Introduction

Inflammatory bowel disease (IBD) is also known to have extra-intestinal manifestations, particularly rheumatological complications (1). Clinicians need to recognise these manifestations as early diagnosis and treatment leads to better patient outcomes. Spondyloarthritis (SpA) is a term used to refer to a group of inflammatory arthritides that is associated with the HLA-B27 gene including axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), reactive arthritis (ReA) and inflammatory bowel disease (IBD)-related arthritis (Table 1). The SpA spectrum includes involvement of the spine (axial disease), peripheral joints (peripheral SpA), areas where tendons and ligaments attach to bone (enthesitis) and digits (dactylitis).

Table 1. The classification, rheumatological and extra-intestinal manifestations of spondyloarthropathies

Enteropathic arthritis is an umbrella term used to describe rheumatological conditions that have a gastrointestinal association. An example of enteropathic arthritis is the link between SpA and IBD (2). In axSpA, the prevalence of IBD which is an extra-musculoskeletal manifestation (EMM) of the condition is 7%. However, if looking at subclinical inflammatory bowel disease, the prevalence is much higher at 50%. Risk factors include a family history and an elevated CRP (3). As with subclinical gut inflammation, there is also a subclinical joint inflammation that can be observed in patients with IBD. Interestingly, 50% of patients who go on to be diagnosed with IBD initially present with musculoskeletal symptoms and arthralgia (4).

Clinical presentation – screening and questions

AxSpA should be suspected in patients that have lower back pain before the age of 40 years. The prevalence of axSpA is 1 in 200 of the population and in 5% of patients with chronic back pain. The main symptoms are inflammatory joint and back pain (5). These symptoms include: pain and swelling in joints, alternating buttock pain and pain that wakes the patient up at night, particularly in the second half of the night. The symptoms often get better with movement and with using non-steroidal anti-inflammatory drugs (NSAIDs). Peripheral spondyloarthritis is suspected in patients whose symptoms are predominantly in their upper and lower limb joints. The symptoms again include pain/swelling of joints as well as tendons particularly at sites of insertion into bone, also known as enthesitis (6). There is also an association with uveitis and psoriasis.

There are many useful screening tools such as the National Axial Spondyloarthritis Society (NASS) symptom checker and the Spondyloarthritis Diagnostic Evaluation (SPADE) tool (7) that can be utilised by patients and clinicians to identify symptoms correctly and determine the need for a rheumatology referral. The NASS symptom checker is easily accessible online and is very straightforward to use. It consists of eight questions (Table 2) completed by the patient. Based on this, a calculation is made on how likely it is that the patient’s back pain may be due to axSpA. This will lead to referral guidance which can be brought to the GP or physiotherapist to aid onward referral to rheumatology. The NASS symptom checker can be displayed in the GP and specialist clinic waiting areas or be sent to patients to be completed (Supplementary Figure 1).

Table 2. The National Axial Spondyloarthritis Society (NASS) Symptom Checker Questionnaire that can be completed by patients with suspected axial spondyloarthritis (axSpA). Available at http://www.actonaxialspa.com/symptoms-checker/

Investigations

When evaluating rheumatological manifestations in IBD, tests that would be useful to request include blood tests looking at inflammatory markers (ESR, CRP) as well as a HLA-B27 test. Other investigations such as rheumatoid factor and anti-CCP are useful in diagnosing rheumatoid arthritis whilst if lupus was a differential that needed to be excluded, ANA would be a useful investigation. If axSpA is suspected, imaging such as X rays of the affected peripheral and sacroiliac (SI) joints as well as MRI scan of the whole spine and SI joints would aid in reaching a diagnosis (8). X-rays are useful to look for radiographic changes of axSpA. MRI is particularly useful in identifying early inflammatory lesions in the spine before changes appear on X-rays. In patients with peripheral SpA, in addition to blood tests, imaging of the peripheral joints with ultrasound or MRI may be useful to look for evidence of joint or tendon inflammation. In cases of swollen joints, joint aspiration may help differentiate between inflammatory arthritis and other causes, such as septic arthritis or crystal arthropathies (eg. gout or pseudogout).

