HLA-B27 Positivity Research Articles

Prevalence and incidence of uveitis in patients with spondyloarthritis: the impact of the biologics era. Data from International ASAS-COMOSPA Study.

Uveitis is a common extra-musculoskeletal manifestation in Spondyloarthritis (SpA). The aim of this study was to analyze the prevalence of uveitis in SpA patients, its association with geographical areas and to determine whether its incidence was different before and after the biological era. ASAS-COMOSPA is a retrospective study that includes patients fulfilling ASAS SpA classification criteria from 22 countries. The overall prevalence of uveitis was calculated, and factors associated with the onset of a first episode of uveitis were evaluated using a Cox regression. A Log-Rank test was performed to compare the new onset of uveitis in the no biological era (SpA onset before 2000) vs biological era (SpA onset after 2000). 3984 patients were included. The likelihood of presenting a first uveitis episode increased over time, from a prevalence of 10.5% (95%CI 9.5%-11.4%) at the time of the SpA diagnosis to 46.6% (41.6%-51.5%) after 30 years since the SpA diagnosis. HLA-B27 positivity, family history of uveitis, peripheral enthesitis and IBD were associated with higher risk of uveitis. Patients with SpA disease onset after year 2000 showed a lower prevalence of uveitis compared with disease onset before year 2000 (8.2% vs 25.5%, p< 0.01), as well as a lower incidence (2.8 per 100 PY vs 6.1 per 100 PY, respectively). In our study the risk of having suffered from at least one episode of uveitis ranged from 10% at the time of the diagnosis of axSpA to 47% after 30 years of disease duration. Patients with disease onset after biologic therapy introduction showed a significantly lower prevalence and incidence of first episodes of uveitis.

HLA-B27 Frequency and its Association with Ankylosing Spondylitis in Indian Population: A Multi-City Analysis from a Single-Center Study

The human leukocyte antigen HLA-B*27 is a Class 1 antigen of the major histocompatibility complex (MHC) with B locus and has been established in association with pathogenesis of Ankylosing Spondylitis (AS) since 1973. AS is a multifactorial disease which occurs due to interaction between genes, environment, mechanical stress, microbiota and infection. The ankylosing spondylitis is characterized by inflammation of spine, backpain, stiffness of lower back and hips, extrarticular organs such as eyes, and cardiovascular system. In severe cases this may cause the fusion of vertebrae. The current study highlights the mechanism involved in the pathogenesis of AS with a focus to investigate the frequency of HLA B*27 in suspected cases of AS. The patients were recruited from rheumatology clinics of India from age group of 13-69 years. Patients with suspected cases of AS who met the clinical criteria for AS were tested for HLA-B*27. One thousands and four patients were tested for HLA B*27 using RTPCR method. Out of 1004 subjects, 124 (12.35%) were positive for HLA-B*27. Among these, Male/Female ratio was 2.7. Majority of subjects were from North India. The current study highlights the HLA B27 positivity in association with pathogenesis of AS and indicates that HLA B27 serves as a rapid prognostic and diagnostic genetic marker for detection of AS.

Biomarker Changes in Response to Tofacitinib Treatment in Patients with Polyarticular Course Juvenile Idiopathic Arthritis.

Examine levels of candidate blood-based biomarkers (CBB) in juvenile idiopathic arthritis (JIA) treated with tofacitinib. JIA patients who participated in clinical trial NCT02592434 received tofacitinib from baseline to week 18. Serial serum samples were assayed for CBB (S100A8/9, S100A12, IL-18, SAA, resistin, VEGF, Angiopoietin-1, Angiopoietin-2, MMP8, MMP2, TIMP1, Leptin, CXCL9, sIL2R, ICAM-1, sTNFr, IL-6, IL-23, MCP1, CCL18, and CCL20). Association of CBB with JIA response to treatment from baseline to week 18 were assessed. This study included 166 patients with polyarticular-course JIA. Paired serum samples from 143 patients were available at both baseline and week 18. There were 35% (50/143) of patients with a JIA-American College of Rheumatology 90 (JIA-ACR90) level improvement while 90/121/137 (63%/85%/96%) achieved JIA-ACR70/50/30 improvement at wk18. Despite small numerical differences by JIA category, there were no baseline CBB values that independently predicted a decrease in JADAS-27 or JIA-ACR90 response by week 18. Decrease in resistin level (baseline to week 18) was significantly associated with wk18 improvement in JADAS-27 and JIA-ACR90 response, after adjusting for age, sex, JIA disease duration and baseline resistin [(r2 0.79, SE, 0.070, p<0.01 and OR(95%CI) = 1.134(1.018,1.264)]. HLA-B27 positivity was significantly associated with not achieving a JIA-ACR90 response at week 18 (p=0.0097). Among the CBB included, only resistin was significantly associated with treatment response, and no CBB was identified that forecasts JIA improvement after initiation of tofacitinib. The association of HLA-B27 positivity with lower response to tofacitinib in JIA is intriguing and merits further study.

