Hamdan Medical Journal

INVITED REVIEW
Year
: 2020  |  Volume : 13  |  Issue : 2  |  Page : 61--65

Axial spondyloarthritis - A challenging inflammatory rheumatic disease


Johannes Grisar 
 Department of Internal Medicine/Rheumatology, Sanatorium Hera, Vienna, Austria

Correspondence Address:
Johannes Grisar
Sanatorium Hera, 1090 Vienna
Austria

Abstract

Axial spondyloarthritis (ax-SpA) belongs to the most common inflammatory rheumatic diseases. The disease can be subdivided into non-radiographic ax-SpA and radiographic SpA or ankylosing spondylitis. The broad availability of magnetic resonance imaging has enabled us to diagnose this disease earlier. However, the fact that chronic back pain represents one of the most common symptoms and also in a healthy population is a remarkable pitfall for the diagnosis of ax-SpA. Aside from imaging, laboratory parameters, especially HLA-B27 as well as parameters of inflammation in conjunction with the medical history and the clinical examination are required to perform the diagnosis, which still can be challenging. Regarding therapy, biologics and especially tumour necrosis factor blockers have widely broadened our capabilities to treat this disease for patients who are not adequately responding to non-steroidal anti-rheumatic drugs. Interleukin-17 blockade represents a newer option, and Janus Kinase inhibition has shown some promising results in clinical trials. However, despite all efforts that have been achieved in ax-SpA, still the period between the onset of symptoms and diagnosis remains too long and must be further shortened.



How to cite this article:
Grisar J. Axial spondyloarthritis - A challenging inflammatory rheumatic disease.Hamdan Med J 2020;13:61-65


How to cite this URL:
Grisar J. Axial spondyloarthritis - A challenging inflammatory rheumatic disease. Hamdan Med J [serial online] 2020 [cited 2021 Sep 27 ];13:61-65
Available from: http://www.hamdanjournal.org/text.asp?2020/13/2/61/284045


Full Text



 Introduction



There exist several forms of spondyloarthritis (SpA), that all represent inflammatory-mediated diseases which are, at least to a certain extent, genetically mediated. The hallmarks of axial SpA (ax-SpA) are inflammatory lesions, caused by bone marrow oedema in the iliosacral joints, peripheral arthritis, dactylitis, enthesitis and extrasceletal manifestations such as uveitis, psoriatic lesions and inflammatory bowel diseases.

This current review article will focus on ax-SpA, its pathogenesis, clinical manifestations and therapy.

 Definition and Epidemiology



During the past 10–15 years, our knowledge about ax-SpA has dramatically improved. The term ‘axial’ refers to the fact that the primary manifestation is in the iliosacral joints or/and the spine but, however, also other above-mentioned manifestations may occur. SpA can be divided into axial forms, including non-radiographic (nr) ax-SpA and radiographic ax-SpA also termed ankylosing spondylitis (AS) and several forms of peripheral SpA [Table 1].{Table 1}

According to Rudwaleit et al.,[1],[2] ax-SpA can be divided into three stages: Stage 1 (i.e., nr-ax-SpA), where the inflammatory lesions in the iliosacral joint can only be detected using magnetic resonance imaging (MRI); Stage 2, where the inflammatory alterations are already visible in the MRI and finally, the Stage 3, where syndesmophytes are present in other parts of the spine. However, as we will discuss later, not every patient will necessarily develop the later stages.

In former times, when the MRI technique was not yet available, only AS could be diagnosed. Around the millennium and the following years, the assessment of ankylosing spondylitis (ASAS) international society and their members have widened our knowledge about the disease with several publications, criteria and definitions.

Studies investigating the prevalence or incidence of ax-SpA widely differs, but this may be due to (1) geographic variations, since the disease shows a strong genetic association and (2) to the fact that the definitions for fulfilling the criteria vary in the distinct studies.[3],[4] In a systematic review of the literature, the prevalence of AS (not including nr-ax-SpA) is estimated between 0.15% and 0.8% in Europe.[5] However, we also see differences when comparing nr-ax-SpA with AS (or radiographic SpA) since nr-ax-SpA more often occurs in females, whereas AS has a predominance for males.[6]

The symptoms typically begin around the age of 15–40 years; however, rarely, the disease also could start at a later age.

