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Background/aim: Approximately 40 million individuals worldwide have been infected with SARS-CoV-2, the virus responsible for the novel coronavirus disease-2019 (COVID-19). Despite the current literature about the cardiac effects of COVID-19 in children, more information is required. We aimed to determine both cardiovascular and arrhythmia assessment via electrocardiographic and echocardiographic parameters. Materials and methods: We evaluated seventy children who were hospitalized with COVID-19 infections and seventy children as normal control group through laboratory findings, electrocardiography (ECG), and transthoracic echocardiography (TTE). Results: We observed significantly increased levels of Tp-Te, Tp-Te/QT, and Tp-Te/QTc compared with the control group. Twenty-five of 70 (35.7%) patients had fragmented QRS (fQRS) without increased troponin levels. On the other hand, none of the patients had pathologic corrected QT(QTc) prolongation during the illness or its treatment. On TTE, 20 patients had mild mitral insufficiency, among whom only five had systolic dysfunction (ejection fraction < 55%). There was no significant difference between the patient and control groups, except for isovolumic relaxation time (IVRT) in terms of mean systolic and diastolic function parameters. IVRT of COVID patients was significantly lower than that of control group. Conclusion: Despite all the adult studies, the effects of COVID (R) 19 on myocardial function are not well established in children. The thought that children are less affected by the illness may be a misconception.

Introduction The public–private ADVANCE collaboration developed and tested a system to generate evidence on vaccine benefits and risks using European electronic healthcare databases. In the safety of vaccines, background incidence rates are key to allow proper monitoring and assessment. The goals of this study were to compute age-, sex-, and calendar-year stratified incidence rates of nine autoimmune diseases in seven European healthcare databases from four countries and to assess validity by comparing with published data. Methods Event rates were calculated for the following outcomes: acute disseminated encephalomyelitis, Bell’s palsy, Guillain–Barré syndrome, immune thrombocytopenia purpura, Kawasaki disease, optic neuritis, narcolepsy, systemic lupus erythematosus, and transverse myelitis. Cases were identified by diagnosis codes. Participating organizations/databases originated from Denmark, Italy, Spain, and the UK. The source population comprised all persons registered, with at least 1 year of data prior to the study start, or follow-up from birth. Stratified incidence rates were computed per database over the period 2003 to 2014. Results Between 2003 and 2014, 148,947 incident cases of nine autoimmune diseases were identified. Crude incidence rates were highest for Bell’s palsy [23.8/100,000 person-years (PYs), 95% confidence interval (CI) 23.6–24.1] and lowest for Kawasaki disease (0.7/100,000 PYs, 95% CI 0.6–0.7). Specific patterns were observed by sex, age, calendar time, and data sources. Rates were comparable with published estimates. Conclusion A range of autoimmune events could be identified in the ADVANCE system. Estimation of rates indicated consistency across selected European healthcare databases, as well as consistency with US published data. Supplementary Information The online version contains supplementary material available at 10.1007/s40264-020-01031-1.

© 2022 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).Aim: Multisystem inflammatory syndrome in children (MIS-C) may cause shock and even death in children. The aim of this study is to describe the clinical features, laboratory characteristics and outcome of children diagnosed with MIS-C in 25 different hospitals in Turkey. Methods: The retrospective study was conducted between 8 April and 28 October 2020 in 25 different hospitals from 17 cities. Data were collected from patients' medical records using a standardised form. Clinical and laboratory characteristics and outcomes according to different age groups, gender and body mass index percentiles were compared using multivariate logistic regression analysis. Results: The study comprised 101 patients, median age 7 years (interquartile range (IQR) 4.6–9.3); 51 (50.5%) were boys. Reverse-transcriptase polymerase chain reaction (PCR) assay was positive in 21/100 (21%) patients; 62/83 (74.6%) patients had positive serology for SARS-CoV-2. The predominant complaints were fever (100%), fatigue (n = 90, 89.1%), and gastrointestinal symptoms (n = 81, 80.2%). Serum C-reactive protein (in 101 patients, median 165 mg/L; range 112–228), erythrocyte sedimentation rate (73/84, median 53 mm/s; IQR 30–84) and procalcitonin levels (86/89, median 5 μg/L; IQR 0.58–20.2) were elevated. Thirty-eight patients (37.6%) required admission to intensive care. Kawasaki disease (KD) was diagnosed in 70 (69.3%) patients, 40 of whom had classical KD. Most patients were treated with intravenous immunoglobulin (n = 92, 91%) and glucocorticoids (n = 59, 58.4%). Seven patients (6.9%) died. Conclusion: The clinical spectrum of MIS-C is broad, but clinicians should consider MIS-C in the differential diagnosis when persistent fever, fatigue and gastrointestinal symptoms are prominent. Most patients diagnosed with MIS-C were previously healthy. Immunomodulatory treatment and supportive intensive care are important in the management of cases with MIS-C. Glucocorticoids and intravenous immunoglobulins are the most common immunomodulatory treatment options for MIS-C. Prompt diagnosis and prompt treatment are essential for optimal management.

