• Psoriasis affects approximately 1–3% of the global population (higher in northern Europe ~2–3%, lower in East Asian populations ~0.1–0.5%) ^[4][5].
• Psoriatic arthritis develops in up to 30% of patients with psoriasis ^[2][5][6].
• PsA prevalence in the general population: approximately 0.3–1% (Western data); lower in Hong Kong/Southern Chinese (~0.1–0.3%) but likely under-recognised ^[3].

• M:F ≈ 1:1 (equal sex distribution — an important distinguishing feature from RA where F:M = 3:1) ^[3][5][6].
• Age of onset: generally 25–40 years ^[3], though can present at any age.
• Peak incidence is in the 4th–5th decade of life.

• 60% of cases: psoriasis precedes arthritis (often by many years, mean ~10 years).
• 20%: arthritis precedes psoriasis — this is the clinically tricky scenario where you must differentiate from RA (look for nail changes, family history of psoriasis, hidden psoriasis in scalp/umbilicus/natal cleft/behind ears).
• 20%: concurrent onset.

Only a weak relationship exists between severity of skin disease and arthritic involvement ^[3]. A patient with minimal skin disease can have severe, destructive arthritis and vice versa.

• Psoriasis prevalence in Chinese populations is lower than in Caucasians but still clinically significant.
• HLA-B27 prevalence in Southern Chinese is ~6–8% ^[3], relevant because HLA-B27 is associated with the spondylitic pattern of PsA.
• HLA-B5801 screening is important before allopurinol initiation in Han Chinese (8% carrier frequency)*, relevant because hyperuricaemia/gout commonly coexists with PsA and metabolic syndrome ^[7].

• The enthesis is the site where tendons, ligaments, or joint capsules insert into bone.
• In PsA (and all SpA), enthesitis (inflammation at the enthesis) is the primary pathological event — this is fundamentally different from RA where the primary target is the synovium.
• Key entheseal sites: Achilles tendon insertion, plantar fascia insertion, patellar tendon, epicondyles, supraspinatus insertion, costochondral junctions.
• The enthesis has a unique anatomy: it is adjacent to the synovio-entheseal complex (SEC) — meaning that inflammation starting at the enthesis can spread to adjacent synovium, explaining why you get both enthesitis and synovitis in PsA.

• The DIPJ is the most characteristic joint affected in PsA.
• Anatomically, the nail root (nail matrix) is closely connected to the DIPJ — the extensor tendon inserts into the distal phalanx via an enthesis that is intimately related to the nail matrix.
• This explains why nail disease and DIP arthritis so commonly coexist in PsA — inflammation at the DIP enthesis spreads to the nail matrix and vice versa.
• RA characteristically spares the DIP joints ^[6], making DIP involvement a strong differentiator.

• The SI joints and spinal facet joints contain entheses and fibrocartilage — targets for SpA.
• PsA spondylitis tends to be asymmetric (unlike AS which is classically symmetric).
• Syndesmophytes in PsA are often chunky, asymmetric, and non-marginal (paravertebral ossification), unlike the thin, flowing, marginal syndesmophytes of AS.

• Dactylitis ("sausage digit") involves inflammation of the entire digit — not just the joints but also the tenosynovium (flexor tendon sheath) and soft tissue.
• This is different from the focal joint swelling seen in RA.
• Anatomically, the flexor tendon sheaths run the entire length of the digit, so inflammation here causes uniform swelling.

PsA is a polygenic disease with a strong hereditary component:

• Concordance in monozygotic twins: ~35–70% for psoriasis, lower for PsA but still substantial.
• HLA associations:
  • HLA-C*06:02: strongest association with psoriasis itself (especially type I/early onset)
  • HLA-B27: associated with axial PsA/psoriatic spondylitis (~20–50% of axial PsA)
  • HLA-B08, B38, B39: associated with peripheral PsA patterns
• Non-HLA genes: IL-23R, IL-12B, TNIP1, TRAF3IP2, TNFAIP3 — all converge on the IL-23/IL-17 inflammatory axis.

Unlike psoriasis which has well-defined genetics, the genetics of PsA are complex and overlap with but are distinct from psoriasis itself — some genetic loci predispose to psoriasis alone, some to PsA specifically. This explains why only 30% of psoriasis patients develop arthritis.

The pathophysiology of PsA involves a complex interplay between innate and adaptive immunity, with the enthesis as the primary site of inflammation:

Step-by-Step Pathophysiology:

1. Initiation: In a genetically susceptible individual, an environmental trigger activates dendritic cells (DCs) in the skin and at entheseal sites. These DCs present antigens via MHC molecules (including HLA-C*06 and HLA-B27) to T cells.

