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Objective To determine laboratory parameters that may be useful in identifying polymyalgia rheumatica (PMR) patients who require long-term corticosteroid therapy. Methods A prospective followup study of 94 consecutive untreated patients with PMR were assessed for relapse/recurrence for a mean of 39 months. This cohort represented all the patients diagnosed over a 4-year period in 2 Italian secondary referral centers. Patients were monitored for clinical signs and symptoms, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum interleukin-6 (IL-6). IL-6 levels were also measured in 43 controls matched to the patients for age and sex. Results The ESR was elevated in 91.5% of the patients prior to therapy initiation, as were CRP in 98.9% and serum IL-6 in 92.6%. Forty-seven (50.0%) patients had at least 1 relapse/recurrence during the followup period and 24 (25.5%) had at least 2. After 4 weeks of prednisone therapy, ESR was elevated in 13.2% patients, CRP in 41.9%, and serum IL-6 in 37.2%. IL-6 levels remained persistently elevated in 9.9% and CRP in 8.7% of patients during the first year of followup, whereas no patient had persistently elevated ESR. Persistently elevated CRP and IL-6 levels were significantly associated with an increased risk of relapse/recurrence. In particular, patients with persistently elevated levels of IL-6 during the first year of therapy had the highest relative risk. Conclusion Despite the control of clinical symptoms, corticosteroids do not adequately control the inflammatory process in a subset of patients with PMR who have persistently elevated levels of CRP and IL-6 and who have a higher risk of relapsing.

A 61-year-old female with a history of vaginal dryness, Raynaud's phenomenon, xerostomia and xerophthalmia presented with exertional dyspnoea and weakness. Laboratory and instrumental examinations enabled us to make the diagnosis of primary Sjögren's syndrome, while cardiologic and imaging investigations evidenced isolated pulmonary hypertension and ruled out pulmonary fibrosis. Oral anticoagulant and furosemide therapy induced a partial improvement of exertional dyspnoea and weakness.

Objective: To summarize the evidence about the relationship between polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). Methods: Review of relevant articles from the English-language literature. Results: Epidemiologic studies suggest that PMR and GCA are closely related conditions affecting people over 50 years and frequently occurring in the same patient. PMR symptoms have been observed in 40 to 60 percent of GCA clinical series. Also, temporal artery biopsy may yield positive results for GCA in patients with isolated PMR. Conflicting HLA-DRB1 genotype results have been reported, and recent studies have shown that PMR and GCA have different expression of RANTES, TNF microsatellite, and IL-6 promoter genetic polymorphisms. Search for a possible common infectious agent have yielded disappointing results. Although parvovirus B19 DNA is present in the artery wall of patients with GCA, this virus may be only an innocent bystander. Cytokine studies on a limited number of temporal artery biopsy specimens have shown that interferon- is produced in GCA and not in PMR, suggesting that this cytokine may be crucial to the development of overt vasculitis. Conclusions: PMR and GCA frequently occur together but no definitive conclusions can be drawn about the nature of this association. Semin Arthritis Rheum 33:294-301. © 2004 Elsevier Inc. All rights reserved. INDEX WORDS: Polymyalgia rheumatica; giant cell arteritis; pathogenesis; relationship.

Objective To evaluate the efficacy and safety of the anti-tumor necrosis factor α monoclonal antibody infliximab in the treatment of active psoriatic arthritis (PsA) resistant to previous symptom modifying antirheumatic drugs. Methods Sixteen patients with peripheral active PsA with at least 6 months of methotrexate (MTX) therapy at a stable dosage were treated with infliximab administered at a dosage of 3 mg/kg at 0, 2, 6, 14, 22, and 30 weeks while continuing to receive MTX. Intake of nonsteroidal antiinflammatory drugs and corticosteroids was stable during the study period. Standard clinical assessments, erythrocyte sedimentation rate (ESR), and C reactive protein (CRP) were determined at baseline and at weeks 2, 6, 14, 22, and 30. Results By week 2, significant improvements were registered in the number of swollen and tender joints, visual analog scale for pain, patient and doctor global disease assessment scores, Health Assessment Questionnaire, Dougados functional index, ESR, and CRP. At week 30, the percentages of patients satisfying American College of Rheumatology (ACR) 20%, ACR 50%, and ACR 70% response rates were 64%, 57%, and 57%, respectively. In the 3 patients with active axial disease, spinal stiffness and pain resolved almost completely at week 2 and the improvement did not diminish over time. Psoriasis Area Severity Index improvement was 37% at week 2 and 86% at week 30. No patients dropped out for treatment failure. Side effects were observed in 4 of 16 patients, 2 of whom suspended the therapy due to a severe allergic reaction. Conclusion In patients with resistant PsA, infliximab is an effective therapy without major side effects.

