Psoriatic Arthritis
Psoriatic arthritis is a chronic inflammatory seronegative spondyloarthropathy associated with psoriasis, characterized by joint inflammation, enthesitis, and dactylitis affecting peripheral and/or axial joints.
Psoriatic Arthritis (PsA)
Psoriatic arthritis (PsA) is a chronic, immune-mediated inflammatory arthritis that occurs in association with psoriasis, a skin and nail disease characterised by dry, red, scaly plaques [1][2]. Breaking down the name: "psoriatic" = related to psoriasis (from Greek psōra = itch); "arthritis" = joint inflammation (arthro- = joint, -itis = inflammation).
PsA belongs to the spondyloarthritis (SpA) family — a group of related inflammatory joint disorders that share key features [3]:
- Asymmetrical oligoarthritis with possible sacroiliitis and spondylitis
- HLA-B27 association with familial aggregation tendency
- RF-negative and anti-CCP negative (hence historically called "seronegative spondyloarthropathies," though this term is now considered obsolete)
- Prominent extra-synovial inflammation: enthesitis, dactylitis, uveitis, mucosal inflammation
PsA is one of the four classic spondyloarthritides: ankylosing spondylitis, psoriatic arthritis, reactive arthritis (Reiter's disease), and enteropathic arthritis (IBD-associated) [1][3].
Key Concept – SpA vs RA
PsA was previously thought to be a variant of RA with negative RF. It is now understood to be a fundamentally different disease with distinct pathogenesis (entheseal-driven, IL-17/IL-23 axis predominant vs synovial-driven, IL-6/TNF axis predominant in RA), different joint distribution, and different radiological features. Understanding this distinction is essential for exams and clinical practice.
Epidemiology
- 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].
- 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].
| Category | Risk Factor | Mechanism / Explanation |
|---|---|---|
| Genetic | Family history of psoriasis/PsA | Strong hereditary component; ~40% of PsA patients have first-degree relative with psoriasis or PsA |
| HLA-B27 | Associated particularly with axial (spondylitic) PsA; prevalence 20–50% in PsA with axial disease | |
| HLA-C*06:02 (formerly Cw6) | Strongest genetic association with psoriasis vulgaris (type I, early-onset) | |
| Other HLA: B38, B39, B08 | Associated with various PsA patterns | |
| Non-HLA genes: IL-23R, IL-12B, TNFAIP3, TRAF3IP2 | Polymorphisms in IL-23/IL-17 pathway genes | |
| Environmental | Streptococcal pharyngitis | Triggers guttate psoriasis → can subsequently trigger PsA [2] |
| HIV infection | Paradoxically worsens psoriasis and PsA despite immunosuppression (CD8+ T cell-driven); psoriasis/PsA flare can be first presentation of HIV | |
| Trauma / Koebner phenomenon | Mechanical stress at entheses may trigger PsA in genetically susceptible individuals (deep Koebner phenomenon) | |
| Medications | Lithium, β-blockers, TNF-α inhibitors (paradoxical), corticosteroid tapers can trigger/worsen psoriasis [2] | |
| Metabolic | Obesity | Strongly associated; adipose tissue produces pro-inflammatory cytokines (TNF-α, IL-6); obesity prevalence significantly higher in psoriasis patients (34% vs 18% in one study) [4] |
| Smoking | Risk factor for PsA development and poorer treatment response | |
| Metabolic syndrome | Associated metabolic syndrome: overweight, DM, HTN, hyperlipidaemia, hyperuricaemia [3] | |
| Psoriasis Severity | Severe psoriasis | Higher risk of PsA than mild, though not linearly correlated |
| Nail involvement | Nail changes (pitting, onycholysis) are a strong predictor of future PsA development | |
| Scalp/inverse psoriasis | May carry higher PsA risk |
High Yield – Nail Disease Predicts Arthritis
Nail changes are found in 80–90% of PsA patients but only 46% of non-arthritic psoriasis patients [3]. Nail dystrophy (especially in DIP pattern) is one of the most useful clinical clues to distinguish PsA from RA and is a scored criterion in CASPAR.
Anatomy and Function (Relevant Structures)
Understanding PsA requires knowing the anatomy of three key structures:
- 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.
Etiology and Pathophysiology
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.
| Trigger | Mechanism |
|---|---|
| Streptococcal pharyngitis | Molecular mimicry between streptococcal M-protein and keratin; triggers guttate psoriasis which can progress to chronic psoriasis and PsA [2] |
| HIV infection | Loss of CD4+ T cells paradoxically unleashes CD8+ T cell responses; CD8+ T cells are key effectors in psoriasis and PsA |
| Physical trauma | Deep Koebner phenomenon: mechanical stress at entheseal sites triggers inflammation in genetically predisposed individuals |
| Medications | Lithium (impairs cAMP signalling → ↑keratinocyte proliferation); β-blockers (block β2-adrenergic receptors on keratinocytes → ↑proliferation); corticosteroid tapers can precipitate severe pustular psoriasis flare [2] |
| Stress | Neuroendocrine mechanisms; substance P and nerve growth factor in skin |
| Obesity | Adipokines from visceral fat drive systemic inflammation |
Must Know
Systemic corticosteroids are NOT used for psoriasis because corticosteroid taper can precipitate a very severe psoriatic flare, including pustular psoriasis [2]. This is a classic exam trap. Even in PsA, systemic steroids should be used cautiously and at the lowest effective dose, with gradual taper if used at all.
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:
-
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.
-
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.
-
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.
-
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.
-
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.
-
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.
-
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].
-
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].
Classification
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:
| Pattern | Frequency | Description | Key Features |
|---|---|---|---|
| 1. Asymmetric oligoarthritis | ~40% (most common) | Acute onset of synovitis with periarticular inflammation; 1–4 joints | Hands and feet most common; can involve large or small joints; associated with dactylitis [3] |
| 2. Symmetric polyarthritis | ~25% | Resembles RA; symmetric involvement of small and large joints | More common in women; nodules and extra-articular RA features are absent; generally less extensive than RA [3] |
| 3. DIP joint predominant | ~5–15% | Targets DIP joints and surrounding periarticular tissues | More common in men; almost invariably associated with nail dystrophy; classic "psoriatic arthritis" pattern [3] |
| 4. Psoriatic spondylitis | ~5% | Similar to AS but less severe, asymmetric/unilateral | May occur alone or with any pattern above; HLA-B27 associated [3] |
| 5. Arthritis mutilans | <5% (rarest) | Severe, destructive, deforming arthritis | "Opera-glass hand" (telescoping fingers due to massive bone resorption); pencil-in-cup deformity on XR |
GC Lecture Slide – PsA Patterns
From GC Derm 2026 lecture: Oligoarthritis (60–70%), Asymmetric DIP (16%), RA-like Pattern (15%), Ankylosing Spondylitis (5%), Arthritis Mutilans (5%) [2]. Note the percentages differ slightly from traditional Moll & Wright; the GC lecture uses a slightly different breakdown. For exams, know both — but the GC slide percentages are likely what the in-house paper will test.
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].
Clinical Features
A. Symptoms
| Symptom | Pattern | Pathophysiological Basis |
|---|---|---|
| Joint pain | Inflammatory pattern: worse in the morning and after rest, improves with activity | Cytokine-mediated inflammation (TNF-α, IL-17) accumulates during rest → fluid accumulates in joint → stiffness and pain; movement promotes lymphatic drainage and reduces stiffness |
| Morning stiffness | Prolonged > 30 minutes (often > 1 hour), characteristic of inflammatory arthritis | Overnight immobility → accumulation of inflammatory mediators and oedema fluid in joint and periarticular tissues |
| Joint swelling | May be subtle (oligoarticular) or widespread (polyarticular) | Synovitis (synovial hypertrophy + effusion) + periarticular soft tissue oedema |
| Reduced range of motion | Progressive; worse in destructive disease | Pannus formation → cartilage erosion → mechanical obstruction; entheseal ossification → ankylosis |
| Dactylitis ("sausage digit/toe") | ~50% of PsA patients; often presenting feature | Inflammation of the entire digit: combination of flexor tenosynovitis + synovitis of MCP/PIP/DIP joints + soft tissue oedema [3]. Unlike focal joint swelling in RA, the uniform swelling of the entire digit reflects inflammation throughout the tendon sheath. Classically associated with PsA [3]. |
| Back pain (if axial disease) | Inflammatory back pain: insidious onset, age < 40, morning stiffness > 30 min, improves with exercise, does not improve with rest, alternating buttock pain | Sacroiliitis and spondylitis → inflammation at vertebral entheses and facet joints |
| Symptom | Pathophysiological Basis |
|---|---|
| Enthesitis (~35%) [3]: heel pain (Achilles tendinitis, plantar fasciitis), pain at tibial tuberosity, epicondyle pain | Primary pathology in SpA — IL-17-driven inflammation at tendon/ligament insertion into bone. The enthesis is biomechanically stressed and contains resident innate immune cells. |
| Pain worse with activity at the specific entheseal site | Mechanical loading on an inflamed enthesis exacerbates pain |
| Symptom | Description | Pathophysiological Basis |
|---|---|---|
| Itchy, scaly plaques | Well-demarcated, erythematous plaques with silvery-white scales | Keratinocyte hyperproliferation (turnover ↓ from 28 days to 3–4 days) → thick stratum corneum with parakeratosis → silvery scale. Dermal angiogenesis → erythema. |
| Distribution | Extensor surfaces (elbows, knees) ± hidden areas (scalp, umbilicus, natal cleft, behind ears, genitalia) [5] | Koebner phenomenon — areas of mechanical stress/trauma develop lesions |
| Guttate psoriasis | Raindrop-like, small scattered papules; triggered by streptococcal pharyngitis [2] | Molecular mimicry between streptococcal M-protein and keratin → T cell activation |
| Inverse psoriasis | Smooth, shiny, erythematous patches in skin folds (axillae, groin, submammary) | Maceration in flexural areas removes scale |
Clinical Pearl – Hidden Psoriasis
When arthritis precedes psoriasis (20% of cases), always examine hidden areas: scalp hairline, behind ears, umbilicus, natal cleft (intergluteal), and genitalia. A few small patches of psoriasis in these areas can clinch the diagnosis and save you from misdiagnosing as RA.
| Symptom | Description | Pathophysiological Basis |
|---|---|---|
| Nail pitting | Small, punctate depressions in the nail plate | Focal parakeratosis in the nail matrix → defective keratinisation of nail plate |
| Onycholysis | Separation of nail plate from nail bed, starting distally | Inflammation and hyperkeratosis of the nail bed → disruption of attachment |
| Subungual hyperkeratosis | Thickening under the nail | Hyperproliferation of nail bed keratinocytes |
| Oil-drop sign | Translucent yellow-red discolouration seen through nail plate | Psoriatic changes in the nail bed produce yellowish material |
| Horizontal ridging (Beau's lines) | Transverse grooves | Episodes of inflammation in the nail matrix temporarily halt nail growth |
| Splinter haemorrhages | Longitudinal dark lines under the nail | Disruption of nail bed capillaries by inflammation |
Nail changes are found in 80–90% of PsA patients but only 46% of non-arthritic psoriasis [3]. Nail pitting ≥ 20 pits is highly suggestive of PsA.
