Spondyloarthropathy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief:

Spondyloarthropathy or Spondyloarthrosis are entities refer to any kind of joint disease of vertebral column (spine), albeit it demonstrate a class or category of diseases more than a single entity. Another entity in disease of vertebra itself is spondylopathy, which is founded mostly with spondyloarthropathy. Th term of spondyloarthropathy in the broadest sense, includes any type of joint involvement of vertebral column such as rheumatoid arthritis and osteoarthritis, however, the term is often used for a certain group of disease with specific common features, which eventuate to call them as a seronegative spondyloarthropathies due to their negative serum rheumatoid factor and ANA, with an increased incidence of HLA-B27.^[1][2]

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• The first clinical description of AS is credited to Bernard Conner (1666 – 1698), an Irish physician who did this in his medical thesis. At early 1690s, Bernard Connor discovered fortuitously one specimen of a fused spine and thorax, which is now recognized as the skeleton with incontrovertible AS changes .The previous history has been developed according to Bywaters in to five stages from the ‘fossil’ stage (1693–1824) over the clinical description (1824–1885) to the clinical and pathological correlations (1884 – 1898), radiological ‘penetration’ and ‘insight’ (1897 – 1931), and finally epidemiology and family studies (1936–1950).

• Till 1950s, RA was considered as s nonspecific syndrome that could be triggered off by various diverse etiological factors such as urethritis, psoriasis, and ulcerative colitis.

• As early as 1954, the French rheumatologist Jean Marche for the first time suggested that AS and Reiter’s syndrome are two aspects of the same disease.

• Oates in 1959 also questioned if AS and Reiter’s syndrome may have the same origin.

• Bernard Amor in 1968 further advanced the view of the inter-relationship of this two entities reviewing reports on endemic Reiter’s syndrome with the frequent outcome as AS and a postulated common genetic background.

• Finally, from the study on psoriatic arthritis and other work on seronegative arthritis Moll et al. formulated the pivotal

• Unified concept of a group of seronegative arthritides termed spondarthritides closely interlinked by clinical, serological, radiological, and genetic features. The evidence for lumping together a group of diseases derived from clinical associations, familial aggregation, and epidemiological studies.^[1]

spondyloarthropathies (SpA) are a group of inflammatory arthritis that consist of ankylosing spondylitis (AS), juvenile onset arthritis, reactive arthritis, non-radiographic ankylosing spondylitis, psoriasis arthritis, and inflammatory bowel disease associated arthritis.

Classification criteria ,that combine different type of information such as imaging, laboratory findings, symptoms, and signs, have been made to describe and define groups for better understanding of clinical and epidemiological studies.

Assessment of spondyloarthritis international society (ASAS criteria) have been widely used to classify the axial spondyloarthritis, which have been described as back pain more than or equal to 3 months and age of onset less than 45 years. ASAS suggest these two sort of criteria:

• Sacroiliitis on imaging plus 1 SpA feature. or
• HLA-B27 plus 2 other SpA features

Sacroiliitis on imaging will be describe as:

• Active inflammation on MRI highly suggested of SpA-assocoated sacroiliitis and/or
• Definite radiograohic sacroiliitis

SpA features:

• Inflammatory back pain
• Arthritis
• Enthesitis
• Anterior uveitis
• Dactylitis
• Psoriasis
• Crohn’s disease or ulcerative colitis
• Good response to NSAID
• Family history of SpA
• HLA-B27
• Elevated CRP

• Ankylosing spondylitis
• Axial spondylitis
• Peripheral spondylitis
• spondylitis in general
• Psoriatic arthritis

Spondyloarthropathies (SpA) is an inflammatory disease, which mainly affect the axial skeleton and peripheral joints same as other rheumatic disease but with different pathophysiology. there are two main processes that eventuate in symptoms of this disease:

• Inflammation of bone marrow or entheses
  • This can cause pain and stiffness in affected joints
• Ankylosis (overgrowth of the bone)
  • Eventuate in impaired function of the spine and reduction in range of motion of affected joints

Association of SpA with HLA-B27 gene have been known since 1973. In 95% of patients with Ankylosing spondylitis (AS) this allele is present, however, the reason why HLA-B27 is really strongly correlated to SpA is somehow uncleared.

There are some key points that can help to find the mechanism of SpA :

• SpA does not display the prototypical genetic, clinical and immunological features of T-cell and/or B-cell- mediated autoimmune diseases.
• B-cell and T-cell targeted therapies are not effective in SpA
• HLA-B27-dependent UPR leads to augmented IL-23 production, but the role of UPR in vivo remains to be investigated in more detail.
• Alternative macrophage polarization is a hallmark of SpA.
• Innate immune cells rather than T cells are the main producers of IL-17 in SpA.

The genetic responsibility in SpA have been discussed and is concluded in numerous studies, albeit, by the advent of new technological devices, HLA-B27 subtypes are known better than before.

