CT-based comprehensive scoring system for assessing hip arthropathy in ankylosing spondylitis: feasibility study with clinical correlation.

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.

Use of posturography in patients with ankylosing spondylitis: A systematic review.

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.

Comparative study of two laboratory techniques for the detection of HLA-B27 in patients with axial spondyloarthritis: a cross-sectional analysis.

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.

To be or not to B27 positive: implications for the phenotypes of axial spondyloarthritis outcomes. Data from a large multiracial cohort from the Brazilian Registry of Spondyloarthritis.

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.

Genetic Variant of DNAM-1 rs763361 C>T Is Associated with Ankylosing Spondylitis in a Mexican Population.

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.

MICA and NLRP3 gene polymorphisms interact synergistically affecting the risk of ankylosing spondylitis.

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.

Foot pain and disability in patients with ankylosing spondylitis is associated to disease activity / Dor e deficiência no pé em pacientes com espondilite anquilosante estão associadas à atividade da doença

ABSTRACT BACKGROUND AND OBJECTIVES: The feet may be involved in patients with ankylosing spondylitis (AS), causing pain and walking difficulties. This research aimed to study the involvement of the foot in a sample of Brazilian patients with AS. METHODS: The Brazilian version of the Foot Function Index (FFI-BR) was applied to 103 individuals (57 AS patients and 46 controls). Clinical profiles were obtained in AS patients as well as the measurement of disease activity by the ASDAS (Ankylosing Spondylitis Disease Activity Score)-ESR (erythrocyte sedimentation rate), ASDAS-CRP (C reactive protein) and BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and function by BASFI (Bath Ankylosing spondylitis functional score). RESULTS: Only 19.2% of AS patients did not have any foot complaints and the FFI-BR score presented worse results than the control group (p = 0.02). The "pain" domain of FFI-BR scored highest in AS patients, followed by "disability". There was no association between the results of the FFI-BR and the clinical profile of patients with AS, but there was an association between the score and the disease activity indexes (r = 0.50, p = 0.003 with ASDAS-ESR; r = 0.44, p = 0.005 with ASDAS-CRP; and r = 0.60, p < 0.0001 with BASDAI). The BASFI also showed a positive correlation (r = 0.72; p < 0.0001). CONCLUSION: Pain and disability are common in AS patients and these symptoms are associated with disease activity.

RESUMO JUSTIFICATIVA E OBJETIVOS: Os pés podem ser acometidos em pacientes com espondilite anquilosante (EA), causando dor e dificuldade de locomoção. O objetivo deste trabalho foi estudar o envolvimento do pé em uma amostra de pacientes brasileiros com EA. MÉTODOS: A versão brasileira do Foot Function Index (FFI-BR) foi aplicada a 103 indivíduos (57 pacientes com EA e 46 controles). O perfil clínico foi obtido para pacientes com EA, bem como a medição da atividade da doença por meio do ASDAS (Ankylosing Spondylitis Disease Activity Score)-ESR. (velocidade de hemossedimentação), ASDAS-CRP (proteína C reativa) e BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) e função pelo BASFI (Bath Ankylosing Spondylitis Functional Score). RESULTADOS: Apenas 19,2% dos pacientes com EA não apresentaram queixas nos pés e o escore FFI-BR apresentou resultados piores do que os do grupo controle (p = 0,02). O domínio "dor" do FFI-BR apresentou a maior pontuação nos pacientes com EA seguido pelo domínio "disfunção". Não se observou associação dos resultados do FFI-BR com o perfil clínico dos pacientes com EA, mas houve associação do escore com os índices de atividade da doença (r = 0,50, p = 0,003 com ASDAS-ESR; r = 0,44, p = 0,005 com ASDAS-CRP; e r = 0,60, p < 0,0001 com BASDAI). O BASFI também apresentou correlação positiva (r = 0,72; p< 0,0001). CONCLUSÃO: Dor e disfunção são comuns em pacientes com EA e estes sintomas se associam com atividade de doença.

Escala de discapacidad de Oswestry en la corrección de la cifosis toracolumbar por espondilitis anquilopoyética

Introducción: Cuando se valora la cifosis toracolumbar por espondilitis anquilopoyética, se debe medir la repercusión funcional para mejorar la calidad de vida del paciente y solucionar los problemas de una atención adecuada. En consecuencia, se necesitan nuevos conocimientos que implementen una técnica quirúrgica y la escala de discapacidad de Oswestry, método innovador con cambios cualitativos en beneficio de los enfermos. Objetivo: Evaluar los resultados funcionales con la escala de Oswestry en la corrección de la cifosis toracolumbar por espondilitis anquilopoyética. Método: Se realizó un estudio tipo descriptivo, retrospectivo, longitudinal a 16 pacientes con cifosis toracolumbar por espondilitis anquilopoyética, intervenidos con la técnica de osteotomía de sustracción pedicular, en el Servicio de Ortopedia del Hospital Clínico Quirúrgico "Hermanos Ameijeiras", durante el período de marzo de 2001 a marzo de 2021. Resultados: Se obtuvo un buen resultado funcional y mejoró la calidad de vida de los pacientes. Conclusiones: La escala de Oswestry resulta viable, fácil de administrar y puntuar; además, presenta características métricas adecuadas para la evaluación funcional en la corrección de la cifosis toracolumbar por espondilitis anquilopoyética.

