Spondyloarthritis

Definition

Ankylosing spondylitis (AS) is a chronic inflammatory disease of the axial skeleton that manifests itself with deep-seated pain at night or early in the morning (lumbar spine, buttocks) and morning stiffness. These symptoms must persist for at least 3 months and usually improve with movement. Typically, progressive stiffening of the spine occurs over the course of several years. In addition, some patients may experience symptoms (swelling, pain, stiffness) in the peripheral joints and involvement of internal organs.

Frequency and incidence

The disease occurs more frequently in young men (ratio m:f about 3:1) in the 3rd and 4th decade of life. Approx. 90-95% of those affected are carriers of the HLA-B27 antigen.

Pathogenesis

The exact cause of AS is still unknown. However, several aspects are being discussed and researched, with the most likely cause being a combination of genetic predisposition and a trigger (usually infection).

Diagnosis

The diagnosis of AS is primarily based on clinical and radiological criteria, and due to the breadth of the clinical spectrum, there are a number of "diagnostic" and "classification" criteria (1) according to the ESSG (European Spondyloarthropathy Study Group) (2), according to the New York criteria modified in 1984 (3).

The modified New York Classification Criteria of AS:

    Inflammatory back pain lasting at least three months, which improves with movement and worsens at rest.
    Restriction of mobility in the spinal column at the sagittal and spinal levels.
    Chest expansion is reduced compared to normal values for the same gender and age.
    Bilateral sacroiliitis of grade 2-4 or unilateral sacrolitiitis of grade 3-4

AS is present if the 4th and any other criterion is fulfilled.

Diagnostische Methoden

Imaging
A radiological examination (conventional X-ray) should be performed as a basic examination. If the inflammatory activity of AS persists for a long time, native radiological changes can be depicted. If AS is suspected and the radiological findings are unremarkable (as in the early stages), an MRI of the iliosacral joints is indicated. Computed tomography of the iliosacral joints is helpful for further diagnosis in patients with contraindications to MRI.

Laboratory
The genetic background of AS is confirmed by the frequent presence of HLA-B27 (up to 90-95% of AS patients in Central Europe and the USA). Furthermore, most AS patients are rheumatoid factor ("sero-") negative. The occurrence of chronic polyarthritis is therefore also very rare.

Clinic

• Inflammatory back pain

A classic clinical criterion that has not yet been sufficiently validated is the so-called "inflammatory back pain". This is characterised by the following clinical signs: morning stiffness, waking up due to back pain in the second half of the night, improvement with movement but not at rest, alternating radiation into the buttocks. These criteria have a sensitivity of 70.3% and a specificity of 81.2% if at least two parameters were fulfilled (positive "likelihood ratio" 3.7).

• Peripheral joint and tendon involvement

 Peripheral joint involvement can occur as arthritis (especially in the hips or shoulder). Inflammatory involvement of tendon and ligament attachments (enthesitis) is also very typical.

• Extra-articular involvement

Extra-articular manifestations in the eyes (anterior uveitis in up to 30% of patients, posterior uveitis, and macular oedema), heart (aortic insufficiency, aortitis of the ascending aorta) and/or lungs (recurrent infections, extrapulmonary restrictive disorder, and upper lobe fibrosis) are also possible. Amyloid deposition can lead to chronic renal insufficiency.

Therapy

Therapy goals

1. Maximum reduction of pain and joint stiffness.
2. Recovery of functional capacity.
3. Prevention of progression of erosive changes and ankylosis in the spine in order to maintain function and avoid deformities.
4. Prevention of joint destruction (shoulder, hip and/or peripheral joints) and ankylosis.
5. Minimisation of extraspinal and extra-articular manifestations.
6. Prevention of complications: WK fracture, flexion contracture, especially of the cervical spine.

The decision to start treatment depends on the exact assessment of disease activity (assessed by activity scores such as BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) score and BASFI (Bath Ankylosing Spondylitis Functional Index) score (4) or the core set parameters of the ASAS (Assessments in AS Working Group)(5) and pre-existing damage.

Until a few years ago, therapeutic options were limited to the combined use of NSAIDs and long-term continuous physical therapy of the spine.

For some years now, TNF-α blocker therapy has been available for patients with an inadequate response to the above-mentioned conventional therapies or for patients with highly active disease.

General measures

Physiotherapy
Regular physical therapy (hydrotherapy, cryotherapy, heat therapy) or ankylosing spondylitis gymnastics (posture training, functional gymnastics) can improve the mobility of the spine and significantly alleviate the pain.

