Ilaria Tinazzi

Lower limb enthesopathy in patients with psoriasis without clinical signs of arthropathy: a hospital-based case–control study

Background: Psoriasis is associated with a form of spondyloarthropathy in 10–30% of cases. A major feature of psoriatic arthritis is enthesitis. In some patients with psoriasis the presence of enthesitis could be underdiagnosed. Objective: To investigate the presence of lower limbs entheseal abnormalities in patients with chronic plaque psoriasis without signs and symptoms of psoriatic arthritis. Methods: Thirty patients with psoriasis and 30 controls underwent ultrasonographic evaluation of Achilles, quadriceps, patellar entheses and plantar aponeurosis. Ultrasonographic findings were scored according to the Glasgow Ultrasound Enthesitis Scoring System (GUESS). Results: Mean GUESS score was significantly higher in patients with psoriasis as compared with controls: 7.9 (0.6) vs 2.9 (0.3); p<0.0001. In particular, the thickness of all tendons examined was significant higher in cases than in controls (p<0.0001), as well as the number of enthesophytes in all sites examined. In both cases and controls, the GUESS score was directly correlated with age (ru200a=u200a0.22; pu200a=u200a0.008), body mass index (ru200a=u200a0.23, pu200a=u200a0.0067) and waist circumference (ru200a=u200a0.17; pu200a=u200a0.02). In contrast, the GUESS score was not correlated with the duration and severity of psoriasis according to the Psoriasis Area and Severity Index (ru200a=u200a0.03; pu200a=u200a0.8) and body surface area involvement (ru200a=u200a0.07; pu200a=u200a0.6). Conclusions: Entheseal abnormalities can be documented by ultrasonography in clinically asymptomatic patients with psoriasis. These findings could be related to a subclinical entheseal psoriatic inflammation. We suggest close follow-up of patients with psoriasis with entheseal abnormalities for early diagnosis of psoriatic arthritis.

Soluble TNF-like cytokine (TL1A) production by immune complexes stimulated monocytes in rheumatoid arthritis

TNF-like cytokine (TL1A) is a newly identified member of the TNF superfamily of ligands that is important for T cell costimulation and Th1 polarization. However, despite increasing information about its functions, very little is known about expression of TL1A in normal or pathological states. In this study, we report that mononuclear phagocytes appear to be a major source of TL1A in rheumatoid arthritis (RA), as revealed by their strong TL1A expression in either synovial fluids or synovial tissue of rheumatoid factor (RF)-seropositive RA patients, but not RF−/RA patients. Accordingly, in vitro experiments revealed that human monocytes express and release significant amounts of soluble TL1A when stimulated with insoluble immune complexes (IC), polyethylene glycol precipitates from the serum of RF+/RA patients, or with insoluble ICs purified from RA synovial fluids. Monocyte-derived soluble TL1A was biologically active as determined by its capacity to induce apoptosis of the human erythroleukemic cell line TF-1, as well as to cooperate with IL-12 and IL-18 in inducing the production of IFN-γ by CD4+ T cells. Because RA is a chronic inflammatory disease with autoimmune etiology, in which ICs, autoantibodies (including RF), and various cytokines contribute to its pathology, our data suggest that TL1A could be involved in its pathogenesis and contribute to the severity of RA disease that is typical of RF+/RA patients.

Psoriasis patients with nail disease have a greater magnitude of underlying systemic subclinical enthesopathy than those with normal nails

Objective Enthesopathy is a major feature of psoriatic arthritis (PsA), which is supported by imaging studies. Given that nail disease often predates PsA and that the nail is directly anchored to entheses, the authors asked whether nail involvement in psoriasis equates with a systemic enthesopathy. Methods Forty-six patients with psoriasis (31 with nail disease) and 21 matched healthy controls (HC) were recruited. 804 entheses of upper and lower limbs were scanned by an ultrasonographer blinded to clinical details. Results Psoriasis patients had higher enthesitis scores than HC (median (range) 21 (0–65) vs 11 (3–39), p=0.005). Enthesopathy scores were higher in patients with nail disease (23 (0–65)) than in patients without nail disease (15 (5–26), p=0.02) and HC (11 (3–39), p=0.003). Inflammation scores of patients with nail disease (13 (0–34)) were higher than patients without nail disease (8 (2–15), p=0.02) and HC (5 (0–19), p<0.001). Modified nail psoriasis severity index scores were correlated to both inflammation (r2=0.45, p=0.005) and chronicity scores (r2=0.35, p=0.04). No link between the psoriasis area and severity index and enthesitis was evident. Conclusion The link between nail disease and contemporaneous subclinical enthesopathy offers a novel anatomical basis for the predictive value of nail psoriasis for PsA evolution.

