EULAR/EFORT recommendations for management of patients older than 50†years with a fragility fracture and prevention of subsequent fractures.

The European League Against Rheumatism (EULAR) and the European Federation of National Associations of Orthopaedics and Traumatology (EFORT) have recognised the importance of optimal acute care for the patients aged 50 years and over with a recent fragility fracture and the prevention of subsequent fractures in high-risk patients, which can be facilitated by close collaboration between orthopaedic surgeons and rheumatologists or other metabolic bone experts. Therefore, the aim was to establish for the first time collaborative recommendations for these patients. According to the EULAR standard operating procedures for the elaboration and implementation of evidence-based recommendations, 7 rheumatologists, a geriatrician and 10 orthopaedic surgeons met twice under the leadership of 2 convenors, a senior advisor, a clinical epidemiologist and 3 research fellows. After defining the content and procedures of the task force, 10 research questions were formulated, a comprehensive and systematic literature search was performed and the results were presented to the entire committee. 10 recommendations were formulated based on evidence from the literature and after discussion and consensus building in the group. The recommendations included appropriate medical and surgical perioperative care, which requires, especially in the elderly, a multidisciplinary approach including orthogeriatric care. A coordinator should setup a process for the systematic investigations for future fracture risk in all elderly patients with a recent fracture. High-risk patients should have appropriate non-pharmacological and pharmacological treatment to decrease the risk of subsequent fracture.

Arthritis and osteoporosis: pathogenetic correlations in function of arthroplasty.

Osteoarthritis is being increasingly characterised as an inflammatory incoming and recurrent disease, with the specific symptoms of inflammation at every stage of the disease. With regard to the pathogenesis over time, the degenerative and inflammatory components are combined and lead to osteocartilaginous degeneration. Such deterioration involves other joint tissues as well as the subchondral bone tissue, the suffering of which is the key event of the beginning and progression of OA; its involvement concerns the same pathogenetic mechanisms and the same chemical mediators of the chondropathy. The increase in joint inflammatory events leads to suspect the onset or the worsening of the osteometabolic disorder, which is documented by the MR as “bone edema” or as algodystrophic syndrome. The pain appears both while moving and resting and with signs of inflammation. The treatment of OA requires drugs, such as paracetamol, selective and nonselective NSAIDs and opiates, for pain control. Treatment should ensure the pharmacological control of the pain related to the osteometabolic juxta-articular alteration, through bisphosphonates, favouring those which can control bone loss, inflammation and pain.

Osteoporosis in the elderly.

Osteoporosis is predominantly a condition of the elderly with a consequent increase in bone fragility and susceptibility to fracture. A number of clinical as well as biological studies have been pivotal in providing us with an understanding of the pathophysiology of this condition. This article discusses the current concepts of age-related osteoporosis.

Endothelin receptor antagonists: effects on extracellular matrix synthesis in primary cultures of skin fibroblasts from systemic sclerosis patients.

Endothelin-1 (ET-1) seems to enhance the pro-fibrotic protein synthesis by skin fibroblasts and its effects are mediated by endothelin-A and B (ETA and ETB) receptors. This study aimed to investigate the effects of ETA and ETB receptor antagonists (ETARA-sitaxsentan and ETA/BRA-bosentan) on type I collagen (COL-1), fibronectin (FN) and fibrillin-1 (FBL-1) synthesis in primary cultures of skin fibroblasts from systemic sclerosis patients. Primary cultures of fibroblasts were obtained from skin biopsies of 6 female systemic sclerosis patients and were treated with ET-1 (100 nM) for 24 and 48 hrs with or without pre-treatment (1 hr) with ETARA (2 µM) or ETA/BRA (10 µM). Primary culture of human scleroderma skin fibroblasts not treated with ET-1 or ET receptor antagonists (ETARA and ETA/BRA) were used as controls. COL-1, FN and FBL-1 synthesis was evaluated by immunocytochemistry and Western blot analysis. Immunocytochemistry and Western blot analysis showed that ET-1 significantly increased COL-1 and FN synthesis at 24 and 48 hrs and FBL-1 synthesis at 48 hrs vs untreated cells. ETARA significantly contrasted the ET-1-mediated increase in COL-1 and FN at 24 hrs as well as COL-1 and FBL-1 at 48 hrs, but not FN synthesis vs ET-1-treated fibroblasts. Conversely, ETA/BRA significantly antagonized the ET-1-mediated overproduction of COL-1 and FN both at 24 and 48 hrs and the FBL-1 synthesis at 48 hrs vs ET-1-treated cells. The single ETARA treatment seems to contrast significantly the increase in COL-1 synthesis, whereas the dual ETA/BRA treatment seems active in significantly antagonizing both COL-1 and FN overproduction induced by ET-1. In conclusion, ET-1 antagonism might have positive effects in contrasting the profibrotic activity of systemic sclerosis skin fibroblasts.

