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Background. To assess the influence of the co-presence of psoriasis (PsO) on the clinical and therapeutic pattern of a single-centre cohort of patients with spondyloarthritis (SpA) associated with chronic inflammatory bowel disease (IBD).   Methods. This study represents a preliminary phase of an ancillary analysis of the DIAMANTE project (Early diagnosis of spondyloarthritis in a cohort of patients with chronic inflammatory bowel disease), developed with the overall objective of determining the prevalence, predictors and outcomes of SpA in a cohort of subjects with IBD, in the context of close and structured collaboration between gastroenterologists and rheumatologists. Within the DIAMANTE cohort, two subgroups of patients were identified for the study: patients with SpA and a concomitant personal diagnosis of PsO (Group 1: IBD+SpA+PsO) and patients with a diagnosis of SpA alone (Group 0: IBD+SpA). For both groups, the following demographic, clinical and therapeutic data were recorded and compared: gender, association between IBD patterns, peripheral joint involvement, axial involvement, history of dactylitis, need for biological therapy, multi-resistance to targeted drugs (discontinuation due to ineffectiveness of at least two small molecule biological drugs). A significance threshold of p<0.05 was used with Fisher's and X² tests.   Results. Data from 665 consecutive patients with IBD recruited from November 2023 to April 2025 were analysed. Within this cohort, 95 (14%) had a concomitant diagnosis of SpA; among these, 21 (22%) also had a diagnosis of PsO (IBD+SpA+PsO group), while 74 (78%) had only SpA associated with IBD (IBD+SpA group). Comparative analysis of the two groups revealed significant, albeit only trending towards statistical significance, differences in terms of female prevalence (71% vs 54%, p=0.15), frequency of peripheral involvement (62% vs 49%, p=0.28) and use of biologic drugs (91% vs 77%; p=0.17). Most notably, a significantly higher frequency of multidrug resistance to biological drug treatment was observed in patients with concomitant PsA compared to patients with IBD and SpA alone (29% vs 11% p=0.04). No significant differences were observed in terms of destruction of the different IBD conditions (ulcerative colitis, Crohn's disease, undifferentiated forms) between the two study groups.   Conclusions. In patients with SpA associated with IBD, the simultaneous association with PsO, another extra-articular domain typical of the spectrum of spondyloarthropathies, was also frequently demonstrated. The results of this exploratory analysis suggest that it would be useful to investigate, in larger prospective case series, the impact that this dual combination of extra-articular manifestations may have on disease characteristics and, in particular, on treatment management.

We aim to estimate the incidence of IBD-SpA in a population of Crohn’s disease (CD) patients and to identify risk factors associated with the development of IBD-SpA. This retrospective observational cohort study included all consecutive patients with a CD diagnosis followed by our IBD outpatient clinic who underwent at least one magnetic resonance enterography (MRE) between 2011 and 2023. Patients without a full scan of sacroiliac joints (SIJs) on MRE, having other rheumatic diseases, diagnosed with SpA before CD diagnosis, missing key clinical or imaging data, death or lost to follow-up at the time of data collection, were excluded. The identification of new onset IBD-SpA during the follow-up was based on the fulfillment of the ASAS classification criteria. Baseline demographic and clinical data, and immunosuppressive therapies performed were collected. Presence of articular and intestinal lesions at MRE was established according to the most recent definitions by ASAS and the Society of Abdominal Radiology, respectively. Incidence rates were calculated as the number of new cases of SpA divided by the total person-time at risk, expressed per 1,000 person-years. Log-rank test and univariate Cox proportional hazards regression analyses were performed to estimate hazard ratios (HR) for categorical and continuous predictors. A total of 147 CD patients [M:F 1:1, median age (IQR) 46.3 (23.3) years, median CD duration (IQR) was of 4.50 (16.4) years] were selected. Descriptive statistics of the sample are shown in Table 1. The incidence rates of overall, axial, and peripheral IBD-SpA were 3.8, 2.1, and 1.7 cases per 1,000 person-year, respectively. A stricturing CD behavior (HR: 0.22; 95% CI: 0.05–0.93; p=0.040), baseline mesalazine treatment (HR: 0.24; 95% CI: 0.06–0.99; p=0.049), greater age (HR: 0.94; 95% CI: 0.89–1.00; p=0.035), and CD duration (HR: 0.84; 95% CI: 0.72–0.97; p=0.019), were associated with a reduced risk of developing IBD-arthritis. The sub-analysis conducted for each subset of arthritis revealed an increased risk of axial IBD-SpA for active sacroiliitis (HR 6.08; 95% CI 1.11-33.4; p=0.038), and ankylosis of SIJs on MRE (HR 47.7; 95% CI 2.99-763.4; p=0.006), while revealed a reduced risk for baseline mesalazine treatment (HR 0.20; 95% CI 0.04-1.11; p=0.067), greater age (HR: 0.93; 95% CI: 0.86–1.00; p=0.040) and CD duration (HR: 0.84; 95% CI: 0.71–0.99; p=0.033). An increased risk of peripheral IBD-SpA emerged only for ankylosis of SIJs (HR 24.6; 95% CI 2.23-271.8; p=0.009). A reduced incidence rate of IBD-SpA was associated with a stricturing CD behavior, baseline mesalazine treatment, increasing age and CD duration. Active sacroiliitis at baseline MRE was associated with the development of axial IBD-SpA; mesalazine therapy, greater age and CD duration were protective factors. Table 1: descriptive statistics of the sample.

