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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.

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.

During the Great War, the “trench clubs” were used in various armies. These weapons were handcrafted by the soldiers or distributed by the commands, who assigned them mainly to the raiders. On the Italian front, the Regio esercito did not adopt this weapon, unlike the Austro-Hungarian army which gave it to elite units. Therefore, the Italian-Austrian front presented an asymmetrical situation compared to the Western theatre, where the weapon was used by both sides. This had consequences on the ways of perceiving this weapon in Italy. The trench clubs, evoking an archaic and medieval form of combat, were represented by the Italian propaganda and by the public opinion as proof of the barbaric nature of the enemy. The article aims to analyse the representations of the weapon circulating in Italy and how these cultural constructions were transposed by the soldiers, influencing their attitude and behaviours. At the same time, the essay tries to reconstruct the uses of trench clubs in combat, with a focus on the battle of Mount San Michele (29 June 1916), a key moment for understanding the genesis of these propaganda narratives.

Recensione di Alessandra Gribaldo, Unexpected subjects: Intimate partner violence, testimony, and the law, Chicago, HAU Books, 2021, pp. 148.

After presenting a framework of how the LEGO company represented historical and military themes in its sets, this article will analyze the sociocultural phenomenon of the use and collection of historical-themed legos, a phenomenon that is named Lego History. Secondly, it will examine some possible uses of legos – seen as a media with a strong hold upon the audience – in the Public History, considering the problems, methodologies, objectives, and presenting some projects started abroad. Finally, we will illustrate our project, Italian BrickHistory, a website that is proposed as a meeting point between “lego historical builders”, fans, historians and cultural operators who carry out or intend to start Public History projects with legos.

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.

Da qualche tempo il mondo dell’antropologia e delle scienze sociali appare interessato al composito universo dei centri per l’accoglienza dei rifugiati. Non si tratta, tuttavia, di un mero interesse scientifico o etnografico, finalizzato magari allo studio di uno «spazio terzo», in cui «differenze incommensurabili», «proprie delle esistenze al confine» si aprono alle negoziazioni. Al contrario, l’aspirazione montante è quella di trasformare tali centri in spazi di applicazione professionale, entro cui espletare il “mestiere d’antropologo”. Quel mestiere, potremmo dire, la cui essenza consiste nel passaggio dall’osservare al fare. Il “fare” – o il partecipare a fare – l’istituzione.

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.

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.

The article analyses the images of the enemy disseminated by Catholic propaganda and assistance in the Italian army during the Great War, outlining the main features and the evolution of these representations, also comparing them with those disseminated by other propaganda actors. The theme is reconstructed by examining the activity of Catholic institutional actors operating in the army (the Military Ordinariate and the Soldiers’ Homes), a selection of religious publications addressed to the troops, the reports sent by chaplains to the military bishop and the personal accounts of combatants. Firstly, the essay shows that Catholic propaganda in the army focused on moral assistance, but the campaign to demonise the enemy found space in various areas: in the chaplains’ speeches, in the religious materials intended for the soldiers and even in entertainment (puppet theatres) and recreation for the troops. The research also highlights the discrepancy between the direction of the Military Ordinariate, which presented the conflict as a ‘just war’ without inciting hatred towards the enemy, and the aggressive and patriotic rhetoric of various chaplains. [ABSTRACT FROM AUTHOR]

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.

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.

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.

Partendo da una discussione critica delle ricerche che, negli ultimi vent’anni, hanno focalizzato i rapporti tra giovani, violenza e guerra nell’Africa sub-sahariana, l’articolo propone una prospettiva centrata sui processi di riproduzione sociale e sulle loro crisi. A tale scopo viene focalizzata e rielaborata la distinzione la tra la categoria antropologica dei “cadetti” – marcatamente relazionale e gerarchica – e la categoria dei “giovani” – che apre invece ad una definizione della gioventù come soggetto politico autonomo e si connette all’immaginario globale. Il conflitto recente in Costa d’Avorio viene dunque letto sulla base di questa distinzione contrastiva: si mostra come in esso dei “cadetti” (identificati nella figura dei ribelli che hanno lottato contro il presidente Gbagbo) si siano opposti a dei “giovani” (identificati con i jeunes patriotes, ossia con i giovani nazionalisti che hanno sostenuto il presidente contro la ribellione). Queste forme differenti di soggettivazione politica vengono ricondotte alle crisi di riproduzione che hanno investito due parti diverse della società avoriana.

