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Treatment approach for Ankylosing Spondylitis & the role of HLA B27: Dr. Jyostna Oak

M3 India Newsdesk Aug 13, 2019

Dr. Jyotsna Oak discusses clinical and radiographic classification criteria for ankylosing spondylitis, skeletal and extra articular manifestations, treatment modality, and the disease's connection with HLA B27.


Ankylosing Spondylitis (AS) belongs to the group of diseases known as spondyloarthritides (SpA). This group constitutes a family of related conditions rather than a single disease with different clinical manifestations. Radiographic Sacroiliitis is a hallmark of AS. Inflammation of sacroiliac joints and the spine leads to bony ankylosis. Spinal ankylosis appears in the late stage of the disease and is absent in mild form of AS. The disease has predilection in young males. There is asymmetric oligoarthritis, familial aggregation, persistent seronegativity for rheumatoid factor and strong association with HLA B27.

Clinical features of AS

Backache during the 3rd decade, which typically worsens at rest and relieves after exercise.There is nocturnal exacerbation of pain, especially in the second half of the night.

Definite radiographic sacroiliitis or conventional plain X-rays/radiographs can take many years and hence MRI can reveal it early. Non Radiographic Axial Spondyloarthritis (nr axSpA) is a term used for such cases who have characteristic clinical symptoms of AS but no radiographic findings. Axial SpA (ax SpA) comprises both nonradiological AS and Classic AS.

Classification criteria of AS and Axial SpA

ROME Criteria 1961

The clinical and radiographic criteria under ROME Criteria are described below.

  1. Clinical criteria:
  • Low backache and stiffness for >3 months not relieved by rest
  • Pain and stiffness in thoracic region
  • Limited motion of lumbar spine
  • Limited chest expansion
  • History of evidence of iritis or its sequele
  1. Radiographic criteria:
  • Radiograph showing bilateral sacroiliac changes of ankylosing spondylitis
  • Definite AS – grade 3 or 4 Bilateral sacroiliatis with at least one clinical criteria

Modified New York Criteria 1984

  1. Clinical criteria:
  • Low backache of at least 3 months duration
  • Improved by exercise and not relieved by rest.
  • Limited Lumbar spine motion in saggital and frontal plane
  • Chest expansion decreased relative to normal value for age and sex
  1. Radiological criteria:
  • Bilateral sacroiliitis grade 2 to 4
  • Unilateral sacroiliatis grade 3 or 4

Definite Ankylosing Spondylitis (AS)

  • Unilateral grade 3 or 4 sacroiliitis
  • Or bilateral grade 2 to 4 sacroiliatis and any clinical criteria

Skeletal manifestations

Low backache: Back pain in AS and ax SpA has special features that differentiate it from mechanical back pain. The pain is felt in the gluteal region, is dull in character and difficult to localise.

The pain is severe in the early phase and does not radiate to ankle like root compression. The lower lumbar area becomes stiff and is worse in the morning and may awaken the patient from sleep. The morning stiffness can last upto 3 hours. The pain tends to be relieved by activity and does not improve by rest.

Due to involvement of thoracic spine and due to costovertebral and costotranverse joints, the patient may experience chest pain. Reduction of chest expansion may be detected.

Features of inflammatory back pain:

  • Onset of complaints before the age of 45 years
  • Duration of symptoms more than 3 months
  • Pain located at lower back
  • Alternate buttock pain
  • Morning stiffness for more than 30 minutes
  • Improvement with exercise
  • No improvement of backpain with rest
  • Improvement with NSAIDS


It can lead to pain and tenderness at spinous process, iliac crest, tibial tubercles and heels, for example, Achilles tendinitis or plantar fasciitis. Joint involvement- shoulder, hip, knee or ankle may get involved in as many as 35% of the patients. Hip joint is commonly involved in Juvenile AS as a presenting manifestation.

Extra articular manifestations

  1. Eye: Acute anterior uveitis or iridocyclitis is the most common extra-articular manifestation. The onset of eye inflammation is acute and typically unilateral but the episodes can be alternate. The eye becomes red and painful and there is photophobia and increased lacrimation. Acute anterior uveitis (AAV) is more common in HLA B27 +ve patients.
  2. Cardiac: Ascending aortitis, aortic valve incompetence, pericarditis is seen in 3.5% of patients.
  3. Pulmonary: Rare and late manifestation and is due to the restricted chest wall movement spontaneous anterior atlantoaxial subluxation is a well recognised complication in 2% of patients and can manifest as with or without spinal cord compression.


  1. The treatment objective is to relieve pain, stiffness, fatigue and maintain good posture and good physical functioning. Exercise is a mainstay of treatment.
  2. Swimming, extension promoting exercises can help to counteract kyphotic effects of pain and fatigue and reduce stiffness.
  3. NSAIDs (non-steroidal anti-inflammatory drugs) including coxibs are recommended as first line treatment and persistent treatment is required for active disease.
  4. Glucocorticoid injections can be considered at the local site for musculoskeletal inflammation.
  5. Anti Tumour Necrosis Factor (TNF) Therapy should be given to a patient with persistently high disease activity despite conventional therapy. The other biological agents are not useful in Spondyloarthritis (SpA). Both clinical as well as radiological improvement has been reported with infliximab.
  6. DMARDs: There is no evidence of efficacy of DMARDs including methotrexate and suphasalazine for the axial disease. However in routine practice these drugs are used for axial and peripheral disease.

Role of HLA B27

Despite more than 40 years of research, the precise role of HLA B27 in AS remains unclear. The dominant role of class I HLA B27 molecule is in presentation of antigen to CD8 T lymphocytes.The arthritogenic peptide model of AS pathogenesis suggests that in genetically predisposed individuals aberrant presentation of self peptides by HLA molecule results in recognition of innocuous self antigens as harmful, inducing autoreactivity from CD8 T cell response. But these studies have not been convincingly replicated.


Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author is a Consultant in Internal Medicine & Rheumatology at a prominent Mumbai hospital.

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