Frequency of HLA-B27 Haplotype Among Patients with Acute Anterior Uveitis and Controls in Ethiopia

ABSTRACT Purpose We compared the distribution of the HLA-B27 allele among Ethiopian patients with acute anterior uveitis (AAU) and controls without that disease. Methods The clinical features of patients were collected from their medical records. HLA-B27 genotyping was performed for 64 patients, with AAU using the real-time polymerase chain reaction (RT-PCR), and the results were compared to those from a panel of 192 healthy, unrelated volunteer control participants (refraction patients and volunteers) free of signs of anterior uveitis. Other outcomes were assessed comparing HLA-B27 positive vs. negative patients. Results The histocompatibility antigen HLA-B27 was identified in 6 out of 64 (9.4%) AAU patients, compared with 1.0% in controls (Odds Ratio = 9.8, 95% CI (1.93, 50.01)). Sub-group analysis of the cases revealed that patients with HLA-B27 positivity had a higher incidence of ocular hypertension (Odds Ratio = 5.93, 95% CI (1.29, 27.2)). Conclusion The antigen HLA-B27 was represented ~10-fold more frequently in the patient group than in the control group. HLA-B27 allele distribution in both cases and controls is lower than in reports from Caucasian and Asian populations, but similar to South Africa.

Prevalence of HLA-B27, clinical characteristics and treatment outcomes in children with enthesitis-related arthritis

BackgroundEnthesitis-related arthritis (ERA) is a subtype of juvenile idiopathic arthritis with high disease burden. The objectives of this study were to explore the prevalence of HLA-B27, clinical characteristics, and treatment outcomes in children with ERA and compare the differences between HLA-B27 positive and negative patients.MethodsA retrospective cohort study at a pediatric rheumatology clinic in a tertiary referral hospital in Bangkok, Thailand, including ERA patients with at least 6 months of follow-up (July 2011-April 2022) was performed. Data were collected from medical records from diagnosis to recent follow-up, assessing disease activity and treatment outcomes, with an analysis comparing HLA-B27 positive and negative patients. Descriptive statistics were used for data analysis.ResultsThere were 59 ERA patients with mean age ± SD at diagnosis 11.2 ± 2.5 years, 53 males (89.8%), and positive HLA-B27 in 38 patients (64.4%). The HLA-B27 positive group had significantly higher levels of inflammatory markers at initial diagnosis (p = 0.001), lower baseline hemoglobin (p = 0.001) and hematocrit (p = 0.002), higher disease activity assessed by the Juvenile Spondyloarthritis Disease Activity score at 6 and 12 months of follow-up (p = 0.028 and 0.040, respectively), increased utilization of bridging systemic corticosteroids (60.5% vs. 14.3%, p = 0.001) and anti-TNF (39.5% vs. 9.5%, p = 0.018), and longer duration of methotrexate (median[IQR] 1.7[1.1–3.1] vs. 1.3[0.6–1.9] years, p = 0.040). The HLA-B27 negative group had more prevalent hip arthritis than the positive group at initial diagnosis (66.7% vs. 28.9%, p = 0.005) and during the course of the disease (71.4% vs. 36.8%, p = 0.011).ConclusionMost of the ERA patients tested positive for HLA-B27. Throughout the follow-up period, these patients demonstrated greater disease activity, greater use of corticosteroids and anti-TNF, and longer duration of methotrexate to control the disease.

Potential difficult-to-treat psoriatic arthritis real-world prevalence and contributing factors.

