Relationship between sex and clinical and imaging features of early axial spondyloarthritis: results from a 48 month follow-up (Italian arm of the SPondyloArthritis Caught Early (SPACE) study).

OBJECTIVES: To assess the association between sex and clinical and disease activity indices, and X-rays and magnetic resonance imaging (MRI) features, in early-stage axial spondyloarthritis (axSpA). METHOD: Baseline data analysis was conducted on the Italian SPACE cohort, including patients with chronic back pain (duration ≥ 3 months and ≤ 2 years; onset < 45 years). Patients underwent MRI and X-rays of the sacroiliac joints (SIJs) to establish the diagnosis of axSpA, according to Assessment of SpondyloArthritis international Society criteria and physician's judgement. Clinical features, disease activity and functional indices, and images were collected at baseline and yearly during 48 months. Spinal and SIJ X-rays and MRI images were scored by two readers following Spondyloarthritis Research Consortium of Canada (SPARCC), modified Stoke Ankylosing Spondylitis Spinal Score, and modified New York criteria. Characteristics of axSpA patients according to sex (male/female) were compared over time using descriptive statistics. RESULTS: Ninety-one patients had axSpA (83.5% non-radiographic; 16.5% radiographic); 47.3% were male. Males were younger, with shorter duration of axial symptoms, and more frequently had HLA-B27 positivity, radiographic sacroiliitis with a bilateral/symmetric pattern, and more signs of spondylitis. Females more frequently showed peripheral/entheseal involvement and the non-radiographic phenotype. Males showed increased pelvic/spinal radiographic progression and more often had active sacroiliitis on MRI. Although the frequency of inflammatory corner lesions did not differ between males and females, localization varied, with more cervical/thoracic MRI-spine lesions in females and more lumbar lesions in males. We observed a significant downward trend of SPARCC SIJ/spine scores in all patients, irrespective of sex. More fat lesions were observed on MRI-spine in females and on MRI-SIJ in males. CONCLUSION: Sex was associated with distinct axSpA features: females showed low-grade radiographic sacroiliitis and spinal progression, and a higher prevalence of cervical and thoracic spine MRI signs.

SARS-CoV-2 infection in patients with autoimmune rheumatic diseases in northeast Italy: A cross-sectional study on 916 patients.

BACKGROUND: Whether patients with autoimmune rheumatic diseases (ARD) have a higher risk for SARS-CoV-2 infection (COVID-19) and how SARS-CoV-2 pandemic impacts on adherence to therapy has not been fully elucidated. We assessed the rate and clinical presentation of COVID-19, and adherence to therapy in a large cohort of patients with ARD followed-up in a tertiary University-Hospital in Northeast Italy. METHODS: Between April 9th and April 25th, 2020, after SARS-CoV-2 infection peak, a telephone survey investigating the impact of COVID-19 on patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), ANCA-associated vasculitis (AAV), and idiopathic inflammatory myopathies (IIM) was administered. Demographics, disease activity status, therapy, occupational exposure, and adherence to social distancing advise were also collected. RESULTS: 916 patients (397 SLE, 182 AAV, 176 SSc, 111 RA, 50 IIM) completed the survey. 148 patients developed at least one symptom compatible with COVID-19 (cough 96, sore throat 64, fever 64, arthromyalgias 59, diarrhea 26, conjunctivitis 18, ageusia/hyposmia, 18). Among the 916 patients, 65 (7.1%) underwent SARS-CoV-2 nasopharyngeal swab (18 symptomatic and 47 asymptomatic), 2 (0.21%) tested positive, a proportion similar to that observed in the general population of the Veneto region. No deaths occurred. 31 patients (3.4%) withdrew ≥1 medication, mainly immunosuppressants or biologics. Adoption of social distancing was observed by 860 patients (93.9%), including 335 (36.6%) who adopted it before official lockdown. CONCLUSIONS: COVID-19 incidence seems to be similar in our cohort compared to the general population. Adherence to therapy and to social distancing advise was high.

Biomarkers, imaging and disease activity indices in patients with early axial spondyloarthritis: the Italian arm of the SpondyloArthritis-Caught-Early (SPACE) Study.

