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Papers by Pavla Dolezalova

European Journal of Pediatrics

The worldwide outbreak of the novel 2019 coronavirus disease (COVID-19) has led to recognition of... more The worldwide outbreak of the novel 2019 coronavirus disease (COVID-19) has led to recognition of a new immunopathological condition: paediatric inflammatory multisystem syndrome (PIMS-TS). The Czech Republic (CZ) suffered from one of the highest incidences of individuals who tested positive during pandemic waves. The aim of this study was to analyse epidemiological, clinical, and laboratory characteristics of all cases of paediatric inflammatory multisystem syndrome (PIMS-TS) in the Czech Republic (CZ) and their predictors of severe course. We performed a retrospective-prospective nationwide observational study based on patients hospitalised with PIMS-TS in CZ between 1 November 2020 and 31 May 2021. The anonymised data of patients were abstracted from medical record review. Using the inclusion criteria according to World Health Organization definition, 207 patients with PIMS-TS were enrolled in this study. The incidence of PIMS-TS out of all SARS-CoV-2-positive children was 0.9:1,000. The estimated delay between the occurrence of PIMS-TS and the COVID-19 pandemic wave was 3 weeks. The significant initial predictors of myocardial dysfunction included mainly cardiovascular signs (hypotension, oedema, oliguria/anuria, and prolonged capillary refill). During follow-up, most patients (98.8%) had normal cardiac function, with no residual findings. No fatal cases were reported. Conclusions: A 3-week interval in combination with incidence of COVID-19 could help increase pre-test probability of PIMS-TS during pandemic waves in the suspected cases. Although the parameters of the models do not allow one to completely divide patients into high and low risk groups, knowing the most important predictors surely could help clinical management. What is Known: • Preliminary evidence, majority from relatively small, and mostly single-centre patient cohorts, has shown some insights in the basic epidemiological and clinical data of children with a paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). What is New: • To our knowledge, this is the unique published national population-wide cohort allowing to study the epidemiology (including overall incidence), time gap between viral exposure and clinical symptoms of PIMS-TS, and clinical presentations and outcomes within the individual pandemic waves of COVID-19 that were characterised by various prevailing genetic variants of SARS-CoV-2. • We estimated 3-week interval as a most probable period between SARS-CoV-2 infection and PIMS-TS based on nationwide population data using cross-correlation method.

recommendations for diagnosis and treatment of kawasaki disease and henoch schönlein purpura

The overall data retrieved by the Eurofever project have been presented and discussed in this report

Arthritis Research & Therapy, 2020

Background Few clinical trials have investigated the prevention of radiographic progression in ch... more Background Few clinical trials have investigated the prevention of radiographic progression in children with juvenile idiopathic arthritis treated with antirheumatic drugs. This study aimed to investigate radiographic progression in patients with systemic juvenile idiopathic arthritis (sJIA) and patients with polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with the anti–interleukin-6 receptor antibody tocilizumab for 2 years in the TENDER and CHERISH randomized controlled trials, respectively. Methods Standard radiographs of both wrists and both hands in the posteroanterior view were obtained within 4 weeks of baseline and were repeated at weeks 52 ± 4 and 104 ± 4 in both trials. All films were scored by two independent readers using the adapted Sharp–van der Heijde (aSH) and Poznanski scoring methods. Although the Poznanski score indicates bone growth limitation or cartilage growth decrease, which are not the same as joint space narrowing in rheumatoid arthritis,...

