BACKGROUND: Systemic autoinflammatory disorders (SAIDs) represent a growing spectrum of diseases characterized by dysregulation of the innate immune system. The most common pediatric autoinflammatory fever syndrome, Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA), has well defined clinical diagnostic criteria, but there is a subset of patients who do not meet these criteria and are classified as undefined autoinflammatory diseases (uAID). This project, endorsed by PRES, supported by the EMERGE fellowship program, aimed to analyze the evolution of symptoms in recurrent fevers without molecular diagnosis in the context of undifferentiated AIDs, focusing on PFAPA and syndrome of undifferentiated recurrent fever (SURF), using data from European AID registries. METHODS: Data of patients with PFAPA, SURF and uSAID were collected from 3 registries including detailed epidemiological, demographic and clinical data, results of the genetic testing and additional laboratory investigations with retrospective application of the modified Marshall and PRINTO/Eurofever classification criteria on the cohort of PFAPA patients and preliminary SURF criteria on uSAID/SURF patients. RESULTS: Clinical presentation of PFAPA is variable and some patients did not fit the conventional PFAPA criteria and exhibit different symptoms. Some patients did not meet the criteria for either PFAPA or SURF, highlighting the heterogeneity within these groups. The study also explored potential overlaps between PFAPA and SURF/uAID, revealing that some patients exhibited symptoms characteristic of both conditions, emphasizing the need for more precise classification criteria. CONCLUSIONS: Patients with recurrent fevers without molecular diagnoses represent a clinically heterogeneous group. Improved classification criteria are needed for both PFAPA and SURF/uAID to accurately identify and manage these patients, ultimately improving clinical outcomes.

• Klíčová slova
• AID-Net, Autoinflammatory diseases, Eurofever, JIR-cohort, PFAPA, SURF,
• MeSH
• aftózní stomatitida * diagnóza   epidemiologie   MeSH
• dědičné zánětlivé autoimunitní nemoci * diagnóza   MeSH
• dítě MeSH
• faryngitida * diagnóza   MeSH
• horečka etiologie   diagnóza   MeSH
• kojenec MeSH
• lidé MeSH
• lymfadenitida * diagnóza   epidemiologie   MeSH
• mladiství MeSH
• předškolní dítě MeSH
• recidiva MeSH
• registrace * MeSH
• retrospektivní studie MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa epidemiologie   MeSH

Familial Mediterranean Fever is an autosomal recessive inherited disease with a course of autoinflammation, which is characterized by the episodes of fever and serositis. It affects the populations from Mediterranean basin. Genetic mutation of the disease is on MEFV gene located on short arm of Chromosome 16. The disease is diagnosed based on clinical evaluation. Amyloidosis is the most important complication. The only agent that decreases the development of amyloidosis and the frequency and severity of the episodes is colchicine, which has been used for about 40 years. In this review, we aimed to discuss especially the most recent advances about Familial Mediterranean Fever which is commonly seen in our population.

• MeSH
• amyloidóza etiologie   MeSH
• cytoskeletální proteiny genetika   MeSH
• diferenciální diagnóza MeSH
• familiární středomořská horečka * komplikace   diagnóza   farmakoterapie   genetika   MeSH
• genetická predispozice k nemoci MeSH
• kolchicin terapeutické užití   MeSH
• lidé MeSH
• modulátory tubulinu terapeutické užití   MeSH
• mutace MeSH
• prognóza MeSH
• pyrin MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• cytoskeletální proteiny MeSH
• kolchicin MeSH
• MEFV protein, human MeSH Prohlížeč
• modulátory tubulinu MeSH
• pyrin MeSH

Lipomatous hypertrophy of the interatrial septum (LHIS) is characterized by excessive accumulation of adipose tissue within some segments of the interatrial septum. Only one published case so far describes fever as a presenting feature of LHIS. On the other hand, systemic symptoms including anemia and fever are well-known clinical presentations of cardiac myxomas. We report an unusual case of a 79-year-old woman who was thoroughly but unsuccessfully investigated for recurrent fever and anemia in several specialized departments over the course of 4 years. Computed tomography scan showed a pathological mass localized in the interatrial septum and spreading to ascending aorta. Histological analysis of the biopsy samples from surgery revealed the unexpected diagnosis of regressively changed LHIS. We discuss the clinical and pathologic features of this lesion suggesting that its regressive changes may be associated with inflammation and can cause systemic symptoms such as fever and anemia.

• Klíčová slova
• Anemia, Fever, Inflammation, Lipomatous hypertrophy of the interatrial septum,
• MeSH
• anemie etiologie   MeSH
• horečka etiologie   MeSH
• hypertrofie MeSH
• lidé MeSH
• lipomatóza komplikace   patologie   MeSH
• nemoci srdce komplikace   patologie   MeSH
• senioři MeSH
• síňová přepážka patologie   MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Venous blood samples were obtained from 42 children hospitalized for the recurrent episode of scarlet fever: immediately after admission and toward the end of one week's hospitalisation, after a three-week period and at a later control after four months. The 14 specific proteins were simultaneously quantitated in the serum specimens using radial immunodiffusion on antibodyagar plates. Antistreptolysin O titres were also determined and compared with the corresponding immunoglobulin levels. However, the titres showed only minor differences in various stages of illness the course of which was mild and without complications. Serum levels of prealbumin, albumin, alpha2HS-glycoproetin, transferrin and beta 2-glycoprotein I were found decreased at the acute clinical stage. Of the "negative acute phase reactants" prealbumin proved to be the most expressive one. Of a triad of "positive reactants" the largest relative increments showed haptoglobin, its increase was twofold of orosomucoid and that threefold of ceruloplasmin. C-reactive protein was increased almost in two thirds of patients on admission, but normalized in all cases about the end of the first week of penicillin therapy. No significant changes were found for alpha 2-macroglobulin. We could demonstrate significant rise and fall of IgD concentration in serum together with IgG, IgA, and IgM, all manifested the peak values already after one week's hospitalisation. In the recurrent episode of scarlet fever IgA showed significantly minor increments compared with the first illness.