Background: Paediatric Multisystem Inflammatory Syndrome temporally associated with SARS-CoV-2 (PIMS-TS), first identified in April 2020, shares features of both Kawasaki disease (KD) and toxic shock syndrome (TSS). The surveillance describes the epidemiology and clinical characteristics of PIMS-TS in the United Kingdom and Ireland. Methods: Public Health England initiated prospective national surveillance of PIMS-TS through the British Paediatric Surveillance Unit. Paediatricians were contacted monthly to report PIMS-TS, KD and TSS cases electronically and complete a detailed clinical questionnaire. Cases with symptom onset between 01 March and 15 June 2020 were included. Findings: there were 216 cases with features of PIMS-TS alone, 13 with features of both PIMS-TS and KD, 28 with features of PIMS-TS and TSS and 11 with features of PIMS-TS, KD and TSS, with differences in age, ethnicity, clinical presentation and disease severity between the phenotypic groups. There was a strong geographical and temporal association between SARS-CoV-2 infection rates and PIMS-TS cases. Of those tested, 14.8% (39/264) children had a positive SARS-CoV-2 RT-PCR, and 63.6% (75/118) were positive for SARS-CoV-2 serology. In total 44·0% (118/268) required intensive care, which was more common in cases with a TSS phenotype. Three of five children with cardiac arrest had TSS phenotype. Three children (1·1%) died. Interpretation: the strong association between SARS-CoV-2 infection and PIMS-TS emphasises the importance of maintaining low community infection rates to reduce the risk of this rare but severe complication in children and adolescents. Close follow-up will be important to monitor long-term complications in children with PIMS-TS. Funding: PHE

Background: Following the spread of the coronavirus disease 2019 (COVID-19) pandemic a new disease entity emerged, defined as Pediatric Inflammatory Multisystem Syndrome temporally associated with COVID-19 (PIMS-TS), or Multisystem Inflammatory Syndrome in Children (MIS-C). In the absence of trials, evidence for treatment remains scarce.Purpose: To develop best practice recommendations for the diagnosis and treatment of children with PIMS-TS in Switzerland. It is acknowledged that the field is changing rapidly, and regular revisions in the coming months are pre-planned as evidence is increasing.Methods: Consensus guidelines for best practice were established by a multidisciplinary group of Swiss pediatric clinicians with expertise in intensive care, immunology/rheumatology, infectious diseases, hematology, and cardiology. Subsequent to literature review, four working groups established draft recommendations which were subsequently adapted in a modified Delphi process. Recommendations had to reach >80% agreement for acceptance.Results: The group achieved agreement on 26 recommendations, which specify diagnostic approaches and interventions across anti-inflammatory, anti-infectious, and support therapies, and follow-up for children with suspected PIMS-TS. A management algorithm was derived to guide treatment depending on the phenotype of presentation, categorized into PIMS-TS with (a) shock, (b) Kawasaki-disease like, and (c) undifferentiated inflammatory presentation.Conclusion: Available literature on PIMS-TS is limited to retrospective or prospective observational studies. Informed by these cohort studies and indirect evidence from other inflammatory conditions in children and adults, as well as guidelines from international health authorities, the Swiss PIMS-TS recommendations represent best practice guidelines based on currently available knowledge to standardize treatment of children with suspected PIMS-TS. Given the absence of high-grade evidence, regular updates of the recommendations will be warranted, and participation of patients in trials should be encouraged.