In the table below association of some genes and their association in the specific type of SpA are described

Not only HLA-B gene are suspected for SpA, but also there are other genes that their association in presence of SpA are under investigation, which included:

• HLA-B (Associated with Ankylosing spondylitis )
• ERAP1 (Associated with Ankylosing spondylitis )
• IL23R (Associated with Ankylosing spondylitis )
• TNFRSF1A (Probably associated with Ankylosing spondylitis )
• TRADD (Probably associated with Ankylosing spondylitis )
• TNFRSF15 (Probably associated with Ankylosing spondylitis )
• IL1A (Probably associated with Ankylosing spondylitis )
• IL1R2 (Probably associated with Ankylosing spondylitis )
• CARD9 (Probably associated with Ankylosing spondylitis )
• ANTXR2 (Probably associated with Ankylosing spondylitis )

Albiet, all the progresses have been made through investigating the cause of spondyloarthropathies, the exact cause of this disease remained unclear, however, the role of genetic have been seen through numerous studies have been made in this field of study. Studies demonstrated the role of HLA-B27 in the occurrence of spondyloarthropathies.

Here are some locus, gene, and function of definite and probable genetic risk factors for SpA.

The diagnosis of spondyloarthropathies are generally based on the various clinical criteria and some symptoms and signs such as Inflammatory back pain enthesitis or arthritis with radiographic findings.

• Ankylosing spondylitis
• Axial spondylitis
• Peripheral spondylitis
• spondylitis in general
• Psoriatic arthritis

Here are some clinical criteria which have been made throughout different studies to make the diagnosis even more specific and sensitive. These criteria are: 1-ESSG ( The European spondyloarthropathy study group) 2- Amor criteria 3- New York criteria 4- Rome criteria

The New York criteria For diagnosis AS (Clinical and radiographic)

• Chest expansion limitation to 1 inch or less ( measured in 4th intercostal space)
• History or presence of pain in thoracolumbar junction or lumbar spine
• Limitation of the lumbar spine rotation in all directions

Grading of radiographic sacroiliac changes :

• Grade 0 → Normal
• Grade 1 → Suspicious
• Grade 2 → Minimal sacroiliitis
• Grade 3 → Moderate sacroiliitis
• Grade 4 → Ankylosis

Spondyloarthropathy (SpA) is a world wide disease but it has been seen mostly throughout Europe, Asia, North Africa, and North America, which are the places for presence of HLA-B27. SpA and HLA-B27 is somehow absent among genetically unmixed native populations of South Africa and Australia.

Here are some labeled data that shows not only the prevalence of spondyloarthropathies but also the prevalence of HLA-B27 and its subtype.

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Since the role of genetic in the presence of spondyloarthropathies have been known since several years ago, genetically predisposing individuals are who have HLA-B27 gene, are at risk of developing spondyloarthropathies.

The risk of developing spondyloarthropathies in individuals with HLA-B27 gene is 1-2%, however, it can increase to 15-20% if he/she have a first-degree relative with positive HLA-B27 gene and developed spondyloarthropathy.

There some genes that are suspicious for their association in SpA, which are included:

• HLA-B27
  • HLA-B*2702 (Association with AS)
  • HLA-B*2704 (Association with SpA)
  • HLA-B*2705 (Strong association with AS)
  • HLA-B*2706 (Very weak association with SpA)
  • HLA-B*2709 (AS sparing)
• ERAP1
• IL23R
• TNFRSF1A
• TRADD
• TNFSF15
• IL1A
• IL1R2
• CARD9
• ANTXR2

There is not specific screening test for diagnosis of Spondyloarthropathy

Since spondyloarthropathies categorize into different type, each category can have their complication. The most common disease of this category is Ankylosing spondylitis and at the next one is Psoriasis arthritis.

individuals with psoriasis may develop the following complications:

• High-output cardiac failure in erythroderma
• Psoriatic arthritis
• Infections
• Cachexy
• Amyloidosis
• Common complications of ankylosing spondylitis(AS) include:
  • Acute anterior uveitis
  • Inflammatory bowel disease
  • Psoriasis
  • Psychosocial  issues
  • Cardiovascular problems
  • Pulmonary problems
  • Osteopenia
  • Fractures
  • Neurologic manifestations
  • Renal manifestations

Due to recent biological treatment of spondyloarthropathies, complications of these medications are important, which included:

• Anti-TNF medications given during the management of spondyloarthropathy may lead to:
  • Progressive multifocal leukoencephalopathy
  • Optic neuritis
  • Transverse myelitis
  • Multiple sclerosis
  • Infections

• It is hard to predict the lon-term outcome of the spondyloarthropathy and its treatment in each individual’s life due to its variation among people, however it is obvious that its prognosis is better than other rheumatologic disease such as rheumatoid arthritis.
• At the onset of the disease, symptoms may be intermittent, unilateral and received by less aggressive treatment, though by the progression of the disease, symptoms may be gone constant and sever.
• Sever constant disability is not common among individuals with Spondyloarthropathies.
• Psychological assistance may be required due to the chronic feature of the disease.