Axial spondyloarthritis

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Axial spondyloarthritis
Sacroiliac joint.svg
Sacroiliac joint

Axial spondyloarthritis (also often referred to as axSpA) is a chronic, immune-mediated disease predominantly affecting the axial skeleton (sacroiliac joints and spine). [1] The term itself is an umbrella term characterizing a diverse disease family united by shared clinical and genetic features, such as the involvement of the axial skeleton. [2] The 2009 introduced term axial spondyloarthritis is a preferred term nowadays and substitutes the old term ankylosing spondylitis. [3]

Contents

Classification

Along with peripheral spondyloarthritis, reactive arthritis, psoriatic arthritis and enteropathic arthritis (or inflammatory bowel disease-associated spondyloarthritis), axial spondyloarthritis belongs to the spondyloarthritis disease family, also known as the spondyloarthritides or spondyloarthropathies. [4] [5] [6] These arthritic conditions can sometimes overlap with one another. For example, psoriatic arthritis can cause both peripheral and axial symptoms. [7] Likewise, reactive arthritis can transform into chronic axial spondyloarthritis. [8] All are considered inflammatory rheumatic disorders because they involve immune system-mediated attacks on the joints, muscles, bones and organs. [9]

Axial spondyloarthritis can be differentiated from peripheral spondyloarthritis in terms of the areas of the body affected. The axial form of the disease primarily affects the spine, pelvis and thoracic cage, whereas the peripheral form mainly targets the arms and legs. [10]

Axial spondyloarthritis can be divided into two classes:

  1. Non-radiographic axial spondyloarthritis (nr-axSpA):
    This term encompasses both the early disease stage of ankylosing spondylitis, in which no radiographic changes are visible yet, as well as less severe forms of ankylosing spondylitis.
  2. Radiographic axial spondyloarthritis:
    Synonym for ankylosing spondylitis. This class is termed radiographic axial spondyloarthritis due to the unambiguous diagnosis through radiographic changes in the sacroiliac joints and/or spine.

Signs and symptoms

Axial spondyloarthritis is predominantly marked by inflammatory pain and/or stiffness affecting the lower back, hips and/or buttocks. [11] [12] The side affected may alternate. [11] Some may also experience symptoms in the eyes, rib cage, shoulders or cervical spine or neck as well. [12] [13] Inflammatory back pain tends to come on gradually, become worse at night or after periods of rest (such as in the morning after waking up) and improve after exercise or the use of anti-inflammatory medications such as ibuprofen. [11] [12] People with axial spondyloarthritis may experience alternating periods of remission and flare-ups. [14]

It is recommended that patients be formally evaluated for axial spondyloarthritis if they complain of inflammatory back pain and stiffness lasting at least three months, particularly if they are under the age of 45 and/or have a family history of the disease. [11]

Pathophysiology

Significant progress has been made in understanding the genetic and immunological aspects of axSpA. Research has focused on the mechanisms of chronic inflammation and pathological new bone formation, which are characteristic of the disease. The enthesis, a critical site of disease activity, is particularly affected. [15] The role of cytokine dysregulation in the immune pathogenesis of axSpA has been highlighted, with a notable skew towards a Th17 phenotype, tumor necrosis factor (TNF) and interleukin 23 (IL-23) / interleukin 17 (IL-17) pathways and a pro-inflammatory cytokine profile. The disease typically begins with enthesopathic inflammation and progresses to ossifying enthesitis. The molecular pathways involved in syndesmophyte formation are complex, involving factors such as bone morphogenetic protein, Wnt signaling pathway, Dickkopf-1, sclerostin, and various cytokines, all of which are intricately regulated. [16] [17]

Diagnosis

Patients being examined for axial spondyloarthritis may have x-rays, or radiographs, taken of their pelvis to check for signs of sacroilitis (often one of the first manifestations of the disease) and structural damage. [18] It can take several years from symptom onset for these changes to be visible, and some may never develop these changes at all. [19] [20] Their presence distinguishes radiographic axial spondyloarthritis from nr-axSpA.