• MeSH
• C-reaktivní protein metabolismus   MeSH
• ceruloplasmin metabolismus   MeSH
• dítě MeSH
• glykoproteiny metabolismus   MeSH
• haptoglobiny metabolismus   MeSH
• imunodifuze MeSH
• krevní proteiny metabolismus   MeSH
• lidé MeSH
• makroglobuliny metabolismus   MeSH
• novorozenec MeSH
• orosomukoid metabolismus   MeSH
• prealbumin metabolismus   MeSH
• předškolní dítě MeSH
• recidiva MeSH
• spála imunologie   MeSH
• transferin metabolismus   MeSH
• tvorba protilátek MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• C-reaktivní protein MeSH
• ceruloplasmin MeSH
• glykoproteiny MeSH
• haptoglobiny MeSH
• krevní proteiny MeSH
• makroglobuliny MeSH
• orosomukoid MeSH
• prealbumin MeSH
• transferin MeSH

Familial Mediterranean fever (FMF) is a well-described monogenic autosomal recessive disorder with highest occurrence in the Mediterranean region. In this article, we describe the experience of a center in the Czech Republic that follows four families with members bearing mutations in MEFV gene without provable ancestry from the Mediterranean region. We also discuss the clinical picture of the heterozygous variants that were present in our cohort. The typical clinical presentation in heterozygotes corresponds to data described in the international literature. The possibility of combination of mutations and/or polymorphisms in different genes and epigenetic or environmental influences on the clinical symptoms are taken into account.

• Klíčová slova
• Familial Mediterranean fever, MEFV gene, amyloidosis, autoinflammatory syndromes, colchicine,
• MeSH
• cytoskeletální proteiny genetika   MeSH
• dospělí MeSH
• familiární středomořská horečka genetika   MeSH
• heterozygot * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace * MeSH
• pyrin MeSH
• rodokmen MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• cytoskeletální proteiny MeSH
• MEFV protein, human MeSH Prohlížeč
• pyrin MeSH

• Klíčová slova
• RHEUMATIC FEVER *,
• MeSH
• biomedicínský výzkum * MeSH
• dítě MeSH
• lidé MeSH
• recidiva * MeSH
• revmatická horečka * MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

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.

• Klíčová slova
• Clinical features, Diagnostic role of MRI, Protracted febrile myalgia syndrome, Treatment,
• MeSH
• dítě MeSH
• familiární středomořská horečka * komplikace   diagnóza   MeSH
• horečka * diagnóza   etiologie   MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• myalgie * diagnóza   etiologie   MeSH
• syndrom MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• systematický přehled MeSH

Familiar Mediterranean fever (FMF) is a well defined autosomal recessive disease occurring mostly in Mediterranean regions. Here we present the experience from one center from Czech Republic, where we follow 4 families with patients with genetically proven FMF. Three out of these 4 families cluster to one limited region in Moravia, in the heart of Europe, without any linkage to Mediterranean origin. Furthermore, majority of these patients are heterozygots presenting with well defined typical clinical symptoms. Potential pseudodominant inheritance and/or epigenetic and environmental factors might influence clinical presentation of the disease.

• MeSH
• dospělí MeSH
• familiární středomořská horečka genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• rodokmen MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Evropa MeSH

Familial Mediterranean fever (FMF) is the most prevalent genetically determined autoinflammatory disease. FMF significantly decreases the quality of life and limits life expectancy due to the development of amyloidosis in affected individuals. Prevalence of FMF is highest in the south-eastern Mediterraneans. In other parts of the world, its occurance is often restricted to high-risk ethnic groups. In Central Europe, experience with FMF is scarse to none, as in the case of Slovakia, where no cases have been reported, so far. Herein we report the first five patients (3 adults and 2 children, 4 native Slovaks) in whom the diagnosis of FMF could be confirmed in Slovakia. Our experience demonstrates that FMF does occur in low-risk populations in Central Europe. Due to low prevalence and lack of experience, FMF diagnosis may be significantly delayed (4.5-30 years) and undiagnosed cases are to be expected in our population.

• MeSH
• dítě MeSH
• dospělí MeSH
• familiární středomořská horečka diagnóza   epidemiologie   MeSH
• lidé MeSH
• prevalence MeSH
• riziko MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Slovenská republika epidemiologie   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.

• Klíčová slova
• CAPS, FMF, IL-1, TRAPS, anakinra, canakinumab, rilonacept,
• MeSH
• antiflogistika terapeutické užití   MeSH
• dědičné zánětlivé autoimunitní nemoci farmakoterapie   imunologie   MeSH
• interleukin-1 antagonisté a inhibitory   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antiflogistika MeSH
• interleukin-1 MeSH