Introduction: When evaluating thoracolumbar kyphosis due to ankylopoietic spondylitis, the functional impact should be measured to improve the patient's quality of life and solve the problems of adequate care. Consequently, knowledge is needed to implement a surgical technique and the Oswestry disability scale, an innovative method with qualitative changes for the benefit of patients. Objective: To evaluate the functional results with the Oswestry scale in the correction of thoracolumbar kyphosis by ankylopoietic spondylitis. Method: A descriptive, retrospective, longitudinal study was performed on 16 patients with thoracolumbar kyphosis due to ankylopoietic spondylitis, who underwent surgery using the technique of pediatric subtractive osteotomy, in the Orthopedic Service of "Hermanos Ameijeiras" Clinical Surgical Hospital during the period from March 2001 and March 2021. Results: A good functional result was obtained and the quality of life of the patients improved. Conclusions: The Oswestry scale is feasible, easy to administer and score; in addition, it has adequate metric characteristics for the functional evaluation in the correction of thoracolumbar kyphosis by ankylopoietic spondylitis.

HLA-B27 positivity in a large miscegenated population of 5,389,143 healthy blood marrow donors in Brazil.

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.

Kidney Disease in Ankylosing Spondylitis: a case series and review of the literature / Doença Renal na Espondilite Anquilosante: uma série de casos e revisão da literatura

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.

Ulcerative Colitis Induced by Secukinumab in the Treatment of Ankylosing Spondylitis

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.

Interaction of TNFi and conventional synthetic DMARD in SARS-CoV-2 vaccine response in axial spondyloarthritis and psoriatic arthritis.

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).

Effectiveness and safety of secukinumab in ankylosing spondylitis and psoriatic arthritis: a 52-week real-life study in an Italian cohort

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.

HLA-B27 positivity in a large miscegenated population of 5,389,143 healthy blood marrow donors in Brazil

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.

Prevalence of sleep disturbance in patients with ankylosing spondylitis: a systematic review and meta-analysis

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.

Use of the Oswestry Disability Index in ankylosing spondylitis

SUMMARY OBJECTIVE: The Oswestry Disability Index is considered the gold standard in the evaluation of disability in patients with chronic mechanical back pain. The aim of this study was to assess the applicability of Oswestry Disability Index in patients with ankylosing spondylitis and its relationship with disease assessment parameters for ankylosing spondylitis. METHODS: A total of 100 patients diagnosed with ankylosing spondylitis were included in the study group. The control group consisted of 50 individuals with nonspecific low back pain. The Oswestry Disability Index and Bath Ankylosing Spondylitis Disease Activity Index were applied to both groups. In addition, the Visual Analog Scale, the Ankylosing Spondylitis Disease Activity Score C-Reactive Protein, the Ankylosing Spondylitis Disease Activity Score-the Erythrocyte Sedimentation Rate, the Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Metrology Index, and the Ankylosing Spondylitis Quality of Life scales were applied in the study group. the Erythrocyte Sedimentation Rate, C-Reactive Protein levels, and HLA-B27 analysis were noted as laboratory markers in ankylosing spondylitis patients. RESULTS: The scores of Oswestry Disability Index had a significant correlation with scores of Bath Ankylosing Spondylitis Disease Activity Index in ankylosing spondylitis patients (r=0.543) and in the control group (r=0.401). There was a significant correlation between the scores of Oswestry Disability Index and the Bath Ankylosing Spondylitis Functional Index (r=0.544), Bath Ankylosing Spondylitis Metrology Index (r=0.317), the Ankylosing Spondylitis Quality of Life (r=0.723), the Ankylosing Spondylitis Disease Activity Score-the Erythrocyte Sedimentation Rate (r=0.501), the Ankylosing Spondylitis Disease Activity Score C-Reactive Protein (r=0.530), Visual Analog Scale-Rest (r=0.476), and Visual Analog Scale-Activity (r=0.441) values in patients with ankylosing spondylitis. CONCLUSION: Evaluation of Oswestry Disability Index in conjunction with Bath Ankylosing Spondylitis Disease Activity Index may warn the physician to interpret high Bath Ankylosing Spondylitis Disease Activity Index scores in the context of mechanical pain. Therefore, the use of Oswestry Disability Index in patients with ankylosing spondylitis will be beneficial.

Evaluation of the relationship between blood cell markers and inflammation, disease activity, and general health status in ankylosing spondylitis

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.

