INTRODUCTION: Protracted febrile myalgia syndrome (PFMS) is a rare manifestation of familial Mediterranean fever (FMF), characterized by myalgia, fever and elevated inflammatory markers lasting several weeks. As the hallmark of FMF are short episodes of disease symptoms, the long duration of PFMS may lead to a delayed diagnosis and treatment. OBJECTIVES: 1. To perform a review of literature and rheumatology textbooks focused on clinical features and treatment of PFMS in children. 2. To present our own case. METHODS: All articles in Pub Med generated using the keywords "protracted febrile myalgia" and information on PFMS in seven rheumatology textbooks were collected. The systematic review was supplemented with our own case presentation. RESULTS: In total, 18 articles with 78 pediatric patients (including our own) were retrieved. More than half of the patients presented with PFMS as the first manifestation of FMF. All complained of myalgia, 65% of abdominal pain and 26% had a rash. Corticosteroids (CS) were effective in 77%. In all CS-refractory cases, anakinra was shown efficient. MRI was used in 5 patients and showed myositis in all of them. The scrutiny of seven rheumatology textbooks showed that PFMS presenting with myalgia was mentioned in six. Possible accompanying symptoms were described only once, the long duration of symptoms twice, the efficacy of corticosteroids three times and anakinra only once. The presented 6 year old patient manifested with fever, myalgia, abdominal pain and petechial rash lasting 6 weeks. She had undergone multiple diagnostic procedures before her parents mentioned a positive family history for FMF. The subsequent genetic testing confirmed a homozygosity for M694V pathogenic variant in the MEFV gene. CONCLUSION: The long duration of PFMS may be misleading to clinicians especially if PFMS occurs at manifestation of FMF. The fact that more than half of the reported patients experienced PFMS as the presenting symptom of FMF is one of the key findings of our study. Our case presentation demonstrates the importance of genetic testing early in suspected autoinflammatory diseases. Furthermore, MRI may be an important diagnostic tool showing myositis in PFMS.

• MeSH
• Child MeSH
• Familial Mediterranean Fever * complications   diagnosis   MeSH
• Fever * diagnosis   etiology   MeSH
• Humans MeSH
• Magnetic Resonance Imaging methods   MeSH
• Myalgia * diagnosis   etiology   MeSH
• Syndrome MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH
• Systematic Review MeSH

We established efficient first trimester prediction models for small-for-gestational age (SGA) and fetal growth restriction (FGR) without the presence of preeclampsia (PE) regardless of the gestational age of the onset of the disease [early FGR occurring before 32 gestational week or late FGR occurring after 32 gestational week]. The retrospective study was performed on singleton Caucasian pregnancies (n = 6440) during the period 11/2012-3/2020. Finally, 4469 out of 6440 pregnancies had complete medical records since they delivered in the Institute for the Care of Mother and Child, Prague, Czech Republic. The study included all cases diagnosed with SGA (n = 37) or FGR (n = 82) without PE, and 80 selected normal pregnancies. Four microRNAs (miR-1-3p, miR-20a-5p, miR-146a-5p, and miR-181a-5p) identified 75.68 % SGA cases at 10.0 % false positive rate (FPR). Eight microRNAs (miR-1-3p, miR-20a-5p, miR-20b-5p, miR-126-3p, miR-130b-3p, miR-146a-5p, miR-181a-5p, and miR-499a-5p) identified 83.80 % SGA cases at 10.0 % FPR. The prediction model for SGA based on microRNAs was further improved via implementation of maternal clinical characteristics [maternal age and BMI, an infertility treatment by assisted reproductive technology (ART), first trimester screening for PE and/or FGR and for spontaneous preterm, both by FMF algorithm]. Then 81.08 % and 89.19 % pregnancies developing SGA were identified at 10.0 % FPR in case of utilization of 4 microRNA and 8 microRNA biomarkers. Simplified prediction model for SGA based on limited number of maternal clinical characteristics (maternal age and BMI, an infertility treatment by ART, and 4 microRNAs) does not improve the detection rate of SGA (70.27 % SGA cases at 10.0 % FPR) when compared with prediction model for SGA based just on the expression profile of 4 or 8 microRNAs biomarkers. Seven microRNAs only (miR-16-5p, miR-20a-5p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-342-3p, and miR-574-3p) identified 42.68 % FGR cases at 10.0 % FPR (AUC 0.725). However, the combination of 10 microRNAs only (miR-16-5p, miR-20a-5p, miR-100-5p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-342-3p, and miR-574-3p) reached a higher discrimination power (AUC 0.774). It identified 40.24 % FGR cases at 10.0 % FPR. The prediction model for any subtype of FGR based on microRNAs was further improved via implementation of maternal clinical characteristics [maternal age and BMI, an infertility treatment by ART, the parity (nulliparity), the occurrence of SGA or FGR in previous gestation, and the occurrence of any autoimmune disorder, and the presence of chronic hypertension]. Then 64.63 % and 65.85 % pregnancies destinated to develop FGR were identified at 10.0 % FPR in case of utilization of 7 microRNA biomarkers or 10 microRNA biomarkers. When other clinical variables next to those ones mentioned above such as first trimester screening for PE and/or FGR and for spontaneous preterm, both by FMF algorithm, were added to the prediction model for FGR, the detection power was even increased to 74.39 % cases and 78.05 % cases at 10.0 % FPR.

