ankylosing spondylitis

ankylosing spondylitis
Field	Rheumatology

ankylosing spondylitis. It is a chronic, systemic inflammatory disease primarily affecting the axial skeleton, including the sacroliac joints and spine. The condition is a prototypical member of the spondyloarthritis family and is strongly associated with the human leukocyte antigen HLA-B27. Over time, inflammation can lead to ankylosis, where vertebrae fuse together, resulting in a rigid spine.

Signs and symptoms

The hallmark feature is inflammatory back pain that improves with exercise and worsens with rest, often beginning in the sacroliac joints. Patients may experience stiffness, especially in the morning. Extra-articular manifestations are common and can include acute anterior uveitis, psoriasis, and inflammatory bowel disease such as Crohn's disease. Enthesitis, inflammation at sites where ligaments and tendons attach to bone, frequently affects the Achilles tendon and plantar fascia. Advanced cases can lead to reduced chest expansion due to involvement of the costovertebral joints and, rarely, aortitis or cardiac conduction system abnormalities.

Causes and pathophysiology

The etiology is multifactorial, involving a strong genetic predisposition, particularly the presence of the HLA-B27 allele, though most carriers do not develop the disease. Genome-wide association studies have identified other genetic loci within the major histocompatibility complex and in genes like ERAP1 and IL23R. The prevailing pathophysiological model suggests that HLA-B27 misfolding triggers an unfolded protein response in cells, leading to pro-inflammatory cytokine production, including tumor necrosis factor alpha and interleukin-17. This immune dysregulation targets the entheses and joints, with contributions from the gut microbiome and environmental triggers.

Diagnosis

Diagnosis is clinical and radiographic, often following criteria such as the Modified New York Criteria. Key laboratory findings include an elevated C-reactive protein or erythrocyte sedimentation rate, though these can be normal. Testing for HLA-B27 is supportive but not diagnostic. Radiographic evidence of sacroliitis on plain radiographs of the pelvis is a cornerstone, with magnetic resonance imaging able to detect active inflammation before structural damage occurs. Differential diagnosis includes other forms of spondyloarthritis, diffuse idiopathic skeletal hyperostosis, and mechanical back pain.

Management

Management aims to control symptoms, maintain function, and prevent structural progression. First-line pharmacological therapy consists of nonsteroidal anti-inflammatory drugs like naproxen or celecoxib. For those with inadequate response, biologic disease-modifying antirheumatic drugs targeting tumor necrosis factor alpha, such as adalimumab and infliximab, or interleukin-17 inhibitors like secukinumab are used. Non-pharmacological therapy is crucial and includes structured exercise, ideally supervised by a physiotherapist, and patient education. Surgical interventions, such as total hip arthroplasty or, in severe spinal deformity, osteotomy, may be required.

Prognosis

The disease course is highly variable, with periods of flares and remission. While structural damage to the spine is often progressive, the prognosis for function has improved dramatically with modern therapies. Major determinants of poor outcome include early hip involvement, elevated inflammatory markers, and smoking. Complications can include spinal fractures, cauda equina syndrome, and severe restrictive lung disease. With effective management, most individuals maintain good functional capacity and quality of life.

Epidemiology

It has a global prevalence of approximately 0.1% to 1.4%, with significant variation linked to the population frequency of HLA-B27. It is most common in populations of Northern European descent, particularly among the Hämeenlinna region of Finland and in some Native American groups. The disease typically presents in late adolescence or early adulthood, with a peak onset in the third decade, and is about three times more common in males than females, though this ratio may narrow with increased diagnostic awareness.

Category:Rheumatology Category:Autoimmune diseases