1. Brief Overview of the Spondyloarthropathies
Stacy P. Ardoin, MD, MS
Adult and Pediatric Rheumatology
Wexner Medical Center at The Ohio State University
and Nationwide Children’s Hospital

2. Objectives
Identify the spondyloarthropathies (ankylosing spondylitis, reactive arthritis, psoriatic arthritis, enteropathic arthritis) and the clinical features they have in common.
Describe the relationship between the HLA-B27 antigen and the spondyloarthropathies.
Relate the general approach to treatment of the spondyloarthropathies
Identify the spondyloarthropathies (ankylosing spondylitis, reactive arthritis, psoriatic arthritis, enteropathic arthritis) and the clinical features they have in common.
Describe the relationship between the HLA-B27 antigen and the spondyloarthropathies.
Relate the general approach to treatment of the spondyloarthropathies

3. Objectives 1
Identify the spondyloarthropathies (ankylosing spondylitis, reactive arthritis, psoriatic arthritis, enteropathic arthritis) and the clinical features they have in common. 2
Describe the relationship between the HLA-B27 antigen and the spondyloarthropathies. 3
Relate the general approach to treatment of the spondyloarthropathies.

4. Spondyloarthropathies
Family of chronic inflammatory diseases with common clinical features
Ankylosing spondylitis (AS)
Reactive arthritis
Psoriatic arthritis
Enteropathic arthritis
Undifferentiated spondyloarthropathies
Common (1-2% population)
Family of chronic inflammatory diseases with common clinical features
Ankylosing spondylitis (AS)
Reactive arthritis
Psoriatic arthritis
Enteropathic arthritis
Undifferentiated spondyloarthropathies
Common (1-2% population)

5. Spectrum of Spondyloarthropathies
reactive
arthritis
undifferentiated
spondyloarthritis
enteropathic
arthritis
ankylosing
spondylitis
psoriatic
arthritis
Spectrum of Spondyloarthropathies
Common: overall prevalence 1-2% of adult population

6. Common Clinical Features of Spondyloarthroapthies
Involvement of axial skeleton
especially sacroiliac (SI joints)
Peripheral arthritis
Lower limbs > upper limbs
Often asymmetric, oligoarticular
Enthesitis
Extra-articular features
Mucocutaneus
Uveitis
Male predominance, familial clustering
HLA-B27 association, absence of autoantibodies
Involvement of axial skeleton
especially sacroiliac (SI joints)
Peripheral arthritis
Lower limbs > upper limbs
Often asymmetric, oligoarticular
Enthesitis
Extra-articular features
Mucocutaneus
Uveitis
Male predominance, familial clustering
HLA-B27 association, absence of autoantibodies

7. How is SpA different from RA?
Male > Female
Female > Male
Asymmetric oligoarthritis, dominant in lower extremities
Symmetric polyarthritis; dominant in upper extremities
Usually RF negative
80% RF positive
Cervical, lumbosacral spine involvement
Cervical spine involvement
How is SpA different from RA?

8. Inflammatory Back Pain
Insidious onset before age 45 yrs
Persistence for at least 3 months
Accentuation of back pain in morning after waking or after prolonged rest
Back pain improves with exercise
Insidious onset before age 45 yrs
Persistence for at least 3 months
Accentuation of back pain in morning after waking or after prolonged rest
Back pain improves with exercise
Calin & Fries. NEJM 1975; 293: 835

9. Spondyloarthropathies
Inflammatory Peripheral Arthritis
Inflammatory Peripheral Arthritis

10. Enthesitis
Definition: inflammation of tendon, ligament, joint capsule at site of attachment to bone
Clinical manifestations
Tendonitis
Fasciitis
Dactylitis
Spondylitis
Definition: inflammation of tendon, ligament, joint capsule at site of attachment to bone
Clinical manifestations
Tendonitis
Fasciitis
Dactylitis
Spondylitis

11. Inflammatory Enthesitis

12. Dactylitis Also seen in sarcoidosis, sickle cell anemia

13. Spondyloarthropathies
Symptomatic
anterior uveitis
Likelihood of Iritis
Disease Percent AS
Reiter’s
PsA w/ spondylitis 7-16
IBD
Undiff SA ND
Likelihood of Iritis
Disease Percent AS
Reiter’s
PsA w/ spondylitis 7-16
IBD 2-9
Undiff SA ND

14. Spondyloarthropathies
Urethritis or Cervicitis
Acute urethritis or cervicitis due to Chlamydia or Gonorrhea can trigger reactive arthritis.
In addition, some SpA patients may have noninfections circinate balanitis.
Acute urethritis or cervicitis due to Chlamydia or Gonorrhea can trigger reactive arthritis.
In addition, some SpA patients may have noninfections circinate balanitis.

