Factors associated with fertility abnormalities in women with systemic lupus erythematosus: a systematic review and meta-analysis.

BACKGROUND: Fertility is thought to be not affected in women with systemic lupus erythematosus (SLE), however disease-related factors, psychosocial effects of chronic disease, as well as medications exposure might impair gonadal function. OBJECTIVE: This systematic literature review (SLR) aimed to explore clinical, hormonal, serological and treatment factors associated with fertility outcomes in women of childbearing age with SLE. METHODS: This SLR was conducted following the Preferred Reporting Items for systematic reviews and Meta-analysis (PRISMA) statement. All articles available in English (1972 - 30th April 2021) in Pubmed, EMBASE, Scopus and Cochrane Library were screened. Studies selection and data collection were performed by two independent reviewers. All data were extracted using a standardized template. The risk of bias of the included studies was assessed using the NIH risk-of-bias tool. RESULTS: Of 789 abstracts evaluated, we included in this review 46 studies, of which 1 SLR, 16 cross-sectional studies, 18 cohort studies, 10 observational studies and 1 case-series, with data pertaining to 4704 patients (mean age 31.5 ± 3.7 years, disease duration 83.27 ± 38.3 months). Definitions of premature ovarian failure (POF) adopted in the studies varied in terms of the number of months of amenorrhea considered and the age of onset of amenorrhea. Clinical factors associated with the development of POF were older age at the time of initiation of therapy, and older age at the onset of SLE disease. Cyclophosphamide exposure (CYC) and its cumulative dose influenced gonadal function in SLE women, leading to amenorrhoea and POF, as reported in 19 studies. Mycophenolate, azathioprine, calcineurin inhibitors and steroids associated with a lower risk of POF compared to CYC. POF was less frequent in patients co-treated with CYC and gonadotropin-releasing hormone analogues (GnRH-a) compared with patients not receiving GnRH-a (risk ratio 0.28, 95%-CI [0.14; 0.55]). 11 studies evaluated the impact of damage accrual and disease activity on ovarian reserve with conflicting evidence. Finally, 18 studies investigated exposure to hormonal and serological factors and, among others, neither anti-Müllerian Hormone nor anti-corpus luteum antibodies were associated with POF. CONCLUSION: The strongest evidence regarding management factors associated with fertility in SLE women of childbearing age remains the treatment with CYC, as well as its cumulative dosage. Hormonal and serological factors appeared not to impact fertility outcomes, but they might be used as a surrogate of fertility, especially during the treatment with disease-specific drugs.

Radiotherapy in cancer and rheumathoid arthritis patients: cancer treatment or control of articular flares? We can achieve both.

OBJECTIVE: The study was aimed to investigate the role of radiotherapy (RT) as a risk factor for reactivation or worsening of symptoms in patients affected by rheumatoid arthritis (RA) PATIENTS AND METHODS: This is a single-center retrospective observational study on RA patients who developed cancer requiring RT during the course of the disease. The control group consisted of RA patients with cancer who did not undergo RT. In both groups, the disease activity was evaluated at baseline and at 6 and 12 months through the DAS28 index. A relapse was defined as an increase of >20% in DAS28. A radiotherapist evaluated total and daily doses and timing of radiation. Acute and late toxicity was defined as events occurring within 90 days from the start and more than 90 days after the completion of RT, respectively. RESULTS: Seventy-two RA patients (38F/34M; mean age: 70±9 years; mean disease duration: 13±9 years), 29 (40.2%) of whom received radiotherapy (mean age 72.9±9 years), were enrolled. The most frequent malignancies were breast (27.2%), thyroid (9.8%), and skin (7%). Between radio-treated and non-radio-treated patients, no significant differences in RA reactivation (6/29 vs. 17/43; p=0.12) or mean exacerbation time (6.7 ± 4.9 months compared to 6.4 ± 4.1 months; p=0.78) were found. Overall, RT was well tolerated with low rates of both acute and late toxicity. CONCLUSIONS: In RA patients, RT was well tolerated and not associated with an increased risk of articular flares. Properly designed prospective clinical studies with a larger number of patients should be performed to confirm these data.

Conventional brain magnetic resonance imaging in the longitudinal evaluation of newly diagnosed systemic lupus erythematosus patients: a retrospective analysis from a single-centre cohort.

INTRODUCTION: Neuropsychiatric (NP) manifestations occur mostly in the early phases of the systemic lupus erythematosus (SLE) course. Nonspecific alterations are evident in conventional brain magnetic resonance imaging (MRI), regardless of clinically overt NP symptoms. The main aims of this study were to assess the prevalence of MRI abnormalities in newly diagnosed SLE, and to evaluate the impact of MRI changes during follow-up (FU) and the clinical course of NP symptoms. MATERIALS AND METHODS: Newly diagnosed SLE patients with a baseline brain MRI and with available repeated MRI during FU were retrospectively evaluated. White-matter lesions and atrophy were recorded, comparing NPSLE and non-NPSLE patients. Cox proportional hazard models were used to compare NP events during FU with MRI data. RESULTS: Forty-four patients were included, 22 with NP events attributed to SLE. The baseline MRI scan was abnormal in 21 patients (47.73%). New NP events occurred in 17 patients, and worsening was found in repeated MRIs in 12 (27.27%). A worsening of MRI was associated with higher occurrence of new NP events during FU (adjusted hazard ratio 3.946 (1.175-13.253)). CONCLUSION: Baseline MRI is useful in patients with an early diagnosis of SLE, allowing comparison with subsequent scans. In our study, radiological worsening of repeated brain MRI was associated with new NP events.

