Ankylosing Spondylitis and the Heart

Basics

Description

Ankylosing spondylitis (AS) is a chronic inflammatory disorder predominantly affecting the axial skeleton and sacroiliac joints.
AS is classified among the seronegative spondyloarthropathies (category also includes reactive (Reiter) arthritis, enteropathic arthropathy, psoriatic arthritis, juvenile spondo-arthritis, anterior uveitis, and peripheral enthesitis).
In 1973, the strong association between human leukocyte antigen (HLA)-B27 gene and spondyloarthropathies was determined.
Cardiac involvement occurs in only 5-10% of AS patients and includes aortic root dilatation and aortic regurgitation (AR) and atrioventricular node block.

Epidemiology

~95% of AS patients are HLA-B27 positive, yet only 1-5% of the HLA-B27 positive general population develop AS.
Prevalence

AS prevalence 0.2-1.2% in U.S.
Male > Female, 3:1
AS prevalence parallels to some degree HLA B27 prevalence in different populations:
- Whites 8% HLA B27 positive
- Whites with AS 96% HLA B27 positive,
- African Americans 4% HLA B27 positive
- African Americans with AS 50% HLA B27 positive.

Risk Factors

A 1st-degree relative with AS increases a patient's risk by 5-16-fold.
HLA-B27-positive children who have siblings with AS have a 10-20% risk of getting AS.
Male gender

Genetics

Different subtypes of HLA-B27 have different associations with AS, and other susceptibility factors likely include the Il 23/17 axis.
HLS-B27 is a strong genetic risk factor for cardiac conduction disease in males, especially with aortic insufficiency even in the absence of AS.

Pathophysiology

Aortic root and ascending aorta show intimal proliferation, obliterative endarteritis, and fibrosis.
The majority of patients have aortic root and aortic valve (AV) involvement.
AS may cause aortic regurgitation (AR) through fibrotic thickening, retraction and rolling of the AV cusps, and aortic root dilatation. Aortic valve stenosis is not associated.
The fibrotic lesions may extend down to the anterior mitral valve (MV) leaflet, causing a "subaortic hump" and MV insufficiency; mitral valve involvement is rare. In patients with severe AR, mitral insufficiency most likely results from LV dilation.
Fibrosis is common in the conduction system.
Vascular changes seen with AS in the aorta and joints may also occur in the:
- Sinus node artery: Sinus node dysfunction
- AVN artery: AVN conduction block
- Aortic root vasa vasorum: Aortic root dilatation
Coronary arteritis is not a feature of AS.

Etiology

It is estimated that only 20-50% of the genetic susceptibility to AS is attributed to the HLA-B27 gene and that other factors and genes in non-MHC (major histocompatibility complex) regions play a role in disease susceptibility. HLA-B27 gene expression, as well as different alleles (26 known) play an as yet undefined role.
There is no evidence that AS results from an infectious trigger, as with Reiter disease.
All spondyloarthropathies appear to result from T cell-mediated autoimmune response
The pathogenesis of disease development remains unknown.

Associated Conditions

AR associated with AS, or even conduction delays (AV block), can precede joint manifestations of the disease.
Extraskeletal involvement:
- Cardiovascular: Aortic root disease, AR, conduction disturbances
- Pulmonary: Apical lung fibrosis or restrictive lung disease secondary to spinal changes
- Ophthalmologic: Anterior uveitis and cataracts
- Renal: IgA nephropathy, renal amyloidosis, NSAID nephropathy, very rare
- Neurologic: Spinal cord compression
- GI: Usual asymptomatic bowel ulcers and Crohn disease, rarely

Diagnosis

History

Insidious onset of symptoms usually prior to age 40 yr
Patients with early AS may have nonspecific symptoms of fever, malaise, loss of appetite.
Low back pain is the presenting symptom in 70-80% of AS patients, yet <5% of patients with chronic low back pain have AS.
Back pain worsens with inactivity and improves with exercise.
Alternating buttock pain
Frequently a family history of a spondyloarthropathy in a 1st- or 2nd-degree relative
Cardiac syndrome of AR and heart block may precede other symptoms
Cardiac conduction disturbances may be intermittent and widely spaced in time.
HLA-B27-associated heart block usually involves the AV node and not the His bundle.

Physical Exam

Impaired spinal mobility
Impaired chest expansion
Asymmetric inflammatory arthritis or arthritis predominantly of the lower extremities
Sacroiliitis
May have enthesitis; pain and inflammation at tendon insertion sites, especially Achilles tendon and plantar tendon
Chronic AR may present as a holodiastolic decrescendo murmur. As in other patients with dilated roots, the murmur may be best appreciated along the right sternal border.
In patients with significant AR, a systolic flow murmur is often heard due to increased stroke volume not to aortic stenosis.

Tests

Lab

In the proper clinical setting when AS is being considered, HLA-B27 positivity can be helpful. It is not a useful screening test nor is it necessary when the clinical diagnosis is clear.
No specific serologic marker for diagnosis and disease activity
ESR and/or CRP levels may be elevated, but normal ESR or normal CRP levels do not exclude active AS.
Rheumatoid factor and antinuclear antibodies are negative.
ECG:
- AV nodal block most commonly associated.
- Atrial fibrillation may be more frequent.