15. Schober Test
Schober Test

16. Ankylosing spondylitis (AS)
Epidemiology
Males affected more than females
Peak age at diagnosis: 20 and 40 years
Affects up to 1% of adult population
Juvenile AS
Onset at age < 16 years
Epidemiology
Males affected more than females
Peak age at diagnosis: 20 and 40 years
Affects up to 1% of adult population
Juvenile AS
Onset at age < 16 years

17. AS: Clinical Diagnosis
Must have inflammatory arthritis of axial skeleton
Most common symptom: Inflammatory low back or buttock pain
Can have peripheral arthritis, usually oligoarticular, and enthesitis
Extra-articular symptoms:
Acute, symptomatic iritis
Ulcerations of gastrointestinal tract
Rare: interstitial lung disease, aortic valve insufficiency.
Must have inflammatory arthritis of axial skeleton
Most common symptom: Inflammatory low back or buttock pain
Can have peripheral arthritis, usually oligoarticular, and enthesitis
Extra-articular symptoms:
Acute, symptomatic iritis
Ulcerations of gastrointestinal tract
Rare: interstitial lung disease, aortic valve insufficiency.

18. Progressive deformity due to AS over a period of 36 years.
Little et al. Am J Med 1976; 60:

19. Psoriatic Arthritis (PsA)
Epidemiology
Affects males and females equally
Peak age at diagnosis: 20 and 40 years
Prevalence: 1-2 per 1000 adults
Incidence: 6 per 100,000 adults/year
Juvenile PsA
Onset at age < 16 years
Considered a juvenile idopathic arthritis subtype.
Epidemiology
Affects males and females equally
Peak age at diagnosis: 20 and 40 years
Prevalence: 1-2 per 1000 adults
Incidence: 6 per 100,000 adults/year
Juvenile PsA
Onset at age < 16 years
Considered a juvenile idopathic arthritis subtype.

20. PsA: Clinical Diagnosis
Psoriasis
Classic skin lesions
Nail lesions (pits, onycholysis)
Arthritis occurs before skin lesions in about 15% of patients
Inflammatory arthritis
Axial
Peripheral - usually oligoarticular, can be polyarticular. Often involves DIP joints unlike RA.
Enthesitis
Extra-articular: symptomatic uveitis
Psoriasis
Classic skin lesions
Nail lesions (pits, onycholysis)
Arthritis occurs before skin lesions in about 15% of patients
Inflammatory arthritis
Axial
Peripheral - usually oligoarticular, can be polyarticular. Often involves DIP joints unlike RA.
Enthesitis
Extra-articular: symptomatic uveitis

21. Psoriatic Arthritis
In this image, note the nail findings and swelling of DIP joints in a patient with PsA.
This image shows extensive and destructive joint involvement of finger joints in a patient with PsA.
In this image, note the nail findings and swelling of DIP joints in a patient with PsA.
This image shows extensive and destructive joint involvement of finger joints in a patient with PsA

22. Skin and Nail Changes in PsA
Classic silvery plaques over elbows and in umbilicus.
Classic silvery plaques over elbows and in umbilicus.
Nail thickening, discoloration, onycholysis. This patient also has psoriatic plaques on hands and obvious DIP swelling.
Nail pitting in PsA
Nail thickening, discoloration, onycholysis. This patient also has psoriatic plaques on hands and obvious DIP swelling.
Nail pitting in PsA

23. Enteropathic Arthritis
Complication of inflammatory bowel disease (IBD)
Arthritis can parallel IBD disease activity
Arthritis can be axial, peripheral
Complication of inflammatory bowel disease (IBD)
Arthritis can parallel IBD disease activity
Arthritis can be axial, peripheral

24. Signs of Enteropathic Arthritis due to IBD
Pyoderma gangrenosum
Symptomatic uveitis
Signs of Enteropathic Arthritis due to IBD
Oral ulcers
Erythema nodosum

