Ankylosing SpondylitisAnkylosing SpondylitisLate ComplicationsLate Complications

Atul Deodhar MDAtul Deodhar MDAssociate Professor of MedicineAssociate Professor of Medicine

Medical Director, Rheumatology ClinicsMedical Director, Rheumatology ClinicsOregon Health & Science UniversityOregon Health & Science University

Portland, ORPortland, OR

Spondylitis Association of America Webinar March 21st, 2009

General Comments on ASGeneral Comments on AS Major part of the disease progression occurs in the Major part of the disease progression occurs in the

first 10 years of the diseasefirst 10 years of the disease11

‘‘Bamboo spine’ occurs in 20% after 20 yearsBamboo spine’ occurs in 20% after 20 years3

Women have more involvement of cervical spine & Women have more involvement of cervical spine & peripheral joints than menperipheral joints than men2

AS has no adverse effect on fertility, pregnancy or AS has no adverse effect on fertility, pregnancy or fetusfetus

Unlike in RA, pregnancy has no consistent effect on Unlike in RA, pregnancy has no consistent effect on AS disease activityAS disease activity

Men have worse radiographic progression than Men have worse radiographic progression than women, but ‘self-reported’ functional limitations are women, but ‘self-reported’ functional limitations are worse in womenworse in women44

1Carette S. et al. Arthritis Rheum 1983;26:186-90 2Lee W et al. Arthritis Rheum 2008;59:449-54 3Sampaio-Barros PD J Rheumatol 2001;28:560-65 4Lee w et al. Ann Rheum Dis 2007;66:633-8

Self-Reported AS Symptoms andQuality-of-Life Concerns*

Ward M. Arthritis Care Res. 1999

*7 greatest QOLconcerns reported

Prognosis of ASPrognosis of AS Following factors at presentation indicate increased Following factors at presentation indicate increased

disease severity disease severity Hip arthritis — odds ratio (OR) 23 Hip arthritis — odds ratio (OR) 23 Sausage-like finger or toe — OR 8 Sausage-like finger or toe — OR 8 Poor response to NSAID — OR 8 Poor response to NSAID — OR 8 High ESR (>30 mm/h) — OR 7 High ESR (>30 mm/h) — OR 7 Limitation in range of motion @ lumbar spine — OR 7 Limitation in range of motion @ lumbar spine — OR 7 Oligoarthritis — OR 4 Oligoarthritis — OR 4 Onset less than 16 years of age — OR 3 Onset less than 16 years of age — OR 3

If no factor is present: mild outcome is likely (sensitivity If no factor is present: mild outcome is likely (sensitivity 93%, specificity 78%)93%, specificity 78%)

If hip is involved or 3 other factors are present, severe If hip is involved or 3 other factors are present, severe disease is predicted: sensitivity 50%, specificity 98%disease is predicted: sensitivity 50%, specificity 98%

29 3135

383944

4853

2225

0

20

40

60

<41 41-50 51-60 61-70 >70

Years

Pro

po

rtio

n o

f P

atie

nts

(%

)

RA (n=11,643) AS (n=5,581)

Zink A, et al. J Rheumatol. 2000;27:613-22.

* P<0.0025 **

*

AS Burden of Disease: % of Male AS Burden of Disease: % of Male Patients with Disability (Steinbrocker > II)Patients with Disability (Steinbrocker > II)

2833

4246

2634

44

60

20 16

0

20

40

60

80

<41 41-50 51-60 61-70 >70

Years

Pro

po

rtio

n o

f P

atie

nts

(%

)

RA (n=38,180) AS (n=2,487)

Zink A, et al. J Rheumatol. 2000;27:613-22.

* P<0.0025

*

AS Burden of Disease: % of Female AS Burden of Disease: % of Female Patients with Disability (Steinbrocker >II)Patients with Disability (Steinbrocker >II)

1Boonen A Clin Exp Rheumatol 2002;20(suppl 28):S23-S26.2Gran JT et al. Br J Rheumatol 1997;36:766-71

Early Retirement in ASEarly 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

0

20

40

60

Disease duration at retirement Retirement age

Ye

ars

Men Women

96.2% retired due to AS

P<0.02

Other Disease Manifestations in ASOther Disease Manifestations in AS

Eyes(Acute Anterior Uveitis)

Heart(Aortic Insufficiency, Heart Block)

Gut (Inflammatory bowel disease,

Microscopic inflammatory lesion)

Dactylitis Cauda Equina Syndrome

Osteopenia, OsteoporosisSpinal Fracture

Skin(Psoriasis & Nail Changes)

Kidneys(Amyloidosis)

Lungs(Restrictive Lung Disease, Apical Fibrocystic Disease)

Up to 40%

Microscopic involvement 20-70%6.5% have Crohn’s Disease Up to 10%

3% to 10%

Courtesy of J. Cush, MD

Spectrum of ASSpectrum of ASEarly Moderate Severe

Late Complications of ASLate Complications of AS

Skeletal Complications

Bamboo spineBamboo spine OsteoporosisOsteoporosis Spinal fracturesSpinal fractures Fused hips and shouldersFused hips and shoulders Fused ribs: reduced chest Fused ribs: reduced chest

wall expansionwall expansion

Non-skeletal Complications

Heart: valvular (aortic and Heart: valvular (aortic and mitral) regurgitation, mitral) regurgitation, conduction abnormalities, conduction abnormalities, diastolic dysfunctiondiastolic dysfunction

Lung: apical fibrosis, Lung: apical fibrosis, restrictive lung diseaserestrictive lung disease

Kidney: amyloidosisKidney: amyloidosis Neurological: cauda equina Neurological: cauda equina

syndrome, spinal cord syndrome, spinal cord compressioncompression

Aortic regurgitation seen in 3.5% of patients after 15yrs; 10% Aortic regurgitation seen in 3.5% of patients after 15yrs; 10% at 30 yrs, and is associated with peripheral arthritisat 30 yrs, and is associated with peripheral arthritis

