Tommaso Schioppo

Choroidal impairment and macular thinning in patients with systemic sclerosis: the acute study.

Raynauds phenomenon (RP) is a reversible vasospastic response of the extremities to cold or emotion, and can be the first manifestation or may be present before the development of an overt systemic sclerosis (SSc). The disturbance of the balance between vasodilation and vasoconstriction is not limited to the peripheral microcirculation of the skin, but it is also observed in other organs, such as the choroidal plexus of the eye. We aimed to examine the choroidal thickness (CT), the macular thickness and ganglion cell complex (GCC) average in thirty consecutive patients, without visual symptoms, classified as primary RP (pRP), RP secondary to suspected SSc, and overt SSc. All the patients underwent rheumatologic and ophthalmologic examination, capillaroscopy, test for anti-nuclear antibodies, anti-dsDNA, and anti-extractable nuclear antigens. Ophthalmologic examination included: best corrected visual acuity; slit lamp biomicroscopy; intraocular pressure measurements, fundus examination, and Spectral Domain-Optical Coherence Tomography (SD-OCT) with enhanced depth imaging scan system. Twenty-seven healthy subjects similar for gender and age were analyzed. In pRP, CT was significantly thinner than controls in the outer nasal and temporal regions. In secondary RP, the inner and outer nasal areas were significantly thinner than controls. In SSc, the central, inner inferior, inner nasal, inner superior, outer temporal, outer inferior, and outer nasal regions were significantly thinner than controls. A decreasing trend of central foveal thickness was noted. All the patients had GCC average significantly lower than controls. A thinning of choroidal and macular thickness, as well as of GCC was observed in patients with pRP and becomes more severe and extensive in RP secondary to suspected SSc and overt SSc. To our knowledge, this is the first study to analyze the choroidal features using SD-OCT in RP. These data may be clinically useful in suggesting an early involvement of ocular microcirculation with significant reduction of choroidal perfusion.

Potential Effect of Anti-Inflammatory Treatment on Reducing the Cardiovascular Risk in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory polyarthritis with increased mortality largely attributable to cardiovascular disease. There is extensive evidence that patients with RA experience accelerated atherosclerosis, which is considered as the main responsible of this increased cardiovascular burden. Nowadays atherosclerosis is regarded as an inflammatory condition: hence, the cumulative inflammation of RA, with the abundant synthesis of proinflammatory cytokines, contributes directly to the early formation of the atheromatic plaque. It is therefore reasonable to postulate that, by alleviating inflammation, drugs commonly used in RA treatment may ameliorate the cardiovascular profile of these patients. Here we provide an extensive review of the literature, focusing on the effects of the available anti-rheumatic agents on cardiovascular mortality, and morbidity among RA sufferers.

N-TproBNP as biomarker in systemic sclerosis

Systemic sclerosis (SSc) is a connective tissue disorder characterized by tissue fibrosis affecting the skin and internal organs, fibroproliferative vasculopathy, and autoimmune activation. SSc still heralds a poor prognosis with significant morbidity and mortality. Early detection of organ involvement is critical as currently available treatments are most effective when started early. Many candidate biomarkers have been investigated in the past two decades. However, despite the enormous efforts, no accurate tool to predict the pattern of organ involvement and to assess disease activity has been yet identified. The N-terminal fragment of probrain natriuretic peptide (N-TproBNP) is a neurohormone released by ventricular myocytes in response to pressure overload. N-TproBNP is highly relevant for diagnosis, prognosis, and prediction of pulmonary arterial hypertension in SSc. Moreover, several studies support its potential benefit for cardiac assessment of scleroderma patients. Conversely, the role of N-TproBNP as surrogate marker of pulmonary fibrosis and skin involvement is much less clear. We provide an extensive review of the studies that have previously investigated the role of N-TproBNP as candidate biomarker in scleroderma manifestations, presenting also the findings of a recent study we conducted in a cohort of 87 SSc patients.

