Axial Involvement in Psoriatic Arthritis: Analysis of Its Characteristics in a Group of Patients with Early Diagnosis in South America.
https://doi.org/10.46856/grp.10.e001
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Garcia Salinas R, Sanchez Prado E, Torres Chichande J, Ruta A, Salvatori F, Magri S, et al.. Axial Involvement in Psoriatic Arthritis: Analysis of Its Characteristics in a Group of Patients with Early Diagnosis in South America. [Internet]. Global Rheumatology. Vol. 1 / Jun - Dic [2020]. Available from: https://doi.org/10.46856/grp.10.e001
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Axial Involvement in Psoriatic Arthritis: Analysis of Its Characteristics in a Group of Patients with Early Diagnosis in South America.
Introduction: Reported data on axial involvement in psoriatic arthritis (PsA) are variable (25 to 70%), and this frequency is linked to the different ways it is defined.
Objectives: To estimate the prevalence of axial involvement in a group of patients diagnosed with PsA in the Reuma-Check program, perform a clinical, laboratory, and imaging characterization, and analyze the differences between patients who present axial involvement versus those who do not.
Methods: Patients admitted to the Reuma-Check program with musculoskeletal symptoms—arthralgia/arthritis, dactylitis, or enthesitis associated with psoriasis or family history—were included. Once diagnosed, patients were questioned about the presence of axial symptoms: low back pain lasting more than 3 months associated with at least one of the following: BASDAI >4, positive sacroiliac maneuvers, and inflammatory characteristics. A second Reuma-Check evaluation was conducted for a complete study of axial involvement (imaging, HLA B27, BASFI).
Results: Of 139 patients, 73 (52%) were finally diagnosed with PsA; 33% presented clinical axial involvement. Compared to those without axial involvement, there was a higher presence of non-musculoskeletal manifestations such as uveitis and inflammatory bowel disease, 42% vs. 12% (p: 0.004), a higher number of enthesitis sites, median 0.5 vs. 0 (p: 0.04), and greater functional impairment (HAQ), 0.8 vs. 0.5 (p: 0.0002). In multivariate analysis, the presence of non-musculoskeletal manifestations and MASES were independently associated with axial involvement.
Conclusion: The prevalence of axial symptoms was 33%, with inflammatory characteristics and disease activity measured by BASDAI. Patients with axial symptoms presented a more severe PsA phenotype.
Psoriatic Arthritis (PsA) is a chronic inflammatory disease that primarily affects the joints. In 80% of cases, it is preceded by plaque psoriasis and is part of the group of spondyloarthritis (1).
Currently, it is known that the main structure where this pathology begins is the enthesis (enthesis organ). From this, we can deduce that the main musculoskeletal manifestations, in addition to peripheral arthritis, are dactylitis, enthesitis, and spondylitis (2). Additionally, PsA is associated with an increased risk of major cardiovascular events, leading to higher morbidity and mortality (3).
Regarding axial involvement, reported data are variable, ranging between 25% and 70%, and this variability is linked to the different ways of defining this clinical feature (4). Gladman et al. established that the prevalence of axial involvement in PsA was close to 50% and was associated with HLA B27 (5). Likewise, psoriatic spondylitis, unlike “pure” ankylosing spondylitis, is characterized by a lack of male predominance, greater skin involvement (plaque psoriasis), and a less severe course, as well as specific radiological differences in each (6).
Regarding treatment, international guidelines, to varying extents, divide PsA by domains (peripheral, enthesis, skin, dactylitis, and nails). In axial involvement, therapeutic choices are based on specific axial spondyloarthritis guidelines (7-8).
Our objective is to estimate the prevalence of axial involvement in a group of patients diagnosed with PsA within the Reuma-Check program, to carry out a comprehensive characterization (clinical, laboratory, and imaging), and to analyze differences between patients with and without axial involvement.
