Distinctive clinical traits of lupus-related myocarditis: a multicentre retrospective study.

OBJECTIVES: Cardiovascular involvement in systemic lupus erythematosus (SLE) is frequent but little is known about possible distinctive traits of SLE-related myocarditis (myoSLE) in comparison to patients with SLE (onlySLE) or myocarditis alone (onlyMyo). METHODS: A retrospective analysis was performed comparing patients with myoSLE (n = 25) from three centres with consecutive patients with onlySLE (n = 279) and onlyMyo (n = 88). SLE patients were dichotomised by disease duration ≤1 vs >1 year into recent onlySLE/early myoSLE vs longstanding onlySLE/late myoSLE. Further stratification into disease duration of 1-5, 5-10 and >10 years was also performed. SLE disease activity index 2000 (SLEDAI-2K) was used to estimate disease activity. Myocarditis was diagnosed through biopsy or magnetic resonance. RESULTS: Women were significantly more frequent among myoSLE than among onlyMyo (72% vs 43%; p= 0.013). Compared with onlyMyo, myoSLE patients had a higher frequency of conduction abnormalities (22% vs 5%; p= 0.046) and presented with numerically higher frequencies of left ventricular function compromise (48% vs 30%), along with higher pro-brain natriuretic peptide levels. Inflammation markers were higher in myoSLE compared with onlyMyo and to patients with onlySLE with >10 years of disease duration. SLEDAI-2K was significantly higher in late myoSLE than in longstanding onlySLE. Antiphospholipid syndrome was more frequent in myoSLE than in onlySLE. Multivariate analysis showed an association among myoSLE, anti-beta-2-glycoprotein I antibodies (aB2GPI, p= 0.014) and a higher number of involved British Isles Lupus Assessment Group domains in patient history (p= 0.003). CONCLUSION: myoSLE has unique clinical traits compared with other forms of myocarditis and is associated with aB2GPI and a more severe SLE course.

Clinical Characteristics and Outcomes of Polyarteritis Nodosa: An International Study.

OBJECTIVE: We describe the demographics, clinical features, disease course, and survival of polyarteritis nodosa (PAN) through an international collaboration (GLOBAL-PAN). METHODS: Patients with PAN were recruited between 1990 and 2020 from observational cohorts of nine countries across Europe, Japan, and North America. Eligibility was retrospectively defined using the European Medicines Agency classification algorithm. Patients with PAN related to hepatitis B virus (n = 12) and two monogenic diseases mimicking PAN, deficiency of adenosine deaminase 2 enzyme (n = 16) or familial Mediterranean fever (n = 11), were excluded. Data regarding organ involvement, relapse, disease-related damage, and survival were analyzed. RESULTS: Three hundred fifty-eight patients (female:male ratio 174:184), including those with systemic PAN (sPAN, n = 282) and cutaneous PAN (n = 76), were included. Twenty-five were pediatric onset. Mean ± SD age at diagnosis was 44.3 ± 18.1 years. Constitutional symptoms (71.5%), cutaneous involvement (70.5%), musculoskeletal findings (69.1%), and neurologic features (48.0%) were common manifestations. Among patients with sPAN, gastrointestinal involvement and proteinuria over 400 mg/day were reported in 52.2% and 11.2%, respectively. During a median (interquartile range) 59.6 (99.5) months of follow-up, relapse occurred in 48.5% of patients. One, 5- and 10-year survival rates for sPAN were 97.1%, 94.0%, and 89.0%, respectively. Predictors of death for sPAN included age ≥65 years at diagnosis, serum creatinine at diagnosis >140 µmol/L, gastrointestinal manifestations, and central nervous system (CNS) involvement. CONCLUSION: The spectrum of PAN remains a complex, multifaceted disease. Relapse is common. Age ≥65 years and serum creatinine >140 µmol/L at diagnosis, as well as gastrointestinal and CNS involvement, are independent predictors of death in sPAN.

Dupilumab for relapsing or refractory sinonasal and/or asthma manifestations in eosinophilic granulomatosis with polyangiitis: a European retrospective study.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is often associated with glucocorticoid-dependent asthma and/or ear, nose and throat (ENT) manifestations. When immunosuppressants and/or mepolizumab are ineffective, dupilumab could be an option. We describe the safety and efficacy of off-label use of dupilumab in relapsing and/or refractory EGPA. PATIENTS AND METHODS: We conducted an observational multicentre study of EGPA patients treated with dupilumab. Complete response was defined by Birmingham Vasculitis Activity Score (BVAS)=0 and prednisone dose ≤4 mg/day, and partial response by BVAS=0 and prednisone dose >4 mg/day. Eosinophilia was defined as an eosinophil count >500/mm3. RESULTS: Fifty-one patients were included. The primary indication for dupilumab was disabling ENT symptoms in 92%. After a median follow-up of 13.1 months, 18 patients (35%) reported adverse events (AEs), including two serious AEs. Eosinophilia was reported in 34 patients (67%), with a peak of 2195/mm3 (IQR 1268-4501) occurring at 13 weeks (IQR 4-36) and was associated with relapse in 41%. Twenty-one patients (41%) achieved a complete response and 12 (24%) a partial response. Sixteen (31%) patients experienced an EGPA relapse while on dupilumab, which was associated with blood eosinophilia in 14/16 (88%) patients. The median eosinophil count at the start of dupilumab was significantly lower in relapsers than in non-relapsers, as was the median time between stopping anti-IL-5/IL-5R and switching to dupilumab. CONCLUSION: These results suggest that dupilumab may be effective in treating patients with EGPA-related ENT manifestations. However, EGPA flares occurred in one-third of patients and were preceded by eosinophilia in 88%, suggesting that caution is required.

