An engineered glove to follow finger function in rheumatoid arthritis: an observational prospective study.

The engineered Hand Test System (HTS) glove has shown high reliability in assessing the baseline functional status of rheumatoid arthritis (RA) hand. Starting from this achievement, the aim of the present observational prospective study was to assess the functionality of the single fingers of rheumatoid hand at follow-up. Eighty RA patients performed HTS glove tests at baseline and among these fifty-six patients were re-tested after 7 months. The HTS glove parameters [Touch Duration (TD), Movement Rate (MR), Inter Tapping Interval (ITI)] were correlated with disease activity and disability clinimetric indexes [Disease Activity Score 28 joint count-C-reactive protein (DAS28-CRP), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), Health Assessment Questionnaire-Disability Index (HAQ-DI), grip strength, visual analogue scale of pain (VAS), patient global assessment (PGA)], and with laboratory values. HTS glove parameters (TD, ITI, and MR) showed statistically significant correlations with clinimetric and clinical indexes at both time points (p < 0.05). During follow-up, a statistically significant variation of all HTS glove parameters for the fingers that have performed both the worst or best HTS test at baseline was detected (p < 0.05), while the mean HTS glove parameter values by considering all fingers did not show a statistically significant variation over time, as well as the traditional clinimetric indexes. Besides the objective role in assessing the RA hand function by integrating the traditional clinimetric indexes, the HTS glove seems a useful tool for evaluating worst or best finger function during time by measuring the movement speed.

Cost-effectiveness and cost-utility of add-on, low-dose prednisolone in patients with rheumatoid arthritis aged 65+: The pragmatic, multicenter, placebo-controlled GLORIA trial.

BACKGROUND: The GLORIA placebo-controlled trial found a favorable balance of benefit and harm for two years of prednisolone (5 mg/day) as add-on treatment for rheumatoid arthritis (RA) patients aged 65+. This study evaluated the cost-effectiveness of low-dose prednisolone in the treatment of RA. METHODS: The economic evaluation had a societal perspective with a time horizon of two years. Cost data were collected with questionnaires and from recorded events, and valued with standard Dutch unit prices of 2017. The primary effectiveness outcome was the disease activity score in 28 joints (DAS28). For cost-utility, quality-adjusted life years (QALYs) were estimated from the EuroQol-5 Dimension (EQ-5D) questionnaire. Bootstrapping assessed the uncertainty around the average differences in costs and health outcomes. RESULTS: In total, 444 of 451 randomized patients were included in the modified intention-to-treat analysis. Patients had median four active comorbidities at baseline. Mean total costs over two years were k€10.8 in the prednisolone group, k€0.5 (95% CI -4.0; 1.8) lower than in the placebo group. Total direct medical costs were k€0.5 (95% CI -4.0; 1.5) lower in the prednisolone group. The mean number of QALYs was similar in both groups (difference 0.02 [-0.03; 0.06] in favor of prednisolone). The DAS28 was 0.38 lower in the prednisolone group than in the placebo group (0.19; 0.56). CONCLUSION: With greater effectiveness (DAS28) at non-significantly lower costs, low-dose, add-on prednisolone is cost-effective for RA compared to placebo over two years. QALYs were equal in both groups, most likely due to the impact of multiple comorbidities.

Patients' and rheumatologists' perspectives on the efficacy and safety of low-dose glucocorticoids in rheumatoid arthritis-an international survey within the GLORIA study.

