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1.
Clin Exp Rheumatol ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33822703

RESUMO

OBJECTIVES: Polymyalgia rheumatica (PMR) is an inflammatory disorder, more common in the elderly, characterised by girdle pain and stiffness, constitutional symptoms and raised serological markers of inflammation. Studies on the seasonality of onset of PMR have shown conflicting results, possibly due to the different diagnostic criteria and onset recognition. In this study, the month of onset of PMR was evaluated in patients originating from one geographical area, visited by the same clinician. METHODS: In 383 PMR patients (245 women, median age 73 years, range 47-92 years) examined between 1990 and 2014, PMR was diagnosed according to Bird's criteria. The month of onset was recorded systematically during the patient's interview. Clinical features initially recorded included the location of joint involvement, the coexistence of temporal arteritis (TA) or peripheral arthritis, and the type of onset (acute if reported of 72h or less). Patient follow-up, PMR severity and outcome were also recorded throughout the study. RESULTS: We failed to identify any peak month (p=0.93) or season (p=0.45) for the onset of PMR. Timing of onset did not correlate with the clinical features, severity or outcome of PMR. Only when patients were also affected by concomitant TA, the onset of PMR was more often seen in autumn (p=0.02). Patients with PMR onset in autumn also has a greater risk of developing TA during their follow-up (p=0.03). By multiple regression, the only outcome predicted by autumn onset was the use of methotrexate (p=0.039). CONCLUSIONS: PMR showed no seasonality of onset, except for the subset associated with TA. A risk factor with seasonal variation is suggested for the pathogenesis of this form of PMR.

2.
Clin Exp Rheumatol ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33822711

RESUMO

OBJECTIVES: We aimed to evaluate joint and vessel uptake in patients with polymyalgia rheumatica (PMR) by FDG-PET and correlate it with clinical findings. METHODS: Consecutive PMR patients, without clinical signs of giant cell arteritis, underwent a standardised clinical examination and FDG-PET/CT. Controls were consecutive subjects undergoing FDG-PET for the suspicion of neoplasm not confirmed by the examination. Uptake was evaluated by a qualitative visual score, using the liver uptake as reference and by the semi-quantitative mean standardised uptake value (SUV) and target-to-background ratio (TBR) methods. RESULTS: Eighty-four patients and 84 controls (55 women, median age 73 years, range 50-92 years in both groups) were studied. Sixteen patients were taking glucocorticoids (GC). PMR patients showed a higher articular uptake than controls. GC-treated patients showed uptake lower than GC-naïve patients, but still higher than controls. PMR patients showed a higher vascular uptake than controls in all districts except in the carotid arteries, when evaluated by the visual score. Conversely, the semi-quantitative approach yielded no significant differences. Forty-two patients (50%) showed PET evidence of large-vessel vasculitis (LVV), defined as uptake ≥ than that of the liver, and 11.9% showed LVV with vascular uptake higher than that of the liver. The correlation between clinical findings and uptake was scarce. Neither clinical nor laboratory findings could predict the presence of LVV. CONCLUSIONS: Patients with PMR show a typical joint pattern at FDG-PET. There are no clinical or laboratory predictors of LVV. Imaging appears to be the only tool to assess LVV in these patients.

3.
Curr Rheumatol Rep ; 23(3): 17, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33569633

RESUMO

PURPOSE OF REVIEW: Large vessel vasculitides (LVVs) are inflammatory conditions of the wall of large-sized arteries, mainly represented by giant cell arteritis (GCA) and Takayasu arteritis (TA). The inflammatory process within the vessel wall can lead to serious consequences such as development of aneurysms, strokes and blindness; therefore, early diagnosis and follow-up of LVV are fundamental. However, the arterial wall is poorly accessible and blood biomarkers are intended to help physicians not only in disease diagnosis but also in monitoring and defining the prognosis of these conditions, thus assisting therapeutic decisions and favouring personalised management. The field is the object of intense research as the identification of reliable biomarkers is likely to shed light on the mechanisms of disease progression and arterial remodelling. In this review, we will discuss the role of blood biomarkers in LVVs in the light of the latest evidence. RECENT FINDINGS: In clinical practice, the most widely performed laboratory investigations are the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). However, these indices may be within normal limits during disease relapse and they are not reliable in patients receiving interleukin-6 (IL-6) receptor inhibitors. New biomarkers struggle to gain traction in clinical practice and no molecule with good accuracy has been identified to date. IL-6, a pro-inflammatory cytokine that drives CRP synthesis and increases the ESR, is one of the most promising biomarkers in the field. IL-6 analysis is increasingly performed, and serum levels are more sensitive than ESR for active GCA and might reflect persistent inflammation with high risk of relapse in patients on IL-6 receptor inhibitors. A future with biomarkers that reflect different disease features is an important aspiration. Accordingly, intense effort is being made to identify IL-6-independent inflammatory biomarkers, such as S100 proteins, pentraxin-3 and osteopontin. Moreover, metalloproteinases such as MMP2/9 and angiogenic modulators such as VEGF, YLK-40 and angiopoietins are being studied as markers of arterial remodelling. Lastly, biomarkers indicating organ damage may guide prognostic stratification as well as emergency therapeutic decisions: the most promising biomarkers so far identified are NT-proBNP, which reflects myocardial strain; pentraxin-3, which has been associated with recent optic nerve ischemia; and endothelin-1, which is associated with ischaemic complications. Currently, the use of these molecules in clinical practice is limited because of their restricted availability, lack of sufficient studies supporting their validity and associated costs. Further evidence is required to better interpret their biological and clinical value.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33200216