Very low levels of vitamin D in systemic sclerosis patients

Vitamin D displays many extraosseous immunomodulatory effects. The aim of the study was to evaluate the level of vitamin D in patients with systemic sclerosis (SSc) and to analyze the associations between the concentration of the vitamin and clinical manifestations. In March-April 2009, 65 consecutive SSc patients underwent evaluation of vitamin D concentrations by the LIAISON immunoassay (normal 30-100xa0ng/ml). Serum levels between 10 and 30xa0ng/ml were classified as vitamin D insufficiency, while concentrations <10xa0ng/ml as vitamin D deficiency. None of the patients were receiving vitamin D supplementation at the time of or during the year prior to study entry. The mean level of vitamin D was 15.8u2009±u20099.1xa0ng/ml. Only three cases showed normal values; vitamin D insufficiency and deficiency were found in 43 and 19 cases, respectively. Patients with vitamin D deficiency showed longer disease duration (13.1u2009±u20096.8 versus 9.4u2009±u20095.5xa0years, Pu2009=u20090.026), lower diffusing lung capacity for carbon monoxide (63.7u2009±u200912.4 versus 76.4u2009±u200920.2, Pu2009=u20090.014), higher estimated pulmonary artery pressure (28.9u2009±u20099.9 versus 22.8u2009±u200910.4, Pu2009=u20090.037) and higher values of ESR (40u2009±u200925 versus 23u2009±u200913xa0mm/h, Pu2009=u20090.001) and of CRP (7u2009±u20097 and 4u2009±u20092xa0mg/l, Pu2009=u20090.004) in comparison with patients with vitamin D insufficiency; moreover, late nailfold videocapillaroscopic pattern was more frequently found (52.6% versus 18.6%, Pu2009=u20090.013). None of the patients showed evidence of overt mal-absorption. Low levels of vitamin D are very frequent in patients with SSc. Intestinal involvement is not likely the cause of vitamin D deficit; other factors such as skin hyperpigmentation and reduced sun exposition for psychological and social reasons may be implicated. Patients with vitamin D deficiency showed more severe disease in comparison with patients with vitamin D insufficiency, above all concerning lung involvement. Further trials are awaited to determine whether vitamin D could represent a modifiable factor able to interfere with SSc evolution.

The early psoriatic arthritis screening questionnaire: a simple and fast method for the identification of arthritis in patients with psoriasis

OBJECTIVEnDermatologists usually see patients with psoriasis before arthritis develops, making them well placed to diagnose early PsA (ePsA). This study aimed to develop a rapid and robust screening questionnaire for predicting PsA in patients with psoriasis referred to a specialized joint dermatology-rheumatology combined clinic.nnnMETHODSnIn all, 228 psoriasis patients naïve to DMARD treatment were administered two screening questionnaire: the new Early ARthritis for Psoriatic patients (EARP) questionnaire and the existing Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire. The diagnostic accuracy of the two questionnaires for the diagnosis of ePsA was compared by receiving operating characteristics curves.nnnRESULTSnAfter psychometric analysis, a simplified questionnaire of 10 items was found to have good internal reliability (Cronbachs αu2009=u20090.83) and was much faster and simpler to administer than the PASE. Both the EARP and PASE questionnaires presented similar receiving operating characteristics curves (specificity 91.6 and 67.2 and sensitivity 85.2 and 90.7, respectively) in identifying ePsA patients by using the cut-off value of 3 for EARP-10 and the standard cut-off value of 44 for PASE. The CASPAR criteria for PsA were present in 61 (26.7%) of the patients at clinical presentation and in 32.9% at 1-year follow-up, and the EARP score of ≥3 correlated with clinically determined arthropathy by a rheumatologist.nnnCONCLUSIONnThe EARP questionnaire is simple and fast to administer and proved robust for the identification of PsA in the dermatological setting. Dermatologists should consider the EARP for patients attending clinics, as it correlates well with early PsA diagnosis.