[CTLA4-Ig interferes and downregulates the proinflammatory activities of rheumatoid synovial macrophages in monoculture]. / CTLA4-Ig influenza e inibisce le attività proinfiammatorie di macrofagi sinoviali reumatoidi in monocoltura.

OBJECTIVE: CTLA4-Ig, a biologic agent employed in rheumatoid arthritis (RA) treatment, downregulates the immune response and exerts anti-inflammatory effects acting on different cells including dendritic/T cells interaction and directly on osteoclasts. We investigated the anti-inflammatory effects of CTLA4-Ig in primary monocultures of RA synovial macrophages (SM). METHODS: SM were obtained, from 8 RA patients (7 F, 1 M; DAS28>5.2) who underwent therapeutic arthroscopic synoviectomy and were cultured in the absence and in the presence of CTLA4-Ig at the concentration of [500 microg/ml], the most reliable dose related to the previous pharmacological clinical and experimental experiences. Inflammatory cytokine (IL-6, TNFalpha, IL-1beta) expression was evaluated by immunocytochemistry (ICC with relative image analysis), western blot (WB), and quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: ICC analysis revealed that CTLA4-Ig treatment significantly downregulated cytokine expression (p<0.001 for IL-6, TNFalpha and IL-1beta) when compared to untreated RA SM. WB and qRT-PCR confirmed partially the data. CONCLUSIONS: CTLA4-Ig was found to exert a direct and significant anti-inflammatory effect on primary monocultures of RA SM, suggesting a therapeutic power in different phases of the disease activity.

Endothelin and sex hormones modulate the fibronectin synthesis by cultured human skin scleroderma fibroblasts.

OBJECTIVE: To evaluate the influence of endothelin-1 (ET-1) and sex hormones on cell proliferation and extracellular matrix (ECM) synthesis (ie, fibronectin, laminin) by cultured normal and scleroderma (SSc) human skin fibroblasts (FBs). METHODS: Primary cultures of FBs were treated with ET-1 and sex hormones (17beta-oestradiol or testosterone) for 24 h. Cell growth was analysed by methiltetrazolium salt test, ECM synthesis was evaluated by immunocytochemistry and western blot, both at 24 h. RESULTS: In normal FBs, ET-1 and 17beta-oestradiol, as well as their combination, increased cell growth (p<0.001, p<0.001, p<0.01 vs untreated cells (control), respectively) and fibronectin synthesis (p<0.05, p<0.05, p<0.01 vs control, respectively). By contrast, testosterone either alone or in combination with ET-1 did not influence cell proliferation, but decreased fibronectin synthesis (p<0.05, testosterone vs control). In SSc FBs, ET-1 and 17beta-oestradiol alone or their combination induced an increased fibronectin synthesis (p<0.05, p<0.05, p<0.01 vs control, respectively). Unexpectedly, testosterone induced an increase of fibronectin synthesis (p<0.05 vs control). CONCLUSIONS: ET-1 and 17beta-oestradiol seem to exert a profibrotic effect in normal and SSc culture FBs and might suggest their synergistic effect in the pathogenesis of the fibrotic process in SSc.

[Role of videocapillaroscopy in early detection of transition from primary to secondary Raynaud's phenomenon in systemic sclerosis]. / Ruolo della videocapillaroscopia periungueale nella identificazione precoce della progressione del fenomeno di Raynaud da primario a secondario nella sclerosi sistemica.