• MeSH
• Biomarkers MeSH
• Child MeSH
• Gestational Age MeSH
• Infertility * MeSH
• Infant MeSH
• Humans MeSH
• MicroRNAs * genetics   metabolism   MeSH
• Infant, Newborn MeSH
• Fetus metabolism   MeSH
• Pre-Eclampsia * genetics   MeSH
• Pregnancy Trimester, First MeSH
• Retrospective Studies MeSH
• Fetal Growth Retardation genetics   diagnosis   MeSH
• Pregnancy MeSH
• Check Tag
• Child MeSH
• Infant MeSH
• Humans MeSH
• Infant, Newborn MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Autoinflamatorní onemocnění (AID) zahrnují pestrou skupinu chorob definovaných porušenou regulací vrozeného imunitního systému. Rychlost rozvoje této oblasti umožňují především citlivější metody genetického vyšetření. Klinickým projevem sterilního zánětu bývá epizodická horečka v doprovodu různého orgánového postižení. Detailnější pochopení etiopatogenetického pozadí AID otevírá nové perspektivy cílené terapii. Cílem léčby je kontrola aktivity onemocnění a prevence poškození orgánů. Péče o pacienty s AID by měla být vedena multidisciplinárním týmem v rámci centra vysoce specializované péče. Nejdéle známou skupinou AID jsou syndromy periodické horečky, kam řadíme familiární středomořskou horečku (FMF), deficit mevalonátkinázy (MKD), periodický syndrom asociovaný s receptorem pro tumor nekrotizující faktor (TRAPS), periodické horečky asociované s kryopyrinem (CAPS) a periodickou horečku s afty, faryngitidou a krční adenitidou (PFAPA ). Článek poskytuje základní obecné informace o skupině autoinflamatorních nemocí a nejčastějších typech periodických horeček.

Autoinflammatory diseases (AID) include a diverse group of diseases defined by dysregulation of the innate immune system. Clinical manifestations of sterile inflammation include usually episodic fever with variable presence of organ involvement. A more detailed understanding of the etiopathogenetic background of AID opens new perspectives for targeted therapies. Disease activity control and prevention of organ damage are the main treatment goals. Multidisciplinary management of AID should be concentrated in specialised centers. The best known group of AIDs,periodic fever syndromes,include Familial Mediterranean fever (FMF), Mevalonate kinase deficiency (MKD), Tumor necrosis factor receptor-associated periodic syndrome (TRAPS), Cryopyrin-associated periodic syndromes (CAPS) and Periodic fever with aphthae, pharyngitis and cervical adenitis (PFAPA ). The article provides general information about the group of autoinflammatory diseases and the most common types of periodic fevers.

