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

OBJECTIVE: Granulomatosis with polyangiitis (GPA) is an ANCA-associated vasculitis. The 2022 ACR/EULAR-endorsed classification criteria for GPA was derived using data only from adult patients. We aimed to assess the performance of the ACR/EULAR classification criteria for GPA in paediatric patients and compare it with the EULAR/Pediatric Rheumatology International Trials Organization (PRINTO)/Pediatric Rheumatology European Society (PReS)-endorsed Ankara 2008 criteria for GPA. METHODS: Retrospective data of paediatric patients with GPA in 20 centres from 9 countries were evaluated. The diagnosis of GPA was made according to the expert opinion. The sensitivity, specificity, positive predictive value, and negative predictive value of the criteria sets were evaluated. RESULTS: The study included 77 patients with GPA and 108 controls [IgA vasculitis (n = 44), Takayasu's arteritis (n = 20), microscopic polyangiitis (n = 16), polyarteritis nodosa (n = 14), Behçet's disease (n = 12), eosinophilic granulomatosis with polyangiitis (n = 1) and Cogan's syndrome (n = 1)] with a median age of 17.8 and 15.2 years, respectively. Among patients with GPA, constitutional symptoms (85.7%) and ENT involvement (79.2%) were the most common presentations. In the GPA group, 73 patients fulfilled the Ankara 2008 criteria and 69 the ACR/EULAR classification criteria. Sensitivities of the Ankara 2008 criteria and the ACR/EULAR classification criteria were 94.8% and 89.6%, while specificities were 95.3% and 96.3%, respectively. No significant difference was found between sensitivities and specificities of both classification criteria (P = 0.229 and P = 0.733, respectively). CONCLUSION: In children, both the ACR/EULAR and EULAR/PRINTO/PReS Ankara 2008 classification criteria for GPA perform well and similarly.

• Klíčová slova
• ANCA-associated vasculitis, classification criteria, granulomatosis with polyangiitis,
• MeSH
• Behcetův syndrom klasifikace   diagnóza   MeSH
• Churgův-Straussové syndrom diagnóza   klasifikace   MeSH
• dítě MeSH
• granulomatóza s polyangiitidou * klasifikace   diagnóza   MeSH
• IgA vaskulitida diagnóza   klasifikace   MeSH
• lidé MeSH
• mikroskopická polyangiitida klasifikace   diagnóza   MeSH
• mladiství MeSH
• polyarteritis nodosa klasifikace   diagnóza   MeSH
• prediktivní hodnota testů MeSH
• předškolní dítě MeSH
• retrospektivní studie MeSH
• revmatologie normy   MeSH
• senzitivita a specificita * MeSH
• Takayasuova arteriitida * klasifikace   diagnóza   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• srovnávací studie MeSH
• Geografické názvy
• Evropa MeSH

The aim of this study was to describe the clinical and molecular genetic findings in seven individuals from three unrelated families with Blau syndrome. A complex ophthalmic and general health examination including diagnostic imaging was performed. The NOD2 mutational hot spot located in exon 4 was Sanger sequenced in all three probands. Two individuals also underwent autoinflammatory disorder gene panel screening, and in one subject, exome sequencing was performed. Blau syndrome presenting as uveitis, skin rush or arthritis was diagnosed in four cases from three families. In two individuals from one family, only camptodactyly was noted, while another member had camptodactyly in combination with non-active uveitis and angioid streaks. One proband developed two attacks of meningoencephalitis attributed to presumed neurosarcoidosis, which is a rare finding in Blau syndrome. The probands from families 1 and 2 carried pathogenic variants in NOD2 (NM_022162.3): c.1001G>A p.(Arg334Gln) and c.1000C>T p.(Arg334Trp), respectively. In family 3, two variants of unknown significance in a heterozygous state were found: c.1412G>T p.(Arg471Leu) in NOD2 and c.928C>T p.(Arg310*) in NLRC4 (NM_001199139.1). In conclusion, Blau syndrome is a phenotypically highly variable, and there is a need to raise awareness about all clinical manifestations, including neurosarcoidosis. Variants of unknown significance pose a significant challenge regarding their contribution to etiopathogenesis of autoinflammatory diseases.

• Klíčová slova
• Blau syndrome, NOD2, autoinflammation, early onset sarcoidosis, neurosarcoidosis, uveitis,
• MeSH
• artritida * genetika   diagnóza   MeSH
• dědičné zánětlivé autoimunitní nemoci MeSH
• lidé MeSH
• lymfedém genetika   diagnóza   MeSH
• mutace * MeSH
• nemoci centrálního nervového systému MeSH
• neuropatická artropatie genetika   diagnóza   MeSH
• rodokmen * MeSH
• sarkoidóza * genetika   diagnóza   MeSH
• sekvenování exomu MeSH
• signální adaptorový protein Nod2 * genetika   MeSH
• synovitida * genetika   diagnóza   MeSH
• uveitida * genetika   diagnóza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• NOD2 protein, human MeSH Prohlížeč
• signální adaptorový protein Nod2 * MeSH

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

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.