Patients initially diagnosed as having primary Raynaud's phenomenon (PRP) may shift to secondary (SRP) during the follow-up. Nailfold videocapillaroscopy (NVC) is a tool that allows to distinguish between PRP and SRP through the identification of the "early" scleroderma-pattern of microangiopathy. The aim of this study was to evaluate the transition from PRP to SRP in an Italian cohort of patients during their follow-up. 129 patients with PRP were identified and followed-up for 2721 months. The diagnosis of PRP was achieved as suggested by LeRoy. The NVC diagnosis of scleroderma-pattern was based on the presence of specific "early" capillary abnormalities (i.e. giant capillaries, microhaemorrhages, and/or slight reduction of capillary density). Based on the identification of the "early" scleroderma-pattern by NVC, 14% of patients changed from PRP to SRP during the follow-up. Interestingly, 4.6% of these patients showed at baseline a fully normal NVC pattern (transition from normal to scleroderma NVC pattern in 3427 months), and 10% showed slight and not-specific nailfold capillary abnormalities (i.e. dystrophic capillaries and/or enlarged capillaries) at baseline (transition to scleroderma NVC pattern in 2515 months). Following a careful NVC analysis, we showed the progression from PRP to SRP in 14% of the analyzed patients. We suggest the capillaroscopic analysis twice a year in presence of PRP, in order to early detect the transition to SRP in patients showing at the beginning a normal pattern or not-specific nailfold capillary abnormalities, as assessed by NVC.

[Are there any positive effects of TNF-alpha blockers on bone metabolism?]. / La terapia con anti TNF-alfa ha effetti positivi sul metabolismo osseo?

UNLABELLED: Secondary osteoporosis (OP) is a well-recognized complication of rheumatoid arthritis (RA). Treatment with TNF-alpha blockers, might influence bone metabolism and prevent structural bone damage in RA, in particular at the periarticular regions. OBJECTIVE: To assess the influence of anti-TNF-alpha therapy, on bone metabolism in RA patients. 36 RA patients were treated with stable therapy of prednisone (7.5 mg/day) and methotrexate (MTX=10 mg/week). Nine of these RA patients further received etanercept (25 mg, twice/weekly) and eleven infliximab (3mg/kg on 0, 2, 6, and every 8 weeks thereafter). A control group included 16 RA patients only with stable therapy (some dosage of prednisone and MTX). Quantitative Ultrasound (QUS) bone densitometry was obtained at the metaphyses of the proximal phalanges of both hands with a DBM Sonic 1200 QUS device (IGEA, Carpi, Italy). Bone mineral density (BMD) of the hip and lumbar spine were performed with a densitometer ( Lunar Prodigy, GE, USA) at baseline and after 12 months. Soluble bone turnover markers [osteocalcin (OC), bone alkaline phospatase (ALP) deoxypyridinoline/creatinine ratio (Dpd/Cr) and cross-linked N-telopeptide of type I collagen / creatinine ratio (NTx/Cr)] were measured using ELISA tests. RESULTS: AD-SoS values were found increased by +4.55% after 12 months of treatment in the RA patients treated with anti-TNF-alpha therapy. On the contrary, the Ad-SoS levels decreased by -4.48% during the same period in the control RA group. BMD increased by +3.64% at lumbar spine and +2.90% at the hip (both p<0.001) in TNF-alpha blockers-treated patients and decreased by -2.89% and -3.10% (both p<0.001, respectively at lumbar spine and at the hip) in RA patients without anti-TNF-alpha therapy. In RA patients treated with TNF-alpha blockers, OC and bone ALP levels were found significantly increased (p<0.01) and Dpd/Cr or NTx/Cr levels were found significantly decreased (p<0.01) at 12 months when compared to baseline values. CONCLUSION: During 12 months of treatment of RA patients with TNF-alpha blockers, bone formation seems increased while bone resorption seems decreased. The reduced rate of OP seems supported by the same mechanisms involved in the decreased bone joint resorption during anti-TNF-alpha therapy (i.e. increase of osteoblastic activity and decrease osteoclastic activity).

Serum cytokines and steroidal hormones in polymyalgia rheumatica and elderly-onset rheumatoid arthritis.

