RESUMO Objetivo: Avaliar as doenças autoinflamatórias (DAI) de acordo com sexo e idade no momento do diagnóstico e a resposta terapêutica em uma grande população. Métodos: Este é um estudo observacional transversal de um registro latino-americano que usou um sistema de dados coletados entre 2015 e 2018. Quaisquer achados alterados ao longo do acompanhamento foram registrados. Os formulários foram traduzidos para os idiomas português e espanhol, incluindo características demográficas, clínicas, laboratoriais, genéticas e de tratamento. Resultados: Incluímos 152 pacientes, sendo 51,3% do sexo masculino e 75% da raça branca. A média de idade de início da doença foi de 2,1 anos (0–15,6 anos) e a média de idade de diagnóstico 6,9 anos (0–21,9 anos); 111 (73%) eram crianças (0–9 anos) e 41 (27%) adolescentes/adultos jovens (10–21 anos). A síndrome de febre periódica, estomatite aftosa, faringite e adenite (PFAPA) ocorreu em 46/152 (30%), osteomielite não bacteriana crônica (CNO) em 32/152 (21%) e febre familiar do Mediterrâneo (FMF) em 24/152 (15,7%). A PFAPA foi significativamente maior em crianças pequenas (38,7 vs. 7,3%, p<0,001), e a CNO, em adolescentes/adultos jovens (13,5 vs. 41,5%, p<0,001). A frequência do sexo feminino foi significativamente maior na CNO (28,4 vs. 14,1%, p=0,031) e menor na FMF (8,1 vs. 23,1%, p=0,011). Os medicamentos mais utilizados foram glicocorticoides, anti-inflamatórios não esteroidais (AINE) e colchicina. O tratamento com glicocorticoides e colchicina foi usado em todas as DAI com resposta boa a moderada. No entanto, as síndromes periódicas associadas à criopirina (CAPS) pareciam não responder aos glicocorticoides. AINE e metotrexato foram os principais medicamentos utilizados no tratamento da CNO. Conclusões: Diferenças de pacientes com DAI foram observadas na população latino-americana em pacientes agrupados por sexo e idade ao diagnóstico da doença. Objetivo (DAI Métodos latinoamericano latino americano 201 2018 registrados espanhol demográficas clínicas laboratoriais Resultados 15 513 51 3 51,3 75 branca 21 2 1 2, 0–15,6 0156 0 6 (0–15, 69 9 6, 0–21,9 0219 (0–21, 11 73% 73 (73% 0–9 09 (0– 4 27% 27 (27% adolescentesadultos adolescentes adultos 10–21 1021 10 (10–2 anos. . periódica aftosa (PFAPA 46152 46 46/15 30%, 30 30% , (30%) (CNO 32152 32 32/15 21% (21% (FMF 24152 24 24/15 15,7%. 157 15,7% 7 (15,7%) 38,7 387 38 (38, vs 7,3% p<0,001, p0001 p p<0,001 001 p<0,001) 13,5 135 13 5 (13, 415 41,5% p<0,001. 28,4 284 28 (28, 141 14 14,1% p=0,031 p0031 031 8,1 81 8 (8, 231 23 23,1% p=0,011. p0011 p=0,011 011 p=0,011) antiinflamatórios anti inflamatórios (AINE moderada entanto CAPS (CAPS Conclusões latinoamericana americana 20 51, 0–15, 015 (0–15 0–21, 021 (0–21 (73 0– (0 (27 10–2 102 (10– 4615 46/1 (30% 3215 32/1 (21 2415 24/1 15,7 (15,7% 38, (38 7,3 p000 p<0,00 00 13, (13 41,5 28, (28 14,1 p=0,03 p003 03 8, (8 23,1 p001 p=0,01 01 0–15 (0–1 0–21 02 (0–2 (7 ( (2 10– (10 461 46/ (30 321 32/ 241 24/ 15, (15,7 (3 7, p00 p<0,0 (1 41, 14, p=0,0 23, 0–1 0–2 (15, p0 p<0, p=0, (15 p<0 p=0 p< p=

