1. Ankylosing Spondylitis Late Complications
Atul Deodhar MD
Associate Professor of Medicine
Medical Director, Rheumatology Clinics
Oregon Health & Science University
Portland, OR
Spondylitis Association of America Webinar March 21st, 2009

2. General Comments on AS
Major part of the disease progression occurs in the first 10 years of the disease1
‘Bamboo spine’ occurs in 20% after 20 years3
Women have more involvement of cervical spine & peripheral joints than men2
AS has no adverse effect on fertility, pregnancy or fetus
Unlike in RA, pregnancy has no consistent effect on AS disease activity
Men have worse radiographic progression than women, but ‘self-reported’ functional limitations are worse in women4
Need references
1Carette S. et al. Arthritis Rheum 1983;26: Lee W et al. Arthritis Rheum 2008;59: Sampaio-Barros PD J Rheumatol 2001;28: Lee w et al. Ann Rheum Dis 2007;66:633-8

3. Self-Reported AS Symptoms and Quality-of-Life Concerns*
While there is no burden-of-illness data available for SpA in general, there is data available – specifically European studies – on symptom burden in AS. As with most rheumatic diseases, the severity of AS symptoms varies greatly among patients and over time.1
Ward assessed the importance of quality-of-life (QOL) issues of 175 AS patients using both a cross-sectional survey of health status and the Medical Outcomes Study Short Form 36 Health Survey (SF-36). The figure above highlights the seven greatest QOL concerns reported in the study.2
AS is associated with a relatively early age of onset, thus the impact of pain, fatigue, and progressive disability on the individual’s lifestyle, career, family, and social life are likely to be long term and far reaching. Daily pain and stiffness are common, as reported in 70% of patients, and 81% of AS patients who have lost most of their spinal mobility become restricted within the first 10 years.3-5
The AS Life-Impact Study, a cross-sectional, QOL study sponsored by the Spondylitis Association of America, was conducted to learn more about the long-term outcomes of people with AS and the impact of the disease on their daily lives.
2,384 adults with AS were surveyed by mail
The outcomes of the study reinforce the burden of illness of AS; an abstract has been submitted to ACR and submission for publication to follow
Chorus AM, et al. Employment perspectives of patients with ankylosing spondylitis. Ann Rheum Dis. 2002;61:
Ward M. Health-related quality of life in ankylosing spondylitis: a survey of 175 patients. Arthritis Care Res. 1999:12(4):
Barlow JH, Wright CC, Williams B, Keat A. Work disability among people with ankylosing spondylitis. Arthritis Care Res. 2001;45:
Ward M. Quality of life in patients with ankylosing spondylitis. Rheum Dis Clin North Am. 1998;24(4):
Carette S, Graham D, Little H, Rubenstein J, Rosen P. The natural disease course of ankylosing spondylitis. Arthritis Rheum.1983 Feb;26(2):
*7 greatest QOL concerns reported
Ward M. Arthritis Care Res. 1999

4. Prognosis of AS
Following factors at presentation indicate increased disease severity
Hip arthritis — odds ratio (OR) 23
Sausage-like finger or toe — OR 8
Poor response to NSAID — OR 8
High ESR (>30 mm/h) — OR 7
Limitation in range of lumbar spine — OR 7
Oligoarthritis — OR 4
Onset less than 16 years of age — OR 3
If no factor is present: mild outcome is likely (sensitivity 93%, specificity 78%)
If hip is involved or 3 other factors are present, severe disease is predicted: sensitivity 50%, specificity 98%

5. Proportion of Patients (%)
AS Burden of Disease: % of Male Patients with Disability (Steinbrocker > II)
RA (n=11,643)
AS (n=5,581) 60 53
* P<0.0025 * 48 * 44 * 39 38 40 35 31 29 25
Proportion of Patients (%) 22 20
<41
41-50
51-60
61-70
>70
Years
Zink A, et al. J
Rheumatol .
2000;27:613 -
22.

6. Proportion of Patients (%)
AS Burden of Disease: % of Female Patients with Disability (Steinbrocker >II)
RA (n=38,180)
AS (n=2,487) 80
* P<0.0025 60 60 46 44 42 40 33 34
Proportion of Patients (%) 28 26 * 20 16 20
<41
41-50
51-60
61-70
>70
Years
Zink A, et al. J
Rheumatol .
2000;27:613 -
22.