The challenge of achieving low disease activity or remission in psoriatic arthritis (PsA) is an unmet need for many patients. Persistent disease activity in PsA may require treatment adjustments due to its complex pathogenesis and varied tissue involvement, highlighting the need for dedicated definitions. This study evaluates patients' frequency and contributing factors with potential "difficult-to-treat PsA (D2TPsA)", similar to the EULAR definition of D2T rheumatoid arthritis. A retrospective study was conducted at two tertiary centres to define potential D2TPsA, defined as failure of ≥1 conventional synthetic disease-modifying anti-rheumatic drug (DMARD) and ≥2 biological or targeted synthetic DMARDs with different mechanisms of action. Of the 171 patients included in the study, 116 (67.8%) were women; the average age was 48.16 ±11.23 years. D2TPsA was detected in 33 patients (19.3%). This group exhibited a longer disease duration, higher disease burden (median number of tender and swollen joints, patient and physician global evaluation, morning stiffness, erythrocyte sedimentation rate and C-reactive protein, DAPSA), HLA-B27 positivity, and higher prevalence of peripheral involvement. Secukinumab usage and mean glucocorticosteroid dosage were significantly higher in the D2TPsA group. Comorbidities such as fibromyalgia (FM) and diabetes mellitus (DM) and the median number of comorbidities were significantly higher in D2TPsA. In multivariate analysis, FM, DM, and HLA-B27 positivity were independently associated with D2TPsA. This study underscores the impact of comorbidities on PsA disease activity and emphasises the need for further research to differentiate treatment challenges influenced by comorbidities from true treatment resistance.

Sex differences in patient-reported outcomes and the association with clinical factors in axial spondyloarthritis patients treated with tumour necrosis factor inhibitors.

To investigate sex differences in patient-reported outcome measures (PROMs) among axSpA patients initiating their first TNFi and identify factors contributing to these disparities over the follow-up. Data were included from 15 EuroSpA registries and consisted of axSpA patients initiating their first TNFi, with ≥2 measurements for each analysed PROM (BASDAI and BASFI, scale 0-100) taken at any time point. Linear mixed models were employed to analyse sex differences in PROMs over 24 months and to evaluate how baseline characteristics were related to the observed sex differences. We analysed 13 102 (38% women) in the BASDAI analyses and 10 623 (38% women) in the BASFI analyses. At follow-up, mean sex differences in BASDAI increased from 4.3 units at baseline (95% CI, 3.5-5.1)-8.0 (7.2-8.8) at 6 months, and in BASFI from 2.2 (1.4-3.1)-4.6 (3.6-5.5), with consistently worse scores in women. Baseline characteristics could not substantially account for the observed sex differences over time; however, the magnitude of the sex differences was reduced by HLA-B27 positivity, longer disease duration, and increased CRP levels, but increased by TNFi initiation in later years and peripheral arthritis. In axSpA patients initiating their first TNFi, baseline sex differences in BASDAI and BASFI increased two-fold after 6 months of treatment and persisted thereafter, with worse scores in women. Several baseline characteristics moderated the sex differences, though none could fully account for them. These findings improve our understanding of sex differences and underscore their importance in axSpA.

A short review on deciphering Vyadhikshamatva: insights from HLA-B27-ankylosing spondylitis relation.

Various aspects of the concept of Vyadhikshamatva have been thoroughly explored, highlighting its profound significance in resisting disease manifestation, particularly in the context of Ankylosing spondylitis. Investigated the relationship between HLA-B27 and Ankylosing spondylitis (AS) by examining current knowledge and hypotheses Furthermore, efforts were made to portray the influence of prakruti (constitution) and balam (strength) on disease manifestation and progression. Ayurvedic literature along with contemporary research works was analyzed for correlating various aspects like vyadhikshamatva,oja (The final essence of all body elements), and balam along with their influence on the defensive mechanism of the body. A thorough literature search was conducted to explore the strong association between HLA-B27 and AS by examining various hypotheses like the Arthritogenic peptide hypothesis, the Misfolding hypothesis, the Surface Homodimer hypothesis, and the β2 microglobulin hypothesis that attempts to explain the pathogenic role of HLA-B27 in AS. Alongside classical Ayurvedic texts, databases like PubMed and Scopus were searched using keywords such as Immunity, Ankylosing spondylitis, Vyadhikshamatva, HLA-B27, Balam, and Autoimmune disorder with the help of Boolean operators. The review highlighted the critical role of Vyadhikshamatva in disease prevention, particularly in influencing the manifestation of conditions like AS despite genetic predisposition (HLA-B27). Further, the understanding of the Ayurvedic concepts can clearly explain the conflict that has arisen in the determination of the positive HLAB27 gene in Ankylosing Spondylitis as a definite diagnosing criteria. This comprehensive understanding will uplift the need for personalized medicine in disease management. Further research must be needed to understand the interaction between genetic factors (HLAb27), individual constitution, and their vyadikshamatva.