OBJECTIVE: To evaluate the current perspectives of patients and health professionals regarding the efficacy and safety of low-dose glucocorticoids (GCs) in RA. METHODS: Two online surveys were disseminated to patients and health professionals, in their native language, through national patient organizations and national rheumatology medical societies, respectively. SurveyMonkey®, MediGuard.org and the Glucocorticoid Low-dose Outcome in RA Study (GLORIA) website were used to offer and deliver these surveys. RESULTS: A total of 1221 RA patients with exposure to GCs, and 414 rheumatologists completed the surveys. Patients and rheumatologists reported high levels of agreement regarding the efficacy of low-dose GCs: at least 70% considered that they are very rapid and effective in the control of signs and symptoms of RA. However, half of the patients also reported having suffered serious adverse events with GCs, and 83% described concerns about safety. The majority of rheumatologists estimated that endocrine, ophthalmologic and cutaneous adverse events affect >4% of all patients treated with low-dose GCs for 2 years, based on a heat map. CONCLUSIONS: RA patients with self-reported exposure to GCs express high levels of satisfaction with low-dose GCs efficacy, as do rheumatologists. However, both expressed excessive concerns regarding the safety of GCs (greatly exceeding the published evidence data), which may compromise the optimal use of this medication. This study indicates that there is an unmet need for appropriately designed prospective trials that shed light on the real risk associated with low-dose GCs, as well as a need for renovated educational programs on the real benefits and harms of low-dose GCs, for both patients and physicians.

Body composition and bone status in relation to microvascular damage in systemic sclerosis patients.

AIM: To evaluate, in Systemic sclerosis (SSc) patients, the body composition and the bone status according to the peripheral microcirculatory condition, assessed and scored by nailfold videocapillaroscopy (NVC, "Early", "Active", "Late" patterns). METHODS: Body composition and bone mineral density (BMD) were assessed by Dual X-ray absorptiometry and dedicated software (GE Lunar USA) in 37 female SSc patients classified according to the 2013 EULAR/ACR criteria and 40 sex-matched healthy subjects. Clinical, laboratory, body composition and bone parameters were analyzed according to the different NVC patterns. Means were compared by the Student's t test or one-way analysis of variance; medians were compared by the Kruskal-Wallis test; and frequencies by the chi-square test. RESULTS: Higher prevalence of vertebral (21% vs 7%) and femoral (35% vs 7%) osteoporosis (OP) was found in SSc. Particularly SSc patients with "Late" NVC pattern showed a significantly higher prevalence of vertebral (p = 0.018) and femoral OP (p = 0.016). Regional assessment of bone mass (BM) in seven different body areas showed a significantly lower BMD only at the total spine (p = 0.008) and femoral neck (p = 0.027) in advanced microvascular damage. Patients with "Late" NVC pattern showed a lower whole-body lean mass (LM) compared to "Early" and "Active" NVC patterns, particularly at upper limbs. To note, in all body sites, BMD correlates with LM and BMC according to NVC pattern severity. CONCLUSIONS: SSc patients with most severe microvascular damage show a significantly altered body composition and bone status suggesting a strong link between microvascular failure and associated muscle/bone sufferance.

Progression of nailfold capillaroscopic patterns and correlation with organ involvement in systemic sclerosis: a 12 year study.

OBJECTIVE: The aim of this observational study was to investigate the evolution of scleroderma microangiopathy throughout different nailfold videocapillaroscopy (NVC) patterns ('early', 'active', 'late') as well as the prevalence of organ involvement in SSc patients during a 12-year follow-up. METHODS: Thirty-four SSc patients showing at baseline (first capillaroscopic analysis) the 'early' NVC pattern of microangiopathy were enrolled and followed for 12 years (s.d. 2). Complete NVC analysis and clinical and serological findings were collected. Patients were in a standard therapeutic care setting. Statistical analysis was carried out by non-parametric tests. RESULTS: After a 12-year follow-up, the 'early' NVC pattern changed from baseline in 76% of the patients. The NVC pattern was found to be 'active' in 9 patients (26%), 'late' in 13 (38%) and characterized by non-specific capillary abnormalities in 4 (12%). In the subgroup whose microangiopathy progressed from the 'early' to the 'late' NVC pattern, the median time of progression from the 'early' to the 'active' pattern was significantly shorter (11 months) when compared with patients who progressed from the 'early' to the 'active' NVC pattern (55 months) (P = 0.002). The median time of progression between NVC patterns was significantly shorter in SSc patients showing either a nucleolar ANA pattern or Scl70 autoantibodies (P = 0.048). Organ involvement was progressively greater in SSc patients with 'early', 'active' and 'late' NVC patterns, respectively. CONCLUSIONS: This longitudinal study confirms over a 12-year follow-up the evolution of specific NVC patterns associated with the progressive severity of organ involvement in SSc patients in a standard clinical care setting.

