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Modern Rheumatology 04/2013; · 1.58 Impact Factor
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Fulvia Ceccarelli,
Carlo Perricone, Francesco Trotta,
Giovanna Cuomo,
Raffaele Pellerito,
Gianfilippo Bagnato,
Fausto Salaffi,
Roberto Caporali,
Maurizio Cutolo,
Mauro Galeazzi,
Ugo Fiocco,
Giovanni Lapadula,
Stefano Bombardieri,
Girolamo Bianchi,
Roberto Gorla,
Anna Rita Giardina,
Gaia Gallo,
Angela Maria Giardino,
Guido Valesini,
On Behalf Of The Arpa Study Group
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ABSTRACT: OBJECTIVES: To provide a survey of disease activity in patients treated with standard care in Italian clinical practice. METHODS: This was an observational prospective cohort study in patients with early, aggressive rheumatoid arthritis (RA; duration ≤2 years but ≥6 weeks; DAS28 >3.2) naïve to anti-tumour necrosis factor (TNF) therapy who were treated with disease-modifying anti-rheumatic drugs (DMARDs) and/or biologics according to standard practice at 15 Italian ARPA (Artrite Reumatoide Precoce Aggressiva) centres. Patients were evaluated at baseline and after 6, 12 and 24 months. The primary endpoint was the proportion of patients achieving remission, as defined by disease activity score in 28 joints (DAS28) <2.6, after 1 year. RESULTS: Among the 152 patients enrolled, 92 were evaluable after 1 year and 77 after 2 years for DAS28. At baseline, patients had a mean DAS28 of 6.1±1.0. At 12 months, 62.6% of patients were treated with DMARDs (in monotherapy or in combination), and 37.4% with anti-TNFs (in monotherapy or in association with DMARDs). At 24 months, 35.1% were receiving anti-TNF therapy. The rate of DAS28 remission rates at 12 months and 24 months were 28.3% (95% confidence interval [CI] 19.1-37.5) and 41.6% (95% confidence interval [CI] 30.6-52.6), respectively. CONCLUSIONS: The remission rate was lower at 12 months compared with previous large randomised clinical trials for early, aggressive RA, but significantly improved at 24 months. These results suggest that patients in real-world clinical settings in Italy may experience a delay in receiving the best possible care.
Clinical and experimental rheumatology 02/2013; · 2.15 Impact Factor
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The Journal of Dermatology 01/2013; · 1.49 Impact Factor
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ABSTRACT: Multicentric reticulohistiocytosis (MRH) and fibroblastic rheumatism (FR) are uncommon disorders with similar joint and skin manifestations. They are usually included among the non-Langerhans histiocytoses, but recent insights drive some criticism. The diagnosis is often challenging and must be confirmed by the histological typical features. If the skin manifestations are missing, the arthritic complaints may be confused with those of other rheumatic disorders. In these cases, only a careful clinical and radiological evaluation leads to the correct diagnosis. The natural course of the diseases may rapidly develop into disabling manifestations, making an aggressive treatment strongly recommendable. There is emerging evidence that anti-tumour necrosis factor-α agents and bisphosphonates are promising drugs for MRH, while a course of methotrexate and steroids seems to be the best option for FR. Finally, the clinician should be aware that in many cases MRH, but not FR, is associated with a large number of systemic manifestations and with malignancy. This eventuality must be accurately ruled out.
Best practice & research. Clinical rheumatology 08/2012; 26(4):543-57. · 2.90 Impact Factor
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ABSTRACT: In this study we analyzed whether the polymorphisms 676T>G in the tumor necrosis factor receptor (TNFR) II gene and −308G>A
in the TNFα promoter gene may influence the response grading to anti-TNFα therapy in rheumatoid arthritis. We enrolled and
genotyped 105 RA patients treated with etanercept (n=55), infliximab (n=40) and adalimumab (n=10) for 1year. The clinical response was evaluated according to the ACR criteria every 3months. Patients with TNFRII
676TG genotype was significantly associated with lower ACR response compared with 676TT genotype, at 3 (OR 3.78 95% CI 1.07–13.31)
and 12months (OR 4.30 95% CI 1.16–15.99) of treatment. No significant association between TNFα −308G>A polymorphism and the
clinical response was found. TNFRII 676TG genotype is associated with a lower response to anti-TNFα therapy, independently
from the specific agent used. This polymorphism could become a useful genetic marker for predicting the different response
grading to anti-TNFα therapy.