The study aimed to evaluate biomarkers facilitating early diagnosis of axial spondyloarthritis (axSpA) and correlations between them and disease activity parameters and imaging indexes. Patients with low back pain (LBP) (≥3 months, ≤2 years, onset ≤45 years) participating in the Italian arm of the SpondyloArthritis-Caught-Early SPACE study underwent a physical examination, questionnaires, laboratory tests, X-rays and MRI of the spine and sacroiliac joints (SIJ). An expert rheumatologist formulated axSpA diagnosis in accordance with Assessment of SpondyloArthritis International Society (ASAS) criteria. Disease activity and physical functioning were assessed using imaging, clinical and serological indices. Spine and SIJ MRI and X-rays were scored independently by 2 readers using the SPARCC, mSASSS and NY-criteria. Patients were classified as: subjects with signs of radiographic sacroiliitis (r-axSpA), subjects with signs of sacroiliitis on SIJ-MRI but not on X-rays (nr-axSpA MRI SIJ+) or subjects with no signs of sacroiliitis on MRI/X-rays but with >2 SpA features and signs of bone oedema on MRI spine (nr-axSpA MRI SIJ-/undifferentiated SpA). Significant differences were found in the prevalence of radiographic sacroiliitis, active sacroiliitis on MRI and SPARCC SIJ scores. Biomarker levels were not significantly increased in any of the patient groups. The correlations between IL-17 and IL-23 and other indices were not significant; correlations were found between IL-22 and BASFI, BASG1, HAQ, VAS pain, between mSASSS and MMP3, and between the latter and hsCRP. Although not significantly higher in any of the three groups, IL-22, MMP3 and hsCRP values were correlated with some disease activity indexes and with mSASSS. Large observational studies are required to confirm these preliminary findings.

Presence of multiple spondyloarthritis (SpA) features is important but not sufficient for a diagnosis of axial spondyloarthritis: data from the SPondyloArthritis Caught Early (SPACE) cohort.

OBJECTIVES: Concerns have been raised about overdiagnosis of axial spondyloarthritis (axSpA). We investigated whether patients with chronic back pain (CBP) of short duration and multiple SpA features are always diagnosed with axSpA by the rheumatologist, and to what extent fulfilment of the Assessment of SpondyloArthritis International Society (ASAS) axSpA criteria is associated with an axSpA diagnosis. METHODS: Baseline data from 500 patients from the SPondyloArthritis Caught Early cohort which includes patients with CBP (≥3 months, ≤2 years, onset <45 years) were analysed. All patients underwent full diagnostic workup including MRI of the sacroiliac joints (MRI-SI) and radiograph of sacroiliac joints (X-SI). For each patient, the total number of SpA features excluding sacroiliac imaging and human leucocyte antigen B27 (HLA-B27) status was calculated. RESULTS: Before sacroiliac imaging and HLA-B27 testing, 32% of patients had ≤1 SpA feature, 29% had 2 SpA features, 16% had 3 SpA features and 24% had ≥4 SpA features. A diagnosis of axSpA was made in 250 (50%) of the patients: 24% with ≤1 SpA feature, 43% with 2 SpA features, 62% with 3 SpA features and 85% with ≥4 SpA features. Of the 230 patients with a positive ASAS classification 40 (17.4%) did not have a diagnosis of axSpA. HLA-B27 positivity (OR 5.6; 95% CI 3.7 to 8.3) and any (MRI-SI and/or X-SI) positive imaging (OR 34.3; 95% CI 17.3 to 67.7) were strong determinants of an axSpA diagnosis. CONCLUSIONS: In this cohort of patients with CBP, neither the presence of numerous SpA features nor fulfilment of the ASAS classification criteria did automatically lead to a diagnosis axSpA. Positive imaging was considered particularly important in making a diagnosis of axSpA.

Spine and sacroiliac joints on magnetic resonance imaging in patients with early axial spondyloarthritis: prevalence of lesions and association with clinical and disease activity indices from the Italian group of the SPACE study.

Our aim was to determine the prevalence of spine and sacroiliac joint (SIJ) lesions on magnetic resonance imaging (MRI) in patients with early axial spondyloarthritis (axSpA) and their correlation with disease activity indices. Sixty patients with low back pain (LBP) (≥3 months, ≤2 years, onset ≤45 years), attending the SpA-clinic of the Unità Operativa Complessa Reumatologia of Padova [SpondyloArthritis-Caught-Early (SPACE) study], were studied following a protocol including physical examination, questionnaires, laboratory tests, X-rays and spine and SIJ MRI. Positive spine and SIJ MRI and X-rays images were scored independently by 2 readers using the SPARCC method, modified Stoke ankylosing spondylitis spine score and New York criteria. The axial pain and localization of MRI-lesions were referred to 4 sites: cervical/thoracic/lumbar spine and SIJ. All patients were classified into three groups: patients with signs of radiographic sacroiliitis (r-axSpA), patients without signs of r-axSpA but with signs of sacroiliitis on MRI (nr-axSpA MRI SIJ+), patients without signs of sacroiliitis on MRI and X-rays (nr-axSpA MRI SIJ-). The median age at LBP onset was 29.05±8.38 years; 51.6% of patients showed bone marrow edema (BME) in spine-MRI and 56.7% of patients in SIJ-MRI. Signs of enthesitis were found in 55% of patients in the thoracic district. Of the 55% of patients with BME on spine-MRI, 15% presented presented a negative SIJMRI. There was a significant difference between these cohorts with regard to the prevalence of radiographic sacroiliitis, active sacroiliitis on MRI and SPARCC SIJ score. The site of pain correlated statistically with BME lesions in thoracic and buttock districts. Since positive spine-MRI images were observed in absence of sacroiliitis, we can hypothesize that this finding could have a diagnostic significance in axSpA suspected axSpA.