• Keywords
• autoinflamatorní nemoci,
• MeSH
• Autoimmune Diseases * diagnosis   physiopathology   therapy   MeSH
• Hereditary Autoinflammatory Diseases diagnosis   physiopathology   therapy   MeSH
• Familial Mediterranean Fever diagnosis   physiopathology   therapy   MeSH
• Fever MeSH
• Interleukin-1 MeSH
• Humans MeSH
• High-Throughput Nucleotide Sequencing MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Monogenní syndromy periodických horeček představují heterogenní skupinu autoinflamatorních onemocnění zahrnující syndromy, jako jsou periodické horečky asociované s kryopyrinem (CAPS), receptorem pro tumor nekrotizující faktor (TRAPS), deficitem mevalonátkinázy (MKD/HIDS) a familiární středomořská horečka (FMF). Navzájem se odlišují patogenezí, klinickými projevy a závažností. Klíčovou roli u všech těchto syndromů ovšem hrají cytokiny z rodiny interleukinu 1 (IL-1). Inhibice zmíněných cytokinů, především IL-1, tak hraje zásadní roli v jejich léčbě. V současnosti je k dispozici řada léčivých přípravků, které se liší strukturou, mechanismem působení, účinností a spektrem nežádoucích účinků. Mezi nejdostupnější patří anakinra, kanakinumab a rilonacept. Zároveň však probíhá řada klinických hodnocení s jinými velmi nadějnými léčivy, například gevokizumabem, tadekinigem alfa či tranilastem. V následujícím přehledu přinášíme nový pohled na účinnost a bezpečnost inhibitorů IL-1, který poskytly výsledky recentních klinických studií.

Monogenic periodic fever syndromes are heterogeneous group of autoinflammatory diseases including distinct syndromes, such as cryopyrin-associated periodic syndrome (CAPS), tumor necrosis factor alpha receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency/hyper IgD syndrome (MKD/HIDS), and familial Mediterranean fever (FMF). Individual diseases differ in pathogenesis, clinical manifestations, and severity. However, cytokines from the interleukin 1 (IL-1) family play a key role in all of them. Inhibition of these cytokines, especially IL-1, thus plays a crucial role in their treatment. At present, we have a wide range of drugs that differ in structure, mechanism of action, efficacy, and spectrum of side effects. The most available are anakinra, canakinumab and rilonacept. Moreover, several clinical trials are currently underway with other very promising drugs, such as gevokizumab, tadekinig alfa or tranilast. In the following review, we provide a new perspective on the efficacy and safety of IL-1 inhibitors that have provided the novel results coming from recently published clinical trials.

• Keywords
• kanakinumab, Rilonacept,
• MeSH
• Interleukin 1 Receptor Antagonist Protein * immunology   therapeutic use   MeSH
• Anti-Inflammatory Agents therapeutic use   MeSH
• Hereditary Autoinflammatory Diseases * drug therapy   immunology   pathology   MeSH
• Antibodies, Monoclonal, Humanized immunology   therapeutic use   MeSH
• Clinical Trials as Topic MeSH
• Humans MeSH
• Cryopyrin-Associated Periodic Syndromes drug therapy   immunology   pathology   MeSH
• Recombinant Fusion Proteins immunology   therapeutic use   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