Correlations between nailfold microvascular damage and skin involvement in systemic sclerosis patients.

OBJECTIVE: The aim of this study was to identify any correlations between microvascular damage, assessed by nailfold videocapillaroscopy and skin impairment, evaluated by three different methods, the modified Rodnan skin score (mRSS), skin high-frequency ultrasound (US) and the plicometer skin test (PST) in systemic sclerosis (SSc) patients. METHODS: Sixty-three SSc patients and 63 healthy subjects were enrolled. Nailfold videocapillaroscopy (NVC) was used to assess the nailfold capillaroscopy pattern ("Early", "Active" or "Late"), according to the Cutolo classification. All subjects were assessed by mRSS, US and PST to evaluate their dermal thickness (DT) in the seventeen skin areas of the body usually evaluated by mRSS (zygoma, fingers, hands, dorsum of hands, forearms, arms, chest, abdomen, thighs, legs, feet). Statistical evaluation was performed by nonparametric tests. RESULTS: All the three methods demonstrated progressively higher values of skin impairment in patients with "Early", "Active" or "Late" pattern of nailfold microangiopathy (for mRSS p < 0.01, US p < 0.02 and PST p < 0.02). A positive correlation was also observed in SSc patients between the three methods used to evaluate skin involvement (mRSS vs US, mRSS vs PST, PST vs US, p < 0.0001 respectively). CONCLUSIONS: This study demonstrates that there is a correlation between two of the most important aspects to classify and monitor the SSc patients, i.e. microvascular damage progression (evaluated by NVC) and skin damage (assessed by mRss, US and PST).

Long-term follow-up of nailfold videocapillaroscopic changes in dermatomyositis versus systemic sclerosis patients.

To identify nailfold videocapillaroscopy (NVC) changes in patients with dermatomyositis (DM) during a 3-year follow-up and to compare the NVC findings between DM and systemic sclerosis (SSc) patients at their first visit. Retrospective study of 24 DM and 24 SSc patients, matched for age and disease duration at first NVC. Capillaroscopic patterns/scores and clinical parameters had been yearly assessed. Nineteen out of 24 DM patients (79%) showed a NVC "scleroderma-like pattern." No statistically significant variation of all the capillaroscopic scores was observed during the 3-year follow-up. By comparing DM patients with or without anti-Jo-1 positivity, no statistically significant difference of the scores of the main capillary parameters was observed at baseline between the groups. Comparing at baseline DM with SSc patients, the giant capillary and microhemorrhage scores were significantly higher in SSc than those in DM patients (p = 0.04 and p = 0.05, respectively), while capillary density, ramification (abnormally shaped capillaries, expression of angiogenesis), and disorganization scores were higher in DM patients (p = 0.05, p = 0.002, p = 0.004, respectively). The absolute number of ramified capillaries was significantly higher in DM patients (p = 0.002), while the absolute capillary number was significantly higher in SSc patients (p = 0.05) at baseline. This pilot study demonstrates, for the first time, over long-term, that the capillaroscopic manifestations of DM persist in contrast to the progressive changes described in SSc patients, and the anti-Jo-1 positivity does not seem to modify the NVC pattern.

Correlations between blood perfusion and dermal thickness in different skin areas of systemic sclerosis patients.

