The association between refractory plantar fasciitis and insertional Achilles tendinopathy and peripheral spondyloarthritis: a report of human leukocyte antigen B-27 investigation and treatment outcome.

PURPOSE: This study aimed to determine the presence of peripheral spondyloarthritis and investigate the clinical characteristics of patients with concurrent peripheral spondyloarthritis in those presenting with refractory plantar fasciitis and Achilles tendinopathy by conducting human leukocyte antigen B-27 (HLA-B27) testing. METHODS: This retrospective study aimed to investigate patients who complained of persistent pain and significant limitations in daily activities due to their respective foot pain, despite receiving conservative treatment for over one year under the diagnosis of plantar fasciitis or insertional Achilles tendinopathy. The study included 63 patients who underwent HLA-B27 testing. The patients were classified into two groups based on the presence or absence of HLA-B27 positivity. The Mann-Whitney U test assessed significant relationships between continuous variables, and the chi-square test was used to compare categorical variables. RESULTS: Among the 63 included patients, HLA-B27 positivity was confirmed in 11 patients (17.5%), which was significantly associated with a lower average age (22.8 years versus 31.7 years, P = 0.01) and a substantially lower proportion of females compared to HLA-B27-negative patients (9.1% vs. 25.0%, P = 0.001). Ten of the 11 patients initiated treatment with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) combined with oral steroids as the first-line medication after being diagnosed as HLA-B27 positive. Six patients experienced pain relief with the first-line medication (60%). Four patients who did not achieve pain control with the first-line medication received tumour necrosis factor-alpha inhibitors as the second-line medication. Two patients experienced pain relief, while two experienced reduced but persistent pain. CONCLUSIONS: Among the patients with "refractory" plantar fasciitis and insertional Achilles tendinopathy, 17.5% were diagnosed with peripheral spondyloarthritis. Patients diagnosed with peripheral spondyloarthritis had a higher proportion of men and relatively younger mean age compared to those without the diagnosis. Approximately 70% of these patients achieved symptom improvement in foot and ankle joints by taking conventional synthetic DMARDs, TNF-α inhibitors, or both appropriate for spondyloarthritis.

Comparative Analysis of a Developed Probe-Based Real-Time PCR and PCR-SSP for HLA-B*27 Detection among Thai Blood Donors.

BACKGROUND: The human leukocyte antigen (HLA) class I gene, the B locus, allele 27, HLA-B*27 is one of the most fascinating risk factors that is strongly associated with developing spondyloarthropathies (SpA). HLA-B27 testing has been routinely available in the diagnosis of those diseases. This study aimed to develop a fluorogenic real-time PCR and to compare it with PCR-SSP to detect the HLA-B*27 allele among Thai blood donors. METHODS: A total of 391 DNA samples were obtained from Thai blood donors at Thammasat University Hospital and tested for HLA-B*27 allele detection. A new real-time PCR was developed and validated to identify this allele and subsequently compared with those results tested with PCR-SSP. The sensitivity of detection was performed using known HLA-B*27-positive and -negative samples with concentrations ranging from 0.001 to 100 ng/µL. Additionally, HLA-B27 subtyping was performed by DNA sequencing containing second and third exons of this gene among all the HLA-B*27-positive donors. RESULTS: The validity of real-time PCR using known DNA controls and the results obtained by PCR-SSP techniques were in 100% concordance. The method was sensitive even at low DNA concentrations (1 ng/µL). Of 391 donors, 24 (6.14%; 95% CI, 3.97 - 9.00) were found to have the HLA-B*27 allele, while the remaining 367 (93.86%; 95% CI, 91.00 - 96.03) did not have this allele. Donors presented HLA-B*27-positive, HLA-B*27:06, the most common allele, followed by HLA-B*27:04, -B*27:05, and -B*27:07. CONCLUSIONS: HLA-B*27 using fluorogenic real-time qualitative PCR was found to be superior compared with that of PCR-SSP. The method is rapid, accurate, reliable, and sensitive for detection. In addition, this method provides convenience in the early treatment of SpA patients and relieves their suffering.

STAT3 and SPI1, may lead to the immune system dysregulation and heterotopic ossification in ankylosing spondylitis.

