Seronegative spondyloarthropathies - psoriatic arthritis
Description
- Inflammatory arthritis with psoriasis, RF-negative, part of the spondyloarthritis family
- Multi-domain disease - each domain responds to different drugs, so the domains must be counted individually
Six domains
- Peripheral arthritis
- Axial disease
- Enthesitis
- Dactylitis
- Skin psoriasis
- Nail disease
Moll and Wright patterns (may change over time in the same patient)
- Asymmetric oligo/monoarthritis (<5 joints) - historically the commonest at presentation
- Symmetric polyarthritis - RA-like
- Axial (AS-like) - often asymmetric sacroiliitis, less severe than AS
- DIP-predominant with nail disease
- Arthritis mutilans - severe osteolysis, telescoping digits (<5%)
The pattern discriminators from RA
- "Ray" not "row": all joints of one digit (ray/axial), not the same joint across digits (row)
- DIP involvement
- Dactylitis ("sausage digit") - whole-digit swelling from tenosynovitis + synovitis
- Enthesitis - Achilles, plantar fascia
- Asymmetry
- Nail disease
Epidemiology
- ~20-30% of people with psoriasis develop PsA
- Prevalence ~0.1-0.25% of the population
- M=F overall (axial disease M>F; polyarticular F>M)
- Peak onset 30-50 yr
- Skin precedes joints in ~70-80% (median ~10 years); simultaneous ~15%; joints first in ~10-15%
- Risk of PsA in psoriasis rises with: nail disease, scalp and intergluteal/perianal psoriasis, extensive skin disease, obesity, family history, trauma
Aetiopathogenesis
- Enthesitis is the primary lesion - as in the whole spondyloarthritis family
- IL-23/IL-17 axis from enthesis-resident T cells; TNF-alpha
- -> inflammation, erosion, and simultaneous new bone formation (periostitis, ankylosis)
- *Uniquely both erosive and proliferative* - the radiographic signature
- Genetic
- *HLA-C06:02* - psoriasis, early skin onset, less arthritis*
- *HLA-B27** - axial PsA (~25%)
- *HLA-B38/39** - peripheral polyarticular
- IL23R, IL12B, TNIP1
- Koebner phenomenon at the enthesis - physical trauma as a trigger ("deep Koebner")
- Obesity, metabolic syndrome, streptococcal infection, HIV (may cause explosive PsA)
Diagnosis
CASPAR criteria - inflammatory articular disease + score >=3
| Item | Points |
|---|---|
| Current psoriasis | 2 |
| Personal history of psoriasis, or family history in a 1st/2nd-degree relative | 1 |
| Psoriatic nail dystrophy (pitting, onycholysis, hyperkeratosis) | 1 |
| Negative rheumatoid factor | 1 |
| Dactylitis (current, or history documented by a rheumatologist) | 1 |
| Juxta-articular new bone formation on hand/foot X-ray | 1 |
- Specificity ~99%, sensitivity ~91%
- Works even in RF-positive patients and in those without current skin disease
Examination
- Look for hidden psoriasis: scalp, behind the ears, umbilicus, natal cleft, extensor elbows/knees
- Nails - the single most useful cutaneous sign
- Pitting, onycholysis, nail-plate crumbling, oil-drop sign, subungual hyperkeratosis
- Nail change correlates best with joint disease of all psoriasis features - the nail matrix is contiguous with the DIP enthesis
- Dactylitis - count digits
- Enthesitis - Achilles insertion, plantar fascia, lateral epicondyle, iliac crest (Leeds Enthesitis Index)
- Spinal mobility, sacroiliac tenderness
- Eyes - uveitis; PsA uveitis is more often insidious, bilateral and posterior than the acute unilateral anterior uveitis of AS
Laboratory
- *No diagnostic test*
- RF and anti-CCP negative by definition (though ~5-15% have low-titre RF and ~5% anti-CCP - anti-CCP predicts erosive disease)
- ESR/CRP normal in up to 50% - normal markers do not exclude active disease
- Hyperuricaemia common from skin turnover - gout and PsA coexist
- HLA-B27 if axial features
Radiographic features - the "erosion plus proliferation" signature
- Asymmetric distribution
- NORMAL bone density - no periarticular osteopenia (the key discriminator from RA)
- Fluffy periostitis and periarticular new bone proliferation
- "Pencil-in-cup" deformity - erosion of the proximal phalanx head with expansion of the distal base
- Osteolysis, including resorption of the distal phalangeal tuft (acro-osteolysis)
- Ankylosis of interphalangeal joints
- Asymmetric sacroiliitis; chunky, non-marginal, asymmetric syndesmophytes (paravertebral ossification)
- Contrast AS: symmetric sacroiliitis and thin, vertical, marginal syndesmophytes
- Three radiographic patterns: DIP-predominant, RA-like symmetric (but no osteopenia), and arthritis mutilans
- US/MRI: enthesitis, dactylitis (flexor tenosynovitis), bone marrow oedema; MRI sacroiliac joints for axial disease
Assessment tools
- MDA (minimal disease activity) - the treat-to-target endpoint; DAPSA, PASDAS
- PASI/BSA for skin, NAPSI for nails
Management
Axis: by domain. Count the domains present, then choose the drug that covers all of them.