25. Reactive Arthritis
Definition – Aseptic peripheral arthritis occurring within one month of infection
Infections: GI, urethral, cervical (other)
Extra-articular manifestations common
Can be self limited or chronic
HLA-B27+ increases risk of chronicity
Definition – Aseptic peripheral arthritis occurring within one month of infection
Infections: GI, urethral, cervical (other)
Extra-articular manifestations common
Can be self limited or chronic
HLA-B27+ increases risk of chronicity

26. Reactive Arthritis Clockwise from top left.
Keratoderma blenorrhagicum: Scaly pustules on feet that can occur in reactive arthritis
Urethritis: Chlamydia or gonorrhea may trigger reactive arthritis
Cervicitis: Chlamydia or gonorrhea my trigger reactive arthritis
Vulvitis may occur in reactive arthritis
Circinate balinitis may occur in reactive arthritis
Inflammatory eye disease may occur – in this image, conjunctivitis. May also have symptomatic uveitis.

27. Radiographic Findings in the Spondyloarthropathies
Sacroiliitis: Can be unilateral or bilateral. See widening and irregularity of joint space, sclerosis, erosions.

28. Lumbar spine: bridging syndesmophytes, “bamboo spine”.
New bone forms along the interosseous ligaments.
Lumbar spine: bridging syndesmophytes, “bamboo spine”.
New bone forms along the interosseous ligaments.

29. Enthesitis
Erosion
Enthesitis
New bone

30. HLA-B27 and the Spondyloarthropathies
Condition
Percent of people with the condition who are HLA-B27 positive
Ankylosing Spondylitis
Caucasians: 90-95%
African-Americans:50%
Reactive Arthritis
60-80%
Enteropathic Arthritis
60%
Psoriatic Arthritis
Undifferentiated Spondyloarthropathy
20-25%
Adult AS is inherited as an autosomal dominant trait w/ penetrance of 20%

31. HLA-B27 in Different Populations
Prevalence
Haida Indians
50%
Eskimos
20%
Norwegians
16%
US Caucasians 8%
African-Americans 2%
Japanese
<1%
HLA-B27 in Different Populations

32. HLA-B27: Is it important?
HLA-B27 not sufficient to cause disease but appears to increase risk
HLA-B27antigen may impact the way the immune system reacts to bacteria, especially in the gut.
Overzealous reactions to bacteria may trigger systemic inflammation.
Animal models required presence of bacterial components
HLA-B27 neither sufficient or necessary as SpA may develop w/o.
Intestinal inflammation plays HLA-B27 independent role in development of SpA

33. Treatment Approach to Spondyloarthropathies
NSAID sulfasalazine, methotrexate (often ineffective for axial disease)
intraarticular
steroids 
topical steroids
PT, OT
Treatment Approach to Spondyloarthropathies 
Anti-TNF agents
Anti-TNF agents are usually the most effective therapy for moderate to severe spondyloarthropathies.

34. Case 1

35. Case 1
History: A 42 yr old man develops swelling, morning stiffness in his left ankle and low back stiffness for 1 hour every morning. He also has pain in heels and bottoms of feet. This has been going on for about 3 weeks. Seven weeks ago he had urethral discharge and pain on urination. This improved without treatment but persists.
History: A 42 yr old man develops swelling, morning stiffness in his left ankle and low back stiffness for 1 hour every morning. He also has pain in heels and bottoms of feet. This has been going on for about 3 weeks. Seven weeks ago he had urethral discharge and pain on urination. This improved without treatment but persists.

36. Case 1 - continued
Other past medical history: None Other symptoms: No fevers, weight loss. No nasal or oral ulcers. No rash. No GI symptoms. Dysuria improved. Family history: He has an uncle with chronic back pain, worst in mornings. Social history: He is a married accountant who’s had 3 sexual partners in the past year.
Other past medical history: None
Other symptoms: No fevers, weight loss. No nasal or oral ulcers. No rash. No GI symptoms. Dysuria improved.
Family history: He has an uncle with chronic back pain, worst in mornings.
Social history: He is a married accountant who’s had 3 sexual partners in the past year.