Early increase in eosinophil count may predict long-term hypereosinophilia during dupilumab treatment: a 2-year observational study.

KEY POINTS: In a limited subset of patients, dupilumab-induced hypereosinophilia is persistent. Two-month follow-up eosinophil count may predict long-lasting hypereosinophilia.

Role of systemic immunosuppression on subglottic stenosis in granulomatosis with polyangiitis: Analysis of a single-centre cohort.

PURPOSE: Subglottic stenosis (SGS) is a potentially life-threatening manifestation of granulomatosis with polyangiitis (GPA). Endoscopic dilation is effective, but relapses are frequent and the benefit of systemic immunosuppression in this setting is still controversial. We aimed to investigate the role of immunosuppressive treatment on SGS relapse risk. METHODS: This is a retrospective observational study based on review of medical charts among our cohort of patients with GPA. RESULTS: Twenty-one patients with SGS-GPA were identified, with a prevalence of 20% among our entire GPA cohort (n = 105). Compared to patients without SGS, patients with SGS-GPA had an earlier disease onset (mean age 30.2 vs. 47.3 years, p<0.001), and lower BVAS (mean 10.5 vs 13.5; p = 0.018). Five patients didn't receive systemic immunosuppression for SGS and they all (100%) relapsed after the first procedure, while among medical treatment group relapse rate was 44% (p = 0.045). When single treatment regimens are considered, rituximab (RTX) and cyclophosphamide (CYC) yielded a protective role towards the need of subsequent dilation procedure after the first if compared with absence of medical treatment. Patients with SGS and generalized disease, who initially received either a RTX- or a CYC-based induction treatment, and higher cumulative doses of glucocorticoids, showed a delayed median time to SGS relapse (36 vs. 12 months, p = 0.024). CONCLUSIONS: Subglottic stenosis is highly prevalent in patients with GPA and may define a milder systemic disease subset occurring more frequently in younger patients. Systemic immunosuppression provides benefit in preventing recurrence of SGS in GPA patients and regimens based on cyclophosphamide or rituximab might have a non-redundant role in this setting.

Mepolizumab for Eosinophilic Granulomatosis With Polyangiitis: A European Multicenter Observational Study.

OBJECTIVE: Mepolizumab proved to be an efficacious treatment for eosinophilic granulomatosis with polyangiitis (EGPA) at a dose of 300 mg every 4 weeks in the randomized, controlled MIRRA trial. In a few recently reported studies, successful real-life experiences with the approved dose for treating severe eosinophilic asthma (100 mg every 4 weeks) were observed. We undertook this study to assess the effectiveness and safety of mepolizumab 100 mg every 4 weeks and 300 mg every 4 weeks in a large European EGPA cohort. METHODS: We included all patients with EGPA treated with mepolizumab at the recruiting centers in 2015-2020. Treatment response was evaluated from 3 months to 24 months after initiation of mepolizumab. Complete response to treatment was defined as no disease activity (Birmingham Vasculitis Activity Score [BVAS] = 0) and a prednisolone or prednisone dose (or equivalent) of ≤4 mg/day. Respiratory outcomes included asthma and ear, nose, and throat (ENT) exacerbations. RESULTS: Two hundred three patients, of whom 191 received a stable dose of mepolizumab (158 received 100 mg every 4 weeks and 33 received 300 mg every 4 weeks) were included. Twenty-five patients (12.3%) had a complete response to treatment at 3 months. Complete response rates increased to 30.4% and 35.7% at 12 months and 24 months, respectively, and rates were comparable between mepolizumab 100 mg every 4 weeks and 300 mg every 4 weeks. Mepolizumab led to a significant reduction in BVAS score, prednisone dose, and eosinophil counts from 3 months to 24 months, with no significant differences observed between 100 mg every 4 weeks and 300 mg every 4 weeks. Eighty-two patients (40.4%) experienced asthma exacerbations (57 of 158 [36%] who received 100 mg every 4 weeks; 17 of 33 [52%] who received 300 mg every 4 weeks), and 31 patients (15.3%) experienced ENT exacerbations. Forty-four patients (21.7%) experienced adverse events (AEs), most of which were nonserious AEs (38 of 44). CONCLUSION: Mepolizumab at both 100 mg every 4 weeks and 300 mg every 4 weeks is effective for the treatment of EGPA. The 2 doses should be compared in the setting of a controlled trial.

Palliative care in a COVID-19 Internal Medicine ward: A preliminary report.

