Age at diagnosis influences the clinical phenotype, treatment strategies and outcomes in patients with giant cell arteritis: results from the observational GCAGE study on a large cohort of 1004 patients.

BACKGROUND: Immune and vascular ageing are proposed risk factors for giant cell arteritis (GCA). Data on the impact of age at diagnosis of GCA on the clinical presentation and course of the disease are scarce. METHODS: Patients with GCA followed at referral centres within the Italian Society of Rheumatology Vasculitis Study Group were enrolled up to November 2021. Patients were grouped according to age at diagnosis: ≤64, 65-79 and ≥80 years old. RESULTS: The study included 1004 patients, mean age 72.1±8.4, female 70.82%. Median follow-up duration was 49 (IQR 23-91) months. Patients in the oldest group (≥80 years) had significantly more cranial symptoms, ischaemic complications and risk for blindness compared with the groups 65-79 and ≤64 years (blindness: 36.98% vs 18.21% vs 6.19%; p<0.0001). Large-vessel-GCA was more frequent in the youngest group (65% of patients). Relapses occurred in 47% of patients. Age did not influence the time to first relapse, nor the number of relapses. Older age was negatively associated with the number of adjunctive immunosuppressants. Patients >65 years old had 2-3 fold increased risk for aortic aneurysm/dissection up to 60 months follow-up. Serious infections, but not other treatment-related complications (hypertension, diabetes, osteoporotic fractures), were significantly associated with older age. Mortality occurred in 5.8% of the population with age >65, cranial and systemic symptoms as independent risk factors. CONCLUSIONS: The highest risk of ischaemic complications, aneurysm development, serious infections and the possible undertreatment make of GCA a very challenging disease in the oldest patients.

The impact of diet on disease activity in spondyloarthritis: A systematic literature review.

OBJECTIVES: Our study aimed to systematically review the evidence about the effect of diet or dietary supplements on spondyloarthritis (SpA) disease activity. METHODS: a systematic literature review (SLR) was conducted in MEDLINE, EMBASE, Cochrane and SCOPUS according to the "PEO" format (Population, Exposure, Outcome). The population was SpA (axial or peripheral, axSpA/pSpA, including Psoriatic Arthritis-PsA); the intervention any kind of diet/dietary supplement; the outcome disease activity. Inclusion criteria were: adult patients, Randomized Controlled Trials (RCTs) and longitudinal studies (so that a pre-and post-intervention assessment were available), papers in English. Risk of bias (RoB) was conducted with different tools according to the design of the study. RESULTS: Literature search yielded 1390 publications, of which 15 were finally inlcuded: 12 interventional and 3 observational studies. Among those with the lower RoB: a) 2 RCTs, one at unclear and one at low RoB, failed to show benefit of probiotics in SpA b) Two RCTs at unclear RoB provided evidence that weight loss, but not hypocaloric diet, was associated to MDA achievement in PsA. The remaining interventional studies were at high RoB. Among the observational studies, one study on Mediterranean diet demonstrated an association between diet adherence and a ≥ 20% decrease of ASDAS in axSpA. The other two observational studies were judged of poor quality. CONCLUSIONS: weight loss seem to be able to impact disease activity in PsA, while probiotics do not seem useful in SpA; evidence for dietary behaviors is scarce and heterogeneous.

Interstitial lung disease in microscopic polyangiitis and granulomatosis with polyangiitis: demographic, clinical, serological and radiological features of an Italian cohort from the Italian Society for Rheumatology.

OBJECTIVES: Interstitial lung disease (ILD) has been described as a possible pulmonary involvement in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV), mainly granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Aim of this cross-sectional Italian national study was to describe demographic, clinical and serological profile of ILD related to MPA and GPA and investigate possible correlations between radiologic patterns of ILD and vasculitis features. METHODS: We enrolled 95 consecutive patients with AAV-ILD, 56 affected by MPA (58.9%) and 39 by GPA (41.1%). RESULTS: NSIP was the most frequently detected ILD pattern, observed in c-ANCA patients in 60.9% of cases, followed by UIP pattern mainly observed in p-ANCA patients (47.7%, p=0.03). ILD represented the first clinical manifestation, preceding vasculitis diagnosis in 22.1% of cases and, globally, ILD was already detectable at AAV diagnosis in 66.3% of patients. The diagnosis of ILD preceded that of AAV in 85.7% of p-ANCA positive-patients, while only one patient with c-ANCA developed ILD before AAV (p= 0.039). Multivariate analysis confirmed the correlation of UIP pattern with p-ANCA-positivity and a diagnosis of ILD before AAV, also when adjusted for age and sex. CONCLUSIONS: Our study confirms that UIP is a frequent pattern of lung disease in AAVILD patients. Our results also suggest that ILD can represent an early complication of AAV but also occur in the course of the disease, suggesting the need of a careful evaluation by both pulmonologist and rheumatologist to achieve an early diagnosis. Further prospective studies are needed to define ILD prevalence and evolution in AAV patients.

