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.

Consensus statement on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: Localized scleroderma, systemic sclerosis and overlap syndromes.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present consensus provides an update to the 2017 European Dermatology Forum Guidelines, focusing on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, updated strategies for the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 1 of this consensus provides clinicians with an overview of the diagnosis and treatment of localized scleroderma (morphea), and systemic sclerosis including overlap syndromes.

Emerging nailfold capillaroscopic patterns in COVID-19: from acute patients to survivors.

The SARS-CoV-2 infection causing the Coronavirus disease-19 (COVID-19) is characterized by a broad range of clinical manifestations, implicating microvascular damage with endothelial dysfunction and different organ involvement.

Nailfold capillaroscopy in the rheumatological current clinical practice in Italy: results of a national survey.

This cross-sectional online study was designed by the study group on Capillaroscopy and Microcirculation in Rheumatic Diseases (CAP) of the Italian Society of Rheumatology (SIR) to provide an overview of the management of nailfold capillaroscopy in Italian rheumatology centers. Therefore, SIR distributed the survey to its members in July 2021, and each center's physician with the most expertise in capillaroscopy completed the questionnaire. The survey was completed by 102 centers, with at least one representative from each Italian region. Ninety-three centers perform capillaroscopy, and 52 (56) conduct more than 200 investigations annually. Seventy-eight (84%) of respondents have more than five years of experience with the technique, and 75 centers (80.6%) have received certification from specific national or international training courses. In 85 centers, a videocapillaroscope with 200x magnification is employed (91.4%). The average waiting period for the examination is 2.4 months, and less than 3 months in 64 of the locations (68.8%). The study demonstrates that capillaroscopy is an integral part of both the diagnostic phase of Raynaud's phenomenon and the monitoring of autoimmune connective tissue diseases (CTDs). However, the reporting methods and timing of patient followup are heterogeneous.

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.

Management of giant cell arteritis among general practitioners from Genoa, Italy: a web-based survey.

Giant cell arteritis (GCA) is the most common form of vasculitis of the adult. General practitioners (GPs) are usually the first physicians who take care of GCA patients. In this study, the awareness of GPs from Genoa, Italy, regarding GCA was investigated by a web-based survey. A web-based questionnaire was sent by mail to 775 Italian GPs. It included 12 multiple choice questions regarding practice seniority, practice population size, number of GCA patients followed, and GPs' diagnostic and therapeutic approach. Of the 775 GPs involved, 76 (9.8%) answered. Thirty-three/75 (44%) declared that they did not see patients with GCA and the remaining 42 (56%) that they diagnose between one and two patients per year. New headache onset was the presenting feature of GCA for the majority of GPs (78.3%). GCA was diagnosed on the basis of clinical presentation alone by 35.2% of them, of temporal artery biopsy by 49.3%, and by imaging, including ultrasound and magnetic resonance imaging, by 15.5%. The referral pattern was mainly toward rheumatologists (68.5%). Only 27.8% GPs declared they start treatment at the first clinical suspicion, with the others waiting for laboratory and imaging examinations or specialist consultation. The doses of glucocorticoids used were in keeping with current guidelines. The management of GCA by GPs from Genoa is in general correct, with the exceptions of excessive confidence in headaches for diagnosis and of the timing of GC initiation. These points suggest that a program of information and education for GPs is warranted.

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.

Alternative and complementary therapies in osteoarthritis and cartilage repair.