• Klíčová slova
• anakinra, canakinumab, cardiovascular disease, interleukin 1, monogenic periodic fever syndromes, rilonacept,
• MeSH
• dědičné zánětlivé autoimunitní nemoci * farmakoterapie   MeSH
• inhibitory interleukinu MeSH
• interleukin-1 terapeutické užití   MeSH
• lidé MeSH
• nedostatek mevalonátkinázy * farmakoterapie   MeSH
• periodické syndromy asociované s kryopyrinem * farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• inhibitory interleukinu MeSH
• interleukin-1 MeSH

Autoinflammatory diseases represent a group of disorders that are distinct from autoimmune diseases, infections and malignancies. They are characterised by attacks of unprovoked noninfectious inflammation. A key feature of autoinflammatory diseases is dysregulation of innate immune system and overproduction of pro-inflammatory cytokines. The best-characterized group of autoinflammatory diseases arises from mutations in single genes. They are typically manifested by recurrent attacks of fever and serositis as well as arthralgia, myalgia and skin exanthema.

• Klíčová slova
• autoinflammatory disease, inflammasome, innate immunity, periodic fever,
• MeSH
• autoimunitní nemoci * genetika   MeSH
• cytokiny MeSH
• dědičné zánětlivé autoimunitní nemoci * genetika   MeSH
• horečka MeSH
• lidé MeSH
• zánět MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cytokiny 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

OBJECTIVES: To describe the clinical characteristics, treatment response and genetic findings in a large cohort of patients with undefined systemic autoinflammatory diseases (SAIDs). METHODS: Clinical and genetic data from patients with undefined SAIDs were extracted from the Eurofever registry, an international web-based registry that retrospectively collects clinical information on patients with autoinflammatory diseases. RESULTS: This study included 187 patients. Seven patients had a chronic disease course, 180 patients had a recurrent disease course. The median age at disease onset was 4.3 years. Patients had a median of 12 episodes per year, with a median duration of 4 days. Most commonly reported symptoms were arthralgia (n=113), myalgia (n=86), abdominal pain (n=89), fatigue (n=111), malaise (n=104) and mucocutaneous manifestations (n=128). In 24 patients, relatives were affected as well. In 15 patients, genetic variants were found in autoinflammatory genes. Patients with genetic variants more often had affected relatives compared with patients without genetic variants (p=0.005). Most patients responded well to non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, colchicine and anakinra. Complete remission was rarely achieved with NSAIDs alone. Notable patterns were found in patients with distinctive symptoms. Patients with pericarditis (n=11) were older at disease onset (33.8 years) and had fewer episodes per year (3.0/year) compared with other patients. Patients with an intellectual impairment (n=8) were younger at disease onset (2.2 years) and often had relatives affected (28.6%). CONCLUSION: This study describes the clinical characteristics of a large cohort of patients with undefined SAIDs. Among these, patients with pericarditis and intellectual impairment appear to comprise distinct subsets.

• Klíčová slova
• autoinflammatory diseases, eurofever, inflammation, recurrent fever,
• MeSH
• antagonista receptoru pro interleukin 1 terapeutické užití   MeSH
• antirevmatika terapeutické užití   MeSH
• chronická nemoc MeSH
• dědičné zánětlivé autoimunitní nemoci farmakoterapie   genetika   patologie   MeSH
• dítě MeSH
• dospělí MeSH
• genetická variace genetika   MeSH
• hormony kůry nadledvin terapeutické užití   MeSH
• kolchicin terapeutické užití   MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• předškolní dítě MeSH
• registrace MeSH
• retrospektivní studie MeSH
• rodokmen MeSH
• věk při počátku nemoci MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• antagonista receptoru pro interleukin 1 MeSH
• antirevmatika MeSH
• hormony kůry nadledvin MeSH
• kolchicin MeSH

