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BACKGROUND: Ankylosing spondylitis (AS) is an inflammatory disease that affects the spine and can cause peripheral arthritis, enthesitis, and dactylitis, as well as extra-articular manifestations such as uveitis and inflammatory bowel disease. ß-Defensins are antimicrobial peptides involved in the activation and regulation of several immune cell types that may influence the inflammatory response in AS. The aim was to analyze the association and interaction of two functional variants of the DEFB1 gene in AS patients, and their role with inflammatory markers. METHODS AND RESULTS: The rs11362 and rs1800972 variants were genotyped using TaqMan probes in Mexican AS patients and controls. C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR) were quantified. SPSS software was used for statistical analysis and multifactor dimensionality reduction (MDR) for interactions. The AA and GG genotypes were associated with AS risk in the age- and sex-adjusted model (OR = 6.89, P = 0.008 and OR = 3.43, P = 0.046, respectively); furthermore, the A-G haplotype showed a significant association with AS risk (OR = 2.94, P = 0.012). ESR and CRP were elevated in carriers of the AA genotype compared to the GA and GG genotypes of the rs11362 variant (20.89 ± 9.78 vs. 5.63 ± 4.61 and 4.10 ± 2.65 mm/h, P < 0.0001; and 10.92 ± 14.09 vs. 2.14 ± 2.02 and 2.15 ± 2.13 mg/L, P < 0.001, respectively). Using the MDR method, strong interactions of the rs11362 variant with sex were identified in the adjusted and unadjusted models. CONCLUSIONS: These results suggest that the DEFB1 gene may play a key role in AS pathogenesis.
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Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Espondilite Anquilosante , beta-Defensinas , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Alelos , beta-Defensinas/genética , Sedimentação Sanguínea , Proteína C-Reativa/genética , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Frequência do Gene/genética , Estudos de Associação Genética , Genótipo , Haplótipos/genética , México , Espondilite Anquilosante/genéticaRESUMO
SUMMARY OBJECTIVE: This study aimed to assess the prevalence of temporomandibular dysfunction in ankylosing spondylitis patients and healthy controls, examining the relationship between temporomandibular dysfunction and disease activity in ankylosing spondylitis patients, as well as associations with psychosocial factors. METHODS: The study included 113 ankylosing spondylitis patients and 110 healthy individuals aged 18-75. Temporomandibular dysfunction presence was evaluated using Diagnostic Criteria for Temporomandibular Disorders Axis I. Disease activity was assessed with the Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Metrology Index, and Bath Ankylosing Spondylitis Functional Index. RESULTS: Among healthy individuals, 60.9% did not receive a temporomandibular dysfunction diagnosis, while 39.1% received at least one diagnosis. In contrast, 69.9% of the 113 ankylosing spondylitis patients received at least one temporomandibular dysfunction diagnosis, and only 30.1% were not included in any diagnosis group (p<0.001). Joint (p=0.001) and pain disorders (p=0.008) were significantly more common in the ankylosing spondylitis group than in the healthy controls. Significant associations emerged between Bath Ankylosing Spondylitis Disease Activity Index (p<0.001) and Bath Ankylosing Spondylitis Functional Index (p=0.005) scores and pain disorders. CONCLUSION: Temporomandibular dysfunction is more prevalent in ankylosing spondylitis patients than in healthy individuals, linked to increased joint issues and pain associated with disease activity. ClinicalTrials.gov ID: NCT05839925.
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OBJECTIVES: To evaluate the tuberculin skin test (TST) conversion in chronic inflammatory arthropathies (CIA) patients on TNFα inhibitors (TNFi) and without previous latent tuberculosis infection (LTBI) treatment. METHODS: Patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) with negative LTBI were retrospectively evaluated for TST conversion and active tuberculosis (TB) after six months of exposition to TNFi. Two groups were compared: patients who repeated TST (TST-repetition) during the follow-up and patients who did not (non-TST-repetition). RESULTS: A total of 355 CIA patients on TNFi were screened and 138 (38.9%) did not fulfill the inclusion criteria. Of the remaining 217 CIA patients, 81 (37.3%) repeated TST during TNFi treatment. TST conversion rate was observed in 18 (22.2%) patients without significant differences among CIA (p = 0.578). The number of TB cases was low (n = 10; 4.6%) and was similar in TST-repetition and non-TST-repetition groups [2 (2.5%) vs. 8 (5.9%), p = 0.328]. Of note, 30% of active TB occurred early (6-12 months of TNFi exposure) and the median (full range) time to incident TB was 1.3 (0.6-10.6) years, whereas the median (full range) time to TST repetition was later [3.3 (0.5-13.4) years]. The incidence of active TB was lower among RA patients than AS patients [342 (95% CI 41 - 1446) vs. 1.454 (95% CI 594-2993)/100,000 patient-years, p = 0.049]. CONCLUSION: These results indicate that TST repetition is associated with a high conversion rate, suggesting the need for recommended treatment. The delayed repetition of TST and low number of active TB cases hampered the evaluation of this strategy effectiveness to prevent active infection. Larger studies with systematic repetition patterns are necessary. In addition, the study highlights the need for a greater surveillance for TB in AS patients.