OBJECTIVE: To identify possible correlations between skin blood perfusion (BP) and dermal thickness (DT) in different skin areas of systemic sclerosis (SSc) patients. METHODS: Sixty-two SSc patients, according to 2013 EULAR/ACR criteria, and 62 healthy subjects (CNT) were enrolled. Skin BP was analysed by laser speckle contrast analysis (LASCA) at the level of dorsum of the middle phalanx of the third fingers, dorsal aspect of the hands and zygoma. DT was assessed by both skin high frequency ultrasound (US) and modified Rodnan skin score (mRSS) in the same above reported areas. All patients were studied also by nailfold videocapillaroscopy (NVC) to assess the proper pattern of microvascular damage ("Early", "Active", or "Late"). RESULTS: At the level of finger dorsum a statistically significant negative correlation was observed in SSc patients between skin BP and both ultrasound-DT (p=0.0005 r=0.43) and mRSS (p=0.0007 r=0.42), but not at the level of hand dorsum and zygoma. No statistically significant correlation was present between skin BP and ultrasound-DT at any level in CNT. In detail, SSc patients, compared to CNT, showed a statistically significant lower BP only at level of fingers (median PU 72.6 vs 136.1 respectively, p<0.0001) and a statistically significant higher ultrasound-DT at the level of dorsum of 3th finger bilaterally (median mm 0.9 vs 0.7, p<0.0001), dorsum of hands (median mm 0.9 vs 0.7, p<0.0001) and zygoma (median mm 0.8 vs 0.7, p<0.0001). A significant positive correlation between ultrasound-DT and mRSS was observed in SSc patients at level of the three areas (dorsum of fingers p<0.0001 r=0.51; dorsum of hands p=0.03 r=0.27; zygoma p=0.0001 r=0.45). A progressive decrease of skin BP and increase of ultrasound-DT was found correlated with the progression of the severity of NVC patterns. CONCLUSIONS: This study demonstrates for the first time in SSc patients a significant inverse relationship between skin BP, measured by LASCA, and DT, evaluated by both US and mRSS, at the level of dorsum of the middle phalanx of the third fingers.

Assessment of treatment effects on digital ulcer and blood perfusion by laser speckle contrast analysis in a patient affected by systemic sclerosis.

Laser speckle contrast analysis (LASCA) is a good tool to evaluate the variation in peripheral blood perfusion during long-term follow-up and is able to safely monitor digital ulcer evolution in scleroderma patients. It evaluates blood perfusion in different areas within the skin lesions and surrounding them during standard treatment.

Subclinical dermal involvement is detectable by high frequency ultrasound even in patients with limited cutaneous systemic sclerosis.

BACKGROUND: The aim of the study was to detect by skin high-frequency ultrasound (US) possible subclinical skin involvement in patients affected by limited cutaneous systemic sclerosis (lcSSc), in those skin areas apparently not affected by the disease on the basis of a normal modified Rodnan skin score (mRSS). Differences in dermal thickness (DT) in comparison with healthy subjects were investigated. METHODS: Fifty patients with lcSSc (age 62 ± 13 years (mean ± SD), disease duration 5 ± 5 years) and 50 sex-matched and age-matched healthy subjects (age 62 ± 11 years) were enrolled. DT was evaluated by both mRSS and US at the usual 17 skin areas (zygoma, fingers, dorsum of the hands, forearms, upper arms, chest, abdomen, thighs, lower legs and feet). Non-parametric tests were used for the statistical analysis. RESULTS: Subclinical dermal involvement was detected by US even in the skin areas in patients with lcSSc, who had a normal local mRSS. In addition, statistically significantly higher mean DT was found in almost all skin areas, when compared to healthy subjects (p < 0.0001 for all areas). In particular, DT was significantly greater in patients with lcSSc than in healthy subjects in four out of six skin areas with a normal mRSS (score = 0) (upper arm, chest and abdomen), despite the clinical classification of lcSSc. CONCLUSIONS: This study strongly suggests that subclinical dermal involvement may be detectable by US even in skin areas with a normal mRSS in patients classified as having lcSSc. This should be taken into account during SSc subset classification in clinical studies/trials.

Microvascular damage evaluation in systemic sclerosis: the role of nailfold videocapillaroscopy and laser techniques.

Microvascular damage and a decrease in peripheral blood perfusion are typical features of systemic sclerosis (SSc) with serious clinical implications, not only for a very early diagnosis, but also for disease progression. Nailfold videocapillaroscopy is a validated and safe imaging technique able to detect peripheral capillary morphology, as well as to classify and to score any nailfold abnormalities into different microangiopathy patterns. Capillaroscopic analysis is now included in the ACR/EULAR classification criteria for SSc. The decrease in peripheral blood perfusion is usually associated with microvascular damage in SSc, which may be studied by different methods. Several of these make use of safe laser technologies. This paper focuses on these new clinical aspects to assess SSc microvascular impairment.