Map of the natural and semi-natural environments and forest types map for the Latium region (Italy). The paper presents the main methodological aspects and the most important results achieved in the implementation of the “Map of natural and semi-natural environments” and of the “Forest types map” in Lazio region at a scale of 1:10.000. The project was carried out for the Agenzia dei Parchi and for the Area Foreste of Regione Lazio through a collaboration between e-GEOS , the University of Rome "La Sapienza", the University of Tuscia and Forestlab Centre , a spin- off of the University of Molise . The project is based on the integrated use of high-resolution satellite imagery and ADS40 false-color infrared digital orthophotos and led to the creation of two maps geometrically and thematically consistent with each other. The “Map of natural and semi-natural environments” is integrated with the pre-existing land use map of the Lazio region deepening the thematic detail up to the 6th Corine level. The “Forest types map” is based on a typological system organized in 17 categories and 36 forest types .

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.

The objective of this prospective study was to investigate the transition from primary (PRP) to secondary (SRP) Raynaud’s phenomenon (RP), in a large cohort of patients affected by isolated RP. A total of 2065 patients with RP were investigated by clinical interview, laboratory examinations, and nailfold videocapillaroscopy (NVC). Patients with negative NVC at first visit were yearly followed to monitor either the appearance of specific morphological alterations at NVC, or clinical manifestations of an underlying disease. Capillary abnormalities at NVC were scored, as well as the qualitative patterns of microangiopathy (Early, Active and Late). NVC was found negative at first visit in 1500 subjects; among them, 412 patients were evaluable and they were followed for a mean time of 5±4 years (range 2-13 years). Sixty-eight patients (16%) achieved a diagnosis of SRP during follow-up, showing normal or not specific capillary alterations at NVC 4% of patients (the diagnosis was undifferentiated connective tissue diseases), Early scleroderma-pattern 57%, Active scleroderma-pattern 7%, Late scleroderma-pattern 12%, and scleroderma-like pattern 18% of patients. The time of transition from normal/not specific capillary alterations to Early scleroderma-pattern was 4.4±3.8 years. Enlarged capillaries (diameter between 20 and 50 microns) and mild reduction of capillary density were found the more frequent markers at first NVC visit in patients who progressed to a scleroderma pattern (P=0.01). This study demonstrates in a large cohort, that almost 16% of patients initially diagnosed as affected by RP with negative NVC may transit to SRP during a mean follow-up of 4.4 years. PRP patients showing major notspecific alterations of nailfold capillaries at first NVC should be strictly monitored at least once a year since at higher risk of transition to SRP.

A 46-year old man, affected by Darier’s disease (DD), was seen because of right hand pain, later extended to shoulders and ankles. Physical examination showed swelling and tenderness of the wrist, metacarpophalangeal and metatarsophalangeal joints, of the right Achilles tendon’s enthesis and of the left knee, with psoriatic-like lesions of the scalp. A diagnosis of seronegative spondyloarthritis, supported by HLA-B27 positivity and by the magnetic resonance imaging fi nding of hand synovitis and unilateral sacro-iliitis, was made. The correlation between DD, spondyloarthritis and psoriasis has been already anecdotally reported. Further observations may clarify if this association is more than casual.

Book review of Valentina Lusini, Destinazione mondo. Forme e politiche dell’alterità nell’arte contemporanea, Verona, Ombre Corte, 2013, pp. 191.

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-sitaxentan 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.