Observational, cross-sectional, single-center study. We included patients over 18 years old admitted to the Reuma-Check program between August 2017 and 2019 according to the following criteria: musculoskeletal symptoms such as arthralgias/arthritis, dactylitis, or enthesitis associated with psoriasis or a family history of psoriasis. Once diagnosed with Psoriatic Arthritis (PsA), patients were questioned about the presence of axial symptoms, defined as low back pain lasting more than 3 months associated with at least one of the following: BASDAI score greater than 4, positive sacroiliac clinical maneuvers, or inflammatory features according to ASAS criteria.
If patients met these criteria, a second Reuma-Check evaluation was performed for a complete study of axial involvement.
Description of the Reuma-Check circuit:
All patients underwent on the same day: clinical evaluation, laboratory tests, and diagnostic imaging including plain radiographs (X-rays) and ultrasound of joints and heel entheses. If the patient met the criteria for axial involvement, additional tests were performed: HLA B27 typing, panoramic pelvic X-ray, and sacroiliac joint magnetic resonance imaging (MRI). All evaluators (physicians, laboratory personnel, and imaging specialists) were blinded to the results of other studies. The full “Reuma-Check” program takes between 3 and 4 hours, and all data, including clinical evaluation, are entered into an electronic medical record system.
Figure 1 shows the Reuma-Check program circuit.
Clinical evaluation: Demographic characteristics were assessed, including age and sex. Information on age at symptom onset, family history (psoriasis, uveitis, inflammatory bowel disease, axial and peripheral spondyloarthritis – SpA), and SpA features (psoriasis, uveitis, inflammatory bowel disease) was collected. Musculoskeletal evaluation followed standard clinical procedures and included: tender joint count (68 joints), swollen joint count (66 joints), and calculation of DAPSA (Disease Activity index for Psoriatic Arthritis) (9). Enthesitis was assessed using the Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) (10). In cases of axial involvement, additional evaluation included: presence of inflammatory low back pain according to ASAS criteria (11), use and response to non-steroidal anti-inflammatory drugs (NSAIDs), and duration of morning stiffness. Provocative tests for sacroiliac joints (thigh thrust and FABER) and visual analog scale (VAS) for pain were also performed. All necessary information was collected to complete the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (12) and Bath Ankylosing Spondylitis Functional Index (BASFI) (13). Function was assessed using the Argentine version of the Health Assessment Questionnaire-Disability Index (HAQ-DI) (14).
Laboratory tests: Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and HLA-B27 typing were determined.
Radiographic evaluation: Digital radiographs of both hands and feet were performed. If axial involvement was present, sacroiliac joint X-rays were added. The presence and grade of sacroiliitis were determined by an experienced rheumatologist according to modified New York criteria. Bilateral grade 2 sacroiliitis or unilateral grade 3 or 4 sacroiliitis was considered a positive X-ray (15).
Magnetic resonance imaging evaluation: MRI of both sacroiliac joints without intravenous paramagnetic contrast was performed using a General Electric Signa Horizon LX 1.5 Tesla scanner. The presence or absence of active inflammatory lesions (STIR sequences) such as bone marrow edema (osteitis), capsulitis, synovitis, and enthesitis, as well as chronic inflammatory lesions (T1 sequences) such as sclerosis, erosions, fat deposits, and bone bridges/ankylosis, were determined by an experienced radiologist. Bone marrow edema (osteitis) was considered a positive MRI finding. If only one slice showed bone marrow edema, the lesion had to be present in at least two consecutive slices. If multiple areas of edema appeared on a single slice, one slice was sufficient (16).
Ultrasound evaluation: All ultrasound exams were performed by an experienced rheumatologist-sonographer using a MyLab 25 (Esaote) machine with a 6–18 MHz broadband linear multifrequency transducer. Scanning technique followed the European League Against Rheumatism (EULAR) guidelines (17).
Heel entheses were examined bilaterally with the patient in the prone position, feet hanging off the edge of the examination table at 90° flexion.