Fully integrated [18F]FDG PET/MR in large vessel vasculitis.

BACKGROUND: The aim of this study is to evaluate the usefulness of [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET)/magnetic resonance (MR) in large vessels vasculitis (LVV) patients. METHODS: We performed an observational retrospective study based on our records. Images were acquired on a PET/MR scanner using [18F]FDG-PET whole body imaging. For each PET scan, a qualitative analysis and a semi-quantitative measure using the maximum of the standardized uptake value (SUVmax) were performed. SUVmax measurements normalized to the liver uptake were categorized using a grading scale. Vessel's wall thickness (WT) was measured at five fixed points (inferior margin of T5, T9, T12, L3, thickest area [max WT]). RESULTS: Twenty-three LVV patients were included, 56.5% giant cells arteritis, 34.8% Takayasu's arteritis and 8.7% isolated aortitis, all Caucasian, mostly females (82%). We considered 32 PET scans for the LVV group (from a minimum of one to a maximum of three scans per patient) mainly during follow-up (29/32 scans), and 23 PET scans from a control group of non-metastatic malignancies patients. We found higher SUVmax compared to controls, in all sites, irrespective of clinical disease activity. Mean WT resulted higher in patients than in controls but was not correlated to SUVmax. Mean WT positively correlated with age in both cohorts, inversely correlated to disease duration, while no correlation with SUVmax was observed. The concordance between clinically active disease and PET hypermetabolism was poor (Cohen' κ=0.33). CONCLUSIONS: PET/MR is a safe imaging technique capable of detecting inflammation in aortic wall. Low radiological exposure of PET/MR should be considered especially in young women receiving follow-up studies.

Health-Related Quality of Life in Patients With ANCA-Associated Vasculitis and Sinonasal Involvement: A Single-Center Cross-Sectional Study.

BACKGROUND/OBJECTIVE: The aim of this study was to assess the impact of sinonasal morbidity on quality of life (QoL) in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: This cross-sectional case-control study enrolled 71 patients-44 AAV cases with (ear, nose, and throat [ENT]-AAV) or without ENT involvement (non-ENT-AAV) undergoing multidisciplinary evaluations and 27 chronic rhinosinusitis (CRS) cases. Three validated QoL questionnaires (Sino-Nasal Outcomes Test-22 [SNOT-22], Nasal Obstruction Symptom Evaluation [NOSE], and Short-Form 36) were administered, and the 3 groups were compared. RESULTS: The ENT-AAV patients were significantly younger (p = 0.01), with less antineutrophil cytoplasmic antibody positivity frequency (p = 0.035) and lower renal involvement (p = 0.003) than the non-ENT-AAV patients.The SNOT-22 questionnaire demonstrated significantly greater sinonasal morbidity in ENT-AAV patients compared with CRS patients (p < 0.001). The NOSE score of ENT-AAV patients was comparable to those of CRS patients, but higher than that of non-ENT-AAV patients (p < 0.001). The SNOT-22 and NOSE scores positively correlated with disease activity (p = 0.037; p = 0.004, respectively). Short-Form 36 domain-by-domain analysis revealed a significantly poorer QoL in ENT-AAV patients, especially with physical functioning being progressively impaired in CRS, non-ENT-AAV, and ENT-AAV patients (p < 0.001). No significant differences in QoL came to light when AAV patients were stratified according to current systemic o local treatments. CONCLUSIONS: The QoL in AAV patients is significantly reduced, especially in the presence of ENT involvement. The AAV-related nasal morbidity is consistent and comparable to that reported by CRS patients. It significantly affects patients' QoL and in particular social functioning, leading to limitation in daily/work activities. Organ-focused questionnaires and multidisciplinary management are warranted to pursue a treat-to-target approach in these patients.