2. IL-23/IL-17 axis activation: Activated DCs produce IL-23, which drives differentiation and expansion of Th17 cells. Th17 cells produce IL-17A, IL-17F, and IL-22 — the key effector cytokines in PsA.

3. Skin pathology (psoriasis): IL-17 and IL-22 act on keratinocytes → hyperproliferation (epidermal turnover accelerates from normal ~28 days to ~3–4 days), abnormal differentiation (parakeratosis = retention of nuclei in stratum corneum), and angiogenesis in the dermis. This produces the classic thick, silvery-scaled erythematous plaques.

4. Entheseal pathology (enthesitis): IL-17 and TNF-α drive inflammation at the enthesis. The enthesis is a biomechanically stressed site with resident immune cells (γδ T cells, innate lymphoid cells type 3 [ILC3]) that can produce IL-17 locally even without classical T cell activation. This is why enthesitis is so prominent in PsA/SpA.

5. Synovial pathology: Via the synovio-entheseal complex (SEC), inflammation spreads from the enthesis to adjacent synovium → synovitis with pannus formation, similar to but generally less extensive than RA.

6. Bone remodelling — the unique PsA paradox: Unlike RA (which is primarily erosive), PsA shows simultaneous bone erosion AND new bone formation:

   • Erosion: TNF-α and RANKL activate osteoclasts → bone destruction at joint margins.
   • New bone formation: IL-17, IL-22, and prostaglandins stimulate osteoblast activity and entheseal ossification → periostitis (fluffy new bone), syndesmophytes, ankylosis.
   • This explains the radiological hallmark of PsA: "pencil-in-cup" deformity (erosion of one side + proliferation on the other), juxta-articular new bone formation, and periostitis.

7. Psoriasis can also affect arteries → stiffness, increased risk of cardiovascular disease ^[2]. The same IL-17/TNF-α inflammatory milieu promotes endothelial dysfunction, accelerated atherosclerosis, and increased risk of MI. A 30-year-old with severe psoriasis has an adjusted RR of MI of 3.10 ^[4].

8. Nail pathology: The nail matrix sits directly over the DIP enthesis. Entheseal inflammation extends to the nail matrix → pitting (focal parakeratosis of nail plate), onycholysis (separation of nail plate from nail bed due to inflammation), subungual hyperkeratosis, oil-drop sign (translucent yellow-red discolouration), horizontal ridging (Beau's lines).

Protection against secondary infection occurs due to antimicrobial peptide (AMP) production ^[2] — psoriatic skin overproduces AMPs like cathelicidin (LL-37), β-defensins, and S100 proteins. This is why, despite having a damaged skin barrier, psoriasis patients rarely get secondary bacterial skin infections (unlike eczema patients who commonly do). These AMPs can also act as autoantigens, perpetuating the inflammatory cycle.

A working model proposes that following a stimulus, activation of dendritic cells and T cells leads to the formation of an 'immunological synapse' that enhances their interactions. This results in the release of cytokines, chemokines, and growth factors that trigger keratinocyte proliferation, altered differentiation, and angiogenesis. Within the chronic psoriatic plaque, a vicious cycle of continuous T cell and dendritic cell activation is envisioned ^[4].

TNF-α is a key component in the cytokine cascade. It binds to two cell-surface receptors — type I TNF receptor (p55) and type II TNF receptor (p75) — on numerous cell types. Activated T cells migrate into the joint and stimulate a multi-molecular immune-inflammatory cascade, secreting pro-inflammatory cytokines which stimulate macrophages, fibroblasts, chondrocytes and osteoclasts. These cells secrete TNF-α which promotes articular cartilage destruction, pannus formation and subchondral bone erosion ^[4].

Under the modern ASAS framework, PsA can be classified as:

• Axial SpA (axSpA): if predominantly axial involvement (sacroiliitis/spondylitis) → follows axSpA classification criteria
• Peripheral SpA: if predominantly peripheral involvement → follows peripheral SpA classification criteria

This is the classic and most commonly tested classification:

Important: These patterns are not mutually exclusive. Patients frequently evolve from one pattern to another over time (e.g., oligoarthritis → polyarthritis), and axial disease can coexist with any peripheral pattern.

Psoriatic arthritis is a systematic (systemic) condition. Skin disease: dry, red and scaly skin rashes. 5–20% develop associated arthritis with inflamed synovium. Usually affects hands but also affects spine, feet and jaw ^[8].

This is the most important and most commonly tested differential for PsA, especially the symmetric polyarticular pattern (~25% of PsA) which can strongly mimic RA ^[1][3][5].

RA spares DIP ^[6][10]. This is the single most useful differentiating feature at the bedside.

