Large-vessel involvement in ANCA-associated vasculitis: A multicenter case-control study.

OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) primarily affects small vessels. Large-vessel involvement (LVI) is rare. We aimed to describe the characteristics of LVI, to identify associated risk factors, and to describe its therapeutic management. METHODS: This multicenter case-control (1:2) study included patients with AAV according to the ACR/EULAR classification and LVI as defined by the Chapel Hill nomenclature, together with controls matched for age, sex, and AAV type. RESULTS: We included 26 patients, 15 (58 %) of whom were men, with a mean age of 56.0 ± 17.1 years. The patients had granulomatosis with polyangiitis (n = 20), or microscopic polyangiitis (n = 6). The affected vessels included the aorta (n = 18; 69 %) supra-aortic trunks (n = 9; 35 %), lower-limb arteries (n = 5; 19 %), mesenteric arteries (n = 5; 19 %), renal arteries (n = 4; 15 %), and upper-limb arteries (n = 2; 8 %). Imaging showed wall thickening (n = 10; 38 %), perivascular inflammation (n = 8; 31 %), aneurysms (n = 5; 19 %), and stenosis (n = 4; 15 %). Comparisons with the control group revealed that LVI was significantly associated with neurological manifestations (OR=3.23 [95 % CI: 1.11-10.01, p = 0.03]), but not with cardiovascular risk factors (OR=0.70 [95 % CI: 0.23-2.21, p = 0.60]), or AAV relapse (OR=2.01 [95 % CI: 0.70-5.88, p = 0.16]). All patients received corticosteroids, in combination with an immunosuppressant in 24 (92 %), mostly cyclophosphamide (n = 10, 38 %) or rituximab (n = 9, 35 %). CONCLUSION: Regardless of distinctions based on vessel size, clinicians should consider LVI as a potential manifestation of AAV, with the aorta commonly affected. The risk of developing LVI appears to be greater for clinical phenotypes of AAV with neurological involvement. Standard AAV treatment can be used to manage LVI.

Clinical significance of the anti-Nucleolar Organizer Region 90 antibodies (NOR90) in systemic sclerosis: Analysis of the European Scleroderma Trials and Research (EUSTAR) cohort and a systematic literature review.

BACKGROUND: The anti-Nucleolar Organizer Region 90 antibodies (NOR90) are rare antinuclear antibodies (ANA) reported in systemic sclerosis (SSc). Especially due to low prevalence, the clinical relevance of NOR90 in SSc remains uncertain. OBJECTIVES: To analyze the clinical associations of NOR90 in patients with SSc in a multicentric cohort. METHODS: Post-hoc, cross-sectional study of prospectively collected data from the European Scleroderma Trials and Research (EUSTAR) database, with additional information on NOR90. Further, we performed a systematic literature search, using the terms "systemic sclerosis" and "NOR90" across three databases: Medline via PubMed, Scopus, and Thomson Reuters' Web of Science Core Collection, from inception to November 1st, 2023. RESULTS: Overall, 1318 patients with SSc were included (mean age 58.3 ± 13.7 years, 81.3 % female), of whom 44 (3.3 %) were positive for NOR90. Of these, 32 were also positive for one of the SSc-criteria antibodies: 9/44 (20.5 %) for anti-topoisomerase I, 18/42 (42.9 %) for anti-centromere, and 5/40 (12.5 %) for anti-RNA polymerase III. NOR90-positive patients were more frequently female, had lower modified Rodnan skin score (mRSS), and lower prevalence of upper and lower gastrointestinal (GI) symptoms compared to NOR90-negative patients. In multivariable analysis, NOR90 remained significantly associated with lower mRSS and less frequent GI symptoms. The literature search identified 17 articles, including a total number of 87 NOR90-positive out of 3357 SSc patients, corresponding to an overall prevalence of 2.6 %. CONCLUSION: To our best knowledge, this is the largest SSc cohort tested for NOR90 to date, confirming the NOR90 prevalence in SSc patients is around 3 %.