Osteoarthritis (OA) is the most common joint condition and, with a burgeoning ageing population, is due to increase in prevalence. Beyond conventional medical and surgical interventions, there are an increasing number of 'alternative' therapies. These alternative therapies may have a limited evidence base and, for this reason, are often only afforded brief reference (or completely excluded) from current OA guidelines. Thus, the aim of this review was to synthesize the current evidence regarding autologous chondrocyte implantation (ACI), mesenchymal stem cell (MSC) therapy, platelet-rich plasma (PRP), vitamin D and other alternative therapies. The majority of studies were in knee OA or chondral defects. Matrix-assisted ACI has demonstrated exceedingly limited, symptomatic improvements in the treatment of cartilage defects of the knee and is not supported for the treatment of knee OA. There is some evidence to suggest symptomatic improvement with MSC injection in knee OA, with the suggestion of minimal structural improvement demonstrated on MRI and there are positive signals that PRP may also lead to symptomatic improvement, though variation in preparation makes inter-study comparison difficult. There is variability in findings with vitamin D supplementation in OA, and the only recommendation which can be made, at this time, is for replacement when vitamin D is deplete. Other alternative therapies reviewed have some evidence (though from small, poor-quality studies) to support improvement in symptoms and again there is often a wide variation in dosage and regimens. For all these therapeutic modalities, although controlled studies have been undertaken to evaluate effectiveness in OA, these have often been of small size, limited statistical power, uncertain blindness and using various methodologies. These deficiencies must leave the question as to whether they have been validated as effective therapies in OA (or chondral defects). The conclusions of this review are that all alternative interventions definitely require clinical trials with robust methodology, to assess their efficacy and safety in the treatment of OA beyond contextual and placebo effects.

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).

Don't forget the jumper's knee in the young sportsman: evaluation of patellar tendinopathy with a high frequency ultrasound probe.

Patellar tendinopathy, or Jumper's knee, is a painful knee condition caused by inflammation of the patella tendon. This condition is most frequently observed in subjects who play sports that require repetitive regular jumping. Jumper's knee is frequently misdiagnosed as a minor injury and many athletes, like our patient, keep on training and competing and either tend to ignore the injury or attempt to treat it themselves. However, jumper's knee is a serious condition that requires a correct and timely diagnosis, which often necessitates ultrasound investigation in order to start the most appropriate treatment.

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.

Evidence for increase in finger blood flow, evaluated by laser Doppler flowmetry, following iloprost infusion in patients with systemic sclerosis: a week-long observational longitudinal study.

OBJECTIVES: Iloprost plays an important role in the treatment of Raynaud's phenomenon (RP), but has transient vasodilatory effects owing to its very short half-time. We aimed to evaluate short- and medium-term haemodynamic effects of iloprost by measuring dorsal finger microvessel blood flow using laser Doppler flowmetry (LDF), in patients with RP associated with systemic sclerosis (SSc). METHOD: In 24 consecutive SSc patients with RP (disease duration 10.5 ± 1.3 years), LDF with heating probes was used to measure blood flow in four fingers by occlusive and heating tests, at baseline, after 3 consecutive days of iloprost infusion, and at 24 h and 7 days after last iloprost infusion. Nailfold videocapillaroscopy (NVC) patterns of microvascular damage were investigated. Sixteen healthy controls were studied to compare baseline flows. RESULTS: Compared to controls, SSc patients showed significantly impaired axon reflex vasoregulation and nitric oxide responses at baseline (p = 0.001 and p = 0.03, respectively). After iloprost, a prompt but transient significant improvement in endothelial-dependent vasodilation (occlusive test) was seen only in SSc patients with an 'active' NVC pattern (p ≤ 0.05). The iloprost effects vanished within 7 days after the last infusion. No significant differences were found, in the whole study, between patients with and without digital ulcers. CONCLUSIONS: Microcirculatory blood flow increases following 3 days of iloprost infusion but fades shortly after treatment. Although iloprost is effective in reducing the severity of RP in SSc, the most suitable regimen and timing to obtain longer lasting vasodilatory benefits remain to be established.

There is a need for new systemic sclerosis subset criteria. A content analytic approach.