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Artrite Psoriásica , Artrite Reumatoide , Tuberculose Latente , Espondilite Anquilosante , Teste Tuberculínico , Fator de Necrose Tumoral alfa , Humanos , Estudos Retrospectivos , Artrite Reumatoide/tratamento farmacológico , Masculino , Feminino , Artrite Psoriásica/tratamento farmacológico , Pessoa de Meia-Idade , Espondilite Anquilosante/tratamento farmacológico , Tuberculose Latente/diagnóstico , Tuberculose Latente/epidemiologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Antirreumáticos/uso terapêutico , Antirreumáticos/efeitos adversos , Idoso , Estudos de Coortes , Doenças Endêmicas , Inibidores do Fator de Necrose Tumoral/uso terapêuticoRESUMO
OBJECTIVE: To develop a CT-based scoring system for assessment of hip arthropathy in AS. METHODS: All AS patients were prospectively recruited, consented, and underwent whole-body stereoradiographs and pelvis CT, which were assessed by two independent radiologists. Stereoradiographs were assessed according to Kellgreen-Lawrence and BASRI-h. For the Hip arthropathy CT score in AS (HACTSAS), joints were divided into 7 segments and scored for joint space, osteophytes, subchondral cysts/erosions. Patients were clinically assessed for range of motion (ROM), pain, and clinical scores (BASMI, BASFI, ASQol, BASDAI and ASDAS). Radiological scores correlations with clinical parameters were compared. ROM sensitivity and specificity for hip arthropathy (BASRI-h ≥ 2) were calculated. RESULTS: Sample included 112 patients, with 36/112 females and 76/112 males. Average age was 51.0 ± 11.2 years and mean duration of AS was 20.9 ± 9.6 years. ICC for HACTSAS, Kellgreen-Lawrence and BASRI-h were 0.89, 0.89 and 0.82 respectively. HACTSAS showed moderate absolute correlation with ROM (ρ=-0.41) and BASMI (ρ = 0.45), and weak with pain (ρ = 0.18) and BASFI (ρ = 0.25). BASRI-h and Kellgreen-Lawrence exhibited moderate correlation with ROM (ρ=-0.44 and ρ=-0.40, respectively), weak with pain (ρ=-.27and ρ=-0.23, respectively) and BASFI (ρ=-0.16 and ρ=-0.18, respectively), but only weak with BASMI (ρ=-0.34 and ρ=-0.36, respectively). Internal rotation <15°, abduction <31°, and intermalleolar distance <75cm were, respectively, 73%, 70% and 73% sensitivity and 81%, 65% and 68% specific for hip arthropathy. CONCLUSION: HACTSAS exhibited higher correlation with BASMI and BASFI when compared with BASRI-h, but less correlation with pain and ROM. Internal rotation was the best clinical discriminator for hip arthropathy.
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Background: Ankylosing spondylitis (AS) is characterised as a chronic inflammatory disease of the axial skeleton. The force platform is an option for performing the postural assessment of these individuals. Objectives: To review and evaluate the behaviour of the centre of pressure (CoP) variables during the postural control examination in patients with AS compared to a control group. Method: A systematic review, registered in PROSPERO, that followed the PRISMA Statement. A search was carried out in the following databases: Medline, Web of Science, Embase, Scopus, and Scielo, from 1945 to 2023. Studies were selected that aimed to understand the use of the force platform for the assessment of postural control. The risk of bias assessment was performed using the AXIS tool. Results: Five studies were included, with a total of 247 participants. The assessment of risk of bias presented high scores in the AXIS tool. Patients with a diagnosis of AS presented increased thoracic kyphosis in most of the studies, as well as large displacements in the anteroposterior (AP) and mediolateral (ML) directions, and altered total mean velocity (TMV) and frequency, indicating worse postural stability. Regarding the functional status, the most used questionnaires were the Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI) and Bath Ankylosing Disease Activity Index (BASDAI). Conclusion: Patients with ankylosing spondylitis present postural instability, verified by means of higher values of centre of posture variables. Clinical implications: Individuals with ankylosing spondylitis presented postural instability and balance deficit. Therefore, exercises for balance training and postural control are essential in the clinical management of these patients.