Rheumatology International 04/2012; 28(9):901-908. · 1.88 Impact Factor
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ABSTRACT: Paget’s disease of bone (PDB) is a condition of unknown etiology characterized by excessive and abnormal bone remodeling.
It may be localized to one or several skeletal segments. The disease seldom appears before the age of 40years, but its prevalence
tends to double each decade from the age of 50 onwards, reaching about 10% after ninth decade. PDB may virtually affect every
bone in the skeleton. Affected bones are involved right away with no new involvement during the evolution. The basic symptom
of the disease is bone pain, while complications depend on skeletal sites involved and range from secondary osteoarthritis
to malignant degeneration. Diagnosis is usually based upon clinical features, imaging, and laboratory analyses. Therapeutic
approach is currently based on second-generation bisphosphonates. Their use is recommended when bone alkaline phosphatase
is high and/or when the disease localizations are highly suspected for determining complications.
Rheumatology International 04/2012; 28(11):1069-1075. · 1.88 Impact Factor
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ABSTRACT: Adult-onset Still’s disease (AOSD) is a rare systemic inflammatory disorder characterised by high spiking fever, an evanescent
salmon pink rash and arthritis, frequently accompanied by sore throat, myalgias, lymphadenopathies, splenomegaly and neutrophilic
leukocytosis. Aetiology is still unknown, however, it seems that an important role is played by various infectious agents,
which would act as triggers in genetically predisposed hosts. Diagnosis is a clinical one and may be lengthy because it requires
exclusion of infectious neoplasms, including malignant lymphomas and leukaemias, and other autoimmune diseases. Different
diagnostic or classification criteria have been proposed, but not definitely accepted. There are no specific laboratory tests
for AOSD, but they reflect the systemic inflammation: the ESR is consistently high, while the rheumatoid factors and antinuclear
antibodies are negative. High serum ferritin levels associated with a low fraction of its glycosylated component are assessed
as useful diagnostic and disease activity markers. The clinical course can be divided into three main patterns with different
prognoses: self-limited or monophasic, intermittent or polycyclic systemic and chronic articular pattern. Therapy includes
non-steroidal anti-inflammatory drugs, corticosteroids and disease modifying anti-rheumatic drugs: biological agents have
recently been introduced and they seem to be very promising not only for the treatment but also for understanding the pathogenic
mechanisms underlying the disease.
KeywordsAdult-onset Still’s disease-FUO-Systemic diseases-Autoinflammatory syndromes
Rheumatology International 04/2012; 30(7):855-862. · 1.88 Impact Factor
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Clinical and experimental rheumatology 03/2012; 30(3):451. · 2.15 Impact Factor
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ABSTRACT: To evaluate, by a retrospective cross-sectional case-control study from a single center, the distribution of a number of factors and comorbidities potentially related to central nervous system involvement in SLE Italian patients, a number of "generic" (i.e. not strictly SLE related) and "specific" (i.e. SLE related) risk factors were checked and their distribution analyzed in SLE patients with (NPSLE) and without (SLE) neuropsychiatric (NP) involvement. One hundred and fifty-three SLE patients with NP involvement observed from 1999 to 2008 and 247 SLE patients without NP manifestations, matched for sex, age and disease duration were included in the study. A neuropsychiatric (NP) event represented the heralding symptom of the disease in 40.5% of NPSLE. Headache, cerebrovascular events, mood disorders and seizures were the most frequent NP manifestations. NPSLE patients had a major cumulative number of the investigated factors than controls without NP involvement. Antiphospholipid antibodies (aPL), lupus anticoagulant (LA), Antiphospholipid antibodies syndrome (APS), Raynaud's phenomenon, smoke, assumption of contraceptives and higher cumulative dose of glucocorticosteroids (GC) were significantly more commonly observed among NPSLE. APS and systemic arterial hypertension were more frequently detected among patients with focal NP manifestations, especially cerebrovascular events. aPL, LA, APS, Raynaud's phenomenon, smoke, contraceptives intake and higher cumulative dose of GC did prove more frequently detected in NPSLE patients than in controls. In particular, overall, arterial hypertension should be regarded as a potential independent "risk factor" for focal involvement, especially for cerebrovascular events.