OBJECTIVES: Systemic sclerosis (SSc) is heterogenous. The objectives of this study were to evaluate the purpose, strengths and limitations of existing SSc subset criteria, and identify ideas among experts about subsets. METHODS: We conducted semi-structured interviews with randomly sampled international SSc experts. The interview transcripts underwent an iterative process with text deconstructed to single thought units until a saturated conceptual framework with coding was achieved and respondent occurrence tabulated. Serial cross-referential analyses of clusters were developed. RESULTS: Thirty experts from 13 countries were included; 67% were male, 63% were from Europe and 37% from North America; median experience of 22.5 years, with a median of 55 new SSc patients annually. Three thematic clusters regarding subsetting were identified: research and communication; management; and prognosis (prediction of internal organ involvement, survival). The strength of the limited/diffuse system was its ease of use, however 10% stated this system had marginal value. Shortcomings of the diffuse/limited classification were the risk of misclassification, predictions/generalizations did not always hold true, and that the elbow or knee threshold was arbitrary. Eighty-seven percent use more than 2 subsets including: SSc sine scleroderma, overlap conditions, antibody-determined subsets, speed of progression, and age of onset (juvenile, elderly). CONCLUSIONS: We have synthesized an international view of the construct of SSc subsets in the modern era. We found a number of factors underlying the construct of SSc subsets. Considerations for the next phase include rate of change and hierarchal clustering (e.g. limited/diffuse, then by antibodies).

Hashimoto's encephalopathy in a patient with septal panniculitis: a case report.

Hashimoto's encephalopathy (HE) is an autoimmune form of encephalopathy, associated with autoimmune thyroiditis. Its prevalence is estimated to be 2:100,000. HE is characterized by behavioral changes, mental confusion, dysarthria, ataxia, psychosis, paranoia, convulsions, hallucinations, headache and hyperthermia. Elevated thyroid antibodies are necessary for diagnosis and the disease responds dramatically to glucocorticoid therapy. We describe a patient with HE and panniculitis, an association reported twice in the literature.

European dermatology forum S1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 2: Scleromyxedema, scleredema and nephrogenic systemic fibrosis.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present guideline focuses on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, current strategies in the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 2 of this guideline provides clinicians with an overview of the diagnosis and treatment of scleromyxedema, scleredema (of Buschke) and nephrogenic systemic sclerosis (nephrogenic fibrosing dermopathy).

European Dermatology Forum S1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: localized scleroderma, systemic sclerosis and overlap syndromes.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present guideline focuses on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, current strategies in the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 1 of this guideline provides clinicians with an overview of the diagnosis and treatment of localized scleroderma (morphea), and systemic sclerosis including overlap syndromes of systemic sclerosis with diseases of the rheumatological spectrum.

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.

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.

Biosimilars in immune-mediated inflammatory diseases: initial lessons from the first approved biosimilar anti-tumour necrosis factor monoclonal antibody.

The introduction of targeted biological therapies has revolutionised the management of immune-mediated inflammatory diseases (IMIDs) such as rheumatoid arthritis, ankylosing spondylitis, psoriasis and inflammatory bowel disease. Following treatment with these therapies, many patients experience significant improvements in different aspects of their disease, including symptoms, work productivity and other outcomes relevant for individuals and society. However, due to the complexity of biological drug development and manufacturing processes, the costs of these therapies are relatively high. Indeed, the financial burden on healthcare systems due to biological therapies is considerable and lack of patient access to effective treatment remains a concern in many parts of the world. As many reference biological therapies have now reached or are near to patent expiry, a number of 'biosimilar' drugs have been developed for use in various clinical settings, and some of these drugs are already in use in several countries. While the potential pharmacoeconomic benefits of cost-effective biosimilars seem clear, several issues have been raised regarding, for example, the definition of biosimilarity and the validity of indication extrapolation, as well as the 'switchability' and relative immunogenicity of biosimilars and their reference drugs. In this review, these issues will be discussed with reference to CT-P13, a biosimilar of the anti-tumour necrosis factor monoclonal antibody infliximab, which is approved in Europe and elsewhere for the treatment of various IMIDs. Other important issues, including those related to data collection during nonclinical and clinical development of biosimilars, are also discussed.