Spondyloarthritis (SpA) is a group of diseases with overlapping skeletal and extra-articular features. Acute anterior uveitis (AAU) is the most common extra-articular manifestation of SpA. The relation between AAU and SpA is well defined in the current literature. Our study aims to analyze the frequency and factors associated with AAU in different forms of SpA in a large nationwide cohort of Turkish SpA patients.
Retrospective cohort study.
The data were obtained from the TReasure database, which compiles data from records of the web-based Rheumatoid Arthritis (RA) and SpA patients treated with biological disease-modifying anti-rheumatismal drugs from different regions of Turkey. The clinical characteristics of SpA and uveitis are recorded.
Data of the 4,297 SpA patients were included in the study. Overall, 475 of 4,297 patients (11.0%) had experienced 1 or more episodes of uveitis. SpA patients with older age ( P < .001), a smoking history ( P = .004), delayed diagnosis ( P = .001), longer disease duration ( P < .001), arthritis ( P < .001), positive HLA-B27 ( P < .001), a family history of SpA ( P < .001), and radiographic damage (presence of sacroiliitis, syndesmophytes, bamboo spine, hip involvement) ( P < .001 for all) more commonly had uveitis. On the other hand, uveitis was less prevalent in patients with psoriasis and psoriatic arthritis ( P < .001 for both).
Uveitis may be the key feature leading to SpA diagnosis. Patients with radiographic damage and long disease duration have an increased risk for uveitis in both male and female SpA patients. Patients with uveitis should be referred to a rheumatologist for a thorough evaluation of SpA.
S pondyloarthritis (SpA) is a group of diseases with overlapping clinical features and underlying pathogenic mechanisms. Ankylosing spondylitis (AS), nonradiographic axial spondyloarthritis, psoriatic arthritis, reactive arthritis, enteropathic arthritis, and undifferentiated spondyloarthritis are the disorders that are classified as SpA. SpA has the longest delay in the diagnosis of all inflammatory joint diseases.
The concept of SpA incorporates skeletal and extra-articular features such as inflammatory back pain, sacroiliitis, enthesitis, dactylitis, psoriasis, inflammatory bowel disease, HLA-B27 positivity, and uveitis. Acute anterior uveitis (AAU) is the most common extra-articular manifestation of SpA. Among other causes, SpA is a frequent cause of noninfectious AAU, and in a substantial number of SpA cases, AAU leads to the recognition of a previously undiagnosed SpA. Nearly 40% of AAU patients have undiagnosed SpA. Therefore, it is advisable to screen patients with AAU for symptoms and laboratory features of SpA. Also, uveitis, as an extra-articular feature of SpA, shapes the follow-up and treatment. Association of acute anterior uveitis and SpA is well defined in the current literature. Our study aims to analyze the frequency and factors associated with AAU in different forms of SpA in a large nationwide cohort of Turkish SpA patients.
Patient Characteristics of TReasure Database
The current study has a retrospective design, and the data were obtained from the TReasure database, in which RA and SpA patients treated with bDMARDs were registered. The TReasure database compiles data from the web-based patient records from different regions of Turkey. The entry of patient data began in December 2017 and patients treated with bDMARDs are recorded. At the time of analysis, there was a total of 2,767 patients with RA and 5,416 patients with SpA in the database. Recorded patient data at each contributing TReasure center is given in Table 1 . Ethics committee approval for the use of the TReasure database was obtained from Hacettepe University (KA-17/058) in May 2017 and from the Ministry of Health–Turkey (93189304-14.03.01) in October 2017. A written informed consent form was obtained from all participants.
|Co-morbid diseases||Diabetes mellitus, hypertension, hyperlipidemia, chronic obstructive lung disease, asthma, thyroid disease, coronary artery disease, valvular cardiac disease, cerebrovascular disease, thromboembolic events, hepatitis, chronic liver disease, malignancy|
|Laboratory findings||HLA-B27, acute phase reactants (ESR and C-RP)|
|Clinical manifestations a||Enthesitis, dactylitis, psoriasis, inflammatory bowel disease (Crohn disease and Ulcerative colitis), family history of SpA|
|X-ray||Pelvic||The grade of sacroiliitis|
|Lumbosacral||The presence of syndesmophytes, bamboo spine, and radiographic hip involvement and/or the need for joint replacement|
|Treatment||Biological DMARDs||adalimumab, infliximab, etanercept, certolizumab, golimumab, secukinumab|
|Synthetic DMARDs||sulphasalazine, methotrexate, leflunomide, hydroxychloroquine|
a Enthesitis was evaluated according to the Leeds enthesis index (LEI). Other clinical manifestations were stated as yes or no .
Electronic records of the SpA patients registered in the TReasure database are screened for uveitis. Patients without a physician-recorded data for uveitis are excluded. Data on uveitis are analyzed in the whole SpA group and the subgroups of SpA ( Figure 1 ).
Assessment of Uveitis
AAU diagnosed by an ophthalmologist was defined as a history of uveitis. The time of uveitis diagnosis, the number of uveitis attacks, and unilateral or bilateral involvement were recorded. Any degree of loss in the vision is recorded as permanent eye disease. The anatomic localization of uveitis was not available for every patient in the database.