| Symptom | Pathophysiological Basis |
|---|---|
| Eye symptoms: pain, redness, photophobia, blurred vision (uveitis and conjunctivitis) [3] | Anterior uveitis from HLA-B27-mediated immune response; shared IL-17/IL-23 pathway between joint and eye |
| Fatigue | Chronic systemic inflammation → cytokine-mediated central fatigue (TNF-α, IL-6 cross BBB) |
| Constitutional symptoms: low-grade fever, malaise | Systemic inflammatory response |
B. Signs
| Sign | Description | Pathophysiological Basis |
|---|---|---|
| Asymmetric joint swelling | Warm, swollen joints; often involves a few joints in a "ray" pattern (e.g., DIP + PIP + MCP of one finger) | Synovitis + enthesitis in a segmental pattern along the digit |
| DIP joint involvement | Swelling, tenderness, and erythema of DIP joints | DIP enthesitis spreading from nail matrix; RA spares DIP [6] — this is because DIP joints have minimal synovium but prominent entheseal attachments |
| Dactylitis | Diffuse, uniform swelling of an entire digit ("sausage finger/toe") | Flexor tenosynovitis + adjacent joint synovitis + soft tissue oedema [3]; differentiate from the focal joint swelling of RA |
| Deformity | Swan-neck, boutonnière deformities (less common than RA); "opera-glass" hand (main-en-lorgnette) in arthritis mutilans | Tendon imbalance from chronic synovitis; bone resorption → telescoping digits |
| "Less tender, may present with deformity" [5] | PsA joints are characteristically less tender than RA joints for the same degree of swelling | Possibly due to different inflammatory mediator profile; also entheseal fibrosis may reduce acute tenderness |
| Reduced ROM | Limited flexion/extension | Mechanical obstruction from pannus, erosions, or ankylosis |
| Sign | Pathophysiological Basis |
|---|---|
| Tenderness at entheseal sites: Achilles tendon insertion, plantar fascia, patellar tendon, lateral epicondyle | Direct palpation over inflamed enthesis; avoid IA steroid use in Achilles tendon: risk of tendon rupture [5] |
| Swelling/thickening at entheses | Chronic enthesitis → entheseal fibrosis and ossification |
| Sign | Description |
|---|---|
| Well-demarcated erythematous plaques with silvery scale | Classic plaque psoriasis; typically on extensor surfaces |
| Auspitz sign | Pinpoint bleeding when scale is removed (due to dilated capillaries close to surface) |
| Koebner phenomenon | New psoriatic lesions appearing at sites of skin trauma |
| Hidden psoriasis | Scalp, ears, umbilicus, natal cleft, genitalia — must examine these areas |
| Inverse psoriasis | Erythematous, non-scaly patches in flexures |
| Sign | Frequency | Notes |
|---|---|---|
| Nail pitting | Very common | ≥ 20 pits strongly suggests PsA |
| Onycholysis | Common | Can mimic fungal nail infection — always scrape for fungal culture |
| Subungual hyperkeratosis | Common | Especially under distal nail plate |
| Oil-drop sign | Characteristic | Yellow-red translucency |
| Ridging (horizontal/longitudinal) | Common | |
| Nail plate crumbling | Severe disease | Progressive destruction of nail plate |
| Sign | Pathophysiology |
|---|---|
| Uveitis (anterior most common) | Spondyloarthritis is the commonest systemic cause of uveitis [9]; HLA-B27-mediated; anterior chamber shows cells + flare, ciliary flush, miotic pupil |
| Conjunctivitis | Mucosal surface inflammation — shared SpA feature |
- Evidence of metabolic syndrome: central obesity, hypertension, acanthosis nigricans
- Premature atherosclerosis may manifest as abnormal BP, peripheral vascular disease signs
This comparison is explicitly flagged as "important" in senior notes [5]:
| Feature | RA | PsA |
|---|---|---|
| Sex ratio | M:F = 1:3 | M:F = 1:1 |
| Symmetry | Symmetrical polyarthritis | Asymmetrical (5 patterns) |
| DIP involvement | Spares DIP | DIP involvement is characteristic |
| Tenderness | Tenderness precedes deformity | Less tender, may present with deformity |
| Extra-articular joints | Erosive cervical disease (C1/2) | Enthesitis, dactylitis, spondylitis/sacroiliitis |
| Skin | Rheumatoid nodules | Psoriasis (extensor surfaces ± hidden areas); nail dystrophy: onycholysis, pitting, ridging |
| Serology | RF+, anti-CCP+ | RF−, anti-CCP− (usually) |
| Radiology | Joint erosions, periarticular osteopenia, joint space narrowing | Erosions PLUS new bone formation (periostitis), pencil-in-cup, juxta-articular new bone formation, asymmetric syndesmophytes |
| Pathogenesis | Synovium-driven, IL-6/TNF axis | Enthesis-driven, IL-23/IL-17 axis |
| Spinal involvement | Cervical (C1/2 subluxation) | Sacroiliitis (often asymmetric), spondylitis |
PsA is increasingly recognised as a systemic inflammatory disease with significant comorbidity burden:
| Comorbidity | Mechanism |
|---|---|
| Cardiovascular disease | Chronic IL-17/TNF-α → endothelial dysfunction → accelerated atherosclerosis; increased risk of MI, especially in severe psoriasis [4] |
| Metabolic syndrome (obesity, DM, HTN, dyslipidaemia) | Shared inflammatory pathways; adipokines from visceral fat amplify systemic inflammation |
| Hyperuricaemia / Gout | Increased cell turnover in psoriasis → purine metabolism → ↑uric acid; PsA and gout can coexist [1]; be aware of HLA-B*5801 before allopurinol |
| Non-alcoholic fatty liver disease (NAFLD) | Systemic inflammation + metabolic syndrome → hepatic steatosis; relevant for methotrexate use (hepatotoxicity risk) |
| Depression/Anxiety | Chronic visible skin disease + chronic pain → psychosocial burden |
| Osteoporosis | Chronic inflammation → ↑RANKL → bone loss; also immobility-related |
High Yield Summary
Definition: PsA is a chronic immune-mediated inflammatory arthritis associated with psoriasis, belonging to the spondyloarthritis family.
Epidemiology: Affects up to 30% of psoriasis patients; M:F = 1:1; onset 25–40 years; 60% psoriasis precedes arthritis, 20% after, 20% concurrent.
Pathophysiology: IL-23/IL-17 axis-driven; enthesis is the primary target (unlike RA where synovium is primary); results in simultaneous bone erosion AND new bone formation — a unique PsA paradox.
Classification (Moll & Wright): Asymmetric oligoarthritis (~40%), symmetric polyarthritis (~25%), DIP predominant (~5–15%), psoriatic spondylitis (~5%), arthritis mutilans (<5%). GC slide: Oligoarthritis 60–70%, Asymmetric DIP 16%, RA-like 15%, AS 5%, Mutilans 5%.
Key Clinical Features:
- DIP joint involvement (RA spares DIP)
- Dactylitis (~50%) and enthesitis (~35%)
- Nail changes (80–90%): pitting, onycholysis, subungual hyperkeratosis, oil-drop sign
- Less tender than RA, may present with deformity
- Asymmetric, RF-negative
- Hidden psoriasis: always check scalp, ears, umbilicus, natal cleft
- Associated metabolic syndrome and CV risk
Key Differentiator from RA: M:F 1:1 (vs 1:3), asymmetric (vs symmetric), DIP (vs spares DIP), RF−/anti-CCP− (vs positive), enthesitis/dactylitis (vs absent), nail changes (vs nodules), new bone formation on XR (vs osteopenia).
Systemic corticosteroids should NOT be used for psoriasis — taper can cause severe psoriatic flare including pustular psoriasis.
Active Recall - Psoriatic Arthritis (Definition to Clinical Features)
[1] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf – Psoriatic Arthritis section (p. 1708–1710) [2] Lecture slides: Derm General Clerkship 2026 Part1.pdf – Slides 28, 55–56 (triggering factors, PsA patterns) [3] Senior notes: Ryan Ho Rheumatology.pdf – Spondyloarthritis and PsA sections (p. 57–65) [4] Senior notes: Block A - Treatments for skin diseases (eczema, psoriasis and urticaria).pdf – Psoriasis pathogenesis, obesity, CV risk (p. 33–36) [5] Senior notes: Maksim Medicine Notes.pdf – Psoriatic arthritis section (p. 325) [6] Senior notes: Block A - Multiple joint pain_ Rheumatoid arthritis and the concept of inflammatory arthritis.pdf – RA vs PsA comparison [7] Senior notes: Learning_Points_All_Lectures.txt – HLA-B*5801 screening [8] Lecture slides: Upper Limb Painful Conditions_Dr. Margaret Woon Man FOK_3. Inflammatory conditions.pdf – Slides 20–21 [9] Senior notes: Ryan Ho Opthalmology.pdf – Uveitis section (p. 30)
Differential Diagnosis of Psoriatic Arthritis
PsA is a clinical diagnosis — there is no single pathognomonic laboratory test. The challenge is threefold:
- When psoriasis is present: you must decide whether the arthritis is truly PsA or a coincidental arthropathy (e.g., RA, gout, OA can all occur in someone who happens to have psoriasis).
- When psoriasis is absent or occult (20%): arthritis precedes skin disease, so you must distinguish PsA from RA, reactive arthritis, and other inflammatory arthritides based on pattern recognition, serology, and imaging.
- Overlap conditions: PsA and gout can coexist (hyperuricaemia is common in psoriasis due to increased cell turnover), and PsA must be distinguished from other SpA subtypes.
The approach rests on a systematic framework: joint pattern (number, symmetry, which joints), extra-articular features (skin, nails, eyes, entheses, GI), serology (RF, anti-CCP, HLA-B27), and radiology (erosive vs proliferative changes).
Detailed Differential Diagnoses
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.
| Feature | RA | PsA |
|---|---|---|
| Sex | M:F = 1:3 | M:F = 1:1 [3][5] |
| Symmetry | Symmetrical polyarthritis | Asymmetrical (5 patterns) [3][5] |
| DIP joints | Spared | Characteristically involved [3][6] |
| Tenderness | Tenderness precedes deformity | Less tender, may present with deformity [5] |
| Enthesitis / dactylitis | Absent | Present (~35% enthesitis, ~50% dactylitis) [3] |
| Skin | Rheumatoid nodules (subcutaneous, firm, non-tender, extensor surfaces) | Psoriasis (extensor surfaces ± hidden areas); nail dystrophy [5] |
| Nails | Not involved | Pitting, onycholysis, ridging, subungual hyperkeratosis (80-90%) [3] |
| Serology | RF+, anti-CCP+ | RF−, anti-CCP− (usually) [1][5] |
| Radiology | Erosions, periarticular osteopenia, joint space narrowing | Erosions + new bone formation, periostitis, pencil-in-cup, juxta-articular new bone formation [5] |
| Spine | Cervical (C1/2 subluxation) | SI joints (often asymmetric), lumbar/thoracic spondylitis |
| Extra-articular | ILD, pericarditis, scleritis, Felty syndrome, vasculitis | Uveitis (anterior), conjunctivitis, CV disease, metabolic syndrome |
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.
Exam Trap
A patient with psoriasis and symmetric polyarthritis who is RF-positive — is this RA or PsA? The answer is: it could be either. ~5-10% of PsA patients are RF-positive, and psoriasis can coincidentally occur in RA patients. The key differentiators become: DIP involvement, dactylitis, enthesitis, nail changes, and radiological pattern (new bone formation vs pure erosion). Nodules and other extra-articular features of RA are absent in PsA, and arthritis is generally less extensive [3].
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].
| Feature | Reactive Arthritis | PsA |
|---|---|---|
| Preceding infection | Yes — urethritis/cervicitis or dysenteric illness within one month prior [1][3] | Absent |
| Classical triad | "Can't see, can't pee, can't climb a tree" — conjunctivitis + urethritis + asymmetric LL arthritis [11] | Not present |
| Sex | M:F = 15:1 [11] | M:F = 1:1 |
| Skin | Keratoderma blennorrhagica (hyperkeratotic palms/soles — histologically identical to pustular psoriasis); circinate balanitis | Psoriatic plaques |
| Nails | Subungual hyperkeratosis (same as PsA) [11] | Pitting, onycholysis, ridging |
| Joint pattern | Asymmetric oligoarthritis (LL predominant) | Variable (5 patterns) |
| HLA-B27 | Positive in ~90% | Positive in 20-50% (mainly axial) |
| Course | Often self-limiting (weeks to months) | Chronic, rarely remits |
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].
| Feature | AS | Psoriatic Spondylitis |
|---|---|---|
| Axial involvement | Predominant, bilateral sacroiliitis (symmetric) | Similar picture but less severe, asymmetric/unilateral [3] |
| Syndesmophytes | Thin, marginal, flowing (bamboo spine) | Chunky, non-marginal (paravertebral ossification), asymmetric |
| HLA-B27 | > 95% positive | 20-50% positive |
| Psoriasis | Absent (by definition in pure AS) | Present [1] |
| Peripheral arthritis | Less prominent (hip involvement common) | Often prominent |
| Sex | M > > F | M = F |
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].
| Feature | Enteropathic Arthritis | PsA |
|---|---|---|
| GI symptoms | Diarrhoea (bloody/mucoid), abdominal pain, weight loss; confirmed by endoscopy + biopsy [1] | Absent (unless coincidental IBD) |
| Joint pattern | Peripheral: acute pauciarticular, LL predominant; Type 1 coincides with bowel flare [12] | Variable (5 patterns) |
| Skin | Erythema nodosum, pyoderma gangrenosum [12] | Psoriatic plaques |
| Sacroiliitis | Present in ~16% [12] | Present in spondylitic pattern |
| Eye | Uveitis, episcleritis | Uveitis, conjunctivitis |
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
| Feature | Gout | PsA |
|---|---|---|
| Onset | Acute, explosive (peak within 12-24 hours) | Insidious or subacute |
| Pattern | 1st MTP classically ("podagra"); distal > proximal; migratory [13] | Variable, ray pattern, DIP predominant |
| Crystals | MSU crystals: needle-shaped, strongly negatively birefringent under polarised microscopy | Absent |
| Tophi | Present in chronic gout (firm, chalky deposits) | Absent |
| Skin | No psoriasis (unless coexistent) | Psoriatic plaques, nail changes |
| Serology | RF−, ↑serum uric acid (though can be normal during acute attack) | RF−, uric acid may be elevated |
| XR | Punched-out erosions with overhanging edges, no new bone formation | Erosions + juxta-articular new bone formation, pencil-in-cup |
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].