Preliminary Evidence That Subclinical Enthesopathy May Predict Psoriatic Arthritis in Patients with Psoriasis

To the Editor: nnThe importance of enthesitis as the key pathological lesion underpinning the pathogenesis of psoriatic arthritis (PsA) has been increasingly recognized1. Studies for more than 3 decades have shown a high frequency of osseous and entheseal abnormalities in patients with psoriasis without clinical signs of arthritis2,3. From a clinical viewpoint, about 10% of patients with psoriasis develop PsA over a decade, so there is a need to better define predictive factors for the identification of future PsA in patients with psoriasis4. The ability to accurately predict development of PsA in subjects with psoriasis could have implications for prevention of the morbidity associated with PsA and also for studies aimed at elucidation of the early phases of disease.nnWe previously used ultrasound (US) to show a high frequency of subclinical entheseal involvement in patients presenting with psoriasis but without clinically evident arthritis5. We investigated whether subclinical enthesopathy in patients with psoriasis predicted the future development of PsA.nnA longitudinal evaluation was performed in a cohort of 30 cases of psoriasis with a mean duration of 3.5 years using clinical and repeat ultrasound assessment of lower-limb tendons, using the Glasgow Ultrasound Enthesitis Scoring System (GUESS)6. Of the 30 patients originally evaluated5, 28 returned for a re-evaluation. No patient received systemic treatment with a disease-modifying antirheumatic drug. The criteria of the ClASsification of Psoriatic ARthritis (CASPAR) study group were used to define the presence or absence of PsA7. Evidence for osteoarthritis (OA) was also sought, as this can affect the same joints involved in PsA, including distal interphalangeal (DIP) … nnAddress correspondence to Dr. I. Tinazzi, Unit of Rheumatology, University of Verona, P.le Scuro 1, 37134 Verona, Italy. E-mail: ilariatinazzi{at}yahoo.it

The link between enthesitis and arthritis in psoriatic arthritis: a switch to a vascular phenotype at insertions may play a role in arthritis development

Objective Subclinical enthesopathy is recognised in both psoriasis and psoriatic arthritis (PsA). This study used ultrasonography with power Doppler (PD) to test the hypothesis that subclinical enthesopathy in PsA was associated with an ‘inflammatory’ or vascular phenotype compared to that seen in psoriasis. Methods 100 patients with a mean age of 46.3u2005years (SD 15) (42 with psoriasis and 58 with PsA) and 23 matched healthy controls (HC) from two centres were included. 1230 lower limb entheses were scanned by ultrasonographers blinded to clinical details. Both inflammatory and chronic features of enthesopathy were scored. Results Psoriasis patients (with or without arthritis) were more likely to express a vascular phenotype, with higher inflammation-related enthesopathy scores than HC (for inflammation p<0.0001, for chronicity p=0.02, for total ultrasound scores p<0.0001). The PsA patients had higher ultrasound enthesopathy scores than psoriasis patients (inflammation p=0.04, chronicity p=0.02) and HC (inflammation p<0.0001, chronicity p=0.003). When symptomatic entheses were excluded, PsA patients still had higher PD scores than psoriasis patients (p=0.003). Doppler positivity in at least one entheseal site was observed more frequently in PsA (21/58, 36.2%) versus psoriasis (4/42, 9.5%; p=0.002). Conclusions This study shows that the ultrasound appearances of subclinical enthesitis in psoriasis differ from the subclinical enthesitis in PsA, with PsA patients having more PD. This is suggestive of a more inflammatory or vascular process in PsA, and offers potentially novel insights into the progression from skin to joint disease in psoriasis.