Patients may also undergo an MRI in place of or in addition to radiography. MRI technology is sensitive to inflammatory changes such as enthesitis and synovitis and is more specific overall. [19] [21]

Blood work may also play a role in the diagnosis of axial spondyloarthritis. More than 80% of patients with the ankylosing spondylitis variant test positive for the HLA-B27 biomarker, but not everyone with this biomarker will develop disease. [22] Some people with axial spondyloarthritis may test positive for elevated C-reactive protein, or CRP, depending on their disease activity. [22] Spondyloarthritis is generally considered to be a seronegative disease, meaning tests for rheumatoid factor and other autoantibodies typically come back negative. [19] [23]

Depending on the results of the above tests, patients may be referred to a rheumatologist for confirmation and follow-up. [24]

Prognosis

Some with more severe disease may experience fusion of their vertebrae, a condition referred to as bamboo spine. [25] Men are more likely to accrue radiographic joint damage, whereas women tend to experience comparatively worse quality of life and disease activity. [26]

Management

There is currently no cure for axial spondyloarthritis, but there are various disease management strategies. [27]

Traditional NSAIDs and COX-2 inhibitor NSAIDs are effective for treating axSpA. [28] The potential harms may not differ when compared to a placebo treatment in the short term. [28] Various NSAIDs are equally effective (e.g.: Cox2 NSAIDS and traditional NSAIDS). [28] Continuous NSAID use may reduce radiographic spinal progression, but this requires confirmation. [28]

Those who cannot tolerate these medications or who require more intensive treatment may be prescribed biologic medications such as a TNF-alpha inhibitor in an attempt to alter the immune response driving the disease. [27]

Physical therapy and exercise have also been found to effectively address symptoms. [29]

In 2019 the American College of Rheumatology, Spondylitis Association of America and Spondyloarthritis Research and Treatment Network published updated recommendations for the treatment of the condition [30] based on updated literature reviews.

History

In 1984, a joint effort led to the definition of specific classification criteria for ankylosing spondylitis, called the "Modified New York criteria". [31] One of the central New York criteria was the existence of radiographically visible changes in the sacroiliac joints and/or spine, which have formed due to bone fusion, erosion and/or formation caused by the disease. [32] Even though these criteria helped to improve uniformly define ankylosing spondylitis, such radiologic changes often only manifested several years after the first disease symptoms appeared. [32] In order to be able to study also patients with early and less typical forms, new criteria were needed that could identify the disease already at an early stage. In 2009 the Modified New York criteria were extended by a broad set of new classification criteria that aimed to classify patients based on the presence of typical spondyloarthritis disease features. [2] These included inflammatory back pain, family history for axial spondyloarthritis, response to treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), history of or current inflammation in the joints (arthritis), tendon-bone attachment of the heel (enthesitis), or eyes (uveitis), bowel (inflammatory bowel disease), skin (psoriasis) or signs of elevated inflammation (C-reactive protein and erythrocyte sedimentation rate). [2] [33] Important parts of the ASAS axSpA criteria are the biomarker HLA-B27 and magnetic resonance imaging (MRI). [2] [33] The criteria can only be applied in people that have chronic back pain (at least 3 months duration) started before the age of 45 years and only in those patients that already have a diagnosis of axial SpA. Since the disease ankylosing spondylitis was still defined by the Modified New York criteria of 1984, there was the need to find a new disease term that would also include the less severe forms or early onset of ankylosing spondylitis. This expression was found in the umbrella term axial spondyloarthritis. The 2009 classification criteria are called the ASAS (Assessment of SpondyloArthritis international Society) classification criteria for axial spondyloarthritis. [34] [35]

Society and culture

Notable cases

Related Research Articles

<span class="mw-page-title-main">Rheumatoid arthritis</span> Type of autoimmune arthritis

Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involved, with the same joints typically involved on both sides of the body. The disease may also affect other parts of the body, including skin, eyes, lungs, heart, nerves, and blood. This may result in a low red blood cell count, inflammation around the lungs, and inflammation around the heart. Fever and low energy may also be present. Often, symptoms come on gradually over weeks to months.