Proximal musculoskeletal symptoms mimicking the clinical picture of polymyalgia rheumatica may herald the onset of solid malignancies. We report on three patients presenting with polymyalgia-like symptoms, who had renal cell carcinoma. The review of the literature and our cases suggest that the absence of prolonged morning stiffness, the atypical clinical findings, the inefficacy of corticosteroids, and the absence of shoulder sonographic pathologic findings may help to facilitate the proper diagnosis.

Background TNF-alpha was demonstrated in up to 60% of the cells in all areas of inflamed arteries of patients with GCA, suggesting a primary role in the inflammatory process. Infliximab, a chimeric monoclonal anti-TNF-alpha, demonstrated remarkable efficacy and safety in the treatment of several rheumatic conditions associated with a chronic inflammatory response. Objectives To date, no data are available on the therapeutic employment of infliximab in patients with GCA. The aim of this study was to evaluate the efficacy of infliximab infusions in longstanding, still requiring corticosteroids (CS) GCA. Methods Four patients (3F,1M; median age:75 ys.) with longstanding (median disease duration: 4 ys.), biopsy proven, active GCA, still requiring CS and whose disease course hab been complicated by serious CS-related adverse events, were scheduled to receive 3 infusions of infliximab (3 mg/Kg) at weeks 0, 2 and 6. If a clinical and humoral remission was obtained, CS were withdrawn after the 2nd infusion. Results Three patients had a complete remission of clinical signs/symptoms and normalisation of ESR and CRP after the 2nd infusion. The remission persisted after the 3rd infusion and over the follow-up (7, 6 and 6 months, respectively). The fourth patient did not respond to therapy and withdrew from the study after the 2nd infusion. Infliximab was well tolerated without any side-effects. Conclusion Our encouraging results suggest that TNF-alpha blockade may represent a valid alternative therapeutic approach to longstanding GCA, still requiring CS and complicated by severe adverse events. The small number of patients and the open study design do not allow conclusive considerations.

Objective: To determine the frequency and clinical features of patients with polymyalgia rheumatica (PMR) and normal erythrocyte sedimentation rate (ESR) at diagnosis or during relapse/recurrence. To evaluate the usefulness of C-reactive protein (CRP) and ESR in the assessment of PMR activity. Methods: A prospective follow-up study on 177 consecutive patients meeting the criteria for PMR diagnosed over a 5-year period was conducted in two Italian secondary referral centers of rheumatology. At diagnosis and during follow-up, ESR (Westergren method) and CRP (nephelometry) were measured in all patients. Phenotypic analysis of lymphocyte subpopulations was performed on 78 PMR patients at diagnosis. A two-color technique using the association of specific monoclonal antibodies was applied. A control group consisting of 18 healthy adults older than 60 years was matched for age and sex with the PMR patients. Results: Ten of 177 (6%) patients had normal ESR values at diagnosis (≤30 mm/h). Patients with normal ESR were predominantly men and had lower CRP levels; systemic signs and symptoms were more frequent in patients with higher ESR. The percentages of circulating CD8+ cells were similar in the two groups. CRP values at diagnosis were normal in only 2 of 177 (1%) patients. CRP values were elevated in 9 of 10 patients with normal ESR at diagnosis. Twenty-five episodes of relapse/recurrence with normal ESR occurred in 17 patients. CRP was high in 62% of these episodes. Results of univariate analysis indicated that the 10 th percentile for ESR (40 mm/h) and the 70 th percentile for CRP (7.8 mg/dL) values at diagnosis were the best cutoff points that discriminate between patients with and without relapse/recurrence. Cox proportional hazards modeling showed that ESR greater than 40 mm/h and CRP greater than 7.8 mg/dL at diagnosis were the two variables that independently increased the risk of relapse/recurrence. However, the relative risk related to ESR was twice than that related to CRP (4.9 vs 2.1). Conclusion: PMR with a normal ESR at diagnosis was infrequent in our study compared with previous studies. ESR was a superior predictor of relapse than CRP. However, CRP was a more sensitive indicator of current disease activity. Semin Arthritis Rheum 30:17-24. Copyright © 2000 by W.B. Saunders Company