OBJECTIVE: This study was aimed to identify the biomarkers for diagnosis and reveal the immune microenvironment changes in ankylosing spondylitis (AS). METHODS: GSE73754 was downloaded for the co-expression network construction and immune cell analyses. Flow cytometric analysis was performed to validate the results of bioinformatics analysis. Gene set enrichment analysis (GSEA) was performed to investigate the potential biological characteristic between different phenotypes. Pearson correlation analysis between the hub genes and the xCell score of immune cell types was performed. RESULTS: Signal transducer and activator of transcription 3 (STAT3) and Spi-1 proto-oncogene (SPI1) was identified as the hub genes in the datasets GSE73754. And the t-test showed that the expression level of STAT3 and SPI1 in the GSE73754 was significantly higher in AS and human leukocyte antigen (HLA)-B27(+) groups. Flow cytometric analysis showed that natural killer T cells (NKT) cells were upregulated, while Th1 cells were down-regulated in AS, which was consistent with the results obtained from bioinformatics analysis. STAT3 and SPI1 was correlated with the NKT cells and Th1 cells. CONCLUSION: STAT3 and SPI1 may be a key cytokine receptor in disease progression in AS.

Quantification of bone marrow edema by MRI of the sacroiliac joints in patients diagnosed with axial spondyloarthritis: results from the ESPeranza cohort.

OBJECTIVE: To evaluate whether the quantification of bone marrow edema (BMO) of the sacroiliac (SI) joints by magnetic resonance imaging (MRI) improves capacity for axial spondyloarthritis (axSpA) classification in comparison with the assessment of sacroiliitis by Assessment of SpondyloArthritis international Society (ASAS) classification criteria. METHOD: This prospective study from the ESPeranza cohort involved 66 subjects with an available MRI of the SI joints at baseline. This subgroup includes patients with axSpA (n = 28), peripheral spondyloarthritis (n = 10), and other diagnoses that were not spondyloarthritis (n = 28). Measures of diagnostic usefulness [area under the curve (AUC), sensitivity, specificity, Youden's J statistic, positive and negative likelihood ratios (LR+ and LR-)] were calculated for MRI of the SI joints according to ASAS criteria and for MRI quantified by means of SCAISS (Spanish tool for semi-automatic quantification of sacroiliac inflammation by MRI in spondyloarthritis). This analysis was stratified in patients who were human leucocyte antigen (HLA)-B27 positive and negative. RESULTS: The AUC value with BMO quantification was 0.919 [95% confidence interval (CI) 0.799-1] for HLA-B27-positive patients and 0.884 (95% CI 0.764-1) for HLA-B27-negative patients. A SCAISS cut-off point of 80 units obtained a specificity of 94.4% and LR+ 7.5, while assessment by ASAS criteria showed a specificity value of 90% and LR+ 6.4. CONCLUSION: For patients with suspected axSpA, quantification of BMO improves the predictive capacity of MRI of the SI joints, for both HLA-B27-positive and HLA-B27-negative patients. Axial spondyloarthritis (axSpA) has a dramatic impact on physical function and quality of life (1). Despite its significant impact, patients with axSpA are normally diagnosed several years after presenting symptoms (2). In this respect, magnetic resonance imaging (MRI) of the sacroiliac (SI) joints has gained significance over the past decade, particularly in the early stages of the disease. Nowadays, imaging tests and human leucocyte antigen (HLA)-B27 testing are among the most important diagnostic procedures for patients with suspected axSpA.

A proposed HLA-B*27 screening method for ankylosing spondylitis detection based on tag-single nucleotide polymorphisms: a preliminary study.

BACKGROUND: Ankylosing spondylitis (AS) is a type of inflammatory arthritis that affects primarily the spine. There is a strong association of the HLA-B*27 allele with AS pathogenesis, but recent studies have demonstrated the participation of ERAP1 gene in the genetic susceptibility. The aim of this study was to determine whether HLA-B tag-single nucleotide polymorphisms (SNPs) and ERAP1-related genetic variations associated with AS have equal or similarly performance in patients´ screening compared to HLA-B*27 standard genotyping in Mexican population. METHODS AND RESULTS: Genomic DNA from patients with AS and population-based controls from Mexico City was analyzed for five single nucleotide polymorphisms (SNPs): rs4349859, rs13202464, rs116488202, tagging HLA-B*27; and rs30187 and rs27044 in ERAP1 gene. TaqMan genotype assay method was used for SNPs genotyping. We found a significant association between AS and the heterozygote genotypes and minor alleles of the HLA-B*27 tag-SNPs, as well as for their haplotypes. With respect to ERAP1 polymorphisms, no significant associations were observed (p > 0.05). The sensitivity and specificity analysis showed values of 0.96 and 1.00 for the rs4349859 SNP, and 0.96 and 0.94 for the rs116488202 SNP, respectively, in detecting HLA-B*27 compared to the B27 test as the gold standard. CONCLUSIONS: HLA-B*27 tag-SNPs are associated with AS susceptibility; furthermore, the rs4349859 SNP by its own have an outstanding performance in detecting HLA-B*27 and therefore can be proposed as screening marker in the identification of HLA-B*27 in our population.