Rheumatology International 01/2012; 32(1):129-35. · 1.88 Impact Factor
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ABSTRACT: The reduction of the inflammatory status represents one of the most important targets in rheumatoid arthritis (RA). A central role of A2A and A3 adenosine receptors (ARs) in mechanisms of inflammation has been reported in different pathologies. The primary aim of this study was to investigate the A2A and A3ARs and their involvement in RA progression measured by Disease Activity Score in 28 or 44 joints (DAS28 or DAS).
ARs were analyzed by saturation binding assays, mRNA and Western blotting analysis in lymphocytes from early and established RA patients. The effect of A2A and A3AR agonists in nuclear factor kB (NF-kB) pathway was evaluated. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) release was carried out by A2A and A3AR activation. AR pharmacological regulation in matrix metalloproteinase-1 (MMP-1) and metalloproteinase-3 (MMP-3) release was also studied.
In lymphocytes obtained from RA patients, A2A and A3ARs were up-regulated if compared with healthy controls. A2A and A3AR activation inhibited the NF-kB pathway and diminished inflammatory cytokines such as TNF-α, IL-1β and IL-6. A2A and A3AR agonists mediated a reduction of MMP-1 and MMP-3 release. A2A and A3AR density inversely correlated with DAS28 and DAS suggesting a direct role of the endogenous activation of these receptors in the control of RA joint inflammation.
Taken together these data demonstrate that the inflammatory and clinical responses in RA are regulated by A2A and A3ARs and support the use of A2A and/or A3AR agonists as novel and effective pharmacological treatment in RA patients.
Arthritis research & therapy 12/2011; 13(6):R197. · 4.27 Impact Factor
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Marcello Govoni,
Stefano Bombardieri,
Alessandra Bortoluzzi,
Luisa Caniatti,
Cinzia Casu,
Fabrizio Conti,
Salvatore De Vita,
Andrea Doria,
Ilaria Farina,
Gianfranco Ferraccioli, [......],
Melissa Padovan,
Matteo Piga,
Angela Tincani,
Maria Rosaria Tola,
Paola Tomietto,
Marco Taglietti, Francesco Trotta,
Guido Valesini,
Margherita Zen,
Alessandro Mathieu
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ABSTRACT: To analyse risk factors and comorbidities potentially associated with CNS involvement in a large cohort of Italian patients affected by SLE.
A number of generic (not strictly SLE related) and specific (disease related) risk factors to which all patients have been exposed in the span of 5 years before the first neuropsychiatric (NP) event or before the last available observation were checked for and their distribution was analysed in 959 SLE patients with and without NP involvement; all the first NP events that occurred in a time frame of 10 years were recorded and categorized as SLE related or SLE unrelated.
Three hundred and twenty-six SLE patients with and 633 SLE patients without NP manifestations were included in the study. A total of 469 NP events were recorded. Headache (26.1%), cerebrovascular events (22.7%), mood disorders (8.9%), seizures (14.4%) and cognitive dysfunctions (9.5%) were the most frequent SLE-related NP events. More risk factors [mean 4.52 (2.44) vs 3.73 (2.01); P < 0.0001] were observed in patients with than without NP involvement. Overall, aPLs, LA and APS were factors more strongly associated with NP involvement.