Health status and concomitant prescription of immunosuppressants are risk factors for hydroxychloroquine non-adherence in systemic lupus patients with prolonged inactive disease.

Background/objective The objectives of this paper are to assess the extent of and the factors associated with hydroxychloroquine (HCQ) non-adherence in systemic lupus erythematosus (SLE) patients with prolonged inactive disease and to investigate relationships between blood HCQ concentration and quality of life (QoL). Methods Consecutive SLE patients, in remission for at least one year and taking a stable dose of HCQ were investigated. At study entry (T0) and six months later (T6) a blood venous sample was taken to measure whole blood concentration of [HCQ] and desethylchloroquine ([DCQ]). Moreover, at T0 each patient completed validated questionnaires assessing QoL, disability, anxiety, depression and visual analogue scales for fatigue, pain, general health (GH), and self-assessment of disease activity. Results Eighty-three patients with a median [HCQ] of 327 ng/ml were enrolled. At T0, 24 (29%) were defined as non-adherent ([HCQ] < 100 ng/ml). At multiple logistic regression analysis the physical summary of SF-36 ( p = 0.038), and the concomitant use of immunosuppressants ( p = 0.010) were independently associated with non-adherence. A significant increase of HCQ adherence was observed at T6 ( p < 0.05). Conclusions A better health status and the concomitant prescription of immunosuppressants represent risk factors for HCQ non-adherence in SLE patients in remission. Monitoring HCQ levels might represent an important opportunity to improve adherence.

Glucocorticoids in systemic sclerosis: patients' beliefs and treatment adherence.

OBJECTIVES: To investigate how chronic intake of glucocorticoids (GCs) is perceived by patients with systemic sclerosis (SSc) in terms of necessity and concerns, and whether such beliefs influence treatment adherence. METHOD: Ninety-eight consecutive SSc patients who they had been taking oral GCs for > 3 months prior to the study were enrolled. All patients underwent a clinical evaluation and laboratory investigations, and were asked to complete four self-administered questionnaires: the Beliefs about Medicines Questionnaire (Specific-BMQ), the four-item Morisky Medication Adherence Scale (MMAS-4), the 36-item Short Form Health Survey (SF-36), and the Health Assessment Questionnaire Disability Index (HAQ-DI). Moreover, patients answered two additional questions investigating their knowledge about GC-related adverse events (AEs). RESULTS: Seventy-seven patients (83.6%) believed in the necessity of GCs for maintaining health but 72.8% also reported concerns about potential AEs to GCs. A high adherence rate was recorded in 64.1% of patients. Only about 20% of patients reported knowing that a daily GC dose and treatment duration influence the burden of GC-related AEs. Patients who believed that GC-related AEs were influenced by the dose scored lower concerns (p = 0.043) and were more frequently labelled as accepting (perceiving high necessity and low concerns) (p = 0.009). CONCLUSIONS: The majority of patients taking GCs perceived them as necessary, but high concerns about chronic GC use exist. Patients with a poorer knowledge of the factors associated with GC-related AEs and those with a poorer quality of life were the most worried about these compounds. Experimental studies assessing the efficacy of educational programmes aiming to increase the adherence to GC therapy should be planned in these patients.

Predictive role of capillaroscopic skin ulcer risk index in systemic sclerosis: a multicentre validation study.