Clinical Pearl – Dual Diagnosis
In a middle-aged man with DIP joint swelling, nail changes, elevated uric acid, AND psoriasis — always aspirate the joint if acute monoarthritis is present. Finding MSU crystals confirms gout but does NOT exclude coexistent PsA. Look for nail pitting, dactylitis, enthesitis, and XR evidence of new bone formation to identify both conditions.
OA can mimic PsA because both can affect DIP joints, and both are common conditions that may coexist [6][13].
| Feature | OA | PsA |
|---|---|---|
| Age | Older age [10] | Younger (25-40 years) |
| Onset | Insidious [10] | Insidious or subacute |
| Joint character | Hard and bony swelling (Heberden nodes at DIP, Bouchard nodes at PIP); evening stiffness; worse after effort [6] | Soft, warm, tender swelling; early morning stiffness > 30 min; worse after rest |
| DIP | Yes (Heberden nodes) | Yes (with nail changes) |
| Inflammatory markers | Normal ESR/CRP | Elevated ESR/CRP |
| Radiology | Joint space narrowing, osteophytes, subchondral sclerosis, subchondral cysts | Erosions + new bone formation, pencil-in-cup, periostitis |
| Nail changes | Absent | Present (80-90%) |
| Dactylitis / enthesitis | Absent | Present |
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].
| Feature | Viral Polyarthritis | PsA |
|---|---|---|
| Course | Self-limiting, usually ≤ 6 weeks [13] | Chronic, progressive |
| Pattern | Symmetric, small joints | Variable |
| Viral prodrome | Present (fever, rash, pharyngitis, hepatitis) | Absent |
| Serology | Specific viral serology positive; may have transient RF positivity | RF negative |
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].
| Feature | SLE Arthritis | PsA |
|---|---|---|
| Pattern | Symmetrical small joint polyarthritis but usually NOT associated with evidence of synovitis [13] | Asymmetric, with frank synovitis |
| Morning stiffness | Usually in minutes, not as prolonged as RA [13] | > 30 minutes |
| Deforming? | Typically non-deforming, non-erosive (Jaccoud arthropathy is reducible) | Can be destructive (mutilans) |
| Multi-system | Malar rash, serositis, nephritis, cytopenias, anti-dsDNA/ANA | Psoriasis, nail changes |
| Serology | ANA+, anti-dsDNA+ | ANA usually negative |
Always consider in any acute monoarthritis presentation — hot, swollen tender joint = septic arthritis until proven otherwise [14].
| Feature | Septic Arthritis | PsA |
|---|---|---|
| Onset | Acute, high fever | Subacute, low-grade or no fever |
| Number | Monoarthritis (80-90%) [14] | Often oligo/polyarticular |
| Joint fluid | Purulent; positive culture | Inflammatory but sterile |
| Risk factors | Immunosuppression, IVDU, prosthetic joint, RA | Psoriasis, family history |
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]:
| Feature | JIA-Psoriatic | Adult PsA |
|---|---|---|
| Age | 1-16 years, M=F [15] | 25-40 years |
| Joint pattern | Usually asymmetrical large and small joints [15] | 5 Moll-Wright patterns |
| Extra-articular | Psoriasis (50%), nail pitting/dystrophy, dactylitis, chronic anterior uveitis (20%) [15] | Psoriasis, nail changes, uveitis |
| Definition | Arthritis AND psoriasis; OR arthritis with ≥ 2 of: dactylitis, nail pitting/onycholysis, psoriasis in 1st degree relative [16] | CASPAR criteria |
From GC 074 lecture slide — Clinical features of different arthritis (history): RA: younger age, insidious onset, polyarthritis, small hand joints, sparing DIP joints, early morning stiffness ≥30min. Spondyloarthritis: younger age, insidious onset, mono or polyarthritis, any joint could be involved, psoriasis, IBD, STD/dysentery, uveitis, back pain, family history. OA: insidious onset, DIP joints or weight bearing joints, older age. Gout: acute onset, first metatarsophalangeal joint involvement, usually self limiting, sometimes fever [10].
From GC 074 lecture slide — Clinical features of SpA: Spondylitis, peripheral arthritis, enthesitis (Achilles tendinitis, plantar fasciitis), anterior uveitis, aortitis, associated with HLA-B27. Other associated features: psoriasis, inflammatory bowel disease, dysentery, sexually transmitted disease [10].
| Diagnosis | Key Distinguishing Feature from PsA |
|---|---|
| RA | Symmetric, spares DIP, RF+/anti-CCP+, rheumatoid nodules, no nail changes, no enthesitis/dactylitis |
| Reactive arthritis | Preceding GU/GI infection within 1 month, keratoderma blennorrhagica, circinate balanitis, M >> F |
| AS | Predominantly axial, bilateral symmetric sacroiliitis, HLA-B27 > 95%, no psoriasis |
| Enteropathic arthritis | GI symptoms, endoscopic/histological IBD, erythema nodosum, pyoderma gangrenosum |
| Gout | MSU crystals on aspiration, acute explosive onset, podagra, tophi, can coexist with PsA |
| OA | Hard bony swelling, Heberden/Bouchard nodes, mechanical pain, normal inflammatory markers |
| Viral arthritis | Self-limiting < 6 weeks, viral prodrome, specific serology |
| SLE | Non-erosive, non-deforming, malar rash, ANA+, anti-dsDNA+, multi-system |
| Septic arthritis | Acute, high fever, monoarticular, purulent aspirate, positive culture |
Approach to Differential Diagnosis: What to Ask and Examine
| Question | Diagnostic Implication |
|---|---|
| Psoriasis or family history of psoriasis? | PsA; check hidden areas |
| Preceding infection (urethritis, dysentery)? [10] | Reactive arthritis |
| Chronic diarrhoea, bloody stool? | Enteropathic arthritis |
| Back pain (inflammatory pattern)? [10] | Axial SpA / psoriatic spondylitis |
| Eye symptoms (pain, redness, photophobia)? [10] | Uveitis — common in SpA |
| Acute vs chronic onset? | Acute → gout, septic, reactive; chronic → RA, PsA, OA |
| Symmetry? | Symmetric → RA, SLE; asymmetric → PsA, reactive, gout |
| DIP involvement? | PsA, OA, gout (not RA) |
| Nail changes? | Strongly favours PsA |
| Dactylitis ("sausage digit")? | SpA spectrum (PsA, reactive) |
| Metabolic syndrome components? | Raises suspicion for PsA + gout coexistence |
| Medication history (lithium, β-blockers)? | Can trigger/worsen psoriasis and PsA |
| Sign | Points Towards |
|---|---|
| DIP swelling with nail dystrophy | PsA |
| Sausage digit (dactylitis) | PsA / SpA |
| Entheseal tenderness (Achilles, plantar fascia) | SpA (PsA, AS, reactive) |
| Rheumatoid nodules | RA (absent in PsA) |
| Tophi | Gout |
| Hard bony swelling at DIP (Heberden nodes) | OA |
| Malar rash, oral ulcers | SLE |
| Keratoderma blennorrhagica (palms/soles) | Reactive arthritis |
| Erythema nodosum | IBD-associated arthritis, sarcoidosis |
| Hidden psoriasis (scalp, ears, umbilicus, natal cleft) | PsA — always check these sites |
| Pitting, ridging or crumbly appearance of nails [8] | PsA |
High Yield – GC Lecture Approach
From GC 074: When evaluating multiple joint pain, systematically consider RA, SpA (including PsA), OA, and gout as the major categories. SpA is distinguished by: any joint can be involved, association with psoriasis/IBD/STD/dysentery/uveitis, back pain, and family history [10]. Use this framework as your initial mental scaffold, then refine based on pattern, serology, and imaging.
High Yield Summary
Most important DDx for PsA: RA (symmetric, spares DIP, RF+, no nail/entheseal changes), gout (can coexist! always aspirate acute monoarthritis), reactive arthritis (preceding infection), AS (bilateral sacroiliitis, no psoriasis), enteropathic arthritis (IBD symptoms), OA (mechanical, bony swelling).
Top 3 bedside differentiators of PsA from RA: 1) DIP involvement with nail changes, 2) Dactylitis/enthesitis, 3) RF-negative.
Remember: PsA and gout can coexist — finding MSU crystals does not exclude PsA. Always look for nail changes, dactylitis, and XR new bone formation.
Systemic onset JIA is the most difficult to diagnose — infection and leukaemia are major differentials [17]. In children, psoriatic JIA is defined as arthritis + psoriasis OR arthritis + ≥ 2 of dactylitis/nail changes/FHx psoriasis [16].
Active Recall - Differential Diagnosis of Psoriatic Arthritis
References
[1] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf – Psoriatic Arthritis, Differential Diagnosis sections (p. 1708–1712) [3] Senior notes: Ryan Ho Rheumatology.pdf – Spondyloarthritis and PsA sections (p. 57–66) [5] Senior notes: Maksim Medicine Notes.pdf – Psoriatic arthritis, Reactive arthritis sections (p. 325–328) [6] Senior notes: Block A - Multiple joint pain_ Rheumatoid arthritis and the concept of inflammatory arthritis.pdf – RA vs PsA, RA spares DIP [8] Lecture slides: Upper Limb Painful Conditions_Dr. Margaret Woon Man FOK_3. Inflammatory conditions.pdf – PsA slides (p. 20–22) [10] Lecture slides: GC 074. Multiple joint pain.pdf – Clinical features of different arthritis (p. 4, 31) [11] Senior notes: Maksim Medicine Notes.pdf – Reactive arthritis (p. 326–328) [12] Senior notes: Ryan Ho GI.pdf – IBD extra-intestinal features (p. 121) [13] Senior notes: Ryan Ho Fundamentals.pdf – Polyarthritis and monoarthritis differential diagnoses (p. 406–409) [14] Senior notes: Adrian Lui Pediatrics Notes.pdf – Septic arthritis (p. 453) [15] Senior notes: Adrian Lui Pediatrics Notes.pdf – JIA classification, psoriatic subtype (p. 455) [16] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf – ILAR classification, psoriatic arthritis definition (p. 692) [17] Lecture slides: GC 053. Fingers turn white and blue.pdf – Systemic onset JIA (p. 65)
Diagnostic Criteria for Psoriatic Arthritis
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:
- Inflammatory arthritis — peripheral arthritis, sacroiliitis, or spondylitis
- Presence of psoriasis
- 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]:
| Feature | Points | Explanation |
|---|---|---|
| Skin psoriasis — current | 2 | Active psoriatic lesions assessed by a dermatologist or rheumatologist. Highest-weighted criterion because current psoriasis is the strongest diagnostic clue. |
| Skin psoriasis — previously present by history | 1 | Patient reports prior psoriasis but no current lesions. Less weight because documentation may be uncertain. |
| Family history of psoriasis (if patient not affected) | 1 | First- or second-degree relative with psoriasis. Included to capture patients where arthritis precedes skin disease. |
| Nail lesions — pitting or onycholysis | 1 | Characteristic psoriatic nail changes on current examination. |
| Dactylitis — current, or past documented by a rheumatologist | 1 | "Sausage digit" — current or historically documented. |
| Negative rheumatoid factor | 1 | RF-negative. Included because PsA is typically seronegative. |
| Juxta-articular new bone formation on radiography | 1 | Distinct from osteophytes — periostitis, fluffy new bone near joints. This is the radiological hallmark that separates PsA from RA. |
CASPAR Scoring — Worked Example
A patient with inflammatory oligoarthritis + current psoriasis (2) + nail pitting (1) + RF-negative (1) = 4 points → meets CASPAR criteria. Even without psoriasis, a patient with inflammatory arthritis + dactylitis (1) + nail pitting (1) + RF-negative (1) + juxta-articular new bone formation (1) = 4 points → still meets criteria.
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].
High Yield — CASPAR for Exams
The CASPAR criteria are the most commonly tested diagnostic criteria for PsA in HKUMed exams. Know the mandatory entry criterion (inflammatory MSK disease) and the 5 scoring domains with their point values. Remember: current psoriasis is worth 2 points (the only feature worth 2), everything else is 1 point. Total ≥ 3 needed.
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].
Diagnostic Algorithm
The diagnostic approach to PsA follows a structured pathway: clinical suspicion → history and examination → laboratory investigations → imaging → apply CASPAR criteria → exclude mimics.
Detailed Step-by-Step Approach
This is the mandatory CASPAR entry criterion. Confirm that the patient has:
- Peripheral arthritis: joint swelling, warmth, tenderness, ± effusion
- And/or spondylitis: inflammatory back pain (insidious onset, age < 40, morning stiffness > 30 min, improves with exercise, does not improve with rest, alternating buttock pain)
- And/or enthesitis: spontaneous pain or tenderness at tendon/ligament insertion sites
Without confirmed inflammatory musculoskeletal disease, you cannot diagnose PsA.