RESUMO

PMR is an inflammatory rheumatic disease of elderly people characterized by pain and stiffness in the neck, shoulder and pelvic girdles. No specific diagnostic confirmatory tests exist and clinical symptoms, as well as increased acute phase reactants, are unspecific. The diagnostic value of imaging including ultrasound, MRI and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) with/without CT for PMR is increasingly studied. These techniques, particularly FDG-PET/CT, may help to detect underlying GCA in PMR patients with an incomplete response to glucocorticoids and/or recurrent relapses. Recent imaging studies provide novel insights into the anatomical basis of inflammation in PMR, particularly at hip and spine, which may help to distinguish this disease from other mimicking conditions. In this review, we discuss novel insights into the pathoanatomy of PMR, compare the diagnostic values of different imaging techniques and summarize current data on the role of imaging for monitoring and outcome prediction.

6.
Nat Rev Rheumatol ; 16(11): 662, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32913336

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

7.
Nat Rev Rheumatol ; 16(9): 481-495, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32759996

RESUMO

Giant cell arteritis (GCA) is the most common type of primary vasculitis in Western countries. Polymyalgia rheumatica (PMR) is the second most common inflammatory rheumatic disease of the elderly after rheumatoid arthritis. Glucocorticoids are the cornerstone of treatment for GCA and PMR, which are interrelated diseases. Glucocorticoids are effective, but adverse effects occur in a high proportion of patients. Careful use of glucocorticoids and the application of preventive strategies can minimize these adverse effects. Possible long-term complications of GCA include aneurysm and stenosis of vessels, even in patients with apparently clinically inactive disease; acute blindness is rare during glucocorticoid treatment. In PMR, whether subclinical chronic inflammation can lead to long-term damage is less clear. Management of both GCA and PMR is hampered by the lack of universally accepted definitions of remission and other disease states, such as low disease activity or vessel damage without active disease. In this Review, we outline current evidence on the monitoring and long-term management of patients with GCA and PMR, including the tapering of treatment.

8.
Bone ; 138: 115512, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32603908

RESUMO

Acute phase response (APR) following intravenous zoledronate (ZOL) administration is related to activation and increased proliferation of γδ T cells, attributed to the molecular mechanism of action of nitrogen-containing bisphosphonates (N-BPs). ZOL, however, has also been reported to inhibit the proliferation of regulatory T cells in vitro and to reduce the expression of Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4), a negative regulator of T cell activation that is increased in patients with autoimmune diseases. There are, however, no data on the relationship between ZOL treatment and soluble(s)CTLA-4 either in vivo in relevant patient populations or in vitro with the use of assays relevant to the mechanism of action of N-BPs. The objectives of the present study were firstly, to characterize the ZOL-induced APR in patients with inflammatory rheumatic diseases (IRDs) and its relationship with changes in circulating sCTLA-4 and secondly, to investigate the effects of ZOL on CTLA-4 production and expression by peripheral blood mononuclear cells (PBMCs). We studied 10 postmenopausal women with IRDs treated with intravenous ZOL 5 mg. Five women experienced APR (APR+) associated with significant decreases in blood lymphocytes and increases in granulocytes and serum CRP. Serum sCTLA-4 values were increased in all patients before ZOL administration and decreased significantly 72 h after the ZOL infusion (from 30.0 ± 2.9 to 6.3 ± 1.8 ng/ml; p < 0.001) with no differences between APR+ and APR- patients. Consistent with the results of the in vivo study, ZOL (1 µM) decreased the production of sCTLA-4 by 87% and 57% after 3 and 5 days in cultures of peripheral blood mononuclear cells (PBMCs) in vitro, respectively, and inhibited the expression of both cytoplasmic and membrane-bound CTLA-4. Our results reveal a novel immunoregulatory action of ZOL that is not related to its action on bone resorption but might be associated with reported clinically significant extraskeletal outcomes of ZOL treatment.