Why the distinction matters: Treatment overlaps significantly (both respond to methotrexate, anti-TNFα) but differs in some key areas — e.g., anti-IL-17 (secukinumab) is effective in PsA but NOT in RA, while anti-IL-6 (tocilizumab) is effective in RA but NOT in SpA/PsA ^[5]. Misdiagnosis leads to suboptimal therapy.

Only a small number of patients with psoriatic arthritis will test positive for RF and anti-CCP whereas these tests are positive in a majority of patients with RA ^[1]. However, remember that ~5-10% of the general population can be RF-positive, so a positive RF does not exclude PsA, and a negative RF does not confirm it.

Reactive arthritis ("reactive" = triggered by a distant infection, not direct joint infection) is another SpA subtype that shares many features with PsA ^[1][5][11].

Why these look alike: Both are SpA-spectrum conditions driven by the IL-23/IL-17 axis in HLA-B27-positive individuals. The difference is the triggering event — in reactive arthritis, a specific genitourinary or enteric infection precedes onset; in PsA, the trigger is psoriasis-associated immune dysregulation.

History of antecedent infectious illness with either genitourinary symptoms of urethritis or a dysenteric illness is absent in psoriatic arthritis ^[1].

AS is the prototype axial SpA. The psoriatic spondylitis pattern of PsA can mimic AS, but there are key distinctions ^[1][3].

Presence of psoriasis and radiological features distinguish ankylosing spondylitis from psoriatic arthritis ^[1].

Arthritis occurs in ~20% of Crohn's disease and ~10% of UC patients. It shares the SpA family features ^[1][11][12].

Inflammatory bowel disease can usually be suspected based upon clinical findings and confirmed with endoscopic investigation and biopsy ^[1].

Why IBD matters for PsA: Some patients have overlapping features (e.g., psoriasis + IBD), and certain biologic therapies behave differently — etanercept is less effective for IBD-associated SpA; infliximab/adalimumab are preferred because they also treat the bowel disease ^[3].

This is a critically important differential, especially in Hong Kong, because:

• Hyperuricaemia is common in psoriasis (increased epidermal cell turnover → increased purine metabolism → elevated uric acid)
• PsA and gout can coexist ^[1]
• Both can cause DIP joint involvement and dactylitis-like swelling
• Both are associated with metabolic syndrome

Gout is confirmed by finding monosodium urate crystals on examination of synovial fluid. Psoriatic arthritis and gout can coexist, and recognition of findings suggestive of psoriatic arthritis such as nail changes and prominent DIP joint disease will support the diagnosis of psoriatic arthritis in addition to gout ^[1].

OA can mimic PsA because both can affect DIP joints, and both are common conditions that may coexist ^[6][13].

Why they look alike: Both cause nodal changes at DIP joints. The key differentiator is the inflammatory nature of PsA (morning stiffness, soft/warm swelling, elevated inflammatory markers, nail changes, dactylitis) versus the mechanical/degenerative nature of OA (bony hard swelling, worse with use, normal bloods).

Viral infections (HBV, HCV, parvovirus B19, EBV, dengue, rubella, HIV) can cause symmetric small joint polyarthritis mimicking early RA or PsA ^[6][13].

Why this matters: Viral arthritis is the most important acute mimic in the early stages. If a patient presents with new-onset polyarthritis, always check viral serology before diagnosing RA or PsA. The self-limiting course (< 6 weeks) distinguishes viral arthritis from chronic inflammatory arthritis.

SLE can cause polyarthritis, but its character is quite different from PsA ^[6][13].

Always consider in any acute monoarthritis presentation — hot, swollen tender joint = septic arthritis until proven otherwise ^[14].

Why this matters clinically: PsA patients on immunosuppressive therapy (methotrexate, biologics) are at increased risk of septic arthritis. Any acute flare in a single joint in an immunosuppressed PsA patient mandates joint aspiration to exclude infection before adjusting immunosuppression.

In children, psoriatic arthritis is one of the 7 ILAR subtypes of JIA (7% of JIA) ^[15][16]:

PsA has no single pathognomonic laboratory test. The diagnosis is clinical, supported by a combination of history, examination findings, serology, and imaging. Formal classification criteria exist primarily for research purposes, but they are widely used in clinical practice to standardise diagnosis and are heavily tested in exams. You need to know three sets of criteria: the historical Moll and Wright criteria (1973), the modern CASPAR criteria (2006), and the paediatric ILAR criteria.