- ALWAYS look at the scalp, the nails, post-auricular areas and mucosal areas for possible lesions [1].
- Hidden psoriatic plaques in the scalp, gluteal fold or umbilicus [1].
- Nail involvement is a predictor for psoriatic arthropathy [19].
- Presence of nail disease is important diagnostically, often providing valuable supportive evidence of disease in difficult cases [1].
- More common in patients with psoriatic arthritis and may be one of the strongest clinical predictors for concomitant psoriatic arthritis [1].
- Check all digits for "sausage" swelling.
- Palpate key entheseal sites: Achilles tendon insertion, plantar fascia, patellar tendon insertion, lateral/medial epicondyles.
Step 4: Send Laboratory Investigations (see below)
Step 5: Obtain Imaging (see below)
- Total ≥ 3 → classify as PsA.
- Joint aspiration if acute monoarthritis → exclude septic arthritis and crystal arthropathy.
- Remember: PsA and gout can coexist [1].
Investigation Modalities
A. Laboratory Investigations
| Test | Expected Finding | Why / Interpretation |
|---|---|---|
| ESR | ↑ | Non-specific marker of inflammation; ESR rises with chronic inflammation due to increased fibrinogen and immunoglobulins causing rouleaux formation of RBCs → faster sedimentation. |
| CRP | ↑ | Acute-phase protein synthesised by hepatocytes in response to IL-6. More specific and responsive to acute changes than ESR. CRP reflects current disease activity. |
Bloods: CBC, LRFT, ESR/CRP, HLA-B27, RF (−ve) [5].
Clinical note: Inflammatory markers may be normal in mild/early PsA (~40% of patients have normal CRP/ESR), so normal values do not exclude PsA.
| Finding | Significance |
|---|---|
| Anaemia of chronic disease [1] | Chronic inflammation → IL-6 stimulates hepcidin → blocks iron absorption and recycling → functional iron deficiency; normocytic normochromic anaemia |
| Leukocytosis [1] | Reflecting a non-specific inflammatory response — cytokine-driven marrow stimulation |
| Thrombocytosis | Reactive thrombocytosis from chronic inflammation (IL-6 stimulates thrombopoietin production) |
| Test | Expected Finding | Clinical Importance |
|---|---|---|
| Rheumatoid Factor (RF) | Negative in ~90-95% of PsA | Present in 2–10% of psoriatic arthritis despite being one of the entities in seronegative spondyloarthritis [1]. RF-negative is a CASPAR scoring point (+1). A positive RF does not exclude PsA. |
| Anti-CCP (anti-cyclic citrullinated peptide) | Negative in ~84-92% | Present in 8–16% of patients [1]. More specific for RA than RF, but still can be positive in a minority of PsA patients. |
| ANA (anti-nuclear antibody) | Found in lower titres (≤ 1/40) in 50% of patients; clinically significant titres (≥ 1/80) in 14% [1] | Non-specific; helps exclude SLE if strongly positive with other features. |
Interpretation of Serology in PsA
A common mistake is to exclude PsA because RF or anti-CCP is positive. Remember: ~5-10% of PsA patients ARE RF-positive, and ~8-16% are anti-CCP-positive. The CASPAR criteria give 1 point for RF-negative, but a positive RF does not disqualify the diagnosis — you just lose that 1 point and need to accumulate 3 points from other domains.
| Finding | Significance |
|---|---|
| HLA-B27 positive in 20-50% of PsA with axial disease | Should be obtained in patients with psoriasis who present with arthritis [1]. Particularly useful when axial involvement (spondylitis, sacroiliitis) is suspected. HLA-B27 positivity does not diagnose PsA but supports SpA classification. HLA-B27 typing: associated with psoriatic and enthesitis types [15]. |
HLA-B27 prevalence: 6-8% for southern Chinese [3]. So a positive HLA-B27 in a Chinese patient with psoriasis and inflammatory back pain is highly supportive of PsA with axial involvement.
| Test | Rationale |
|---|---|
| Fasting glucose / HbA1c | Screen for diabetes (metabolic syndrome association) |
| Lipid profile | Screen for dyslipidaemia |
| Uric acid | Screen for hyperuricaemia — common in psoriasis due to ↑cell turnover; rule out coexisting gout |
| LFT | Baseline before starting methotrexate (hepatotoxic); screen for NAFLD |
| RFT | Baseline before starting NSAIDs/DMARDs; screen for renal impairment |
When to perform: Any acute monoarthritis or oligoarthritis, especially to exclude septic arthritis and crystal arthropathy.
Synovial fluid analysis findings in PsA [1]:
| Measure | Normal | Non-inflammatory | Inflammatory (PsA) | Septic | Haemorrhagic |
|---|---|---|---|---|---|
| Volume (knee) | < 3.5 mL | > 3.5 | > 3.5 | > 3.5 | > 3.5 |
| Clarity | Transparent | Transparent | Transparent to opaque | Opaque | Bloody |
| Colour | Clear | Yellow | Yellow | Yellow | Red |
| Viscosity | High | High | Low | Variable | Variable |
| WBC/mm³ | < 200 | 0–2000 | > 2000 | > 20,000 | Variable |
| PMNs (%) | < 25% | < 25% | ≥ 50% | ≥ 75% | 50–75% |
| Culture | −ve | −ve | −ve | +ve | −ve |
| Crystals | None | None | None | None | None |
Why viscosity drops in inflammatory fluid: Normal synovial fluid contains hyaluronic acid (produced by type B synoviocytes) which gives it high viscosity. Inflammation → enzymatic degradation of hyaluronic acid by inflammatory cell enzymes → low viscosity.
Key point: Always send for crystal analysis under polarised microscopy — needle-shaped, strongly negatively birefringent crystals = MSU (gout); rhomboid, weakly positively birefringent crystals = CPPD (pseudogout). Finding crystals does not exclude PsA (they can coexist), but it confirms crystal arthropathy.
B. Imaging Investigations
XR joints: findings include soft tissue swelling, periarticular osteopenia ± bone/cartilage destruction [15] (general JIA), but PsA has distinctive radiological features that differ from RA:
Characteristic XR findings in PsA [1][5]:
| Finding | Description | Pathophysiological Basis |
|---|---|---|
| Pencil-in-cup deformity | Erosion at head of middle phalanx (pencil) + proliferative new bone at base of distal phalanx (cup) [5] | Simultaneous osteoclast-mediated erosion (TNF-α/RANKL) and osteoblast-mediated new bone formation (IL-17/IL-22) at the IP joints |
| Juxta-articular new bone formation | Fluffy periostitis near joints, distinct from osteophytes | Entheseal ossification driven by IL-17, IL-22, BMP signalling at sites of tendon/ligament insertion |
| Small joint erosion and fusion | Erosion progressing to bony ankylosis [5] | End-stage inflammatory destruction followed by reparative ossification → complete joint fusion |
| "Pencil-in-a-cup" appearance [1] | As above — the classic PsA radiological sign | |
| Asymmetric syndesmophytes | Chunky, non-marginal (paravertebral) ossification [5] | Enthesophyte formation at vertebral body margins; asymmetric because PsA spondylitis is asymmetric |
| Coexistence of erosive changes and new bone formation | "This is typical" [1] — the pathological hallmark of PsA: bone destruction AND bone formation occurring simultaneously | |
| Occurrence of both joint lysis and ankylosis | Gross destruction of isolated joints and new bone formation [1] | Some joints show complete erosion while adjacent joints show fusion |
| Absence of periarticular osteopenia | Unlike RA where periarticular osteopenia is prominent | PsA pathology is entheseal → periosteal new bone formation counteracts osteopenia |
| Sacroiliitis (asymmetric) | Unilateral or asymmetric SI joint erosion/sclerosis | Unlike AS where sacroiliitis is bilateral and symmetric |
XR joints: pencil-in-cup deformity at IP joints (simultaneous erosion at head of middle phalanx + new bone formation at base of distal phalanx), small joint erosion and fusion, syndesmophytes [5].
RA vs PsA on X-ray — Key Distinction
RA: Erosions + periarticular osteopenia + joint space narrowing. NO new bone formation. PsA: Erosions + periostitis + juxta-articular new bone formation + pencil-in-cup. BOTH erosion AND proliferation. OA: Joint space narrowing + osteophytes + subchondral sclerosis + subchondral cysts. NO erosions (usually). This three-way comparison is high-yield for radiology stations and written exams.
MRI of joints: More sensitive than routine radiography in detecting articular, periarticular and soft tissue inflammation [1].
| What MRI Detects | Why It Matters |
|---|---|
| Bone marrow oedema | Precursor to erosion — identifies early/pre-erosive disease before XR changes appear |
| Synovitis | Synovial enhancement on contrast MRI indicates active inflammation |
| Enthesitis | Signal changes at entheseal insertions (e.g., Achilles, plantar fascia) |
| Tenosynovitis / dactylitis | Fluid and enhancement in flexor tendon sheaths — confirms dactylitis mechanism |
| Sacroiliitis | MRI detects active sacroiliitis (bone marrow oedema) before structural damage is visible on XR → crucial for axial PsA diagnosis |
| Erosions | More sensitive than XR, especially at small joints |
When to use MRI:
- Early disease where XR is normal but clinical suspicion is high
- Axial disease assessment (SI joints, spine)
- Differentiating dactylitis from other causes of digit swelling
- Monitoring treatment response in clinical trials
| What US Detects | Clinical Utility |
|---|---|
| Synovitis | Grey-scale thickening of synovium; Power Doppler signal indicates active vascularity/inflammation |
| Enthesitis | Thickening, hypoechogenicity, and Power Doppler signal at entheseal sites; can detect enthesophytes |
| Tenosynovitis | Fluid around flexor tendons in dactylitis |
| Erosions | More sensitive than XR for small cortical erosions |
| Joint effusion | Quantification and guided aspiration |
Advantages over MRI: Bedside, no contrast needed, no radiation, can examine multiple sites rapidly, dynamic assessment, guides aspiration/injection.
- Useful for detailed bony anatomy when XR is equivocal.
- Dual-energy CT (DECT): can detect urate crystal deposits in gout — useful to differentiate PsA from gout when aspiration is not possible.
Slit lamp for chronic anterior uveitis [15].
| Finding | Significance |
|---|---|
| Anterior chamber cells and flare | Active anterior uveitis — leucocytes and protein exudate in aqueous humour |
| Keratic precipitates | Cellular deposits on corneal endothelium — indicates granulomatous (large, "mutton-fat") or non-granulomatous (fine) uveitis |
| Posterior synechiae | Adhesions between iris and lens — indicates chronic/recurrent uveitis |
When to request: All PsA patients should have baseline ophthalmological assessment. Routine slit-lamp screening is recommended, especially if symptomatic (pain, redness, photophobia, blurred vision) or if HLA-B27-positive.
Once PsA is diagnosed, disease activity is monitored using validated composite scores [5]:
| Tool | Components | Purpose |
|---|---|---|
| PASDAS (PsA Disease Activity Score) | Tender and swollen joints, dactylitis, enthesitis, CRP, patient/physician global assessment, SF-36 [5] | Comprehensive composite score for disease activity |
| DAPSA (Disease Activity Index for PsA) | Tender and swollen joints, CRP, patient global VAS, pain VAS [5] | Simpler, focused on peripheral arthritis |
| MDA (Minimal Disease Activity) | 5 of 7 criteria met: tender joints ≤ 1, swollen joints ≤ 1, PASI ≤ 1, patient pain VAS ≤ 15, patient global VAS ≤ 20, HAQ ≤ 0.5, tender entheseal points ≤ 1 | Treatment target |
| PASI (Psoriasis Area and Severity Index) | Skin assessment | Skin disease severity |
| LEI (Leeds Enthesitis Index) | 6 entheseal sites assessed | Enthesitis severity |
| Category | Investigation | Key Finding in PsA |
|---|---|---|
| Blood | CBC | Anaemia of chronic disease, leukocytosis, thrombocytosis |
| ESR/CRP | Elevated (but can be normal in mild disease) | |
| RF | Negative (2-10% positive) | |
| Anti-CCP | Negative (8-16% positive) | |
| ANA | Low titres in ~50%, clinically significant in 14% | |
| HLA-B27 | Positive in 20-50% with axial disease | |
| Uric acid | May be elevated (exclude/confirm coexisting gout) | |
| LFT, RFT | Baseline for DMARD monitoring | |
| Synovial fluid | Aspiration | Inflammatory fluid (WBC > 2000, PMN ≥ 50%), sterile, no crystals |
| Imaging | XR | Pencil-in-cup, juxta-articular new bone formation, erosion + proliferation, asymmetric syndesmophytes |
| MRI | Bone marrow oedema, synovitis, enthesitis, sacroiliitis (early) | |
| US | Synovitis with Power Doppler signal, enthesitis, tenosynovitis | |
| Ophthalmology | Slit-lamp | Anterior uveitis (cells, flare, KPs) |
| Skin biopsy | Punch biopsy (if diagnostic doubt) | Psoriasis histology: acanthosis, parakeratosis, Munro microabscesses |
High Yield Summary
Diagnostic Criteria:
- CASPAR criteria (2006): Mandatory entry = inflammatory MSK disease (arthritis/spondylitis/enthesitis). Then score ≥ 3 from: current psoriasis (+2), personal Hx (+1), FHx (+1), nail lesions (+1), dactylitis (+1), RF-negative (+1), juxta-articular new bone on XR (+1). Sensitivity 91.4%, specificity 98.7%.