In SLE, NP involvement and aPLs were confirmed as closely related. Furthermore, other modifiable generic risk factors, such as hypertension, carotid vasculopathy and dyslipidaemia, appeared to be related to the occurrence of cerebral vascular accident (CVA) and cognitive dysfunctions, suggesting the need for a more intensive preventive strategy to optimize the management of NP lupus.
Rheumatology (Oxford, England) 11/2011; 51(1):157-68. · 4.24 Impact Factor
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Journal of clinical rheumatology: practical reports on rheumatic & musculoskeletal diseases 04/2011; 17(3):164. · 1.19 Impact Factor
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ABSTRACT: Adult-onset Still's disease (AOSD) is a potentially crippling or life-threatening rare disease that may be self-limited, intermittent, and chronic. Clinical predictors of outcome are still lacking, as is information on the rate of progress of its chronic course. The main objective is to identify factors that improve our ability to predict the course of AOSD, and factors associated with the rate of progress of its chronic course. A comparison with the literature is included.
A retrospective cohort observational study conducted at the tertiary-referral Rheumatology Unit in Ferrara, Italy.
Seventy-six patients (44 females and 32 males) referred to the Unit and who satisfied the criteria for AOSD were identified. Our findings on white AOSD patients are largely compatible with those previously published. Ferritin level, as well disease activity score (DAS(28)), is associated with the rate of progression of the articular manifestations of the disease. A polyarthritis persisting over 6 months is associated with the development of a chronic articular course, irrespective of the size of the involved joints.
Ferritin, being associated with the course of AOSD, could play a role in the diagnosis of the disease. Together with DAS(28), it might also serve as a useful predictor for the rate of progress of the chronic course of the disease, as measured with simple erosion narrowing score.
Seminars in arthritis and rheumatism 03/2011; 41(2):279-85. · 4.72 Impact Factor
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ABSTRACT: To describe a rare association between rheumatoid arthritis (RA) and amyotrophic lateral sclerosis (ALS). Two new cases of patients with RA who developed amyotrophic lateral sclerosis (ALS), one receiving anti-TNFα agents, were reported. Only other five cases of this rare association have been previously described in literature. The simultaneous presence of the two diseases represents a difficult diagnostic challenge because RA may mimic some musculoskeletal symptoms of ALS. There is no evidence in favor of a common pathophysiologic mechanism, and thus the possibility of a fortuitous association must be raised. A neurotoxic side effect of various drugs for RA treatment could be considered. Casual or causal association remains a difficult choice. The possibility of a coincidental association must be raised but neurologic side effects of TNFα blockers lead to discussion.
Rheumatology International 01/2011; 31(6):715-9. · 1.88 Impact Factor
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ABSTRACT: Rheumatoid arthritis (RA), is the most common inflammatory musculoskeletal disease inducing diminished quality-of-life in the affected individuals and having major impact on society due to decrease work ability. Early diagnosis and immediate, effective therapy are crucial in order to prevent unfavorable outcome. Treatment of RA has progressed during the past two decades thanks to the advent of a large number of new agents targeting different specific molecules and pathways involved in the modulation of the inflammation. In this scenario an important role is covered by adenosine, a purine nucleoside released from a variety of cells in response to metabolic and inflammatory stress, which is considered to be a potent endogenous regulator acting through its interaction with 4 cell surface receptors named as A(1), A(2A), A(2B) and A(3). Adenosine receptor stimulation has complex effects on the release of pro-inflammatory cytokines depending on selective receptor engagement. Recent data show the involvement of adenosine pathways in RA and its potential therapeutic implications.
Autoimmunity reviews 12/2010; 10(2):61-4. · 6.37 Impact Factor
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Arthritis care & research. 10/2010; 62(10):1513; author reply 1513-4.