ABSTRACT Objective: To evaluate autoinflammatory diseases (AID) according to age at diagnosis and sex, and response to therapy in a large population. Methods: This is a cross-sectional observational study of a Latin American registry using a designed web system for data storage, collected between 2015 and 2018. Any altered findings during follow-up were recorded. The forms were translated into Portuguese and Spanish, including demographic, clinical, laboratory, genetic and treatment characteristics. Results: We included 152 patients, 51.3% male and 75% Caucasian. The median age at disease onset was 2.1 years (0–15.6 years) and median age at diagnosis 6.9 years (0–21.9 years); 111 (73%) were children (0–9 years old), and 41 (27%) were adolescents and young adults (AYA) (10–21 years old). Periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome (PFAPA) occurred in 46/152 (30%), chronic non-bacterial osteomyelitis (CNO) in 32/152 (21%), and familial Mediterranean fever (FMF) in 24/152 (15.7%). PFAPA was significantly higher in young children than in AYA (38.7% vs. 7.3%, p<0.001), while CNO were lower (13.5% vs. 41.5%, p<0.001). The frequency of females was significantly higher in CNO (28.4% vs. 14.1%, p=0.031) and lower in FMF (8.1% vs. 23.1%, p=0.011). The most used drugs were glucocorticoids, non-steroidal anti-inflammatory drugs (NSAID), and colchicine. Glucocorticoids and colchicine treatment were used in all AID with good to moderate response. However, cryopyrin-associated periodic syndromes (CAPS) seemed unresponsive to glucocorticoids. NSAIDs and methotrexate were the main medications used to treat CNO. Conclusions: Differences among AID patients were observed in the LA population regarding sex and age at disease diagnosis. Objective (AID Methods crosssectional cross sectional storage 201 2018 followup follow up recorded Spanish demographic clinical laboratory characteristics Results 15 513 51 3 51.3 75 Caucasian 21 2 1 2. 0–15.6 0156 0 6 (0–15. 69 9 6. 0–21.9 0219 (0–21. 11 73% 73 (73% 0–9 09 (0– old, old , old) 4 27% 27 (27% (AYA 10–21 1021 10 (10–2 old. . stomatitis pharyngitis (PFAPA 46152 46 46/15 30%, 30 30% (30%) nonbacterial non bacterial (CNO 32152 32 32/15 21%, 21% (21%) (FMF 24152 24 24/15 15.7%. 157 15.7% 7 (15.7%) 38.7% 387 38 (38.7 vs 7.3% p<0.001, p0001 p p<0.001 001 p<0.001) 13.5% 135 13 5 (13.5 415 41.5% p<0.001. 28.4% 284 28 (28.4 141 14 14.1% p=0.031 p0031 031 8.1% 81 8 (8.1 231 23 23.1% p=0.011. p0011 p=0.011 011 p=0.011) glucocorticoids nonsteroidal steroidal antiinflammatory anti inflammatory NSAID, NSAID (NSAID) However cryopyrinassociated cryopyrin associated CAPS (CAPS Conclusions 20 51. 0–15. 015 (0–15 0–21. 021 (0–21 (73 0– (0 (27 10–2 102 (10– 4615 46/1 (30% 3215 32/1 (21% 2415 24/1 15.7 (15.7% 38.7 (38. 7.3 p000 p<0.00 00 13.5 (13. 41.5 28.4 (28. 14.1 p=0.03 p003 03 8.1 (8. 23.1 p001 p=0.01 01 (NSAID 0–15 (0–1 0–21 02 (0–2 (7 ( (2 10– (10 461 46/ (30 321 32/ (21 241 24/ 15. (15.7 38. (38 7. p00 p<0.0 13. (13 41. 28. (28 14. p=0.0 8. (8 23. 0–1 0–2 (1 (3 (15. p0 p<0. p=0. (15 p<0 p=0 p< p=