37. Case 1 - continued Physical Exam:
He has no fever and does not appear acutely ill. His exam is normal except for the following findings:
Genitourinary exam: erythema at urethra, no discharge
Musculoskeletal exam – effusion of his left ankle, reduced range of motion of lumbar spine with tenderness over sacroiliac joints on palpation, tender and swollen Achilles tendons.
Physical Exam:
He has no fever and does not appear acutely ill. His exam is normal except for the following findings:
Genitourinary exam: erythema at urethra, no discharge
Musculoskeletal exam – effusion of his left ankle, reduced range of motion of lumbar spine with tenderness over sacroiliac joints on palpation, tender and swollen Achilles tendons.

38. Case 1 - Labs
Complete blood count, liver and kidney tests are normal. Marks of inflammation (sedimentation rate, c-reactive protein) are elevated Arthrocentesis of left ankle is performed: Synovial fluid – WBC 24,000, culture and gram stain are negative, no crystals. Urethral swab studies show that he has Chlamydia HLA-B27 positive
Complete blood count, liver and kidney tests are normal.
Marks of inflammation (sedimentation rate, c-reactive protein) are elevated
Arthrocentesis of left ankle is performed:
Synovial fluid – WBC 24,000, culture and gram stain are negative, no crystals.
Urethral swab studies show that he has Chlamydia
HLA-B27 positive

39. Case 1 - Management
He and partners are treated with antibiotics for Chlamydia urethritis. He is treated with a non-steroidal anti-inflammatory drug (NSAID) for 4 weeks and the arthritis and enthesitis resolve. The fact that he is HLA-B27 positive increases the risk that his symptoms may recur and may become chronic with or without an infection.
He and partners are treated with antibiotics for Chlamydia urethritis. He is treated with a non-steroidal anti-inflammatory drug (NSAID) for 4 weeks and the arthritis and enthesitis resolve.
The fact that he is HLA-B27 positive increases the risk that his symptoms may recur and may become chronic with or without an infection.

40. Case 2

41. Case 2
History: 20 yr old man presents with incapacitating lower back pain and stiffness. These symptoms have been present and worsening for 6 months. He’s had no injury to his back. None of his other joints are bothering him. He denies other symptoms.
History: 20 yr old man presents with incapacitating lower back pain and stiffness. These symptoms have been present and worsening for 6 months. He’s had no injury to his back. None of his other joints are bothering him. He denies other symptoms.

42. Case 2 - continued
Other medical history: None Review of systems: He specifically denies fevers, rash, eye pain or redness, oral ulcers, abdominal pain, diarrhea, dysuria, urethral discharge. Family history: His brother has Crohn’s disease.
Other medical history: None
Review of systems: He specifically denies fevers, rash, eye pain or redness, oral ulcers, abdominal pain, diarrhea, dysuria, urethral discharge.
Family history: His brother has Crohn’s disease.

43. Case 2 - continued Physical Exam: He appears uncomfortable.
His exam is normal except for:
Tenderness at both sacroiliac joints on palpation, decreased lumbar spine range of motion (reduced Schober’s test).
Physical Exam:
He appears uncomfortable.
His exam is normal except for:
Tenderness at both sacroiliac joints on palpation, decreased lumbar spine range of motion (reduced Schober’s test).

44. Case 2 - Labs Blood count, liver and kidney tests are normal.
Markers of inflammation (sedimentation rate and c-reactive protein) are elevated
HLA-B27 positive
Blood count, liver and kidney tests are normal.
Markers of inflammation (sedimentation rate and c-reactive protein) are elevated
HLA-B27 positive

45. He has sacroiliitis of bilateral SI joints
Case 2 – x-rays
He has sacroiliitis of bilateral SI joints
He has sacroiliitis of bilateral SI joints
X-ray shows subchondral sclerosis and irregularities of the joint surface, including erosions in the iliac side of the sacroiliac joints.
X-ray shows subchondral sclerosis and irregularities of the joint surface, including erosions in the iliac side of the sacroiliac joints.

46. Case 2 – Management
He is started on a non-steroidal anti-inflammatory drug but this fails to control his symptoms adequately. Because he has axial disease which usually does not respond well to methotrexate or sulfasalazine, he is started on etanercept, an anti-TNF drug with marked improvement in symptoms.
He is started on a non-steroidal anti-inflammatory drug but this fails to control his symptoms adequately.
Because he has axial disease which usually does not respond well to methotrexate or sulfasalazine, he is started on etanercept, an anti-TNF drug with marked improvement in symptoms.

47. Thanks!