A patient suffering from Behcet’s syndrome and undifferentiated spondyloarthritis developed dactylitis and psoriasis over the next three years.

OBJECTIVE—To determine the clinical characteristics of patients with "pure" remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome, and to investigate its relation with polymyalgia rheumatica (PMR). Magnetic resonance imaging (MRI) was used to describe the anatomical structures affected by inflammation in pure RS3PE syndrome. METHODS—A prospective follow up study of 23 consecutive patients with pure RS3PE syndrome and 177 consecutive patients with PMR diagnosed over a five year period in two Italian secondary referral centres of rheumatology. Hands or feet MRI, or both, was performed at diagnosis in 7 of 23 patients. RESULTS—At inspection evidence of hand and/or foot tenosynovitis was present in all the 23 patients with pure RS3PE syndrome. Twenty one (12%) patients with PMR associated distal extremity swelling with pitting oedema. No significant differences in the sex, age at onset of disease, acute phase reactant values at diagnosis, frequency of peripheral synovitis and carpal tunnel syndrome and frequency of HLA-B7 antigen were present between patients with pure RS3PE and PMR. In both conditions no patient under 50 was observed, the disease frequency increased significantly with age and the highest frequency was present in the age group 70-79 years. Clinical symptoms for both conditions responded promptly to corticosteroids and no patient developed rheumatoid arthritis during the follow up. However, the patients with pure RS3PE syndrome were characterised by shorter duration of treatment, lower cumulative corticosteroid dose and lower frequency of systemic signs/symptoms and relapse/recurrence. Hands and feet MRI showed evidence of tenosynovitis in five patients and joint synovitis in three patients. CONCLUSION—The similarities of demographic, clinical, and MRI findings between RS3PE syndrome and PMR and the concurrence of the two syndromes suggest that these conditions may be part of the same disease and that the diagnostic labels of PMR and RS3PE syndrome may not indicate a real difference. The presence of distal oedema seems to indicate a better prognosis. Keywords: RS3PE; polymyalgia rheumatica; pitting oedema; magnetic resonance imaging

The cause of musculoskeletal symptoms in the proximal extremities of patients who have polymyalgia rheumatica is not completely understood. The diffuse and severe discomfort can only be partially explained by the mild joint synovitis that is observed in these patients.To determine the involvement of the synovial structures of the shoulder girdle of patients who have active symptoms of polymyalgia rheumatica.Case-control study.2 secondary referral centers of rheumatology.13 case-patients who had active symptoms of polymyalgia rheumatica seen during a 6-month period, 9 control-patients who had early symptoms of elderly-onset rheumatoid arthritis, and 10 age-matched healthy controls.Magnetic resonance imaging of the shoulder was done on the 13 case-patients, 9 control-patients, and 10 healthy controls.The frequency of subacromial and subdeltoid bursitis was significantly higher in the case-patients (who had polymyalgia rheumatica) than in the control-patients (who had elderly-onset rheumatoid arthritis). The frequencies of synovitis of the joints and tenosynovitis of the biceps did not significantly differ between the 13 case-patients and the 9 control-patients. None of the healthy controls showed evidence of fluid accumulation in the joints, bursae, or sheaths of the long head of the biceps.Inflammation of subacromial and subdeltoid bursae in association with synovitis of the glenohumeral joints and tenosynovitis of the biceps may contribute to the diffuse discomfort in the shoulder girdle observed in patients with polymyalgia rheumatica.