Checkpoint inhibitor immunotherapy induced inflammatory arthritis secondary to Nivolumab and Ipilimumab: a pediatric first

BackgroundImmune checkpoint inhibitors (ICIs) have expanded the arsenal of cancer therapeutics over the last decade but are associated with a spectrum of immune-related adverse events (irAEs), including inflammatory arthritis. While these complications are increasingly recognized in the adult population, no cases of inflammatory arthritis irAEs have been reported in the pediatric literature.Case PresentationA 14-year-old female with metastatic epithelioid mesothelioma was referred to the pediatric rheumatology clinic after developing progressive inflammatory joint pain in her bilateral shoulders, hips, and small joints of hands following the second cycle of Nivolumab and Ipilimumab. Initial examinations showed bilateral shoulder joint line tenderness, positive FABERs test bilaterally, tenderness over bilateral greater trochanters, and bilateral second PIP effusions. Her serological profile was notable for positive HLA-B27, positive anti-CCP, negative Rheumatoid Factor, and negative ANA. PET-CT scan performed for disease response following immunotherapy showed symmetric increased metabolic activity primarily involving the supraspinatus, gluteus medius and minimus, and semimembranosus tendon insertions. Her presentation was consistent with a grade 1 irAE that worsened to a grade 2 irAE despite NSAID therapy, prompting a short course of oral prednisolone. She achieved clinical remission of her mesothelioma following six cycles of Nivolumab and Ipilimumab and her inflammatory arthritis was controlled on Celebrex monotherapy.ConclusionsTo our knowledge, this is the first pediatric case of ICI-induced inflammatory arthritis and enthesitis. This case highlights the importance of increasing awareness of diagnosis and management of irAEs in children.

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

BackgroundThere 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).MethodsThe 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.ResultsA 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.ConclusionsOur 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.

Coexistence of ankylosing spondylitis and Behçet's disease: Successful treatment with upadacitinib.

Ankylosing spondylitis (AS) and Behçet's disease(BD) are distinct inflammatory disorders, but their coexistence is a rare clinical entity. This case sheds light on managing this complex scenario with Janus kinase (JAK) inhibitors. A 42-year-old woman presented with a decade-long history of lower back pain, nocturnal spinal discomfort, recurrent eye issues, oral and genital ulcers, hearing loss, pus formation in the left eye, and abdominal pain. Multidisciplinary consultations and diagnostic tests confirmed AS (HLA-B27 positivity and sacroiliitis) and BD (HLA-B51). Elevated acute-phase markers were observed. This case fulfills diagnostic criteria for both AS and BD, emphasizing their coexistence. Notably, treatment with upadacitinib exhibited promising efficacy, underscoring its potential as a therapeutic option in patients with contraindications for conventional treatments. Our findings illuminate the intricate management of patients presenting with these two diverse systemic conditions and advocate for further exploration of JAK inhibitors in similar cases.

The Frequency of HLA-B27 Antigen Positivity in Patients with Rheumatoid Arthritis and Anklylosing Spondylitis and The Relationship Between HLA-B27 Antigen and Other Autoantibodies

Aims: The aim of this study is to retrospectively demonstrate frequency of Human Leukocyte Antigen (HLA)-B27 antigen positivity and relationship between HLA-B27 positivity and other autoantibodies and between HLA-B27 positivity and treatment in patients diagnosed with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Material and methods: The study is a retrospective study. Patients who were diagnosed with RA and AS as a result of the examinations performed at Physical Medicine and Rehabilitation polyclinic between January 2017 and September 2022 were retrospectively screened, and patients whose HLA-B27 antigen was tested were included in study. Results: A total of 569 patients, 199 with RA and 370 with AS were included in study. While HLA-B27 was positive in 11% of patients with RA, it was 37.5% in patients with AS and there was a significant difference between the groups. When we analyzed the correlation of autoantibodies with HLA-B27, we found that HLA-B27 was not correlated with RF, ANTI-CCP or ANA. When we analyzed the relationship between HLA-B27 and the treatment method, there was no significant relationship between HLA-B27 and treatment method. Conclusion: While HLA-B27 was found to be 5% positive in the general population in the literature, we found 11% in 199 patients with RA. This study is important because it shows that HLA-B27 positivity is not very common in patients diagnosed with AS recently contrary to popular belief. More studies are needed to evaluate HLA-B27 frequency in RA and AS

Anti-tumor necrosis factor (aTNF) weaning strategy in juvenile idiopathic arthritis (JIA): does duration matter?