Systemic vasculitides (SVs) is a group of diseases characterised by inflammation/necrosis of the blood vessel wall in various organs. Simultaneous brain and heart involvement is a cause of increased morbidity/mortality in SV. We aimed to present evidence of concurrent brain/heart involvement in SV and the role of a combined brain/heart magnetic resonance imaging (MRI) in their risk stratification. Cerebral vasculitis (CV) can be presented as focal deficits, seizures, headache, neuropsychiatric manifestations or cognitive dysfunction and cardiovascular disease (CVD) as myocardial/vascular inflammation, perfusion/function defects and fibrosis. MRI is a non-invasive, non-radiating technique that allows the reliable identification of intraparenchymal brain lesions and the detection of myocardial/vascular inflammation and fibrosis. However, its use in SV is currently hampered by high cost, lack of availability/expertise and lack of awareness among the clinicians. Although there are no clinical data supporting the combined use of brain/heart MRI in asymptomatic SV, it would be called for in cases with clinical suspicion of brain/heart involvement, especially in those at high risk for CVD/stroke such as SLE/APS. Furthermore, it may be of value in SV with multi-organ involvement, cognitive dysfunction or other neuropsychiatric symptoms with concurrent cardiac involvement, presenting as typical or atypical symptoms with normal routine cardiac evaluation, new onset of arrhythmia and/or HF.

Systemic vasculitides (SVs) is a group of diseases characterised by inflammation/necrosis of the blood vessel wall in various organs. Simultaneous brain and heart involvement is a cause of increased morbidity/mortality in SV. We aimed to present evidence of concurrent brain/heart involvement in SV and the role of a combined brain/heart magnetic resonance imaging (MRI) in their risk stratification. Cerebral vasculitis (CV) can be presented as focal deficits, seizures, headache, neuropsychiatric manifestations or cognitive dysfunction and cardiovascular disease (CVD) as myocardial/vascular inflammation, perfusion/function defects and fibrosis. MRI is a non-invasive, non-radiating technique that allows the reliable identification of intraparenchymal brain lesions and the detection of myocardial/vascular inflammation and fibrosis. However, its use in SV is currently hampered by high cost, lack of availability/expertise and lack of awareness among the clinicians. Although there are no clinical data supporting the combined use of brain/heart MRI in asymptomatic SV, it would be called for in cases with clinical suspicion of brain/heart involvement, especially in those at high risk for CVD/stroke such as SLE/APS. Furthermore, it may be of value in SV with multi-organ involvement, cognitive dysfunction or other neuropsychiatric symptoms with concurrent cardiac involvement, presenting as typical or atypical symptoms with normal routine cardiac evaluation, new onset of arrhythmia and/or HF.

Purpose: Nuclear cardiology plays an important role in clinical assessment and has enormous impact on the management of a variety of cardiovascular diseases. Pediatric patients at different age groups are exposed to a spectrum of radiation dose levels and associated cancer risks different from those of adults in diagnostic nuclear medicine procedures. Therefore, comprehensive radiation dosimetry evaluations for commonly used myocardial perfusion imaging (MPI) and viability radiotracers in target population (children and adults) at different age groups are highly desired. Methods: Using Monte Carlo calculations and biological effects of ionizing radiation VII model, we calculate the S-values for a number of radionuclides (T1-201, Tc-99m, I-123, C-11, N-13, O-15, F-18, and Rb-82) and estimate the absorbed dose and effective dose for 12 MPI radiotracers in computational models including the newborn, 1-, 5-, 10-, 15-yr-old, and adult male and female computational phantoms. Results: For most organs, Tl-201 produces the highest absorbed dose whereas Rb-82 and O-15-water produce the lowest absorbed dose. For the newborn baby and adult patient, the effective dose of Rb-82 is 48% and 77% lower than that of Tc-99m-tetrofosmin (rest), respectively. Conclusions: Rb-82 results in lower effective dose in adults compared to Tc-99m-labeled tracers. However, this advantage is less apparent in children. The produced dosimetric databases for various radiotracers used in cardiovascular imaging, using new generation of computational models, can be used for risk-benefit assessment of a spectrum of patient population in clinical nuclear cardiology practice. (C) 2015 American Association of Physicists in Medicine.