Frequency of juvenile idiopathic arthritis and associated uveitis in pediatric rheumatology clinics in Turkey: A retrospective study, JUPITER.

BACKGROUND: Juvenile idiopathic arthritis (JIA), is the most common pediatric rheumatologic disorder with unknown etiology. Currently, no population-based data are available regarding the distribution of categories and frequency of uveitis in patients with JIA in Turkey. The purpose of this study was to evaluate the frequency of JIA-associated uveitis (JIAU) and distribution of JIA categories in a Turkish JIA cohort. METHODS: This was a retrospective study of 500 randomized patients in four pediatric rheumatology clinics in Turkey. RESULTS: Oligoarticular JIA (oJIA) was the most common JIA disease category in this study cohort (38.8%). The frequencies of the other categories were as follows: enthesitis-related arthritis (ERA), 23.2%; rheumatoid factor (RF)-negative polyarthritis, 15.6%; systemic arthritis, 12.2%; juvenile psoriatic arthritis, 5.2%; undifferentiated arthritis, 2.8%; and RF-positive polyarthritis, 2.2%. JIA-associated uveitis was observed in 6.8% of patients at a mean (Standard Deviation, SD) age of 9.1 (3.8) years over a mean JIA disease duration of 4 (1.9) years. Uveitis developed after joint disease, with a mean (SD) duration of 1.8 (1.9) years. Patients with oJIA had the highest rate of uveitis (12.9%) followed by patients with ERA (5.2%) and polyarticular RF-negative disease (3.8%). Compared with persistent oJIA, the extended oJIA category had a > 3-fold higher risk of uveitis (11.3% vs 27.7%; odds ratio, 3.38 [95% Confidence Interval, 1.09-10.4]). The most frequently administered drug after development of uveitis was tumor necrosis factor-alpha inhibitors (38.2%). Five patients (14.7%) had uveitis-related complications that required surgical intervention. CONCLUSIONS: Turkish pediatric patients with JIA experience a lower frequency of oJIA and higher frequency of ERA than their white European counterparts; the occurrence of uveitis is also somewhat lower than expected. Geographic and ethnic factors may affect these differences and need further investigation.

Clinical remission and subsequent relapse in patients with juvenile idiopathic arthritis: predictive factors according to therapeutic approach.

BACKGROUND: Juvenile idiopathic arthritis constitutes a significant cause of disability and quality of life impairment in pediatric and adult patients. The aim of this study was to ascertain clinical remission (CR) and subsequent relapse in juvenile idiopathic arthritis (JIA) patients, according to therapeutic approach and JIA subtype. Evidence in literature regarding its predictors is scarce. METHODS: We conducted an observational, ambispective study. Patients diagnosed of JIA, treated with synthetic and/or biologic disease modifying antirheumatic drugs (DMARD) were included and followed-up to December 31st, 2015. Primary outcome was clinical remission defined by Wallace criteria, both on and off medication. In order to ascertain CR according to therapeutic approach, DMARD treatments were divided in four groups: 1) synthetic DMARD (sDMARD) alone, 2) sDMARD combined with another sDMARD, 3) sDMARD combined with biologic DMARD (bDMARD), and 4) bDMARD alone. RESULTS: A total of 206 patients who received DMARD treatment were included. At the time the follow-up was completed, 70% of the patients in the cohort had attained CR at least once (144 out of 206), and 29% were in clinical remission off medication (59 out of 206). According to treatment group, CR was more frequently observed in patients treated with synthetic DMARD alone (53%). Within this group, CR was associated with female sex, oligoarticular persistent subtypes, ANA positivity, Methotrexate treatment and absence of HLA B27, comorbidities and DMARD toxicity. 124 DMARD treatments (62%) were withdrawn, 64% of which relapsed. Lower relapse rates were observed in those patients with persistent oligoarticular JIA (93%) when DMARD dose was tapered before withdrawal (77%). CONCLUSIONS: More than two thirds of JIA patients attained CR along the 9 years of follow-up, and nearly one third achieved CR off medication. Females with early JIA onset, lower active joint count and ANA positivity were the ones achieving and sustaining remission more frequently, especially when receiving synthetic DMARD alone and in the absence of HLA B27, comorbidities or previous DMARD toxicity.