To compare outcomes of a short and long weaning strategy of anti-tumor necrosis factor (aTNF) in our prospective juvenile idiopathic arthritis (JIA) cohort. JIA patients on subcutaneous adalimumab with at least 6months of follow-up were recruited (May 2010-Jan 2022). Once clinical remission on medication (CRM) was achieved, adalimumab was weaned according to two protocols-short (every 4-weekly for 6months and stopped) and long (extending dosing interval by 2weeks for three cycles until 12-weekly intervals and thereafter stopped) protocols. Outcomes assessed were flare rates, time to flare, and predictors. Of 110 JIA patients, 77 (83% male, 78% Chinese; 82% enthesitis-related arthritis) underwent aTNF weaning with 53% on short and 47% on long weaning protocol. The total flare rate during and after stopping aTNF was not different between the two groups. The time to flare after stopping aTNF was not different (p = 0.639). Positive anti-nuclear antibody increased flare risk during weaning in long weaning group (OR 7.0, 95%CI: 1.2-40.8). Positive HLA-B27 (OR 6.5, 95%CI: 1.1-30.4) increased flare risks after stopping aTNF. Duration of weaning aTNF may not minimize flare rate or delay time to flare after stopping treatment in JIA patients. Recapture rates for inactive disease at 6months remained high for patients who flared after weaning or discontinuing medication.

Association of Endoplasmic Reticulum Aminopeptidase 1 Gene Polymorphism with Susceptibility and Severity of Axial Spondyloarthritis in Egyptian Population: A Single-center Case-Control Study.

Axial spondyloarthritis (axSpA) is a systemic, progressive, autoimmune disease. Complex interactions between environmental factors and host immune responses are the origin of axSpA. Together with human leukocyte antigen (HLA-B27), endoplasmic reticulum aminopeptidase 1 (ERAP1) gene is a potential non-HLA contributor to axSpA susceptibility. This study aimed to identify the role of ERAP1 single-nucleotide polymorphisms (SNPs) (rs30187, rs27044, and rs27037) in susceptibility to and severity of axSpA in Egyptian patients. In this case-control study, we enrolled 120 patients with axSpA and 120 healthy individuals as controls. Real-time polymerase chain reaction was used to identify ERAP1 polymorphisms. The present study revealed no significant association between ERAP1 SNPs (rs30187, rs27044, and rs27037) and axSpA susceptibility in Egyptian patients. A significant relationship was found only between the ERAP1 SNP rs27037 "GT" genotype and axSpA HLA-B27-positive cases, demonstrating a functional interaction between ERAP1 and HLA-B27-positive cases. Our analysis revealed a significant association between the ERAP1 SNP rs27037 "GT and TT" genotypes and Bath Ankylosing Spondylitis Disease Activity Index, in addition to an association between the ERAP1 SNP rs27037 "TT" genotype and active enthesitis. The ERAP1 SNP rs27044 "GG" genotype was significantly associated with active enthesitis, but not with clinical axial involvement. Finally, we did not observe a significant relationship between HLA-B27 positivity and disease severity in the studied cases. Three SNPs (rs30187, rs27044, and rs27037) in ERAP1 do not confer susceptibility to axSpA in Egyptian patients. This association existed exclusively between the ERAP1 SNP (rs27037) "GT" genotype and axSpA HLA-B27-positive cases.

Sex-specific differences in patients with psoriatic arthritis:a nationwide study from the Chinese Registry of Psoriatic Arthritis (CREPAR IV).