Resumo Introdução: A distrofia muscular de Duchenne (DMD) é uma doença genética recessiva ligada ao cromossomo X, que cursa com a perda progressiva do tecido muscular. Inicialmente, observa-se dificuldade para levantar do chão e aumento dafrequência de quedas. A manutenção da deambulação pelo maior tempo possível é importante e o uso de órtese tornozelo-pé (OTP) tem sido investigado como aliado nesse processo. Objetivo: Verificar a prescrição e uso de OTP para meninos deambulantes com DMD. Métodos: As informações foram coletadas dos prontuários de 181 pacientes com DMD do Serviço de Neuropediatria do Instituto de Puericultura e Pediatria Martagão Gesteira, da Universidade Federal do Rio de Janeiro. As variáveis utilizadas foram: idade na primeira consulta, idade aos primeiros sintomas, idade na perda da marcha independente, tempo entre os primeiros sintomas e a perda da marcha, prescrição de órtese, tempo de uso e intervenção cirúrgica nos membros inferiores. Resultados: A órtese foi prescrita para 63,5% dos pacientes e utilizada por 38,1%. A variação do tempo de uso foi de 2 a 4 anos (62,3%). O período noturno foi o mais prescrito para uso da órtese, com 67,2%. Os pacientes que a usaram por mais tempo apresentaram maiores idades na perda da marcha. Crianças que chegaram mais precocemente à primeira consulta tiveram maior frequência de prescrição de órtese e perda da marcha mais tardiamente. Conclusão: O uso de OTP pode ajudar a manter a deambulação por mais tempo em meninos com DMD. Introdução (DMD X Inicialmente observase observa se quedas tornozelopé tornozelo pé (OTP processo Objetivo Métodos 18 Gesteira Janeiro independente inferiores Resultados 635 63 5 63,5 381 38 1 38,1% 62,3%. 623 62,3% . 62 3 (62,3%) 672 67 67,2% tardiamente Conclusão 6 63, 38,1 62,3 (62,3% 67,2 38, 62, (62,3 67, (62, (62 (6 (

Abstract Introduction: Duchenne muscular dystrophy (DMD) is a recessive genetic disease linked to the X chromosome, leading to progressive muscle tissue loss. Initially, there is difficulty getting up from the floor and an increased frequency of falls. Maintaining ambulation as long as possible is essential, and the use of ankle-foot orthosis (AFO) has been investigated as an ally in this process. Objective: To verify the prescription and use of an AFO for ambulant boys with DMD. Methods: Information was collected using the medical records of 181 patients with DMD from the Neuropediatric Service of the Instituto de Puericultura e Pediatria Martagão Gesteira of the Universidade Federal do Rio de Janeiro. Variables used were: age at the first medical appointment, age at first symptoms, age at loss of independent gait, time between the first symptoms and loss of gait, prescription of orthosis, time of use, and surgical intervention in the lower limbs. Results: The orthosis was prescribed for 63.5% of patients and used by 38.1%. The range of orthosis time was 2 to 4 years (62.3%). The night sleep period was the most prescribed for orthosis use, with 67.2%. Patients who used the orthosis for a longer time were older at gait loss. However, the children who arrived earlier for the first appointment had a higher frequency of orthosis prescriptions and later loss of gait. Conclusion: The use of AFO can help maintain ambulation for longer in boys with DMD. Introduction (DMD chromosome Initially falls essential anklefoot ankle foot (AFO process Objective Methods 18 Janeiro limbs Results 635 63 5 63.5 381 38 1 38.1% 62.3%. 623 62.3% . 62 3 (62.3%) 672 67 67.2% However Conclusion 6 63. 38.1 62.3 (62.3% 67.2 38. 62. (62.3 67. (62. (62 (6 (

Abstract Hemophagocytic lymphohistiocytosis (HLH) is a rare genetic hyperinflammatory syndrome that occurs early in life. Macrophage activation syndrome (MAS) usually refers to a secondary form of HLH associated with autoimmunity, although there are other causes of secondary HLH, such as infections and malignancy. In this article, we reviewed the concepts, epidemiology, clinical and laboratory features, diagnosis, differential diagnosis, prognosis, and treatment of HLH and MAS. We also reviewed the presence of MAS in the most common autoimmune diseases that affect children. Both are severe diseases that require prompt diagnosis and treatment to avoid morbidity and mortality. (HLH life (MAS autoimmunity malignancy article concepts epidemiology features prognosis children mortality