Poster Presentations, 2019

Background: In 2008 the Paediatric Rheumatology European Society (PReS) promoted an International... more Background: In 2008 the Paediatric Rheumatology European Society (PReS) promoted an International Project for the study of Autoinflammatory Diseases (AIDs) named Eurofever, whose main purpose is to create a web-based registry for the collection of information in AIDs patients. Objectives: To implement the Registry with the new recently described AIDs and to increase the collection of longitudinal data. Methods: The data were extracted from the Eurofever registry, which is hosted in the PRINTO website (http://www. printo.it). From February 2015 we started the longitudinal collection of follow-up data with particular focus on treatment, modification of the clinical picture, onset of complication/adverse events. We have enrolled patients included in the registry up to 28 September 2018. Results: Up to date 4175 patients have been enrolled (3843 of them with complete demographic information, 1903 M e 1940 F) from 62 countries. For 3356 (87%) patients also clinical data from onset to diagnosis, collected during the first visit performed at referred pediatric or adult center, are available. For each disease the number of enrolled patients is: FMF 1086 pts (951 with complete clinical data); TRAPS 273 pts (256 complete); CAPS 298 pts (279 complete); MKD 205 pts (190 complete); Blau's disease 49 pts (26 complete); PAPA 42 pts (41 complete); NLRP12 mediated periodic fever 13 pts (11 complete); DADA2 14 pts (9 complete); DIRA 3 pts (all complete); SAVI 3 pts (all complete); CANDLE 1 pt (complete) and Majeed 4 pts (all complete). Among multifactorial autoinflammatory diseases: PFAPA 676 pts (551 complete); CNO 581 pts (540 complete); Behcet 214 pts (186 complete), undefined periodic fever 368 pts (292 complete) and Schnitzler 13 pts (all complete). The median onset age is 4 years (range 1 month-75 years), the median diagnosis age is 8 years (range 1 month-78 years). Most of patients (3509, 91%) presented disease onset during pediatric age (<16 years), 334 (9%) during adult age (81 FMF, 31 CAPS, 53 TRAPS, 40 CRMO, 12 Schnitzler syndrome e 90 unknown fever). 405 of 3509 (12%) patients with pediatric onset received diagnosis during adult age. The median diagnostic delay is 5 years; diseases with longer diagnostic delay are: NLRP12 (24 years, range 4-76), CAPS (15 years, range 0-77), PAPA (14 years, range 2-57), TRAPS (12 years, range 0-77). 396 patients have been treated with at least one biologic drug, 1031 with DMARDs, 427 with systemic steroid and 686 with others drugs. The most frequent diseases treated with biologic drugs are: CAPS (38%), multifactorial diseases (22%), TRAPS (14%), MKD (11%), rare monogenic (8%: 1 CANDLE, 2 DIRA, 2 NALP12, 3 Majeed, 8 DADA2 and 14 PAPA), and FMF (7%). Since February 2015, longitudinal visits have been inserted for 477 (12%) patients, with detailed data on treatment and safety. Conclusion: The enrollment in Eurofever Registry is still ongoing. The analysis of data will improve our knowledge both on the natural history of the single disease and on the efficacy/safety of treatment commonly used in the clinical practice.

The Lancet Child & Adolescent Health, 2019

Rheumatology, 2018

Objectives. To provide an overview of the paediatric rheumatology (PR) services in Europe, descri... more Objectives. To provide an overview of the paediatric rheumatology (PR) services in Europe, describe current delivery of care and training, set standards for care, identify unmet needs and inform future specialist service provision. Methods. An online survey was developed and presented to national coordinating centres of the Paediatric Rheumatology International Trials Organisation (PRINTO) (country survey) and to individual PR centres (centre and disease surveys) as a part of the European Union (EU) Single Hub and Access point for paediatric Rheumatology in Europe project. The survey contained components covering the organization of PR care, composition of teams, education, health care and research facilities and assessment of needs. Results. Response rates were 29/35 (83%) for country surveys and 164/288 (57%) for centre surveys. Across the EU, approximately one paediatric rheumatologist is available per million population. In all EU member states there is good access to specialist care and medications, although biologic drug availability is worse in Eastern European countries. PR education is widely available for physicians but is insufficient for allied health professionals. The ability to participate in clinical trials is generally high. Important gaps were identified, including lack of standardized clinical guidelines/recommendations and insufficient adolescent transition management planning.