To elucidate the sex-specific differences in demographic features, clinical characteristics, and quality of life in Chinese patients with psoriatic arthritis (PsA). A total of 1,074 patients with PsA registered between December 2018 and June 2021 from the Chinese REgistry of Psoriatic ARthritis (CREPAR) cohort were selected. The baseline data on demographics, clinical characteristics, commonly used laboratory tests, comorbidities, and quality of life assessments were collected for this cross-sectional analysis. A total of 1,074 patients were included in this study, 585 (54.47%) of them were male and 489 (45.53%) were female. The age at PsA onset in male patients was earlier than that in female patients (38.10 ± 12.79 vs 40.37 ± 13.41, p = 0.005). For clinical characteristics, male patients presented with higher rates of axial involvement (43.89% vs 37.74%, p = 0.044) and nail involvement (66.15% vs 58.08%, p = 0.006), while female patients presented with higher rates of peripheral arthritis (89.57% vs 83.93%, p = 0.007). For laboratory tests, men presented with a higher percentage of HLA-B27 positivity than women (24.65% vs 16.70%, p = 0.002) and had higher levels of CRP (median 9.70 vs 5.65, p < 0.001). Regarding disease assessment indices, male patients scored higher in PASI and BASFI (median 5.00 vs 3.00, p = 0.007 and 1.80 vs 1.40, p = 0.012, respectively). No sex difference was found in rates of achieving remission. Factors associated with disease remission were also analyzed in both sexes. Demographic and clinical characteristics tend to vary between male and female patients with PsA. Male patients reported more functional limitations in daily life. Key Points • The demographic and clinical features vary greatly between male and female patients with PsA. • Male patients reported more functional burden in daily life as measured by BASFI.

Clinical and imaging findings in enteropathic spondyloarthritis with special emphasize in diagnostic delay: a cross-sectional study.

Enteropathic spondyloarthritides (eSpAs) are chronic inflammatory joint diseases associated with inflammatory bowel disease (IBD). Limited data are available on the prevalence since arthritis in IBD patients may be underestimated because medications may hide disease activity with a possible diagnostic delay. We aimed to evaluate diagnostic delay in eSpA and explore associated demographic, clinical, and radiographic characteristics. Single-centre cross-sectional study conducted on consecutive out-patients referred to the combined Gi-Rhe clinic (November 2018-October 2019). We analysed eSpA patients for diagnostic delay, disease activity, inflammatory markers, conventional radiography (CR) and magnetic resonance images (MRI) of sacroiliac joints/spine. A total of 190 eSpA patients [118 peripheral SpA, 72 axial (Ax) SpA including 44 non-radiographic (nr)-axSpA] were enrolled. axSpA patients had a higher prevalence of men sex, HLA-B27 positivity, uveitis and pancolitis compared with peripheral eSpA. Median diagnostic delay in eSpA was 48 months (IQR 6-77) with no difference between axial and peripheral patients. Radiographic-axial SpA (r-axSpA) patients displayed a higher diagnostic delay compared with nr-axSpA (median/IQR 36/17-129 versus 31/10-57 months, p = 0.03) and were older, with longer disease duration, low education status and high rate of employment than patients with nr-axSpA. r-axSpA patients with sclerosis, syndesmophytes and bridge at CR had higher diagnostic delay than those without lesions. Men showed higher prevalence of spine damage lesions than women as sclerosis, squaring, syndesmophytes and bridges. Longer disease duration was detected in patients with radiographic damage as bridge and sacroiliitis grade 3. On MRI, sacroiliac bone oedema was associated with reduced diagnostic delay, whereas bone erosions were associated with higher diagnostic delay compared with that in patients without these lesions. Patients with psoriasis displayed a higher diagnostic delay compared to those without skin involvement. Diagnostic delay was higher in r-axSpA compared with nr-axSpA despite the same treatment. Demographic, clinical features and radiological lesions were associated with diagnostic delay.

Thoracic Vertebral Fracture in a Female Case of Ankylosing Spondylitis Complicated with Turner Syndrome and Insufficient Response to Adalimumab