Osteopoikilosis (OPK) is a rare autosomal dominant bone disorder characterized by numerous hyperostotic areas that tend to localize in periarticular osseous regions. It is usually asymptomatic and is often diagnosed incidentally during X-rays. OPK may be an isolated finding or associated with other pathologies, e.g. skin manifestations, rheumatic and/or skeletal disorders. We report a literature review and, for the first time, the coexistence of OPK with seronegative spondyloarthritis and Raynaud’s phenomenon in a 48-year old female. To the best of our knowledge, this is the first case of OPK studied by videocapillaroscopy, demonstrating the absence of specific microvascular abnormalities of nailfold capillaries.

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.

In the article, the literature on the effects of TNFa-antagonists (etanercept, infliximab and adalimumab) on the immune system is reviewed. These biologic agents are employed in chronic inflammatory diseases such as rheumatoid arthritis, seronegative spondyloarthritides, as well as psoriasis and Crohn’s disease. The differences of these drugs, testified by the different effects on the immune response, are discussed. These molecules exert their effect through cytokine inhibition, but they present striking differences since they can modulate macrophage activity, T cells apoptosis, leukocyte migration, and angiogenesis to a different degree. Some studies showed that these agents also affect the hypothalamo- pituitary-adrenal axis. The potential immunogenicity of these biologic agents is also discussed.

It is well known that the immune reactivity is modulated by gender. In fact, women show a more effective immune response as well as a more frequent development of autoimmune diseases. In particular, 17b-estradiol (E2) in patients with systemic inflammatory diseases leads to an higher production of IgG and IgM in peripheral blood mononucleated cells (PBMC) and the secretion of metalloproteinases and IL-6 by synovial fibroblasts. The effect of E2 seems to be partially related to its concentration. In fact, at the physiological concentration, E2 seems to exert a pro-inflammatory effect, while at pharmacological concentrations shows anti-inflammatory effects. Steroid hormones can be converted in downstream hormones along defined pathways. The conversion of dehydroepiandrosterone (DHEA) in peripheral macrophages leads to the androgen production. Subsequently the enzyme aromatase converts androgens in estrogens, and its activity is increased by some inflammatory cytokines such as IL-1b, IL-6 and TNF-a. In the synovial fluids of rheumatoid arthritis (RA) patients the levels of estrogens result significantly increased compared with controls, showing the consequence of this unbalanced steroid metabolism. Furthermore, the metabolism of estrogens leads to some downstream hydroxylated metabolites, that are not waste products, but still active molecules in the inflammatory response. In fact, it has been found that synovial fluids of RA patients present a different ratio of 16-hydroxylated estrogen metabolites/ 2-hydroxylated metabolites, confirming that also the unbalanced metabolism of estrogens and not only the estrogen concentration seems to be related to the development and worsening of rheumatoid arthritis.

Secondary osteoporosis (OP) is a well-recognized complication of rheumatoid arthritis (RA). Treatment with TNF-a 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-a 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-a 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

Objective: The aim of this study was to evaluate the effects of 17b-estradiol (E2) and testosterone (T) on the mRNA expression of IL-1b, IL-6, TNF-a and TGF-b in cultured human monocytic cells (THP-1) after INF-g activation. Methods: THP-1 were cultured with E2 and T (10 nM) for 24 hs and then activated with INF-g (500 U/ml), during different periods of time (1, 3, 6, and 12 hs). After total RNA extraction, all samples were analyzed by multiple RT-PCR to detect mRNA expression of the selected cytokines. Results: Cells cultured without hormonal treatment expressed IL-1b mRNA after 1 h; on the contrary TNF-a, TGF-b and IL-6 mRNA were expressed only after 3 hs. At 6 and 12 hs only IL-6 mRNA was still expressed. Interestingly, cells cultured with testosterone never expressed IL-1b nor TNF-a mRNA and showed an IL-6 mRNA expression similar to the untreated controls at 3, 6 and 12 hours. On the contrary, cells treated with E2 showed the expression of all cytokines at 3 and 12 hs, and in general showed an higher expression of all the analyzed cytokines mRNA when compared to the other conditions. Conclusions: This study suggests that sex hormones may modulate the cytokine mRNA expression in the inflammatory cells. In fact, T inhibits TNF-a production at all the tested times, whereas E2 seems to accelerate and to enhance the inflammatory response. Therefore, the altered sex hormone ratio, as observed in the synovial fluid of RA patients (high E2/low T), might contribute to the occurrence and last of synovitis.

