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VEXAS syndrome is a recently described autoinflammatory syndrome caused by the somatic acquisition of UBA1 mutations in myeloid precursors and is frequently associated with hematologic malignancies, chiefly myelodysplastic syndromes. Disease presentation can mimic several rheumatologic disorders, delaying the diagnosis. We describe a case of atypical presentation resembling late-onset axial spondylarthritis, later progressing to a systemic inflammatory syndrome with chondritis, cutaneous vasculitis, and transfusion-dependent anemia, requiring high doses of steroids. Ruxolitinib was used as the first steroid-sparing strategy without response. However, azacitidine showed activity in controlling both inflammation and the mutant clone. This case raises the question of whether azacitidine's anti-inflammatory effects are dependent on or independent of clonal control. We discuss the potential relevance of molecular remission in VEXAS syndrome and highlight the importance of a multidisciplinary team for the care of such complex patients.
Subject(s)
Azacitidine , Sacroiliitis , Ubiquitin-Activating Enzymes , Humans , Azacitidine/therapeutic use , Sacroiliitis/drug therapy , Sacroiliitis/diagnosis , Sacroiliitis/genetics , Ubiquitin-Activating Enzymes/genetics , Mutation , Male , Middle Aged , Treatment Outcome , Myelodysplastic Syndromes/drug therapy , Myelodysplastic Syndromes/genetics , Myelodysplastic Syndromes/diagnosisABSTRACT
OBJECTIVE: To assess the diagnostic value for GCA in adding the axillary arteries (AX) to the temporal artery (TA) ultrasound, particularly in patients with a cranial phenotype of the disease; and to investigate the utility of facial (FA), occipital (OC), subclavian (SC), and common carotid (CC) ultrasound in patients with suspected GCA. METHODS: Patients with new-onset GCA and a positive ultrasound of the TA, AX, FA, OC, SC or CC, followed at the rheumatology departments of two academic centres, were retrospectively included. RESULTS: 230 patients were assessed. TA halo sign was identified in 206/230 (89.6%) cases, FA in 40/82 (48.8%), OC in 17/69 (24.6%), AX in 56/230 (24.3%), SC in 31/57 (54.4%), and CC in 14/68 (20.6%). Negative TA ultrasound was found in 24/230 (10.4%) patients: 22 had AX involvement, 1 exclusive OC involvement and 1 exclusive SC involvement. Adding AX evaluation to the TA ultrasound increased the diagnostic yield for GCA in 9.6%, whereas adding OC or SCs to the TA and AX ultrasound increased it in 1.4% and 1.8%, respectively. No value was found in adding the FA or CCs. Notably, 13 patients with cranial symptoms and 4 with exclusively cranial symptoms showed negative TA ultrasound but positive AX ultrasound. CONCLUSION: Adding the evaluation of AXs to the TA ultrasound increased the number of patients diagnosed with GCA, even in cases of predominantly cranial symptoms. In the subset of patients where these arteries were assessed, no substantial benefit was found in adding the FA, OC, SC or CC arteries to the TA and AX ultrasonographic assessment.
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Objectives: Systemic extraglandular involvement in SS has been reported in one-third of patients but may be more frequent. We aimed to evaluate systemic disease prevalence at baseline and throughout follow-up and find its predictors. Methods: We conducted a retrospective cohort study including SS patients followed in a tertiary centre. The cumulative EULAR SS disease activity index (ESSDAI) was calculated by adding each domain's maximum score throughout follow-up. We identified independent predictors of systemic involvement (ESSDAI ≥1 at baseline and/or follow-up) through logistic regression modelling. A survival analysis was conducted to identify predictors of new/worsening ESSDAI domains. Results: A total of 216 patients were included, most of whom had systemic involvement (86%), frequently at diagnosis (76%). Biological (53%) and articular ESSDAI domains (44%) were most commonly involved, but all were affected at least once. Around half of the patients with baseline systemic disease developed an additional/worsening domain throughout follow-up. Although most patients had low disease activity at baseline, 60% eventually reached moderately active disease. Younger age at diagnosis [odds ratio (OR) 0.95 (95% CI 0.91, 0.99)], a positive minor salivary gland biopsy [OR 4.08 (95% CI 1.40, 11.86)] and RF [OR 4.67 (95% CI 1.52, 14.33)] were independent predictors of systemic involvement. Patients with baseline constitutional involvement [hazard ratio (HR) 2.23 (95% CI 1.13, 4.40)] and RF [HR 1.89 (95% CI 1.20, 3.00)] were more likely to develop new/worsening systemic disease activity. Conclusion: Systemic involvement is seen in most SS patients. Younger and RF and salivary gland biopsy-positive patients are at higher risk of systemic disease. Around half of patients with systemic involvement experienced aggravated disease over time, especially those with constitutional involvement or RF.