<span class="mw-page-title-main">Ankylosing spondylitis</span> Type of arthritis of the spine

Ankylosing spondylitis (AS) is a type of arthritis characterized by long-term inflammation of the joints of the spine, typically where the spine joins the pelvis. With AS, eye and bowel problems—as well as back pain—may occur. Joint mobility in the affected areas sometimes worsens over time. Ankylosing spondylitis is believed to involve a combination of genetic and environmental factors. More than 90% of people affected in the UK have a specific human leukocyte antigen known as the HLA-B27 antigen. The underlying mechanism is believed to be autoimmune or autoinflammatory. Diagnosis is based on symptoms with support from medical imaging and blood tests. AS is a type of seronegative spondyloarthropathy, meaning that tests show no presence of rheumatoid factor (RF) antibodies.

<span class="mw-page-title-main">HLA-B27</span> Type of antigen

Human leukocyte antigen (HLA) B27 is a class I surface molecule encoded by the B locus in the major histocompatibility complex (MHC) on chromosome 6 and presents antigenic peptides to T cells. HLA-B27 is strongly associated with ankylosing spondylitis and other associated inflammatory diseases, such as psoriatic arthritis, inflammatory bowel disease, and reactive arthritis.

Spondyloarthritis (SpA), also known as spondyloarthropathy, is a collection of clinical syndromes that are connected by genetic predisposition and clinical manifestations. The best-known clinical subtypes are enteropathic arthritis (EA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and reactive arthritis (ReA). Spondyloarthritis typically presents with inflammatory back pain and asymmetrical arthritis, primarily affecting the lower limbs, and enthesitis, inflammation at bone-adhering ligaments, tendons, or joint capsules.

<span class="mw-page-title-main">Rheumatism</span> Medical conditions affecting the joints or connective tissue

Rheumatism or rheumatic disorders are conditions causing chronic, often intermittent pain affecting the joints or connective tissue. Rheumatism does not designate any specific disorder, but covers at least 200 different conditions, including arthritis and "non-articular rheumatism", also known as "regional pain syndrome" or "soft tissue rheumatism". There is a close overlap between the term soft tissue disorder and rheumatism. Sometimes the term "soft tissue rheumatic disorders" is used to describe these conditions.

Etanercept, sold under the brand name Enbrel among others, is a biologic medical product that is used to treat autoimmune diseases by interfering with tumor necrosis factor (TNF), a soluble inflammatory cytokine, by acting as a TNF inhibitor. It has US Food and Drug Administration (FDA) approval to treat rheumatoid arthritis, juvenile idiopathic arthritis and psoriatic arthritis, plaque psoriasis and ankylosing spondylitis. Tumor necrosis factor alpha (TNFα) is the "master regulator" of the inflammatory (immune) response in many organ systems. Autoimmune diseases are caused by an overactive immune response. Etanercept has the potential to treat these diseases by inhibiting TNF-alpha.

<span class="mw-page-title-main">Reactive arthritis</span> Inflammatory arthritis triggered by infection elsewhere in the body

Reactive arthritis, also known as Reiter's syndrome, is a form of inflammatory arthritis that develops in response to an infection in another part of the body (cross-reactivity). Coming into contact with bacteria and developing an infection can trigger the disease. By the time the patient presents with symptoms, often the "trigger" infection has been cured or is in remission in chronic cases, thus making determination of the initial cause difficult.

<span class="mw-page-title-main">Sacroiliitis</span> Medical condition

Sacroiliitis is inflammation within the sacroiliac joint. It is a feature of spondyloarthropathies, such as axial spondyloarthritis, psoriatic arthritis, reactive arthritis or arthritis related to inflammatory bowel diseases, including ulcerative colitis or Crohn's disease. It is also the most common presentation of arthritis from brucellosis.

<span class="mw-page-title-main">Certolizumab pegol</span> Pharmaceutical drug

Certolizumab pegol, sold under the brand name Cimzia, is a biopharmaceutical medication for the treatment of Crohn's disease, rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. It is a fragment of a monoclonal antibody specific to tumor necrosis factor alpha (TNF-α) and is manufactured by UCB.

<span class="mw-page-title-main">Enthesitis</span> Medical condition

Enthesitis is inflammation of the entheses ), the sites where tendons, ligaments and joint capsules attach to bones.

The BASDAI or Bath Ankylosing Spondylitis Disease Activity Index is a validated diagnostic test which allows a physician, usually a rheumatologist, to determine the effectiveness of a current drug therapy, or the need to institute a new drug therapy for the treatment of Ankylosing spondylitis (AS). The BASDAI is one of a group of classification criteria for spondyloarthropathies.