Diagnostic accuracy of a velcro sound detector (VECTOR) for interstitial lung disease in rheumatoid arthritis patients: the InSPIRAtE validation study (INterStitial pneumonia in rheumatoid ArThritis with an electronic device).

BACKGROUND: Interstitial lung disease (ILD) is a severe systemic manifestation of rheumatoid arthritis (RA). High-resolution computed tomography (HRCT) represents the gold standard for the diagnosis of ILD, but its routine use for screening programs is not advisable because of both high cost and X-ray exposure. Velcro crackles at lung auscultation occur very early in the course of interstitial pneumonia, and their detection is an indication for HRCT. Recently, we developed an algorithm (VECTOR) to detect the presence of Velcro crackles in pulmonary sounds and showed good results in a small sample of RA patients. The aim of the present investigation was to validate the diagnostic accuracy of VECTOR in a larger population of RA patients, compared with that of the reference standard of HRCT, from a multicentre study. METHODS: To avoid X-ray exposure, we enrolled 137 consecutive RA patients who had recently undergone HRCT. Lung sounds of all patients were recorded in 4 pulmonary fields bilaterally with a commercial electronic stethoscope (ES); subsequently, all HRCT images were blindly evaluated by a radiologist, and audio data were analysed by means of VECTOR. RESULTS: Fifty-nine of 137 patients showed ILD (43.1%). VECTOR correctly classified 115/137 patients, showing a diagnostic accuracy of 83.9% and a sensitivity and specificity of 93.2 and 76.9%, respectively. CONCLUSIONS: VECTOR may represent the first validated tool for the screening of RA patients who are suspected for ILD and who should be directed to HRCT for the diagnosis. Moreover, early identification of RA-ILD could contribute to the design of prospective studies aimed at elucidating unclear aspects of the disease.

Global Performance Status Score: A New Tool to Assess Physical Performance in Kidney Transplant Patients.

BACKGROUND: Information on physical performance in renal transplantation is limited because of the shortage of specifically designed evaluation instruments. Therefore, we elaborated and validated the Global Performance Status (GloPerSta) score to provide a new and comprehensive tool, exploring the different components of physical performance in kidney transplant patients. METHODS: We elaborated the GloPerSta score on the basis of the data obtained from a cross-sectional study, in which we evaluated the physical performance of a cohort of kidney transplant patients. The results of these analyses were weighted to describe the different contribution of any single test, via the generation of a structural equation model, resulting in the definition of the GloPerSta. Then, to internally validate this score, we studied its correlation with clinical parameters and quality of life (evaluated as KDQOL-SF, Kidney Disease Quality of Life-Short Form) in the same patient population. RESULTS: We enrolled 132 patients in whom the functional tests revealed a great heterogeneity. GloPerSta allowed the stratification of the patients in 3 different physical performance categories (low: score 0-11; medium: 12-22; high: 23-33). Internal validation showed that GloPerSta was directly and significantly correlated with the quality of life and allograft function, independent of the time from transplantation. CONCLUSIONS: The GloPerSta is a reliable tool to assess physical performance in a kidney transplant population. Its application might be of help in identifying patients needing intensive and personalized rehabilitation programs.

Application of SLICC classification criteria in undifferentiated connective tissue disease and evolution in systemic lupus erythematosus: analysis of a large monocentric cohort with a long-term follow-up.

Objectives The objectives of this study were to analyse the performance of the Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria for systemic lupus erythematosus (SLE) in a large cohort of undifferentiated connective tissue disease (UCTD) population at onset of the disease and during a long-term follow-up of 15 years (1999-2013) and to evaluate the transition from UCTD to SLE, according to American College of Rheumatology (ACR) 1997 and SLICC 2012 classification criteria. Methods A cohort of patients who met the classification criteria proposed by Mosca et al. for UCTD, were analysed. The SLICC 2012 classification criteria for SLE were retrospectively applied to each patient at the time of the diagnosis (T0) and also periodically re-applied and compared to ACR 1997 criteria at three different time points in the follow-up. Results 329 patients were enrolled. According to inclusion criteria at T0 no patient met the SLE/ACR criteria, whilst, retrospectively applying the SLE/SLICC criteria, 44 patients already satisfied this set of criteria for SLE. During the follow-up 23 new patients reached the SLE/SLICC criteria and 14 patients met the ACR criteria with a stable rate of progression to SLE over time. Acute or subacute skin rash, antiphospholipid antibody (aPL) positivity and serositis were the variables correlated to the evolution to SLE. Conclusions In our UCTD population, the application of SLICC classification criteria for SLE at disease onset allowed identification of a proportion of otherwise missed SLE cases; during follow-up, and compared with ACR criteria, SLICC criteria expanded the number of patients classifiable as SLE otherwise classified as UCTD.