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OBJECTIVES: During the COVID-19 pandemic, there was a significant impact on the management of non-COVID-19 related diseases, potentially increasing the incidence of paraneoplastic syndromes such as cancer-associated myositis (CAM).The aim of this study is to determine the incidence of CAM in our cohort before and after the COVID-19 pandemic onset. METHODS: We included patients with idiopathic inflammatory myopathy (IIM), diagnosed between June 2016 and June 2023. The patients were divided into two groups according to the date of IIM diagnosis. RESULTS: We included 132 patients; 65.1% (n=86) were diagnosed prior to and 34.9% (n=46) after the COVID-19 pandemic. The most common IIM was dermatomyositis (DM) before and after the COVID-19 pandemic onset (p=0.750). The most frequent myositis-specific antibody (MSA) before the COVID-19 pandemic was anti-Mi2 (15.1%). After the COVID-19 pandemic onset, anti-TIF1γ was the most common MSA (21.7%), with a significantly higher relative prevalence (p=0.006). The incidence of CAM was significantly higher after the COVID-19 pandemic onset (11 vs. 3 new cases, p<0.002). Patients with CAM more frequently had anti-TIF1γ-positivity (p<0.001) and a diagnosis after the pandemic (p=0.001) than non-CAM-IIM patients. No significant differences were found regarding vaccination status or previous COVID-19 infection in CAM and non-CAM-IIM patients. Diagnosis after the COVID-19 pandemic was an independent predictor of CAM among IIM patients (OR 0.012, 95% CI 0.000-0.400, p=0.013), regardless of age, sex or previous COVID-19 infection. CONCLUSIONS: There was a significant increase in the incidence of CAM after the COVID-19 pandemic. IIM diagnosis after the COVID-19 pandemic was an independent predictor of CAM.
Subject(s)
COVID-19 , Myositis , Neoplasms , Humans , Pandemics , Autoantibodies , COVID-19/epidemiology , Myositis/diagnosis , Neoplasms/epidemiologySubject(s)
Sjogren's Syndrome , Humans , Sjogren's Syndrome/genetics , Sjogren's Syndrome/diagnosis , Family , Female , Surveys and Questionnaires , MaleABSTRACT
Intravesical bacillus Calmette-Guérin (BCG) immunotherapy is recommended for non-muscle-invasive bladder cancer after transurethral resection. BCG-associated musculoskeletal adverse events are rare. We report two cases of BCG reactive arthritis that were unusually severe and refractory. These describe two male patients who presented with polyarthritis after BCG exposure. Ultrasonography-guided glucocorticoid injections, high-dose systemic glucocorticoids and the institution of sulfasalazine were required for achievement of remission. Bacillus Calmette-Guérin reactive arthritis can present as polyarthritis of small and medium joints or as mono-oligoarthritis of asymmetrical ankles and knees, frequently associated with tenosynovitis and enthesitis. The mechanism by which BCG promotes arthralgia and arthritis is poorly understood. The most well-accepted theory is that the BCG antigens migrate to different peripheral tissues, including the joints. There is also a lack of knowledge regarding risk factors, with possible genetic factors playing a role. As the two presented cases show, BCG-induced reactive arthritis should be considered in the differential diagnosis of arthritis and refractory tenosynovitis in BCG-exposed patients.