Background: Ankylosing spondylitis (AS) is a chronic disease characterized by inflammatory back pain, with osteoporosis prevalence ranging from 18.7% to 62% 1. Vertebral fractures are four times more likely to occur 2. Turner syndrome (TS) is the most common sex chromosome abnormality in females, with a 1.4- to 2.2-fold increased likelihood of osteoporosis-related fractures 3. Seven cases of AS combined with TS with HLA-B27 positivity have been reported4. Methods: We report a case of a female patient with AS and TS who exhibited an inadequate response to adalimumab (ADA) and suffered a thoracic vertebral fracture. Results: A 41-year-old woman with HLA-B27 negative was diagnosed with AS in 2012 because of low back pain, and began ADA treatment in 2018. The patient had a past history of TS (45X/47XXX) with ultrasound revealing smaller than normal ovaries and uterus. Body weight was 54kg and height was 145cm (BMI25.68). She had primary amenorrhea, a wrist fracture at a young age, and a thoracic spine fracture in 2018. Bone mineral density (BMD) values for orthotopic lumbar vertebrae L1-L4 were 0.74 g/cm2, with Z-score of -2.7, and 0.564 g/cm2 at the left femoral neck with Z-score of -2.4. The FRAX tool predicted a 10-year fracture risk of 2.4% for the occurrence of major osteoporotic fracture (MOF), and a fracture risk of 0.9% for hip fracture. She initiated hormone replacement therapy (HRT). In November 2022, she discontinued ADA due to COVID-19 infection. Laboratory tests identified slightly elevated inflammatory markers (Fig. 1), low trough drug level of 0.31ug/ml and positive anti-drug antibody. In February 2023, she slipped in a snowdrift and experienced increased back pain. Spinal MRI revealed osteoporosis with a T7 compression fracture and a new T9 fracture (Figure 2 A,B). Sacroiliac (SI) joints MRI showed significant improvement of inflammation (Fig. 2 C,D). Spine surgery consultation suspected fracture attributed to obvious kyphosis deformity and stress concentration during falls, resulting in buckling compression. Repeated test determined a BMD value of 0.920 g/cm2 for orthotopic L3-L4 with a Z-score of -1.4, and a BMD value of 0.775 g/cm2 for the left total hip with a Z-score of -1.2, the 10-year probability of MOF was 3.2%, and that of hip fracture was 0.5%. She was diagnosed with severe osteoporosis due to recurrent fracture despite of BMD improvement and anti-osteoporosis medications were postponed. Conclusion: This case further proved the dominant role of disease co-morbidity and insufficient treatment in the unfavorable outcome regardless of genetic predisposition.

Regional differences in clinical phenotype of axial spondyloarthritis: results from the International Map of Axial Spondyloarthritis (IMAS).

To explore differences in axial spondyloarthritis (axSpA) clinical phenotype around the world in a large sample of patients included in the International Map of Axial Spondyloarthritis (IMAS). IMAS was a cross-sectional online survey (2017-2022) of 5557 unselected axSpA patients from 27 countries. We analysed across five geographic regions the age at symptom onset, diagnostic delay, gender, HLA-B27, family history, extra-musculoskeletal manifestations, presence of comorbidities, disease activity (BASDAI), level of spinal stiffness and treatments. Of 5557 IMAS participants, 3493 were from Europe, 770 from North America, 600 from Asia, 548 from Latin America and 146 from South Africa. Age at symptom onset ranged between 25 and 30 years and was higher in Latin America. Diagnostic delay was longest in South Africa and lowest in Asia. The lowest HLA-B27 positivity was observed in Latin America and the highest in Asia. Extra-musculoskeletal manifestations were the lowest in Europe. Mean disease activity (BASDAI) was 5.4, with highest values in South Africa and lowest in Asia. Most of the patients had used NSAIDs for their condition and less than half had ever taken conventional synthetic DMARDS; both were more frequent in Latin America and South Africa. Almost half of the patients had ever taken biologic DMARDs, more frequent use being in the Americas. There is great heterogeneity of axSpA clinical phenotype presentation around the world. AxSpA manifests differently in different regions, so further understanding of these differences of phenotypes is needed to achieve early diagnosis and initiation of optimal disease treatment in axSpA in the different regions.

Clinical and imaging features of infective sacroiliitis in children

Objective: To summarize the clinical, radiological characteristics, and prognosis of infectious sacroiliitis in children. Methods: A case-control study was conducted, including 12 cases of infectious sacroiliitis diagnosed in the Rheumatology and Immunology Department of the Children's Hospital affiliated with the Capital Institute of Pediatrics from June 2018 to June 2023. These cases comprised the case group. Concurrently, 28 cases of pediatric idiopathic arthritis involving the sacroiliac joint in the same department served as the control group. Basic patient information, clinical features, laboratory parameters, and clinical treatment outcomes for both groups were collected and analyzed. Independent sample t-tests and chi-squared tests were used for inter-group comparisons. Results: Among the 12 cases in the case group, there were 5 males and 7 females, with a disease duration of 0.8 (0.5, 1.2) months. Nine patients presented with fever, and 1 patient had limping gait. Human leukocyte antigen (HLA)-B27 positivity was observed in 1 case, and there was no family history of ankylosing spondylitis. In the control group of 28 cases, there were 19 males and 9 females, with a disease duration of 7.0 (3.0, 17.0) months. One patient (4%) had fever, and 14 cases (50%) exhibited limping gait. HLA-B27 positivity was found in 18 cases (64%), and 18 cases (64%) had a family history of ankylosing spondylitis. The case group had higher white blood cell count (WBC), neutrophil ratio, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, as well as a higher proportion of unilateral involvement on magnetic resonance imaging and bone destruction on CT compared to the control group ((11.1±6.2)×109 vs. (7.3±2.3)×109/L, 0.64±0.10 vs. 0.55±0.12, 72 (34, 86) vs. 18 (5, 41) mm/1 h, 24.6 (10.1, 67.3) mg/L vs. 3.6 (0.8, 15.0) mg/L, 11/12 vs. 36% (10/28), 9/12 vs. 11% (3/28), t=2.90, 3.07, Z=-2.94, -3.28, χ2=10.55, 16.53, all P<0.05). Conclusions: Pediatric infectious sacroiliitis often presents as unilateral involvement with a short disease history. Elevated WBC, CRP, and ESR, as well as a high rate of bone destruction, are also common characteristics.