HLA-B27 is associated with reduced disease activity in axial spondyloarthritis.

HLA-B27 is associated with increased susceptibility and disease activity of ankylosing spondylitis, but the effect of HLA-B27 on the activity of the broader category now called axial spondyloarthritis (AxSpA) is apparently the opposite. A modified Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was used to assess disease activity among 3435 patients with spondyloarthritis (SpA) who participated in a survey designed to assess the effect of their disease and its treatment on the susceptibility and severity of Covid-19. Chi square testing was used to compare BASDAI scores between HLA-B27 positive and negative subjects. 2836 survey respondents were HLA B27 positive. The average BASDAI for the HLA-B27 negative cohort was 4.92 compared to 4.34 for the HLA-B27 positive subjects. Based on linear regression, a subject's sex could not fully account for the differing BASDAI score in HLA-B27 negative subjects compared to those who are HLA-B27 positive. The difference between B27 positive and negative subjects was skewed by those with a BASDAI score of one or two. HLA-B27 positive subjects were more than twice as likely to have a BASDAI score of 1 compared to HLA B27 negative subjects and about 60% more likely to have a BASDAI score of 2 (p < 0.0001). HLA-B27 positive subjects have less active spondyloarthritis compared to HLA-B27 negative subjects as measured by a BASDAI score. Our data indicate that patients with mild back pain and a diagnosis of AxSpA are disproportionately HLA-B27 positive. The HLA-B27 test facilitates the diagnosis of axial spondyloarthritis such that patients from a community survey with mild back pain may be disproportionately diagnosed as having AxSpA if they are HLA-B27 positive. The test result likely introduces a cognitive bias into medical decision making and could explain our observations.

The Phenotype of Axial Spondyloarthritis: Is It Dependent on HLA-B27 Status?

OBJECTIVE: To describe the radiographic phenotype of axial spondyloarthritis (SpA) according to the presence of HLA-B27. METHODS: An international collaboration compared the radiographic phenotype of axial SpA according to HLA-B27 status. Patients with ankylosing spondylitis (AS) and axial psoriatic arthritis (PsA) were collected. Radiographs were read centrally, blinded to clinical details. The symmetry of the sacroiliac joints and lumbar syndesmophytes and the morphology of syndesmophytes (typical marginal versus atypical chunky), together with the modified Stoke Ankylosing Spondylitis Spine Score and the Psoriatic Arthritis Spondylitis Radiographic Index, were recorded. RESULTS: A total of 244 patients with PsA and 198 patients with AS were included. In PsA, 60 patients (25%) were HLA-B27 positive while in AS, 148 patients (75%) were HLA-B27 positive. Patients with HLA-B27 were younger and more often male and had a longer duration of disease. In multivariable logistic regression, HLA-B27 was significantly associated with syndesmophyte symmetry (odds ratio [OR] 3.02 [95% confidence interval (95% CI) 1.38, 6.61]) and marginal syndesmophytes (OR 1.97 [95% CI 1.16, 3.36]) but not with sacroiliac symmetry. Mean radiographic scores were higher for patients with HLA-B27. CONCLUSION: Patients with axial SpA who are positive for HLA-B27 have more severe radiographic damage, more marginal syndesmophytes, and more frequent syndesmophyte symmetry compared to patients who are negative for HLA-B27.

Recommendations by the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) on the treatment of patients with inflammatory bowel disease associated with spondyloarthritis. / Recomendaciones del Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) sobre el tratamiento de pacientes con enfermedad inflamatoria intestinal asociada a espondiloartritis.