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BACKGROUND: The diagnostic and prognostic relevance of Human Leukocyte Antigen B-27 (HLA-B27) in Axial Spondyloarthritis (AxSpA) is undeniable, with 70% of Ankylosing Spondylitis (AS) patients carrying the B27 gene, contrasted with a mere 4.35% in the general population. Flow cytometry (FC) and Polymerase Chain Reaction (PCR) have emerged as the predominant techniques for routine HLA-B27 typing. While various studies have compared these methods, none have catered to the unique characteristics of the Brazilian demographic. Therefore, this research aims to compare FC and PCR in a Brazilian cohort diagnosed with AxSpA. METHODS: An analytical cross-sectional study was undertaken involving 62 AxSpA outpatients from a Brazilian University Hospital. Both FC and PCR-SSP assays were utilized to ascertain HLA-B27 typing. The outcomes (either confirming or refuting the allele's presence) underwent rigorous scrutiny. Agreement between the methodologies was assessed using the kappa statistic. A p-value of < 0.05 was deemed statistically significant. RESULTS: Of the participants, 90.3% (n = 56) were HLA-B27 positive according to FC, while 79% (n = 49) were identified as positive using the PCR method. FC exhibited a sensitivity rate of 98% paired with a specificity of 38.5%. The Positive Predictive Value for FC stood at 85.7%, and the Negative Predictive Value was 83.5%. Consequently, the overall accuracy of the FC method was gauged at 85.5%. A kappa coefficient of κ = 0.454 was derived. CONCLUSIONS: FC demonstrated noteworthy sensitivity and satisfactory accuracy in HLA-B27 detection, albeit with a reduced specificity when contrasted with PCR-SSP. Nevertheless, given its cost-effectiveness and streamlined operation relative to PCR, FC remains a pragmatic option for preliminary screening in clinical practice, especially in low-income regions. To optimize resource allocation, we advocate for a refined algorithm that initiates by assessing the relevance of HLA-B27 typing based on Choosing Wisely recommendations. It then leans on FC, and, if results are negative yet clinical suspicion persists, advances to PCR. This approach aims to balance diagnostic accuracy and financial prudence, particularly in regions contending with escalating medical costs.
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Citometria de Fluxo , Antígeno HLA-B27 , Reação em Cadeia da Polimerase , Humanos , Antígeno HLA-B27/genética , Antígeno HLA-B27/sangue , Antígeno HLA-B27/análise , Estudos Transversais , Masculino , Feminino , Adulto , Espondiloartrite Axial/diagnóstico , Brasil , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Espondilite Anquilosante/diagnóstico , Espondilite Anquilosante/genéticaRESUMO
BACKGROUND: There is a remarkable variability in the frequency of HLA-B27 positivity in patients with spondyloarthritis (SpA), which may be associated with different clinical presentations worldwide. However, there is a lack of data considering ethnicity and sex on the evaluation of the main clinical and prognostic outcomes in mixed-race populations. The aim of this study was to evaluate the frequency of HLA-B27 and its correlation with disease parameters in a large population of patients from the Brazilian Registry of Spondyloarthritis (RBE). METHODS: The RBE is a multicenter, observational, prospective cohort that enrolled patients with SpA from 46 centers representing all five geographic regions of Brazil. The inclusion criteria were as follow: (1) diagnosis of axSpA by an expert rheumatologist; (2) age ≥18 years; (3) classification according to ASAS axial. The following data were collected via a standardized protocol: demographic data, disease parameters and treatment historical. RESULTS: A total of 1096 patients were included, with 73.4% HLA-B27 positivity and a mean age of 44.4 (±13.2) years. Positive HLA-B27 was significantly associated with male sex, earlier age at disease onset and diagnosis, uveitis, and family history of SpA. Conversely, negative HLA-B27 was associated with psoriasis, higher peripheral involvement and disease activity, worse quality of life and mobility. CONCLUSIONS: Our data showed that HLA-B27 positivity was associated with a classic axSpA pattern quite similar to that of Caucasian axSpA patients around the world. Furthermore, its absence was associated with peripheral manifestations and worse outcomes, suggesting a relevant phenotypic difference in a highly miscegenated population.
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Espondiloartrite Axial , Antígeno HLA-B27 , Fenótipo , Sistema de Registros , Humanos , Antígeno HLA-B27/sangue , Antígeno HLA-B27/genética , Masculino , Brasil/epidemiologia , Feminino , Adulto , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores Sexuais , Estudos de Coortes , Qualidade de Vida , Espondilartrite/etnologia , Idade de Início , Índice de Gravidade de DoençaRESUMO
DNAM-1 (CD226) is an activating receptor expressed in CD8+ T cells, NK cells, and monocytes. It has been reported that two SNPs in the DNAM-1 gene, rs763361 C>T and rs727088 G>A, have been associated with different autoimmune diseases; however, the role of DNAM-1 in ankylosing spondylitis has been less studied. For this reason, we focused on the study of these two SNPs in association with ankylosing spondylitis. For this, 34 patients and 70 controls were analyzed using endpoint PCR with allele-specific primers. Our results suggest that rs763361 C>T is involved as a possible protective factor under the CT co-dominant model (OR = 0.34, 95% CI = 0.13-0.88, p = 0.022) and the CT + TT dominant model (OR = 0.39, 95% CI = 0.17-0.90, p = 0.025), while rs727088 G>A did not show an association with the disease in any of the inheritance models. When analyzing the relationships of the haplotypes, we found that the T + A haplotype (OR = 0.31, 95% CI = 0.13-0.73, p = 0.0083) is a protective factor for developing the disease. In conclusion, the CT and CT + TT variants of rs763361 C>T and the T + A haplotype were considered as protective factors for developing ankylosing spondylitis.