HLA-B27 did not protect against COVID-19 in patients with axial spondyloarthritis – data from the ReumaCov-Brasil Registry

BackgroundSome studies have suggested the HLA-B27 gene may protect against some infections, as well as it could play a benefit role on the viral clearance, including hepatitis C and HIV. However, there is lack of SARS-CoV-2 pandemic data in spondyloarthritis (SpA) patients.AimTo evaluate the impact of HLA-B27 gene positivity on the susceptibility and severity of COVID-19 and disease activity in axial SpA patients.MethodsThe ReumaCoV-Brasil is a multicenter, observational, prospective cohort designed to monitor immune-mediated rheumatic diseases patients during SARS-CoV-2 pandemic in Brazil. Axial SpA patients, according to the ASAS classification criteria (2009), and only those with known HLA-B27 status, were included in this ReumaCov-Brasil’s subanalysis. After pairing them to sex and age, they were divided in two groups: with (cases) and without (control group) COVID-19 diagnosis. Other immunodeficiency diseases, past organ or bone marrow transplantation, neoplasms and current chemotherapy were excluded. Demographic data, managing of COVID-19 (diagnosis, treatment, and outcomes, including hospitalization, mechanical ventilation, and death), comorbidities, clinical details (disease activity and concomitant medication) were collected using the Research Electronic Data Capture (REDCap) database. Data are presented as descriptive analysis and multiple regression models, using SPSS program, version 20. P level was set as 5%.ResultsFrom May 24th, 2020 to Jan 24th, 2021, a total of 153 axial SpA patients were included, of whom 85 (55.5%) with COVID-19 and 68 (44.4%) without COVID-19. Most of them were men (N = 92; 60.1%) with mean age of 44.0 ± 11.1 years and long-term disease (11.7 ± 9.9 years). Regarding the HLA-B27 status, 112 (73.2%) patients tested positive. There were no significant statistical differences concerning social distancing, smoking, BMI (body mass index), waist circumference and comorbidities. Regarding biological DMARDs, 110 (71.8%) were on TNF inhibitors and 14 (9.15%) on IL-17 antagonists. Comparing those patients with and without COVID-19, the HLA-B27 positivity was not different between groups (n = 64, 75.3% vs. n = 48, 48%, respectively; p = 0.514). In addition, disease activity was similar before and after the infection. Interestingly, no new episodes of arthritis, enthesitis or extra-musculoskeletal manifestations were reported after the COVID-19. The mean time from the first symptoms to hospitalization was 7.1 ± 3.4 days, and although the number of hospitalization days was numerically higher in the B27 positive group, no statistically significant difference was observed (5.7 ± 4.11 for B27 negative patients and 13.5 ± 14.8 for B27 positive patients; p = 0.594). Only one HLA-B27 negative patient died. No significant difference was found regarding concomitant medications, including conventional or biologic DMARDs between the groups.ConclusionsNo significant difference of COVID-19 frequency rate was observed in patients with axial SpA regarding the HLA-B27 positivity, suggesting a lack of protective effect with SARS-CoV-2 infection. In addition, the disease activity was similar before and after the infection.Trial registrationThis study was approved by the Brazilian Committee of Ethics in Human Research (CONEP), CAAE 30186820.2.1001.8807, and was registered at the Brazilian Registry of Clinical Trials – REBEC, RBR-33YTQC. All patients read and signed the informed consent form before inclusion.