Extraintestinal manifestations, in general, and in particular arthropathies, are a common problem in patients with inflammatory bowel disease. In fact, the relationship between those 2entities is close and there are increasingly more data which suggest that the bowel plays a significant role in the aetiopathogenesis of spondyloarthritis. The association of inflammatory bowel disease with any kind of spondyloarthritis represents a challenging clinical scenario. It is therefore necessary that both gastroenterologists and rheumatologists work together and establish a fluent communication that enables the patient to receive the most appropriate treatment for each specific situation. The aim of this review is to make some recommendations about the treatment of patients with inflammatory bowel disease and associated spondyloarthritis, in each different clinical scenario.

Does psoriatic axial spondyloarthritis phenotype correlate with imaging morphotype?

OBJECTIVES: To compare the magnetic resonance imaging (MRI) morphology of inflammatory and chronic lesions in the sacroiliac joints (SIJs) and spine between patients with non-psoriatic and psoriatic non-radiographic axial spondyloarthritis (axSpA and p-axSpA, respectively). METHODS: Patients from the EMBARK trial (NCT01258738) with axSpA (n=179) and p-axSpA (n=24) who had MRI data available were compared in terms of baseline demographics, clinical characteristics, and the frequency (n/N [%]) and distribution of inflammatory and structural SIJ and spinal lesions. RESULTS: Patients with p-axSpA were on average older (35.1 years vs. 31.7 years, p=0.047), had a higher occurrence of asymmetric sacroiliitis (54.2% vs. 29.6%, p=0.042), and a lower occurrence of human leukocyte antigen (HLA)-B27 positivity (41.7% vs. 73.7%, p=0.010) than patients with axSpA. There were no significant differences in the frequency of lesions in any of the SIJ or spinal quadrants between the two subgroups. CONCLUSIONS: These data suggest that differences between axSpA and p-axSpA extend beyond presence of psoriasis, and include age, SI symmetry, and HLAB27 status. These findings may help explain the morphotype-phenotype relationship across axSpA, similar to those described in older radiographic studies.

Effect of Gut Involvement in Patients with High Probability of Early Spondyloarthritis: Data from the DESIR Cohort.

OBJECTIVE: Inflammatory bowel disease (IBD) is a well-known extraarticular feature of spondyloarthritis (SpA). The aims of this study were to evaluate factors associated with IBD and incidence over 5 years of followup in the DESIR cohort. METHODS: DESIR is a prospective observational cohort of patients with recent-onset inflammatory back pain suggestive of axial SpA. All available variables in the database were compared between patients with and without IBD at baseline and 5 years, and occurrence over 5 years of followup, with uni- and then multivariable analysis. RESULTS: At baseline, of 708 patients, 35 had IBD (prevalence 4.94%, CI 95% 3.3-6.5). IBD was associated (multivariable) with history of uveitis, levels of Dickkopf-1, and tumor necrosis factor, but not with phenotypic presentation (peripheral arthritis, enthesitis, dactylitis, uveitis) or baseline serum levels of other cytokines. At 5 years, 480 patients were analyzed, 58 with IBD. IBD was associated (multivariable) with fulfillment of modified New York criteria, sick leave, Bath Ankylosing Spondylitis Disease Activity Index, and smoking. There was no association with magnetic resonance imaging scores, enthesitis, psoriasis, and bone mineral density. Twenty-three incident cases of IBD were recorded: estimated occurrence rate of 0.95/100 (95% CI 0.57-1.35) patient-years (PY). Incidence of IBD is associated (multivariable) with HLA-B27 (OR 0.36, 95% CI 0.22-0.59), fulfillment of modified New York criteria (OR 3.35, 95% CI 1.85-6.08), and familial history of IBD (OR 3.31, 95% CI 1.62-6.77). CONCLUSION: In early SpA, IBD occurs with an incidence of 1/100 PY, and is associated with poor outcome, familial history of IBD, absence of HLA-B27, and fulfillment of modified New York criteria.

Reasons for diagnostic delays of axial spondyloarthritis.

