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Spondyloarthropathies

I. Introduction

A. Spondyloarthropathies (SPA) are a collection of related disorders: HLA-B27 and enthesopathy.

B. Involvement of L-S spine, entheses and certain extraarticular organs typically involved.

C. Classification

1. Ankylosing spondylitis (AS).

a. Undifferentiated spondyloarthropathy (UspA). SEA syndrome (syndrome of seronegativity, enthesopathy and arthropathy) used to describe similar syndrome in pediatric patients.

2. Postinfectious arthritis.

a. Reiter's syndrome (GU) (RS).

b. Reactive arthritis (GI).

3. Arthritis associated with inflammatory bowel disease.

a. Crohn's disease.

b. Ulcerative colitis.

c. Other - Whipple's disease, Behcet's disease.

4. Psoriatic arthritis (PSA).

D. Etiology and Pathogenesis

1. Strong association of SpA with HLA-B27 especially in Caucasians with AS.

2. Shared amino acid sequence between HLA-B*2705 antigen and Klebsiella pneumoniae nitrogenase: QTDRED.

a. The shared epitope involves the antigen binding site of HLA-B27.

b. Possible that molecular mimicry resulting in a cross reaction between exogenous antigen (Klebsiella pneumoniae nitrogenase) and self antigen (HLA-B27) could lead to autoimmune reaction leading to tissue damage.

c. HLA-B27 transgenic rat model of spondyloarthropathy - requires the presence of

F. HIV and spondyloarthropathies

1. Association of HIV with RS (often incomplete), PsA, overlap and UspA. 

2. HIV may be associated with new onset of aggressive disease. 

3. HIV is associated with severe exacerbation of preexisting SpA.

4.Articular and skin/nail disease tends to be worse in RS and PsA patients with HIV. 

a. Articular disease can be rapidly progressive with early onset erosions. 

b. Prominent enthesopathy.

II. Ankylosing Spondylitis

A. Definition - chronic inflammatory disease involving the axial skeleton predominantly but may also involve peripheral joints, entheses and extraarticular organs.

B. Epidemiology.

1. Association with HLA-B27

                                                             

Healthy Caucasians        8%
Ankylosing spondylitis (Caucasian)     92%
Ankylosing spondylitis (black)      50%
Reiter's syndrome        80%
IBD associated with spondylitis      60%
Psoriasis associated with spondylitis    60%
Uveitis     50%

2. Prevalence - up to 1% of general population.

3.Approximately 2-5% of all HLA-B27+. people will develop AS and up to 20% of HLA-B27+ first-degree relatives of patients with HLA-B27+ AS.

4.Other genetic factors.

a. HLA-B60, HLA-B40 associated with AS.

b. HLA-B7 associated with UspA.

5. Prevalence in males and females is likely approximately equal.

a. Diagnosed much more frequently in males; M:.F as high as 10:1 for clinical AS. 

b. Females have lower incidence of and less severe axial skeletal involvement and more frequent peripheral joint disease making diagnosis more difficult.

6. Peak age of onset late teens to early adulthood.

7. Undifferentiated SpA is probably even more common than AS.

a. Inflammatory low back pain, buttock pain (unilateral or alternating), peripheral arthritis (asymmetric osteoarthritis), dactylitis, enthesopathy.

b. May have extraarticular manifestations such as acute anterior uveitis. 

c. Do not fulfill criteria for any specific spondyloarthropathy. 

d. Lower incidence of positive HLA-B27.

C. Clinical features of spinal involvement.

2. Typical spinal symptoms include stiffness and dull ache in L-S spine especially in AM with vague radiation of pain into buttocks, a. 3-5% of all back pain patients have a SpA.

3.Spinal disease progresses proximally at a slow rate and occasionally results in a bamboo spine.

a. Fused spine is prone to fracture. 

b. Spinal fracture may occur with minimal trauma resulting in increased pain and mobility.

D. Extraspinal articular disease.

1. 35% of AS patients exhibit peripheral arthritis at some point in their illness.

2. Up to 20% may present with peripheral arthritis.

3.Usually asymmetric oligoarticular arthritis of large joints of lower extremity.

a. Destructive arthritis may involve hips or shoulders.

4.Enthesopathy

E. Extraarticular manifestations

1. Constitutional - fatigue, weight loss; low-grade fever.

2.Eye disease - conjunctivitis and acute anterior uveitis.

a. Occurs in up to 25%.

b. Unrelated to severity of spondylitis but may be related to peripheral arthritis. 

F. Physical examination.

1. Decreased spinal mobility.

2. Decreased lumbar lordosis.

3.Schober test - 10 cm length along L-S spine should increase to >16 cm with spinal flexion. Test is not specific.

4.Measurement of chest wall expansion is very insensitive as it is a late finding.

5.L-S spine and SI joints may be tender.