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ABSTRACT: Glucocorticoid Receptors (GRs) have been identified in all bone cells. The molecular structure of human GR is organized into 3 major functional domains: the N-terminal immunogenic domain, the central DNA-binding domain and the C-terminal ligand-binding domain. Human GR is a product of a gene composed of 10 exons, located in the chromosome 5q31-32. An alternative splicing in exon 9 gives rise to 2 mRNAs encoding the classical hGRα and hGRβ isoforms. Human GRα is present in the cytoplasm of almost all cells, as a multiprotein complex and works as a ligand-dependent transcription factor. In contrast to hGRα, hGRβ is located in the nucleus, does not bind hormone or activate glucocorticoid (GC)-response genes. It works as a dominant negative inhibitor of hGRα. The effects of GCs are - at least in part - mediated via specific GRs (genomic effect), however GCs also have acute non genomic effects. Osteoblasts are the most obvious target of GCs in bone, suppressing their maturation, activity and survival. Osteoblasts stimulate osteoclastic activity through the RANKL-osteoprotegerin-RANK system, but this effect is weaned off rapidly by the incoming suppression of the global osteoblast activity. The direct action of GCs on osteoclasts results almost invariably in a suppression of cell activity. When exposed to high concentrations of GCs, osteocytes undergo a slow process of apoptosis. Osteocytes with their dendritic network sense the skeletal strain and stress of normal daily activities. This continuous stimulus prevents the production of sclerostin and possibly DKK1, which are able to strongly suppress osteoblast formation by interacting with the Wnt system. GCs are thought to stimulate sclerostin secretion from osteocytes.
Current pharmaceutical design 10/2010; 16(32):3586-92. · 4.41 Impact Factor
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ABSTRACT: To assess the relationship between serum concentrations of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and osteoprotegerin (OPG) and the therapeutic response to disease-modifying antirheumatic drugs (DMARD) in patients with early rheumatoid arthritis (RA).
Circulating levels of TRAIL and its soluble receptor OPG were measured by ELISA in paired serum samples obtained from 66 patients with early RA at their first visit (baseline) and after 1 year of therapy. Levels of TRAIL and OPG were analyzed in relation to the clinical response, defined by the 28-joint count Disease Activity Score (DAS28).
Both serum TRAIL and OPG increased after DMARD therapy. Baseline levels of TRAIL, but not OPG, were significantly higher (p < 0.05) in the patients that achieved a clinical response by DAS28 after 1 year of therapy, versus patients without clinical response to DMARD. Baseline serum levels of TRAIL were higher (p < 0.01) in rheumatoid factor-negative patients.
Our data suggest that the basal level of circulating TRAIL is an important determinant in the therapeutic response to DMARD in patients with early RA.
The Journal of Rheumatology 07/2010; 37(7):1461-6. · 3.69 Impact Factor
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Rheumatology (Oxford, England) 05/2010; 49(5):1019-21; author reply 1021-2. · 4.24 Impact Factor
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ABSTRACT: To perform an observational retrospective cross-sectional case-control study to evaluate prevalence, clinical patterns and outcomes of CNS involvement in a large cohort of primary SS (pSS) patients.
A total of 424 pSS patients, diagnosed according to the 2002 criteria proposed by the American-European Consensus Group, were checked for CNS involvement after exclusion of secondary causes. Demographic, clinical, seroimmunological data were compared between patients with and without CNS involvement. Neuroimaging data were also analysed.
CNS involvement was detected in 25 (5.8%) patients (24 females and 1 male) both at disease onset (52%) and later (48%) with a mean latency after diagnosis of 7 years. Diffuse (40%), focal/multifocal (36%), multiple sclerosis (MS)-like disease (20%) and isolated optic neuritis (4%) were the most common CNS clinical pictures. Disease duration, lung involvement and decreased C(4) were associated with CNS involvement, while articular manifestations were more frequently observed in patients without neurological complications. Most cases had an acute, often recurrent course with spontaneous remission or only mild neurological impairment.
CNS involvement represents a rare but not negligible complication of pSS, which may occur with a bimodal temporal pattern, both at onset and later, prompting attention in the differential diagnosis of apparently isolated neurological syndromes. Lung involvement emerged as the strongest risk factor for CNS involvement with a relative risk of 7.9, along with disease duration and decreased C(4).
Rheumatology (Oxford, England) 05/2010; 49(8):1540-9. · 4.24 Impact Factor