BACKGROUND: Polymyalgia rheumatica (PMR) may create some difficulties in the differential diagnosis of elderly-onset rheumatoid arthritis (EORA) and of EORA with PMR-like onset (EORA/PMR). AIM: To investigate possible differences between three groups of patients, with regard to serum levels of inflammatory cytokines and steroidal hormones at baseline and after 1 month of treatment with glucocorticoids (prednisone 7.5-12.5 mg/day). PATIENTS AND METHODS: 14 patients with PMR, 15 with EORA and 14 with EORA/PMR, as well as 15 healthy, matched controls were analysed. Tumour necrosis factor alpha (TNFalpha), interleukin (IL)6, IL1 receptor antagonist (IL1Ra), cortisol, dehydroepiandrosterone sulphate (DHEAS) and 17-hydroxy-progesterone (PRG) were evaluated. RESULTS: Serum levels of both TNFalpha and IL6 were significantly higher in all three groups of patients than in controls (p<0.01). Serum IL6 levels were significantly higher in patients with both PMR and EORA/PMR than in patients with EORA (p<0.05). IL1Ra serum levels were significantly higher in patients with EORA than in controls (p<0.001) and in patients with PMR and EORA/PMR (p<0.05). DHEAS was significantly lower in patients with EORA/PMR than in those with EORA (p<0.05). PRG was significantly higher in all patient groups (p<0.05). After glucocorticoid treatment, serum TNFalpha and IL6 levels significantly decreased in all patient groups; IL1Ra significantly increased in patients with PMR and in those with EORA/PMR; cortisol, DHEAS, and PRG significantly decreased in patients with PMR and in those with EORA/PMR (p<0.05). CONCLUSIONS: Different cytokine and steroidal hormone patterns suggest that patients with PMR and those with EORA/PMR seem to be have a more intensive inflammatory reaction and are more efficient responders to glucocorticoid treatment than patients with EORA.

Anti-inflammatory effects of leflunomide in combination with methotrexate on co-culture of T lymphocytes and synovial macrophages from rheumatoid arthritis patients.

OBJECTIVES: To investigate the anti-inflammatory effects of the active leflunomide metabolite A771726 (Lef-M) in combination with methotrexate (MTX) on synovial macrophages (SM) from rheumatoid arthritis (RA) patients co-cultured with an activated T cell line (Jurkat cell line). METHODS: Pro-inflammatory cytokines (TNFalpha, IL1beta, IL6), adhesion molecule ICAM-1, cyclooxygenase isoenzymes (COX1, COX2), and the nuclear factor kappaB (NF-kappaB) complex were analysed on SM co-cultured with a T cell line, as intracellular protein expression by immunocytochemistry (ICC) and western blot analysis, as extracellular protein expression by ELISA assay, and as mRNA expression by reverse transcriptase-multiplex PCR (RT-MPCR) after treatment with Lef-M (1, 10, 30 micromol/l) alone or in combination with MTX (50 ng/ml). RESULTS: The most significant intracellular decrease in cytokines was observed by ICC in SM treated with the combination of Lef-M (1, 10, 30 micromol/l) and MTX (50 ng/ml) versus untreated SM (TNFalpha 29%, 37%, 49%, IL1beta 56%, 43%, 50%, and IL6 59%, 62%, 71%, respectively). Furthermore, a significant decrease was confirmed concerning cytokine levels evaluated by ELISA in the medium of SM treated with the combination Lef-M+MTX (TNFalpha 40%, 41%, 44%; IL1beta 10%, 20%, 60%; IL6 37%, 41%, 49%, respectively). Western blot and RT-PCR analysis confirmed these results. Concordant decreased expression was observed for ICAM-1, COX1, COX2, and the NF-kappaB complex after Lef-M+MTX treatment. CONCLUSIONS: The combination of MTX and Lef-M shows additive inhibitory effects on the production of inflammatory mediators from SM co-cultured with a T cell line. These observations might support the positive results obtained in RA clinical studies by combination therapy.

Circannual vitamin d serum levels and disease activity in rheumatoid arthritis: Northern versus Southern Europe.