6.Peripheral arthritis especially involving large joints of lower extremities.

a. Destructive arthritis of hips and occasionally shoulders.

7.Enthesopathy

8.Evidence of extraarticular disease - eyes, heart, lungs.

G. Laboratory evaluation

1. Normochromic, normocytic anemia.

2. Elevated ESR, often has no correlation with disease activity. 

3. Elevated alkaline phosphatase - 50%. 

4. Elevated CPK not uncommon. 5. HLA-B27+.

H. Radiology

1. Sacroiliitis

a. Grade 0 - normal.

b. Grade I - suspicious but not specific.

c. Grade II - minimal, loss of definition of edge of joints, mild sclerosis, erosions. 

d. Grade I!1 - moderate, sclerosis of both sides of joints, blurring, erosions, of joint space.

e. Grade IV - severe, fusion or ankylosis. 

f. Sacroiliitis of AS is usually symmetric. 

g. Must differentiate from osteitis condensans ilii, Paget's disease, metastases. 

h. MRI with gadolinium contrast is more sensitive in detecting acute and chronic sacroiliitis; not cost effective.

2. Vertebral changes

a. Squaring of vertebral bodies, syndesmophytes, ossification of ligaments.

b. Spinal disease in AS is gradually ascending and continuous.

3. Extraspinal changes

a. Ossification of enthesopathic lesions - plantar spurs, fluffy periostitis of Achilles tendon insertion.

b. Destructive arthritis of hips and shoulders.

I. Diagnostic criteria (New York, 1984).

1. back pain with inflammatory characteristics.

2. Limitation of lumbar spine motion in sagital and frontal planes.

3. Decreased chest expansion.

4. Bilateral sacroiliitis grade 2 or higher.

5. Unilateral sacroiliitis grade 3 or higher.

6. Definite AS if x-rays changes in criterion 4 or 5 plus any clinical criterion.

J. Prognosis - fair to good; better than RA.

III. Reiter's syndrome and Reactive arthritis

A. Definition - reactive arthritis occurring after a GU or G! infection.

1. Seronegative asymmetric oligoarticular arthritis (especially lower extremities)

2.Plus at least one of the following: 

a. Urethritis/cervicitis. 

b. Dysentery.

c. Inflammatory eye disease - conjunctivitis, uveitis.

d. Mucocutaneous disease - oral ulcers, balanitis, keratoderma blennorrhagica. 

B. Etiology

1. Genetics - association with HLA-B27.

2. Infectious etiology.

a. Postvenereal- Chlamydia, Mycoplasma.

(1) Prolonged antibiotic therapy may be beneficial.

b. Postdysenteric- Yersinia enterocolitica, Salmonella typhimurium, Shigella flexneri.

C. Epidemiology

1. Underdiagnosed because of difficulty in making diagnosis, especially in females. 

2. Sex distribution is M:F = 10:1.

3. Age range from late childhood to 50-60 years. Peak age of onset is 20-30 years. 

D. Clinical features

1. Arthritis 100%.

a. Asymmetric oligoarticular arthritis involving predominantly in lower extremities. 

b. Occurs 1-3 weeks after GU or GI infection. 

c. Spinal disease - 20-30%.

(1) Asymmetric sacroiliitis and discontinuous spinal disease.

2. Enthesopathy - 70%.

3. Extraarticular manifestations.

a. Constitutional symptoms -fatigue, weight loss, fever.

b. Urethritis/cervicitis 90%

(1) Sterile reactive inflammation may occur in postdysenteric form.

c. Eyes- 60%; conjunctivitis, uveitis.

d. Mucocutaneous manifestations.

(1) Oral ulcers - 25%.

(2) Keratoderma blennorrhagica - 20%.

(3) Circinate balanitis - 50%.

(4) Nail changes (onycholysis) - 10%.

e. Cardiovascular disease - conduction defects, aortic regurgitation, pericarditis.

f. Nervous system - peripheral neuropathy, transient hemiplegia, cranial nerve lesions.

g. Pulmonary - pleuritis, infiltrates.

(1) Chest wall pain may occur secondary to enthesopathy.

h. Rarely - purpura, thrombophlebitis, amyloidosis.

E. Prognosis

1. Difficult to assess because patients with Reiter's syndrome are usually young and mobile and therefore difficult to follow.

2. Centers that have a strong interest in Reiter's syndrome tend to accumulate patients with more severe disease.

3. Patients frequently have recurrent or persistent arthropathy of spine and/or peripheral joints and recurrent uveitis.

4. Morbidity may result in unemployment or occupation change.

5.Outcome may be improved by 3 month course of antibiotics with GU associated Reiter's syndrome.

F. Postdysenteric reactive arthritis.

1. Definition - sterile arthritis following infection in other organs. a. Strong association with HLA-B27. b. M:F is 1:1.