11.
Rheum Dis Clin North Am ; 45(4): 549-567, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31564296

RESUMO

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are common inflammatory diseases of the elderly. They have variable clinical courses and are usually treated with glucocorticoids (GCs). Relapses are frequent in both conditions. Physicians should balance the tradeoff of treatment-related adverse events and risk of relapse. The ultimate goal of treatment is control of the disease while maintaining patient well-being. A treat-to-target approach may achieve the aim of controlling inflammation and preserving patient's functioning and quality of life, and would require pursuit and evaluation of clinical, laboratory, imaging, and structural targets to tackle the different manifestations of GCA and PMR.


Assuntos
Arterite de Células Gigantes/terapia , Planejamento de Assistência ao Paciente , Polimialgia Reumática/terapia , Prevenção Secundária/métodos , Tomada de Decisão Clínica , Gerenciamento Clínico , Humanos
12.
Drugs Aging ; 36(11): 1015-1026, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31493201

RESUMO

Polymyalgia rheumatica is an inflammatory rheumatic disease of the elderly characterised by pain and stiffness in the neck and pelvic girdle, and is the second most common inflammatory rheumatic condition in this age group, after rheumatoid arthritis. Polymyalgia rheumatica can occur independently or in association with giant cell arteritis, which is the most common form of primary vasculitis. The diagnosis of polymyalgia rheumatica is usually based on clinical presentation and increase of inflammatory markers. There are no pathognomonic findings that can confirm the diagnosis. However, different imaging techniques, especially ultrasonography, can assist in the identification of polymyalgia rheumatica. Glucocorticoids are the cornerstone of the treatment of polymyalgia rheumatica, but they might be associated with different adverse events. A subgroup of patients presents with a refractory disease course and, in these cases, adding methotrexate as a steroid-sparing agent could be useful. In this review, we summarise the latest findings regarding the pathogenesis, diagnosis and management of polymyalgia rheumatica and try to highlight the possible pitfalls, especially in elderly patients.


Assuntos
Antirreumáticos/uso terapêutico , Produtos Biológicos/uso terapêutico , Arterite de Células Gigantes , Glucocorticoides/uso terapêutico , Polimialgia Reumática , Idoso , Diagnóstico Diferencial , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/tratamento farmacológico , Arterite de Células Gigantes/etiologia , Humanos , Polimialgia Reumática/diagnóstico , Polimialgia Reumática/tratamento farmacológico , Polimialgia Reumática/etiologia
14.
Rheumatol Int ; 38(9): 1699-1704, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29946742

RESUMO

The efficacy of tocilizumab (TCZ), a monoclonal antibody to the interleukin (IL)-6 receptor, in suppressing disease activity in glucocorticoid-naïve patients with new-onset polymyalgia rheumatica (PMR) was studied. Its effect on a panel of cytokines and growth factors was evaluated. Three patients, fulfilling the PMR ACR/EULAR criteria, received TCZ at the dosage of 8 mg/kg every 4 weeks for three times followed by prednisone 0.2 mg/kg in case of inefficacy. Concentrations of IL-10, IL-6, tumour necrosis factor (TNF)-α, IL-1ß, IL-10, IL-17, interferon (IFN)-γ, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and leukaemia inhibitory factor (LIF) were measured at baseline, after 72 h of the first TCZ infusion and then at weeks 1, 4, 5, 8, 9, 12, 13, 14, 16, and 22. A slight clinical improvement was seen only after the first TCZ infusion, but was largely inferior to that of conventional doses of GC administered subsequently. An ischaemic visual accident suggestive of GCA occurred in one patient during TCZ treatment. IL-6 was increased at baseline compared to controls, further increased after the first TCZ infusion, and was suppressed by GC. IL-17 production decreased during TCZ treatment and reverted to pre-treatment levels after GC. VEGF e PDGF showed a less constant pattern, but an increase of VEGF concentration antedated visual symptoms. The other cytokines were not detectable in patients and controls. In our small sample, TCZ was not able to suppress inflammation at the same degree as GC. As a result, monotherapy with TCZ in PMR cannot be recommended, although its efficacy as adjunctive treatment in GC-resistant patients should be further evaluated.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Interleucina-6/antagonistas & inibidores , Interleucina-6/fisiologia , Polimialgia Reumática/imunologia , Idoso , Diabetes Mellitus Tipo 2 , Feminino , Humanos , Itália , Masculino , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Fator A de Crescimento do Endotélio Vascular
15.
Recenti Prog Med ; 108(5): 221-231, 2017 May.
Artigo em Italiano | MEDLINE | ID: mdl-28643813