Abstract Background Increased malignancy frequency is well documented in adult-systemic lupus erythematosus (SLE), but with limited reports in childhood-onset SLE (cSLE) series. We explored the frequency of malignancy associated with cSLE, describing clinical and demographic characteristics, disease activity and cumulative damage, by the time of malignancy diagnosis. Method A retrospective case-notes review, in a nationwide cohort from 27 Pediatric Rheumatology centres, with descriptive biopsy-proven malignancy, disease activity/damage accrual, and immunosuppressive treatment were compiled in each participating centre, using a standard protocol. Results Of the 1757 cSLE cases in the updated cohort, 12 (0.7%) developed malignancy with median time 10 years after cSLE diagnosis. There were 91% females, median age at cSLE diagnosis 12 years, median age at malignancy diagnosis 23 years. Of all diagnosed malignancies, 11 were single-site, and a single case with concomitant multiple sites; four had haematological (0.22%) and 8 solid malignancy (0.45%). Median (min–max) SLEDAI-2 K scores were 9 (0–38), median (min–max) SLICC/ACR-DI (SDI) score were 1 (1–5) Histopathology defined 1 Hodgkin's lymphoma, 2 non-Hodgkin's lymphoma, 1 acute lymphoblastic leukaemia; 4 gastrointestinal carcinoma, 1 squamous cell carcinoma of the tongue and 1 anal carcinoma; 1 had sigmoid adenocarcinoma and 1 stomach carcinoid; 3 had genital malignancy, being 1 vulvae, 1 cervix and 1 vulvae and cervix carcinomas; 1 had central nervous system oligodendroglioma; and 1 testicle germ cell teratoma. Conclusion Estimated malignancy frequency of 0.7% was reported during cSLE follow up in a multicentric series. Median disease activity and cumulative damage scores, by the time of malignancy diagnoses, were high; considering that reported in adult series. adultsystemic systemic SLE, , (SLE) childhoodonset childhood onset (cSLE series characteristics casenotes notes review centres biopsyproven biopsy proven activitydamage accrual centre protocol 175 07 0 7 (0.7% 91 females malignancies singlesite, singlesite site, site single-site sites 0.22% 022 22 (0.22% 0.45%. 045 0.45% . 45 (0.45%) min–max minmax min max (min–max SLEDAI2 SLEDAI SLEDAI- 0–38, 038 0–38 38 (0–38) SLICC/ACRDI SLICCACRDI SLICC/ACR DI SLICC ACR SDI (SDI 1–5 15 5 (1–5 Hodgkins Hodgkin s lymphoma nonHodgkins non leukaemia carcinoid carcinomas oligodendroglioma teratoma 0.7 diagnoses high (SLE 17 (0.7 0.22 02 (0.22 04 0.45 (0.45% 03 0–3 (0–38 ACRDI SLICCACR 1– (1– 0. (0. 0.2 (0.2 0.4 (0.45 0– (0–3 (1 (0 (0.4 (0– (