Leukocytoclastic vasculitis associated with multifocal sensory neuropathy responsive to intravenous immunoglobulins: a case report.

Leukocytoclastic vasculitis (LCV) is a common form of small-vessel vasculitis, which commonly presents as palpable purpura or petechiae, caused by deposition of circulating immune complexes on vessels walls that attracts granulocytes which damage the vascular endothelium and leading to erythrocytes extravasation. The skin is the most commonly involved organ, but also renal, gastrointestinal, pulmonary, cardiovascular and neurological systems may be affected. Skin lesions may be the initial signs of systemic vasculitis. Systemic symptoms may be present, such us fever, myalgia, abdominal pain and arthralgia. The presence of neuropathy/mononeuritis multiplex is expression of severe vasculitic involvement. Herein, we describe the case of a patient with leucocytoclastic vasculitis associated to sensitive neuropathy, responsive to intravenous immunoglobulins (IVIg) therapy, after the failure of classic systemic treatments.

An Italian Disease-Based Registry of Axial and Peripheral Spondyloarthritis: The SIRENA Study.

Introduction: Data about the clinical presentation and management of early and mild spondyloarthritis (SpA) are limited. Objectives: The objective of this study was to describe the baseline characteristics of disease-modifying antirheumatic drug (DMARD)-naïve patients with axial or peripheral SpA. Methods: The Spondyloarthritis Italian Registry: Evidence from a National Pathway (SIRENA) study is an ongoing, Italian, multicenter, prospective registry of patients with a first or newly confirmed diagnosis of SpA according to the Assessment of SpondyloArthritis International Society (ASAS) criteria. To be included, patients had to be naïve to conventional, targeted, and biological DMARDs for SpA. Patients were enrolled between June 2017 and June 2019 and classified into groups according to disease presentation: predominantly axial or peripheral manifestations. The study is ongoing, and patients are being followed for 2 years, with an evaluation every 6 months according to clinical practice. Differences in baseline demographics, lifestyle, and clinical characteristics between axial and peripheral SpA were evaluated. Results: In this study, 350 patients were enrolled, of which 123 (35.1%) were axial and 227 (64.9%) were peripheral patients. Patients with axial SpA were significantly younger at enrollment (median age: 44 vs. 53 years), had significantly more anxiety/depression (13 vs. 2.6%), and expressed higher disease activity compared to patients with peripheral SpA. Patients with peripheral SpA had significantly more cardiometabolic disorders (33 vs. 18.7%), skin psoriasis (65.2 vs. 21.1%), and nail psoriasis (35.5 vs. 17.1%) than patients with axial SpA. Dactylitis, enthesitis, and fibromyalgia were observed, respectively, in 17.6, 51.2, and 5.7% of patients with axial SpA and 24.3, 40, and 3.1% of patients with peripheral SpA. In both disease groups, women tended to report depression, joint tenderness, and higher disease activity more frequently than their male counterparts. At inclusion, a new diagnosis of SpA was performed in 58% of axial and 77% of peripheral patients, with a median time from symptom onset to diagnosis of 36 and 24 months, respectively. At baseline, most patients with axial SpA (77%) started a biological DMARD, while over half of the peripheral patients started a conventional DMARD. Conclusions: Based on a well-characterized clinical registry of SpA, we provided real-world insights on the clinical features of DMARD-naïve SpA patients, pointing out major differences between axial and peripheral disease in terms of clinical characteristics and treatment pattern. Future prospective evaluations within the SIRENA study will improve knowledge on SpA and contribute to defining the best therapeutic approach.

IgG anti-Pentraxin 3 antibodies are a novel biomarker of ANCA-associated vasculitis and better identify patients with eosinophilic granulomatosis with polyangiitis.