Capillaroscopy 2016: new perspectives in systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune disorder of unknown aetiology characterized by early impairment of the microvascular system. Nailfold microangiopathy and decreased peripheral blood perfusion are typical clinical aspects of SSc. The best method to evaluate vascular injury is nailfold videocapillaroscopy, which detects peripheral capillary morphology, and classifies and scores the abnormalities into different patterns of microangiopathy. Microangiopathy appears to be the best evaluable predictor of the disease development and has been observed to precede the other symptoms by many years. Peripheral blood perfusion is also impaired in SSc, and there are different methods to assess it: laser Doppler and laser speckle techniques, thermography and other emerging techniques.

Systemic sclerosis: markers and targeted treatments.

Systemic sclerosis (SSc) is characterized by autoantibody production, progressive microvasculopathy, and aberrant extracellular matrix protein (ECM) synthesis in tissues. The disease presents two major clinical hallmarks: Raynaud's phenomenon (RP) and skin involvement, followed by varying prevalences of internal organ involvement. Despite significant advances in the management of certain organ-specific involvements and symptoms, the research for efficient markers and targets, to be used for an optimized treatment, is still ongoing. Therapies targeting the vasculature (i.e. ET-1 receptor antagonists, phosphodiesterase-5 (PDE-5) inhi bitor, agiotensin-converting enzyme inhibition, prostacyclins), the immune system and/or the fibrotic process (i.e. traditional disease modifying anti-rheu - matic drugs DMARDs such as methotrexate, cyclospo - rine or mycophenolate mofetil, biologicals like rituxi - mab, tocilizumab or abatacept) have been or are being eva luated in SSc. Advanced approaches, reserved to unres ponsive SSc patients, include autologous haema - topoietic stem cell transplantation (HSTC) and intravenous immunoglobulins (IVIG). Interestingly, it is expected that new and future possible diagnostic and therapeutical approaches in SSc will come from epigenetic studies (MicroRNAs). Ideally, combination therapy in SSc seems the best approach, together with the early intervention on the major hallmarks of the disease in "at risk" patients, that consists of the microvascular damage/altered function and the autoimmune reaction, followed by the progressive and systemic fibrotic process.

Correlations between skin blood perfusion values and nailfold capillaroscopy scores in systemic sclerosis patients.

OBJECTIVES: To correlate blood perfusion (BP) values assessed by laser speckle contrast analysis (LASCA) in selected skin areas of hands and face with nailfold capillary damage scores in systemic sclerosis (SSc) patients. METHODS: Seventy SSc patients (mean SSc duration 6 ± 5 years) and 70 volunteer healthy subjects were enrolled after informed consent. LASCA was performed at different areas of the face (forehead, tip of nose, zygomas and perioral region) and at dorsal and volar regions of hands. Microvascular damage was assessed and scored by nailfold videocapillaroscopy (NVC) and the microangiopathy evolution score (MES) was calculated. RESULTS: SSc patients showed a significantly lower BP than healthy subjects at fingertips, periungual areas and palm of hands (p<0.0001), but not at the level of face and dorsum of hands. A gradual decrease of BP at fingertips, periungual and palm areas, was found in SSc patients with progressive severity of NVC patterns of microangiopathy ("early", "active", or "late") (p<0.01). A negative correlation was observed between MES and BP values, as well as between loss of capillaries and BP, at the same areas (p<0.001 and p<0.01, respectively). Patients with diffuse cutaneous SSc (dcSSc) showed lower BP than those with limited cutaneous SSc (p<0.04). CONCLUSIONS: LASCA detects a significant reduction of BP only in those areas usually affected by Raynaud's phenomenon (fingertips, periungual and palm areas), especially in dcSSc patients, and BP values significantly correlate with the nailfold capillaroscopy scores of microangiopathy.