7. Disease duration at retirement
Early Retirement in AS
AS patients 3 times more likely to become disabled1
31% after 20 years in Dutch study
36% after 20 years in French study
Survey of 100 Norwegian AS patients2 (mean age: 42 years, disease duration: 16.5 years)
26% of patients were retired2
15.6
42.9
6.4
36.1 20 40 60
Disease duration at retirement
Retirement age
Years
Men
Women
96.2% retired due to AS
P<0.02
Do you categorize patients as having mild, moderate, severe disease?
Do you use some other method to categorize patients – early disease, established disease?
How do you currently assess a patient’s likelihood of progression in AS?
Do you believe that earlier intervention with biologics leads to better clinical outcomes?
If treated early and aggressively, do you believe that the natural course of AS can be altered?
1Boonen A Clin Exp Rheumatol 2002;20(suppl 28):S23-S26.
2Gran JT et al. Br J Rheumatol 1997;36:766-71

8. Other Disease Manifestations in AS
Eyes
(Acute Anterior Uveitis)
Up to 40%
Lungs
(Restrictive Lung Disease,
Apical Fibrocystic Disease)
Heart
(Aortic Insufficiency, Heart Block)
3% to 10%
Kidneys
(Amyloidosis)
Gut
(Inflammatory bowel disease,
Microscopic inflammatory lesion)
Extra-articular sites may be affected in AS. The most common of these is acute anterior uveitis, which occurs in up to 40% of patients.1-6
Approximately 20% to 70% of AS patients have microscopic evidence of gut inflammation and 6.5% develop Crohn’s disease during the course of their disease. Up to 10% of patients with AS may have psoriatic skin involvement.
Banares A, Hernandez-Garcia C, Fernandez-Gutierrez B, Jover JA. Eye involvement in the spondyloarthropathies. Rheum Dis Clin North Am Nov;24(4):771–784.
Khan MA: Ankylosing spondylitis: Clinical features. In: Hochberg M, et al (Editors). RHEUMATOLOGY (3rd Edition), London, Mosby: A Division of Harcourt Health Sciences Ltd
Khan MA. Update on spondyloarthropathies. Ann Intern Med. 2002;136:
Smale S, Natt RS, Orchard TR, Russell AS, et al. Inflammatory bowel disease and spondyloarthropathy. Arthritis Rheum Dec;44(12):
De Vos M, Mielants H, Cuvelier C, Elewaut A. Long-term evolution of gut inflammation in patients with spondyloarthropathy. Gastroenterology. 1996;110:
Lautermann D, Braun J. Ankylosing Spondylitis – Cardiac manifestations. Clin Exper Rheum. 2002;6(suppl 28):S11-S115.
Skin
(Psoriasis & Nail Changes)
Microscopic involvement 20-70% 6.5% have Crohn’s Disease
Up to 10%
Dactylitis
Cauda Equina Syndrome
Osteopenia, Osteoporosis
Spinal Fracture

9. Spectrum of AS
Early Moderate Severe
Courtesy of J. Cush, MD

10. Late Complications of AS
Skeletal Complications
Bamboo spine
Osteoporosis
Spinal fractures
Fused hips and shoulders
Fused ribs: reduced chest wall expansion
Non-skeletal Complications
Heart: valvular (aortic and mitral) regurgitation, conduction abnormalities, diastolic dysfunction
Lung: apical fibrosis, restrictive lung disease
Kidney: amyloidosis
Neurological: cauda equina syndrome, spinal cord compression

11. Aortic Dilatation in AS
Aortic regurgitation seen in 3.5% of patients after 15yrs; 10% at 30 yrs, and is associated with peripheral arthritis
Warning signs: None! Be aware of the complication
Treatment: medical management. In severe cases: valve replacement
Bergfeldt Am J Med 1988;85:12-18, Bulkley & Roberts Circulation 1973;48:

12. Heart & Lung Disease in AS
Conduction abnormalities (heart block) & diastolic dysfunction seen in a minority of patients with long-standing AS
Whether these changes are more common in AS compared to general population, is controversial. One Swiss study found no increased prevalence1
Pulmonary manifestations of long-term AS: Interstitial lung disease, upper lobe fibrosis, reduced chest expansion (due to fused ribs and restricted chest cage movement)
Warning signs: New onset of shortness of breath, cough, palpitations, missed heart beats, swelling on legs
Treatment: pacemaker, diuretics, vasodilators, bronchodilators etc
Ankylosing spondylitis and heart abnormalities: do cardiac conduction disorders, valve regurgitation and diastolic dysfunction occur more often in male patients with diagnosed ankylosing spondylitis for over 15 years than in the normal population?
Brunner F, Kunz A, Weber U, Kissling R.
Department of Physical Medicine and Rheumatology, Balgrist University Hospital, Forchstrasse 340, 8008 Zurich, Switzerland.
The objective of this study was to determine the rate of selected cardiac pathologies (conduction disorders, valve regurgitation and diastolic dysfunction) in patients with long-standing ankylosing spondylitis (AS) and compare the results with the prevalence in the normal population. A rheumatologic (structured questionnaire interview) and cardiac evaluation (resting electrocardiography and echocardiography) was performed in 100 male subjects with AS and a disease duration of more than 15 years. The rates for conduction disorders, aortic and mitral valve regurgitation and diastolic dysfunction were compared with the corresponding results in the literature among the normal population. In patients with long-standing AS there was no increased rate for valve regurgitation (mitral and aortic valve) and for arrhythmia. Diastolic dysfunction occurred more often in patients with long-standing AS. However, this might be caused by the presence of other cardiovascular risk factors such as age and hypertension. According to these results, a cardiologic evaluation with echocardiography should not be recommended routinely in patients with long-standing AS. To confirm these results, a large prospective study with patients with long-standing AS and with a matched control group should be performed in the future.
1Lang U et al. Eur J Med Res 2007;12(12):573-81