Subject(s)
Arthritis, Reactive , BCG Vaccine , Tenosynovitis , Urinary Bladder Neoplasms , Humans , Male , Administration, Intravesical , Arthritis, Reactive/chemically induced , Arthritis, Reactive/diagnosis , Arthritis, Reactive/drug therapy , BCG Vaccine/adverse effects , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/diagnosisABSTRACT
AIMS: To characterise the idiopathic inflammatory myopathies (IIM) module of the Rheumatic Diseases Portuguese Register (Reuma.pt/myositis) and the patients in its cohort. METHODS: Reuma.pt is a web-based system with standardised patient files gathered in a registry. This was a multicentre open cohort study, including patients registered in Reuma.pt/myositis up to January 2022. RESULTS: Reuma.pt/myositis was designed to record all relevant data in clinical practice and includes disease-specific diagnosis and classification criteria, clinical manifestations, immunological data, and disease activity scores. Two hundred eighty patients were included, 71.4% female, 89.4% Caucasian, with a median age at diagnosis and disease duration of 48.9 (33.6-59.3) and 5.3 (3.0-9.8) years. Patients were classified as having definite (N=57/118, 48.3%), likely (N=23/118, 19.5%), or possible (N=2/118, 1.7%) IIM by 2017 EULAR/ACR criteria. The most common disease subtypes were dermatomyositis (DM, N=122/280, 43.6%), polymyositis (N=59/280, 21.1%), and myositis in overlap syndromes (N=41/280, 14.6%). The most common symptoms were proximal muscle weakness (N=180/215, 83.7%) and arthralgia (N=127/249, 52.9%), and the most common clinical signs were Gottron's sign (N=75/184, 40.8%) and heliotrope rash (N=101/252, 40.1%). Organ involvement included lung (N=78/230, 33.9%) and heart (N=11/229, 4.8%) involvements. Most patients expressed myositis-specific (MSA, N=158/242, 65.3%) or myositis-associated (MAA, 112/242, 46.3%) antibodies. The most frequent were anti-SSA/SSB (N=70/231, 30.3%), anti-Jo1 (N=56/236, 23.7%), and anti-Mi2 (N=31/212, 14.6%). Most patients had a myopathic pattern on electromyogram (N=101/138, 73.2%), muscle oedema in magnetic resonance (N=33/62, 53.2%), and high CK (N=154/200, 55.0%) and aldolase levels (N=74/135, 54.8%). Cancer was found in 11/127 patients (8.7%), most commonly breast cancer (N=3/11, 27.3%). Most patients with cancer-associated myositis had DM (N=8/11, 72.7%) and expressed MSA (N=6/11) and/or MAA (N=3/11). The most used drugs were glucocorticoids (N=201/280, 71.8%), methotrexate (N=117/280, 41.8%), hydroxychloroquine (N=87/280, 31.1%), azathioprine (N=85/280, 30.4%), and mycophenolate mofetil (N=56/280, 20.0%). At the last follow-up, there was a median MMT8 of 150 (142-150), modified DAS skin of 0 (0-1), global VAS of 10 (0-50) mm, and HAQ of 0.125 (0.000-1.125). CONCLUSIONS: Reuma.pt/myositis adequately captures the main features of inflammatory myopathies' patients, depicting, in this first report, a heterogeneous population with frequent muscle, joint, skin, and lung involvements.
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OBJECTIVES: The main goal of this study was to characterise the frequency and phenotype of B, T follicular helper (Tfh) and T follicular regulatory (Tfr) cells in peripheral blood and the cytokine environment present in circulation in children with extended oligoarticular juvenile idiopathic arthritis (extended oligo JIA) and polyarticular JIA (poly JIA) when compared with healthy controls, children with persistent oligoarticular JIA (persistent oligo JIA) and adult JIA patients. METHODS: Blood samples were collected from 105 JIA patients (children and adults) and 50 age-matched healthy individuals. The frequency and phenotype of B, Tfh and Tfr cells were evaluated by flow cytometry. Serum levels of APRIL, BAFF, IL-1ß, IL-2, IL-4, IL-6, IL-10, IL-17A, IL-21, IL-22, IFN-γ, PD-1, PD-L1, sCD40L, CXCL13 and TNF were measured by multiplex bead-based immunoassay and/or ELISA in all groups included. RESULTS: The frequency of B, Tfh and Tfr cells was similar between JIA patients and controls. Children with extended oligo JIA and poly JIA, but not persistent oligo JIA, had significantly lower frequencies of plasmablasts, regulatory T cells and higher levels of Th17-like Tfh cells in circulation when compared with controls. Furthermore, APRIL, BAFF, IL-6 and IL-17A serum levels were significantly higher in paediatric extended oligo JIA and poly JIA patients when compared with controls. These immunological alterations were not found in adult JIA patients in comparison to controls. CONCLUSIONS: Our results suggest a potential role and/or activation profile of B and Th17-like Tfh cells in the pathogenesis of extended oligo JIA and poly JIA, but not persistent oligo JIA.