Abstract Systemic autoinflammatory diseases (SAIDs) arise from dysregulated innate immune system activity, which leads to systemic inflammation. These disorders, encompassing a diverse array of genetic defects classified as inborn errors of immunity, are significant diagnostic challenges due to their genetic heterogeneity and varied clinical presentations. Although recent advances in genetic sequencing have facilitated pathogenic gene discovery, approximately 40% of SAIDs patients lack molecular diagnoses. SAIDs have distinct clinical phenotypes, and targeted therapeutic approaches are needed. This review aims to underscore the complexity and clinical significance of SAIDs, focusing on prototypical disorders grouped according to their pathophysiology as follows: (i) inflammasomopathies, characterized by excessive activation of inflammasomes, which induces notable IL-1β release; (ii) relopathies, which are monogenic disorders characterized by dysregulation within the NF-κB signaling pathway; (iii) IL-18/IL-36 signaling pathway defect-induced SAIDs, autoinflammatory conditions defined by a dysregulated balance of IL-18/IL-36 cytokine signaling, leading to uncontrolled inflammation and tissue damage, mainly in the skin; (iv) type I interferonopathies, a diverse group of disorders characterized by uncontrolled production of type I interferons (IFNs), notably interferon α, β, and ε; (v) anti-inflammatory signaling pathway impairment-induced SAIDs, a spectrum of conditions characterized by IL-10 and TGFβ anti-inflammatory pathway disruption; and (vi) miscellaneous and polygenic SAIDs. The latter group includes VEXAS syndrome, chronic recurrent multifocal osteomyelitis/chronic nonbacterial osteomyelitis, Schnitzler syndrome, and Still’s disease, among others, illustrating the heterogeneity of SAIDs and the difficulty in creating a comprehensive classification. Therapeutic strategies involving targeted agents, such as JAK inhibitors, IL-1 blockers, and TNF inhibitors, are tailored to the specific disease phenotypes. (SAIDs activity immunity presentations discovery 40 diagnoses phenotypes needed follows i (i inflammasomopathies inflammasomes IL1β ILβ IL 1β β release ii (ii relopathies NFκB NF κB iii (iii IL18/IL36 IL18IL36 ILIL 18/IL 36 18 IL-18/IL-3 defectinduced defect induced damage skin iv (iv interferonopathies IFNs, IFNs , (IFNs) α ε v (v antiinflammatory anti inflammatory impairmentinduced impairment IL10 10 disruption vi (vi syndrome osteomyelitischronic osteomyelitis Stills Still s others classification agents inhibitors IL1 1 IL- blockers 4 IL18 IL36 IL18/IL3 IL18IL3 18IL 3 IL-18/IL- (IFNs IL3 IL18/IL IL18IL IL-18/IL

Abstract Sarcoidosis is a systemic inflammatory disease of unknown origin, which consists of the formation of multiple sterile noncaseating granulomas. Inhaled antigens are believed to initiate disease in prone individuals, considering that almost all patients present pulmonary or mediastinal lymph node disease. Extrapulmonary manifestations are common and diverse: practically any organ system can be affected, and treatment can range from simple watchful waiting to intense immunosuppression. In this article, we review current concepts about sarcoidosis in an overview, focusing on recognition and treatment of its major clinical phenotypes. origin granulomas individuals diverse affected immunosuppression article overview phenotypes

Abstract Amyloidosis is a localized or systemic disease caused by deposition of proteins in the extracellular space of various organs and tissues. As part of the disease, proteins that were originally soluble misfold and acquire a fibrillar conformation that renders them insoluble and resistant to proteolysis. Systemic amyloidosis is a rare, often underdiagnosed condition. In recent years, the incidence of newly diagnosed cases of amyloidosis has been increasing in association with the aging of the population and greater access to diagnostic tests. From a clinical perspective, systemic amyloidosis is frequently associated with involvement of the kidneys (causing nephrotic syndrome), heart (cardiac failure and arrhythmia), and peripheral nervous system (sensorimotor polyneuropathy and autonomic dysfunction). This condition is important to the rheumatologist for several reasons, such as its systemic involvement that mimics autoimmune rheumatic diseases, its musculoskeletal manifestations, which when recognized can allow the diagnosis of amyloidosis, and also because reactive or secondary AA amyloidosis is a complication of rheumatic inflammatory diseases. The treatment of amyloidosis depends on the type of amyloid protein involved. Early recognition of this rare disease is fundamental for improved clinical outcomes. tissues proteolysis years tests perspective causing syndrome, syndrome , syndrome) cardiac arrhythmia, arrhythmia arrhythmia) sensorimotor dysfunction. dysfunction . dysfunction) reasons diseases manifestations involved outcomes

Abstract Although the terms "rare diseases" (RD) and "orphan diseases" (OD) are often used interchangeably, specific nuances in definitions should be noted to avoid misconception. RD are characterized by a low prevalence within the population, whereas OD are those inadequately recognized or even neglected by the medical community and drug companies. Despite their rarity, as our ability on discovering novel clinical phenotypes and improving diagnostic tools expand, RD will continue posing a real challenge for rheumatologists. Over the last decade, there has been a growing interest on elucidating mechanisms of rare autoimmune and autoinflammatory rheumatic diseases, allowing a better understanding of the role played by immune dysregulation on granulomatous, histiocytic, and hypereosinophilic disorders, just to name a few. This initiative enabled the rise of innovative targeted therapies for rheumatic RD. In this review, we explore the state-of-the art of rare RD and the critical role played by rheumatologists in healthcare. We also describe the challenges rheumatologists may face in the coming decades. diseases (RD orphan (OD interchangeably misconception population companies rarity expand decade granulomatous histiocytic disorders few review stateofthe state healthcare decades