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Ankylosing spondylitis (AS) is an autoinflammatory disease that affects the sacroiliac joints, causing stiffness and pain in the back. MICA is a ligand of the NKG2D receptor, and an increase in its expression affects the immune response in various diseases. NLRP3 is a multiprotein complex that promotes the release of IL-1ß, but its role in AS has been minimally explored. The objective of this study was to analyze the association and interaction of polymorphic variants of the MICA and NLRP3 genes in patients with AS. In this case-control study, patients with AS were included and compared with healthy controls of Mexican origin. The polymorphisms rs4349859 and rs116488202 of MICA and rs3806268 and rs10754558 of NLRP3 were genotyped using TaqMan probes. Associations were determined using logistic regression models, while interactions were analyzed by the multifactorial dimensionality reduction (MDR) method. A P value < 0.05 was considered statistically significant. The minor allele of rs4349859 (A) and rs116488202 (T) of MICA polymorphisms showed risk associations with AS (OR = 9.22, 95% CI = 4.26-20.0, P < 0.001; OR = 9.36, 95% CI = 4.17-21.0, P < 0.001), while the minor allele of the rs3806268 (A) polymorphism of NLRP3 was associated with protection (OR = 0.55, 95% CI = 0.33-0.91, P = 0.019). MDR analysis revealed synergistic interactions between the MICA and NLRP3 polymorphisms (P = 0.012). In addition, high- and low-risk genotypes were identified among these variants. The study findings suggest that the MICA rs4349859 A allele and rs116488202 T allele are associated with AS risk. An interaction between MICA and NLRP3 was observed which could increase the genetic risk in AS.
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Espondilite Anquilosante , Humanos , Espondilite Anquilosante/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Estudos de Casos e Controles , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , GenótipoRESUMO
Abstract Introduction/Objectives: To assess people's level of recognition of rheumatic disease symptoms and their awareness that the rheumatologist is the main effector when it comes to these disorders. Materials and methods: Survey performed in 8 towns in the Buenos Aires Province. Every town had at least one rheumatologist. Three clinical cases were presented: (1) inflammatory low back pain, (2) systemic disease, and (3) chronic polyarthritis. The population was asked whether (a) a physician should be immediately consulted, or (b) they could wait. They were asked whether they would advocate any initial treatment. They were also asked which physician should be consulted. Results: Out of 150 surveys, 68% were female, the average age was 51.7 years old. Most people asserted that treatment with anti-inflammatory drugs should come first: 83% in inflammatory low back pain, 70% in systemic disease, and 70% in chronic polyarthritis (p = 0.02). The number of men that suggested waiting was higher (47% vs. 28% of women; p = 0.04). A rheumatologist was recommended by 51% for chronic polyarthritis, 15% for systemic disease, and 8% for inflammatory low back pain (p < 0.0001). Thirty-eight percent of those who never considered consulting a rheumatologist had elementary education vs. 19% of those who considered consulting a rheumatologist for one of the 3 cases (p = 0.01) Conclusions: Chronic polyarthritis was the disease people identified best as within the rheumatologist's field of expertise. Men tended to delay consultation more than women. Consultation is less likely when the level of education is lower.
RESUMEN Introducción/Objetivos: Evaluar el nivel de conocimiento de la población con respecto a los síntomas reumáticos y determinar si se reconoce al reumatólogo como el profesional que debe ser consultado en primer lugar ante su aparición. Materiales y métodos: Encuesta realizada en 8 localidades del interior de la provincia de Buenos Aires. Cada ciudad tenía al menos un reumatólogo. Se presentaron tres casos clínicos: (1) lumbalgia inflamatoria, (2) enfermedad sistémica y (3) poliartritis crónica. Se preguntó si (a) aconsejarían consultar a un médico de inmediato, o (b) aconsejarían esperar. Se preguntó si aconsejarían algún tratamiento y a qué médico aconsejarían consultar en primer lugar. Resultados: Sobre 150 encuestados, el 68% fueron mujeres y la edad promedio fue de 51,7 años. El 83% de los encuestados aconsejó usar antiinflamatorios en lumbalgia inflamatoria vs. 70% en enfermedad sistémica y 70% en poliartritis crónica (p = 0,02). Los hombres sugirieron esperar con mayor frecuencia que las mujeres (47% vs. 28%; p = 0,04). Un 51% de los encuestados recomendó consultar al reumatólogo en primer lugar en poliartritis crónica vs. 15% en enfermedad sistémica y 8% en lumbalgia inflamatoria (p < 0,001). Entre aquellos que nunca consideraron consultar a un reumatólogo, el 38% tenía educación primaria vs. el 19% entre los que sugirieron consultar a un reumatólogo en alguno de los 3 casos (p = 0,01). Conclusiones: La poliartritis crónica fue la enfermedad mejor identificada dentro del campo de la reumatología. Los hombres tienden a retrasar la consulta con el médico. La consulta con el reumatólogo es menos probable cuanto menor es el nivel de educación.