• Publication type
• Meeting Abstract MeSH

Preeklampsia (PE) je jedna z najčastejších a najnebezpečnejších komplikácii tehotenstva. Vysoká mortalita a morbidita matky a plodu poukazujú na potrebu jej včasnej predikcie a prevencie. Množstvo rozsiahlych štúdii sa zameriava na včasný skríning preeklampsie, zamedzenie jej vzniku a úspešnú liečbu. Autorka článku počas dvojročnej praxe v Nadácií fetálnej medicíny v Londýne (The Fetal Medicine Foundation, FMF) pod vedením profesora Nicolaidesa sa podieľala na štúdiách SPREE, ASPRE a EVENTS, ktoré viedli k vytvoreniu nového manažmentu preeklampsie. Cieľom článku je predstaviť vývoj a výhody kombinovaného skríningu v 11. – 13.+6 gestačnom týždni na výpočet rizika preeklampsie. Doposiaľ hlavným výstupom prvotrimestrálneho skríningu boli riziká aneuploidií, ale v súčasnosti sa výpočet rizík rozšíril aj na tehotenské komplikácie ako sú preeklampsia, intrauterinná rastová reštrikcia a predčasný pôrod. Štúdia ASPRE ukázala efektivitu v preventívnom podávaní aspirínu 150 mg vo večerných hodinách pacientkam s vysokým rizikom PE od 12. do 36. týždňa gravidity. Tento rok FMF tím navrhol nové skríningové stratégie, ktoré závisia od toho, ktorý biomarker sa využíva (PAPP-A vs. PlGF). Najefektívnejší skríning preeklampsie je s využitím PlGF. Keďže sa rutinne v prvom trimestri odoberá PAPP-A pre skríning aneuploidií, z tohto dôvodu bolo v štúdiách sledované a potvrdené aj jeho využitie v rôznych kombináciách skríningových stratégií v snahe dosiahnuť porovnateľnú senzitivitu ako pri skríningu s PlGF. Ďalším nedávnym úspechom bolo vypracovanie prvotrimestrálneho kombinovaného skríningu preeklampsie u dvojčiat.

Preeclampsia (PE) is one of the most common and dangerous pregnancy complications. High mortality and morbidity of mother and foetus refer to the need of early predicition and prevention of PE. In an attempt to screen early and to prevent PE many strategies have been studied. The author of this paper worked for 2 years in the Fetal Medicine Foundation (FMF) under the supervision of Professor Nicolaides and partici-pated in the studies SPREE, ASPRE and EVENTS which lead to establishment of a new managment of PE. The purpose of this paper is to present the development and advantages of the combined screening in the 11 – 13+6 weeks for risk calculation of PE. Up to now the main result of the first-timester combined screening was the risk calculation of aneuploidies. Nowadays the results extended to pregnancy complications as PE, growth restriction and preterm delivery. The ASPRE study presented the efficacy in the preventive treatment of the high-risk patients for PE with aspirin 150 mg taken at bed time from 12 to 36 weeks. This year FMF proposed new screening strategies which depend on the biomarker (PAPP-A vs PlGF) used in the screen cal-culation. The best performance of screening for PE is achieved by applying PlGF. Since PAPP-A is used rou-tinely as part of the screening for aneuploidies, its additive value was examined in different combinations of screening strategies and confirmed its application with similar detection rate as screening by PlGF. The most recent success was a development of the first-trimester screening for PE in twins.

• MeSH
• Risk Assessment methods   MeSH
• Pregnancy Complications diagnosis   classification   prevention & control   MeSH
• Humans MeSH
• Disease Management MeSH
• Pre-Eclampsia * diagnosis   prevention & control   MeSH
• Prenatal Diagnosis methods   MeSH
• Pregnancy Trimester, First physiology   MeSH
• Pregnant People MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Review MeSH

Tato práce popisuje zavedení a optimalizaci metody umožňující analýzu produkce prozánětlivých cytokinů buňkami vrozené imunity. Diagnos-tika autoinflamatorních onemocnění, jako jsou familiární středozemní horečka (Familial Mediterranean Fever, FMF), syndrom Schnitzlerové či hyper IgD syndrom (HIDS), imunodysregulačních a autoimunitních onemocnění s autoinflamatorní složkou, je často složitá pro nespecifický klinický obraz. Přesná diagnóza je možná až genetickým vyšetřením, které však není u všech pacientů průkazné a u některých onemocnění ani není genetický původ znám. Nejasnosti v diagnostice onemocnění a rozlišení patogenetických pochodů u konkrétních pacientů ztěžují či zcela znemožňují nastavení cílené terapie, která v současné době zahrnuje i možnosti specifické blokády jednotlivých prozánětlivých cytokinů. Z tohoto důvodu jsme se zaměřili na zavedení, nastavení a optimalizaci metody, která by umožnila rychle a ekonomicky v malém množství lehce dostupného biomateriálu (periferní krve) odhalit aberantní produkci vybraných prozánětlivých cytokinů, a přispěla by tak ke správné diagnostice a výběru vhodné terapie. Produkce základních prozánětlivých cytokinů (IL-1β, IL-6, TNFα) tvořených zejména monocyty po stimulaci lipopo-lysacharidem (LPS) byla v práci testována pomocí dvou rozdílných metod – průtokovou cytometrií detekující intracelulární produkci cytokinů a metodou ALBIA (Addressable Laser Bead Immuno Assay) – Luminex, která umožňuje stanovení množství cytokinů uvolněných do superna-tantu. Na zdravých dárcích byla optimalizována délka stimulace, koncentrace LPS a čas zastavení uvolňování cytokinů z buněk Brefeldinem A.