Annals of the Rheumatic Diseases, 2015

Background In the traditional model nursing and physiotherapy staff (allied health professionals,... more Background In the traditional model nursing and physiotherapy staff (allied health professionals, AHP) competencies are limited and funding to support adequate AHP input in paediatric rheumatology service is not automatically provided. A case needs to be presented to healthcare providers and hospital managers. Objectives A comprehensive system of therapeutic interventions provided by AHP to paediatric patients with JIA has been developed as an add-on to the standard rheumatology care. It covers theoretical and practical patient and parent education as well as psychosocial support in the form of standardized interview and a practical session provided independently by a nurse specialist and a physiotherapist (PT). We have prospectively tested performance of these interventions in a cohort of JIA patients and report interim results of the first year of the study. Methods Patients younger than 18 years fulfilling ILAR classification of JIA were eligible. Study inclusion criteria were: 1. Active disease (at least 1 joint with active synovitis). 2. Newly diagnosed JIA or JIA relapse requiring new drug therapy. 3. Informed consent. Performance of interventions was tested by standardized quality of life (QOL) assessments (CHAQ, parent/patient global assessment PaG, PedsQL, SMILY-illness, JAMAR) along physician-derived disease activity measures (physician global-PhG, active and limited joint count-AJC, LJC, ESR/CRP, JADAS71). Consecutive patients have been randomised into 3 groups according to the frequency of AHP interventions (A:3-monthly, B:6-monthly, C: control group with standard care only). Results Total of 88 patients (61 girls) were recruited, all Caucasians, 54 with new JIA and 34 relapses. Distribution of JIA onset subtypes was as follows: PolyJIA (RF-): 44, OligoJIA: 27, Systemic JIA: 9, Psoriatic JIA: 3, Enthesopathic JIA: 5. Their main characteristics at study entry were:age 8 years, active joint count 6.4, ESR 22mm/h, CHAQ 0.43, PhG 32mm, PaG 22mm, PedsQL 71, JADAS 12.7. There were no significant differences between the 3 groups A, B, C with 29, 28 and 30 patients respectively. 77 patients received methotrexate (MTX, s.c. in 60) and in 15 biologic was added (9 TNF blockers, 3 tocilizumab, 2 abatacept, 1 canakinumab). 35 patients received intraarticular triamcinolone hexacetonide (IATH). In 38 patients 6 months follow-up data were available showing improved disease activity. When QOL assessments were compared between intervention groups AB and control group there were no significant differences found, but there was a trend towards better PaG and PedsQL scores after 6 months. Conclusions Standardized comprehensive AHP interventions covering patient education and psychosocial support are feasible when provided by trained professionals in the clinic setting accommodating increased staff requirements. This is well compensated by more effective use of physician's clinic time when education is partly covered and augmented by AHP. Patient perception and true impact on QOL measures needs to be assessed in larger patient cohorts and in longer follow-up. Acknowledgements Supported by the grant IGA NT/14149-3 Disclosure of Interest None declared

Clinical and experimental rheumatology

This paper aims to describe clinical and laboratory features and disease outcome in a single-cent... more This paper aims to describe clinical and laboratory features and disease outcome in a single-centre cohort of patients with PFAPA syndrome (Periodic Fever, Aphtous stomatitis, Pharyngitis, and Adenitis) and to test performance of diagnostic and therapeutic algorithms. Patients fulfilling criteria were selected from the fever clinic population. Prospective follow-up together with recruitment of newly diagnosed patients followed pre-defined guidelines. Diagnostic and therapeutic algorithms and definitions of outcome and therapy response were formulated. Paired blood samples during febrile and afebrile periods were compared. Out of 176 patients referred for suspected periodic fever 125 children fulfilled criteria. Their age at onset was 23 months, median episode duration 3.5 days at 4-week intervals. Fever was associated with pharyngitis (91%), cervical adenitis (78%) and aphtae (41%). Among therapeutic options, episodic prednisone proved to be the most common first-line treatment. Adm...