OBJECTIVE: Introduction: The probability of development of axial spondyloarthritis (axSpA) is estimated to be above 90% among patients with chronic back pain, presence of HLA B27 antigen and positive family history of ankylosing spondylitis (AS), psoriasis, reactive arthritis, inflammatory bowel disease or uveitis. The nonradiographic axSpA and ankylosing spondylitis diseases' activity has a comparable impact on the patients' quality of life and from the practical point of view the approach to treatment of each of them is the same. The aim: The attempt to identify the reasons of diagnostic delays of AS among patients hospitalized in the Rheumatology and Connective Tissue Diseases Department in Lublin and to suggest the ways of improving the accuracy of diagnostic track among other healthcare providers than rheumatologists. PATIENTS AND METHODS: Material and methods: We performed a retrospective analysis of the records of 82 patients' with the established diagnosis of AS, hospitalized in the Rheumatology and Connective Tissue Diseases Department in Lublin in 2000-2019, and of 45 years of age and older. RESULTS: Results: From among 82 patients (28 women and 54 men) the diagnosis of AS after 45 years of age was established in 25 patients (10 women and 15 men) - group t, and in the other 57 patients (group n) the diagnosis was established before 45 years of age. On average the age at the time of diagnosis in the whole group (t+n) was 40,7±10,2 (18-76) years, the age at the beginning of inflammatory back pain (age of axial symptoms) was 30,9±8,5 (13-51) years and the diagnostic delay (period between first axial symptoms and diagnosis establishment) was 9,75±9,5 (0-46) years. We did not find any statistically significant associations between sex and age at the moment of diagnosis, age of the beginning of axial symptoms and the time of diagnostic delay. There was no significant difference of incidence of enthesitis, uveitis, arthritis, prevalence of family history of spondyloarthritis and CRP level between group t and n. Antigen HLA B27 was more frequently present in group t. CONCLUSION: Conclusions: Instead of the recognition progress and worldwide popularization of knowledge about axSpA, the diagnostic delays in this field are still estimated to last many years, the patients are looking for other specialists' help, and they can be not knowledgeable of the inflammatory back pain criteria. Currently, HLA B27 antigen and C-reactive protein are the two most commonly used biomarkers for diagnostic and disease activity monitoring purposes of axSpA and magnetic resonance is the only "imaging biomarker". The presence of extra-axial symptoms does not improve the diagnostic sensitivity.

[Identification of patients with axial spondylarthritis in primary care (AWARE study)]. / Identifikation von Patienten mit axialer Spondyloarthritis in der Primärversorgung (AWARE-Studie).

BACKGROUND: Early detection of patients with axial spondylarthritis (axSpA) in primary care is difficult. The combination of various parameters indicative of inflammatory back pain (AWARE criteria) was found to be beneficial in an initial study. OBJECTIVE: Review of the criteria for the identification of young patients with axSpA and chronic back pain (≥3 months of back pain). MATERIAL AND METHODS: In adult patients with chronic back pain and age at onset of symptoms <45 years, orthopedic surgeons documented various possible axSpA characteristics before referral to the rheumatologist. RESULTS: Overall, the data from 1306 patients were recorded. Of these, ultimately 500 patients were also seen by rheumatologists, 199 patients (39.8%) were diagnosed with axSpA while 301 (60.2%) had non-specific back pain. A total of 87 patients had ankylosing spondylitis (44%) and 112 non-radiographic axSpA (56%). The ASAS classification criteria were fulfilled by 226 patients (45.2%). The mean age of axSpA patients was 38 years, 56% were male with a mean duration of back pain of 98 months. The AWARE criteria had a sensitivity and specificity of 69.3% and 40.3% (n = 343), respectively, when ≥4/5 criteria were chosen. Positive imaging for sacroiliitis using magnetic resonance imaging (MRI) or X­ray was present in 77% of patients and positive HLA-B27 was identified in 59% of axSpA patients. The combination of positive imaging and HLA-B27 had the highest likelihood ratio for diagnosis of axSpA. CONCLUSION: Although the study design used here led to a preselection and thus to a bias in the statistical evaluation, the study confirmed the benefit of the AWARE criteria for the early detection of patients with axSpA. In further studies, the 2­stage approach with initially 3 clinical questions and then an optional HLA-B27 test is currently being investigated further.

Is a positive family history of spondyloarthritis relevant for diagnosing axial spondyloarthritis once HLA-B27 status is known?