13. Spinal cord injury in AS
Osteoporosis is common in AS
Spinal BMD can be falsely increased due of new bone formation – femoral BMD measurement recommended
Patients with AS suffer spinal fractures at an increased rate with minimal trauma (lifetime incidence 4%-18%)
Incidence of spinal cord injury increased > 10-fold when compared to the general population of Finland
Compression of the spinal cord at atlanto-axial level can occur with paraparesis or tetraparesis
Warning signs for fracture: sudden onset of new severe back pain after stable disease
Warning signs for spinal cord injury: new onset sensory or motor symptoms (tingling, numbness, weakness, bladder/bowel involvement)

14. Cauda Equina Syndrome in AS
Neurological complications are rare (2%) in AS
Cauda equina syndrome is very rare complication, seen in long standing AS
Affects nerve roots from lumbar & sacral spine
May be secondary to inflammation of the covering of the spinal cord (called arachnoiditis)
Warning signs: Slowly progressive pain, numbness in the saddle distribution, bowel/bladder incontinence
Rarely, muscle weakness symptoms seen
Diagnosed by imaging (CT, MRI)
Treatment: recently, surgery (laminectomy, lumbo-peritoneal shunt) has been shown to be effective
Lumboperitoneal shunt for treatment of dural ectasia in ankylosing spondylitis.
Dinichert A, Cornelius JF, Lot G.
Neurosurgery, Hôpital Lariboisière, 2 rue Ambroise Paré, Paris, France.
Neurological complications of ankylosing spondylitis (AS) are reported in 2.1% of patients. Cauda equina syndrome (CES) is rare and occurs at the ankylosing stage. MRI and CT of the lumbar spine show a cauda equina deformation with dural ectasia and bony erosion. We report three patients with AS presenting with progressive CES. These patients underwent lumboperitoneal shunting (LPS) surgery. The motor deficit improved in all cases. We suggest that CES develops from arterial pulsation of the CSF on a dural sac with reduced elasticity and that LPS reduces these intradural pressure shock waves. A meta-analysis by Ahn et al. [Ahn NU, Ahn UM, Nallamshetty L, et al. Cauda equina syndrome in ankylosing spondylitis (the CES-AS syndrome): meta-analysis of outcomes after medical and surgical treatments. J Spinal Disord 2001;14:427-33] concludes that surgical treatment has a better outcome than conservative or no treatment. Adding our 3 patients to this analysis, it appears that LPS for CES in AS is more efficient than laminectomy. LPS is a routine procedure for a rare indication, which promises improvement or atleast a stabilization of this disabling evolution of the disease.

15. Mortality in Ankylosing Spondylitis
Mortality in AS is slightly increased (1.5 times the normal population) Major causes are:
Cardiovascular disease
Pulmonary diseases
Spinal fractures
Violence, alcohol
Gastrointestinal bleeding
Amyloidosis, nephritis
Colon cancer
Myllykangas-Luosujarvi R et al. Br J Rheumatol 1998; 37:688 (N = 71)
Lehtinen K. Ann Rheum Dis 1993; 52: (N = 398)
Khan MA et al. J Rheumatol 1981; 8:86 (N = 56)
Radford EP et al. NEJM 1977; 15:297 (N = 836)

16. In Conclusion:
Late stage complications of Ankylosing Spondylitis can involve skeleton as well as internal organs
Skeleton: Bamboo spine, osteoporosis
Heart: valve disease, conduction abnormality, heart contractility reduced
Lungs: Apical fibrosis, restrictive lung & chest-wall disease
Kidneys: amyloidosis
Neurological system: spinal cord injury and cauda equina syndrome
Early detection by recognizing warning signs is the key
All complications are treatable with symptomatic treatment
Whether anti-TNF agents can prevent/treat these complications remains to be seen

17. With determination, you can achieve anything!
Mr. KM on Mount Hood, OR, at 11,000 feet, May 2003