Subject(s)
Arthritis, Juvenile , Interleukin-17 , Humans , Child , Interleukin-6 , T-Lymphocyte Subsets , CytokinesSubject(s)
Lung Diseases, Interstitial , Myositis , Humans , Myositis/complications , Antibodies , Autoantibodies , Antibodies, AntinuclearABSTRACT
Background: Idiopathic inflammatory myopathies (IIM) are a rare heterogeneous group of diseases characterised by chronic skeletal muscle inflammation, but other organs are also frequently involved. IMM represent a diagnostic challenge and a multidisciplinary approach is important to ensure successful diagnosis and adequate follow-up of these patients. Objective: To describe the general functioning of our multidisciplinary myositis clinic, highlighting the benefits of multidisciplinary team management in patients with confirmed or suspected IIM and to characterise our clinical experience. Methods: Description of the organization of a dedicated multidisciplinary myositis outpatient clinic, supported by IMM specific electronic assessment tools and protocols based on our Portuguese Register - Reuma.pt. In addition, an overview of our activity between 2017 and 2022 is provided. Results: An IIM multidisciplinary care clinic, based on a close collaboration between Rheumatologists, Dermatologists and Physiatrist is detailed in this paper. One hundred and eighty-five patients were assessed in our myositis clinic; 138 (75%) of those were female, with a median age of 58 [45-70] years. At the last appointment, 130 patients had a confirmed IIM diagnosis, and the mean disease duration was 4 [2-6] years. The most frequent diagnosis was dermatomyositis (n = 34, 26.2%), followed by antisynthetase syndrome (n = 27, 20.8%) and clinically amyopathic/paucimyopathic dermatomyositis (n = 18, 13.8%). Twenty-four patients (18.5%) were on monotherapy and 94 (72.3%) were on combination therapy. Conclusion: A multidisciplinary approach is important to ensure the correct diagnosis and follow-up of these patients. A myositis clinic, with a standardised practice at a tertiary hospital level, contributes to a standardization of care and opens research opportunities.
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Objectives: Idiopathic inflammatory myopathies (IIM) are a group of rare disorders that can affect the heart. This work aimed to find predictors of cardiac involvement in IIM. Methods: Multicenter, open cohort study, including patients registered in the IIM module of the Rheumatic Diseases Portuguese Register (Reuma.pt/Myositis) until January 2022. Patients without cardiac involvement information were excluded. Myo(peri)carditis, dilated cardiomyopathy, conduction abnormalities, and/or premature coronary artery disease were considered. Results: 230 patients were included, 163 (70.9%) of whom were females. Thirteen patients (5.7%) had cardiac involvement. Compared with IIM patients without cardiac involvement, these patients had a lower bilateral manual muscle testing score (MMT) at the peak of muscle weakness [108.0 ± 55.0 vs 147.5 ± 22.0, p=0.008] and more frequently had oesophageal [6/12 (50.0%) vs 33/207 (15.9%), p=0.009] and lung [10/13 (76.9%) vs 68/216 (31.5%), p=0.001] involvements. Anti-SRP antibodies were more commonly identified in patients with cardiac involvement [3/11 (27.3%) vs 9/174 (5.2%), p=0.026]. In the multivariate analysis, positivity for anti-SRP antibodies (OR 104.3, 95% CI: 2.5-4277.8, p=0.014) was a predictor of cardiac involvement, regardless of sex, ethnicity, age at diagnosis, and lung involvement. Sensitivity analysis confirmed these results. Conclusion: Anti-SRP antibodies were predictors of cardiac involvement in our cohort of IIM patients, irrespective of demographical characteristics and lung involvement. We suggest considering frequent screening for heart involvement in anti-SRP-positive IIM patients.