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BACKGROUND: The prevalence of HLA-B27 gene positivity in healthy Caucasian communities varies between 8 and 14%. However, there is a lack of information in countries with a high rate of miscegenation, such as Brazil. AIM: To estimate the frequency of HLA-B27 in the Brazilian general population using a large national registry database. METHODS: This is a cross-sectional ecological study using the Brazilian Registry of Volunteer Bone Marrow Donors (REDOME) database on HLA-B27 allelic frequency and proportion of positives of healthy donors (18-60 years old). Data were analyzed according to sex, age, race (by self-reported skin color recommended by the Brazilian Institute of Geography and Statistics - IBGE), and geographic region of residence. RESULTS: From 1994 to 2022, a total of 5,389,143 healthy bone marrow donors were included. The overall positivity for HLA-B27 was 4.35% (CI 95% 4.32-4.37%), regardless of sex and age (57.2% were women, mean age was 41.7yo). However, there was a difference between races: 4.85% in Whites; 2.92% in Blacks; 3.76% in Pardos (Browns i.e. mixed races); 3.95% in Amarelos (Yellows i.e. Asian Brazilians); and 3.18% in Indigenous. There was also a difference regarding geographic region of residence (North: 3.62%; Northeast: 3.63%; Southeast: 4.29%; Midwest: 4.5% and 5.25% in South). The homozygosity rate for the HLA-B27 was 1.32% of all the positives and only 0.06% in the general population. CONCLUSIONS: Our findings provide the first Brazilian national prevalence for HLA-B27 in 4.35%. There is a gradient gene positivity from North to South, suggesting that the genetic background related to the miscegenation due to colonization, slavery, and some later waves of immigration together with internal migratory flows, could explain our findings.
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Antígeno HLA-B27 , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Medula Óssea , Brasil , Estudos Transversais , Frequência do Gene , Antígeno HLA-B27/genéticaRESUMO
Abstract Background Kidney disease is a rare manifestation of ankylosing spondylitis (AS) and its pathological alterations remain poorly described. The aim of this study was to investigate the clinical presentation and pathological alterations on kidney biopsy of AS patients and review and discuss the current literature on the issue. Methods: We retrospectively studied the clinical presentation and kidney pathological alterations of 15 Caucasian AS patients submitted to kidney biopsy between October 1985 and March 2021. Results: Patients were predominantly male (66.7%) with median age at the time of kideney biopsy of 47 years [IQR 34 - 62]. Median serum creatinine at presentation was 1.3 mg/dL [IQR 0.9 - 3] and most patients also had either proteinuria (85.7%) and/or hematuria (42.8%). The most common indication for kidney biopsy was nephrotic syndrome (33.3%), followed by acute or rapidly progressive kidney injury (20%) and chronic kidney disease of unknown etiology (20%). Chronic interstitial nephritis (CIN) (n=3) and AA amyloidosis (n=3) were the most common diagnosis. Others included IgA nephropathy (IgAN) (n=2), focal segmental glomerulosclerosis (n=2), membranous nephropathy (n=1), and immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN)(n=1). Conclusions: We present one of the largest series of biopsy-proven kidney disease in Caucasian AS patients. We found a lower prevalence of IgAN than previously reported in Asian cohorts. We found a higher prevalence of CIN and a lower prevalence of AA amyloidosis than that described in previous series of Caucasian patients. We also present the first case of AS-associated IC-MPGN.
Resumo Antecedentes: A doença renal é uma manifestação rara de espondilite anquilosante (EA) e as suas alterações patológicas permanecem pouco descritas. O objetivo deste estudo foi investigar a apresentação clínica e alterações patológicas na biópsia renal de doentes com EA bem como rever e discutir a literatura atual sobre o assunto. Métodos: Estudamos retrospectivamente a apresentação clínica e alterações patológicas renais de 15 doentes caucasianos com EA submetidos a biópsia renal entre Outubro de 1985 e Março de 2021. Resultados: Os doentes eram predominantemente homens (66,7%) com idade mediana no momento da biópsia de 47 anos [IIQ 34 - 62]. A creatinina sérica mediana na apresentação foi de 1,3 mg/dL [IIQ 0,9 - 3] e a maioria dos pacientes apresentava também proteinúria (85,7%) e/ou hematúria (42,8%). A indicação mais comum para biópsia renal foi a síndrome nefrótica (33,3%), seguida de lesão renal aguda ou rapidamente progressiva (20%) e doença renal crónica de etiologia desconhecida (20%). A Nefrite intersticial crónica (NIC) (n=3) e a amiloidose AA (n=3) foram os diagnósticos mais comuns. Outros incluíram nefropatia por IgA (NIgA) (n=2), glomeruloesclerose segmentar focal (n=2), nefropatia membranosa (n=1) e glomerulonefrite membranoproliferativa mediada por imunocomplexos (GNMP-IC) (n=1). Conclusões: Apresentamos uma das maiores séries de doenças renais comprovadas por biópsia em doentes caucasianos com EA. Encontramos uma prevalência de NIgA menor do que a relatada anteriormente em coortes asiáticas. Encontramos uma maior prevalência de NIC e uma prevalência menor de amiloidose AA do que a descrita em séries anteriores de pacientes caucasianos. Também apresentamos o primeiro caso de GNMP-IC associada à EA.