Current perspective on rituximab in rheumatic diseases

The steadily increasing knowledge regarding pathogenetic mechanisms in autoimmune rheumatic diseases has paved the way to different therapeutic approaches. In particular, the market entry of biologics has dramatically modified the natural history of rheumatic chronic inflammatory diseases with a meaningful impact on patients’ quality of life. Among the wide spectrum of available biological treatments, rituximab (RTX), first used in the treatment of non-Hodgkin’s lymphoma, was later approved for rheumatoid arthritis and anti-neutrophil cytoplasmic antibodies-associated vasculitis. Nowadays, in rheumatology, RTX is also used with off-label indications in patients with systemic sclerosis, Sjögren’s syndrome and systemic lupus erythematosus. RTX is a monoclonal antibody directed to CD20 molecules expressed on the surfaces of pre-B and mature B lymphocytes. It acts by causing apoptosis of these cells with antibody- and complement-dependent cytotoxicity. As inflammatory responses to cell-associated immune complexes are key elements in the pathogenesis of several autoimmune rheumatic diseases, such an approach might be effective in these patients. In fact, RTX, by promoting the rapid and long-term depletion of circulating and lymphoid tissue-associated B cells, leads to a lower recruitment of these effector cells at sites of immune complex deposition, thus reducing inflammation and tissue damage. RTX is of the most interest to rheumatologists as it represents an important additional therapeutic approach. Thus, the advent in clinical practice of approved RTX biosimilars, such as CT-P10, may be of help in improving treatment access as well as in reducing costs.

Challenges and treatment options for rheumatoid arthritis during pregnancy

ABSTRACT Introduction: Rheumatoid arthritis (RA) can spontaneously improve during pregnancy. However, a considerable proportion of patients can experience a flare and high disease activity has been associated with an increased risk of adverse pregnancy outcome. Thus, the treatment of RA in pregnant women should be selected taking into account both the potential harmful effects of the treatment and the risk associated with discontinuation. Areas covered: Recent publications regarding safety of the most important disease modifying anti-rheumatic drugs (DMARDs) during pregnancy has been reviewed. A systematic literature search of MEDLINE was conducted using pregnancy, teratogenicity, adverse effects, embryo/foetal-toxicity as key search terms for each DMARD. Expert opinion: A great body of evidence suggest that hydroxychloroquine, sulfasalazine, and non-fluorinated steroids can be continued throughout pregnancy, while methotrexate and leflunomide should be discontinued 3 months before pregnancy. Continuation of TNFi during the first part of pregnancy should be considered when benefits outweigh the potential risk of teratogenicity. Data regarding other biologics are scant and, at present, they should be stopped before pregnancy.

Clinical evaluation of a novel chemiluminescent immunoassay for the detection of anti-citrullinated peptide antibodies.

BACKGROUND We evaluated the analytical and clinical performances of a novel, automated chemiluminescent immunoassay in comparison with several anti-citrullinated protein antibody (ACPA) assays (2nd and 3rd generations) based on various platforms and technologies. METHODS Samples from rheumatoid arthritis (RA) patients (n=141) and controls (n=153) were collected based on an ordered ACPA test. All samples were tested with QUANTA Flash® CCP3, QUANTA Lite® CCP3, QUANTA Lite® CCP3.1, CCPlus and EliA® CCP assays. Rheumatoid factor (RF) was determined using Quantex RF(II). An additional cohort consisting of RA patients from three different sources (116, 79 and 50 samples), 61 juvenile idiopathic arthritis (JIA) patients and 233 controls were used in an extended evaluation on QUANTA Flash® CCP3 only. Precision and linearity of the QUANTA Flash® CCP3 were assessed according to CLSI guidelines. RESULTS All ACPA assays showed good qualitative and quantitative agreements. The Quanta Flash CCP3 assay showed good analytical and clinical performance. Based on the extended cohort, the sensitivity, specificity and likelihood ratios of the novel Quanta Flash® CCP3 were defined as 70.2%, 97.4% and 27.3/0.31, respectively. CONCLUSION Good agreements between different ACPA assays based on diverse platforms were found. Quanta Flash CCP3 is a reliable test for the fully automated and rapid detection of ACPA.

Uniphasic Blanching of the Fingers, Abnormal Capillaroscopy in Nonsymptomatic Digits, and Autoantibodies: Expanding Options to Increase the Level of Suspicion of Connective Tissue Diseases beyond the Classification of Raynaud's Phenomenon