PURPOSE OF REVIEW: Infections have been suggested to contribute to disease induction and reactivation in many of the idiopathic vasculitides. This review describes and evaluates the evidence that microbes are involved in the etiopathogenesis of these diseases. RECENT FINDINGS: Large-vessel vasculitis has recently been associated with two specific bacteria. Mycobacterium tuberculosis is thought to have an inducing role in Takayasu arteritis and a Burkholderia bacterium might be involved in giant cell arteritis. Hepatitis B and C viruses have been linked to polyarteritis nodosa. In antineutrophil cytoplasmic autoantibody-associated vasculitis, and more specifically granulomatosis with polyangiitis (GPA), Staphylococcus aureus has been the focus of many studies. Chronic nasal carriage of S. aureus is related to endonasal activity and disease relapses in GPA patients. Moreover, antibacterial treatment is known to reduce the risk for disease relapses. If and how pathogens trigger vasculitis is still unclear, but several potential mechanisms have been suggested and are briefly reviewed here. SUMMARY: Although many observations suggest a link between infections and the development of vasculitis, no direct proof exists. Transcriptomic and proteomic studies of the pathogens involved could aid in identifying specific or common traits of pathogens that are relevant for the development and reactivation of vasculitis.

PURPOSE OF REVIEW: Infections have been suggested to contribute to disease induction and reactivation in many of the idiopathic vasculitides. This review describes and evaluates the evidence that microbes are involved in the etiopathogenesis of these diseases.RECENT FINDINGS: Large-vessel vasculitis has recently been associated with two specific bacteria. Mycobacterium tuberculosis is thought to have an inducing role in Takayasu arteritis and a Burkholderia bacterium might be involved in giant cell arteritis. Hepatitis B and C viruses have been linked to polyarteritis nodosa. In antineutrophil cytoplasmic autoantibody-associated vasculitis, and more specifically granulomatosis with polyangiitis (GPA), Staphylococcus aureus has been the focus of many studies. Chronic nasal carriage of S. aureus is related to endonasal activity and disease relapses in GPA patients. Moreover, antibacterial treatment is known to reduce the risk for disease relapses. If and how pathogens trigger vasculitis is still unclear, but several potential mechanisms have been suggested and are briefly reviewed here.SUMMARY: Although many observations suggest a link between infections and the development of vasculitis, no direct proof exists. Transcriptomic and proteomic studies of the pathogens involved could aid in identifying specific or common traits of pathogens that are relevant for the development and reactivation of vasculitis.

Motivation We introduce PRINCESS, a privacy-preserving international collaboration framework for analyzing rare disease genetic data that are distributed across different continents. PRINCESS leverages Software Guard Extensions (SGX) and hardware for trustworthy computation. Unlike a traditional international collaboration model, where individual-level patient DNA are physically centralized at a single site, PRINCESS performs a secure and distributed computation over encrypted data, fulfilling institutional policies and regulations for protected health information. Results To demonstrate PRINCESS’ performance and feasibility, we conducted a family-based allelic association study for Kawasaki Disease, with data hosted in three different continents. The experimental results show that PRINCESS provides secure and accurate analyses much faster than alternative solutions, such as homomorphic encryption and garbled circuits (over 40 000× faster). Availability and Implementation https://github.com/achenfengb/PRINCESS_opensource Supplementary information Supplementary data are available at Bioinformatics online.

Will vaccination raise the incidence of autoimmune diseases, what is the impact of increasingly crowded vaccination schedules, the vaccination in age groups and the risk of coincidental temporal association? All these issues are still under debate. However, for the time being, to avoid confusion in the medical community and the media, we have to adhere to guidelines established consensually by experts while ensuring a strict surveillance and reporting possible side effects. Recommendation for vaccination in patients with autoimmune inflammatory rheumatic diseases (AIIRD) based on the currently available evidence and expert opinion were recently formulated by an EULAR task force. Major recommendations for AIIRD include: i) vaccination should ideally be administered during stable disease; ii) influenza vaccination and pneumococcal vaccination should be strongly considered; iii) vaccination can be administered during the use of DMARDs and TNF-inhibitors, but before starting rituximab; iv) live attenuated vaccines should be avoided whenever possible in immunosuppressed patients; v) BCG vaccination is not recommended. (C) 2011 Elsevier B.V. All rights reserved.