2. Many bacteria, protozoa and viruses may precipitate.

3. Most common- Yersinia, Salmonella, Shigella.

4. Arthritis is similar in presentation to RS.

5. Extraarticular manifestations include systemic symptoms such as fever and skin rashes such as erythema multiforme and erythema nodosum. 

6. Prognosis is very good; better than AS.

a. Patients may have continued pain in affected joints, entheses or low back but the arthritis is rarely destructive.

IV. Psoriatic arthritis

A. Definition

1.Presence of psoriasis or psoriatic nail changes and a seronegative peripheral arthritis, with or without spinal involvement.

B. Epidemiology

1. Uncommon disease.

2. Psoriasis is present in 1-3% of the general population.

3.Of all psoriatics, 5% have sacroiliitis and/or spondylitis while 10-20% have peripheral arthritis.

4.M:F is 1:1.

5.Peak age of onset is 35-45.

6.HLA-B27 is associated with spondylitis but not peripheral arthritis.

a. HLA-DR7 with peripheral arthritis.

b. HLA-B27, B39, DR3, DR4, DQw3 - risk factors for progressive peripheral arthritis. 

C. Clinical features

1. Onset is usually insidious.

2. Patterns of joint involvement.

a. Asymmetric oligoarticular arthritis - 50%

(1) Most joints may be involved.

(2) Small joints of hands and feet are frequently involved including DIPs.

(3) Sausage digits.

b. Predominant DIP involvement- 5-10%

(1) "Classic" form commonly associated with nail changes.

c. Arthritis mutilans - 5%.

(1) Severe deforming arthritis of small joints of hands with osteolysis

(2) May display constitutional symptoms.

(3) Usually associated with severe skin disease and sacroiliitis.

d. Symmetric polyarthritis 25%.

(1) to RA but seronegative and less severe.

(2) Those patients with psoriasis and RF+ symmetric polyarthritis are considered to have coincidental RA.

e. Spondylitis - 20-40%

(1) May occur alone or with other forms of psoriatic arthritis.

(2) Often asymptomatic.

(3) Sacroiliitis is usually asymmetric and spinal disease, discontinuous.

f. Other rare forms of psoriatic arthritis.

(1) Isolated acro-osteolysis.
(2) Destructive arthritis of sternomanubrial joint.

(3) C-spine disease with C1-C2 subluxation.

3. Skin disease.

a. Psoriasis usually precedes arthritis.

b. Although psoriasis tends to more severe in patients with severe, deforming polyarthritis, skin and joint disease tends to correlate very little.

c. Nail changes are present in 80% of psoriatic arthritis patients compared with 1:5% of general psoriatics.

4. Extraarticular manifestations.

a. Eyes; conjunctivitis - 20%, uveitis - 10%.

b. Rarely aortic insufficiency, pulmonary fibrosis, amyloidosis.

5. Laboratory

a. No specific laboratory tests.

(1) Hyperuricemia is associated with severe psoriasis but not psoriatic arthritis.

b. Radiology

(1) Radiographic changes frequently found in DIPs and SI joints.

(2) Bony ankylosis of IP joints, destruction of DIPs, periosteal new bone formation, resorption of distal phalanges.

(a) Pencil in cup deformities.

(3) Asymmetric sacroiliitis and spondylitis.

D. Prognosis - fair; overall somewhat better than RA.

V. Enteropathic arthritis

A. Definition -spondyloarthropathy associated with a defined gastrointestinal disease.

B. Inflammatory bowel disease (IBD).

1. HLA-B27 is strongly associated with AS associated IBD but not isolated sacroiliitis or peripheral arthritis.

2.Peripheral arthritis.

a. Somewhat more common with Crohn's disease (20%) than UC (10%). 

b. M:F is 1:1. 

c. Usually becomes manifest after the onset of IBD.

(1) In children arthritis may precede IBD.

d. One of the most frequent extracolonic manifestations. 

e. More frequent with severe IBD and with other extracolonic manifestations.

 f. Asymmetric oligoarticular arthritis usually involving the large joints of the lower extremities.

g. Occurs as fairly acute bouts of arthritis often correlating with flares of IBD. 

h. Attacks usually resolve after several weeks to months. 

i. Peripheral arthritis is rarely destructive and prognosis very good.

3. Spinal disease.

a. Similar to AS in clinical and radiographic features. 

b. Sacroiliitis - 15%. 

c. AS - 5%. 

d. Onset may precede IBD. 

e. No correlation with course of IBD.

C. Others - Whipple's disease, Behcet's disease.

VI. Management of spondyloarthropathies

A. NSAIDs

1. Indomethacin (and Phenylbutazone) may be more effective than other NSAIDs.

2. Salicylates not generally effective except in psoriatic arthritis.

B. Sulfasalazine

1. Start at 500 mg po bid and increase up to 3000 mg/day as