Abstract Advances in DNA sequencing technologies, especially next-generation sequencing (NGS), which is the basis for whole-exome sequencing (WES) and whole-genome sequencing (WGS), have profoundly transformed immune-mediated rheumatic disease diagnosis. Recently, substantial cost reductions have facilitated access to these diagnostic tools, expanded the capacity of molecular diagnostics and enabled the pursuit of precision medicine in rheumatology. Understanding the fundamental principles of genetics and diversity in genetic variant classification is a crucial milestone in rheumatology. However, despite the growing availability of DNA sequencing platforms, a significant number of autoinflammatory diseases (AIDs), neuromuscular disorders, hereditary collagen diseases, and monogenic bone diseases remain unsolved, and variants of uncertain significance (VUS) pose a formidable challenge to addressing these unmet needs in the coming decades. This article aims to provide an overview of the clinical indications and interpretation of comprehensive genetic testing in the medical field, addressing the related complexities and implications. technologies nextgeneration next generation NGS, NGS , (NGS) wholeexome whole exome WES (WES wholegenome genome WGS, WGS (WGS) immunemediated immune mediated diagnosis Recently tools rheumatology However platforms AIDs, AIDs (AIDs) disorders unsolved VUS (VUS decades field implications (NGS (WGS (AIDs

Abstract The aim of this study was to characterize the salivary metabolomic profile in adolescents with juvenile systemic lupus erythematosus (jSLE). A total of 24 adolescents with jSLE (15.92 ± 2.06 years) and 12 systemically healthy controls (15.25 ± 2.7 years) were included in the study. Participants underwent rheumatologic testing and periodontal examination, with the recording of plaque index (PI), probing depth (PD), clinical attachment level (CAL), and bleeding on probing index (BPI). Unstimulated whole saliva was collected from both groups and stored at -80 ºC. The salivary proton nuclear magnetic resonance (1H-NMR) spectra were acquired in a spectrometer operating at 500 MHz. Partial least squared discriminant analysis (PLS-DA) and orthogonal PLS-DA (O-PLS-DA) were used for statistical analysis. Mean CAL and PI were significantly increased in the group with jSLE (p < 0.01). Patients with jSLE presented a significantly different salivary metabolic profile (accuracy = 0.54; R2 = 0.86; Q2 = -0.293), significantly higher salivary levels of N-acetyl sugars, and significantly reduced levels of phenylalanine, glycine, taurine, hydroxybutyrate, and valerate compared with healthy controls (p < 0.05). It is suggested that the salivary metabolomic profile analyzed by 1H NMR in patients with jSLE presents a different fingerprint that the systemically healthy subjects. Integrating the variation of metabolites with the identification of the metabolic pathways involved seems to provide a better understanding of the influence of systemic disease on salivary metabolites.

Abstract Background Juvenile systemic lupus erythematosus (JSLE) is a chronic inflammatory disease that affects the heart in 50% of cases. The behavior of diastolic function in adolescents and the predictors of its occurrence by conventional echocardiography are poorly established. Objectives This study aimed to evaluate diastolic function in adolescents with JSLE and to identify possible predictors of its occurrence by conventional echocardiography. Methods Cross-sectional, observational, control group study in a tertiary hospital of 49 adolescents with JSLE and 49 controls, using the EACVI 2016 guideline classification. Statistical methods used were Fisher and Mann-Whitney tests. Multivariate logistic regression models were constructed. A significance level of 5% was adopted. Results Among 98 patients, the JSLE group had higher indexed left atrial volume (p <0.001), lower lateral E' value (p<0.001) and lower E/A ratio value (p<0.001). The diagnosis of JSLE was associated with a higher chance of increased left atrial index volume (OR 3.3; p value 0.03). Conclusions Based on the 2016 guideline, no diastolic dysfunction was found in JSLE. However, differences in the analyzed echocardiographic parameters were found in these adolescents. (JSLE 50 cases established Crosssectional, Crosssectional Cross sectional, sectional Cross-sectional observational 4 controls 201 classification MannWhitney Mann Whitney tests constructed 5 adopted 9 patients <0.001, 0001 <0.001 , 0 001 <0.001) E p<0.001 p0001 (p<0.001 EA p<0.001. . OR 3.3 33 3 0.03. 003 0.03 03 0.03) However 20 000 <0.00 00 p<0.00 p000 (p<0.00 3. 0.0 2 <0.0 p<0.0 p00 (p<0.0 0. <0. p<0. p0 (p<0. <0 p<0 (p<0 < p< (p<