The disease group of ANCA-associated vasculitis (AAV) includes granulomatosis with polyangiitis (GPA, Wegener’s granulomatosis) and microscopic polyangiitis (MPA), entities that share the features of necrotizing vasculitis of small blood vessels in multiple organ systems, and anti-neutrophil cytoplasmic antibodies (ANCA). Before effective treatments were discovered, AAV was usually fatal after a monophasic illness. Aggressive immunosuppressive therapy has not led to cure, but instead has converted GPA and MPA into chronic diseases. Relapse is common but not universal, unpredictable in its timing, and highly variable in severity. Most patients require chronic immunosuppressive therapy to reduce the risk of severe relapse or to control musculoskeletal, constitutional, or upper airway symptoms. Because of the highly variable course of disease, long-term management of AAV is challenging. Changes in ANCA titers correlate with changes in disease activity, but discordance between ANCA status and clinical status is high (1–5); in one large study, changes in PR3-ANCA titers explained only 8% of the observed changes in disease activity (5). Generic markers of inflammation [erythrocyte sedimentation rate (ESR) and C reactive protein (CRP)] are typically elevated in active AAV (6–8) but in addition to being non-specific with regard to other inflammatory conditions, these markers do not distinguish active AAV from remission as well as one might think (6, 8) (and data to be shown in this paper). Additional markers are needed to guide therapy and help distinguish highly active disease, mildly active disease, and remission. Markers of vascular injury and the linked process of angiogenesis are of particular interest in vasculitis and have been investigated as biomarkers in AAV. For example, thrombomodulin is released by damaged endothelial cells; P-selectin is released by platelets activated by damaged microvessels; vascular endothelial growth factor (VEGF) is an inducible mediator of vascular permeability and of angiogenesis following tissue damage; and multiple matrix metalloproteinases (MMPs) are induced during angiogenesis and tissue remodeling. Several of these markers have been reported to be elevated in patients with active AAV, either in comparison to healthy controls, or in comparison to patients in remission, or both (9–14). Evaluation of these markers in a larger, independent cohort is needed. Utilizing serum specimens collected during the conduct of randomized, controlled, clinical trial of AAV, we performed a study to determine if markers of vascular injury and angiogenesis distinguish between active AAV and remission. We also assessed whether these new markers distinguish important subsets of active AAV.

Objectives: To analyze available evidence on vaccinations in paediatric patients with rheumatic and auto-inflammatory diseases. This evidence formed the basis of the recently constructed European League against Rheumatism (EULAR) recommendations for vaccination of these patients.Methods: A systematic literature review in the MEDLINE and EMBASE databases was conducted using various terms for vaccinations, paediatric rheumatic and autoinflammatory diseases and immunosuppressive drugs. Only papers on paediatric patients (Results: 27 papers were available. No studies were found on autoinflammatory diseases. 14 studies considered live-attenuated vaccines. Evidence so far supports the safety and immunogenicity of non-live composite vaccines, although studies were underpowered to accurately assess safety. Live-attenuated vaccines did not cause disease flares or severe adverse events, not even in patients on methotrexate and low dose glucocorticosteroids. Seven patients on anti-TNFalpha therapy were described receiving the live-attenuated measles, mumps, rubella (n = 5) or varicella (n = 2) booster without severe adverse events.Conclusions: Data on safety and efficacy of vaccinations in paediatric patients with rheumatic diseases is reassuring, but too limited to draw definite conclusions. More research is needed on the safety and efficacy of especially live-attenuated vaccines in patients with rheumatic and autoinflammatory diseases using high dose immunosuppressive drugs. (C) 2011 Elsevier B.V. All rights reserved.

