Definition
Seronegative spondyloarthropathies are a group of overlapping conditions that are characterized by absence of serum auto-antibodies (e.g. rheumatoid factor, cyclic citrullinated peptide, antinuclear antibodies), axial skeletal and/or peripheral joint involvement, dactylitis, enthesitis (inflammation at insertions of tendons into bone), and mucocutaneous, gastrointestinal, and ocular inflammation. More common in men and associated with human leukocyte antigen HLA-B27.
|
Disease |
MSK manifestations |
Extra-articular manifestations & comorbidities |
Clinical associations and clinical course |
|
Ankylosing spondylitis |
Sacroiliitis Arthritis of axial skeleton (hips, shoulders, spine) Ankylosis (fusion) of the spine Peripheral arthritis Enthesitis/Dactylitis |
Acute anterior uveitis Osteoporosis (decreased BMD at spine and hip) Cardiac conduction block (rare) Aortitis, aortic insufficiency (rare) Inflammatory bowel disease Restrictive lung disease (reduced chest wall and spinal mobility) Psoriasis |
Impaired spinal mobility (more severe in advanced cases with progressive spinal fusion) Osteoporotic fractures (vertebral fragility fractures 2x more common in AS compared to non-AS controls) Spinal fractures may lead to spinal cord or spinal nerve compression |
|
Reactive arthritis |
Acute, asymmetric oligoarthritis (lower extremity predominant) Enthesitis/Dactylitis |
Ocular symptoms: conjunctivitis > anterior uveitis, episcleritis, keratitis GU: dysuria, urethritis, pelvic pain, cervicitis, prostatitis, cystitis Gastrointestinal symptoms (e.g. diarrhea) Mucocutaneous lesions (keratoderma blennorrhagicum, circinate balanitis) |
Sterile synovitis, dactylitis, and/or enthesitis 1-3 weeks after infection with GU (chlamydia trachomatis) or GI (Shigella, Salmonella, Yersinia, Campylobacter, E coli, Clostridioides) 25-40% experience complete recovery while others experience relapsing or chronic course 10-30% develop chronic arthritis |
|
Psoriatic arthritis |
Arthritis may be peripheral, axial or both Enthesitis/dactylitis There are 5 described patterns of synovitis:
|
Nail changes (pitting, onycholysis) Psoriasis: chronic plaque psoriasis is the most common sub-type and tends to affect the elbows, knees, scalp, & gluteal cleft; other psoriasis sub-types = guttate, pustular, and erythrodermic psoriasis Conjunctivitis>uveitis |
Occurs in up to 30% of patients with psoriasis Timing of onset of skin & joint disease is variable: ~70% have psoriasis prior to onset of inflammatory arthritis while ~15% develop arthritis before skin disease and ~15% co-occur Tends to be chronic |
|
Enteropathic IBD-associated arthritis |
3 arthritis subtypes:
Dactylitis/Enthesitis |
Skin lesions associated with inflammatory bowel disease (pyoderma gangrenosum and erythema nodosum) Ocular: uveitis, episcleritis, scleritis |
Course depends on subtype Usually non-destructive |
Evaluation
- History: chronic inflammatory back pain (age of onset <40 years, insidious onset, improvement with exercise, no improvement with rest, pain at night), family history of SpA or psoriasis, improves with NSAIDs, preceding infection, urethritis in absence of ongoing infection, psoriasis, IBD, and/or ocular inflammation
- Exam: impaired spinal mobility, postural abnormalities (e.g. hyperkyphosis in advanced AS), peripheral inflammatory arthritis, dactylitis, enthesitis (e.g. tenderness and swelling of Achilles and/or plantar fascia), psoriatic nail changes, ocular inflammation
- Serologies: positive HLA-B27 (negative test does not rule out), elevated CRP/ESR
- Imaging: plain films of SI joints and spine. If X-ray negative, consider MRI of SI joints and plain films of symptomatic peripheral joints to look for erosions and new bone formation. Avoid CT if possible to minimize lifetime radiation exposure
Treatment
- Conventional synthetic oral DMARDs are not effective for axial disease, enthesitis, or dactylitis
- Spondylitis: NSAIDs, second line TNF-alpha inhibitors, exercise program preserves mobility, PT, smoking cessation
- Reactive arthritis: usually resolves in 6 months with symptomatic management including NSAIDs +/- intra-articular steroid injections, DMARDs such as sulfasalazine for chronic cases; patients with chronic chlamydia-induced reactive arthritis warrant treatment with antibiotics (doxycycline and rifampin) whereas enteropathic reactive arthritis is NOT treated with antibiotics
- Psoriatic arthritis: NSAIDs can treat pain, but do not prevent erosions. Avoid/minimize use of systemic steroids as cessation often flares skin disease. Methotrexate is 1st line for peripheral arthritis; axial disease and refractory peripheral arthritis warrant biologic DMARD treatment – antagonists to TNF-alpha, IL-17, IL-12/23
- IBD-associated peripheral arthritis: NSAIDs (caution as may exacerbate bowel inflammation) conventional non-biologic DMARD (SSZ, MTX, AZA, or 6-MP) monoclonal antibody TNF inhibitor
References
Dougados, M and Baeten, D. Spondyloarthritis. Lancet 2011;377: 2127-37.
Joseph A, Brasington,R, Kahl L, et al. Immunologic Rheumatic Disorders. Journal of Allergy and Clinical Immunology 2010;125: S205-S215.
Kataria, RK and Brent LH. Spondyloarthropathies. Am Fam Physician. 2004;69(12):2853-2860.
Khan, MA. Update on spondyloarthropathies. Ann Intern Med 2002;136: 896-907.
Taurog JD, Chhabra A, Colbert RA. Ankylosing Spondylitis and Axial Spondyloarthritis. N Engl J Med. 2016;374(26): 2563-2574.