A. Non-pharmacological - all
- Weight loss - obesity reduces response to every drug class and worsens skin
- Smoking cessation, exercise, physiotherapy
- Cardiovascular and metabolic risk assessment - PsA carries independent excess risk
B. Peripheral arthritis
- NSAIDs +/- intra-articular corticosteroid for mild oligoarticular disease
- Systemic corticosteroid: use sparingly and taper slowly - withdrawal can precipitate pustular psoriasis**
- csDMARD - methotrexate first (also treats skin), leflunomide, sulfasalazine
- Effective for peripheral arthritis and skin; INEFFECTIVE for axial disease, enthesitis and dactylitis
- Escalate to a b/tsDMARD without further delay if the csDMARD fails
C. Choose the biologic by domain
| Dominant problem | Preferred |
|---|---|
| Peripheral arthritis | TNF inhibitor, IL-17i, IL-23i, JAK inhibitor - no clear hierarchy |
| Severe skin disease | IL-23 inhibitor (guselkumab, risankizumab), IL-17 inhibitor, or ustekinumab |
| Axial disease | TNF inhibitor or IL-17 inhibitor (IL-23 inhibitors FAILED in axSpA) |
| Enthesitis / dactylitis | TNF inhibitor, IL-17i, IL-23i - not csDMARDs |
| Uveitis | TNF monoclonal antibody (not etanercept) |
| Concomitant IBD | TNF monoclonal, IL-23i or ustekinumab - AVOID IL-17 inhibitors |
| Nail disease | IL-17i or IL-23i |
- Classes
- TNF inhibitors - adalimumab, etanercept, infliximab, golimumab, certolizumab
- IL-17 - secukinumab, ixekizumab, bimekizumab (dual IL-17A/F; high joint and skin response; oral candidiasis is the class effect)
- IL-23 (p19) - guselkumab, risankizumab, tildrakizumab
- IL-12/23 (p40) - ustekinumab
- JAK inhibitor - tofacitinib, upadacitinib; deucravacitinib (TYK2 allosteric inhibitor) - a different safety profile from classic JAK inhibitors
- PDE4 - apremilast; modest efficacy, useful in mild disease or where immunosuppression is unwanted; diarrhoea, weight loss, low mood
- JAK inhibitors: assess cardiovascular, malignancy and VTE risk first
- Screen for latent TB, hepatitis B/C, HIV; vaccinate before starting
D. Axial disease
- NSAIDs first, then straight to TNF inhibitor or IL-17 inhibitor
- csDMARDs have no role
E. Treat to target
- Target: minimal disease activity (MDA) or remission, reviewed every 1-3 months while active
- Reassess and change therapy if the target is not met by 3-6 months
- Coordinate with dermatology - one drug should ideally cover skin and joints
Associations
- Psoriasis (skin and nail) - by definition
- Uveitis ~7% - insidious, bilateral, posterior more often than in AS
- Inflammatory bowel disease - Crohn > UC
- Metabolic syndrome, obesity, type 2 diabetes, non-alcoholic fatty liver disease
- NAFLD matters - it constrains methotrexate use
- Cardiovascular disease - independent excess risk, similar to RA
- Depression and anxiety - higher than in RA at equivalent disease activity
- Gout / hyperuricaemia
- Osteoporosis
- HIV - can cause severe explosive PsA; test in atypical or fulminant presentations
Natural history & complications
- Erosive damage occurs in ~40-60% within 10 years if untreated
- Radiographic progression is slower on average than RA, but arthritis mutilans is uniquely destructive
- Skin and joint activity do NOT track together - either can flare independently
- Excess mortality, driven by cardiovascular disease
Poor prognostic markers
- Polyarticular disease at presentation (>5 joints)
- Existing radiographic erosions
- Raised ESR/CRP
- Dactylitis
- Nail dystrophy and extensive skin disease
- Delayed diagnosis (even 6 months of delay worsens erosive outcomes)
- Obesity - worse response to all therapy
- Failure to achieve MDA
Complications
- Joint destruction, arthritis mutilans with telescoping digits and "opera glass hand"
- Ankylosis, functional loss, work disability
- Spinal fusion and restricted mobility
- Uveitis and visual loss
- Accelerated cardiovascular disease - the leading cause of death
- Depression
- Drug toxicity - MTX hepatotoxicity (amplified by NAFLD and alcohol), biologic infection risk
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