Overview of Spondyloarthropathies

Introduction[edit | edit source]

Spondyloarthropathy (or spondyloarthritis) is an umbrella term for a group of inflammatory rheumatic diseases.[1][2] It is considered a common condition, but there is significant variation in the reported prevalence rates of spondyloarthropathy and its subgroups.[3]

Spondyloarthropathies are progressive and painful. They often involve the axial skeleton (i.e. the spine and the sacroiliac joints), but they can also affect the peripheral skeleton.[1] They are associated with enthesitis (inflammation of the site where tendons / ligaments insert into bone[4]) and dactylitis (i.e. diffuse swelling of the digits[5]). Other areas affected include the heart, eyes, lungs, skin, gut and genitourinary tract.[2]

There are five types of spondyloarthritis:[1]

Epidemiology / Aetiology[edit | edit source]

Symptoms associated with spondyloarthropathy typically start before the age of 45.[1] They affect men and women almost equally, with a 1.1:1 (male: female) ratio, although men tend to be younger at diagnosis than women.[1][9] With a prevalence rate of 0.5-1.9 percent, they are one of the most common rheumatic diseases - as common as rheumatoid arthritis.[10] However, unlike other rheumatic diseases, spondyloarthropathies are seronegative for rheumatoid factors.[11]

"So, unlike other rheumatic diseases, such as rheumatoid arthritis, the spondyloarthropathies are often negative for acute-phase inflammatory markers, such as C-reactive protein. They may be mildly raised, but certainly aren't often raised as much as would be in some other rheumatic diseases."[1] -- Christopher Martey

The aetiology and pathogenesis of spondyloarthropathies are complex and not fully understood. An initial systemic inflammatory response to a known or unknown source causes local tissue changes. These changes can be long-lasting in the local joint environment, and the persistent inflammation causes a cycle of unbalanced bone remodelling and axial bone loss.[12]

While the cause of spondyloarthropathy is not known, research suggests that there are environmental and genetic triggers.[2] In particular, spondyloarthropathies have been found to share genetic links with the HLA-B27 gene.[1][13] 90 percent of patients with axial spondyloarthritis have this gene. However, having this gene is not, in itself, diagnostic of spondyloarthropathy, as five to ten percent of patients who carry the HLA-B27 gene do not go on to develop these conditions.[1]

This optional video provides a general overview of spondyloarthropathy.

[14]

Characteristics / Clinical Presentation[edit | edit source]

Back pain is extremely prevalent. [15] The occurrence of back pain lasting for three months or longer and back pain onset before 45 years of age is a starting point for the diagnosis of spondyloarthritis.[15] It is important to be able to differentiate between different types of back pain (i.e. mechanical or inflammatory back pain), and the different types of spondyloarthropathy. The specific features of each type of spondyloarthropathy are discussed below.

Axial Spondyloarthritis[edit | edit source]

Axial spondyloarthritis is the prototypic form of spondyloarthropathy.[16] Patients with axial spondyloarthritis (axSpA) can have either non-radiographic or radiographic axial spondyloarthritis. Radiographic axial spondyloarthritis (r-axSpA) is also called ankylosing spondylitis.[17] While non-radiographic axial spondyloarthritis (nr-axSpA) does not show on x-ray, changes are evident on MRI.[1]

Axial spondyloarthritis tends to start when patients are aged in their 20s. There is a male-to-female ratio of 2:1 for radiographic axial spondyloarthritis and 1:1 for non-radiographic axial spondyloarthritis.[17]

Axial spondyloarthritis predominantly affects the spine, with inflammatory changes causing pain, stiffness and a loss of motion in the back.[1][18] Patients will often present with impaired spinal movement, abnormal posture, buttock and hip pain, peripheral arthritis, enthesitis and dactylitis.[18]

"The inflammatory changes that occur don't just cause pain, but also ongoing stiffness and a loss of range of motion throughout the spine. This can lead to progressive deformity and the change in posture. Not only that, these painful conditions affect one's sleep and also have a huge impact on fatigue. This affects their livelihood, also how they interact with their loved ones and also their work productivity."[1] -- Christopher Martey

The following optional video provides a short summary of the main features of axial spondyloarthritis.

[19]

It has been estimated that axial spondyloarthritis has a heritability of 90%, with the HLA-B27 gene being the most significant genetic factor.[17][18][20] The actual role of HLA-B27 in the pathogenesis of axial spondyloarthritis remains unclear, but evidence suggests that the cytokines, tumour necrosis factor (TNF)-α and interleukin-17 are involved.[17]

Radiographic axial spondyloarthritis has also been linked to an increased risk of cardiovascular disease due to the systemic inflammation associated with this condition. Because it results in diminished chest wall expansion and decreased spinal mobility, it can lead to a restrictive pulmonary pattern in individuals with this condition. These individuals are also more prone to vertebral fragility fractures, atlantoaxial subluxation, spinal cord injury and, occasionally, cauda equina syndrome.[18]

The following optional video presents the key features of axial spondyloarthritis.