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Interleukin 17 (IL-17) inhibitors are approved for treating psoriasis, psoriatic arthropathy, and ankylosing spondylitis. IL-17 is involved in the pathogenesis of inflammatory bowel disease (IBD); however, paradoxical events have been reported using selective IL-17 inhibitors such as secukinumab, whose pathophysiological mechanisms have not been fully clarified. Although the incidence of IBD in this group of patients is low, the risk could be reduced by carefully assessing risk factors such as family history, gastrointestinal symptoms, and fecal calprotectin before starting treatment.
Los inhibidores de interleucina 17 (IL-17) se encuentran aprobados para el tratamiento de psoriasis, artropatía psoriásica y espondilitis anquilosante. La IL-17 se encuentra involucrada en la patogenia de la enfermedad inflamatoria intestinal (EII); sin embargo, hasta la fecha se han reportado eventos paradójicos con el uso inhibidores selectivos de IL-17 como el secukinumab, cuyos mecanismos fisiopatológicos no han sido del todo aclarados. Aunque la incidencia de EII en este grupo de pacientes es baja, el riesgo podría disminuirse mediante una evaluación cuidadosa de factores de riesgo tales como historia familiar, síntomas gastrointestinales y la realización de calprotectina fecal previo al inicio del tratamiento.
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OBJECTIVES: To evaluate humoral responses to three doses of the inactivated SARS-CoV-2 vaccine (CoronaVac) in patients with spondyloarthritis (SpA) and the effect of therapy, compared with a control group (CG). METHODS: Prospective cohort of axial SpA/psoriatic arthritis patients and age/sex-balanced CG from the CoronavRheum phase 4 trial (NCT04754698). CoronaVac was given in two doses (28-days interval) with a booster at day 210. Blood samples were collected in the days 0/28 (D28)/69 (D69) and 240 (D240) to evaluate anti-SARS-CoV-2 IgG seropositivity (SP) and neutralising antibodies (NAb). RESULTS: One hundred and ninety-four SpA patients were enrolled and 183 patients were age/sex-balanced with 183 CG. At D69, SpA patients showed a high SP (80.2% vs. 95.7%, P<0.001) and moderate NAb positivity (61.6% vs. 82.7%, P<0.001), but lower than CG. In patients, older age prednisone (P<0.001), methotrexate (MTX) (P<0.001) and TNF inhibitors (TNFi) (P<0.001) were independently associated with lower SP, while Caucasian ethnicity (P<0.05) and prednisone (P<0.01) were associated with diminished NAb. In contrast, sulfasalazine (SSZ) use was associated with NAb presence (P<0.05). In monotherapy, only TNFi was also associated with absence of SP (P<0.05). Further comparison with CG revealed that TNFi and/or MTX negatively impacted SP/NAb (P<0.05). In contrast, patients under SSZ monotherapy achieved 100% SP (P>0.999) and 83.3% NAb positivity (P>0.999). SSZ+TNFi combination resulted in a similar response than CG [SP (P=0.153) and NAb (P=0.715)]. After third dose (D69-D240), a major increment occurred for SP (81.3% to 93.1%, P<0.001) and NAb (63.2% to 86.1%, P<0.001), but still lower than CG (P<0.05), and only TNFi impaired both SP (P=0.016)/NAb (P=0.002). CONCLUSIONS: We provided novel data demonstrating that TNFi attenuates immunogenicity in SpA patients while SSZ has a positive impact on vaccine antibody production. We also confirmed that MTX in combination with TNFi had a major negative impact in vaccine humoral response (CoronavRheum clinicaltrials.gov #NCT04754698).
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Antirreumáticos , Artrite Psoriásica , Espondiloartrite Axial , COVID-19 , Espondilartrite , Humanos , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Vacinas contra COVID-19/uso terapêutico , Metotrexato/uso terapêutico , Prednisona/uso terapêutico , Estudos Prospectivos , SARS-CoV-2 , Espondilartrite/tratamento farmacológico , Sulfassalazina/uso terapêutico , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Fator de Necrose Tumoral alfa/uso terapêutico , Masculino , FemininoRESUMO
Abstract Background Secukinumab has shown high efficacy in randomized controlled trials in both ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Here, we investigated its real-life effectiveness and tolerability in a cohort of AS and PsA patients. Methods We retrospectively analyzed medical records of outpatients with AS or PsA treated with secukinumab between December 2017 and December 2019. ASDAS-CRP and DAS28-CRP scores were used to measure axial and peripheral disease activity in AS and PsA, respectively. Data were collected at baseline and after 8, 24, and 52 weeks of treatment. Results Eighty-five adult patients with active disease (29 with AS and 56 with PsA; 23 males and 62 females) were treated. Overall, mean disease duration was 6.7 years and biologic-naïve patients were 85%. Significant reductions in ASDAS-CRP and DAS28-CRP were observed at all time-points. Body weight (in AS) and disease activity status at baseline (particularly in PsA) significantly affected disease activity changes. ASDAS-defined inactive disease and DAS28-defined remission were achieved in comparable proportions between AS and PsA patients, at both 24 weeks (45% and 46%) and 52 weeks (65.5% and 68%, respectively); male sex was found an independent predictor of positive response (OR 5.16, P = 0.027). After 52 weeks, achievement of at least low disease activity and drug retention were observed in 75% of patients. Secukinumab was well-tolerated and only mild injection-site reactions were recorded in 4 patients. Conclusion In a real-world setting, secukinumab confirmed great effectiveness and safety in both AS and PsA patients. The influence of gender on treatment response deserves further attention.