Imaging

MRI has come to the forefront of diagnostic testing in AS, since it can demonstrate early as well as late (structural) changes
MRI scoring systems quantify bone edema, inflammation, sacroiliitis, and enthesitis prior to radiographic evidence and allow assessment of drug (anti-tumor necrosis factor [TNF]) effectiveness.
Radiographic findings are a late manifestation of disease sequelae and not sensitive to early stages of inflammation.
Sacroiliitis on anteroposterior pelvis radiograph
Classic "bamboo spine" on radiograph is diagnostic of AS.
Bone loss (osteoporosis) may be seen in the spine, but not elsewhere.
Impaired chest expansion on CXR
US is useful for assessment of joint and periarticular soft tissue, especially in detection of enthesitis.
Aortic root disease and aortic insufficiency can be diagnosed by echo. MRI may be useful as well.

Differential Diagnosis

Other spondyloarthropathies
Rheumatoid arthritis
Reiter syndrome
Systemic lupus erythematosus
Other causes of aortic insufficiency: In rheumatic heart disease (RHD), the aortic valve is also thickened but usually has some degree of stenosis. The mitral valve will inevitably be involved with stenosis and/or insufficiency in RHD but not AS.

Treatment

Medication

First Line

NSAIDs and possibly corticosteroids are effective for the inflammatory musculoskeletal symptoms and may inhibit osteoblasts and new bone formation.
TNF-Î± antagonists (infliximab, etanercept, adalimumab) have shown improvement of the inflammatory musculoskeletal symptoms of AS but have not been shown to inhibit new bone formation.
Disease modifying antirheumatic medications (DMARDs) such as corticosteroids, methotrexate, other immunosuppressive therapies: Long-term use of corticosteroids may have adverse effects on coronary disease risk factors.
Patients with chronic severe AR who are not surgical candidates or who do not yet meet the criteria for aortic valve replacement may be treated with usual medical therapy.
Systemic HTN, if present should be treated with ACEI or other vasodilators.
No definite long-term benefit, in terms of disease progression, has been show with the use of nifedipine or ACEI and their use for this purpose cannot be recommended.

Second Line
Pamidronate and thalidomide may be of some benefit against the musculoskeletal symptoms.

Additional Treatment

General Measures

Usual management of coronary artery disease risk factors including counseling on smoking cessation.
The skeletal involvement of AS is treated with regular exercise, physical therapy, and NSAIDs.
General osteoporosis prophylaxis and treatment should be considered.
Aortic insufficiency should be treated and followed similar to standard practice. Endocarditis prophylaxis is no longer recommended.

Issues for Referral

Rheumatologist
Physical therapist
Patients with chronic AR should be monitored periodically by a cardiologist.

Surgery

Total hip replacement and spinal surgery may be beneficial in some patients.
Severe AR may require surgery.
See Aortic Regurgitation, Adult chapter for indications for surgery.
High-degree heart block requires implantation of a permanent pacemaker.

Ongoing Care

Follow-Up Recommendations

Patient Monitoring

Monitoring AR and LV size and function must be followed by exam and echo every 1-2 yr.
Asymptomatic patients with chronic severe AR and normal LV size and function need exams and echos every 6 mo.
Aortic valve surgery is indicated as soon as the patient develops symptoms or abnormal LV size or function (LV ejection fraction <50% or LV end diastolic dimension >75 mm or LV end systolic dimension >55 mm).

Diet

Low-sodium diet if heart failure develops

Patient Education

Activity ad lib:
- Activity limited by back and spine discomfort, and by heart failure symptoms if they develop
Prevention:
- Infective endocarditis prophylaxis is not currently recommended without prior endocarditis history.
- Patient counseling for symptoms of HF or heart block

Prognosis

AS alone does not affect overall long-term mortality.
The progression of cardiac involvement is not well known and varies among reported series.
Secondary amyloidosis and cardiovascular complications are the major causes of death due to AS.

Complications

Aortic valve endocarditis has been described as a consequence of AS.
AS patients may be at risk for spinal fractures and neurologic compromise.
Atrial fibrillation may occur more commonly than expected in patients with AS.

Limited data on surgical outcomes for AR in elderly patients
Symptoms are generally the primary indication for aortic valve surgery in elderly patients >80.

No contraindications exist for pregnancy with AS alone, but patients with AR need special consideration. AS is much less common in women than men, therefore information is limited.
Aortic regurgitation in pregnancy: See Aortic Regurgitation, Adult

Additional Reading

1
Guglielmi G, Scalzo G, Cascavilla A. Imaging of the sacroiliac joint involvement in seronegative spondyloarthropathies. Clin Rheumatol. 2009;28:1007-1009. [View Abstract] 2
Libby P.
Braunwald's heart disease: A textbook of cardiovascular medicine, 8th ed.Philadelphia: Elsevier Saunders, 2007. 3
Peters MJ, van der Horst-Bruinsma IE, Dijkmans BA. Cardiovascular risk profile of patients with spondyloarthropathies, particularly ankylosing spondylitis and psoriatic arthritis. Semin Arthritis Rheumat. 2004;34:585-592. [View Abstract] 4
Reveille JD, Arnett FC.
Spondyloarthritis: Update on pathogenesis and management. Am J Med. 2005;118:592-603. [View Abstract] 5
Sheehan NJ.
The ramifications of HLA-B27. JR Soc Med. 2004;97:10-14. [View Abstract] 6
Sieper J.
Can structural damage be prevented in ankylosing spondylitis?
Curr Opin Rheumatol. 2009;335-339. 7
Sims AM, Wordsworth BP, Brown MA.
Genetic susceptibility to ankylosing spondylitis. Curr Molec Med. 2004;4:13-20. [View Abstract] 8
Topol EJ
Textbook of cardiovascular medicine, 2nd ed.Philadelphia: Lippincott Williams & Wilkins, 2002. 9
Zochling J, Braun J.
Management and treatment of ankylosing spondylitis. Curr Opin Rheumatol. 2005;17:418-425. [View Abstract]

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