- Moll and Wright (1973): All 3 of inflammatory arthritis + psoriasis + RF-negative. Simple but limited.
- ILAR (paediatric): Arthritis + psoriasis, OR arthritis + ≥ 2 of (dactylitis, nail changes, FHx psoriasis).
Key Investigations:
- Bloods: CBC, LRFT, ESR/CRP, HLA-B27, RF (−ve) [5].
- RF negative in ~90-95%; anti-CCP negative in ~84-92%; ANA low-titre positive in ~50%.
- XR: pencil-in-cup deformity, juxta-articular new bone formation (distinct from osteophytes), simultaneous erosion and proliferation.
- MRI: more sensitive than XR for early disease, enthesitis, sacroiliitis.
- Joint aspiration: inflammatory fluid, sterile, no crystals (but crystals can coexist with PsA).
- Always examine hidden psoriasis sites and nails; nail involvement is the strongest clinical predictor of PsA.
Active Recall - Diagnostic Criteria and Investigations for PsA
[1] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf – Psoriatic Arthritis: Diagnosis, Biochemical tests, Radiological tests, CASPAR criteria (p. 1710–1713) [3] Senior notes: Ryan Ho Rheumatology.pdf – CASPAR criteria, Moll and Wright criteria, ASAS peripheral SpA criteria, SpA overview (p. 57–65) [5] Senior notes: Maksim Medicine Notes.pdf – CASPAR criteria, Investigations, Disease activity scores (p. 323–326) [8] Lecture slides: Upper Limb Painful Conditions_Dr. Margaret Woon Man FOK_3. Inflammatory conditions.pdf – PsA slides (p. 20–22) [15] Senior notes: Adrian Lui Pediatrics Notes.pdf – JIA investigation and HLA-B27 (p. 455–456) [16] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf – ILAR classification (p. 692) [18] Lecture slides: GC 144. A child with recurrent infections Primary immunodeficiencies.pdf – Psoriatic arthritis JIA criteria (p. 57) [19] Senior notes: Block A - Dermatology PBL 1.pdf – Nail involvement predictor for psoriatic arthropathy (p. 12)
Management of Psoriatic Arthritis
Before diving into individual therapies, understand the overarching management philosophy of PsA:
- Treat-to-target: Aim for minimal disease activity (MDA) or remission across all disease domains — joints, entheses, dactylitis, skin, nails, and function [3][5][20].
- Multi-domain disease: PsA is not just arthritis — it simultaneously involves skin, nails, entheses, axial skeleton, and systemic comorbidities. The ideal treatment addresses multiple domains simultaneously.
- Early DMARD initiation: Early DMARD treatment for psoriatic arthritis [20] — structural joint damage occurs within the first 2 years; delay increases irreversible damage.
- Active arthritis defined as > 3 tender/swollen joints, dactylitis counted as one active joint [20] — this threshold triggers DMARD initiation.
- Domain-specific approach: Different manifestations respond to different drugs (e.g., conventional DMARDs work for peripheral arthritis but NOT for axial disease or enthesitis).
- Corticosteroid caution: Oral corticosteroid: risk of psoriasis flare upon tapering. So be cautious with starting oral steroid [3][20]. Corticosteroid taper can precipitate very severe psoriatic flare, pustular psoriasis — so that is why systemic corticosteroids not used for this condition [2].
Non-pharmacological: education, stretching exercise, physiotherapy, smoking cessation [3][5].
| Intervention | Rationale |
|---|---|
| Patient education | Understanding the chronic nature of PsA, importance of adherence, and the concept of treat-to-target improves outcomes. Patients need to know PsA is manageable but not curable. |
| Physiotherapy / Exercise | Stretching exercise [5] — maintains joint mobility, prevents contractures, strengthens periarticular muscles to offload joints. Swimming is particularly beneficial (non-weight-bearing, full ROM exercise). |
| Occupational therapy | Supportive care: splints, PT/OT [15] — joint protection strategies, adaptive devices for ADLs, ergonomic advice. Splints reduce stress on inflamed joints. |
| Smoking cessation | Smoking cessation [3][5] — smoking worsens psoriasis, increases CV risk (already elevated in PsA), reduces treatment response (esp. to anti-TNF), and contributes to the restrictive lung disease burden. |
| Weight management | Obesity drives systemic inflammation via adipokines, worsens psoriasis, reduces biologic efficacy (pharmacokinetic and pharmacodynamic reasons — higher volume of distribution, adipose tissue sequesters drug), and accelerates joint damage. |
| Psychological support | Chronic visible skin disease + chronic pain → high rates of depression and anxiety. Screening and referral to psychological services is important. |
B. Pharmacological Management — By Domain
Domain 1: Peripheral Arthritis
This is the most systematically treated domain. The treatment escalation ladder follows: NSAIDs → csDMARDs → bDMARDs/tsDMARDs.
| Aspect | Detail |
|---|---|
| Indication | NSAIDs for mild arthritis [3]; symptomatic relief of pain and stiffness in early/mild peripheral arthritis |
| Examples | Naproxen 500 mg BD, ibuprofen 400–800 mg TDS, diclofenac 50 mg TDS, celecoxib 200 mg BD |
| Mechanism | Inhibit cyclooxygenase (COX) → block prostaglandin synthesis → reduce inflammation, pain, and fever. COX-1 is constitutive (protective: gastric mucosa, platelets, renal blood flow). COX-2 is inducible (inflammation). Non-selective NSAIDs block both; COX-2 selective inhibitors (celecoxib) spare COX-1 → fewer GI side effects. |
| GI protection | Addition of gastroprotective agents or use selective COX-2 inhibitor in patients with high GI risks (elderly, history of peptic ulcer, comorbidity) [20]. PPI raises gastric pH, ulcerogenic effects become reduced [21]. |
| Contraindications | Active PUD, CKD (renal vasoconstriction), uncontrolled heart failure, third-trimester pregnancy, aspirin-exacerbated respiratory disease |
| Key caution | NSAID with concurrent corticosteroids for treatment of arthritis: increased risk of peptic ulcer disease [22]. Long-term use of NSAID > 3 months for symptom relief of OA where paracetamol has not been tried is flagged in STOPP criteria [22]. |
Important note on axial vs peripheral disease: Unlike in axial SpA where continuous NSAID use has a modest disease-modifying effect, in peripheral PsA NSAIDs are purely symptomatic — they do not prevent structural joint damage. This is why early DMARD initiation is critical.
Start DMARDs early if active arthritis (> 3 joints incl dactylitis) [3]. Early DMARD treatment for psoriatic arthritis [20].
| Drug | Dose | Why This Drug | Mechanism | Key Side Effects | Monitoring |
|---|---|---|---|---|---|
| Methotrexate (MTX) | Up to 25 mg Q1w [3] | Preferred in PsA to co-treat skin psoriasis [3][5][20] — the anchor DMARD because it addresses both joints AND skin simultaneously | Folate antimetabolite → inhibits dihydrofolate reductase → blocks purine/pyrimidine synthesis → reduces lymphocyte proliferation; also increases adenosine (anti-inflammatory); inhibits IL-17 and TNF-α production | Interstitial pneumonitis, hepatotoxicity, nephrotoxicity, bone marrow suppression [15]; nausea, oral ulcers, teratogenicity | CBC, LFT, RFT Q1–3 months; baseline CXR; supplement with folic acid 5 mg (given on non-MTX day) to reduce side effects |
| Sulphasalazine (SSZ) | 2–3 g/day [3] | Preferred in IBD and non-psoriatic SpA [3] — less commonly used in PsA but useful if MTX contraindicated | "Sulpha-" = sulfapyridine (carrier); "-salazine" = 5-aminosalicylic acid (active moiety); local anti-inflammatory action in gut; immunomodulatory via NF-κB inhibition | Skin rash, haemolysis, neutropenia, male infertility, pancreatitis, hepatotoxicity | CBC, LFT |
| Leflunomide | 20 mg QD [3] | Alternative csDMARD; effective for peripheral arthritis and skin psoriasis | Inhibits dihydroorotate dehydrogenase (DHODH) → blocks pyrimidine synthesis → reduces lymphocyte proliferation. "Leflunomide" → think "left behind" = lymphocytes left without building blocks | Hepatotoxicity, diarrhoea, hypertension, teratogenicity (very long half-life due to enterohepatic recirculation — requires cholestyramine washout before conception) | LFT, BP, CBC |
| Cyclosporin | Variable | Also active against skin psoriasis [5] | Calcineurin inhibitor → blocks T cell activation by inhibiting IL-2 transcription → reduces T cell-mediated immunity. Particularly effective for skin because T cells are the primary effectors in psoriasis | Nephrotoxicity, hypertension, gingival hyperplasia, hirsutism, tremor | RFT, BP, drug levels |
Must Know — Avoid HCQ in PsA
Avoid HCQ (hydroxychloroquine): may exacerbate psoriasis [5]. This is a classic exam point. HCQ is widely used in RA and SLE but is contraindicated in PsA because it can trigger severe psoriasis flares, including erythrodermic and pustular forms. The mechanism is not fully understood but may relate to HCQ's interference with epidermal growth regulation.
Methotrexate: weekly tablet/liquid/injection. Effect: ~70% effective in polyarthritis, less effective in systemic subtype. S/E: interstitial pneumonitis, hepatotoxicity, nephrotoxicity, bone marrow suppression [15].
| Aspect | Detail |
|---|---|
| Role | Oral corticosteroids: as bridging therapy until action of DMARD sets in [3] — DMARDs take 6–12 weeks to reach full effect; short-course low-dose steroids bridge this gap |
| Dose | Prednisolone 5–15 mg/day, tapered over 4–8 weeks |
| Critical caution | Note risk of psoriasis flare upon tapering → CAUTIOUS with starting oral steroids [3]. Corticosteroid taper precipitate very severe psoriatic flare, pustular psoriasis → so that is why systemic corticosteroids not used for this condition [2]. If used, taper VERY slowly (e.g., 1–2.5 mg reduction per week). |
| Local steroids | Intra-articular corticosteroid injection: useful for individual swollen joints (quick relief, avoids systemic exposure). Avoid IA steroid use in Achilles tendon: risk of tendon rupture [3][5]. |
Why Steroid Taper Causes Psoriasis Flare
During steroid therapy, psoriasis is suppressed via broad immunosuppression (↓IL-17, ↓TNF-α, ↓T cell activation). Upon taper, a rebound phenomenon occurs — the IL-23/IL-17 axis "overshoots" due to removal of negative feedback, leading to massive keratinocyte hyperproliferation. The worst outcome is generalised pustular psoriasis (von Zumbusch type), which is a dermatological emergency with systemic toxicity (fever, deranged LFT, electrolyte disturbance, high-output cardiac failure).
Anti-TNFα therapy, anti-IL17, anti-IL12/23, JAK inhibitors (refer to rheumatologist) [20].