OBJECTIVE: To investigate prevalence of anti-Pentraxin 3 (PTX3) antibodies in sera of anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) patients. METHODS: Anti-PTX3 and PTX3 levels were analysed by enzyme-linked immunosorbent assays in sera from unselected patients with AAV and compared with patients with systemic lupus erythematosus (SLE, n = 130), other connective tissue diseases (CTDs, n = 97) and matched healthy controls (n = 97). Optical density (OD) cut-off for positive anti-PTX3 antibodies was determined by ROC curve analysis and set as 0.234. Indirect immunofluorescence (IIF) on fixed human granulocytes was used to analyze the fluorescence pattern of anti-PTX3 antibodies. Liquid-phase inhibition tests were conducted to assess potential interferences. RESULTS: We included 101 AAV patients (females 58%, median age 60[51-69] years) affected either with granulomatosis with polyangiitis (GPA, n = 51), microscopic polyangiitis (MPA, n = 12) or eosinophilic granulomatosis with polyangiitis (EGPA, n = 38). Anti-PTX3 antibodies were detected in 29.7% AAV patients, being significantly higher than in healthy controls (p < 0.001) and CTDs (p = 0.030) but lower than in SLE (p = 0.004). Anti-PTX3 antibody prevalence was 44.7% in EGPA, 25% in MPA and 19% in GPA (p = 0.034). Among ANCA negative patients, 35.7% displayed positive anti-PTX3 antibodies. Anti-PTX3 were associated with a lower prevalence of systemic (p = 0.002), ear-nose-throat (p = 0.006) and renal manifestations (p = 0.016). Anti-PTX3 antibodies were characterized by a specific IIF pattern on fixed granulocytes. PTX3 serum levels resulted lower in AAV than healthy controls (p < 0.001). PTX3 inhibited anti-PTX3 binding in a dose-dependent manner. CONCLUSIONS: Anti-PTX3 autoantibodies appear a promising novel biomarker of AAV, especially EGPA.

Anti-neutrophil cytoplasmic antibody specificity determines a different clinical subset in granulomatosis with polyangiitis.

OBJECTIVES: It has been suggested that anti-neutrophil cytoplasmic antibody (ANCA) specificity, rather than clinical diagnosis influences the phenotype and course of ANCA-associated vasculitis (AAV). However, preliminary evidence suggests that further combined levels of categorisation might be of clinical relevance. The aim of this study was to investigate differences in clinical presentation at disease onset and outcomes based on clinical diagnosis and ANCA specificity. METHODS: Newly diagnosed patients with GPA or MPA assessed in three referral centres between 2000 and 2016 were included. Patients were grouped as MPO-ANCA-positive granulomatosis with polyangiitis (MPO-GPA), PR3-ANCA-positive-GPA (PR3-GPA), and MPO-ANCA-positive microscopic polyangiitis (MPO-MPA). RESULTS: Of the 143 AAV patients included (female 52%), 87 were categorised as PR3-GPA, 23 as MPO-GPA, and 33 as MPO-MPA. Patients with MPO-GPA were significantly younger than MPA patients (age 49±15 versus 63±10; p<0.001). MPO-GPA had significantly more frequent subglottic stenosis compared to PR3-GPA. Ear, nose, throat involvement was significantly more frequent in both GPA groups compared to MPA. Type of pulmonary involvement differed between both GPA groups and MPA with diffuse pulmonary haemorrhage being significantly more frequent in the latter (7% in PR3-GPA, 0% in MPO-GPA, 27% in MPOMPA; p<0.001). Renal involvement was more frequent in MPO-MPA compared to both MPO-GPA and PR3-GPA (impaired renal function in 84%, 39%, and 36%, respectively; p<0.001). PR3-GPA relapsed significantly more than the other two groups. After adjusting for age, MPO-GPA was a significant risk factor for mortality [HR 4.44 (95%CI 1.46-13.52), p=0.009]. CONCLUSIONS: ANCA specificity identifies specific subsets of disease characterised by different clinical presentation and outcome within the clinical diagnosis of GPA.