Background: 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. Objectives: We aimed to evaluate diagnostic delay in eSpA and explore associated demographic, clinical, and radiographic characteristics. Design: Single-centre cross-sectional study conducted on consecutive out-patients referred to the combined Gi-Rhe clinic (November 2018–October 2019). Methods: We analysed eSpA patients for diagnostic delay, disease activity, inflammatory markers, conventional radiography (CR) and magnetic resonance images (MRI) of sacroiliac joints/spine. Results: 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. Conclusion: 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. Plain language summary Diagnostic delay in patients affected by enteropathic spondyloarthritis Enteropathic Spondyloarthritides (eSpA) 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. We analysed eSpA patients for diagnostic delay, disease activity, inflammatory markers, conventional radiography and magnetic resonance images of sacroiliac joints/spine. 190 eSpA patients (118 peripheral SpA, 72 axial (Ax) SpA including 44 non-radiographic (nr)-axSpA)) were enrolled. Median diagnostic delay in eSpA was 48 months with no difference between axial and peripheral patients. Radiographic-axial SpA (r-axSpA) patients displayed a higher diagnostic delay compared with nr-axSpA and were older, with longer disease duration, low education status and high rate of employment than patients with nr-axSpA. 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.

Phosphodiesterases (PDEs) are a heterogeneous superfamily of enzymes which catalyze the degradation of the intracellular second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Among PDEs, PDE4 is the most widely studied and characterized isoenzyme. PDE4 blocking can lead to increased levels of intracellular cAMP, which results in down-regulation of inflammatory responses by reducing the expression of tumor necrosis factor (TNF), interleukin (IL)-23, IL-17, interferon-γ, while increasing regulatory cytokines, such as IL-10. Therefore, PDE4 has been explored as a therapeutic target for the treatment of different chronic inflammatory conditions such as psoriatic arthritis (PsA) and inflammatory bowel disease (IBD). PsA shares clinical, genetic, and pathogenic features with IBD such as ulcerative colitis (UC) and Crohn’s disease (CD), and enteropathic spondyloarthritis (eSpA) represent a frequent clinical evidence of the overlap between gut and joint diseases. Current therapeutic options in PsA patients and underlying UC are limited to synthetic immunosuppressants and anti-TNF. Apremilast is an oral PDE4 inhibitor approved for the treatment of active PsA patients with inadequate response to synthetic immunosuppressants. The efficacy and a good safety profile observed in randomized clinical trials with apremilast in PsA patients have been confirmed by few studies in a real-life scenario. In addition, apremilast led to significant improvement in clinical and endoscopic features in UC patients in a phase II RCT. By now there are no available data regarding its role in eSpA patients. In view of the above, the use of apremilast in eSpA patients is a route that deserves to be deepened.