Objectives. To evaluate the performance of the Birmingham Vasculitis Activity Score (BVAS) v3 and... more Objectives. To evaluate the performance of the Birmingham Vasculitis Activity Score (BVAS) v3 and the Disease Extent Index (DEI) for the assessment of disease activity in 4 primary childhood (c-) systemic vasculitides. Methods. Patients fulfilling the EULAR/PRINTO/PRES (Ankara) c-vasculitis classification criteria for Henoch-Schonlein purpura (HSP), childhood (c) polyarteritis nodosa (c-PAN), c-Wegener’s granulomatosis (c-WG) and c-Takayasu arteritis (c-TA) with disease duration at the time of diagnosis ≤3 months were extracted from the PRINTO database. The performance of the BVAS and DEI were examined by assessing convergent validity, the pattern of disease involvement, and responsiveness. We also evaluated alternative unweighted scoring methods for both tools. Results. The analysis set included 796 patients with 669 HSP, 80 c-PAN, 25 cWG and 22 c-TA. The median age at diagnosis was 6.9 years (6.6–12) and median delay in making the diagnosis from the onset of signs/symptoms was 0.01 (0.003-0.027) years. A strong correlation was found between the BVAS and DEI (r s =0.78) while correlation with the physician global assessment was moderate (r s =0.48) with BVAS and poor with DEI (r s =0.25). Both the BVAS and DEI sub-scores and total scores were able to descrive the disease involvement in the 4 childhood vasculitides. Responsiveness was large (>1.5) for both tools. The performance characteristics of the BVAS and DEI with the unweighted methods were comparable. Conclusion. This study demonstrates that both the BVAS and DEI are valid tools for the assessment of the level of disease activity in a large cohort of childhood acute and chronic vasculitides.

Pediatric Rheumatology, 2011

Journal of the American Society of Nephrology, 2009

Recent studies have suggested that mycophenolate mofetil (MMF) may offer advantages over intraven... more Recent studies have suggested that mycophenolate mofetil (MMF) may offer advantages over intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis, but these therapies have not been compared in an international randomized, controlled trial. Here, we report the comparison of MMF and IVC as induction treatment for active lupus nephritis in a multinational, two-phase (induction and maintenance) study. We randomly assigned 370 patients with classes III through V lupus nephritis to open-label MMF (target dosage 3 g/d) or IVC (0.5 to 1.0 g/m 2 in monthly pulses) in a 24-wk induction study. Both groups received prednisone, tapered from a maximum starting dosage of 60 mg/d. The primary end point was a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine. Secondary end points included complete renal remission, systemic disease activity and damage, and safety. Overall, we did not detect a significantly different response rate between the two groups: 104 (56.2%) of 185 patients responded to MMF compared with 98 (53.0%) of 185 to IVC. Secondary end points were also similar between treatment groups. There were nine deaths in the MMF group and five in the IVC group. We did not detect significant differences between the MMF and IVC groups with regard to rates of adverse events, serious adverse events, or infections. Although most patients in both treatment groups experienced clinical improvement, the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis.

Annals of the Rheumatic Diseases, 2014

Background: Giant cell arteritis (GCA) is the most common systemic vasculitis in adults aged 50 y... more Background: Giant cell arteritis (GCA) is the most common systemic vasculitis in adults aged 50 years or above. Annual incidence rates vary widely from 6.9-76.6 per 10 5 of adults in this age group, depending on the region. 1 Objectives: To determine the incidence rate of GCA in our population. Methods: We prospectively collected incident cases of GCA from January 1st 2011 to December 31st 2012 at our department of rheumatology which is a part of an integrated secondary/tertiary university teaching hospital that is the only referral center serving a region representing approximately a quarter of the national adult population. Additionally, newly diagnosed cases of GCA between January 1st 2009 and December 31st 2010 were retrospectively identified by searching the electronic patient records for ICD-10 codes M31.5 and M31.6 at our department. The retrospective approach and search strategy was also applied on electronic medical records at the departments of infectious diseases and ophthalmology between January 1st 2009 and December 31st 2012. To further reduce possibility of underreporting, the attached medical faculty's Institute of Pathology provided a list of all temporal artery biopsies examined during the observation period which were then cross-referenced with the hospital's electronic medical records. Annual incidence rate for GCA was then calculated. Results: During the four year observation period we identified 97 new cases of GCA (68% female; mean (SD) age 75.6 (8.1) years) from a well-defined adult white Caucasian population of 232,041 inhabitants aged 50 or above. The temporal artery biopsy was consistent with GCA, negative or not performed in 75.3%, 18.6, and 6.2% of cases, respectively. Thus, the annual incidence of GCA in our population is 10.5 (95% CI 8.5-12.7), and 4.7 (95% CI 3.8-5.7) per 10 5 adults aged 50, and 20 years or above, respectively. Conclusions: The annual incidence rate of 10.5 per 10 5 adults aged 50 or above makes GCA the most common systemic vasculitis in this age group of our population. Although the GCA almost exclusively affects adults over 50 years of age, the incidence rate of 4.7 per 10 5 adults aged 20 and above, also makes it the most common systemic vasculitis in the adult population overall, with IgA vasculitis coming a close second with 3.7 per 10 5 adults aged 20 years or above.