Evidence-based recommendations for vaccination of paediatric patients with rheumatic diseases (PaedRD) were developed by following the EULAR standardised procedures for guideline development. The EULAR task force consisted of (paediatric) rheumatologists/immunologists, one expert in vaccine evaluation, one expert in public health and infectious disease control, and one epidemiologist. A systematic literature review was conducted in MEDLINE, EMBASE, and abstracts of the EULAR and American College of Rheumatology meetings of 2008/9. The level of evidence and strength of recommendation were based on customary scoring systems. Delphi voting was applied to assess the level of agreement between task force members. 107 papers and eight abstracts were used. The majority of papers considered seasonal influenza (41) or pneumococcal (23) vaccination. 26 studies were performed specifically in paediatric patients, and the majority in adult rheumatoid arthritis and systemic lupus erythematosus patients. Fifteen recommendations were developed with an overall agreement of 91.7%. More research is needed on the safety and immunogenicity of (live-attenuated) vaccination in PaedRD, particularly in those using biologicals, and the effect of vaccination on prevention of infections.

Purpose of reviewMicrobial factors are supposed to play an inducing and/or reactivating role in many of the idiopathic systemic vasculitides. This review evaluates the evidence that microbes are involved in the etiopathogenesis of the disease focusing on possibilities for antimicrobial intervention.Recent findingsThe clinical presentation of hepatitis B virus (HBV)-associated polyarteritis nodosa (PAN) is different from that of non-HBV-PAN and requires antiviral treatment. In hepatitic C virus (HCV)-associated autoimmune diseases, type 2 cryoglobulinemia is present in 52% of cases. Chronic nasal carriage of Staphylococcus aureus is related to endonasal activity of Wegener's granulomatosis and recurrent relapses, and prophylactic treatment with co-trimoxazole is effective in reducing relapse rate.SummaryPatients with PAN should be tested for HBV, and patients with type 2 cryoglobulinemia for HCV. When tested positive, antiviral treatment should be considered. Patients with Wegener's granulomatosis should be tested for nasal carriage of S. aureus, and prophylactic treatment with co-trimoxazole should be considered in case of persistent endonasal activity of Wegener's granulomatosis together with S. aureus carriage. The efficacy of S. aureus elimination for preventing relapses of Wegener's granulomatosis should be evaluated.

Purpose of review Microbial factors are supposed to play an inducing and/or reactivating role in many of the idiopathic systemic vasculitides. This review evaluates the evidence that microbes are involved in the etiopathogenesis of the disease focusing on possibilities for antimicrobial intervention. Recent findings The clinical presentation of hepatitis B virus (HBV)-associated polyarteritis nodosa (PAN) is different from that of non-HBV-PAN and requires antiviral treatment. In hepatitic C virus (HCV)-associated autoimmune diseases, type 2 cryoglobulinemia is present in 52% of cases. Chronic nasal carriage of Staphylococcus aureus is related to endonasal activity of Wegener's granulomatosis and recurrent relapses, and prophylactic treatment with co-trimoxazole is effective in reducing relapse rate. Summary Patients with PAN should be tested for HBV, and patients with type 2 cryoglobulinemia for HCV. When tested positive, antiviral treatment should be considered. Patients with Wegener's granulomatosis should be tested for nasal carriage of S. aureus, and prophylactic treatment with co-trimoxazole should be considered in case of persistent endonasal activity of Wegener's granulomatosis together with S. aureus carriage. The efficacy of S. aureus elimination for preventing relapses of Wegener's granulomatosis should be evaluated.

Purpose: Nuclear cardiology plays an important role in clinical assessment and has enormous impact on the management of a variety of cardiovascular diseases. Pediatric patients at different age groups are exposed to a spectrum of radiation dose levels and associated cancer risks different from those of adults in diagnostic nuclear medicine procedures. Therefore, comprehensive radiation dosimetry evaluations for commonly used myocardial perfusion imaging (MPI) and viability radiotracers in target population (children and adults) at different age groups are highly desired. Methods: Using Monte Carlo calculations and biological effects of ionizing radiation VII model, we calculate the S-values for a number of radionuclides (T1-201, Tc-99m, I-123, C-11, N-13, O-15, F-18, and Rb-82) and estimate the absorbed dose and effective dose for 12 MPI radiotracers in computational models including the newborn, 1-, 5-, 10-, 15-yr-old, and adult male and female computational phantoms. Results: For most organs, Tl-201 produces the highest absorbed dose whereas Rb-82 and O-15-water produce the lowest absorbed dose. For the newborn baby and adult patient, the effective dose of Rb-82 is 48% and 77% lower than that of Tc-99m-tetrofosmin (rest), respectively. Conclusions: Rb-82 results in lower effective dose in adults compared to Tc-99m-labeled tracers. However, this advantage is less apparent in children. The produced dosimetric databases for various radiotracers used in cardiovascular imaging, using new generation of computational models, can be used for risk-benefit assessment of a spectrum of patient population in clinical nuclear cardiology practice. (C) 2015 American Association of Physicists in Medicine.