The temporal relation of the onset of uveitis and the SpA symptoms as well as the SpA diagnosis was evaluated. The frequency of a uveitis diagnosis was compared for the following time frames: within the first 5 years after the SpA diagnosis, within 5-10 years after the diagnosis of SpA, and ≥10 years after the diagnosis of SpA.
The Predictive Analytics Software (PASW), version 18.0 (SPSS Inc, Chicago, Illinois, USA) was used for the analysis. The normality of data was tested using the visual (histogram and probability plots) and analytical (Kolmogorov-Smirnov/Shapiro-Wilk tests) methods. Descriptive statistics were expressed as numbers and percentages for categorical variables and as median, 25th percentile (Q1), and 75th percentile (Q3) for numerical variables. In the comparison of the patients with and without uveitis as well as the patients diagnosed with uveitis before or simultaneously with the SpA diagnosis and those diagnosed with uveitis after the SpA diagnosis, the χ 2 test was used for categorical variables and the Mann-Whitney U test was used for non-normally distributed numerical variables. In determination of the risk factors for uveitis, logistic regression analysis was performed using the backward likelihood ratio method and statistically significant independent variables were analyzed with the Enter method. A P value of less than 5% was interpreted as statistically significant. The odds ratio with 95% confidence interval was calculated by univariate analysis to compare the clinical and demographic characteristics between study groups.
Distribution and Clinical Characteristics of Spondyloarthritis Patients
As of May 2020, there were 5,416 registered SpA patients on the TReasure database. Patients with missing data were excluded, and data of the remaining 4,297 patients were included in the study. Of the 4,297 SpA patients, 2,449 (57%) were male. The median (Q1-Q3) age of the patients was 42 (35-51) years. The median delay in diagnosis and duration of disease were 24 (6-72) and 95 (49-156) months, respectively. In the SpA cohort, 3,082 patients (71.7%) had AS. Number of patients with other SpA subtypes and the clinical features of SpA patients in the cohort are listed in Table 2 .
|All patients (N=4,297)||Without Uveitis (n=3,822)||With Uveitis (n=475)||OR||95% CI||P|
|Gender (male) n, (%)||2,449 (57)||2,173 (56.9)||276 (58.1)||1.052||0.87-1.28||.604 a|
|Age (y), median (Q1-Q2)||42 (35-51)||42 (35-50)||46 (38-53)||1.024||1.02-1.03||<.001 b|
|Age at the diagnosis of SpA (y), median (Q1-Q2)||33 (26-41)||33 (26-41)||32 (25-41)||.325 b|
|Age at the diagnosis of uveitis (y), median (Q1-Q2)||—||—||35 (28-43)||—|
|Delay in diagnosis (mo), median (Q1-Q2)||24 (6-72)||24 (6-66)||37 (7.5-97)||1.002||1.00-1.00||.001 b|
|Disease duration (mo), median (Q1-Q2)||95 (49-156)||88 (46-143)||141 (83-217)||1.005||1.00-1.01||<.001 b|
|Smoking (never)||1,691 (40.7)||1,532 (41.6)||159 (34.0)||.004 a|
|Ex-smoker||774 (18.6)||668 (18.1)||106 (22.7)||1.529||1.18-1.99|
|Smoker||1,688 (40.6)||1,486 (40.3)||202 (43.3)||1.310||1.05-1.63|
|Arthritis||992 (23.5)||918 (24.5)||74 (15.8)||0.577||0.45-0.75||<.001 a|
|Enthesitis||728 (23.4)||649 (23.2)||79 (25)||1.105||0.84-1.45||.466 a|
|Dactylitis||208 (5.6)||190 (5.7)||18 (4.4)||0.760||0.46-1.25||.274 a|
|Psoriasis||629 (14.8)||603 (15.9)||26 (5.5)||0.308||0.21-0.46||<.001 a|
|Inflammatory bowel disease||220 (5.2)||191 (5)||29 (6.2)||1.234||0.82-1.85||.305 a|
|HLA-B27 positivity||1,413 (53)||1,186 (50.4)||227 (73)||2.661||2.05-3.46||<.001 a|
|Family history of SpA||1,157 (29.1)||986 (27.9)||171 (38.4)||1.614||1.32-1.98||<.001 a|
|Sacroiliitis||3,272 (86.1)||2,874 (85.3)||398 (92.6)||2.146||1.48-3.12||<.001 a|
|Syndesmophytes||752 (23.4)||614 (21.6)||138 (38.1)||2.240||1.78-2.82||<.001 a|
|Bamboo spine||383 (11.5)||303 (10.2)||80 (21.1)||2.347||1.78-3.09||<.001 a|
|Hip involvement||649 (18.3)||542 (17.2)||107 (26.9)||1.774||1.40-2.26||<.001 a|
|Ankylosing spondylitis||3,082 (71.7)||2,688 (70.3)||394 (82.9)||2.052||1.60-2.63||<.001 a|
|Psoriatic arthritis||536 (12.5)||519 (13.6)||17 (3.6)||0.236||0.14-0.39||<.001 a|
|Enteropathic arthritis||387 (9)||118 (3.1)||15 (3.2)||1.024||0.59-1.77||.933 a|
|Nonradiographic axial SpA||492 (11.4)||353 (9.2)||34 (7.2)||0.758||0.53-1.09||.136 a|
|Peripheral spondyloarthritis||133 (3.1)||436 (11.4)||56 (11.8)||1.038||0.77-1.4||.805 a|