This work aims at the introduction and optimization of methods for innate immune parameters analysis with a detailed focus on proinflammatory cytokines. Autoinflammatory diseases like Familial Mediterranean Fever (FMF), Schnitzler syndrome and Hyper-IgD syndrome (HIDS), as well as autoimmune diseases that involve the inflammatory component, are usually characterized by a non-specific clinical manifestation. Therefore, obtaining a proper diagnosis of these disorders remains complicated. Genetic examination serves as an accurate diagnostic method for the esta-blishment of monogenic autoinflammatory disease diagnosis. However, genetic profiling cannot be provided to all patients. Moreover, some of the mutations responsible for the development of the disease haven’t been defined yet. Therapy of inflammatory diseases is currently based on molecules that are capable of blocking the function of inflammatory cytokines. In inflammatory diseases, the proper understanding of disease pathogenesis is still far from satisfactory and therefore, selecting the right therapeutic treatment modality keeps causing difficulties. For this reason, we focused on the introduction and optimization of a novel method which has a potential to detect activation of inflammatory cytokines and may, therefore, contribute to the correct diagnosis and direct therapeutic strategy. Production of main proinflammatory cytokines (IL-1β, IL-6, TNFα), which are produced by monocytes after lipopolysaccharide stimulation, was tested with two different methods – flow cytometry, detecting the intracellular production of cytokines, and ALBIA (Addressable Laser Bead Immuno Assay) - Luminex method, which can detect extracellular cytokine release into supernatant. Using flow cytometry we optimized the setting by detecting the optimal time of stimulation, concentration of LPS and the optimal time to stop cytokine exocytosis after adding Brefeldin A.

• Keywords
• metoda Luminex,
• MeSH
• Data Analysis MeSH
• Time Factors MeSH
• Cytokines * immunology   blood   MeSH
• Fever of Unknown Origin * diagnosis   genetics   immunology   MeSH
• Humans MeSH
• Flow Cytometry MeSH
• Check Tag
• Humans MeSH

Autoinflammatory diseases (AIDs) represent a rare and heterogeneous group of disorders characterized by recurrent episodes of inflammation and a broad range of clinical manifestations. The most common symptoms involve recurrent fevers, musculoskeletal symptoms, and serositis; however, AIDs can also lead to life-threatening complications, such as macrophage activation syndrome (MAS) and systemic AA amyloidosis. Typical monogenic periodic fever syndromes include cryopyrin-associated periodic fever syndrome (CAPS), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency/hyper IgD syndrome (MKD/HIDS), and familial Mediterranean fever (FMF). However, a number of other clinical entities, such as systemic juvenile idiopathic arthritis (sJIA), adult-onset Still's disease (AOSD), Kawasaki disease (KD) and idiopathic recurrent pericarditis (IRP), display similar phenotypical and immunological features to AIDs. All these diseases are pathophysiologicaly characterized by dysregulation of the innate immune system and the central pathogenic role is attributed to the IL-1 cytokine family (IL-1α, IL-1β, IL-1Ra, IL-18, IL-36Ra, IL-36α, IL-37, IL-36β, IL-36g, IL-38, and IL-33). Therefore, reasonable therapeutic approaches aim to inhibit these cytokines and their pathways. To date, several anti-IL-1 therapies have evolved. Each drug differs in structure, mechanism of action, efficacy for the treatment of selected diseases, and side effects. Most of the available data regarding the efficacy and safety of IL-1 inhibitors are related to anakinra, canakinumab, and rilonacept. Other promising therapeutics, such as gevokizumab, tadekinig alfa, and tranilast are currently undergoing clinical trials. In this review, we provide sophisticated and up-to-date insight into the therapeutic uses of different IL-1 inhibitors in monogenic periodic fever syndromes.

