits.

The trial was carried out to investigate the effects of adding to the diet of rabbits vitamin E (40; 300; 500 ppm) and C (0; 500 ppm), on vitamin E deposition in the muscles and organs, on the oxidative stability of muscular lipids, and on various meat quality characteristics. The α-tocopherol content in muscles and organs was roughly doubled by feeding the highest levels of vitamin E; it was also increased by giving 500 ppm of vitamin C, but only in those muscles of rabbits receiving 40 ppm of vitamin E. The α-tocopherol content in tissues was negatively correlated with TBARS values of the longissimus dorsi (LD) at days 6 and 8 post mortem (p.m.). Five hundred parts per million (ppm) of vitamin C increased lipid stability of the LD at both 6 and 8 days p.m., though its effect was significant only with 40 ppm of vitamin E. Moreover, 500 ppm of vitamin C resulted in the lowest L(*) and highest pH values at all p.m. times, when the dietary vitamin E was equal to 40 ppm, and in the highest L(*) and lowest pH values when the vitamin E was equal to 300 ppm. Conversely, weight losses of the LD were the lowest, at days 6 and 8 p.m., in the group fed the highest levels of both vitamins.

A comparison of cyclosporine, sulfasalazine, and symptomatic therapy in the treatment of psoriatic arthritis.

OBJECTIVE: To compare the efficacy and tolerability of cyclosporine (CSA) with that of symptomatic therapy (ST) alone and sulfasalazine (SSZ) in the treatment of psoriatic arthritis (PsA). METHODS: Twelve rheumatology centers recruited 99 patients with active PsA in a 24 week, prospective, randomized, open, controlled study. The patients were treated with CSA (3 mg/kg/day) or SSZ (2,000 mg/day) plus ST, or ST alone (nonsteroidal antiinflammatory drugs, analgesics, and/or prednisone < or = 5 mg/day). The primary endpoint was the 6 month change in pain. Analyses were on the basis of the intention-to-treat principle. RESULTS: In comparison with both SSZ and ST, there was a statistically significant difference in favor of CSA in terms of the mean changes in the pain score (p < 0.05), which was considered the primary response variable. A significant decrease in favor of CSA versus ST alone was also observed for swollen joint count (p = 0.05), tender joint count (p = 0.01), joint/pain tenderness score (p = 0.002), patient and physician global assessment by at least one point (p = 0.04 and 0.01, respectively), total Arthritis Impact Measurement Scale score (p = 0.002), and spondylitis functional index (p = 0.002). There was a statistically significant difference in the ACR 50% and ACR 70% response rates between the CSA and ST groups (p = 0.02, 0.05). Comparing the SSZ and ST alone groups, only the spondylitis functional index decreased significantly in the SSZ treated patients (p = 0.03). The Psoriasis Area and Severity Index was significantly lower in the CSA than in the ST and SSZ groups (p = 0.0001 and 0.01, respectively). Decrease in erythrocyte sedimentation rate was significant only in the SSZ versus the ST group (p = 0.02), whereas reduction in C-reactive protein was significant in the CSA treated patients compared with the ST group (p = 0.006). The most common adverse event in the CSA group was mild, reversible kidney dysfunction. CONCLUSION: The results of this open trial confirm that CSA is well tolerated by patients with PsA and suggest that it is more efficacious than ST or SSZ.

Muscoloskeletal manifestations in inflammatory bowel disease.

Muscoloskeletal manifestations are the most common extraintestinal complications of inflammatory bowel disease. Wide ranges in prevalence have been reported, depending on the criteria used to define spondylarthropathy. In 1991, the European Spondylarthropathy Study Group developed classification criteria that included previously neglected cases of undifferentiated spondylarthropathies, which had been ignored in most of the oldest epidemiological studies on inflammatory bowel disease. The spectrum of muscoloskeletal manifestations in inflammatory bowel disease patients includes all of the clinical features of spondylarthropathies: peripheral arthritis, inflammatory spinal pain, dactylitis, enthesitis (Achilles tendinitis and plantar fasciitis), buttock pain and anterior chest wall pain. Radiological evidence of sacroiliitis is common but not obligatory. The articular manifestations begin either concomitantly or subsequent to the bowel disease; however, the onset of spinal disease often precedes the diagnosis of inflammatory bowel disease. The prevalence of the different muscoloskeletal manifestations is similar in ulcerative colitis and Crohn's disease. Symptoms usually disappear after proctocolectomy. The pathogenetic mechanisms that produce the muscoloskeletal manifestations in inflammatory bowel disease are unclear. Several arguments favour an important role of the intestinal mucosa in the development of spondylarthropathy. The natural history is characterized by periods of flares and remission; therefore, the efficacy of treatment is difficult to establish. Most patients respond to rest, physical therapy and nonsteroidal anti-inflammatory drugs, but these drugs may activate bowel disease. Sulphasalazine may be recommended in some patients. There is no indication for the systemic use of steroids.

Inflamed shoulder structures in polymyalgia rheumatica with normal erythrocyte sedimentation rate.

OBJECTIVE: To investigate the inflammatory involvement of shoulder articular and extraarticular structures in polymyalgia rheumatica (PMR) patients with a normal erythrocyte sedimentation rate (ESR) at diagnosis. METHODS: This was a case-control study. All consecutive, untreated new outpatients diagnosed as having PMR with a normal ESR (<40 mm/hour) during a 6-month period were included in the study (case patients). Controls were 12 consecutive, untreated PMR outpatients with an ESR of >40 mm/hour who were observed after the case patients. Before starting corticosteroid therapy, all case patients and controls underwent bilateral shoulder ultrasonography (US) and magnetic resonance imaging (MRI). US and MRI scans were evaluated independently by two radiologists who were blinded to the reciprocal results. RESULTS: Six case patients (4 men and 2 women) and 12 controls (4 men and 8 women) were studied. Both US and MRI demonstrated bilateral subacromial/subdeltoid bursitis in all 6 case patients and in 11 of the 12 (92%) controls (P not significant [NS]). One control had unilateral bursitis. Glenohumeral joint synovitis was found in 4 of 6 case patients (67%) by MRI and in 3 of 6 case patients (50%) by US (P NS), as well as in 8 of 12 controls (67%) by MRI and in 7 of 12 controls (58%) by US (P NS). Both MRI and US detected biceps tenosynovitis in 5 of 6 case patients (83%) and in 8 of 12 controls (67%) (P NS). The severity of bursitis did not differ significantly between the groups. US was as effective as MRI in detecting inflammatory changes of the shoulder. CONCLUSION: MRI and US studies showed that PMR patients with normal or high ESRs have similar inflammatory shoulder lesions. Moreover, bilateral subacromial/subdeltoid bursitis represents the imaging hallmark in PMR patients with a high or normal ESR. MRI or US of the shoulder may facilitate the proper diagnosis in patients with the typical proximal symptoms of PMR who also have normal ESRs.