These are the original criteria, simple but limited (poor sensitivity when psoriasis is absent or occult) ^[3]:

Diagnosis of PsA requires demonstration of ALL THREE:

1. Inflammatory arthritis — peripheral arthritis, sacroiliitis, or spondylitis
2. Presence of psoriasis
3. Absence of rheumatoid factor

Limitations: Too restrictive — excludes the ~5-10% of PsA patients who are RF-positive, and does not account for patients in whom psoriasis has not yet manifested (the 20% where arthritis precedes skin disease). Also no weighting for highly characteristic features like dactylitis and nail changes.

The Classification criteria for Psoriatic Arthritis (CASPAR) are the current gold standard for classifying PsA. "CASPAR" = Classification criteria for Psoriatic AR**thritis. These have sensitivity of 91.4% and specificity of 98.7% — far superior to Moll and Wright ^[1][3][5].

Patients with an inflammatory musculoskeletal disease (peripheral arthritis, spondylitis or enthesitis) can be classified as having psoriatic arthritis if total score ≥ 3 points ^[1]:

The mandatory entry criterion is inflammatory musculoskeletal disease: peripheral arthritis, spondylitis, or enthesitis ^[1][5]. Without this, the CASPAR scoring system should not be applied — you cannot diagnose PsA in someone who does not have inflammatory musculoskeletal disease.

Classification of Psoriatic Arthritis (CASPAR) criteria — Entry criteria: Inflammatory articular disease (joint, spine, enthesitis) PLUS 3 points: Evidence of psoriasis: current (+2) → if not, personal history (+1) → if not, family history (+1). Psoriatic nail dystrophy: onycholysis / pitting / hyperkeratosis (+1). Evidence of dactylitis: current (+1) → if not, personal history (+1). RF −ve (+1). Imaging evidence of juxta-articular new bone formation (+1) ^[5].

When PsA presents as predominantly peripheral disease without current inflammatory back pain, it can also be classified under the ASAS peripheral SpA criteria ^[3]:

Entry criteria: At least ONE of arthritis, enthesitis, or dactylitis (without current inflammatory back pain). Then:

• Group A (≥ 1 feature): uveitis, psoriasis, IBD, preceding infection, HLA-B27+, sacroiliitis on imaging
• OR Group B (≥ 2 features): arthritis, enthesitis, dactylitis, inflammatory back pain in the past, family history of SpA

Sensitivity 78%, specificity 83% ^[3].

From GC 144 lecture slide: Psoriatic Arthritis (JIA subtype) = Psoriasis and arthritis, OR arthritis with 2 of the following: psoriasis in first-degree relative, dactylitis, finger nail pitting or onycholysis. Exclude if ERA, sJIA, +RF. Enthesitis common in PsA ^[18].

From ILAR Classification: Psoriatic arthritis = Arthritis and psoriasis, OR arthritis including ≥ 2 of: dactylitis, nail pitting and onycholysis, psoriasis in a 1st degree relative ^[16].

The diagnostic approach to PsA follows a structured pathway: clinical suspicion → history and examination → laboratory investigations → imaging → apply CASPAR criteria → exclude mimics.

Once PsA is diagnosed, disease activity is monitored using validated composite scores ^[5]:

Treatment of axial symptoms: as in axial SpA (conventional DMARDs not effective) ^[3].

Treatment of enthesitis: NSAIDs (1st line) ± local steroid injections (except Achilles tendon due to ↑ risk of tendon rupture). TNF-α inhibitor if refractory (conventional DMARDs not effective for extra-articular manifestations) ^[3].

Treatment of dactylitis: NSAIDs (1st line), anti-TNFα (if refractory) ^[3].

Dactylitis involves the entire digit (flexor tenosynovitis + synovitis + soft tissue oedema), so local steroid injection into the flexor tendon sheath can also be considered. Anti-IL-17 and anti-IL-12/23 also have demonstrated efficacy.

For skin psoriasis ^[20]:

Uveitis: topical glucocorticoids + cycloplegics → TNF-α inhibitor (if refractory, prefer infliximab/adalimumab) ^[3].

Prognosis: 68% progressive disease at 5 years ^[3]. This underscores the importance of early DMARD initiation — most structural damage occurs in the first 2 years if untreated.

Why PsA can be more destructive than expected: Because PsA joints are less tender ^[5], patients and clinicians may underestimate disease activity. The patient is "living with it" while subclinical inflammation causes irreversible erosion. This is why objective assessment (swollen joint count, imaging, inflammatory markers) is essential, not just pain scores.

Several long-term complications occur in pauciarticular JIA. The most frequent complications are uveitis and leg length discrepancy ^[25] — relevant to juvenile PsA which shares the uveitis risk.

• Mild, non-specific mucosal inflammation — part of the shared SpA extra-articular spectrum.
• Usually self-limiting but can be recurrent.