Do Obesity and Overweight Influence Disease Activity Measures in Axial Spondyloarthritis? A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of our systematic review and meta-analysis was to investigate whether overweight/obesity are associated with higher disease activity measures in patients with axial spondyloarthritis (SpA). METHODS: MEDLINE, PubMed, and Web of Science were searched using key terms corresponding to population (axial SpA patients), exposure (overweight/obesity), and outcome (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] and Ankylosing Spondylitis Disease Activity Score [ASDAS]). Predefined inclusion criteria were adult patients with axial SpA, exposure classified according to body mass index (BMI), BASDAI/ASDAS reported for each BMI group, and observational studies. The Newcastle-Ottawa Scale for cohort, cross-sectional, and case-control studies was used for quality check. Random-effects meta-analysis was used to pool results, which were expressed as the mean difference (MD) in BASDAI and ASDAS between BMI groups, with 95% confidence intervals (95% CIs). RESULTS: A total of 10 articles were included in the meta-analysis. The MD in BASDAI between normal BMI and overweight/obese patients was -0.38 (95% CI -0.56, -0.21; P < 0.0001); the MD in ASDAS between the same groups was -0.19 (95% CI -0.29, -0.09; P < 0.0001). The MD in BASDAI between normal BMI and overweight patients was -0.09 (95% CI -0.33, 0.15; P = 0.45), and the MD between normal BMI and obese patients was -0.78 (95% CI -1.07, -0.48; P < 0.0001). For ASDAS, the MD between normal BMI and overweight patients was -0.02 (95% CI -0.19, 0.15; P = 0.79), and the MD between normal BMI and obese patients was -0.42 (95% CI -0.60, -0.23; P < 0.0001). CONCLUSION: Overweight and obese patients with axial SpA tend to present higher disease activity scores compared to patients with a normal BMI. This difference seems to be clinically meaningful only for the comparison between obese patients and patients with normal BMI, and more for BASDAI than ASDAS.

Subclinical atherosclerosis evolution during 5 years of anti-TNF-alpha treatment in psoriatic arthritis patients.

OBJECTIVES: Our aim was to evaluate subclinical atherosclerosis progression during 5 years of anti-tumour necrosis factor (TNF)-α treatment in psoriatic arthritis (PsA) patients. METHODS: Thirty-two consecutive PsA patients starting TNF-α inhibitors were enrolled and evaluated at baseline (T0), 2 years (FU1) and 5 years (FU2) of treatment. Arterial structural properties were evaluated by B-mode ultrasound of mean carotid intima-media thickness (mean-IMT) and maximum IMT (M-MAX) in each segment (common, bulb, internal), bilaterally. Endothelial function was assessed by post-occlusion flow-mediated dilation (FMD) of the brachial artery using high-sensitivity ultrasonography. Treatment response was studied through DAS28 (disease activity score) and inflammatory biomarkers (C-reactive protein, TNF-α, osteoprotegerin). Metrologic and metabolic data were collected. RESULTS: At T1, a significant decrease of DAS28 (4.2±0.7 vs. 2.3±0.8, p<0.001) and CRP (11.25±9.16 vs. 2.91±1.72, p<0.01) was observed. Efficacy was preserved at FU2 (DAS28 2.4±0.9, CRP 2.73±2.51; p=ns vs. FU1). Systolic blood pressure and BMI remained stable throughout the follow-up, while diastolic blood pressure decreased significantly from FU1 to FU2 (80±10 vs. 74±7 mmHg, p=0.001). From T0 to FU1 there was an increase of IMT-mean and M-MAX (0.7±0.1 vs. 0.9±0.4 and 0.9±0.2 vs. 1.1±0.4, p<0.01). At FU2, IMT-mean and M-max did not change significantly (0.9±0.3 and 1.1±0.3, p=ns vs. FU1). No significant variation in FMD values was observed during the study period. CONCLUSIONS: A slight progression of subclinical atherosclerosis in PsA was observed in the first 2 years of anti-TNF-α treatment. This process seemed to decelerate in follow-up extension to 5 years.

Validation of the Italian Version of the Educational Needs Assessment Tool in Rheumatoid Arthritis Patients and Factors Associated with Educational Needs.

The educational needs assessment tool (ENAT) is a seven-domain questionnaire assessing the educational needs (EN) of patients with rheumatoid arthritis (RA). The aim of this study was to validate the Italian version of the ENAT and to identify factors associated with EN in people with RA. The original English ENAT version was translated into Italian according to Beaton's method and subjected to Rasch analysis for validity testing. Socio-demographic and clinical variables were tested for associations with the ENAT domain scores using a multivariable linear regression model. The ENAT translated well into Italian and retained its construct validity. Some adjustments were needed when pooling the Italian and English datasets. The overall score of the ENAT had a high median: 82.8 (interquartile range (IQR): 57.5 to 100) i.e., 72.4% of the maximum score. The highest score was observed in the domain "Arthritis process" and the lowest was in "Support systems". Only gender was independently associated with EN (females having higher EN than males). The Italian ENAT is feasible for the use in the clinical setting and may help the health care practitioners to tailor educational interventions for RA patients. The characteristics of the patients, particularly female gender, may be associated with higher EN.

Skin ulcers in systemic sclerosis: correlation with clinical phenotype in a monocentric cohort from the north-east of Italy.