The Lancet, 2008

Background Systemic-onset juvenile idiopathic arthritis does not always respond to available trea... more Background Systemic-onset juvenile idiopathic arthritis does not always respond to available treatments, including antitumour necrosis factor agents. We investigated the effi cacy and safety of tocilizumab, an anti-interleukin-6-receptor monoclonal antibody, in children with this disorder. Methods 56 children (aged 2-19 years) with disease refractory to conventional treatment were given three doses of tocilizumab 8 mg/kg every 2 weeks during a 6-week open-label lead-in phase. Patients achieving an American College of Rheumatology Pediatric (ACR Pedi) 30 response and a C-reactive protein concentration (CRP) of less than 5 mg/L were randomly assigned to receive placebo or to continue tocilizumab treatment for 12 weeks or until withdrawal for rescue medication in a double-blind phase. The primary endpoint of the double-blind phase was an ACR Pedi 30 response and CRP concentration of less than 15 mg/L. Patients responding to tocilizumab and needing further treatment were enrolled in an open-label extension phase for at least 48 weeks. The analysis was done by intention to treat. This study is registered with ClinicalTrials.gov, numbers NCT00144599 (for the open-label lead-in and doubleblind phases) and NCT00144612 (for the open-label extension phase). Findings At the end of the open-label lead-in phase, ACR Pedi 30, 50, and 70 responses were achieved by 51 (91%), 48 (86%), and 38 (68%) patients, respectively. 43 patients continued to the double-blind phase and were included in the effi cacy analysis. Four (17%) of 23 patients in the placebo group maintained an ACR Pedi 30 response and a CRP concentration of less than 15 mg/L compared with 16 (80%) of 20 in the tocilizumab group (p<0•0001). By week 48 of the open-label extension phase, ACR Pedi 30, 50, and 70 responses were achieved by 47 (98%), 45 (94%), and 43 (90%) of 48 patients, respectively. Serious adverse events were anaphylactoid reaction, gastrointestinal haemorrhage, bronchitis, and gastroenteritis. Interpretation Tocilizumab is eff ective in children with systemic-onset juvenile idiopathic arthritis. It might therefore be a suitable treatment in the control of this disorder, which has so far been diffi cult to manage. Funding Chugai Pharmaceuticals.

Pediatric Rheumatology, 2014

Arthritis Research & Therapy

Background To derive a list of opportunistic infections (OI) through the analysis of the juvenile... more Background To derive a list of opportunistic infections (OI) through the analysis of the juvenile idiopathic arthritis (JIA) patients in the Pharmachild registry by an independent Safety Adjudication Committee (SAC). Methods The SAC (3 pediatric rheumatologists and 2 pediatric infectious disease specialists) elaborated and approved by consensus a provisional list of OI for use in JIA. Through a 5 step-procedure, all the severe and serious infections, classified as per MedDRA dictionary and retrieved in the Pharmachild registry, were evaluated by the SAC by answering six questions and adjudicated with the agreement of 3/5 specialists. A final evidence-based list of OI resulted by matching the adjudicated infections with the provisional list of OI. Results A total of 772 infectious events in 572 eligible patients, of which 335 serious/severe/very severe non-OI and 437 OI (any intensity/severity), according to the provisional list, were retrieved. Six hundred eighty-two of 772 (88.3%) ...