Nicotine cessation
This general measure is particularly important for patients with ankylosing spondylitis in whom chronic obstructive disease could significantly worsen the pulmonary situation.

Drug therapy

• NSAIDS

Treatment with NSAIDs can lead to control of pain (arthralgia and lumbalgia), joint stiffness and consistently to an improvement in the patient's general state of health. The study by Wanders et al. on 215 patients (6) showed a reduction in radiological progression in patients undergoing continuous therapy with NSAIDs compared to those taking them irregularly. The effectiveness was best described for naproxen and indomethacin. These should be administered continuously in their maximum dosage for at least 2-3 weeks.
There is less data on COX-2 inhibitors (celecoxib or etoricoxib). They appear to be just as effective as conventional NSAIDs, but - as with other NSAIDs - the potential cardiovascular risk must be weighed up.
   

• Glucocorticoids

 Clinical studies have repeatedly shown that patients with ankylosing spondylitis do not benefit from systemic glucocorticoid therapy. In addition, these patients already suffer from an increased loss of bone density, which would deteriorate even more significantly with glucocorticoid therapy. Only local application is recommended in cases of pronounced pain in the sacroiliac joints, peripheral arthritis or enthesitis such as plantar fasciitis.

• DMARDS

Among the disease-modifying antirheumatic drugs (DMARDS), only sulfasalazine has proven to be effective in patients with peripheral joint involvement and/or anterior uveitis, but not in axial skeletal involvement of the spine, nor are methotrexate and leflunomide of any significance in the treatment of ankylosing spondylitis.

• TNF-alpha blockers

TNF-alpha (TNF-α) blockers offer a new therapeutic option for patients with permanently high inflammatory activity.
The inhibition of TNF-α leads to an increased susceptibility to infections with intracellular pathogens, so that the therapies should only be administered after exclusion of tuberculosis exposure (C/P, Mendel-Mantoux test, quantiferon test) and an active infection of other origins (e.g. bronchitis, urinary tract infection).
The majority of patients with ankylosing spondylitis respond to one of the TNF-α blockers. The indication should always be evaluated by a specialist (rheumatologist).

Indication criteria for TNF-α therapy

1. Confirmed ankylosing spondylitis according to the modified New York criteria (2)
2. Pain despite administration of NSAIDs/other analgesics in sufficient dosage
3. BASDAI ≥ 4
4. CRP or lowering increased

A rapid response (reduction of the BASDAI by at least 50%) is often seen within the first six weeks of starting therapy. Patients who do not respond after 12 weeks of TNF-α blocker therapy are classified as "non-responders". The therapy should be discontinued or switched to other TNF-α blockers. Clinical studies have confirmed that patients can benefit from switching to another TNF-α blocker if there is no response or intolerance to one of the TNF-α preparations (7, 8). 

Referenzen

1. Calin A, Porta J, Fries JF, Schurman DJ. Clinical history as a screening test for ankylosing spondylitis. Jama 1977;237(24):2613-4.
2. Dougados M, van der Linden S, Juhlin R, Huitfeldt B, Amor B, Calin A, et al. The European Spondylarthropathy Study Group preliminary criteria for the classification of spondylarthropathy. Arthritis Rheum 1991;34(10):1218-27.
3. van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 1984;27(4):361-8.
4. Calin A, Garrett S, Whitelock H, Kennedy LG, O'Hea J, Mallorie P, et al. A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath Ankylosing Spondylitis Functional Index. J Rheumatol 1994;21(12):2281-5.
5. van der Heijde D, Calin A, Dougados M, Khan MA, van der Linden S, Bellamy N. Selection of instruments in the core set for DC-ART, SMARD, physical therapy, and clinical record keeping in ankylosing spondylitis. Progress report of the ASAS Working Group. Assessments in Ankylosing Spondylitis. J Rheumatol 1999;26(4):951-4.
6. Wanders A, Heijde D, Landewe R, Behier JM, Calin A, Olivieri I, et al. Nonsteroidal antiinflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis: a randomized clinical trial. Arthritis Rheum 2005;52(6):1756-65.
7. Cantini F, Niccoli L, Benucci M, Chindamo D, Nannini C, Olivieri I, et al. Switching from infliximab to once-weekly administration of 50 mg etanercept in resistant or intolerant patients with ankylosing spondylitis: results of a fifty-four-week study. Arthritis Rheum 2006;55(5):812-6.
8. Coates LC, Cawkwell LS, Ng NW, Bennett AN, Bryer DJ, Fraser AD, et al. Real life experience confirms sustained response to long-term biologics and switching in ankylosing spondylitis. Rheumatology (Oxford) 2008;47(6):897-900.