BACKGROUND: in the current pandemic emergency, increased attention has given to treating symptoms that cause suffering in patients with COVID-19. This study aims to describe the role of palliative care in the management of these patients. METHODS: palliative consultation was requested by the staff as per protocol. In brief, the criteria for referring patients to a palliative care physician or to undergo palliative care were left to the discretion of the physician in charge. We recorded data regarding age, gender, length of stay, type of discharge (dead or alive, and transfer to long-term or hospice facilities). RESULTS: Between March 18 to May 8, 2020, 412 patients with COVID-19 were admitted to the Internal Medicine wards of Magenta Hospital, Italy. The palliative care physician was directly involved in 105 cases (25.5%) and performed 236 consultations. Of the 105 patients who received palliative care counselling, 66 (63%) died. The average number of days in care was 2.26 days. The principal reason for counseling was controlling symptoms (54%) and 12% deal with the end of life management. The prevalent symptom, among those which led to the counseling, was restlessness/agitation (41%), followed by emotional issues (26%) such as anxiety, fear, and demoralization. In only 20% of cases, dyspnoea was the reason for symptomatic treatment. CONCLUSIONS: A large number of hospitalized Covid-19 patients are at high risk of clinical deterioration and death. This leads to the opportunity to integrate a palliative physician into the staff, who treat these patients. There is an urgent need for protocol standardization and formal trials to verify the effectiveness of this approach.

Obesity and its role in the management of rheumatoid and psoriatic arthritis.

In the last decade, interest has been growing in the relationship between obesity and several other clinical conditions, besides the well-established links between body mass index (BMI) and cardiovascular diseases or cancer. A particular focus has been put on the impact of a higher BMI on immune-mediated diseases such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Obesity has been found to be associated with greater arthritis activity and a reduced probability of response to anti-tumor necrosis factor (TNF) agents. On the other hand, weight loss increases the chances of treatment success. Although the direct effect of a higher body mass on drug clearance might in part account for this obesity-related effect, other biological mechanisms could be involved. The evidence of a negative influence of obesity on arthritis treatment is particularly strong as far as anti-TNF inhibition is concerned; on the contrary, the response to biologic agents targeting interleukin-6, cytotoxic T lymphocyte antigen 4, or CD20 seems not to be negatively affected by a higher BMI. In this review, we will consider the main studies investigating the influence of obesity on anti-rheumatic treatment in RA and PsA patients. We will also try to hypothesize about a possible pathogenic explanation of this phenomenon and its role in the choice of an appropriate and personalized therapy.

Evaluation of Endothelial Function by Flow-Mediated Dilation: a Comprehensive Review in Rheumatic Disease.

Flow-mediated dilation (FMD) represents a non-invasive marker of endothelial function to evaluate vascular homeostasis, which reflects the effects of several mechanisms, including vessel tone regulation, cell proliferation, and inflammatory responses. Beyond classical atherosclerotic risk factors such as arterial hypertension, diabetes mellitus, smoking, obesity, and dyslipidemia, chronic inflammation contributes to the endothelial dysfunction causing plaque formation and there is growing evidence of a significantly higher cardiovascular morbidity associated with autoimmune diseases. The endothelium reacts to several endogenous and exogenous stimuli, through surface receptors and intracellular signalling, and releases numerous vasoactive substances, including endothelins, prostacyclins, and nitric oxide (NO). Chronic inflammatory rheumatic diseases are commonly associated with decreased endothelial NO production, vascular damage, and premature atherosclerosis. Despite partially eclipsed by pulse wave velocity measure in the modern scientific literature, we provide a comprehensive overview and critically discuss the available data supporting FMD as a surrogate marker of endothelial function and, therefore, its potential role in predicting early atherosclerosis in patients with rheumatic diseases.

Safety and efficacy of percutaneous nephrolithotomy in the Galdakao - Modified Supine Valdivia position: A prospective analysis.

OBJECTIVE: Aim of the present study was to evaluate the safety and efficacy of Percutaneous Nephrolithotomy (PCNL) in the Galdakao- Modified Supine Valdivia (GMSV) position in order to predict operative time, stone-free rate and onset of complications taking into account comorbidity, stone-related parameters and anatomic upper urinary tract abnormalities. MATERIAL AND METHODS: A prospective evaluation of patients who underwent to PCNL in GMSV position for renal stones > 2 cm, from January 2009 to February 2015 was performed. According to the technique, upper urinary tract abnormalities, stone chemical and morphological characteristics, and patients' history were matched with operative outcome, in terms of stone-free, intervention time and incidence of perioperative complications. RESULTS: Seventy-two cases were collected; mean operative time was 105 minutes (DS 41): staghorn stones and the presence of comorbidity resulted statistically significant variables. The complication-rate resulted in line with data showed in literature: hyperpyrexia and hemorrhage were the more frequently complications found. The overall stone-free was reached in 48 patients (67%), and it was influenced by patients' anatomic abnormalities. CONCLUSIONS: In the treatment of renal stones, PCNL may be a safe and effective choice; nevertheless, patients' anatomic abnormalities or staghorn-stones may influence the outcomes. Thus, a prospective study with a larger population is needed to verify our outcomes.