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Myocarditis , Myositis , Rheumatic Diseases , Female , Humans , Male , Cohort Studies , HeartABSTRACT
Background: Vaccination is one of the most important measures to contain the COVID-19 pandemic, especially for frail patients. VACCINATE is a multicentre prospective observational study promoted by the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET) aimed at assessing the long-term outcomes of COVID-19 vaccination in patients with rare and complex connective tissue diseases (rcCTDs) in terms of efficacy and safety. Methods: Adult rcCTDs patients were eligible for recruitment. Demographic, clinical and vaccination data were collected at enrolment. Follow-up visits were scheduled 4, 12, 24, 36 and 48 weeks after completion of the first vaccination cycle; data on adverse events, disease exacerbations and the occurrence of new SARS-CoV-2 infections were collected at these time-points. Findings: 365 rcCTDs patients (87 % female, mean age 51.8 ± 14.6 years) were recruited. Overall, 200 patients (54.8 %) experienced at least one adverse event, generally mild and in most cases occurring early after the vaccination. During follow-up, 55 disease exacerbations were recorded in 39 patients (10.7 %), distributed over the entire observation period, although most frequently within 4 weeks after completion of the vaccination cycle. The incidence of new SARS-CoV-2 infections was 8.9 per 1000 person-months, with no cases within 12 weeks from vaccine administration and an increasing trend of infections moving away from the primary vaccination cycle. Only one case of severe COVID-19 was reported during the study period. Interpretation: COVID-19 vaccination seems effective and safe in rcCTDs patients. The rate of new infections was rather low and serious infections were uncommon in our cohort. No increased risk of disease flares was observed compared to previous disease history; however, such exacerbations may be potentially severe, emphasising the need for close monitoring of our patients.
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OBJECTIVES: To characterise the key epidemiological, clinical, immunological, imaging, and pathological features of the coexistence between sarcoidosis and Sjögren's syndrome (SS). METHODS: All centres included in two large multicentre registries (the Sjögren Syndrome Big Data Consortium and the Sarco-GEAS-SEMI Registry) were contacted searching for potential cases of coexistence between SS and sarcoidosis seen in daily practice. Inclusion criteria were the fulfilment of the current classification criteria both for SS (2016 ACR/EULAR) and sarcoidosis (WASOG). The following features were considered for evaluating a coexisting immunopathological scenario between the two diseases: non-caseating granulomas (NCG), focal lymphocytic sialadenitis (FLS) and positive anti-Ro antibodies. RESULTS: We identified 43 patients who fulfilled the inclusion criteria (38 women, with a mean age of 53 years at diagnosis of SS and of 52 years at diagnosis of sarcoidosis). In 28 (65%) cases, sarcoidosis was diagnosed concomitantly with SS, or during the follow-up of patients with an already diagnosed SS, while in the remaining 15 (35%), SS was diagnosed during the follow-up of an already diagnosed sarcoidosis. Patients in whom sarcoidosis was diagnosed first showed a lower mean age (43.88 vs. 55.67 years, p=0.005) and were less frequently women (73% vs. 96%, p=0.04) in comparison with those in whom sarcoidosis was diagnosed concomitantly with SS, or during the follow-up of an already diagnosed SS. We identified the following immunopathological scenarios: a combination of NCG involving extrasalivary tissues and anti-Ro antibodies in 55% of patients, a coexistence of both pathological scenarios (extrasalivary NCG and FLS in MSGB) in 42% (with positive anti-Ro antibodies in two thirds of cases), and NCG involving salivary glands and anti-Ro antibodies in 3% of cases. CONCLUSIONS: We have characterised the largest reported series of patients who fulfilled the current classification criteria for both SS and sarcoidosis. This implies that sarcoidosis (and not just the presence of isolated NCG on salivary gland biopsy) may, like other systemic autoimmune diseases, coexist with SS, and that a sarcoidosis diagnosis does not preclude the development of SS in the future.
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Sarcoidosis , Sialadenitis , Sjogren's Syndrome , Humans , Female , Middle Aged , Sjogren's Syndrome/complications , Sjogren's Syndrome/diagnosis , Sjogren's Syndrome/epidemiology , Sarcoidosis/complications , Sarcoidosis/diagnosis , Sarcoidosis/epidemiology , Salivary Glands/pathology , Biopsy , Sialadenitis/diagnosis , Sialadenitis/epidemiology , Sialadenitis/complicationsABSTRACT
Background: Patient registries play a crucial role in supporting clinical practice, healthcare planning and medical research, offering a real-world picture on rare and complex connective tissue diseases (rCTDs). ERN ReCONNET launched the first European Registry Infrastructure with the aim to plan, upgrade and link registries for rCTDs, with the final goal to promote a harmonized data collection approach all over Europe for rCTDs. Methods: An online survey addressed to healthcare professionals and patients' representatives active in the field of rCTDs was integrated by an extensive database search in order to build a mapping of existing registries for rCTDs. Findings: A total of 140 registries were found, 38 of which include multiple diseases. No disease-specific registry was identified for relapsing polychondritis, mixed connective tissue disease and undifferentiated connective tissue disease. Discussion: This overview on the existing registries for rCTDs provides a useful starting point to identify the gaps and the strengths of registries on the coverage of rCTDs, and to develop a common data set and data collection approach for the establishment of the TogethERN ReCONNET Infrastructure.