Molecular mechanisms of pain in crystal-induced arthritis.

Crystal-induced arthritis (CIA) is characterized by an intense inflammatory reaction triggered by the deposition of monosodium urate, calcium pyrophosphate, and basic calcium phosphate crystals in articular and periarticular tissues. Severe, acute pain constitutes the most important clinical symptom in patients affected by these diseases. Pain along with redness, warmness, swelling, and stiffness in the affected joint arises abruptly in gout and disappears when the acute phase of the attack resolves. While an acute joint attack caused by calcium pyrophosphate crystals can mimic a gout flare, basic calcium phosphate crystal arthritis gives rise to a series of clinical manifestations, the most severe of which are calcific periarthritis, mostly asymptomatic, and a highly destructive arthritis known as Milwaukee shoulder syndrome, which is characterized by painful articular attacks. Pain development in CIA is mediated by several inflammatory substances that are formed after cell injury by crystals. The most important of these molecules, which exert their effects through different receptor subtypes present in both peripheral sensory neurons and the spinal cord, are prostaglandins, bradykinin, cytokines (in particular, interleukin (IL)-1ß), and substance P. The pharmacological treatment of pain in CIA is strictly associated with the treatment of acute phases and flares of the disease, during which crystals trigger the inflammatory response. According to international guidelines, colchicines, nonsteroidal anti-inflammatory drugs, and/or corticosteroids are first-line agents for the systemic treatment of acute CIA, while biologics, namely anti-IL-1ß agents, should be used only in particularly refractory cases.

Pain and microcrystalline arthritis.

Microcrystals are responsible for some of the most common and complex arthropathies which are often accompanied by intense, severe pain and inflammatory reactions. The main pathogens are crystals of monosodium urate (MSU), responsible for the gout, calcium pyrophosphate (CPP), which deposits also in various clinical forms of arthopathies, and basic calcium phosphate associated with osteoarthritis. In this context, the microcrystal arthritis is characterized by multiple, acute attacks followed by chronic pain, disability, impaired quality of life, and increased mortality. Given their chronic nature, they represent an ever more urgent public health problem. MSU and CPP crystals are also able to activate nociceptors. The pain in mycrocrystalline arthritis (MCA) is an expression of the inflammatory process. In the course of these diseases there is an abundant release of inflammatory molecules, including prostaglandins 2 and kinins. Interleukin-1 represents the most important cytokine released during the crystal-induced inflammatory process. Therefore, clinically, pain is the most important component of MCA, which lead to functional impairment and disability in a large proportion of the population. It is fundamental to diagnose these diseases as early as possible, and to this aim, to identify appropriate and specific targets for a timely therapeutic intervention.

Impact of hypertension on vascular remodeling in patients with psoriatic arthritis.

We studied the impact of hypertension along with traditional and new cardiovascular risk factors on the structural and functional properties of arteries in psoriatic arthritis (PsA) patients. We examined 42 PsA subjects (aged 51±9 years) stratified according to hypertensive status (19 normotensive, PsA-NT and 23 hypertensives, PsA-HT). Thirty-eight normotensive subjects (C-NT) and 23 hypertensives (C-HT) comparable by age and sex served as controls. Mean carotid intima-media thickness (mean-IMT) and mean of the maximum IMT (M-Max) were evaluated by ultrasound in carotid artery segment bilaterally. Post-occlusion flow-mediated dilation (FMD) of the brachial artery was evaluated by ultrasonography. These parameters were correlated with risk factors, markers of inflammation and disease activity. Values of mean-IMT were higher in both groups of PsA patients compared with C-NT (0.68 mm in PsA-NT and 0.75 mm in PsA-HT versus 0.61 mm in C-NT). PsA-HT displayed higher M-Max (0.95 mm) versus both C-HT (0.71 mm) and PsA-NT (0.79 mm). FMD was impaired in PsA subjects compared with C-NT (5.7% in PsA-NT and 6.0% PsA-HT versus 9.3% in C-NT), whereas there was no difference among PsA-HT, PsA-NT, and C-HT groups. Values of carotid IMT were directly related to tumor necrosis factor (TNF)-α, osteoprotegerin (OPG), blood pressure and lipid profile levels. FMD showed an inverse relationship with TNF-α and blood pressure, but no correlation with lipids. In conclusion, PsA per se implies a pro-atherogenic remodeling, which is enhanced by the hypertensive status. TNF-α and OPG may have an independent role in the development of such vascular damage.