OBJECTIVES: A positive family history (PFH) of spondyloarthritis, in particular a PFH of AS or acute anterior uveitis, is associated with HLA-B27 carriership in chronic back pain patients. As it is unknown, the study aimed to investigate if a PFH contributes to diagnosing axial spondyloarthritis (axSpA) once HLA-B27 status is known. METHODS: In axSpA-suspected patients from the Assessment of SpondyloArthritis international Society (ASAS), DEvenir des Spondyloarthropathies Indifférenciéés Récentes (DESIR) and SPondyloArthritis Caught Early (SPACE) cohorts, logistic regression analyses were performed with HLA-B27 status and PFH according to the ASAS definition (ASAS-PFH) as determinants and clinical axSpA diagnosis as outcome at baseline. Analyses were repeated with a PFH of AS or acute anterior uveitis. RESULTS: In total, 1818 patients suspected of axSpA were analysed (ASAS n = 594, DESIR n = 647, and SPACE n = 577). In patients from the ASAS, DESIR and SPACE cohorts, respectively 23%, 39% and 38% had an ASAS-PFH, 52%, 58% and 43% were HLA-B27 positive, and 62%, 47% and 54% were diagnosed with axSpA. HLA-B27 was independently associated with an axSpA diagnosis in each cohort but an ASAS-PFH was not [ASAS cohort: HLA-B27 odds ratio (OR): 6.9 (95% CI: 4.7, 10.2), ASAS-PFH OR: 0.9 (95% CI: 0.6, 1.4); DESIR: HLA-B27 OR: 2.1 (95% CI: 1.5, 2.9), ASAS-PFH OR: 1.0 (95% CI 0.7, 1.3); SPACE: HLA-B27 OR: 10.4 (95% CI: 6.9, 15.7), ASAS-PFH OR: 1.0 (95% CI: 0.7, 1.5)]. Similar negative results were found for PFH of AS and acute anterior uveitis. CONCLUSION: In three independent cohorts with different ethnical backgrounds, ASAS, DESIR and SPACE, a PFH was not associated independently of HLA-B27 with a diagnosis of axSpA. This indicates that in the vast majority of patients presenting with back pain, a PFH does not contribute to the likelihood of an axSpA diagnosis if HLA-B27 status is known.

Electrocardiographic changes in spondyloarthritis and use of anti-TNF-α drugs: a retrospective study with 100 patients.

OBJECTIVE: To investigate the prevalence of electrocardiographic changes in patients with spondyloarthritis and to correlate these changes with use of anti-tumor necrosis factor-alpha (TNF-α) drugs and HLA-B27 positivity. METHODS: Retrospective study including 100 patients diagnosed with spondyloarthritis according to Assessment of SpondyloArthritis International Society (ASAS) criteria and 50 controls. Epidemiological and clinical features, results of inflammatory activity tests, HLA-B27 positivity, and medication use data were extracted from medical records. Disease activity was assessed using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). All participants were submitted to electrocardiogram performed using a 12-lead device; rhythm, heart rate, conduction disorders and QT interval corrected using the Bazett formula were analyzed. RESULTS: Of 100 patients with spondyloarthritis, 51 were on anti-TNF-α drugs and 49 were not. HLA-B27 was detected in 53.1% of patients in the sample. Patients with spondyloarthritis had lower heart rate (p=0.06), longer QT interval (p<0.0001) and higher prevalence of right bundle branch block (p=0.014) compared to controls. Duration of disease was weakly correlated with heart rate (Rho=0.26; 95%CI: 0.06-0.44; p=0.008). The prevalence of right bundle branch block was positively correlated with HLA-B27 positivity. Use of Anti-TNF-α drugs did not interfere with electrocardiographic parameters. CONCLUSION: Patients with spondyloarthritis had lower heart rate, longer QT interval and a higher prevalence of right bundle branch block compared to controls. HLA-B27 positivity was associated with the prevalence of right bundle branch block. Anti-TNF-α drugs had no impact on electrocardiographic findings.

Withdrawal of infliximab therapy in ankylosing spondylitis in persistent clinical remission, results from the REMINEA study.

BACKGROUND: Recent data suggest that anti-TNF doses can be reduced in ankylosing spondylitis (AS) patients. Some authors even propose withdrawing treatment in patients in clinical remission; however, at present there is no evidence to support this. OBJECTIVE: To assess how long AS patients with persistent clinical remission remained free of flares after anti-TNF withdrawal and to evaluate the effects of treatment reintroduction. We also analyze the characteristics of patients who did not present clinical relapse. METHODS: Multicenter, prospective, observational study of a cohort of patients with active AS who had received infliximab as a first anti-TNF treatment and who presented persistent remission (more than 6 months). We recorded at baseline and every 6-8 weeks over the 12-month period the age, gender, disease duration, peripheral arthritis or enthesitis, HLA-B27 status, BASDAI, CRP, ESR, BASFI, and three visual analogue scales, spine global pain, spinal night time pain, and patient's global assessment. RESULTS: Thirty-six out of 107 patients (34%) presented persistent remission and were included in our study. After treatment withdrawal, 21 of these 36 patients (58%) presented clinical relapse during follow-up. Infliximab therapy was reintroduced and only 52% achieved clinical remission, as they had before the discontinuation of infliximab; in an additional 10%, reintroduction of infliximab was ineffective, obliging us to change the anti-TNF therapy. No clinical or biological factors were associated with the occurrence of relapse during the follow-up. CONCLUSIONS: Two thirds of patients in clinical remission presented clinical relapse shortly after infliximab withdrawal. Although the reintroduction of infliximab treatment was safe, half of the patients did not present the same clinical response that they had achieved prior to treatment withdrawal.