Abstract Background: To date there are no specific classification criteria for childhood-onset systemic lupus erythematosus (cSLE). This study aims to compare the performance among the American College of Rheumatology (ACR) 1997, the Systemic Lupus International Collaborating Clinics criteria (SLICC) and the new European League Against Rheumatism (EULAR)/ACR criteria, in a cSLE cohort. Methods: We conducted a medical chart review study of cSLE cases and controls with defined rheumatic diseases, both ANA positive, to establish each ACR1997, SLICC and EULAR/ACR criterion fulfilled, at first visit and 1-year-follow-up. Results: Study population included 122 cSLE cases and 89 controls. At first visit, SLICC criteria had higher sensitivity than ACR 1997 (89.3% versus 70.5%, p < 0.001), but similar specificity (80.9% versus 83.2%, p = 0.791), however performance was not statistically different at 1-year-follow-up. SLICC better scored in specificity compared to EULAR/ACR score ≥ 10 at first visit (80.9% versus 67.4%, p = 0.008) and at 1-year (76.4% versus 58.4%, p = 0.001), although sensitivities were similar. EULAR/ACR criteria score ≥ 10 exhibited higher sensitivity than ACR 1997 (87.7% versus 70.5%, p < 0.001) at first visit, but comparable at 1-year, whereas specificity was lower at first visit (67.4% versus 83.2%, p = 0.004) and 1-year (58.4% versus 76.4%, p = 0.002). A EULAR/ACR score ≥ 13 against a score ≥ 10, resulted in higher specificity, positive predictive value, and cut-off point accuracy. Compared to SLICC, a EULAR/ACR score ≥ 13 resulted in lower sensitivity at first visit (76.2% versus 89.3%, p < 0.001) and 1-year (91% versus 97.5%, p = 0.008), but similar specificities at both assessments. When compared to ACR 1997, a EULAR/ACR total score ≥ 13, resulted in no differences in sensitivity and specificity at both observation periods. Conclusions: In this cSLE population, SLICC criteria better scored at first visit and 1-year-follow-up. The adoption of a EULAR/ACR total score ≥ 13 in this study, against the initially proposed ≥10 score, was most appropriate to classify cSLE. Further studies are necessary to address if SLICC criteria might allow fulfillment of cSLE classification earlier in disease course and may be more inclusive of cSLE subjects for clinical studies.

RESUMO Um grande número de estudos tem mostrado uma potencial associação entre doenças periodontais e doenças autoimunes, como artrite reumatoide e lúpus eritematoso sistêmico (LES). Os mecanismos de destruição tecidual semelhantes entre a periodontite e as demais doenças autoimunes têm estimulado o estudo de possíveis relações entre essas condições. O presente estudo tem como objetivo revisar a literatura acerca dessa potencial associação e dos seus diferentes mecanismos patogênicos. Considerando-se a doença periodontal uma doença de caráter inflamatório que sofre influência de fatores infecciosos, assim como o LES, é plausível sugerir que o LES influenciaria sua progressão, assim como a periodontite influenciaria a progressão do LES. Entretanto, essa questão ainda não é totalmente elucidada e vários mecanismos têm sido propostos para explicar tal associação, como desregulações, principalmente no sistema imune inato, com ações de células fagocíticas e de citocinas pró-inflamatórias, como IL-1β e IL-18, na patogênese de ambas as condições, o que contribui para a destruição tecidual. Existem, contudo, poucos estudos na literatura que avaliam a relação entre essas doenças e mais trabalhos focados nos mecanismos imunológicos comuns a ambas as condições devem ser feitos para um maior entendimento.