Fabrizio Cantini, Laura Niccoli, Emanuele Cassarà, Olga Kaloudi, Carlotta NanniniDivision of Rheumatology, Misericordia e Dolce Hospital, Prato, ItalyBackground: The aim of this study was to evaluate the proportion of patients with ankylosing spondylitis maintaining clinical remission after reduction of their subcutaneous etanercept dose to 50 mg every other week compared with that in patients receiving etanercept 50 mg weekly.Methods: In the first phase of this randomized, prospective, follow-up study, all biologic-naïve patients identified between January 2005 and December 2009 as satisfying the modified New York clinical criteria for ankylosing spondylitis treated with etanercept 50 mg weekly were evaluated for disease remission in January 2010. In the second phase, patients meeting the criteria for remission were randomized to receive subcutaneous etanercept as either 50 mg weekly or 50 mg every other week. The randomization allocation was 1:1. Remission was defined as Bath Ankylosing Spondylitis Disease Activity Index < 4, no extra-axial manifestations of peripheral arthritis, dactylitis, tenosynovitis, or iridocyclitis, and normal acute-phase reactants. The patients were assessed at baseline, at weeks 4 and 12, and every 12 weeks thereafter. The last visit constituted the end of the follow-up.Results: During the first phase, 78 patients with ankylosing spondylitis (57 males and 21 females, median age 38 years, median disease duration 12 years) were recruited. In January 2010, after a mean follow-up of 25 ± 11 months, 43 (55.1%) patients achieving clinical remission were randomized to one of the two treatment arms. Twenty-two patients received etanercept 50 mg every other week (group 1) and 21 received etanercept 50 mg weekly (group 2). At the end of follow-up, 19 of 22 (86.3%) subjects in group 1 and 19 of 21 (90.4%) in group 2 were still in remission, with no significant difference between the two groups. The mean follow-up duration in group 1 and group 2 was 22 ± 1 months and 21 ± 1.6 months, respectively.Conclusion: Remission of ankylosing spondylitis is possible in at least 50% of patients treated with etanercept 50 mg weekly. After halving of the etanercept dose, remission is maintained in a high percentage of patients during long-term follow-up, with important economic implications.Keywords: ankylosing spondylitis, anti-tumor necrosis factor, etanercept, remission, dose reduction

The effectiveness of intravenous propafenone for conversion to sinus rhythm (SR) of paroxysmal atrial fibrillation (AF), lasting less than 7 days, was evaluated with a single-blind, randomized, placebo-controlled study, given the possible spontaneous conversion of this arrhythmia. Group 1 (98 patients) received intravenous propafenone (2 mg/kg iv over 10 minutes followed by 0.007 mg/kg/min); and group 2 (84 patients) received intravenous placebo (0.9% saline solution). The infusion was continued until restoration of SR but no longer than 24 hours. Eight-nine patients (90.8%) received propafenone and 27 patients (32%) receiving placebo were converted to SR (p0.005). The mean conversion time was 2.46 +/- 2.59 hours in group 1 and 17.15 +/- 5.78 hours in group 2 (p0.005). In patients treated with propafenone, conversion of SR mostly occurred in the first 4 hours (86.5%), considered to be the optimal infusion time in our experience. In both groups, the left atrial size was significantly larger in nonconverted than in converted patients. Similarly, the duration of the arrhythmia was significantly longer in nonconverted patients. In nonconverted patients, the mean ventricular rate decreased from 143 +/- 16 beats/min to 101 +/- 18 beats/ min after propafenone and from 135 +/- 19 beats/min to 119 +/- 16 beats/min after placebo (group 1 vs. group 2: p0.005). Two episodes of sinus standstill (3.4 and 3.8, seconds, respectively) occurred at SR restoration obtained with propafenone. Intravenous propafenone is an effective, safe, and usually rapid drug for AF treatment. Moreover, it produces a real and significant reduction in the mean ventricular rate in nonconverted patients.