Treatment

The primary goal for treatment is to ensure the optimal patient outcome through a multidisciplinary approach (9). For example, having combined clinics between rheumatologists, gastroenterologists, dermatologists, ophthalmologists, and primary care and community physiotherapists ensures that in addition to the arthritis, the patient’s EMMs are also treated.   It is important that EMMs are taken into account when choosing a treatment for spondyloarthritis as there will be different effects from biologic and small molecule agents. With regards to the use of NSAIDs in IBD, it is not clear whether they could precipitate, worsen or prolong a flare. A 2022 American study suggested that the link between NSAID use and IBD flares could be due to residual bias so a discussion with the patient that follows a shared decision-making structure would be beneficial prior to treating with NSAIDs (10).  Conventional DMARDS such as Methotrexate, Sulfasalazine and Azathioprine may be beneficial for peripheral arthritis. Short term steroids could be beneficial for both active peripheral arthritis and IBD especially during flares of disease. If there is an indication for biologics, anti-TNF monoclonal antibodies can be used for both axial and peripheral disease (11). Other biologics targeting IL-12/23 may also be considered based on the clinical scenario, an example biologic is Ustekinumab as this is useful in treating psoriatic arthritis and IBD but not effective for SpA (12). IL-17 inhibitors, often used to treat spondyloarthritis, is not recommended in IBD as it may exacerbate IBD (13). Another class of medications includes Janus Kinase inhibitors (JAKi) which are used in the management of enteropathic arthritis and can also be used in IBD if used at higher doses (14). However, it is important to note that there has been concerns about the increased risk of cardiovascular events and thrombosis associated with their use and so the risks need to be assessed on a case-by-case basis (15). Table 3 shows the overlap of treatment with IBD, rheumatological and other extra-intestinal conditions.

Table 3. The overlap of treatment with biologic and targeted synthetic disease modifying drugs (DMARDs) in IBD and other extra-intestinal manifestations.

Discussion

The association between IBD and rheumatological manifestations underscores the need for a comprehensive joined up management of these patients (16). Early recognition and treatment of IBD-related arthritis can improve overall outcomes and quality of life. While monitoring gastrointestinal symptoms, it is important to stay vigilant for joint pain, stiffness and swelling, as this can significantly affect patient outcomes and well-being if not assessed and treated early (17). The awareness and understanding of extra-intestinal manifestations can help with the choice of drugs including biologics in IBD.

Conclusion

Rheumatological manifestations associated with IBD can complicate management and adversely impact patients’ quality of life. Clinicians must remain aware of the potential issues and advocate for a multidisciplinary approach to treatment. Timely interventions can mitigate complications and enhance overall care for patients with IBD.

Summary

3 key points for practising clinicians:

1. Recognise the spectrum of rheumatological conditions that are associated with IBD, including axial and peripheral spondyloarthritis.
2. Refer early to Rheumatology if IBD patients have rheumatological manifestations using patient or clinician completed symptom checkers and referral pathways.
3. Effective treatment of patients with IBD related rheumatological manifestations require multidisciplinary care and collaboration including gastroenterology, rheumatology and physiotherapy teams.

Declaration of conflicts of interests

Nikhita Joseph  - none

Antoni Chan  - speaker bureaus with Novartis, UCB, Lilly, Abbvie, Janssen. Advisory boards with Novartis, UCB, Amgen, Janssen.

Supplementary Materials

Supplementary Figure 1. QR code for the NASS symptom checker questionnaire that can be completed by patients with suspected axSpA.

Author Biographies

Dr Nikhita Joseph, MBChB, Foundation Year One Doctor, Royal Berkshire NHS Foundation Trust, UK

Nikhita Joseph is a Foundation Year One (FY1) Doctor at the Royal Berkshire NHS Foundation Trust, UK. She graduated from the University of Birmingham in 2024. During medical school, she developed an interest in Rheumatology and participated in audits with a focus on biologic therapy. In addition to clinical training, she has a passion for research and has been involved in quality improvement projects within the hospital to identify areas of improvement to achieve better patient outcomes. She hopes to pursue a career in Rheumatology or General Practice.

Prof Antoni Chan, MBChB, FRCP, PhD, Professor of Rheumatology and Consultant Rheumatologist and Clinical Lead, University Department of Rheumatology, Royal Berkshire NHS Foundation Trust, UK

Antoni Chan is Consultant Rheumatologist and Clinical Lead in Rheumatology at Royal Berkshire NHS Foundation Trust, UK. His research interest is in the use of data, informatics and artificial intelligence (AI) to improve diagnosis and treatment of rheumatic conditions. Working with the University of Reading, he has been co-applicant for two large grants from UK Research and Innovation (UKRI) and the National Institute for Health Research (NIHR) for the study of AI for early diagnosis of inflammatory arthritis. His team were selected for the National Axial Spondyloarthritis Society (NASS) Aspiring to Excellence Award. He received the Patient Choice Award for Best Care by a Rheumatologist and Gold Changemaker Award in the Houses of Parliament, UK. He is Trustee and Medical Advisory Board Member of NASS. He is a full member of ASAS and GRAPPA. He led the GP educational pogramme (RheumACaN) with his team which won the national British Society for Rheumatology Best Practice Award in 2024.