Indicated when csDMARDs fail (typically inadequate response after 3–6 months of optimised csDMARD therapy) or in patients with poor prognostic factors.
| Class | Examples | Mechanism | Key Indications in PsA | Important Contraindications / Cautions |
|---|---|---|---|---|
| Anti-TNF-α | Etanercept (soluble TNF receptor-Fc fusion protein), infliximab, adalimumab (anti-TNF-α monoclonal antibodies) [4] | Block TNF-α → reduce downstream inflammation, osteoclast activation, synovial proliferation. TNF-α binds to two cell-surface receptors: type I TNF receptor (p55) and type II TNF receptor (p75) [4]. | Peripheral arthritis refractory to csDMARDs; axial disease; enthesitis; dactylitis; severe skin psoriasis; uveitis (prefer infliximab/adalimumab for uveitis and IBD) [3] | Active infection, latent TB, demyelinating disease, heart failure, malignancy [3]. Must screen for TB (CXR, IGRA/Mantoux) and hepatitis B before starting. |
| Anti-IL-17A | Secukinumab (SC), ixekizumab | Block IL-17A → key effector cytokine in IL-23/IL-17 axis; reduces keratinocyte hyperproliferation, entheseal inflammation, and neutrophil recruitment | Peripheral and axial PsA; skin psoriasis; enthesitis. Anti-IL17 (SC secukinumab) [5]. | Caution in IBD — IL-17 blockade can worsen IBD (IL-17 has protective role in gut mucosal immunity). Increased risk of mucocutaneous candidiasis. |
| Anti-IL-12/23 | Ustekinumab | Blocks shared p40 subunit of IL-12 and IL-23 → reduces Th1 and Th17 differentiation respectively | Peripheral arthritis; skin psoriasis. Does NOT worsen IBD (actually effective for CD). Less effective for axial disease. | Generally well-tolerated; infection risk |
| Anti-IL-23 | Guselkumab, risankizumab | Blocks p19 subunit specific to IL-23 → selectively inhibits IL-23-driven Th17 responses while preserving IL-12/Th1 immunity | Peripheral arthritis; skin psoriasis; newer agents with promising data in PsA. Potentially safer profile than anti-IL-17 for patients with IBD. | Infection risk |
| JAK inhibitors | Tofacitinib, upadacitinib | Inhibit Janus kinases (JAK1/2/3) → block intracellular signalling downstream of multiple cytokine receptors (IL-6, IL-12, IL-23, IFN-γ) → broad immunosuppression. Oral small molecules ("targeted synthetic DMARDs"). | Peripheral arthritis refractory to csDMARDs and/or bDMARDs. Oral administration is an advantage. | FDA/EMA warning: increased risk of cancer, cardiovascular events (MI, stroke), VTE — particularly in patients over 50 with CV risk factors. Infection risk. Reactivation of herpes zoster. |
| Anti-PDE4 | Apremilast | Inhibits phosphodiesterase-4 → increases intracellular cAMP → reduces TNF-α, IL-17, IL-23 production from immune cells | Mild-moderate peripheral arthritis and skin psoriasis when csDMARDs are inappropriate. Oral. | Diarrhoea (common), nausea, headache, depression/suicidality (rare). Less efficacious than biologics — positioned for milder disease. |
Drug Choice Based on PsA Domain
| Domain | csDMARD Effective? | Preferred Biologic |
|---|---|---|
| Peripheral arthritis | Yes (MTX, SSZ, LEF) | Anti-TNF, anti-IL-17, anti-IL-12/23, JAK-i |
| Axial disease | No — NO proven effective DMARD for axial disease [5] | Anti-TNF, anti-IL-17 |
| Enthesitis | No — conventional DMARDs not effective for extra-articular manifestations [3] | Anti-TNF, anti-IL-17 |
| Dactylitis | Limited | Anti-TNF, anti-IL-17, anti-IL-12/23 |
| Skin psoriasis | MTX, cyclosporin | Anti-IL-17, anti-IL-23, anti-IL-12/23, anti-TNF |
| Nails | Limited | Anti-IL-17, anti-TNF |
| Uveitis | No | Anti-TNF (prefer infliximab/adalimumab) [3] |
Anti-IL-1 / anti-IL-6: not useful for SpA (cf. RA) [5]. This is an important distinction — tocilizumab (anti-IL-6) works brilliantly in RA but has no proven efficacy in PsA/SpA.
Treatment of axial symptoms: as in axial SpA (conventional DMARDs not effective) [3].
| Step | Treatment | Notes |
|---|---|---|
| 1st line | NSAIDs at optimal tolerated dose [20] | ~70-80% respond. Continuous use may slow radiographic progression (extrapolated from AS data). |
| 2nd line | Biologics (anti-TNF or anti-IL-17) for patients with persistent high disease activity despite adequate trial of 2-3 NSAIDs (at least 2 months for each unless contraindicated) [20] | NO proven effective DMARD for axial disease [5]. Local steroid, methotrexate, sulphasalazine: only for peripheral joints [5]. |
| Adjunctive | Analgesics such as paracetamol and tramadol for patients in whom conventional NSAIDs or COX-2 inhibitor are insufficient, contraindicated or not tolerated [20] |
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].
| Step | Treatment | Why |
|---|---|---|
| 1st | NSAIDs | Reduce prostaglandin-mediated inflammation at the enthesis |
| 2nd | Local steroid injection | Direct anti-inflammatory effect at entheseal site. Avoid IA steroid use in Achilles tendon: risk of tendon rupture [5] — steroids weaken collagen cross-linking in tendons already under high mechanical stress |
| 3rd | Anti-TNF or anti-IL-17 | csDMARDs do not work for enthesitis; biologics target the underlying IL-17/TNF-α-driven entheseal pathology directly |
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]:
| Treatment | Details |
|---|---|
| Topical steroids | Potency ladder: fluocinolone < betamethasone < clobetasol [5][20]. Vehicle matters: lotion < cream < ointment < occlusive dressing [5]. Commonly prescribed: 0.1% betamethasone [5]. Use lowest effective potency; avoid prolonged use of high-potency steroids on face/flexures (skin atrophy risk). |
| Topical tar products | e.g. shampoo, bathing soap [5][20]. Coal tar reduces epidermal proliferation and has anti-inflammatory and antipruritic effects. Messy and cosmetically unappealing but effective. |
| Vitamin D analogues | e.g. Dovonex (calcipotriol) [20]. Inhibit keratinocyte proliferation and promote differentiation. Often used in combination with topical steroids. |
| Phototherapy | UVA or UVB [20]. UVB (narrowband 311 nm) is first-line phototherapy; PUVA (psoralen + UVA) for more severe cases. UV light induces apoptosis of pathogenic T cells in skin and reduces keratinocyte proliferation. |
| Biologics | Anti-TNF-α therapy, anti-IL-12/23, anti-IL-17 and other biologics [20]. For moderate-to-severe psoriasis not responding to topical/phototherapy. Anti-IL-17 and anti-IL-23 have the highest efficacy for skin clearance. |
Uveitis: topical glucocorticoids + cycloplegics → TNF-α inhibitor (if refractory, prefer infliximab/adalimumab) [3].
| Step | Treatment | Mechanism |
|---|---|---|
| 1st | Topical prednisolone acetate 1% eyedrops [9] | Suppress anterior chamber inflammation |
| 1st | Topical cycloplegics (e.g. 1% cyclopentolate) [9] | Paralyse ciliary muscle → relieve pain from ciliary spasm; prevent posterior synechiae by keeping pupil dilated |
| 2nd | Oral steroids | For refractory or bilateral severe uveitis |
| 3rd | Anti-TNF (infliximab/adalimumab preferred over etanercept) [3] | Etanercept is less effective for uveitis and IBD; monoclonal antibodies (infliximab, adalimumab) are preferred because they neutralise both soluble and membrane-bound TNF-α, whereas etanercept (fusion protein) mainly neutralises soluble TNF-α |
| Comorbidity | Management |
|---|---|
| CV risk | Aggressive CV risk factor management — statin therapy, BP control, smoking cessation, exercise. Psoriasis is an independent CV risk factor. |
| Metabolic syndrome | Weight loss, diabetes screening and management, lipid optimisation |
| Osteoporosis | DEXA screening if on steroids or prolonged immobility; calcium, vitamin D, bisphosphonates as indicated |
| Depression/anxiety | Screening, psychological support, pharmacotherapy if needed |
| Infection screening before biologics | TB screening (CXR + IGRA), hepatitis B screening (HBsAg, anti-HBs, anti-HBc) [23], hepatitis C screening. If HBsAg +ve, start prophylactic antiviral therapy irrespective of baseline HBV DNA [23]. |
HBV Reactivation — Must Know Before Starting Biologics
In Hong Kong, where HBV prevalence is significant, always screen for HBsAg, anti-HBs, anti-HBc before starting anti-TNF or other immunosuppression. If HBsAg +ve or HBcAb +ve, check baseline HBV DNA + LFT [23]. For HBsAg-positive patients: start prophylactic antiviral therapy (entecavir or TDF/TAF) — superior and safer than monitoring for reactivation [23].
Surgical (rarely required now): corrective spinal surgery, joint replacement [5].
| Indication | Procedure |
|---|---|
| End-stage joint destruction | Total joint replacement (hip, knee most common) |
| Severe deformity | Arthrodesis (fusion) for small joints (e.g., in arthritis mutilans) |
| Spinal deformity | Corrective osteotomy (very rare, for fixed kyphosis) |
| Tendon rupture | Surgical repair |
Surgery is a last resort — with modern biologics, the need for surgical intervention has declined dramatically.
General measures: NSAIDs for pain relief; supportive care: splints, PT/OT. Immunosuppressants depend on subtypes: methotrexate weekly; ± corticosteroid: pulsed IV methylprednisolone; ± biologics: anti-TNFα, IL-1, IL-6, CTLA-4 for severe disease refractory to MTX. Autologous HSCT if above measures failed [15].
| Drug | Absolute Contraindications | Relative Contraindications / Cautions |
|---|---|---|
| NSAIDs | Active PUD, severe CKD, third-trimester pregnancy | Heart failure, aspirin-sensitive asthma, concomitant steroids or anticoagulants |
| MTX | Pregnancy (teratogenic), chronic kidney disease [20], active infection, severe liver disease, bone marrow failure | Alcohol use, NAFLD (common in PsA — check LFT carefully), interstitial lung disease |
| Leflunomide | Pregnancy (teratogenic — requires cholestyramine washout), severe liver disease | Hypertension, hepatic impairment |
| Cyclosporin | Uncontrolled hypertension, renal impairment, concurrent nephrotoxic drugs | Malignancy (immunosuppression risk) |
| HCQ | Psoriasis (exacerbates psoriatic skin disease) [5] | — |
| Anti-TNF-α | Active infection, latent TB (must screen), demyelinating disease (MS), NYHA III-IV heart failure, malignancy [3] | HBV carrier (requires prophylactic antivirals) |
| Anti-IL-17 | Caution in IBD (may worsen) | Increased mucocutaneous candidiasis risk |
| JAK inhibitors | Active serious infection | FDA warning: cancer and cardiovascular risk [20]; VTE risk; herpes zoster reactivation |
| Systemic corticosteroids | Psoriasis (rebound flare on taper) [2] | Diabetes, osteoporosis, infection |
Poor prognostic factors: young onset, hip arthritis, dactylitis, high ESR, poor response to NSAID [5], smoking, high disease activity at presentation, presence of syndesmophytes at diagnosis [3].
Patients with poor prognostic factors should be escalated to biologics earlier, even without a full csDMARD trial, as per current GRAPPA and EULAR recommendations.
| Parameter | Frequency | Purpose |
|---|---|---|
| Disease activity (PASDAS, DAPSA, MDA) | Every 3–6 months | Treat-to-target assessment |
| Joint count (tender + swollen) | Every visit | Track peripheral arthritis activity |
| Skin assessment (PASI, BSA) | Every visit | Track skin disease activity |
| Enthesitis/dactylitis count | Every visit | Track extra-articular domains |
| Blood monitoring (CBC, LFT, RFT) | Q1–3 months on DMARDs | Drug toxicity surveillance (MTX → liver/marrow; cyclosporin → renal) |
| Inflammatory markers (CRP/ESR) | Every visit | Track inflammatory burden |
| Imaging (XR ± MRI) | Annual or as clinically indicated | Monitor structural progression |
| Ophthalmology | Annual slit-lamp | Screen for uveitis |
| CV risk assessment | Annual | Address metabolic syndrome |
| TB/HBV surveillance | Before and during biologics | Prevent reactivation |
High Yield Summary
Management Principles:
- Treat-to-target: aim for MDA or remission. Start DMARDs early for active arthritis (≥ 3 joints, dactylitis counts as 1) [20].
- Methotrexate is the preferred csDMARD (co-treats skin). Avoid HCQ (exacerbates psoriasis) [5].
- Systemic corticosteroids used cautiously — taper causes severe psoriatic flare [2][3].
- No effective DMARD for axial disease or enthesitis — use NSAIDs then biologics [5].
- Anti-IL-1 / anti-IL-6 NOT useful for SpA (cf. RA) [5].
Biologic Hierarchy:
- Anti-TNF-α (first-line biologic for most domains).
- Anti-IL-17 (excellent for skin + joints + axial; caution in IBD).
- Anti-IL-12/23, anti-IL-23 (excellent for skin; safe in IBD).
- JAK inhibitors (oral; FDA cancer/CV warning).
