Ankylosing Spondylitis

Definition

Ankylosing spondylitis (AS) is a chronic inflammatory arthritis predominantly affecting the facet joints of the spine and the sacroiliac joints, leading to pain, stiffness, and potential fusion of the vertebrae. It often begins in the lower back and can progressively involve other joints, causing reduced flexibility and impaired posture.

Aetiology

AS is recognized as a multifactorial condition influenced by genetic, environmental, and immunological factors. While the precise aetiology of AS remains uncertain, HLA-B27 stands out as the most prominent genetic marker in AS. This is underscored by the observation that approximately 90% of individuals with AS exhibit this genetic mutation, making it a strong predispositional factor for developing AS. The hypothesis is that HLA-B27 may trigger an aberrant immune response by presenting specific self-antigens to immune cells, yet further research is required to validate this hypothesis.

Pathophysiology

The pathophysiology of AS is intricate and not entirely clear. Inflammation, playing a central role in the disease, particularly affects the entheses, junctions where ligaments and tendons attach to bones. Two of the key inflammatory cytokines orchestrating this inflammatory cascade, are tumor necrosis factor-alpha (TNF-alpha) and interleukin-17 (IL-17).

As inflammation persists, concurrent bone remodelling processes take place. Osteoclasts, responsible for bone resorption become hyperactive, leading to bone loss. Meanwhile, osteoblasts, responsible for bone growth, try to repair the damaged bone. Eventually, this dynamic interplay can culminate in the development of syndesmophytes, bony outgrowths bridging joint spaces. In severe cases, this transformative process can progress to ankylosis, known as the fusion or stiffening of affected joints, which characterizes AS.

Signs and symptoms

Ankylosing Spondylitis follows a characteristic episodic course marked by subtle early symptoms that gradually intensify over time. The typical presentation includes chronic lower back pain and stiffness, particularly present in the morning or after periods of inactivity, with a noteworthy alleviation of symptoms upon engaging in physical activity. The primary affected joints are the vertebral joints typically displaying a symmetrical involvement, and the sacroiliac joints, which initially might exhibit an asymmetric pattern, that progresses to bilateral involvement.

Apart from the axial skeleton, the disease can lead to additional manifestations. These include asymmetric oligoarticular peripheral arthritis often impacting shoulders, hips, knees, feet, and enthesiopathies, most commonly affecting the Achilles tendon (Achillodynia).

In advanced AS, spinal ankylosis can result in reduced thoracic expansion causing difficulties in breathing and chest pain. Additionally, the increased spine stiffness poses a threat, to vertebral transverse fractures, known as “Chalk Stick Fractures”, which can potentially result in spinal cord injuries.

Throughout the progression of the disease, extra-articular symptoms can arise, including:

  • Anterior uveitis (observed in approximately a quarter of patients)

  • AV-block 

  • Aortitis with concomitant aortic valve insufficiency

  • Interstitial lung disease primarily affecting the apical lobes

Diagnosis

Clinical evaluation

The combination of the following clinical tests, along with the characteristic presentation of lower back pain that worsens during rest and improves with activity, can contribute to the accurate diagnosis of AS.

  • Schober's Test: In Schober's Test, the patient stands upright as two marks are made along the midline – one at the lumbosacral junction (S1) and another 10 cm above it. While bending forward, the distance between these marks is re-measured. An increase of less than 5 suggests limited lumbar spine flexion, indicating AS.

  • Mennel's Sign: In this test, the patient lies prone, and the examiner palpates the posterior superior iliac spine (PSIS) of one side. While maintaining pressure on the PSIS, the examiner instructs the patient to hyperextend the leg on the same side. The onset of pain or symptom reproduction suggest degenerative or inflammatory processes in the sacroiliac joint.