OBJECTIVES: To evaluate the prevalence of skin ulcers (SUs) and their association with clinical phenotype in a monocentric cohort of patients affected with systemic sclerosis (SSc). METHODS: Patients affected with SSc (ACR/EULAR 2013 criteria) in regular follow-up at the Rheumatology Unit of Padova University Hospital, Italy, were considered and retrospectively evaluated. Demographic, clinical and laboratory data, organ involvement and therapy were recorded. We analysed the occurrence, timing (single episode, recurrent/chronic) and site of SUs. The association between SUs and demographic and clinical variables was assessed by logistic regression analysis. RESULTS: We evaluated 211 SSc patients, aged 60.8±12.4 years, 187 (89%) females, 147 (70%) affected with limited cutaneous SSc. During a median follow-up of 120 months (50-216), 105 (50%) patients experienced at least one episode of SU; among them, 66% had recurrent or persistent SUs. Patients with a history of SUs compared with those never affected were younger at SSc diagnosis (p=0.009), had more frequently a diffuse cutaneous form (p=0.001), chronic anaemia (p<0.001), systemic inflammation (p=0.001), lung (p=0.002) and cardiac (p=0.004) involvement, and calcinosis (p=0.001). At multivariate analysis a younger age at SSc diagnosis (p=0.031), articular involvement (p=0.005) and telangiectasia (p=0.003) were independently associated with SUs. Telangiectasia, articular involvement, chronic anaemia and inflammatory state were found to be associated with the recurrence/chronicisation of SUs. CONCLUSIONS: SUs represent a common complication in our cohort of patients with a long-term follow-up. The association of SUs with some clinical manifestations of SSc suggests a combined role of microcirculatory damage and inflammation in their origin.

Does gender influence clinical expression and disease outcomes in COVID-19? A systematic review and meta-analysis.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) was characterized at the end of 2019, and soon spread around the world, generating a pandemic. It has been suggested that men are more severely affected by the viral disease (COVID-19) than women. OBJECTIVE: The aim of this systematic literature review (SRL) and meta-analysis was to analyse the influence of gender on COVID-19 mortality, severity, and disease outcomes. A SRL was performed in PubMed and Embase, searching terms corresponding to the 'PEO' format: population = adult patients affected with COVID-19; exposure = gender; outcome = any available clinical outcomes by gender, including mortality and disease severity. The search covered the period from January 1 to April 30, 2020. Exclusion criteria were: case reports/series, reviews, commentaries, languages other than English. Full-text, original articles were included. Data on study type, country, and patients' characteristics were extracted. Study quality was evaluated using the Newcastle-Ottawa scale (NOS). From a total of 950 hits generated by the database search, 85 articles fulfilling the inclusion criteria were selected. RESULTS: A random-effects meta-analysis was performed to compare mortality, recovery rates, and disease severity in men compared with women. The male to female ratio for cases was 1:0.9. A significant association was found between male sex and mortality (OR = 1.81; 95% CI 1.25-2.62), as well as a lower chance of recovery in men (OR = 0.72; 95% CI 0.55-0.95). Male patients were more likely to present with a severe form of COVID-19 (OR = 1.46; 95% CI 1.10-1.94). CONCLUSIONS: Males are slightly more susceptible to SARS-CoV2 infection, present with a more severe disease, and have a worse prognosis. Further studies are warranted to unravel the biological mechanisms underlying these observations.

Nasal polyps in eosinophilic granulomatosis with polyangiitis: Structured histopathology and CD105 expression.