To date, in the investigation of the role of S. aureus in WG, we face a paradoxical situation. On the one hand, clinical results obtained from treatment of WG patients with co-trimoxazole and studies assessing the impact of S. aureus on disease relapses strongly suggest that this bacterium contributes to disease pathophysiology. On the other hand, laboratory investigation of the possible mechanisms by which S. aureus is involved in WG is scarce, despite the fact that knowledge and tools to study this microorganism are abundant. In the present review, we discuss recent works investigating the possible pathophysiologic contribution of S. aureus to WG. Moreover, we propose a number of possibly relevant pathways of interaction of this bacterium with lymphoid and non-lymphoid cells of the WG host.

Background Primary systemic vasculitis presenting in childhood is an uncommon but serious condition. As these patients transfer to adult clinics for continuing care, defining long term outcomes with emphasis on disease and treatment- related morbidity and mortality is important. The aim of this study is to describe the long- term clinical course of paediatric patients with ANCA vasculitis. Methods The adult patients in our vasculitis clinics who had presented in childhood, with a follow up time of greater than 10 years were included. We also reviewed the literature for articles describing the clinical outcome of paediatric patients with ANCA vasculitis. Results We describe the clinical course of 8 adults who presented in childhood with ANCA vasculitis. 7 patients had Wegener's granulomatosis and 1 had microscopic polyangiitis. The median age at presentation was 11.5 years, and follow up time ranged form 11 to 30 years. Induction therapy for all patients was steroids and/or cyclophosphamide. Maintenance therapy was with azathioprine or mycophenolate mofetil. Biological agents were used in 3 patients for relapsed disease in adulthood only. Seven patients achieved complete remission. All patients experienced disease relapse, with a median of 4 episodes. Kidney function was generally well preserved, with median eGFR 76 ml/min. Only one patient developed end-stage renal failure and one patient died after 25 years of disease. Treatment-related morbidity rates were high; 7 suffered from infections, 4 were infertile, 2 had skeletal complications, and 1 developed malignancy. Conclusion Close long- term follow up of paediatric patients with ANCA vasculitis is imperative, as this patient cohort is likely to live long enough to develop significant treatment and disease- related morbidities. Prospective cohort studies with novel therapies including paediatric patients are crucial to help us determine the best approach to managing this complex group of patients. In addition, although not yet observed in our series, late cardiovascular morbidity remains a major longer-term potential concern for adult survivors of paediatric vasculitis.

To analyze available evidence on vaccinations in paediatric patients with rheumatic and autoinflammatory diseases. This evidence formed the basis of the recently constructed European League against Rheumatism (EULAR) recommendations for vaccination of these patients.A systematic literature review in the MEDLINE and EMBASE databases was conducted using various terms for vaccinations, paediatric rheumatic and autoinflammatory diseases and immunosuppressive drugs. Only papers on paediatric patients (18 years of age) were selected. A panel of 13 experts in the field graded methodological quality and extracted data using predefined criteria.27 papers were available. No studies were found on autoinflammatory diseases. 14 studies considered live-attenuated vaccines. Evidence so far supports the safety and immunogenicity of non-live composite vaccines, although studies were underpowered to accurately assess safety. Live-attenuated vaccines did not cause disease flares or severe adverse events, not even in patients on methotrexate and low dose glucocorticosteroids. Seven patients on anti-TNFalpha therapy were described receiving the live-attenuated measles, mumps, rubella (n=5) or varicella (n=2) booster without severe adverse events.Data on safety and efficacy of vaccinations in paediatric patients with rheumatic diseases is reassuring, but too limited to draw definite conclusions. More research is needed on the safety and efficacy of especially live-attenuated vaccines in patients with rheumatic and autoinflammatory diseases using high dose immunosuppressive drugs.