TNF-alpha and IL-17 cytokine levels in Brazilian patients with ankylosing spondylitis after anti-TNF therapy

Abstract The aim of this study was to evaluate tumor necrosis factor alpha (TNF-α), interleukin (IL)- 17A/F levels in the serum of ankylosing spondylitis (AS) patients after anti-TNF therapy, in order to understand how these cytokines are involved in this therapeutic response. Forty-four AS patients were included in the study: thirty using anti-TNF therapy were classified according to their therapy response as responders (15) and non-responders (15) and 14 without anti-TNF therapy were classified as AS control. Fifteen healthy individuals formed the control group. Serum levels of TNF-α were determined using Luminex technology and for IL-17A and IL-17F using ELISA. The non-responder patients presented higher serum levels of TNF-α than the responders and AS control; the same results were found when HLA-B*27 positive or negative patients were separately analyzed. IL-17A and IL17F serum levels were similar for all groups. According to the clinical disease activity, AS patients with BASDAI ≥4 had higher serum levels of TNF-α than AS patients with BASDAI <4. Positive correlation was found between TNF-α levels and BASDAI. In AS patients, TNF-α serum levels were associated with anti-TNF therapy and disease activity independently of HLA-B*27, and IL-17A and IL-17F were not related to anti-TNF treatment

[Multilevel tuberculous spondylitis]. / Espondilitis tuberculosa multinivel.

A case of a 20-year-old man with multilevel non-contiguous tuberculous spondylitis (cervical, dorsal 6, dorsal 10 and lumbar) is presented. In the context of disseminated tuberculosis in an HIV-negative patient with serious compromise of his general condition and multiple locations of the disease, some of these with fistulas that secreted caseum. The acute paraplegia led, considering the sensory level at dorsal 6, to a first urgent decompression surgery via the posterior approach. A scheduled surgery was then performed, first in the cervical region via the anterior approach, with corpectomy, placement of a vertebral body replacement plus autologous graft and plate with screws. Subsequently, dislocation of dorsal level 6 was evidenced backwards, compressing the spinal cord and, given the mechanical instability, a third surgical stage was indicated by posterior approach, which included reduction, decompression and fixation, resolving the three levels by posterior approach with bars and screws. The surgical, medical and physiotherapy treatment of this rare form of Pott's disease was successful, with recovery of his mechanical stability and progressive recovery of his neurological status. The surgical, medical and physiotherapy treatment of this rare form of Pott's disease was successful, with recovery of his mechanical stability and progressive recovery of his neurological status.

Se presenta el caso de un varón de 20 años con espondilitis tuberculosa multinivel no contigua (cervical, dorsal 6, dorsal 10 y lumbar). Se trata de un paciente HIV negativo con tuberculosis diseminada con grave compromiso de su estado general y múltiples localizaciones de la enfermedad. Algunas tenían fistulas que secretaban caseum. El paciente presentó paraplejía aguda que requirió, teniendo en cuenta el nivel sensitivo a nivel dorsal 6, una primera cirugía urgente de descompresión por vía posterior. Luego se efectuó la cirugía programada. En primera instancia, la región cervical por vía anterior, con corporectomía, colocación de reemplazo de cuerpo vertebral más injerto autólogo y placa con tornillos. Posteriormente se evidenció luxación del nivel dorsal 6 hacia atrás comprimiendo la médula espinal y, dada la inestabilidad mecánica, se indicó un tercer tiempo quirúrgico por vía posterior que comprendió reducción, descompresión y fijación, resolviendo los tres niveles por vía posterior con barras y tornillos. El tratamiento quirúrgico, médico y kinésico de esta forma poco frecuente del mal de Pott fue exitoso, con recuperación de su estabilidad mecánica y progresiva recuperación de su estado neurológico.

Espondilitis anquilosante. Presentación de caso

La espondilitis anquilosante es una enfermedad sistémica caracterizada por inflamación del esqueleto axial, las grandes articulaciones periféricas y los dedos, así como dolor, rigidez de la espalda y manifestaciones a otros niveles del organismo como puede ser en el ojo. Se presenta el caso de una paciente de 46 años de edad que acudió al Hospital Gustavo Aldereguía Lima, de Cienfuegos, por dolor lumbar y sintomatología urinaria refractaria a terapéutica habitual, por lo cual fue ingresada para estudio. Fue evaluada según su cuadro clínico y a través del empleo de exámenes complementarios, lo que permitió el diagnóstico de una espondilitis anquilosante. Se le impuso tratamiento con antinflamatorios no esteroideos y fue dada de alta médica con seguimiento por su área de salud. Por lo importante que resulta confirmar el diagnóstico temprano, antes de que ocurran deformidades irreversibles y así evitar secuelas e impotencia en los pacientes que la padecen, con lo cual se les garantiza una mayor calidad de vida, se decidió la presentación de este caso.

Ankylosing spondylitis is a systemic disease characterized by inflammation of the axial skeleton, large peripheral joints, and fingers, as well as pain, stiffness of the back, and manifestations at other levels of the body, such as the eye. We present the case of a 46-year-old patient who attended the Gustavo Aldereguía Lima Hospital, in Cienfuegos, due to lumbar pain and urinary symptoms refractory to usual therapy, for which she was admitted for study. She was evaluated according to her clinical picture and through the use of complementary tests, which allowed the diagnosis of ankylosing spondylitis. Treatment with non-steroidal anti-inflammatory drugs was prescribed and she was discharged with follow-up by her health area. Due to the importance of confirming the early diagnosis, before irreversible deformities occur and thus avoiding sequelae and impotence in patients who suffer from it, to guarantee them a better quality of life, it was decided to present this case.