PURPOSE: Distinguishing the prodromal nasal polyposis of eosinophilic granulomatosis with polyangiitis (EGPA) from chronic rhinosinusitis with nasal polyps (CRSwNP) is a challenge for rhinologists and rheumatologists. It has recently been reported that angiogenesis and CD105 expressed on vascular endothelial cells could have a role in the pathogenesis and development of nasal polyps. This exploratory study examined the structured histopathology of nasal polyps in patients with EGPA and CRSwNP, comparing CD105 expression in their nasal tissue with that of a control group with no chronic sinonasal inflammation. METHODS: A structured histopathological study was performed on surgical specimens of nasal tissue from 32 adults (13 with EGPA, 14 with CRSwNP, 5 controls), considering CD105 as a marker to determine microvessel density (MVD). RESULTS: The mean eosinophil count was higher in EGPA patients with tissue inflammation (p = .002), and in CRSwNP patients with sub-epithelial edema (p = .009). Neutrophil infiltration was significantly associated with severe tissue inflammation in EGPA patients (p = .04), but with the absence of fibrosis in CRSwNP patients (p = .04). In the EGPA group, CD105-MVD correlated with tissue eosinophil count (p = .05). Mean CD105-MVD was significantly higher in EGPA patients with mucosal ulceration (p = .004). In the CRSwNP group, a CD105-MVD correlated positively and significantly with tissue eosinophil count (p = .01). CONCLUSION: Alongside the known abundance of eosinophils, other cells might contribute to inflammatory processes. Neutrophils may amplify inflammation, eosinophil recruitment and tissue damage. CD105 expression in CRSwNP and EGPA nasal polyps supports the hypothesized involvement of angiogenesis in the pathogenesis and development of nasal polyps.

An update on serum biomarkers to assess axial spondyloarthritis and to guide treatment decision.

Axial spondyloarthritis (axSpA) is a group of debilitating, chronic, rheumatic conditions characterized by inflammation and new bone formation, mainly involving the spine and the sacroiliac joints. The lack of biomarkers in axSpA is well known. Despite significant treatment advances in recent years thanks to the introduction of drugs with a new mode of action, such as new biologic and targeted synthetic disease-modifying antirheumatic drugs, no relevant improvement in the identification of disease biomarkers has been achieved. Common parameters, such as erythrocyte sedimentation rate and C-reactive protein, which are routinely used to measure systemic inflammation, are the sole markers available to date and are not adequate to assess disease activity in all patients. The aim of this study is to review the most promising serum biomarkers that may help treatment decision in axSpA via a proper assessment of disease activity and identification of negative prognostic factors.

Spine and Sacroiliac Joints Lesions on Magnetic Resonance Imaging in Early Axial-Spondyloarthritis During 24-Months Follow-Up (Italian Arm of SPACE Study).

Objectives: Our study aimed to identify: (1) the prevalence of spine and pelvis magnetic resonance imaging (MRI-spine and MRI-SIJ) inflammatory and structural lesions in patients (pts) with a diagnosis of axial spondyloarthritis (axSpA); (2) the predictive factors for a severe disease pattern with a higher probability of radiographic progression. Materials and Methods: Seventy-five pts with low back pain (LBP) (≥3 months, ≤2 years, onset ≤45 years) underwent physical examination, questionnaires, laboratory tests, X-rays, MRI-spine, and MRI-SIJ at baseline (T0) and during a 24-months follow-up. Two expert rheumatologists made axSpA diagnosis and classification (according ASAS criteria). MRI-spine, MRI-SIJ and X-rays were scored independently by 2 readers following the SPARCC, mSASSS, and mNY-criteria. According to ASAS criteria, 21 pts fulfilled imaging arm only and 29 clinical arm with/without imaging arm; 25 pts did not fulfill ASAS criteria. Results: At T0 the mean ± SD LBP onset was 28.51 ± 8.05 years, 45.3% pts were male, 38.7% were HLA-B27+; 56% showed bone marrow oedema (BMO) at MRI-spine and 64% at MRI-SIJ. Signs of enthesitis were found in 58% pts in the thoracic spine. Eighteen (24%) pts presented BMO at MRI-spine with a negative MRI-SIJ. The prevalence of BMO lesions and the SPARCC SIJ and spine score decreased during the follow-up in the 2 cohorts meeting ASAS criteria. An early onset of LBP, a lower use of NSAIDs, a BASDAI>4 were identified as predictors of spine structural damage; the high SPARCC SIJ score appeared to be a predictor of SIJ structural damage. A higher mSASSS was predicted by a lower age of onset of LBP. Predictor of higher SPARCC spine was a higher NSAIDs and of higher SPARCC SIJ score the HLA-B27 positivity with increased inflammatory biomarkers. Conclusions: At T0 a significant prevalence of BMO lesions was observed both in SIJ and spine, with predominant involvement of thoracic district. Since positive MRI-spine images were observed in the absence of sacroiliitis, these findings seem to be relevant in the axSpA diagnosis. Early age of disease onset, long duration of LBP, increased inflammatory biomarkers, higher use of NSAIDs, male gender, HLA-B27 positivity, SPARCC SIJ score>2 appeared predictors of radiological damage and activity.