Abstract Objectives To assess the risk of major adverse cardiovascular events (MACE) and venous thromboembolism (VTE) in patients with enteropathic arthritis (EA) compared with matched controls. Methods We performed a 1:1 propensity score matched retrospective cohort study using electronic health records. EA was defined using International Classification of Diseases, 10th Revision code M07 and codes for Crohn’s disease or ulcerative colitis, excluding other inflammatory arthritis. Controls had no coded diagnosis of Crohn’s disease, ulcerative colitis or inflammatory arthritis. Primary outcomes were MACE and VTE; secondary outcomes included myocardial infarction (MI), stroke, CVD (composite of ischaemic heart disease and cerebrovascular disease), pulmonary embolism (PE) and deep vein thrombosis (DVT). Cohorts were matched for demographics, comorbidities and medications, with analysis using Cox proportional hazards models. Results We included 5239 matched pairs (mean age 43 years, 63% female), with follow-up of 19 256 person-years (PY) for EA and 42 064 PY for controls. MACE [261 events; incidence rate (IR) 13.6/1000 PY (95% CI 11.9, 15.2)] occurred more frequently in EA compared with controls [407 events; IR 9.7/1000 PY (95% CI 8.7, 10.6)]. Similarly, VTE occurred more frequently in the EA group, with 264 [IR 13.7/1000 PY (95% CI 12.1, 15.4)] compared with 250 events [IR 5.9/1000 PY (95% CI 5.2, 6.7)]. The hazards of MACE [HR 1.40 (95% CI 1.19, 1.66)] and VTE [HR 1.89 (95% CI 1.57, 2.27)] were significantly increased. Results were concordant across CVD, MI and PE, but lacked precision for stroke and DVT. Conclusion EA is associated with an increased risk of MACE, VTE, MI, CVD and PE. Risk-reduction strategies and lifestyle measures should be clinical and research priorities. Lay Summary What does this mean for patients? Enteropathic arthritis (EA) is a condition that may occur in people with inflammatory bowel disease (IBD). This condition affects the joints, causing swelling, pain, stiffness and back problems. IBD and similar joint problems increase the risk of heart attacks, strokes and blood clots. We do not know whether people with EA also have an increased risk of these problems. In our research study, we looked at the healthcare records of >5000 people with EA and >5000 similar people without EA. We compared the groups to see how many people with EA had a heart attack, stroke or blood clot, compared with people without EA. We found that people with EA had an increased risk of having a heart attack or a blood clot in their lungs. People with EA should be given advice to reduce the risk of these, including stopping smoking, as well as diet and exercise advice.

Background: Patients with inflammatory bowel disease (IBD) have an excess burden of axial spondyloarthritis (axSpA), which, if left untreated, may significantly impact on clinical outcomes. We aimed to estimate the prevalence of axSpA, including previously undiagnosed cases, in IBD patients from studies involving cross-sectional imaging and identify the IBD features potentially associated with axSpA. Methods: PubMed, Embase and Cochrane databases were searched systematically between 1990 and 2018. Article reference lists and key conference abstract lists from 2012 to 2018 were also reviewed. All abstracts were reviewed by two authors to determine eligibility for inclusion. The study inclusion criteria were (a) adults aged 18 years or above, (b) a clinical diagnosis of IBD and (c) reporting identification of sacroiliitis using cross-sectional imaging. Results: A total of 20 observational studies were identified: 12 used CT, 6 used MR and 2 utilised both computed tomography (CT) and magnetic resonance (MR) imaging. Sample sizes ranged from 25 to 1247 (a total of 4096 patients); 31 studies were considered to have low selection bias, 13 included two or more radiology readers, and 3 included rheumatological assessments. The prevalence of sacroiliitis, the most commonly reported axSpA feature, ranged from 2.2% to 68.0% with a pooled prevalence of 21.0% [95% confidence interval (CI) 17–26%]. Associated IBD features include increasing IBD duration, increasing age, male sex, IBD location, inflammatory back pain and peripheral arthritis. No significant difference in the prevalence of sacroiliitis between Crohn’s disease and ulcerative colitis was identified. Study limitations include variability in the individual study sample sizes and patient demographics. Conclusion: This review highlights the need for larger, well-designed studies using more sensitive imaging modalities and multivariable modelling to better estimate the prevalence of axSpA in IBD. An improved knowledge of the IBD phenotype(s) associated with axSpA and use of cross-sectional imaging intended for IBD assessment to screen for axSpA may help clinicians identify those patients most at risk.