BACKGROUND: Greater intake of vitamin D has been associated with a lower risk of rheumatoid arthritis (RA) and low serum vitamin D together with higher prevalence of RA seem common among North European people when compared to Southern Europe. OBJECTIVES: To evaluate serum 25-hydroxyvitamin D [25(OH)D] levels in female RA patients from North (Estonia) and South (Italy) Europe and to correlate them with the disease activity score (DAS28) during winter and summer. METHODS: Fifty-four RA Italian patients (IP) and 64 RA Estonian patients (EP) were evaluated for serum 25(OH)D levels in winter and summer time, as well as for DAS28 score. Normal female controls (C) were 35 (IC) and 30 (EC) age-matched subjects, respectively. 25(OH)D concentrations were measured by a competitive radioimmunoassay. Statistical analysis was performed by "r" Pearson correlation, "t" Student with Bonferroni correction and by repeated ANOVA measures (summer and winter) with two factors (country and clinical status). RESULTS: 25(OH)D levels were found significantly higher in IP versus EP (p = 0.0116) both in winter and in summer time. Differences were observed also in controls. The variations (increase) of 25(OH)D levels between winter and summer were found significant (p = 0.0005) in both IP and EP. Differences were observed also in controls. No significant differences were found concerning 25(OH)D levels between RA patients and their controls in either country. Interestingly, a significant negative correlation between 25(OH)D and DAS28, was found in summer only in IP (r =-0.57, p < 0.0001) and in winter in EP (r =-0.40, p < 0.05). CONCLUSION: Significantly lower 25(OH)D serum levels were observed in RA patients from North versus South Europe with a circannual rhythm in winter and summer time. In addition, 25(OH)D values showed a significant correlation (negative) with RA clinical status (DAS28) in both North and South European RA patients, suggesting possible effects of vitamin D among other factors on disease activity.

Estrogens, autoimmunity and the heart.

Systemic inflammatory/autoimmune rheumatic diseases are associated with a significantly increased rate of atherosclerosis and cardiovascular disease. Several mechanisms of accelerated atherosclerosis have been proposed, including abnormal lipid and lipoprotein profiles, oxidative stress, enhanced apoptosis, thrombophilia, immune complexes and increased mononuclear cell infiltration of atherosclerotic lesions, local generation of cytokines and female estrogen deficiency. However, the widely shared enthusiasm about the cardioprotective potential of hormone replacement therapy (HRT) with estrogens, has come to an abrupt halt since very recent randomized trials failed to show a cardiovascular risk reduction in postmenopausal women. Several factors might play a role in these discrepancies, in particular, parts of the striking discrepancy between observational and randomized data have been attributed to an estrogen-mediated adverse effect on inflammation (enhancement, possibly dose-related). In fact, estrogens potentially increase the inflammatory/immune response in autoimmune rheumatic diseases. New roles for estrogen peripheral metabolites (hydroxylated) and their increased formation in inflammatory sites, might partially introduce some explanations for several apparently contrasting evidences.

Altered circadian rhythms in rheumatoid arthritis patients play a role in the disease's symptoms.

The circadian changes in the metabolism or nocturnal secretion of endogenous corticosteroids (reduction) observed in rheumatoid arthritis (RA) patients are responsible, in part, for the time-dependent changes that are observed in the inflammatory response and related early morning clinical symptoms of the disease. Melatonin (MLT), another circadian nocturnal hormone that is the secretory product of the pineal gland, has been implicated in the time-dependent RA inflammatory reaction with effects that are opposite to those of corticosteroids. As a consequence, altered functioning of the HPA axis (early morning reduced corticosteroid production) and of the pineal gland (night increased MLT production) found in RA patients, seem to be important factors in the appearance and perpetuation of the clinical circadian symptoms of the disease. Consistently, human proinflammatory Th1-type cytokine production (related to MLT stimulation) exhibits a diurnal rhythmicity with peak levels during the night and early morning, at a time when plasma cortisol (inducing the Th2-type cytokine production) is lowest and MLT is highest. Reduced daily light exposure as observed in northern Europe (Estonia), at least during the winter, might explain the higher and more prolonged serum MLT concentrations that were observed in northern RA patients, as well as some epidemiological features versus southern Europe patients.

Efficacy and tolerability of lumiracoxib versus placebo in patients with osteoarthritis of the hand.