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SARS-CoV-2 infection can present in different clinical forms, most commonly as bilateral pneumonia, but also with pericardial/myocardial involvement. Cardiac involvement in COVID-19 is associated with worse outcomes. The authors report a case of myopericarditis as the primary manifestation of SARS-CoV-2 infection in a 20-year-old male patient with no known cardiovascular (CV) disorders or risk factors. The patient presented with pleuritic chest pain and high fever, with no respiratory symptoms. Electrocardiogram (ECG) and echocardiogram changes were consistent with pericarditis; concomitant elevation of cardiac enzymes revealed myocardial involvement. The patient had a slow but favourable evolution with no apparent impact on cardiac function. Other causes of myopericarditis were excluded and SARS-CoV-2 admitted as the most likely aetiological agent. This case highlights possible cardiac involvement in SARS-CoV-2 infection with little or no pulmonary disease in a young healthy patient. Such systemic and potentially troublesome manifestations of COVID-19 are increasingly being described. LEARNING POINTS: Acute myopericarditis is a possible manifestation of SARS-CoV-2 infection.SARS-CoV-2 cardiac involvement may occur both in older and in younger previously healthy subjects, and could be more frequent than expected.Further investigation should address the prevalence of myocardium and pericardium involvement in COVID-19 patients, as well as its complications, sequelae and prognostic value for both older and young patients.
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Objective: To identify risk factors for SARS-CoV-2 infection and for severe/critical COVID-19, and to assess the humoral response after COVID-19 in these patients. Methods: Nationwide study of adult patients with inflammatory RMDs prospectively followed in the Rheumatic Diseases Portuguese Register-Reuma.pt-during the first 6 months of the pandemic. We compared patients with COVID-19 with those who did not develop the disease and patients with mild/moderate disease with those exhibiting severe/critical COVID-19. IgG antibodies against SARS-CoV-2 were measured ≥3 months after infection and results were compared with matched controls. Results: 162 cases of COVID-19 were registered in a total of 6,363 appointments. Patients treated with TNF inhibitors (TNFi; OR = 0.160, 95% CI 0.099-0.260, P < 0.001) and tocilizumab (OR 0.147, 95% CI 0.053-0.408, P < 0.001) had reduced odds of infection. Further, TNFi tended to be protective of severe and critical disease. Older age, major comorbidities, and rituximab were associated with an increased risk of infection and worse prognosis. Most patients with inflammatory RMDs (86.2%) developed a robust antibody response. Seroconversion was associated with symptomatic disease (OR 13.46, 95% CI 2.21-81.85, P = 0.005) and tended to be blunted by TNFi (OR 0.17, 95% CI 0.03-1.05; P = 0.057). Conclusions: TNFi and tocilizumab reduced the risk of infection by SARS-CoV-2. Treatment with TNFi also tended to reduce rates of severe disease and seroconversion. Older age, general comorbidities and rituximab were associated with increased risk for infection and worse prognosis, in line with previous reports. Most patients with RMDs developed a proper antibody response after COVID-19, particularly if they had symptomatic disease.
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OBJECTIVES: We aimed to investigate the clinical off-label use of mycophenolate mofetil (MMF), including its safety and efficacy in patients with rare and complex rheumatic connective tissue diseases (rCTDs). METHODS: A survey was distributed across experts from ERN-ReCONNET reference centres in order to assess the experience with MMF off-label use. Patient-level data of patients with rCTDs under treatment with MMF was also collected for analysis of safety and efficacy. RESULTS: Twelve experts from eleven centres distributed throughout Europe (7 countries) answered the survey. The experience was concordant in that, despite of its off-label use, experts reported opting frequently for this therapeutic alternative with robust confidence on its efficacy and safety. The analysis of 108 patients with rCTDs under MMF revealed a good safety profile, as well as good clinical outcomes, especially for systemic lupus erythematosus and idiopathic inflammatory myopathies. The presence of interstitial lung disease was, as expected, associated with a worse clinical outcome despite use of MMF. CONCLUSIONS: MMF is widely used in reference centres for rCTDs. Its safety profile and efficacy seem to be recognised by experts and demonstrated with patient-level analysis. While selected rCTDs will likely remain an off-label indication for MMF, robust data seem to support this therapy as an appropriate alternative for safely and effectively treating many manifestations of rCTDs.