UNLABELLED: Introduction The early detection of systemic sclerosis (SSc) patients at high risk of developing digital ulcers could allow preventive treatment, with a reduction of morbidity and social costs. In 2009, a quantitative score, the capillaroscopic skin ulcer risk index (CSURI), calculated according to the formula 'D×M/N(2'), was proposed, which was highly predictive of the appearance of scleroderma digital ulcers within 3 months of capillaroscopic evaluation. OBJECTIVES: This multicentre study aims to validate the predictive value and reproducibility of CSURI in a large population of SSc patients. METHODS: CSURI was analysed in 229 unselected SSc patients by nailfold videocapillaroscopy (NVC). All patients were re-evaluated 3 months later with regard to the persistence and/or appearance of new digital ulcers. RESULTS: 57 of 229 patients presented with digital ulcers after 3 months. The receiver operating characteristic curve analysis showed an area under the curve of 0.884 (95% CI 0.835 to 0.922), with specificity and sensitivity of 81.4% (95% CI 74.8 to 86.89) and 92.98% (95% CI 83.0 to 98.0), respectively, at the cut-off value of 2.96. The reproducibility of CSURI was validated on a random sample of 81 patients, with a κ-statistic measure of interrater agreement of 0.8514. CONCLUSIONS: The role of CSURI was confirmed in detecting scleroderma patients with a significantly high risk of developing digital ulcers within the first 3 months from NVC evaluation. CSURI is the only method validated to predict the appearance of digital ulcers and its introduction into routine clinical practice might help optimise the therapeutic strategy of these harmful SSc complications.

[Survival and death causes in 251 systemic sclerosis patients from a single Italian center]. / Sopravvivenza e cause di morte in 251 pazienti affetti da sclerosi sistemica arruolati in un singolo centro italiano.

OBJECTIVE: To investigate survival in Italian systemic sclerosis (SSc) patients from a tertiary center, reporting death causes. MATERIALS AND METHODS: We analyzed the charts of 251 SSc patients prospectively enrolled in our Rheumatology Unit from 2000 to 2008. Baseline characteristics were recorded. In 2008 the vital status and the causes of death were assessed. Overall and subgroup survival were analyzed by the Kaplan-Meier method and the log-rank test. RESULTS: In 2008, 82% of patients were alive, 8% were known to have died and 10% were lost to follow-up. Overall 5- and 8-year survival were 94.8% and 77.1%, respectively. Patients with an age greater than the median value of the cohort (χ²=4.4; p=0.036), diffuse cutaneous SSc (χ²=3.9; p=0.048), digital ulcers (χ²=6; p=0.015), articular (χ²=5.3; p=0.021), lung (χ²=5.6; p=0.018) and heart involvement (χ²=9.3; p=0.002) had a poorer survival than patients without these features. The majority of SSc-related deaths (60%) were secondary to interstitial lung disease and heart involvement (both 33.3%); 50% of non-SSc-related deaths were due to cancer. CONCLUSIONS: Our study reports an improvement in survival of Italian SSc patients during the last decade with respect to the previous ones. Moreover, a reduction in deaths from renal involvement and an increase in deaths from interstitial lung disease were recorded in Italian SSc patients. Our data are consistent with those from recent survival studies carried out on SSc patients from other geographic areas.

[Nephrolithiasis in patients with intestinal diseases]. / La nefrolitiasi nelle malattie intestinali.

Intestinal diseases may cause the formation of urinary stones through changes in the metabolism of oxalate, calcium, and uric acid. The oxalate that is excreted into urine comes from the catabolism of ascorbic acid and some amino acids or from intestinal absorption of food oxalate. Calcium is absorbed by the gut after the stimulation of active vitamin D and is excreted by the kidney under the control of the bone/parathyroid hormone axis. Uric acid is generated by the oxidation of exogenous and endogenous purine bases, is excreted by the kidney through glomerular filtration/tubular secretion, and is soluble in alkaline urine. Several data indicate that patients with inflammatory bowel diseases are at high risk of urinary stones containing calcium-oxalate salt or uric acid. Calcium-oxalate stones are caused by colonic oxalate hyperabsorption (secondary to intestinal dysfunction) or by parenteral nutrition. Uric acid stones are typical of patients with severe diarrhea and/or intestinal neostomy, that is, in patients with hyperconcentrated acidic urine. Relationships between malabsorptive intestinal diseases and urinary stones are less well defined. Preventive countermeasures are not the same for all disorders. Hyperoxaluria should be controlled by diets with a low content of lipids and oxalate but supplemented with calcium and probiotics. The presence of hyperconcentrated acidic urine should be controlled by correct hydration and administration of citrate.