All entheses were first scanned in B-mode (grayscale) to detect any morphostructural changes and then with power Doppler (PD) to detect abnormal increased blood flow at the entheses. The following ultrasound findings indicative of enthesopathy were investigated and documented in both transverse and longitudinal views at each enthesis: thickening, structural changes, bursitis, abnormal vascularization by PD technique, calcifications, bone erosions, and enthesophytes (18).
Diagnosis of Psoriatic Arthritis (PsA):
After completing the full Reuma-Check evaluations, a diagnosis of PsA was either established or excluded based on the entire electronic medical record. The diagnosis was made in all cases by an expert rheumatologist. In cases of diagnostic uncertainty, the opinion of a second expert rheumatologist was obtained for the final diagnosis. Once established, CASPAR criteria were verified (19).
Ethical considerations:
The study was conducted following the Declaration of Helsinki and local regulations. Ethical approval was obtained from the local hospital ethics committee.
Statistical analysis:
Descriptive statistics summarized patient characteristics. Continuous variables were expressed as medians and interquartile ranges (IQR) or means and standard deviations (SD). Categorical variables were expressed as percentages. Comparisons were made using parametric and non-parametric tests for continuous variables and chi-square tests for categorical variables. Multivariate logistic regression analysis was performed with axial involvement as the outcome variable.
Characteristics of the patients
One hundred thirty-nine (139) patients with musculoskeletal symptoms plus psoriasis or a family history were admitted to the Reuma-Check program. Fifty-two percent (52%) presented with musculoskeletal symptoms and plaque psoriasis, and the remaining 48% had a family member with psoriasis.
Diagnosis and classification
Of the 139 patients, 73 (52%, 95% CI: 44–60) were ultimately diagnosed with Psoriatic Arthritis (PsA), all fulfilling CASPAR criteria. Table 1 describes the characteristics of the diagnosed patients (both current and past features).
Axial involvement
Of the 73 patients diagnosed with PsA, 33% (95% CI: 22–44) had clinical axial involvement meeting the specified criteria. A total of 37% showed imaging findings. The clinical, laboratory, and imaging characteristics of low back pain are shown in Table 2.
In PsA patients with axial involvement, compared to those without, there was a higher prevalence (current or past) of non-musculoskeletal manifestations such as uveitis and inflammatory bowel disease, 42% vs 12%, respectively (p = 0.004), a higher number of enthesitis with a median of 0.5 vs 0 (p = 0.04), and greater functional impairment measured by HAQ, 0.8 vs 0.5 (p = 0.0002). Table 3 presents the rest of the differential characteristics between patients with and without axial involvement in the univariate analysis.
Variables with p-values less than 0.1 were included in a binomial logistic regression model where axial involvement was the dependent variable; the variables independently associated were the presence of non-musculoskeletal manifestations and MASES score. The full analysis is shown in Table 4.
Axial spondyloarthritis and psoriatic arthritis are two ends of the same disease spectrum. In the former, symptoms of inflammatory involvement of the spine predominate, while in the latter, inflammation of peripheral structures such as arthritis and enthesitis predominates (20). However, just as peripheral involvement exists in patients with axial spondyloarthritis (axSpA), the same occurs in psoriatic arthritis (PsA) with axial involvement. The widest reported prevalence range is between 25% and 70%, and the criteria used to define it have always been extrapolated from those established for ankylosing spondylitis and, more recently, axial spondyloarthritis (15, 21). In our case, we found a prevalence of 33%, comparable with what is reported in the literature (22). Its definition was based on a set of clinical data such as inflammatory-type low back pain, BASDAI activity, and sacroiliac maneuvers. Regarding the first, the classification used is the same as for axSpA; in our experience, its prevalence was close to 90% (in patients with low back pain) and a favorable response to NSAIDs of 75%. In contrast, the prevalence of inflammatory low back pain in patients with PsA or psoriasis is estimated to be 15% and 19%, respectively. In our study, we obtained a prevalence of inflammatory low back pain close to 30%, since most patients with axial symptoms presented these characteristics (23-25).