Key Contraindications:
Active Recall - Management of Psoriatic Arthritis
References
[2] Senior notes: Block A - Dermatology PBL 1.pdf – Corticosteroid taper and psoriasis flare (p. 17) [3] Senior notes: Ryan Ho Rheumatology.pdf – PsA management, enthesitis, dactylitis, axial disease, biologics (p. 62–66) [4] Senior notes: Block A - Treatments for skin diseases (eczema, psoriasis and urticaria).pdf – TNF-α mechanism, biologics (p. 34) [5] Senior notes: Maksim Medicine Notes.pdf – PsA management, CASPAR criteria, pharmacological treatment, axial SpA management (p. 323–326) [9] Senior notes: Ryan Ho Opthalmology.pdf – Uveitis management (p. 31) [15] Senior notes: Adrian Lui Pediatrics Notes.pdf – JIA management, methotrexate, biologics (p. 456) [20] Lecture slides: Handbook of Internal Medicine 2024.pdf – PsA treatment, RA treatment principles, axial SpA treatment (p. 433–437) [21] Senior notes: Block A - Upper abdominal pain_ peptic ulcer; pancreatitis and gallstone.pdf – NSAID GI protection (p. 25) [22] Lecture slides: GC 079 (supp-2) STOPP-START-V3.pdf – NSAID and corticosteroid cautions in arthritis (p. 8) [23] Senior notes: Block A - I am a hepatitis B carrier.pdf – HBV screening and prophylaxis before immunosuppression (p. 70)
Complications of Psoriatic Arthritis
PsA is a multi-system inflammatory disease, not merely a joint condition. Complications arise from three sources: (1) the disease itself (unchecked inflammation), (2) treatment-related adverse effects, and (3) associated comorbidities driven by the same chronic inflammatory state. Understanding why each complication occurs — tracing it back to the underlying pathophysiology — makes them logical rather than a list to memorise.
A. Articular (Joint) Complications
| Complication | Mechanism | Clinical Consequence |
|---|---|---|
| Erosive arthritis | Persistent synovitis and enthesitis → pannus formation → TNF-α/RANKL activate osteoclasts → cartilage and subchondral bone erosion | Progressive loss of joint space, pain, and functional disability |
| Arthritis mutilans | Complete destruction of small joints with telescoping of digits [5] — represents the most severe end of the erosive spectrum | "Opera-glass hand" (main en lorgnette): skin appears invaginated and finger can be pulled back to its original length [3]. Severe disability. This occurs in ~5% of PsA patients. |
| Ankylosis (bony fusion) | Paradoxical new bone formation (IL-17/IL-22-driven osteoblast activation) at damaged joints → complete loss of movement | Fixed deformity, especially in DIP joints and spine. Occurrence of both joint lysis and ankylosis is characteristic [1]. |
| Flexion contractures | Chronic synovitis → peri-articular fibrosis → tendons and capsule shorten in the position of comfort (flexion) | Fixed flexion deformity → inability to fully extend joint → functional impairment |
| Deformities | Swelling in the PIPJ and deformities of the DIPJ of the fingers [8]; swan-neck, boutonnière deformities (less common than RA) | Less tender, may present with deformity [5] — patients may present late because PsA joints are characteristically less painful than RA for the same degree of structural damage |
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.
| Complication | Mechanism | Clinical Consequence |
|---|---|---|
| Sacroiliitis | Entheseal inflammation at SI joint ligament insertions → erosion → sclerosis → eventual fusion | Chronic inflammatory low back pain; restricted spinal mobility |
| Spinal ankylosis | Progressive enthesophyte (syndesmophyte) formation bridging vertebral bodies → eventual "bamboo spine" (less common than in pure AS) | Rigid spine with markedly reduced range of motion; increased fracture risk from trivial trauma (ankylosed spine is brittle) |
| Spinal fractures | Ankylosed spine = long lever arm; osteoporosis from chronic inflammation and steroid use | Even minor falls can cause unstable spinal fractures → cord injury. Must image entire spine (CT/MRI) even for minor trauma in patients with axial PsA. |
| Atlanto-axial subluxation | Rare in PsA (more classic in RA with erosive cervical disease), but can occur with severe axial involvement | Risk of cord compression |
| Complication | Mechanism |
|---|---|
| Tendon rupture | Chronic tenosynovitis weakens tendons; avoid IA steroid use in Achilles tendon: risk of tendon rupture [5] — corticosteroids inhibit collagen cross-linking and tendon fibroblast repair |
| Chronic enthesopathy | Repeated entheseal inflammation → fibrosis → calcification → chronic pain and functional impairment at insertion sites (Achilles, plantar fascia) |
| Persistent dactylitis | Chronic flexor tenosynovitis → digital contracture, functional impairment of grip, may require surgical release |
B. Ocular Complications
Extra-articular: anterior uveitis [5]. Seronegative spondyloarthropathy: most classically uveitis, conjunctivitis may also occur [9].
| Aspect | Detail |
|---|---|
| Frequency | ~7–25% of PsA patients; more common in those with axial disease and HLA-B27 positivity |
| Mechanism | HLA-B27-mediated immune response + shared IL-23/IL-17 axis between uveal tract and entheses → T cell infiltration of anterior chamber → inflammation (cells + flare) |
| Complications of uveitis [9] | Band keratopathy (calcium deposition in corneal Bowman layer from chronic inflammation), posterior synechiae (adhesion of iris to lens → irregular pupil, risk of pupil block glaucoma), cataract (due to chronic inflammation or topical steroid use), intraocular hypertension ± glaucoma (trabecular meshwork blockage by inflammatory debris or steroid-induced), cystoid macular oedema (CME) |
| Clinical significance | Persistent uncontrolled anterior uveitis can be sight-threatening [24]. Even asymptomatic uveitis can cause insidious visual loss → routine slit-lamp screening is essential |
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.
Clinical Pearl — Silent Uveitis in PsA
Unlike acute anterior uveitis in AS (which is typically symptomatic with acute pain, redness, photophobia), uveitis in PsA (especially the juvenile form) can be chronic and insidious — the patient may not complain until irreversible damage (posterior synechiae, cataract, glaucoma) has occurred. This is why routine ophthalmological screening with slit-lamp examination is mandatory, particularly in ANA-positive, HLA-B27-positive, or young-onset PsA patients.
- Mild, non-specific mucosal inflammation — part of the shared SpA extra-articular spectrum.
- Usually self-limiting but can be recurrent.
This is one of the most clinically important and increasingly recognised complications of PsA.
Psoriasis can also affect arteries → stiffness, increased risk of cardiovascular disease [2]. Associated with metabolic syndrome [5].
| Complication | Mechanism | Evidence |
|---|---|---|
| Accelerated atherosclerosis | Chronic systemic inflammation (TNF-α, IL-6, IL-17) → endothelial dysfunction → oxidative stress → LDL oxidation → foam cell formation → premature plaque development | PsA patients have ~1.5–2× increased risk of MI and stroke compared to age-matched controls |
| Myocardial infarction | As above; also arterial stiffness from IL-17-mediated vascular remodelling | A 30-year-old with severe psoriasis has an adjusted RR of MI of 3.10 [4] |
| Metabolic syndrome | Shared inflammatory pathways: TNF-α → insulin resistance; IL-6 → hepatic CRP/lipid dysregulation; adipokines from visceral fat amplify inflammation | Diabetes, heart insufficiency, and obesity occur significantly more often in patients with psoriasis [4] |
| Aortic root inflammation / Aortitis | Part of the SpA extra-articular spectrum — chronic inflammation of the aortic root → fibrosis → aortic regurgitation, conduction defects | Rare but clinically significant; shared mechanism with AS |
The Psoriatic March — Systemic Inflammation to CV Death
The concept of the "psoriatic march" describes how chronic skin and joint inflammation → systemic inflammation → insulin resistance → endothelial dysfunction → atherosclerosis → cardiovascular events. PsA is now recognised as an independent cardiovascular risk factor, and CV risk reduction (statin therapy, smoking cessation, BP control, weight management) should be part of every PsA management plan.
| Complication | Mechanism | Clinical Implication |
|---|---|---|
| Obesity | Bidirectional relationship: adipokines (leptin, resistin, TNF-α from adipose tissue) drive inflammation; inflammation drives sedentary lifestyle; some treatments (steroids) promote weight gain | Reduces biologic drug efficacy (PK/PD changes), worsens psoriasis, increases CV risk |
| Type 2 diabetes mellitus | TNF-α and IL-6 induce insulin resistance via interference with insulin receptor signalling (phosphorylation of IRS-1 on serine residues instead of tyrosine → impaired downstream PI3K/Akt signalling) | Screen regularly; metformin and DM management as needed |
| Dyslipidaemia | Chronic inflammation → ↑hepatic VLDL synthesis, ↓HDL, oxidation of LDL → atherogenic lipid profile | Statin therapy as indicated |
| Hyperuricaemia / Gout | Increased epidermal cell turnover in psoriasis → increased purine metabolism → elevated uric acid; also obesity and metabolic syndrome contribute | PsA and gout can coexist [1]; must aspirate acute monoarthritis; screen HLA-B*5801 before allopurinol in Chinese patients |
| Non-alcoholic fatty liver disease (NAFLD) | Systemic inflammation + metabolic syndrome → hepatic steatosis and steatohepatitis | Particularly relevant because MTX is hepatotoxic — baseline and ongoing LFT monitoring essential; consider FibroScan for hepatic fibrosis assessment |
| Complication | Mechanism |
|---|---|
| Erythrodermic psoriasis | Severe, extensive psoriasis covering > 90% BSA → skin failure: inability to thermoregulate, massive transepidermal water loss → dehydration, electrolyte disturbance, high-output cardiac failure. Can be triggered by inappropriate treatment (e.g., corticosteroid taper, HCQ). |
| Generalised pustular psoriasis (von Zumbusch) | Corticosteroid taper precipitate very severe psoriatic flare, pustular psoriasis [2]. Sterile neutrophilic pustules on erythematous background; fever, deranged LFT, leucocytosis. Life-threatening. |
| Severe nail destruction | Progressive nail matrix involvement → complete nail plate loss → functional impairment (impaired grip, pain) and psychological distress |
| Secondary skin infection | While psoriasis itself is relatively resistant to infection due to antimicrobial peptide production [2], immunosuppressive therapy (MTX, biologics) increases infection risk |
| Complication | Mechanism |
|---|---|
| Depression | Multifactorial: chronic visible skin disease → stigma and social isolation; chronic pain → learned helplessness; inflammatory cytokines (TNF-α, IL-6) cross BBB → neuroinflammation → serotonin depletion |
| Anxiety | Fear of disease progression, treatment side effects, visible disfigurement |
| Functional disability | Joint destruction, deformity, chronic pain → inability to perform ADLs → reduced quality of life, employment difficulty |
| Reduced quality of life | PsA has a similar impact on QoL as RA and greater impact than psoriasis alone (the combined burden of skin + joints is worse than either alone) |
| Complication | Mechanism |
|---|---|
| Osteoporosis | Chronic inflammation → ↑RANKL/OPG ratio → systemic bone loss; steroid use; immobility; vitamin D deficiency |
| Muscle weakness / Sarcopenia | Disuse atrophy from joint pain/immobility; TNF-α-mediated muscle catabolism; steroid myopathy |
| Leg-length discrepancy [25] | In juvenile PsA: chronic inflammation near growth plates → asymmetric growth stimulation (increased blood flow to affected side → premature epiphyseal fusion OR accelerated growth depending on proximity and duration) |
| Micrognathia / TMJ asymmetry | In juvenile PsA: TMJ involvement → mandibular growth disturbance [24] |
These are iatrogenic complications — the price of disease control:
| Treatment | Complication | Mechanism |
|---|---|---|
| Methotrexate | Interstitial pneumonitis, hepatotoxicity, nephrotoxicity, bone marrow suppression [15]; nausea, oral ulcers, teratogenicity | Folate antimetabolite → inhibits rapidly dividing cells (bone marrow, GI mucosa, hepatocytes); pneumonitis is a hypersensitivity reaction (type IV); hepatotoxicity worsened by pre-existing NAFLD and alcohol |
| Corticosteroids | Growth restriction (children), osteoporosis, Cushingoid features [15]; diabetes, cataracts, avascular necrosis, adrenal suppression | Cortisol excess → ↑gluconeogenesis (DM), ↓osteoblast activity (osteoporosis), ↓growth hormone (growth restriction), fat redistribution |
| NSAIDs | PUD/GI bleeding, renal impairment, CV events | COX-1 inhibition → ↓protective prostaglandins in gastric mucosa and renal afferent arteriole |
| Anti-TNF-α | Active infection, TB reactivation, demyelinating disease, heart failure, malignancy [3]; infusion reactions, injection site reactions | TNF-α is essential for granuloma formation (TB containment), anti-tumour immunity, and myelin maintenance |
| Anti-IL-17 | Mucocutaneous candidiasis; IBD flare/worsening | IL-17 is essential for mucosal anti-fungal immunity (neutrophil recruitment against Candida); IL-17 has protective role in gut mucosa |
| JAK inhibitors | Increased risk of serious infections, herpes zoster reactivation, VTE, cancer, CV events | Broad intracellular signalling blockade → immunosuppression; JAK-STAT pathway is involved in anti-viral immunity (IFN signalling) and haematopoiesis |
| Cyclosporin | Nephrotoxicity, hypertension | Calcineurin inhibition → afferent arteriolar vasoconstriction → ↓GFR; also activates sympathetic nervous system and endothelin-1 |
| Complication | Frequency / Context | Mechanism |
|---|---|---|
| Apical fibrosis | Extra-articular: anterior uveitis, apical fibrosis [5] — rare but recognised in PsA (more classically in AS) | Possibly related to chronic chest wall restriction from costovertebral ankylosis → apical hypoperfusion and fibrosis; alternatively direct inflammatory process |
| Methotrexate pneumonitis | Drug-related (see above) | Hypersensitivity reaction → acute onset dyspnoea, dry cough, fever; ground-glass opacities on HRCT; requires MTX cessation and systemic steroids |
PsA patients face increased infection risk from two sources:
- Immune dysregulation from the disease itself (aberrant T cell function)
- Iatrogenic immunosuppression from DMARDs and biologics
| Infection | Treatment Association | Prevention |
|---|---|---|
| TB reactivation | Anti-TNF-α (granuloma disruption) | Screen with CXR + IGRA/Mantoux before starting; treat latent TB (isoniazid 9 months) before biologic initiation |
| HBV reactivation | Anti-TNF-α, MTX, all immunosuppressants | Screen HBsAg/anti-HBc before starting; prophylactic antivirals (entecavir/TDF) if HBsAg-positive [23] |
| Herpes zoster | JAK inhibitors (JAK-STAT pathway mediates IFN signalling which is key for anti-VZV immunity) | Consider recombinant zoster vaccine (Shingrix) before starting JAK inhibitor |
| Opportunistic infections | All biologics and tsDMARDs | Vaccinate with non-live vaccines before starting biologics; avoid live vaccines during treatment |
| Mucocutaneous candidiasis | Anti-IL-17 (IL-17 recruits neutrophils to mucosal surfaces for anti-Candida defence) | Monitor oral/genital mucosa; treat with topical/systemic antifungals |
| Context | Mechanism |
|---|---|
| Chronic inflammation | Persistent inflammation → DNA damage from reactive oxygen species → potential for malignant transformation (particularly lymphoproliferative malignancies) |
| Immunosuppressive therapy | Long-term immunosuppression (MTX, cyclosporin, biologics) → impaired immune surveillance → ↑lymphoma, NMSC risk |
| PUVA therapy | Cumulative UV exposure from phototherapy → ↑ squamous cell carcinoma risk (especially > 200 PUVA sessions) |
| System | Key Complications |
|---|---|
| Articular | Erosive arthritis, arthritis mutilans, ankylosis, flexion contractures, deformity |
| Axial | Sacroiliitis, spinal ankylosis, spinal fractures |
| Periarticular | Tendon rupture, chronic enthesopathy, persistent dactylitis |
| Ocular | Anterior uveitis → posterior synechiae, cataract, glaucoma, band keratopathy, CME |
| Cardiovascular | Accelerated atherosclerosis, MI, aortitis |
| Metabolic | Obesity, DM, dyslipidaemia, hyperuricaemia/gout, NAFLD |
| Dermatological | Erythrodermic/pustular psoriasis, nail destruction |
| Psychological | Depression, anxiety, functional disability |
| Musculoskeletal | Osteoporosis, sarcopenia, growth disturbance (paediatric) |
| Pulmonary | Apical fibrosis, MTX pneumonitis |
| Infection | TB/HBV reactivation, zoster, candidiasis, opportunistic infections |
| Malignancy | Lymphoma, NMSC (treatment-related) |
| Treatment-related | MTX hepato/nephro/myelotoxicity, steroid side effects, NSAID GI/renal/CV toxicity |
High Yield Summary
Disease Complications:
- Arthritis mutilans (5%): complete destruction with telescoping digits ("opera-glass hand") [3][5]. 68% have progressive disease at 5 years [3].