The nucleotide-binding-domain (NBD)-and leucine-rich repeat (LRR)-containing (NLR) family, pyrin-domain-containing 3 (NLRP3) inflammasome drives pathological inflammation in a suite of autoimmune, metabolic, malignant, and neurodegenerative diseases. Additionally, NLRP3 gain-of-function point mutations cause systemic periodic fever syndromes that are collectively known as cryopyrin-associated periodic syndrome (CAPS). There is significant interest in the discovery and development of diarylsulfonylurea Cytokine Release Inhibitory Drugs (CRIDs) such as MCC950/CRID3, a potent and selective inhibitor of the NLRP3 inflammasome pathway, for the treatment of CAPS and other diseases. However, drug discovery efforts have been constrained by the lack of insight into the molecular target and mechanism by which these CRIDs inhibit the NLRP3 inflammasome pathway. Here, we show that the NAIP, CIITA, HET-E, and TP1 (NACHT) domain of NLRP3 is the molecular target of diarylsulfonylurea inhibitors. Interestingly, we find photoaffinity labeling (PAL) of the NACHT domain requires an intact (d)ATP-binding pocket and is substantially reduced for most CAPS-associated NLRP3 mutants. In concordance with this finding, MCC950/CRID3 failed to inhibit NLRP3-driven inflammatory pathology in two mouse models of CAPS. Moreover, it abolished circulating levels of interleukin (IL)-1β and IL-18 in lipopolysaccharide (LPS)-challenged wild-type mice but not in Nlrp3L351P knock-in mice and ex vivo-stimulated mutant macrophages. These results identify wild-type NLRP3 as the molecular target of MCC950/CRID3 and show that CAPS-related NLRP3 mutants escape efficient MCC950/CRID3 inhibition. Collectively, this work suggests that MCC950/CRID3-based therapies may effectively treat inflammation driven by wild-type NLRP3 but not CAPS-associated mutants.

• MeSH
• cytokiny antagonisté a inhibitory   MeSH
• furany farmakologie   MeSH
• HEK293 buňky MeSH
• heterocyklické sloučeniny tetra- a více cyklické MeSH
• indeny MeSH
• inflamasomy antagonisté a inhibitory   MeSH
• lidé MeSH
• lipopolysacharidy MeSH
• makrofágy účinky léků   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• periodické syndromy asociované s kryopyrinem genetika   MeSH
• preklinické hodnocení léčiv MeSH
• protein NLRP3 antagonisté a inhibitory   genetika   MeSH
• proteinové domény MeSH
• sulfonamidy farmakologie   MeSH
• sulfony MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cytokiny MeSH
• furany MeSH
• heterocyklické sloučeniny tetra- a více cyklické MeSH
• indeny MeSH
• inflamasomy MeSH
• lipopolysacharidy MeSH
• N-(1,2,3,5,6,7-hexahydro-S-indacen-4-ylcarbamoyl)-4-(2-hydroxy-2-propanyl)-2-furansulfonamide MeSH Prohlížeč
• NLRP3 protein, human MeSH Prohlížeč
• Nlrp3 protein, mouse MeSH Prohlížeč
• protein NLRP3 MeSH
• sulfonamidy MeSH
• sulfony MeSH

Background: Muckle-Wells syndrome (MWS) represents a moderate phenotype of cryopyrinopathies. Sensorineural hearing loss and AA amyloidosis belong to the most severe manifestations of uncontrolled disease. Simultaneous discovery of MWS in four generations of one large kindred has enabled us to document natural evolution of untreated disease and their response to targeted therapy. Methods: A retrospective case study, clinical assessment at the time of diagnosis and 2-year prospective follow-up using standardized disease assessments were combined. Results: Collaborative effort of primary care physicians and pediatric and adult specialists led to identification of 11 individuals with MWS within one family. Presence of p.Ala441Val mutation was confirmed. The mildest phenotype of young children suffering with recurrent rash surprised by normal blood tests and absence of fevers. Young adults all presented with fevers, rash, conjunctivitis, and arthralgia/arthritis with raised inflammatory markers. Two patients aged over 50 years suffered with hearing loss and AA amyloidosis. IL-1 blockade induced disease remission in all individuals while hearing mildly improved or remained stable in affected patients as did renal function in one surviving individual with amyloidosis. Conclusions: We have shown that severity of MWS symptoms gradually increased with age toward distinct generation-specific phenotypes. A uniform trajectory of disease evolution has encouraged us to postpone institution of IL-1 blockade in affected oligosymptomatic children. This report illustrates importance of close interdisciplinary collaboration.

• Klíčová slova
• AA amyloidosis, Muckle-Wells syndrome (MWS), cryopyrin-associated periodic syndromes (CAPS), cryopyrinopathy, familial cold autoinflammatory syndrome (FCAS), hearing loss, rash,
• MeSH
• charakteristiky rodiny MeSH
• dospělí MeSH
• fenotyp MeSH
• interleukin-1 antagonisté a inhibitory   MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mutace MeSH
• následné studie MeSH
• periodické syndromy asociované s kryopyrinem diagnóza   genetika   patofyziologie   terapie   MeSH
• předškolní dítě MeSH
• progrese nemoci MeSH
• prospektivní studie MeSH
• retrospektivní studie MeSH
• rodokmen MeSH
• zdraví rodiny MeSH
• Check Tag
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• interleukin-1 MeSH