Polymyalgia rheumatica (PMR) is an inflammatory syndrome affecting older people whose prevalence has increased in recent years. The suppression of the hypothalamic-pituitary-adrenal axis (HPA) and ageing may contribute to the pathogenesis of PMR. Chronic stress (i.e. interpersonal, chronic infections etc.) in elderly people may represent a risk factor for the development of PMR. In fact, elderly represent per se a condition of endocrine senescence including adrenal hypofunction, in addition chronic stress represents a further harmful stimulus to seriously compromise endogenous glucocorticoid production. Synovitis and vasculitis characterize the majority of the patients. Serum cytokine and steroidal hormone patterns suggest that patients with PMR have an intensive inflammatory reaction. As a matter of fact, glucocorticoids represent the most useful temporary “replacement” treatment during the active phase of PMR. The use of modified-release glucocorticoids that might induce higher levels during the night (circadian rhythms as in physiological conditions), will represent another important approach to optimize PMR treatment and reduce the side effects. Combination therapy between glucocorticoids and inhibitors of pro-inflammatory cytokines should be tested in large studies and early cases of PMR.

Leishmaniasis represents a complex of diseases with an important clinical and epidemiological diversity. Visceral leishmaniasis is of higher priority than cutaneous leishmaniasis as it is a fatal disease in the absence of treatment. The clinical spectrum of leishmaniasis and control of the infection are influenced by the parasite-host relationship. The role of cellular immune responses of the Th1 type in the protection against disease in experimental and human leishmaniasis is well established. TNF-α has been implicated in cytokine-induced macrophage activation and tissue granuloma formation, two activities linked to control of intracellular visceral infection caused by Leishmania donovani. Anti- tumor necrosis factor-alpha (TNF-α) strategies have had a marked and substantial impact in the treatment of rheumatoid arthritis, however the clinical use of TNF-α antagonists has been accompanied by increased reporting of infections. Here we report the first case of visceral leishmaniasis in a patient treated for a long period of time with human anti TNF-α monoclonal antibody, adalimumab. Due to the low incidence rate of Mediterranean visceral leishmaniasis, a systematic screening for leishmaniasis in all patients treated with biologics may be not recommended. However, for those patients living at high risk of leishmaniasis exposure, a periodical serological monitoring should be performed during therapy with anti-TNF monoclonal antibodies.

Interleukin-1 (IL-1) is one of the pivotal cytokines in initiating and driving the processes of rheumatoid arthritis (RA), and the body’s natural response, IL-1 receptor antagonist (IL-1Ra), has been shown conclusively to block its effects. IL-1 mediate several clinical symptoms of the inflammatory reaction (i.e. fever, pain, sleep disturbances). IL-1 is considered a key mediator in RA joint damage because of its greater capacity (greater than TNF) of increasing matrix degradation by inducing the production of MMPs and PGE2 in synovial cells, as well by its role as mediator of bone and cartilage destruction. In addition, IL-1 decreases the repair process by suppressing matrix synthesis and shows a strong synergism with TNF in inducing many inflammatory genes at both local and systemic level. The induced endogenous production of IL-1Ra, in presence of the RA synovitis, is too low to contrast the high affinity of IL-1 for the cell receptors. Therefore, IL-1Ra presence should result in very effective prevention of IL-1 signal transduction particularly in the inflammatory site. In laboratory and animal studies inhibition of IL-1 by either antibodies to IL-1 or IL-1Ra proved beneficial to the outcome. IL-1Ra is a member of the IL-1 superfamily. The effects of different DMARDs on IL-1Ra levels in RA patients support the important role that selected anticytokine treatments might exert in the pathophysiology of the disease. However, since anti TNFα therapy it is not effective in all RA patients, nor does it fully control the arthritic process in affected joints of good responders and complete TNF suppression should be avoided, the combined treatment with intermediate doses of TNF and IL-1 blockers, reaching synergistic suppression of arthritis, seems warranted in RA.