• MeSH
• Anti-Inflammatory Agents therapeutic use   MeSH
• Hereditary Autoinflammatory Diseases drug therapy   immunology   MeSH
• Interleukin-1 antagonists & inhibitors   MeSH
• Humans MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Brožura, která informuje o různých aspektech autoinflamatorních nemocí. Určeno odborné veřejnosti.

• MeSH
• Hereditary Autoinflammatory Diseases MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• alergologie a imunologie
• dermatovenerologie
• NML Publication type
• brožury
• informační publikace

Typ studie: Systematický přehledový článek. Název a sídlo pracoviště: Oddělení klinické biochemie, Fakultní nemocnice Olomouc; Porodnickogynekologická klinika, Lékařská fakulta Univerzity Palackého v Olomouci, Fakultní nemocnice Olomouc; Ústav pro péči o matku a dítě a 3. lékařská fakulta Univerzity Karlovy, Praha; G-CENTRUM Olomouc, Olomouc; Genetika Plzeň, Plzeň. Metodika, výsledky: Preeklampsie (Preeclampsia, PE) je závažné multiorgánové onemocnění komplikující těhotenství. Je celosvětově hlavní příčinou mateřské a perinatální mortality a morbidity. Z provedených studií vyplynulo, že u těhotných žen se zvýšeným rizikem je možná prevence rozvoje závažných forem onemocnění včasným zahájením léčby kyselinou acetylsalicylovou. Aby byla prevence účinná, měla by být riziková skupina těhotných žen identifikována v 11.–13. gestačním týdnu. Jediná, v mnoha studiích validovaná metodika pro provádění screeningu PE s dostatečnou diagnostickou účinností v I. trimestru těhotenství je dána The Fetal Medicine Foundation (FMF) a byla přijata a publikována v novém doporučení The International Federation of Gynecology and Obstetrics (FIGO). Závěr: Tento článek shrnuje nejnovější poznatky a postupy pro provádění screeningu preeklampsie v rámci kombinovaného screeningu v I. trimestru těhotenství a způsob prevence rozvoje závažných forem PE podáváním nízkých dávek kyseliny acetylsalicylové.

Design: Review article. Setting: Department of Clinical Biochemistry, University Hospital Olomouc; Department of Obstetrics and Gynecology, Palacky University Olomouc, Faculty of Medicine and Dentistry, University Hospital Olomouc; The Institute for the Care of Mother and Child and 3rd Faculty of Medicine Charles University, Prague; G-CENTRUM Olomouc, Olomouc; Genetika Plzeň, Pilsen. Methods, results: Preeclampsia (PE) is a multisystem disorder complicating pregnancy. It is the leading cause of maternal and perinatal mortality and morbidity worldwide. Recent studies have shown that high-risk pregnant women may benefit from low-dose acetylsalicylic acid early therapy in prevention of the development of severe forms of the disease. The risk group of pregnant women should be identified in 11–13 gestational week for effective prevention. The only procedure validated in many studies for performing PE screening with sufficient diagnostic accuracy in the first trimester of pregnancy is given by The Fetal Medicine Foundation (FMF) and has been adopted and published in a new recommendation by The International Federation of Gynecology and Obstetrics (FIGO). Conclusion: This article summarizes the recent findings and recommendation for performing screening of preeclampsia in 1st trimester of pregnancy and how to prevent the development of severe forms of PE by low-dose acetylsalicylic acid therapy.

• Keywords
• pulzatilní index v děložních tepnách,
• MeSH
• Arterial Pressure MeSH
• Aspirin therapeutic use   MeSH
• Pregnancy Complications MeSH
• Humans MeSH
• Health Care Costs MeSH
• Placenta Growth Factor MeSH
• Pre-Eclampsia * diagnosis   prevention & control   MeSH
• Pregnancy MeSH
• Check Tag
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Review MeSH