Added Value of Anti-CD74 Autoantibodies in Axial SpondyloArthritis in a Population With Low HLA-B27 Prevalence.

Axial spondyloarthritis (axSpA) is often diagnosed late due to the non-specific nature of its main symptom [chronic back pain (CBP)] and to the paucity of diagnostic markers, particularly in regions with low HLA-B27 prevalence, such as the Middle-East. We tested the performance of IgG4 and IgA anti-CD74 antibodies as an early diagnostic marker for axSpA, compared with the performance of HLA-B27, in Lebanon. Sera of axSpA patients diagnosed by the rheumatologist and also fulfilling the imaging arm of the ASAS criteria (patients) and of blood donors (BD) (controls) were analyzed for HLA-B27, IgG4 and IgA anti-CD74, blinded to clinical characteristics. Receiver Operating Characteristic curves were constructed to identify an optimal cut-off point for anti-CD74 antibodies. Diagnostic properties were calculated (sensitivity, specificity, positive, and positive predictive values (PPV, NPV), Likelihood ratios) for each marker. Forty-nine axSpA patients and 102 BD were included in the final analysis. IgA anti-CD74 correlated poorly with axSpA (Area Under the Curve (AUC) 0.657), whereas IgG4 anti-CD74 had a good discriminative value (AUC 0.837). Respectively, for HLA-B27, IgG4 anti-CD74, and the combination of both, we found a sensitivity of 33-92-33%, specificity of 96-79-98%, PPV 80-68-89%, NPV 75-95-75%, and LR+ 8.2-4.4-16.5. IgG4 anti-CD 74 were positive in 88% of HLA-B27 negative axSpA patients, and correlated with BASDAI. In this first study in a population with low HLA-B27 prevalence, IgG4 anti-CD74 antibodies combined with HLA-B27 showed higher diagnostic value than HLA-B27 alone for early axSpA. IgG4 anti-CD74 should be considered for further evaluation as an early axSpA diagnostic marker in future dedicated research, particularly in patients with CBP.

Evolving patterns of reactive arthritis.

OBJECTIVE: To characterize rheumatologists' perspectives on evolving trends of reactive arthritis (ReA). METHODS: After ethics approval, 548 members of the Canadian Rheumatology Association were surveyed with 37 questions covering their demographic information, subspecialty, level of experience, practice setting and opinions on prevalence, treatment, and causes of ReA. Results were analyzed with descriptive statistics. RESULTS: Ninety-seven responded to the survey (18% response rate); 66 fully completed it. Nearly half of respondents believed that the incidence of ReA is declining and causes of ReA may be changing. Physicians reported that most of the ReA cases in their practices were caused by an unknown organism, sexually transmitted, or gastrointestinal infection. Full triad ReA increased the chance of recurrence according to their impressions. Common investigations in ReA included inflammatory markers, HLA-B27, chlamydia and gonorrhea testing, stool cultures, synovial fluid analyses, SI joint imaging. ReA treatment included NSAIDs, intra-articular corticosteroid injections, and DMARDs. Two-thirds said they used TNF alpha inhibitors in chronic ReA occasionally or more frequently. CONCLUSION: ReA may be decreasing in frequency and severity in Canada. Changes could be due to less food borne illness, cleaner water, or more rapid treatment of sexually transmitted infections. The cause is often unknown in clinical practice.Key Points• Reactive arthritis (ReA) is likely decreasing in prevalence and severity.• Patients with classic trial of arthritis, urethritis, and conjunctivitis are more likely to have recurrent and/or chronic ReA.• The causal organisms are often not detected and seem to be changing over time.