OBJECTIVE: This multicentre, randomized, double-blind, placebo-controlled parallel-group study was undertaken to investigate the efficacy, safety and tolerability of lumiracoxib (Prexige), a cyclooxygenase-2 selective inhibitor, in patients with primary osteoarthritis (OA) of the hand. METHODS: The study randomized 594 patients aged > or = 18 years with symptomatic OA of the hand. Patients underwent a 3 to 7-day washout for previous nonsteroidal anti-inflammatory drugs and those with pain intensity > or = 40 mm on a 100 mm Visual Analogue Scale (VAS) in the target hand during the 24 hours prior to baseline and an increase in pain intensity of either > or = 20% or > or = 10 mm VAS since screening (whichever was greater) were randomized to lumiracoxib 200 mg once daily (od) (n=205), lumiracoxib 400 mg od (n=193) or placebo (n=196). The primary efficacy variable was overall OA pain intensity (VAS mm) in the target hand after 4 weeks of treatment. Safety and tolerability assessments were performed. RESULTS: After 4 weeks of treatment, overall OA pain intensity in the target hand was significantly lower for patients treated with lumiracoxib compared with patients treated with placebo (both doses p<0.001). There was no significant difference between lumiracoxib doses in terms of the reduction in overall OA pain intensity. Lumiracoxib was well tolerated. The incidence of adverse events was similar for active treatment groups and placebo. CONCLUSIONS: Lumiracoxib 200 and 400 mg od were effective and well tolerated treatments for OA of the hand. Lumiracoxib significantly improved overall OA pain intensity in the target hand versus placebo, with a tolerability profile similar to placebo.

Sex hormones influence on the immune system: basic and clinical aspects in autoimmunity.

Sex hormones seem to play an important role as modulators of the autoimmune disease onset/perpetuation. Generally, steroid hormones are implicated in the immune response, with estrogens as enhancers at least of the humoral immunity and androgens and progesterone (and glucocorticoids) as natural immunosuppressors. Synovial fluid levels (SF) of proinflammatory estrogens relative to androgens are significantly elevated in both male and female rheumatoid arthritis (RA) patients, as compared to controls, which is most probably due to increase of local enzymatic aromatase activity. Serum levels of estrogens have been found altered in RA patients, particularly estradiol in man. Thus, available steroid prehormones are rapidly converted to proinflammatory estrogens in the synovial tissue in the presence of inflammatory cytokines (i.e., TNFalpha, IL-1, IL-6). The increased estrogen concentrations observed in RA SF of both sexes are characterized mainly by the hydroxylated forms, in particular, 16alpha-hydroxyestrone, showing a mitogenic tumor growth stimulating role. Altered serum hydroxylated estrogens have been found also in serum of systemic lupus erythematosus (SLE) patients. As a matter of fact, our recent studies indicate that 17-beta estradiol (E2) clearly enhanced the expression of markers of cell growth and proliferation, whereas testosterone (T) induced an increase of markers indicating DNA damage and apoptosis. In particular, our data further shows that the enhancing role of estrogens on immune/inflammatory response is exerted by activating the NFkB complex pathway. In conclusion, locally increased estrogens (i.e., synovial tissue in RA or skin in SLE) might exert activating effects on cell proliferation, including macrophages and fibroblasts, suggesting new roles for estrogens in autoimmunity.

[Nailfold videocapillaroscopy in systemic sclerosis: diagnostic and follow-up parameters and correlation with both specific serum autoantibodies and subsets of skin involvement]. / La videocapillaroscopia periungueale nella sclerosi sistemica: parametri diagnostici e di follow-up della malattia e correlazione con il tipo di impegno cutaneo e con gli autoanticorpi specifici.

INTRODUCTION: The aim of the present study was to demonstrate, by nailfold videocapillaroscopy (NVC), the existence of diagnostic and follow-up parameters of microvascular damage in systemic sclerosis (SS) (grouped in the "early", "active" and "late" NVC patterns). The presence of the different subsets of skin involvement (limSS and difSS), as well as the role of some specific serum autoantibodies in the expression of the NVC parameters were investigated. METHODS: 245 consecutive SS patients were recruited and clinical data assessed. Antinuclear (ANA), antitopoisomerase I (Scl70) and anticentromere (ACA) antibodies were investigated in all patients. RESULTS: Giant capillaries and hemorrhages were confirmed to be the earliest NVC finding in SS (diagnostic parameters). The loss of capillaries, along with ramified capillaries and vascular architectural disorganization were validated as parameters of progression of SS microangiopathy. Really, both Raynaud's phenomenon (RP) and SS duration were detected longer in patients with the "late" than in those with the "active" or the "early" NVC pattern. Patients affected by limSS were found to have shorter disease duration, as well as showed more frequently the "early" or the "active" NVC patterns. Conversely, patients affected by the difSS showed longer disease duration and mostly the presence of the "active" or "late" NVC pattern. The Scl70 positivity was lower in the patients showing the "early" than in those with the "active" and the "late" NVC patterns, whereas no significant correlation was found between the Scl70 presence and both RP and SS duration. The ACA positivity was higher in patients showing the "early" NVC pattern, as well as in patients with longer disease duration. CONCLUSIONS: This study confirms that the identification of distinct NVC patterns may be useful to evaluate the severity and the stage of the SS microvascular damage. The presence of the Scl70 antibodies seems related to a more rapid progression of the SS microangiopathy. On the contrary, the presence of the ACA seems to be related to a slower progression of the SS microvascular damage. The SS peripheral microangiopathy is similar as in patients with limSS, as in those affected by difSS.