[Subclinical atherosclerosis in patients with psoriatic arthritis: a case-control study. Preliminary data]. / Aterosclerosi subclinica in pazienti con artrite psoriasica: studio caso-controllo. Dati preliminari.

OBJECTIVE: The aim of this study was to evaluate the prevalence of subclinical atherosclerosis in patients with psoriatic arthritis (PsA), correlated with some traditional risk factors of atherosclerosis and with PsA-related disease factors. METHODS: Forty-one patients and 41 healthy subjects were evaluated for intima-media thickness (IMT) and flow-mediated dilation (FMD), using carotid duplex scanning. IMT values were expressed like IMT mean (cumulative mean of all the IMT mean) and M-MAX (cumulative mean of all the higher IMT). Subclinical atherosclerosis markers were correlated with age, body mass index (BMI) and blood pressure in both groups, with duration of arthritis, duration of psoriasis, tender and swollen joints, BASDAI (Bath Ankylosing Spondylitis Disease Activity Index), BASFI (Bath Ankylosing Spondylitis Functional Index), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in patients. RESULTS: IMT mean and M-MAX were both higher in PsA patients compared with controls (0.7+/-0.15 vs 0.62+/-0.09 mm; p<0.01 and 0.86+/-0.21 vs. 0.74+/-0.13 mm; p<0.01 respectively). FMD was smaller in patients than in controls (5.9+/-2 vs 7.5+/-2.8%; p<0.01). Univariate analysis showed a correlation between IMT mean and SBP (r=0.217; p=0.05) and a correlation between M-MAX and age (r=0.392; p<0.001), BMI (r=0.252; p<0.05), SBP (r=0.446; p<0.001) in both groups. In PsA patients M-MAX resulted correlated with ESR (r=0.338; p<0.05) and BASDAI (r=0.322; p<0.05). CONCLUSIONS: PsA patients exhibited endothelial dysfunctions which is an early marker of subclinical atherosclerosis, as well as an higher IMT. An interesting correlation between M-MAX and PsA activity index (ESR and BASDAI) was found.

[Methoxybutropate in the therapy of PID (pelvic inflammatory diseases)]. / Il metossibutropato nella terapia delle PID.

A study has been carried out on patients suffering from pelvic inflammatory disease (PID) in chronic form, so as to evaluate the effectiveness of treatment with methoxybutropate (Benflogin-Angelini). The study was carried out on 20 outpatients treated for eight weeks with 300 mg of methoxybutropate three times a day. The results have highlighted the noteworthy effectiveness and high tolerance of methoxybutropate in the treatment of PID.

[Dynamics of the cervical mucosae during hormonal contraception by low-dose estrogens. A controlled prospective clinical study]. / Dinamica delle mucose cervicali in corso di contraccezione ormonale a basso dosaggio di estrogeni. Studio clinico prospettico controllato.

The Authors report the results of a prospective clinical study by means of colposcopy, planimetric measurements of iodine-light areas, cytology and target biopsy on 140 women taking low-dosage oral contraceptives and 140 controls. A basal examination and a follow up control at a mean interval of 13 months (min. 6, max. 30 months) have been performed. Colposcopy has shown no qualitative changes during follow up, neither in cases nor in controls. Planimetric measurements have shown a significant reduction of Ectropion and AnTZ in cases in comparison to controls, and more NTZ both in cases and controls. Cytology has shown at follow up a higher and significant reduction of phlogosis and viral cytopathic effect in cases. The results related to CIN, although non significant because of the small case group and the relatively short follow up, appeared more favorable in cases. In conclusion, oral contraception appears not to negatively affect the uterine cervix as far as cervical cancer is concerned but possibly to be protective. Nevertheless a longer follow up and a wider case group are needed in order to reach definitive results.

[Colposcopic evaluation of cervical epithelium during oral contraception. A controlled clinical study]. / Valutazione colposcopica degli epiteli cervicali in corso di contraccezione orale. Studio clinico controllato.

The Authors report the results of a controlled clinical study by means of colposcopy, cytology and target biopsy on 525 oral contraceptive (O.C.) users and 519 controls. Except for age class 31-35, more iodine dark cervices are found in cases, more iodine light (AnTZ and/or ectropion) in controls. The difference, although not statistically significant, suggests a protective role of O.C. on cervical epithelia. In 34 women (15 cases and 19 controls) CIN has been diagnosed. O.C. users show a more favorable situation, except for ages over 30 exposed to O.C. for less than 24 months. The Authors hypothesize a protective role of O.C. in younger women. While women aged 30 or more still appear protected when exposed to O.C. for more than two years (possibly from younger ages), these results suggest some caution in beginning oral contraception after the 30th year of age.