Limitations in spinal movement, pain, and positive maneuvers were also reported in patients with PsA, although one-third of patients have asymptomatic sacroiliitis detectable by imaging (24, 27, 28). In our cohort, clinimetric characteristics demonstrated high disease activity and impaired physical function, expressed by BASDAI, BASFI, and HAQ, the latter also showing significant differences between patients with and without axial involvement. Additionally, sacroiliac maneuvers were positive in 71% of patients.
Although the presence of HLA-B27 in PsA is inherently low (less than 40%), and its determination is reserved almost exclusively for pure ankylosing spondylitis, it has been found that its positivity is important not only for susceptibility to PsA with axial involvement but also for determining clinical characteristics, including earlier onset of psoriasis and arthritis. It is also directly related to uveitis, familial aggregation, and imaging involvement, the latter mostly associated with the axial spondyloarthritis phenotype fulfilling criteria for the same (29-31). However, we know that the prevalence of HLA-B27 in several Latin American sites is lower than in Northern European cohorts (32). In a study comparing European and Latin American populations, a statistically significant difference in HLA-B27 positivity was observed, higher in the former (83% vs. 71%, p = 0.0001) (33). In Argentina, reported HLA-B27 prevalence ranges around 40%–50% (33-35). In this study, 17% of PsA patients with axial involvement were positive for HLA-B27.
Only 29% showed positive changes on sacroiliac radiographs and 40% typical changes on MRI. Generally, only a few studies have evaluated the frequency of radiographic spinal involvement in patients diagnosed with PsA. Depending on the classification used, it has been reported that between 25% and 70% of patients diagnosed with PsA have such involvement combined with peripheral symptoms confirming PsA (6), while early disease cohorts have reported a prevalence of 5% to 28% of patients with some spinal involvement (36-38) alongside peripheral arthritis. Part of the difficulty in evaluating radiographic changes in the spine is that these changes, which can be used to confirm the modified New York criteria, may take many years to develop (39). Although in recent years the role of magnetic resonance imaging (MRI) for diagnosis and evaluation of patients with axSpA has been highlighted, in patients with PsA axial involvement may also be evident on MRI but clinically absent, thus the real prevalence of these changes is unknown (40).
In univariate and multivariate analysis, we found that PsA patients with axial involvement had a higher disease burden, with more non-musculoskeletal manifestations such as uveitis, greater enthesitis involvement, and reduced functional capacity; similar data have been reported by other cohorts, which also included greater psoriasis severity, which was not quantified in our study (41).
As limitations of our study, we highlight that axial involvement data were collected retrospectively, so we could not establish temporality between axial and peripheral involvement, although we had diagnostic delay data. We also consider the lack of psoriasis quantification a limitation. Although the study does not evaluate treatment because all patients were recently diagnosed and none were receiving treatments other than NSAIDs, we will follow them prospectively to evaluate their impact on all PsA domains while awaiting ASAS and GRAPPA groups to help us better define this involvement in PsA and results from clinical trials with drugs that use this as a primary outcome rather than extrapolating results from axSpA cohorts (42).
As strengths, this is the first study to comprehensively evaluate axial involvement in PsA in Latin America, providing clinical, imaging (including MRI), and laboratory data (including HLA-B27) and comparing differences between patients with and without axial involvement.
The prevalence of axial symptoms in our cohort was 33%. The characteristics of low back pain were mostly inflammatory, with disease activity assessed by BASDAI and functional impairment measured by BASFI. Patients with axial symptoms exhibited features of more severe psoriatic arthritis.
Consent for publication:
The final manuscript has been critically reviewed and approved by all authors, and due care has been taken to ensure the integrity of the work.
All authors declare no conflicts of interest regarding the present study.
The present study has no funding.
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