- Anterior uveitis: can be chronic and insidious → posterior synechiae, cataract, glaucoma, band keratopathy, CME [9]. Routine slit-lamp screening essential.
- Cardiovascular disease: PsA is an independent CV risk factor. Psoriasis affects arteries → stiffness, increased CV risk [2]. Aggressive CV risk management is mandatory.
- Metabolic syndrome: obesity, DM, dyslipidaemia, hyperuricaemia — all more prevalent and bidirectionally related to PsA.
- Apical fibrosis: rare but recognised extra-articular manifestation [5].
Treatment Complications:
- MTX: interstitial pneumonitis, hepatotoxicity, bone marrow suppression [15].
- Corticosteroid taper → pustular psoriasis flare [2] — life-threatening.
- Anti-TNF: TB reactivation, HBV reactivation, serious infections, demyelination, HF [3].
- Anti-IL-17: candidiasis, IBD worsening.
- JAK inhibitors: cancer, CV events, VTE, zoster.
Paediatric-Specific:
- Uveitis and leg-length discrepancy [25] are the most frequent long-term complications of pauciarticular JIA (including juvenile PsA).
- Growth disturbance from chronic inflammation and steroid use.
Active Recall - Complications of Psoriatic Arthritis
References
[1] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf – Psoriatic arthritis, radiological features, gout coexistence (p. 1708–1713) [2] Senior notes: Block A - Dermatology PBL 1.pdf – Corticosteroid taper and psoriasis flare, CV risk, AMPs (p. 17) [3] Senior notes: Ryan Ho Rheumatology.pdf – PsA clinical features, prognosis, arthritis mutilans, management, biologics (p. 62–65) [4] Senior notes: Block A - Treatments for skin diseases (eczema, psoriasis and urticaria).pdf – CV risk, obesity, MI risk (p. 34–36) [5] Senior notes: Maksim Medicine Notes.pdf – PsA subtypes, extra-articular features, metabolic syndrome, poor prognostic factors (p. 323–326) [8] Lecture slides: Upper Limb Painful Conditions_Dr. Margaret Woon Man FOK_3. Inflammatory conditions.pdf – PsA joint involvement (p. 21–22) [9] Senior notes: Ryan Ho Opthalmology.pdf – Uveitis complications, rheumatological disease and the eye (p. 31, 131) [15] Senior notes: Adrian Lui Pediatrics Notes.pdf – JIA management and methotrexate side effects, uveitis complications (p. 454–456) [23] Senior notes: Block A - I am a hepatitis B carrier.pdf – HBV screening before immunosuppression (p. 70) [24] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf – JIA complications: MAS, uveitis, orthopaedic complications (p. 697) [25] Lecture slides: GC 053. Fingers turn white and blue.pdf – JIA prognosis: uveitis and leg-length discrepancy (p. 61)
High Yield Summary
Definition: PsA is a chronic immune-mediated inflammatory arthritis associated with psoriasis, belonging to the spondyloarthritis family.
Epidemiology: Affects up to 30% of psoriasis patients; M:F = 1:1; onset 25–40 years; 60% psoriasis precedes arthritis, 20% after, 20% concurrent.
Pathophysiology: IL-23/IL-17 axis-driven; enthesis is the primary target (unlike RA where synovium is primary); results in simultaneous bone erosion AND new bone formation — a unique PsA paradox.
Classification (Moll & Wright): Asymmetric oligoarthritis (~40%), symmetric polyarthritis (~25%), DIP predominant (~5–15%), psoriatic spondylitis (~5%), arthritis mutilans (<5%). GC slide: Oligoarthritis 60–70%, Asymmetric DIP 16%, RA-like 15%, AS 5%, Mutilans 5%.
Key Clinical Features:
- DIP joint involvement (RA spares DIP)
- Dactylitis (~50%) and enthesitis (~35%)
- Nail changes (80–90%): pitting, onycholysis, subungual hyperkeratosis, oil-drop sign
- Less tender than RA, may present with deformity
- Asymmetric, RF-negative
- Hidden psoriasis: always check scalp, ears, umbilicus, natal cleft
- Associated metabolic syndrome and CV risk
Key Differentiator from RA: M:F 1:1 (vs 1:3), asymmetric (vs symmetric), DIP (vs spares DIP), RF−/anti-CCP− (vs positive), enthesitis/dactylitis (vs absent), nail changes (vs nodules), new bone formation on XR (vs osteopenia).
Systemic corticosteroids should NOT be used for psoriasis — taper can cause severe psoriatic flare including pustular psoriasis.
High Yield Summary
Most important DDx for PsA: RA (symmetric, spares DIP, RF+, no nail/entheseal changes), gout (can coexist! always aspirate acute monoarthritis), reactive arthritis (preceding infection), AS (bilateral sacroiliitis, no psoriasis), enteropathic arthritis (IBD symptoms), OA (mechanical, bony swelling).
Top 3 bedside differentiators of PsA from RA: 1) DIP involvement with nail changes, 2) Dactylitis/enthesitis, 3) RF-negative.
Remember: PsA and gout can coexist — finding MSU crystals does not exclude PsA. Always look for nail changes, dactylitis, and XR new bone formation.
Systemic onset JIA is the most difficult to diagnose — infection and leukaemia are major differentials [17]. In children, psoriatic JIA is defined as arthritis + psoriasis OR arthritis + ≥ 2 of dactylitis/nail changes/FHx psoriasis [16].
High Yield Summary
Diagnostic Criteria:
- CASPAR criteria (2006): Mandatory entry = inflammatory MSK disease (arthritis/spondylitis/enthesitis). Then score ≥ 3 from: current psoriasis (+2), personal Hx (+1), FHx (+1), nail lesions (+1), dactylitis (+1), RF-negative (+1), juxta-articular new bone on XR (+1). Sensitivity 91.4%, specificity 98.7%.
- Moll and Wright (1973): All 3 of inflammatory arthritis + psoriasis + RF-negative. Simple but limited.
- ILAR (paediatric): Arthritis + psoriasis, OR arthritis + ≥ 2 of (dactylitis, nail changes, FHx psoriasis).
Key Investigations:
- Bloods: CBC, LRFT, ESR/CRP, HLA-B27, RF (−ve) [5].
- RF negative in ~90-95%; anti-CCP negative in ~84-92%; ANA low-titre positive in ~50%.
- XR: pencil-in-cup deformity, juxta-articular new bone formation (distinct from osteophytes), simultaneous erosion and proliferation.
- MRI: more sensitive than XR for early disease, enthesitis, sacroiliitis.
- Joint aspiration: inflammatory fluid, sterile, no crystals (but crystals can coexist with PsA).
- Always examine hidden psoriasis sites and nails; nail involvement is the strongest clinical predictor of PsA.
High Yield Summary
Management Principles:
- Treat-to-target: aim for MDA or remission. Start DMARDs early for active arthritis (≥ 3 joints, dactylitis counts as 1) [20].
- Methotrexate is the preferred csDMARD (co-treats skin). Avoid HCQ (exacerbates psoriasis) [5].
- Systemic corticosteroids used cautiously — taper causes severe psoriatic flare [2][3].
- No effective DMARD for axial disease or enthesitis — use NSAIDs then biologics [5].
- Anti-IL-1 / anti-IL-6 NOT useful for SpA (cf. RA) [5].
Biologic Hierarchy:
- Anti-TNF-α (first-line biologic for most domains).
- Anti-IL-17 (excellent for skin + joints + axial; caution in IBD).
- Anti-IL-12/23, anti-IL-23 (excellent for skin; safe in IBD).
- JAK inhibitors (oral; FDA cancer/CV warning).
Key Contraindications:
High Yield Summary
Disease Complications:
- Arthritis mutilans (5%): complete destruction with telescoping digits ("opera-glass hand") [3][5]. 68% have progressive disease at 5 years [3].
- Anterior uveitis: can be chronic and insidious → posterior synechiae, cataract, glaucoma, band keratopathy, CME [9]. Routine slit-lamp screening essential.
- Cardiovascular disease: PsA is an independent CV risk factor. Psoriasis affects arteries → stiffness, increased CV risk [2]. Aggressive CV risk management is mandatory.
- Metabolic syndrome: obesity, DM, dyslipidaemia, hyperuricaemia — all more prevalent and bidirectionally related to PsA.
- Apical fibrosis: rare but recognised extra-articular manifestation [5].
Treatment Complications:
- MTX: interstitial pneumonitis, hepatotoxicity, bone marrow suppression [15].
- Corticosteroid taper → pustular psoriasis flare [2] — life-threatening.
- Anti-TNF: TB reactivation, HBV reactivation, serious infections, demyelination, HF [3].
- Anti-IL-17: candidiasis, IBD worsening.
- JAK inhibitors: cancer, CV events, VTE, zoster.
Paediatric-Specific:
- Uveitis and leg-length discrepancy [25] are the most frequent long-term complications of pauciarticular JIA (including juvenile PsA).
- Growth disturbance from chronic inflammation and steroid use.
Radiographic Axial Spondyloarthritis (ankylosing Spondylitis)
Radiographic axial spondyloarthritis (ankylosing spondylitis) is a chronic inflammatory disease primarily affecting the sacroiliac joints and spine, characterized by definite structural damage (sacroiliitis) visible on conventional radiographs, leading to progressive spinal stiffness and potential ankylosis.
Reactive Arthritis
Reactive arthritis is a sterile inflammatory arthropathy that develops following a gastrointestinal or genitourinary infection, classically presenting with the triad of arthritis, urethritis, and conjunctivitis.