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Abstract Background The prevalence of HLA-B27 gene positivity in healthy Caucasian communities varies between 8 and 14%. However, there is a lack of information in countries with a high rate of miscegenation, such as Brazil. Aim To estimate the frequency of HLA-B27 in the Brazilian general population using a large national registry database. Methods This is a cross-sectional ecological study using the Brazilian Registry of Volunteer Bone Marrow Donors (REDOME) database on HLA-B27 allelic frequency and proportion of positives of healthy donors (18-60 years old). Data were analyzed according to sex, age, race (by self-reported skin color recommended by the Brazilian Institute of Geography and Statistics - IBGE), and geographic region of residence. Results From 1994 to 2022, a total of 5,389,143 healthy bone marrow donors were included. The overall positivity for HLA-B27 was 4.35% (CI 95% 4.32-4.37%), regardless of sex and age (57.2% were women, mean age was 41.7yo). However, there was a difference between races: 4.85% in Whites; 2.92% in Blacks; 3.76% in Pardos (Browns i.e. mixed races); 3.95% in Amarelos (Yellows i.e. Asian Brazilians); and 3.18% in Indigenous. There was also a difference regarding geographic region of residence (North: 3.62%; Northeast: 3.63%; Southeast: 4.29%; Midwest: 4.5% and 5.25% in South). The homozygosity rate for the HLA-B27 was 1.32% of all the positives and only 0.06% in the general population. Conclusions Our findings provide the first Brazilian national prevalence for HLA-B27 in 4.35%. There is a gradient gene positivity from North to South, suggesting that the genetic background related to the miscegenation due to colonization, slavery, and some later waves of immigration together with internal migratory flows, could explain our findings.
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Abstract Background Ankylosing Spondylitis (AS) patients face several challenges due to the nature of the disease and its physical and psychological complications. Sleep disorders are among the most important concerns. Sleep disorders can aggravate the signs and symptoms of the disease and ultimately reduce the quality of patients' lives. This study uses a systematic review and meta-analysis to pool the reported prevalence of sleep disorders among AS patients. Methods To find related studies, the WoS, PubMed, ScienceDirect, Scopus, Embase, and Google Scholar databases were systematically searched without a lower time limit. Heterogeneity among the identified studies was checked using the I2 index, and the Begg and Mazumdar correlation test examined the existence of published bias. Comprehensive Meta-Analysis (v.2) software was adopted to analyze the data. Results In the review of 18 studies with a sample size of 5,840, the overall pooled prevalence of sleep disorders among AS patients based on the random effects method was found to be 53% (95% CI: 44.9-61). The highest and lowest prevalence was in Egypt at 90% and Australia at 19.2%, respectively. Our meta-regression results show that with the increase in 'sample size' and 'year of publication', the overall prevalence of sleep disorders in patients with AS decreases (p < 0.05). Conclusion The results of the present study indicate a high and significant prevalence of sleep disorders among AS patients. Thus, health policymakers and healthcare providers must focus on timely diagnosis and effective educational and therapeutic interventions for the prevention and proper treatment of sleep disorders in this population of patients.
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SUMMARY OBJECTIVE: The aim of this study was to assess the relation of systemic immune inflammation index, systemic inflammation response index, and systemic inflammation aggregate index with disease activity, functional status, and general health status in ankylosing spondylitis. METHODS: Patients with ankylosing spondylitis and healthy volunteers were included in this cross-sectional study. Demographic data; disease activity measurements such as the Bath Ankylosing Spondylitis Disease Activity Index, the Ankylosing Spondylitis Disease Activity Score with C-reactive protein, and the Ankylosing Spondylitis Disease Activity Score with erythrocyte sedimentation rate; functional status such as the Bath Ankylosing Spondylitis Functional Index; and general health status such as the Assessment of Spondyloarthritis International Society Health Index of the patients were recorded. C-reactive protein, erythrocyte sedimentation rate, platelet to lymphocyte ratio, neutrophil to lymphocyte ratio, monocyte to lymphocyte ratio, systemic immune inflammation index, systemic inflammation response index, and systemic inflammation aggregate index values were recorded. Patients were grouped as active and remission according to the Bath Ankylosing Spondylitis Disease Activity Index score and as inactive-low and high-very high disease activity according to the Ankylosing Spondylitis Disease Activity Score. The correlation of laboratory parameters with disease-related parameters was tested. RESULTS: The indexes were significantly higher in patients compared to controls (p<0.001, for platelet to lymphocyte ratio p=0.03). No significant differences existed in any blood cell-derived indexes among patient groups categorized by disease activity (p<0.05 for all). Systemic immune inflammation index was weakly correlated with Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ρ=0.197 and p=0.049) and Ankylosing Spondylitis Disease Activity Score-erythrocyte sedimentation rate (ρ=0.201 and p=0.045). Systemic immune inflammation index was not correlated with Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, and Assessment of Spondyloarthritis International Society Health Index. No correlation was found between other indexes and disease-related variables. Platelet to lymphocyte ratio, systemic immune inflammation index, systemic inflammation response index, and systemic inflammation aggregate index showed a weak positive correlation with C-reactive protein and erythrocyte sedimentation rate (ρ=0.200-0.381). CONCLUSION: Systemic immune inflammation index, systemic inflammation response index, and systemic inflammation aggregate index can be used to indicate systemic inflammatory burden in ankylosing spondylitis patients. However, these indexes are not effective in indicating patients' disease activity, general health status, and functional status.