 Clinical Manifestations



The main characteristic of the disease is the inflammatory back pain, which is characterised, as shown in [Table 2] and requires at least 4 of 5 symptoms positive.[7] The inflammatory back pain is the most common first symptom. However, on the other hand, only around 30% with inflammatory back pain suffer from ax-SpA. Since back pain is a very common symptom, a patient who fulfils the ASAS criteria for inflammatory back pain should be thoroughly evaluated. Moreover, in a smaller proportion of ax-SpA patients, the leading symptom can also occur in other parts of the spine than the iliosacral joint, mainly the thoracic and the lumbar spine. Moreover, extra-articular manifestations such as peripheral arthritis, enthesitis and dactylitis can be rarely the leading symptom instead of inflammatory back pain.{Table 2}

Enthesitis has been described to occur in between 7% and 74% of the patients and is most likely to affect the Achilles tendon and the elbows.[8],[9]

Uveitis is the most common extra-articular manifestation in AS, which is reported historically in 21% of the newly diagnosed patients and is apparent in approximately 2% at the time of diagnosis. Around 40% of the patients show a least once in their lifetime an event of uveitis.[10],[11]

Psoriasis is prevalent during the disease course in up to 10% of the patients, whereas chronic[11] inflammatory bowel disease only occurs in around 1.5% of the ax-SpA patients.

 Laboratory Findings



Like in many inflammatory diseases, there is no specific laboratory test or marker that is specific for the disease. However, ax-SpA has a strong genetic association with the gene HLA-B27. HLA-B27 is a class 1 major histocompatibility complex and was shown to be positive in 83%–96% of the patients with radiographic ax-SpA. Nevertheless, depending on the geographical region, the general population in Europe has been shown to be HLA-B27 positive in around 6%–9%, so HLA-B27 is not suitable as a screening marker. Moreover, with our increasing knowledge about nr-ax–SpA, it could be shown that the disease is more predominant in females.[11],[12] Moreover, HLA-B27 has been shown to positive in only around 75% of the patients in a German ax-SpA cohort.[11] In fact, for the ‘diagnostic puzzle,’ HLA-B27 is an important marker, but a negative HLA-B27 does not rule out the diagnosis of ax-SpA at all.

Inflammatory parameters such as C-reactive protein (CRP) and erythrocyte sedimentation rate should be determined in all patients with suspected ax-SpA since CRP also represents a parameter in the ASAS classification criteria. It is in note that increased ESR and/or CRP can only be found 38%–63% of the patients.[13],[14] However, increased CRP has been shown to be linked to a more rapid radiographic progression.[14]

 Imaging



When it comes to the diagnosis of ax-SpA, imaging is among the most important tools. With the improvement in MRI technique and the broader availability, our knowledge of the musculoskeletal changes associated with the disease has significantly improved. According to the ASAS classification criteria, the so-called ‘imaging’ arm for nr-ax-SpA requires a positive MRI to fulfil the criteria.[13]

From an imaging perspective, the difference between nr-ax-SpA and AS is defined by the fact, that nr-ax-SpA is only detectable/visible in the MRI and not in the conventional X-ray, whereas radiographic SpA (or AS) shows specific changes in the X-ray.

Per definition, the criteria for sacroiliitis in the MRI are fulfilled when one lesion is visible in at the short inversion time inversion-recovery sequence at least in two layers or alternatively at least different two lesions can be detected.[15]

However, sacroiliitis can also be associated with other alterations such as erosions, fatty lesions or sclerosis, which are mainly considered to be post-inflammatory changes.

Moreover, we should keep in mind that a study testing mainly pain-free healthy individuals, runners or females post-partum also found evidence for sacroiliitis.[16] This fact underlines that we should see the ‘whole picture’ of clinic, imaging and laboratory findings in order not to over-diagnose our patients.

As mentioned above, in a small proportion of ax-SpA patients, no pathologic findings can be observed in the MRI of the sacroiliac joints. In such a case, an MRI of other parts of the spine is recommended. Alternatively, according to the ASAS classification criteria, the diagnosis of nr-ax-SpA is still possible when the patient is HLA-B27 positive and fulfils at least two ax-SpA criteria.[13]

Enthesitis is another common symptom of ax-SpA, which is often challenging to diagnose. Using MRI with contrast medium represents a feasible method to test for enthesitis; however, the differentiation between inflammatory enthesitis and other causes (for example mechanical) might be challenging.[17]

Some decades ago, when MRI was not yet broadly available, rheumatologists relied on X-rays for the diagnosis of ax-SpA. In 1973, the New York criteria for sacroiliitis were published by Moll and Wright.[18] For judging the severity of sacroiliitis, a grading from 0 to 4 [Table 3] is used, and for the diagnosis of sacroiliitis, a score from at least 2 in both the left and the right iliosacral joints is required. These criteria are still valid, and if positive, the criteria for radiographic ax-SpA (or AS) are fulfilled.{Table 3}

Furthermore, as already mentioned within the spine, ax-SpA is not only limited to the iliosacral joints. Moreover, within all other parts of the spine, extra-articular manifestations such as spondylitis anterior (also termed as shiny corners), fatty lesions, syndesmophytes, erosions and finally, ankylosis of the vertebrae can be found. However, these are known to occur more frequently in the thoracic and lumbar spine rather than in the cervical spine.