Warning signs: None! Be aware of the complication None! Be aware of the complication Treatment: medical management. In severe cases: valve Treatment: medical management. In severe cases: valve

replacementreplacement

Aortic Dilatation in ASAortic Dilatation in AS

Bergfeldt Am J Med 1988;85:12-18, Bulkley & Roberts Circulation 1973;48:1014-27

Heart & Lung Disease in ASHeart & Lung Disease in AS Conduction abnormalities (heart block) & diastolic Conduction abnormalities (heart block) & diastolic

dysfunction seen in a minority of patients with long-standing dysfunction seen in a minority of patients with long-standing ASAS

Whether these changes are more common in AS compared Whether these changes are more common in AS compared to general population, is controversial.to general population, is controversial. One Swiss study One Swiss study found no increased prevalencefound no increased prevalence11

Pulmonary manifestations of long-term AS: Interstitial lung Pulmonary manifestations of long-term AS: Interstitial lung disease, upper lobe fibrosis, reduced chest expansion (due disease, upper lobe fibrosis, reduced chest expansion (due to fused ribs and restricted chest cage movement) 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

1Lang U et al. Eur J Med Res 2007;12(12):573-81

Spinal cord injury in ASSpinal cord injury in AS Osteoporosis is common in ASOsteoporosis is common in AS Spinal BMD can be falsely increased due of new bone Spinal BMD can be falsely increased due of new bone

formation – femoral BMD measurement recommended formation – femoral BMD measurement recommended Patients with AS suffer spinal fractures at an increased Patients with AS suffer spinal fractures at an increased

rate with minimal trauma (lifetime incidence 4%-18%)rate with minimal trauma (lifetime incidence 4%-18%) Incidence of spinal cord injury increased > 10-fold when Incidence of spinal cord injury increased > 10-fold when

compared to the general population of Finland compared to the general population of Finland Compression of the spinal cord at atlanto-axial level can Compression of the spinal cord at atlanto-axial level can

occur with paraparesis or tetraparesis occur with paraparesis or tetraparesis Warning signs for fracture: sudden onset of new sudden onset of new

severe back pain after stable diseasesevere back pain after stable disease Warning signs for spinal cord injury: new onset new onset

sensory or motor symptoms (tingling, numbness, sensory or motor symptoms (tingling, numbness, weakness, bladder/bowel involvement) weakness, bladder/bowel involvement)

Cauda Equina Syndrome in ASCauda Equina Syndrome in AS

Neurological complications are rare (2%) in ASNeurological complications are rare (2%) in AS Cauda equina syndrome is very rare complication, seen Cauda equina syndrome is very rare complication, seen

in long standing ASin long standing AS Affects nerve roots from lumbar & sacral spineAffects nerve roots from lumbar & sacral spine May be secondary to inflammation of the covering of the May be secondary to inflammation of the covering of the

spinal cord (called arachnoiditis)spinal cord (called arachnoiditis) Warning signs: Slowly progressive pain, numbness in Slowly progressive pain, numbness in

the saddle distribution, bowel/bladder incontinencethe saddle distribution, bowel/bladder incontinence Rarely, muscle weakness symptoms seenRarely, muscle weakness symptoms seen Diagnosed by imaging (CT, MRI)Diagnosed by imaging (CT, MRI) Treatment: recently, surgery (laminectomy, lumbo-Treatment: recently, surgery (laminectomy, lumbo-

peritoneal shunt) has been shown to be effectiveperitoneal shunt) has been shown to be effective

Mortality in Ankylosing SpondylitisMortality in Ankylosing Spondylitis

Mortality in AS is slightly increased (1.5 times the Mortality in AS is slightly increased (1.5 times the normal population) Major causes are: normal population) Major causes are: Cardiovascular diseaseCardiovascular disease Pulmonary diseases Pulmonary diseases Spinal fracturesSpinal fractures Violence, alcoholViolence, alcohol Gastrointestinal bleedingGastrointestinal bleeding Amyloidosis, nephritisAmyloidosis, nephritis Colon cancerColon cancer

Myllykangas-Luosujarvi R et al. Br J Rheumatol 1998; 37:688 (N = 71)Lehtinen K. Ann Rheum Dis 1993; 52:174 (N = 398)Khan MA et al. J Rheumatol 1981; 8:86 (N = 56)Radford EP et al. NEJM 1977; 15:297 (N = 836)

In Conclusion:In Conclusion: Late stage complications of Ankylosing Spondylitis can Late stage complications of Ankylosing Spondylitis can

involve skeleton as well as internal organsinvolve skeleton as well as internal organs Skeleton: Bamboo spine, osteoporosisSkeleton: Bamboo spine, osteoporosis Heart: valve disease, conduction abnormality, heart Heart: valve disease, conduction abnormality, heart

contractility reducedcontractility reduced Lungs: Apical fibrosis, restrictive lung & chest-wall diseaseLungs: Apical fibrosis, restrictive lung & chest-wall disease Kidneys: amyloidosisKidneys: amyloidosis Neurological system: spinal cord injury and cauda equina Neurological system: spinal cord injury and cauda equina

syndromesyndrome Early detection by recognizing Early detection by recognizing warning signs is the key is the key All complications are treatable with symptomatic treatmentAll complications are treatable with symptomatic treatment Whether anti-TNF agents can prevent/treat these Whether anti-TNF agents can prevent/treat these

complications remains to be seencomplications remains to be seen

Mr. KM on Mount Hood, OR, at 11,000 feet, May 2003

With determination, you can achieve With determination, you can achieve anything!anything!