Biological response modifiers (BRMs) are substances that modify immune responses. They can be endogenous or exogenous, and they can either enhance an immune response or suppress it. Some of these substances arouse the body's response to an infection, and others can keep the response from becoming excessive. Thus they serve as immunomodulators in immunotherapy, which can be helpful in treating cancer and in treating autoimmune diseases, such as some kinds of arthritis and dermatitis. Most BRMs are biopharmaceuticals (biologics), including monoclonal antibodies, interleukin 2, interferons, and various types of colony-stimulating factors. "Immunotherapy makes use of BRMs to enhance the activity of the immune system to increase the body's natural defense mechanisms against cancer", whereas BRMs for rheumatoid arthritis aim to reduce inflammation.

<span class="mw-page-title-main">Golimumab</span> Pharmaceutical drug

Golimumab, sold under the brand name Simponi, is a human monoclonal antibody which is used as an immunosuppressive medication. Golimumab targets tumor necrosis factor alpha (TNF-alpha), a pro-inflammatory molecule and hence is a TNF inhibitor. Profound reduction in C-reactive protein (CRP) levels, interleukin (IL)-6, intercellaular adhesion molecules (ICAM)-1, matrix metalloproteinase (MMP)-3, and vascular endothelial growth factor (VEGF) demonstrates golimumab as an effective modulator of inflammatory markers and bone metabolism. Golimumab is given via subcutaneous injection.

<span class="mw-page-title-main">Enteropathic arthropathy</span> Medical condition

Enteropathic arthropathy commonly referred to as enteropathic arthritis, is a type of arthritis linked to Crohn's disease, ulcerative colitis, and chronic inflammatory bowel diseases.

<span class="mw-page-title-main">Secukinumab</span> Monoclonal antibody against IL-17

Secukinumab, sold under the brand name Cosentyx among others, is a human IgG1κ monoclonal antibody used for the treatment of psoriasis, ankylosing spondylitis, and psoriatic arthritis. It binds to the protein interleukin (IL)-17A and is marketed by Novartis.

The Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire is a patient-reported outcome (PRO) measure which assesses the quality of life of patients with ankylosing spondylitis. The ASQoL is based on the needs-based quality of life model. It is a self-administered questionnaire which contains 18 items and takes up to four minutes to complete.

Interleukin-38 (IL-38) is a member of the interleukin-1 (IL-1) family and the interleukin-36 (IL-36) subfamily. It is important for the inflammation and host defense. This cytokine is named IL-1F10 in humans and has similar three dimensional structure as IL-1 receptor antagonist (IL-1Ra). The organisation of IL-1F10 gene is conserved with other members of IL-1 family within chromosome 2q13. IL-38 is produced by mammalian cells may bind the IL-1 receptor type I. It is expressed in basal epithelia of skin, in proliferating B cells of the tonsil, in spleen and other tissues. This cytokine is playing important role in regulation of innate and adaptive immunity.

In radiology, a Romanus lesion is the erosion of the anterior and posterior vertebral endplates in patients with an inflammatory spondyloarthropathy – such as ankylosing spondylitis or an enteropathic arthropathy. The anterior erosion in particular causes a loss of anterior vertebral body concavity, causing the vertebra to display a squared contour or even a barrel-shape. Healing of the erosion results in a sclerotic increase in density causing what is known as a shiny corner sign, which can later result in syndesmophyte formation. It is most easily diagnosed using MRI, compared to conventional radiography.

Diagnostic delay is the time interval between the onset of symptoms and confirmed diagnosis of a disease. For a variety of reasons, including the mitigation of disease severity and financial expense, it is desirable for this delay to be minimized.

<span class="mw-page-title-main">Josef Smolen</span> Austrian Rheumatologist

Josef Smolen is an Austrian rheumatologist and immunologist and professor emeritus at the Medical University of Vienna. Since 2018 he is chairman emeritus of the Department of Internal Medicine 3 and the Division of Rheumatology at the Medical University of Vienna and Vienna General Hospital and was the chairman of the 2nd Medical Department and Center for Diagnosis and Therapy of Rheumatic Diseases at the Lainz Hospital, now the Hietzing Clinic of the Vienna Health Association from 1989 to 2017.

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