Is psoriatic arthritis (PsA) considered a seronegative spondyloarthritis, typically testing negative for rheumatoid factor (RF) and anti-citrullinated protein antibodies (anti-CCP)?

Is Psoriatic Arthritis a Seronegative Arthritis?

Yes, your understanding is correct—psoriatic arthritis (PsA) is definitively classified as a seronegative inflammatory spondyloarthropathy, characterized by the absence of rheumatoid factor (RF) and typically negative anti-citrullinated protein antibodies (anti-CCP). 1, 2

Core Definition and Classification

PsA is an inflammatory musculoskeletal disease classified among the seronegative spondyloarthropathies, affecting approximately 30-33% of patients with psoriasis. 2 The American Academy of Dermatology explicitly states that PsA is "an inflammatory seronegative spondyloarthropathy associated with psoriasis." 1

Serologic Characteristics

The diagnosis of PsA fundamentally relies on the absence of rheumatoid factor combined with specific clinical patterns of joint inflammation and the presence of psoriatic skin or nail lesions. 1

Key serologic features include:

• Rheumatoid factor negativity is a defining characteristic and is actually included in the CASPAR diagnostic criteria for PsA 1
• Anti-CCP antibodies are typically absent, with only 9.72% of PsA patients testing positive in research studies 3
• When anti-CCP antibodies are present in PsA patients, they typically occur at low titers (mean 7.16 units) compared to rheumatoid arthritis patients (mean 80.61 units) 3

Critical Diagnostic Distinction

The absence of RF is what distinguishes PsA from rheumatoid arthritis (RA), particularly in cases where PsA presents with symmetric polyarticular involvement resembling RA. 1 The guidelines explicitly state: "Patients who display other characteristic signs of RA (ie, rheumatoid nodules, extra-articular involvement, and high titers of rheumatoid factor) should not be given the diagnosis of PsA." 1

Important Clinical Caveats

When Anti-CCP Positivity Occurs

While PsA is seronegative by definition, a small subset (approximately 10-12%) of PsA patients may test positive for anti-CCP antibodies. 3, 4 These patients warrant special attention:

• They more frequently have polyarticular disease patterns (p = 0.005) 4
• They require more aggressive treatment with biologics (p = 0.015) 4
• An anti-CCP titer above 11.6 U/mL suggests the patient may actually have RA with coincidental psoriasis rather than true PsA 4

Differentiating from Seronegative RA

The most challenging diagnostic scenario is distinguishing PsA from seronegative RA when both RF and anti-CCP are negative. 5 In these cases, look for:

• Dactylitis ("sausage digits") - present in PsA, uncommon in RA 1, 5
• Enthesitis (inflammation at tendon/ligament insertion sites) - characteristic of PsA 1, 5
• Distal interphalangeal (DIP) joint involvement - common in PsA, uncommon in RA 1, 5
• Nail changes (pitting, onycholysis, hyperkeratosis) - present in 80-90% of PsA patients 1, 2
• Asymmetric joint distribution - more typical of PsA than RA 1, 6
• Extra-synovial inflammation on ultrasound - helps identify PsA 5

Practical Screening Approach

At every visit with psoriasis patients, actively screen for joint symptoms including prolonged morning stiffness, joint swelling, and immobility-induced stiffness. 1 The CASPAR criteria require established inflammatory arthritis plus at least 3 points from features including current psoriasis, nail dystrophy, dactylitis, negative RF, and radiographic evidence of juxta-articular new bone formation. 1

Early recognition is critical because uncontrolled PsA causes radiologic joint damage in over 50% of patients evaluated in tertiary care centers, leading to permanent joint destruction. 1, 7