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BACKGROUND AND AIMS: Spondyloarthritis (SpA) is a group of autoinflammatory disorders, of which the primary extra-articular manifestation is inflammatory bowel disease (IBD). The oral cavity being a part of gastrointestinal tract, is significantly compromised in IBD, and in many cases, it is the first site of clinical manifestations of IBD. This study aimed to identify changes in the oral mucosa associated with the onset of IBD and their association with endoscopic/histological findings. MATERIALS AND METHODS: The study assessed 80 patients with SpA and 52 healthy controls. Oral, rheumatological, and gastroenterological assessments were performed. The ileocolonoscopy was performed via digital magnification chromoendoscopy. The statistical analysis consisted of Chi-square, Fisher's exact, and multiple correspondence discriminant analysis tests. RESULTS: From the disease cohort, 63.0% patients showed oral lesions (p = 0.050). These manifestations ranged from gingivitis (55.0%, p = 0.001), aphthous stomatitis (3.8%, p = 0.091), angular cheilitis (2.6%, p = 0.200), and perioral erythema with scaling (1.3%, p = 0.300). All patients who presented with alterations in colonic mucosa also had oral lesions associated with IBD (p = 0.039), specifically gingivitis/aphthous stomatitis (p = 0.029). CONCLUSION: The patients with SpA without IBD present significant oral signs and symptoms. Gingivitis seems to be the most relevant because of its associations with early endoscopic and histological findings. CLINICAL RELEVANCE: An integral approach to the diagnostic tests that includes evaluations of oral, rheumatological and gastroenterological tissues may favor timely attention and improve patients' quality of life.
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Gengivite , Doenças Inflamatórias Intestinais , Úlceras Orais , Doenças Reumáticas , Espondilartrite , Estomatite Aftosa , Humanos , Estomatite Aftosa/complicações , Qualidade de Vida , Espondilartrite/complicações , Doenças Inflamatórias Intestinais/complicações , Doença Crônica , Doenças Reumáticas/complicaçõesRESUMO
BACKGROUND: The aim of this study was to evaluate disease activity among patients with axial spondyloarthritis (AS) treated with tumor necrosis factor inhibitors (TNFi) and/or nonsteroidal anti-inflammatory drugs (NSAIDs) for at least 12 weeks in private outpatient settings in Brazil. METHODS: This was a cross-sectional, real-world study conducted in 17 Brazilian private health care institutes. Patients were selected if diagnosed with AS or axial radiographic spondyloarthritis (AxSpA) and treated with NSAIDs or TNFi for at least 12 weeks within the last 26 weeks prior to enrollment. The data were collected from interviewed-based and self-administered questionnaires from patients and physicians. Disease activity was defined as active (≥ 4), low /suboptimal (≥ 2 and < 4) and inactive (< 4) by Bath AS Disease Activity Index (BASDAI) and/or very high (≥ 3.5), high (≥ 2.1 to < 3.5), low (≥ 1.3 to < 2.1), and inactive (< 1.3) by AS Disease Activity Score (ASDAS-CRP). Both patients and physicians' perceptions of disease control were assessed using a numeric rating scale (NRS; 0-inactive to 10-very active disease). RESULTS: The cohort included 378 patients with a mean age of 46 years, and the median time since diagnosis until enrollment was 5.4 years (interquartile range 2.7-10.5). Most patients were treated with TNFi alone (74%), followed by TNFi in combination with NSAID (15%), and NSAID alone (11%). About half AS patients showed active disease and 24% of patients showed low activity/suboptimal disease control despite having been treated for at least 12 weeks. Although TNFi showed better disease control than NSAID, inactive disease was experienced by few patients. The NRS (mean [standard deviation]) score for disease perception was 4.24 (3.3) and 2.85 (2.6) for patients and physicians, respectively. CONCLUSION: This real-world study showed that most AS patients on TNFi and/or NSAID had not achieved an adequate disease control, as almost 75% of them exhibited active disease or low activity/suboptimal disease control. There remains a need for improved disease management among patients with AS.