In patients with Raynauds phenomenon (RP), the role of medical history, capillaroscopy, and autoantibodies in order to provide an early diagnosis of connective tissue disease (CTD) were examined. 115 consecutive adults with uni-, bi-, or triphasic colour changes of the fingers were studied. RP was bilateral in 92.7% of patients. The middle finger was significantly more affected. A lack of association between fingers affected by RP and fingers with capillary abnormalities was observed OR = 0.75 (0.34–1.66). RP with the cyanotic phase had a higher risk at capillaroscopy to have hemorrhages OR = 4.46 (1.50–13.30) and giant capillaries OR = 24.85 (1.48–417.44). The thumb and triphasic involvement have an OR of 1.477 and 1.845, respectively. RP secondary to systemic sclerosis (SSc) had greater value of VAS pain (p = 0.011). The presence of anti-centromere antibodies was significantly associated with a higher risk of SSc (p < 0.001). 44.3% of subjects had uniphasic blanching of the fingers, and among these, 27% was diagnosed as having an overt or suspected CTD. Markers of a potential development of CTDs include severe RP symptoms, positive autoantibodies, and capillary abnormalities. These data support the proposal to not discharge patients with uniphasic blanching of the fingers to avoid missing the opportunity of an early diagnosis.

Practical suggestions on intravenous iloprost in Raynaud's phenomenon and digital ulcer secondary to systemic sclerosis: Systematic literature review and expert consensus

BACKGROUND Systemic sclerosis (SSc) is an autoimmune chronic disease characterized by vascular impairment, immune dysfunction and collagen deposition. Raynauds phenomenon (RP) and digital ulcers (DU) are prominent features of SSc. Intravenous (IV) iloprost (ILO), according to the recently updated EULAR recommendations, is indicated for RP after failure of oral therapy. Moreover, IV ILO could be useful in DU healing. IV ILO is currently available mainly on the European market approved for RP secondary to SSc with 3-5 days infusion cycle. Unfortunately, data published varies regarding regimen (dosage, duration and frequency). Up to now, ILO has been studied in small cohorts of patients and in few randomized controlled trials. METHODS A systematic review of studies on IV ILO in patients with SSc complicated by DU and RP was performed. Insufficient data were available to perform a meta-analysis according to the GRADE system. We performed a three-stage internet-based Delphi consensus exercise. RESULTS Three major indications were identified for IV ILO usage in SSc: RP non-responsive to oral therapy, DU healing, and DU prevention. IV ILO should be administered between 0.5 and 2.0ng/kg/min according to patient tolerability with a frequency depending on the indication. CONCLUSIONS Although these suggestions are supported by this expert group to be used in clinical setting, it will be necessary to formally validate the present suggestions in future clinical trials.

Acute and chronic effects of two different intravenous iloprost regimens in systemic sclerosis: a pragmatic non-randomized trial

Objectives I.v. iloprost (ILO) may be used in the treatment of refractory RP and digital ulcers. We aim to evaluate the acute and chronic effects of two different ILO regimens by power Doppler US (PDUS) and nailfold videocapillaroscopy. Methods In this 3-month single-centre pragmatic non-randomized trial, 96 SSc patients were included and stratified according to ILO treatment as: no ILO (group A), ILO once monthly (group B) and ILO for five consecutive days (group C). Resistivity index (RI), finger pulp blood flow and periungual vascularization by PDUS, and sum of capillaries apex width in 1 mm by nailfold videocapillaroscopy were evaluated. Results were adjusted for the average outdoor temperature at the place of residence. Results An acute ILO effect was observed for only finger pulp blood flow in groups B and C (P < 0.001 and P < 0.005, respectively). An acute effect was observed for RI and periungual vascularization only in group B. A progressive increase was observed for other parameters without statistical difference. ILO effects were not observed any longer before the following infusion. Some parameters (finger pulp blood flow in group B and RI in group C) showed a statistically higher increase the lower the outdoor temperature was. Conclusion ILO had an acute effect as assessed by PDUS, especially in group B. By contrast, an ILO chronic effect was not detectable before the following infusion in both treatment groups. More studies are needed to define how often ILO should be administered.

Fibrosis biomarkers in isolated Raynaud's phenomenon: too little, too soon?

Raynauds phenomenon (RP) can be the first manifestation or may be present before the development of an overt systemic sclerosis (SSc).1 Enhanced liver fibrosis (ELF) test, an algorithm combining tissue inhibitors of matrix metalloproteinases (TIMP-1), hyaluronic acid (HA) and aminoterminal propeptide of type III procollagen (PIIINP), has been related to several measures of fibrosis in SSc patients.2–⇓4 We evaluated whether these biomarkers could discriminate between primary and secondary RP. Consecutive adult patients with RP at the first rheumatologic evaluation were recruited from February 2011 to May 2012 with ethics committee approval. Exclusion criteria were history of any fibrosing disorder, organ transplantation, hepatocellular carcinoma or treatment with interferon. One patient was excluded for interferon treatment. Fifteen limited cutaneous SSc and 15 diffuse …