  • Ott's Sign: This test assesses thoracic spine flexibility, akin to Schober’s Test, but with a focus on the thoracic region. The procedure involves marking the seventh cervical vertebra and placing a second mark 30 cm below. Subsequently, the patient bends forward, and the distance between the two points is measured. An increase of less than 3 cm indicates reduced thoracic spine flexibility.

Laboratory Tests

Laboratory tests for AS diagnosis include assessing inflammatory markers like Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP) to evaluate inflammation levels. In contrast to other rheumatic diseases, where these markers serve as indicators for the disease activity, in AS they rather indicate inflammation in peripheral joints and not in the axial skeleton.

Genetic testing, specifically HLA-B27, may also be considered alongside clinical and imaging findings. While the presence of HLA-B27 is associated with an increased risk of AS, its absence does not rule out the condition.

Imaging

X-rays play a fundamental role in the diagnosis of AS.

Characteristic X-ray findings include: 

  • Symmetric sacroiliitis with subchondral erosions and sclerosis

  • Syndesmophytes, bony outgrowths that vertically originate from the annulus fibrosus

  • In advanced stages, vertebral bodies may square off, resulting in the characteristic "bamboo spine"

Unfortunately, X-ray changes often manifest in more advanced AS stages. To detect AS in earlier stages, the use of MRI is recommended.

Characteristic MRI findings include:

  • Bone marrow oedema, typically originating from the anterior vertebral edges.

  • Vertebral fat infiltration

  • Iliosacral joint synovitis.

  • Enthesiopathies, particularly affecting ligamenta interspinalia, spina iliaca anterior superior, trochanter major and minor.

  • Bone spurs, extending from the vertebral endplate toward adjacent vertebrae.

  • Ankylosis extending across sacroiliac joints or from one vertebra continuously to the adjacent vertebra.

This comprehensive imaging approach enables the early detection of AS, providing valuable insights into inflammatory and structural changes, facilitating prompt and targeted intervention.

Ultrasonography can be particularly useful in assessing peripheral joint involvement and enthesitis, contributing to a more comprehensive understanding of disease manifestations.

Diagnostic Criteria

Diagnostic New York Criteria (1984) for AS.

Clinical Criteria

  • Low back pain of ≥ 3 months duration with inflammatory characteristics (improved by exercise, not relieved by rest)

  • Limitation of lumbar spine motion in sagittal and frontal planes

  • Decreased chest expansion (relative to normal values for age and sex)

Radiological Criteria

  • Bilateral sacroiliitis grade 2 or higher

  • Unilateral sacroiliitis grade 3 or higher.

The diagnosis of AS can be made when one of the radiological criteria is present with any clinical criteria. An inherent limitation of the current diagnostic criteria is the delayed manifestation of sacroiliitis in advanced stages. To address this concern, many have proposed to MRI criteria into the diagnostic criteria, but no common consensus has been reached yet.

Therapy

The treatment of AS aims to alleviate symptoms, control inflammation, and improve overall function and quality of life. Upon diagnosing AS, a medication with NSAIDs with a gradual titration to achieve the best possible symptom control while minimizing side effects should promptly be started. While being under treatment, it is important to remember that regular assessments with the help of the ASDAS (Ankylosing Spondylitis Disease Activity Score) are crucial for tailoring medications based on the patient's symptoms and disease activity.

If after two to four weeks of medication, NSAIDs prove to be ineffective, biologic medications should be considered. These include TNF-α antibodies as a second-line therapy (e.g. Adalimumab, Infliximab, Golimumab), Anti IL-17 antibodies as a third-line therapy (e.g. Secukinumab, Ixekizumab) and JAK-Inhibitors as an alternative third-line therapy (e.g. Tofacitinib, Upadacitinib). In cases of significant peripheral joint involvement glucocorticoid injections and DMARDs, primarily Sulfasalazine and Methotrexate can also be considered.

In addition to pharmacotherapy physical therapy, and lifestyle modifications, including tailored exercises and joint protection techniques, play crucial roles in effectively managing the patient’s symptoms.

References

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