The treatment of SAPHO syndrome is empirical and has recently been reviewed.1–3 Non-steroidal anti-inflammatory drugs (NSAIDs) are the first choice but have limited efficacy. Second line drugs have been tried with mixed results. Positive effects with pamidronate, which partly works by blocking tumour necrosis factor α, have been reported.3,4 Recently, Maksymowych et al suggested that pamidronate is also effective in spondarthritis, which shares manifestations and clinical associations with the SAPHO syndrome.5,6 Infliximab, a chimeric anti-tumour necrosis factor α monoclonal IgG1 antibody, has recently been proved to be effective in the treatment of ankylosing spondylitis7,8 and psoriatic arthritis.7,9 In view of this information we treated two patients affected by refractory SAPHO syndrome with infliximab. Both patients had chest pain limiting normal activity despite adequate treatment with NSAIDs and second line treatment was unsuccessful. Both patients received three intravenous infusions of infliximab (5 mg/kg) at …

Remitting distal extremity swelling with pitting oedema is a clinical manifestation that may be observed in different rheumatic conditions such as RS3PE syndrome,1 polymyalgia rheumatica,2 late onset undifferentiated spondyloarthropathy,3 ankylosing spondylitis,4 psoriatic arthritis,5 and more rarely in other rheumatic disease.5 In RS3PE the swelling with pitting oedema predominantly involves the upper extremities symmetrically.1 This clinical finding may occur unilaterally in polymyalgia rheumatica and upper and lower limbs may be equally affected,2 whereas in seronegative spondyloarthropathies it has been described more frequently in lower extremities with asymmetric involvement.3 4 The oedema is characterised by a rapid response to small doses of corticosteroids. The pathogenesis of swelling with pitting oedema has not been completely defined, but the distribution along the tenosynovial membranes suggests that it probably results from tenosynovitis.5 Sarcoidosis is a …

Proximal musculoskeletal symptoms mimicking the clinical picture of polymyalgia rheumatica may herald the onset of solid malignancies. We report on three patients presenting with polymyalgia-like symptoms, who had renal cell carcinoma. The review of the literature and our cases suggest that the absence of prolonged morning stiffness, the atypical clinical findings, the inefficacy of corticosteroids, and the absence of shoulder sonographic pathologic findings may help to facilitate the proper diagnosis.

Giant cell arteritis (GCA) is a chronic granulomatous vasculitis of unknown aetiology occurring in the elderly. It affects the cranial branches of the arteries originating from the aortic arch and is usually associated with markedly elevated acute-phase reactants. In 10-15% of cases the extra-cranial branches of the aortic arch are involved. GCA is closely related to polymyalgia rheumatica (PMR), although the relationship between the two disorders is still unclear. New-onset headache, scalp tenderness, jaw claudication, temporal artery abnormalities on physical examination, visual symptoms and associated PMR represent the most typical and frequent features of the disease. Systemic manifestations, including fever, anorexia and weight loss, are observed in 50% of cases. Less frequent manifestations are related to the central or peripheral nervous systems, the respiratory tract and extra-cranial large-vessel involvement. As GCA is characterized by a wide spectrum of clinical manifestations, it is important to recognize the different onset patterns of the disease and related diagnostic steps. The diagnosis is relatively straightforward in the presence of typical cranial manifestations, but it may be challenging in the case of a normal erythrocyte sedimentation rate, occult GCA or in patients with isolated extra-cranial features. Temporal artery biopsy still represents the gold standard for diagnosis, while the role of ultrasonography, high-resolution magnetic resonance imaging and positron emission tomography should be better addressed. Corticosteroids remain the therapy of choice. Data supporting the usefulness of antiplatelet agents and anticoagulants combined with corticosteroids to prevent ischaemic complications as well as the corticosteroid-sparing effect of methotrexate and anti-tumour necrosis factor-alpha drugs are limited and non-conclusive.