We evaluated endothelin-1 (ET-1) plasma levels in patients affected by primary Raynaud’s phenomenon (PRP), as well as in patients with systemic sclerosis (SSc) and secondary Raynaud’s phenomenon (SRP). Furthermore, ET-1 levels were investigated in SSc patients with different patterns of peripheral microvascular damage, as evaluated by nailfold videocapillaroscopy (NVC). Methods: 23 PRP patients, 67 SSc patients according to ACR criteria, and 23 healthy subjects were enrolled. SSc microvascular involvement was classified in three different patterns (Early, Active, and Late) by NVC, as previously described. Results: ET-1 was found significantly higher in both PRP and SRP, when compared with controls (median ±IQR: 3.3±2.8, 2.7±2.2, 2.0±2.2, respectively) (p=0.05). No statistically significant difference of ET-1 levels was observed between PRP and SRP patients. ET-1 was found higher in patients with Late NVC pattern, when compared with both Active and Early NVC patterns (median±IQR: 3.4±2.5, 2.4±2.2, 2.5±2.1, respectively), but without statistical significance. Patients with Late NVC pattern showed significantly higher ET-1 plasma levels than controls (p=0.03). No correlation was found between ET-1 levels and disease duration in both groups, as well as between ET-1 levels and age of patients. Conclusions: These data support previous studies, reporting increased ET-1 plasma levels in both PRP and SRP patients. Interestingly, patients with the Late NVC pattern of microangiopathy showed higher ET-1 plasma levels than controls. The high levels of ET-1 detected in the Late NVC pattern of microangiopathy might be related to the larger fibrotic involvement typical of the advanced stages of disease.

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 μg/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

Objectives: Systemic sclerosis (SSc) is characterized by altered microvascular structure and function. Nailfold videocapillaroscopy (NVC) is the tool to evaluate capillary morphological structure and laser-Doppler Blood flowmetry (LDF) can be used to estimate cutaneous blood flow of microvessels. The aim of this study was to investigate possible relationships between capillary morphology and blood flow in SSc. Methods: 27 SSc patients and 12 healthy subjects were enrolled. SSc microvascular involvement, as evaluated by NVC, was classified in three different patterns (“Early”, “Active”, “Late”). LDF analysis was performed at the II, III, IV, V hand fingers in both hands and both at cutaneous temperature and at 36°C. Statistical evaluation was carried out by non-parametric procedures. Results: Blood flow was found significantly lower in SSc patients when compared with healthy subjects (p

Several studies demonstrated the efficacy of the B-cell depletion therapy with rituximab (RTX) in RA patients, including those unresponsive to anti- TNF therapy, underlying the important role of B cells in this disease (1-5). Several recent papers have demonstrated a differential effects of RTX in depleting B-cells and blocking plasma cell generation at the synovial and at the bone marrow level (7-9). This differential effect may explain why among patients who respond to RTX, some relapse while others show a very prolonged response, independently from the reappearance of B-cells in the peripheral blood (6). However, the efficacy of RTX may also depend on the individual genetic predisposition. At this regard, very few data were produced by now.

Several connective tissue diseases, in particular systemic sclerosis (SSc), have Raynaud’s phenomenon (RP) as their first clinical manifestation. Primary RP represents a benign condition often observed in otherwise healthy subjects, especially women: it is due to an exaggerated response to the physiological cold-induced vasospasm, whereas the secondary form of RP is typically associated with connective tissue diseases, especially SSc. Nailfold videocapillaroscopy (NVC), particulary after the recent technological advances, is a safe and reliable method to observe the microvascular structure and its early changes, especially during the transition from primary to secondary RP. In case of SSc, by considering validated patterns and scoring systems, NVC is the main tool that rheumatologists can rely on, besides the presence of specific auto-antibodies, to perform a very early diagnosis of the disease. This implies the possibility of early treatment of SSc, with an eye of predicting and preventing its major clinical complications.

Book review of Dominique Casajus, Fabio Viti, eds, Le terre et le pouvoir. À la mémoire de Michel Izard, Paris, Cnrs Éditions, pp. 2012, IV, 307.