A method for counting monosodium urate crystals in synovial fluid.

This study was aimed to standardize the technique for counting monosodium urate (MSU) crystals in the synovial fluid (SF) of patients with gout. A total of 52 SF specimens were examined under a polarized light microscope. The amount of SF ranged between 0.1 and 45 mL (median 3 mL). MSU crystals were counted in four areas with the same size at 400x magnification. Cytological examination of the same specimens was also performed. Median leukocyte count was 400 cells/mm3 (range 50-14,000 cells/mm3), with a median percentage of polymorphonuclear leukocytes of 9% (range 0%-98%). Median crystal count was 179.5 (range 3-1600). Inter- reader and intra-reader agreement in crystal counting were good with a weighed k of 0.89 [95% confidence interval (CI) 0.85-0.94] and 0.89 (95% CI 0.84-0.93), respectively. Our data indicate that the SF MSU crystal count is a feasible and highly reliable technique.

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.

Systematic review of 2008-2012 literature and update of recommendations for the use of methotrexate in rheumatic diseases, with a focus on rheumatoid arthritis.

The objective of this review is to update the recommendations of the 2010 Italian Consensus on the use of methotrexate (MTX) in rheumatoid arthritis (RA) and other rheumatic diseases. The literature published between 2008 and 2012 was systematically reviewed and updated recommendations on MTX use in rheumatic diseases, particularly RA, were formulated. These recommendations were approved by a panel of expert Italian Rheumatologists. A total of 10,238 references were identified, among which 70 studies were selected for critical evaluation. Sufficient evidence had accumulated to warrant changes to several of the recommendations in the new version. A new recommendation for patients with RA who are in MTX-induced clinical remission was also proposed and approved by the panel. Updated recommendations for the use of MTX in patients with RA or other rheumatologic disease are proposed.

Treatment of rosacea.

A range of treatment options are available in rosacea, which include several topical (mainly metronidazole, azelaic acid, other antibiotics, sulfur, retinoids) and oral drugs (mainly tetracyclines, metronidazole, macrolides). In some cases, the first choice is a systemic therapy because patients may have sensitive skin and topical medications can be irritant. Isotretinoin can be used in resistant cases of rosacea. Unfortunately, the majority of studies on rosacea treatments are at high or unclear risk of bias. A recent Cochrane review found that only topical metronidazole, azelaic acid, and oral doxycycline (40 mg) had some evidence to support their effectiveness in moderate to severe rosacea and concluded that further well-designed, adequately-powered randomised controlled trials are required. In our practice, we evaluate our patients for the presence of two possible triggers, Helicobacter pylori infection and small intestinal bacterial overgrowth. When they are present we use adapted antibiotic protocols. If not, we use oral metronidazole or oral tetracycline to treat papulopustolar rosacea. We also look for Demodex folliculorum infestation. When Demodex concentration is higher than 5/cm(2) we use topical crotamiton 10% or metronidazole.

[Treatment of rosacea]. / Prise en charge thérapeutique de la rosacée.

A range of treatment options are available in rosacea, which include several topical (mainly metronidazole, azelaic acid, other antibiotics, sulfur, retinoids) and oral drugs (mainly tetracyclines, metronidazole, macrolides). In some cases, the first choice is a systemic therapy because patients may have sensitive skin and topical medications can be irritant. Isotretinoin can be used in resistant cases of rosacea. Unfortunately, the majority of studies on rosacea treatments are at high or unclear risk of bias. A recent Cochrane review found that only topical metronidazole, azelaic acid, and oral doxycycline (40 mg) had some evidence to support their effectiveness in moderate to severe rosacea and concluded that further well-designed, adequately-powered randomised controlled trials are required. In our practice, we evaluate our patients for the presence of two possible triggers, Helicobacter pylori infection and small intestinal bacterial overgrowth. When they are present we use adapted antibiotic protocols. If not, we use oral metronidazole or oral tetracycline to treat papulopustolar rosacea. We also look for Demodex folliculorum infestation. When Demodex concentration is higher than 5/cm(2) we use topical crotamiton 10% or metronidazole.