ABSTRACT A large number of studies have shown a potential association between periodontal and autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus (SLE). Similar mechanisms of tissue destruction concerning periodontitis and other autoimmune diseases have stimulated the study of a possible relationship between these conditions. This study aims to review the literature about this potential association and their different pathogenic mechanisms. Considering that periodontal disease is a disease characterized by inflammation influenced by infectious factors, such as SLE, it is plausible to suggest that SLE would influence periodontal disease and vice-versa. However, this issue is not yet fully elucidated and several mechanisms have been proposed to explain this association, as deregulation mainly in innate immune system, with action of phagocytic cells and proinflammatory cytokines such as IL-1β and IL-18 in both conditions’ pathogenesis, leading to tissue destruction. However, studies assessing the relationship between these diseases are scarce, and more studies focused on common immunological mechanisms should be conducted to further understanding.

Resumo Objetivo: Estabelecer diretrizes baseadas em evidências científicas para manejo da síndrome de febre periódica, estomatite aftosa, faringite e adenite (PFAPA). Descrição do método de coleta de evidência: A Diretriz foi elaborada a partir de cinco questões clínicas que foram estruturadas por meio do Pico (Paciente, Intervenção ou Indicador, Comparação e Outcome), com busca nas principais bases primárias de informação científica. Após definir os estudos potenciais para sustento das recomendações, esses foram graduados pela força da evidência e pelo grau de recomendação. Resultados: Foram recuperados e avaliados pelo título e resumo 806 trabalhos e selecionados 32 artigos, para sustentar as recomendações. Recomendações: 1. O diagnóstico da PFAPA é clínico e de exclusão, deve a suspeita ser considerada em crianças que apresentam episódios febris de origem indeterminada recorrentes e periódicos ou amidalites de repetição, intercalados com períodos assintomáticos, sobretudo em crianças em bom estado geral e com desenvolvimento pondero-estatural mantido; 2. Os achados laboratoriais são inespecíficos. Não existem alterações patognomônicas nos exames complementares; 3. A evidência que sustenta a indicação do tratamento cirúrgico (tonsilectomia com ou sem adenoidectomia) é baseada em dois ensaios clínicos randomizados não cegos que incluíram pequeno número de pacientes; 4. O uso de prednisona no início do quadro febril em pacientes com PFAPA mostrou ser eficaz. Melhores evidências ainda são necessárias para apoiar seu uso na PFAPA; 5. Apesar de os resultados obtidos de estudos com inibidores de IL-1ß serem promissores, esses são limitados a poucos relatos de casos.

Abstract Objective: To establish guidelines based on scientific evidence for the management of periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome. Description of the evidence collection method: The Guideline was prepared from 5 clinical questions that were structured through PICO (Patient, Intervention or indicator, Comparison and Outcome), to search in key primary scientific information databases. After defining the potential studies to support the recommendations, these were graduated considering their strength of evidence and grade of recommendation. Results: 806 articles were retrieved and evaluated by title and abstract; from these, 32 articles were selected to support the recommendations. Recommendations: 1. PFAPA is a diagnosis of exclusion established on clinical grounds, and one must suspect of this problem in children with recurrent and periodic febrile episodes of unknown origin, or with recurrent tonsillitis interspersed with asymptomatic periods, especially in children in good general condition and with preservation of weight and height development. 2. Laboratory findings are nonspecific. Additional tests do not reveal pathognomonic changes. 3. The evidence supporting an indication for surgical treatment (tonsillectomy with or without adenoidectomy), is based on two non-blinded randomized clinical trials with small numbers of patients. 4. The use of prednisone at the onset of fever in patients with PFAPA proved to be an effective strategy. There is still need for more qualified evidence to support its use in patients with PFAPA. 5. Despite promising results obtained in studies with IL-1β inhibitors, such studies are limited to a few case reports.