Seronegative arthropathies Flashcards
Seronegative spondyloarthropathies
A spectrum of arthritic conditions characterized by inflammation involving the spine, peripheral joints, and extra-articular sites in the ABSENCE of rheumatoid factor
- ankylosing spondylitis
- reactive arthritis (reiter’s syndrome)
- psoriatic arthritis
- arthritis associated with IBD
What do they have in common?
- Involve the spine in a process of ankylosis –> leads to fusion of the spine vertebrate due to inflammation
- Generally characterized by an asymmetric oligoarthritis
- Inflammation of tendons/ ligaments (enthesitis)
- May involve extra-articular sites such as eye, skin, and bowel
- Association with HLA B27 : Strong association in ankylosing spondylitis, moderately strong in other subtypes
A common pathogenesis?
- reactive arthritis is by definition an arthritis following an infection –> arthritis results from an inappropriate immune response to an infectious pathogen
- possible that all the seronegative spondyloarthropathies also have an infectious cause
HLAB27 transgenic rat
- Transgenic rat expresses human HLA B27 on the surface of its cells
- Rats develop ankylosing spondylitis –> however, if raised in a germ free environment, they do not develop disease
- If reconstitute normal gut flora and disease occurs
Ankylosing spondylitis
- definition
- epidemiology
Characterized by the insidious onset of low back pain, worse in the morning and which improves during the day (inflammatory back pain)
- Involves the axial skeleton including the sacroiliac joints, usually extending caudal to cephalic in symmetric uniform fashion – this is very characteristic for ankyolosing sponditlitis, which differentiates it from the other types of seronegative arthropathies, which can all be more patchy in their presentations
Epidemiology
- primarily presents in men 7% of unaffected caucasians are HLAB27+, so having this haplotype does not necessarily mean you will have AS
- prevalence among caucasians –> estimated to be 1.5/1000
AS - clinical manifestations
- low back pain, worse in the morning, improves with activity
- anterior uveitis
- peripheral arthritis, usually lower extremities
- aortic insufficiency, conduction blocks
- subclinical IBD
- renal amyloidosis –> late manifestation
- reduced lung expansion –> secondary to involvement of costovertebral joints
- pulmonary fibrosis –> usually in the apices (rare)
- cauda equina syndrome –> due to narrowing of the spinal canal
- often see lumbar flattening due to fusion of vertebrate
Schober test - mark 2 spaces on lower back that are 10 cm apart –> when bend over the space between should be at least 15 cm, but in AS its usually much less
AS - radiology
Sacroiliitis –> erosions with eventual fusion (ankylosis) of the SI joints, usually bilateral
—> Natural history is that it will be painful and tender over the joints for a number of years, then the joint eventually calcifies and usually the pain goes away
Syndesmophytes –> ossification of the annulus fibrosus, usually bilateral and progressing from caudad to cephalad (Bamboo Spine)
AS - treatment
- NSAID’s are cornerstone, provide symptom relief only? –> unclear if there is improvement in disease progression
- Anti-TNF agents –> probably retards progression
- Peripheral arthritis and extra-articular manifestations –> may be treated by methotrexate and sulfasalazine; there is some evidence that they are beneficial in axial disease
- Physical therapy is critical component of management
Last joint syndrome –> AS patients are very susceptible to fracture due to any minor trauma
- typically seen in the thoracolumbar spine
- management is typically conservative with rest
- may require surgical fusion
AS - prognosis
- only about 1/3 of these patients become disabled
- mortality - may have slightly increased relative risk
Reactive arthritis (reiter’s)
- definition
- epidemiology
Acute non-purulent arthritis/enthesitis associated with a recent diarrheal or urinary infection
- triad of arthritis, non-purulent urethritis and conjunctivitis
Epidemiology
- Similar to AS
- Onset in 2nd-4th decades
- Sex distribution depends on the causative organism –> More common in males when the infection is genitourinary (GU); If pathogen is enteric (GI), arthritis is equally common in males and females.
- HLA-B27 positive 60-90% of cases – not as strong as AS
Causative agents
- shigella
- salmonella
- yersinia
- campylobacter
- chlamydia
Reactive arthritis - clinical manifestations
- Enthesitis- inflammation of the entheses –> where tendon and ligament meet bone
- Asymetric lower extremity oligoarthritis
- Ocular –> conjunctivitis, anterior uveitis
- Urethritis –> sterile pyuria (leukocytes in the urine, but culture is sterile)
- –> painless lesions of the penis
- Skin
- –> keratoderma blenorrhagica - painless papules that can occur on the palms and soles, can coalesce, scale and look like psoriasis
- –> circinate balanitis
- –> onycholysis - nail lifting with flares
- Axial skeleton –> ankylosis is similar to AS, except it may be asymmetric.
- Cardiac –> Up to 5% may develop aortic insufficiency and conduction delays.
Reactive arthritis - diagnosis
Usually based on the clinical history and physical exam revealing an inflamed joint or tendon.
- Evidence of infection –> from stool or urethral cultures; frequently this is not obtainable.
- Radiologic evidence –> bony proliferation at tendinous insertions.
- HLA-B27+ (usually not necessary)
Reactive arthritis - treatment and disease course
Treatment
- NSAID’s- provide symptomatic relief
- Antibiotics- not helpful, unless used to treat an active infection; they usually do not change the course of disease.
- Corticosteroids- particularly intra-articular use for acute monoarthritis or enthesopathy.
- Sulfasalazine or MTX
Disease course
- many patients continue to have recurrences and frequently complain of arthralgias –> joint symptoms persist in 50% at long term follow up
- 1/3 isolated attack; 1/3 recurrent isolated attacks; 1/3 chronic progressive course
Psoriatic arthritis - epidemiology and clinical patterns of arthritis
Epi
- female: male = 1:1
- associations with various HLA alleles, including B27
Clinical patterns of arthritis
- asymmetric oligoarthritis (>50%)
- symmetric arthritis = pseudo-rheumatoid (25%) –> looks exactly like RA
- spondylitis = AS like (5-10%)
- distal interphalangeal joints (5-10%)
- arthritis mutilans (5%)
Psoriatic arthritis - asymmetric arthritis
- M:F 1:1
- Involves PIP, DIP, knees, hips, ankles, wrists –> characteristic sausage digit (dactylitis) = diffuse involvement of entire finger
- Commonly have finger/ toenail abnormalities –> pitting and hyperkeratosis
- Conjunctivitis, iritis, episcleritis
Psoriatic arthritis - summetric arthritis (RA like)
- 25% of Psoriatic arthritis patients
- Female:Male 2:1
- Involves DIP, PIP, MCP, MTP, knees, wrists, and ankles
- 50% of patients develop erosive, destructive arthritis; fusion of wrists
- differentiate from RA by presence of psoriasis rash on hands
Psoriatric arthritis - spondylitis
- low back pain, morning stiffness
- Female:Male 1:2-6
- Enthesitis
- Radiological- sacroiliitis (can be bilateral or unilateral, unlike AS which is bilateral) + spondylitis
- Sacroiliitis may be asymetric
- Syndesmophytes may affect spine at random levels – not regimented like in AS
Psoriatic arthritis - Distal interphalangeal arthritis
- 5-10% of psoriatic patients
- frequently have nail abnormalities = pitting, onycholysis, hyperkeratosis
- predominant DIP involvement