The Spondyloarthritides (SpA) are a group of chronic inflammatory diseases affecting the spine, peripheral joints and entheses, as well as extra-skeletal structures, including the gastrointestinal tract. On the other hand, inflammatory bowel disease (IBD), either Crohn’s disease or ulcerative colitis, often affects extra-intestinal sites, including the axial and/or peripheral skeleton. IBD-related arthritis is the type of SpA that occurs in patients affected by IBD, with an incidence up to 50% during the IBD course. Although both manifestations are apparently the result of a common pathogenetic process, physicians often fail to recognize the disease in its entirety: thus, IBD-SpA is managed as two separate diseases, a musculoskeletal and a gastrointestinal one, with a profound impact on patient quality of life. Moreover, the specialty of the treating physician determines the clinical and laboratory tools for disease assessment, which, in turn, guide treatment decisions that may overlook either affected system or even act in the opposite direction. Raising awareness of the intestinal and musculoskeletal manifestations among rheumatologists and gastroenterologists will lead to earlier diagnosis and a multidisciplinary approach, particularly regarding pharmacologic treatments. Given the lack of trial evidence on immunomodulatory drugs in IBD-SpA it is imperative for researchers in both medical disciplines to join efforts, in order to determine referral strategies, appropriate composite measures for disease assessment, treatment algorithms and therapeutic targets. Cite this article as: Zioga N, Kogias D, Lampropoulou V, Kafalis N, Papagoras C. Inflammatory Bowel Disease-related Spondyloarthritis: The Last Unexplored Territory of Rheumatology. Mediterr J Rheumatol 2022;33(Suppl 1):126-36.

Juvenile spondyloarthritis may be present in at least 3 subtypes of juvenile idiopathic arthritis according to the classification of the International League of Associations for Rheumatology. By contrast with spondyloarthritis in adults, juvenile spondyloarthritis starts with inflammation of peripheral joints and entheses in the majority of children, whereas sacroiliitis and spondylitis may develop many years after the disease onset. Peripheral joint involvement makes it difficult to differentiate juvenile spondyloarthritis from other juvenile idiopathic arthritis subtypes. Sacroiliitis, and especially spondylitis, although infrequent in childhood, may manifest as low back pain. In clinical practice, radiographs of the sacroiliac joints or pelvis are performed in most of the cases even though magnetic resonance imaging offers more accurate diagnosis of sacroiliitis. Neither disease classification criteria nor imaging recommendations have taken this advantage into account in patients with juvenile spondyloarthritis. The use of magnetic resonance imaging in evaluation of children and adolescents with a clinical suspicion of sacroiliitis would improve early diagnosis, identification of inflammatory changes and treatment. In this paper, we present the imaging features of juvenile spondyloarthritis in juvenile ankylosing spondylitis, juvenile psoriatic arthritis, reactive arthritis with spondyloarthritis, and juvenile arthropathies associated with inflammatory bowel disease.

Seronegative spondyloarthritis (or spondyloarthropathy) is a group of related diseases, which involve the axial skeleton, peripheral joints, and nonarticular structures. The term seronegative implies the absence of serum rheumatoid factor, a marker for rheumatoid arthritis. Diseases that come under this umbrella include ankylosing spondylitis, psoriatic arthritis, reactive arthritis (formerly known as Reiter syndrome), enteropathic arthritis (arthritis associated with inflammatory bowel disease), and undifferentiated spondyloarthropathy. The characteristic clinical symptoms are inflammatory back pain, oligoarticular peripheral arthritis in an asymmetric pattern, enthesitis, uveitis, and dactylitis. Spondyloarthritis is strongly associated with the presence of the HLA B27 gene in the major histocompatibility complex (MHC) on chromosome 6. In conjunction with the medical history and physical exam, conventional radiographs and magnetic resonance imaging of the sacroiliac joints and spine are useful in making the diagnosis. Treatment is mainly based on the use of nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying antirheumatic drugs (DMARDs), and TNF inhibitors. Physical therapy is highly recommended, particularly in patients with ankylosing spondylitis.