Ultrasound is a very adequate and useful tool in ax-SpA diagnosis for the diagnosis of enthesitis since in a large proportion of the patients suffering from this symptom, a typical sonographic pattern of the enthesis can be detected.[19]

 Diagnosis of Axial Spondyloarthritis



The differentiation of ax-SpA from other diseases that causes low back pain can be very challenging. Chronic back pain over a period of at least 3 months is a very common symptom and can have multiple causes. Moreover, it is important to highlight that the vast majority of patients suffering from chronic back pain have other causes than ax-SpA. Therefore, it is even more important that no case of ax-SpA is overseen in clinical rheumatology routine.

In order to improve the diagnosis, the ASAS published recommendations for further assessment of ax-SpA [Figure 1].[13] If a patient aged 45 or younger develops chronic back pain and fulfills at least one of the mentioned criteria, they should undergo a rheumatology assessment.{Figure 1}

Still, the interval between the onset of symptoms and diagnosis is much too long and was estimated to be 9 years in 2003.[20] However, campaigns to increase the awareness for the disease have shown to be efficacious since some local data from smaller geographic regions show that the latency period between the symptom onset and diagnosis can be decreased down to 1 year.[21],[22]

As mentioned, the leading symptom in the majority of patients with ax-SpA is inflammatory back pain. Therefore, a thoroughly clinical examination as well as a detailed medical history, screening for ax-SpA symptoms is necessary. The other parts of the ‘puzzle’ are imaging as mentioned above and the laboratory test with ESR, CRP and HLA-B27 as the most important parameters. When it comes to imaging, an MRI is not necessary if the x-ray reveals already r-ax-SpA or AS. However, in a patient where ax-SpA is a possible differential diagnosis and where the X-rays are negative for inflammatory lesions, an MRI of the iliosacral joints should definitely be considered.

Once the diagnosis has been performed, it is important that adequate therapy is immediately started.

 Therapy of Axial Spondyloarthritis



The therapy of ax-SpA ideally consists of medical therapy as well as physiotherapy. In analogy to rheumatoid arthritis, treat to target recommendations have been postulated in axial spondyloarthritis aiming for remission or at least low disease activity.[23] The measurement of disease activity should be performed using the ‘ankylosing spondylitis disease activity score’ (ASDAS).

Regarding medical therapy, non-steroidal anti-rheumatic drugs (NSAIDs) are recommended as the first-line therapy. In approximately 60% of the patient, a sufficient pain reduction can be achieved using NSAIDs.[24] However, it has also been shown that they inhibit radiographic progression.[25] In addition, the response to NSAIDs can be individually different. In case of a weak response to one of these agents, a switch to another NSAID is recommended. Cox-2 specific NSAIDS can be preferred in patients with bowel involvement.

If NSAIDs fail to achieve remission or low disease activity, biologics should be considered. In ax-SpA, when compared to other inflammatory rheumatic diseases, our armamentarium remains smaller. All tumour necrosis factor blockers (adalimumab, infliximab, etanercept, golimumab and certolizumab) have been approved as therapeutics for ax-SpA and so have the biosimilars from the first three of them.[26] Interleukin (IL)-17 is another target, and its blockade has been shown to be successful in ax-SpA, which led to the approval of secukinumab, an antibody against IL-17 a few years ago[27] and for other IL-17 inhibitors promising clinical trials are ongoing.[28]

Moreover, other therapeutic targets, mainly Janus Kinase inhibition that has already been proven to be very successful in the therapy of rheumatoid arthritis is another option on the horizon for the treatment of ax-SpA.[29]

Physiotherapy also is a another pivotal aspect of ax-SpA therapy. Thus, patients should start with it immediately after the diagnosis. In addition, patients should perform daily exercises to maintain their mobility and functionality.

Furthermore, according to the treat to target recommendations, ax-SpA should be frequently monitored, and disease activity should be evaluated using the distinct instruments.[23]

 Conclusion



Ax-SpA belongs to the most common inflammatory rheumatic diseases, and its main challenge remains the early diagnosis which requires adequate knowledge about the disease. To reduce the delay in diagnosis, it is important that several disciplines such as general practitioners, orthopaedics and physiotherapists work together with a rheumatologist in a network that guarantees rapid assessment once a patient is suspected of suffering from ax-SpA.

Financial support and sponsorship

The author received honorarium as a speaker and/or Consultant from the following companies.: Abbvie,. Astro-Pharma, BMS, Celgene, Lilly, MSD, Novartis-Sanofi, Sobi, UCB.

Conflicts of interest

There are no conflicts of interest.

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