Nailfold videocapillaroscopic patterns and serum autoantibodies in systemic sclerosis.

BACKGROUND: Microvascular lesions are a predominant feature in systemic sclerosis (SSc) and seem to play a central pathogenetic role. Recently, we graded scleroderma microangiopathy by nailfold videocapillaroscopy (NVC) into three NVC patterns (early, active and late). The aim of the present study was to confirm, in a larger number of SSc patients, the presence of three patterns of microvascular damage, and to detect any possible relationship between these patterns and both specific serum autoantibodies and the subsets of cutaneous involvement. METHODS: Two hundred and forty-one consecutive patients (227 women and 14 men) affected by SSc were recruited. One hundred and forty-eight patients were affected by limited cutaneous SSc (lSSc) and 93 patients by diffuse cutaneous SSc (dSSc). The ages at onset of Raynaud's phenomenon (RP) and SSc, the durations of RP and SSc, ANA and antitopoisomerase I (anti-Scl70) and anticentromere (ACA) antibodies were investigated in all patients. The SSc patients were subdivided on the basis of the NVC pattern into three groups. RESULTS: A statistically significant correlation was found between the NVC patterns and the durations of both RP and SSc (P<0.001). Enlarged and giant capillaries, together with haemorrhages, constituted the earliest NVC finding in SSc (early NVC pattern). These abnormalities were mostly expressed in the active NVC pattern. Loss of capillaries, ramified capillaries and vascular architectural disorganization were increased in the late NVC pattern. Age and the duration of both RP and SSc were lower in 24 patients complaining of RP alone. Anti-Scl70 antibodies were statistically less frequent in the early vs both the active and the late NVC pattern, whereas no significant correlation was found between the presence of anti-Scl70 antibodies and the duration of either RP or SSc. ACA positivity was more frequent in patients with longer RP duration. Patients with lSSc had shorter SSc duration and showed the early or active NVC pattern more frequently. Conversely, patients with dSSc showed longer disease duration and mostly showed the late NVC pattern. CONCLUSIONS: NVC is an appropriate tool for differential diagnosis between primary and secondary RP through the clear recognition of the early NVC scleroderma pattern. This study confirms, in a large number of SSc patients, the existence of three distinct NVC patterns that might reflect the evolution of SSc microangiopathy. The presence of anti-Scl70 antibodies seems be related to earlier expression of the active and late NVC patterns of SSc microvascular damage. The presence of ACA seems to be related to delayed expression of the late NVC pattern.

[Rheumatoid arthritis and atherosclerosis]. / Artrite reumatoide ed aterosclerosi.

Evidence continue to accumulate indicating that patients with rheumatoid arthritis (RA) present an increased risk of cardiovascular disease (and death). The risk factors for coronary artery disease (CAD) in RA are not fully understood. However, a number of possible factors have been described, but more than one may be efficient, such as homocysteine, presence of antiphospholipid antibodies, altered serum levels of selected lipoproteins, and all together may have implications for the atherogenesis observed in these patients. Other factors that may facilitate this process, include corticosteroid use, methotrexate therapy and hormonal factors. However, the relative importance of these specific risk factors for the atherogenesis in this disease is poorly known. Recent findings indicate that cardiac death is increased in RA patients when compared with subjects without arthritis and that generally, the inflammatory process may contribute to atherosclerosis. In addition, other studies indicate that serum concentration of pro-inflammatory cytokines are found elevated at baseline, among patients at risk for future coronary occlusion.