Anti-TNFalpha blockers, autoantibodies and autoimmune diseases

Anti-TNFalpha blockers are extensively used in the management of chronic inflammatory disorders. Their administration may be associated with the generation of autoantibodies; this review focuses on the autoimmune phenomena linked to anti-TNFalpha inhibition, on the hypothesized pathogenetic mechanisms and on the clinical implications. While the development of antinuclear and, less frequently, of anti-DNA antibodies is a common finding, the onset of autoimmune diseases during anti-TNFalpha blocker treatment is a rare event, which needs to be promptly recognized in order to plan the appropriate management. Moreover the specific autoantibodies associated with rheumatoid arthritis are considered before and after biotherapy. Similarities and differences among infliximab, etanercept and adalimumab concerning induced autoimmune phenomena are underlined.

A score of risk factors associated with ischemic digital ulcers in patients affected by systemic sclerosis treated with iloprost.

A single series of patients affected by systemic sclerosis (SSc) and cyclically treated with iloprost was reviewed in order to evaluate the incidence of digital ulcers (DUs) and to compare the characteristics between the patients with and without this painful and disabling vascular complication. The record charts of 85 SSc patients were revised. Ischemic DUs and scleroderma contracture ulcers were separately considered. Twenty-nine subjects developed ischemic DUs during the course of the disease; whereas, scleroderma contracture ulcers occurred in six subjects. Ischemic DUs were associated with younger age at scleroderma onset, a longer disease duration, a longer time delay from scleroderma diagnosis to iloprost therapy, a bigger skin involvement, the presence of joint contractures, a videocapillaroscopic late pattern, a history of smoking, and of corticosteroids therapy. After the exclusion of four subjects with concomitant peripheral arterial disease, a forward-stepwise logistic regression analysis showed that only four variables, i.e., age at scleroderma onset, delay in beginning iloprost therapy, history of smoking, and presence of joint contractures remained significantly associated with ischemic DUs. In a score reflecting the sum of these four risk factors, the prevalence of ischemic DUs increased progressively from the lowest to the highest value of the score. The predictivity of this model was evaluated by the receiver-operating characteristics curve, with an estimated area under the curve of 0.836 with 95% confidence interval from 0.736 to 0.937. All the patients with scleroderma contracture ulcers were characterized by both diffuse pattern of disease and positivity for anti-Scl70 antibody. In this retrospective study, scleroderma patients with ischemic DUs are characterized by early disease onset, delay in beginning iloprost therapy, smoking habit, and presence of joint contraction. A score reflecting the sum of these factors may be useful to predict the risk of developing ischemic DUs.

Mature CD10+ and immature CD10- neutrophils present in G-CSF-treated donors display opposite effects on T cells

The identification of discrete neutrophil populations, as well as the characterization of their immunoregulatory properties, is an emerging topic under extensive investigation. In such regard, the presence of circulating CD66b+ neutrophil populations, exerting either immunosuppressive or proinflammatory functions, has been described in several acute and chronic inflammatory conditions. However, due to the lack of specific markers, the precise phenotype and maturation status of these neutrophil populations remain unclear. Herein, we report that CD10, also known as common acute lymphoblastic leukemia antigen, neutral endopeptidase, or enkephalinase, can be used as a marker that, within heterogeneous populations of circulating CD66b+ neutrophils present in inflammatory conditions, clearly distinguishes the mature from the immature ones. Accordingly, we observed that the previously described immunosuppressive neutrophil population that appears in the circulation of granulocyte colony-stimulating factor (G-CSF)-treated donors (GDs) consists of mature CD66b+CD10+ neutrophils displaying an activated phenotype. These neutrophils inhibit proliferation and interferon γ (IFNγ) production by T cells via a CD18-mediated contact-dependent arginase 1 release. By contrast, we found that immature CD66b+CD10- neutrophils, also present in GDs, display an immature morphology, promote T-cell survival, and enhance proliferation and IFNγ production by T cells. Altogether, our findings uncover that in GDs, circulating mature and immature neutrophils, distinguished by their differential CD10 expression, exert opposite immunoregulatory properties. Therefore, CD10 might be used as a phenotypic marker discriminating mature neutrophils from immature neutrophil populations present in patients with acute or chronic inflammatory conditions, as well as facilitating their isolation, to better define their specific immunoregulatory properties.