RESUMO

Polymyalgia rheumatica (PMR) is an inflammatory disease characterized by aching and stiffness in the girdles, which affects typically people over 50 years old and could overlap with giant cell arteritis (GCA) in about 15-20% of cases. Although the diagnosis of PMR is usually considered straightforward, clinicians facing this disease should be aware of its atypical manifestations, which can hamper the correct identification of PMR and, conversely, should be aware of other diseases which may present with polymyalgic features. The aim of this review is to synthetize current knowledge about clinical presentations of PMR, the differential diagnoses, the relationship with cancer, the clues to the presence of a concomitant GCA, the role of ultrasonography at the onset and in the follow-up and, finally, treatment approaches. Besides evidence from the literature, this review will highlight some "tips&tricks" useful in everyday clinical practice. The awareness of the different presentations and pitfalls of PMR could improve patients' management and avoid complications consequent upon unrecognized diseases or, conversely, overtreatment.


Assuntos
Arterite de Células Gigantes/diagnóstico , Polimialgia Reumática/diagnóstico , Diagnóstico Diferencial , Humanos , Pessoa de Meia-Idade , Polimialgia Reumática/fisiopatologia , Polimialgia Reumática/terapia
19.
Clin Exp Rheumatol ; 34(1): 49-52, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26575013

RESUMO

OBJECTIVES: Ankylosis, or spontaneous bone fusion, of the small joints of the hand is a rare event in patients with rheumatoid arthritis (RA), being observed in 0.8% of them on conventional radiographs. It is associated with long-lasting and severe disease. In other settings, such as fracture healing, bone fusion is a reparative process. The aim of this paper is the study of the frequency of wrist ankylosis in patients with RA in comparison with other arthritides; to correlate ankylosis with disease activity. METHODS: A total of 94 patients affected by RA, 71 patients with different rheumatic conditions and 42 controls with no joint disease or with slight hand osteoarthritis were studied. DAS-28 CRP was calculated in patients with RA and psoriatic arthritis. MRI of the clinically most involved wrist was performed with a 0.2 T, extremity-dedicated MRI system. RESULTS: Of RA patients, 10/94 (10.6%) showed ankylosis in comparison with 2/113 (1.8%) controls (p=0.015). RA patients with ankylosis had longer disease duration (p=0.019) but similar disease activity. CONCLUSIONS: MRI-defined bone ankylosis is frequent in RA. It is not limited to seronegative spondyloarthritides and may be part of the bone damage observed in RA.


Assuntos
Anquilose/patologia , Artrite Reumatoide/patologia , Imagem por Ressonância Magnética , Articulação do Punho/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Progressão da Doença , Desenho de Equipamento , Feminino , Humanos , Imagem por Ressonância Magnética/instrumentação , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Índice de Gravidade de Doença
20.
Arthritis Rheumatol ; 67(10): 2569-80, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26352874

RESUMO

Therapy for polymyalgia rheumatica (PMR) varies widely in clinical practice as international recommendations for PMR treatment are not currently available. In this paper, we report the 2015 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) recommendations for the management of PMR. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology as a framework for the project. Accordingly, the direction and strength of the recommendations are based on the quality of evidence, the balance between desirable and undesirable effects, patients' and clinicians' values and preferences, and resource use. Eight overarching principles and nine specific recommendations were developed covering several aspects of PMR, including basic and follow-up investigations of patients under treatment, risk factor assessment, medical access for patients and specialist referral, treatment strategies such as initial glucocorticoid (GC) doses and subsequent tapering regimens, use of intramuscular GCs and disease modifying anti-rheumatic drugs (DMARDs), as well as the roles of non-steroidal anti-rheumatic drugs and non-pharmacological interventions. These recommendations will inform primary, secondary and tertiary care physicians about an international consensus on the management of PMR. These recommendations should serve to inform clinicians about best practices in the care of patients with PMR.


Assuntos
Polimialgia Reumática/tratamento farmacológico , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Europa (Continente) , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Humanos , Fatores de Risco , Estados Unidos
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