[21]

For more information on axial spondyloarthritis, please click here.

Psoriatic Arthritis[edit | edit source]

Psoriatic Arthritis (PsA) is a chronic, immune-mediated inflammatory joint disease associated with psoriasis.[22] It is also known as peripheral spondyloarthritis. Individuals present with joint and entheses inflammation in both the axial skeleton and peripheral joints. It affects multiple organs, including the skin and is associated with an increased risk of mortality from cardiovascular disease.[22][23]

There is a wide variation in the annual incidence of PsA, ranging from 0.1 to 23.1 cases per 100,000. Prevalence rates also vary between countries, as does the mean age at diagnosis (40.7 to 52.0 years).[24]

Hallmark features of PsA are:[24]

  • the presence of psoriasis
  • inflammatory arthritis
  • absence of serological tests for rheumatoid arthritis

Between 60 and 70 percent of patients will develop psoriasis before PsA. However, in 15 to 20 percent of patients, symptoms of arthritis develop first. For 15 to 20 percent of individuals, psoriasis and arthritis will begin within a year.[24]

For more information on PsA, please see Psoriatic Arthritis. The following optional video also provides a general overview of PsA.

[25]

Enteropathic Arthritis[edit | edit source]

Enteropathic Arthritis (EnA) is a spondyloarthropathy that occurs in patients who also have inflammatory bowel disease (IBD) and/or other gastrointestinal diseases, such as ulcerative colitis and Crohn’s disease.[26]

There is no gold standard test for EnA, so diagnosis generally relies on medical history and physical examination.[26] Typically, patients who have IBD and then go on to develop inflammatory back pain and/or synovitis (predominantly in the lower limbs) are diagnosed as having spondyloarthropathy.[26] Women are more likely to have peripheral joint involvement, whereas men are more likely to experience axial skeleton symptoms.[26]

Between 17 and 39 percent of patients with IBD develop rheumatic manifestations. Between two and 16 percent of IBD patients develop EnA in the axial skeleton. The prevalence of sacroiliitis in this population is between 12 and 20 percent of patients.[26]

Like other spondyloarthropathies, there is an association with the HLA-B27 gene, ranging from 3.9 to 18.9 per cent, but the pathogenesis is not fully understood.[26] However, it has been observed that joint inflammation occurs in patients who are genetically predisposed and who have bacterial gut infections. This, therefore, suggests that there is some relationship between inflammation of the gut mucosa and arthritis.[26]

For more information on EnA, please click here.

Reactive Arthritis[edit | edit source]

Reactive arthritis (ReA) is a seronegative spondyloarthropathy, which occurs after an extra-articular infection (usually of the gastrointestinal or genitourinary tract).[27][28] It is associated with inflammatory back pain, oligoarthritis, and extra-articular symptoms.[28] It tends to develop between one and six weeks after a urogenital or gastrointestinal infection.[28][29]

A classic triad of symptoms has been identified:[30]

Dermatological manifestations (such as keratoderma blennorrhagicum, circinate balanitis, ulcerative vulvitis, changes in nails, and oral lesions) can occur.[30] It can also affect the heart and eyes, although symptom severity is varied.[28]

ReA is more common in men[30] and typically affects young adults.[28] Its exact pathophysiology is not yet understood, but it appears likely that infectious and immune factors are involved.[30] Again, those affected are more likely to carry the HLA-B27 gene.[28]

The following optional video provides an overview of the characteristics of ReA.

[31]

Clinical symptoms can be distinguished from septic arthritis. Key signs of septic arthritis are:[28]

  • fever
  • systemic signs of infection
  • monoarthritis

For more information on ReA, please see Reactive Arthritis.

Undifferentiated Spondyloarthritis[edit | edit source]

A diagnosis of undifferentiated spondyloarthropathy is given in cases where individuals exhibit features of spondyloarthropathy, but they do not fit into any of the conditions discussed above.[32] It usually occurs in less than five joints and often involves the knee joint.[33]

Delay to Diagnosis[edit | edit source]

It is important to note that there is often a significant delay in diagnosing these conditions. Reasons for this delay may include:[1]

  • presenting at a young age
  • potentially being missed as a mechanical presentation (rather than inflammatory)
  • lack of healthcare professional and community awareness about these conditions
  • lack of recognition
  • lack of appropriate referrals

On average, the delay to diagnosis is around 8.5 years.[1] Delays are significant because early diagnosis results in better outcomes in terms of disease activity, function, spinal mobility and radiographic damage, as well as a better response to treatment.[34]

"Eight and a half years is too long. [...] But this delay to diagnosis is something that we, as clinicians can really work towards to cut down. If we identify the signs early, suspect spondyloarthritis and refer through to specialist, secondary care rheumatology, we might all be able to better change the management of these patients."[1] -- Christopher Martey

Summary[edit | edit source]

  • Spondyloarthropathy is an umbrella term that encompasses five inflammatory rheumatic diseases:
    • Axial spondyloarthritis
    • Psoriatic arthritis
    • Reactive arthritis
    • Enteropathic arthritis
    • Undifferentiated spondyloarthritis
  • These conditions can impact multiple areas of the body, including joints and entheses, as well as other organs.
  • While the specific aetiology remains unknown, current research suggests a strong genetic component and specific environmental triggers.
  • Understanding the signs of spondyloarthropathy is essential to help ensure appropriate referrals and better outcomes for these individuals

References[edit | edit source]

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 Martey C. Overview of Spondyloarthropathies Course. Plus, 2020.
  2. 2.0 2.1 2.2 Ehrenfeld M, Infection and spondyloarthropathies. In: Shoenfeld Y, Agmon-Levin N, Rose NR editors. Infection and autoimmunity. Elsevier B.V. 2015. p745-57.
  3. Stolwijk C, van Onna M, Boonen A, van Tubergen A. Global prevalence of spondyloarthritis: a systematic review and meta-regression analysis. Arthritis Care Res (Hoboken). 2016 Sep;68(9):1320-31.
  4. Schett G, Lories R, D'Agostino M, Elewaut D, Krikham B, Soriano ER et al. Enthesitis: from pathophysiology to treatment. Nat Rev Rheumatol. 2017; 13: 731–741.
  5. Girolimetto N, Giovannini I, Crepaldi G, De Marco G, Tinazzi I, Possemato N, Macchioni P, McConnell R, McGonagle D, Iagnocco A, Zabotti A. Psoriatic Dactylitis: Current perspectives and new insights in ultrasonography and magnetic resonance imaging. Journal of Clinical Medicine. 2021 Jun 12;10(12):2604.
  6. Fragoulis GE, Siebert S. Treatment strategies in axial spondyloarthritis: what, when and how?. Rheumatology. 2020 Oct;59(Supplement_4):iv79-89.
  7. Ogdie A, Coates LC, Gladman DD. Treatment guidelines in psoriatic arthritis. Rheumatology. 2020 Mar 1;59(Supplement_1):i37-46.
  8. Bentaleb I, Abdelghani KB, Rostom S, Amine B, Laatar A, Bahiri R. Reactive arthritis: update. Current clinical microbiology reports. 2020 Dec;7(4):124-32.
  9. Alzate M, Vargas F, Ramirez F, et al. SAT0414 Differences in a clinical presentation by gender in Colombian patients with spondyloarthropathies. Annals of the Rheumatic Diseases 2017;76(2): 928.
  10. Rudwaleit M, van der Heijde D, Khan MA, Braun J, Sieper J. How to diagnose axial spondyloarthritis early. Annals of the Rheumatic Diseases. 2004; 63: 535-543.
  11. Navallas M, Ares J, Beltrán B, Lisbona MP, Maymó J, Solano A. Sacroiliitis associated with axial spondyloarthropathy: new concepts and latest trends. Radiographics. 2013 Jul-Aug;33(4):933-56.
  12. Lassiter W, Allam AE. Inflammatory Back Pain. [Updated 2020 Jun 22]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK539753/
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  19. Novartis. More than just back pain, what is Axial Spondyloarthritis (axSpA)? Available from: https://www.youtube.com/watch?v=iN2EiKKKJss [last accessed 9/11/2020]
  20. Ebrahimiadib N, Berijani S, Ghahari M, Pahlaviani FG. Ankylosing Spondylitis. J Ophthalmic Vis Res. 2021 Jul 29;16(3):462-469.
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  22. 22.0 22.1 Veale DJ, Fearon U. The pathogenesis of psoriatic arthritis. Lancet. 2018; 391(10136): 2273-2284.
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  24. 24.0 24.1 24.2 Kerschbaumer A, Fenzl KH, Erlacher L, Aletaha D. An overview of psoriatic arthritis - epidemiology, clinical features, pathophysiology and novel treatment targets. Wien Klin Wochenschr. 2016; 128(21-22): 791-795.
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  27. Courcoul A, Brinster A, Decullier E, Larbre JP, Piperno M, Pradat E et al. A bicentre retrospective study of features and outcomes of patients with reactive arthritis. Joint Bone Spine. 2018; 85(2): 201-205.
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  29. Ono K, Kishimoto M, Shimasaki T, Uchida H, Kurai D, Deshpande GA et al. Reactive arthritis after COVID-19 infection. RMD Open 2020; 6: e001350.
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  32. Chou CT, Lin KC, Wei JCC, Tsai WC, Ho HH, Hwang CM et al. Study of undifferentiated spondyloarthropathy among first-degree relatives of ankylosing spondylitis probands. Rheumatology. 2005; 44(5): 662-5.
  33. Hauk L. Spondyloarthritis: NICE Releases Guidelines on Diagnosis and Treatment. Am Fam Physician. 2017; 96(10): 677-678.
  34. Seo MR, Baek HL, Yoon HH, Ryu HJ, Choi HJ, Baek HJ, Ko KP. Delayed diagnosis is linked to worse outcomes and unfavourable treatment responses in patients with axial spondyloarthritis. Clin Rheumatol. 2015; 34(8): 1397-405.