Knee pain is a common musculoskeletal complaint arising from injury, overuse, or degenerative, inflammatory, or infectious processes affecting the bones, cartilage, ligaments, tendons, or bursae of the knee joint.

Knee Pain

Category	Specific Risk Factors
Demographics	Increasing age, female sex (for OA), male sex (for gout, ligament injury in certain sports)
Constitutional	Obesity (every 1 kg of body weight = ~4 kg load across the knee during walking), low bone density
Biomechanical	Malalignment (genu varum/valgum), leg length discrepancy, flat feet (pes planus), muscle weakness (esp. quadriceps)
Previous injury	Previous trauma (meniscal tear, ligament injury, fracture → secondary OA), recurrent dislocations
Occupational/Activity	Repetitive kneeling (prepatellar bursitis — "housemaid's knee"), running/cycling (ITBS, patellofemoral syndrome), heavy manual labour
Genetic	Family history of OA, chondrocalcinosis (familial CPPD — AD inheritance, CCAL1/2 mutation) ^[6]
Metabolic	Hyperuricaemia (gout), haemochromatosis, hyperparathyroidism, Wilson's disease (secondary CPPD) ^[6]
Joint disease	Pre-existing RA, crystal arthropathy, haemophilia (haemarthrosis → haemophilic arthropathy) ^[7]
Systemic	Diabetes mellitus (Charcot arthropathy, increased infection risk), immunosuppression, chronic kidney disease

Anatomy and Function

Understanding knee anatomy is essential because the history and examination findings point you directly to the damaged structure.

Etiology (Hong Kong Focus) and Pathophysiology

The causes of knee pain are best approached by age and mechanism (traumatic vs. atraumatic, acute vs. chronic). The masquerades checklist reminds us to consider depression, diabetes, and spinal dysfunction (referred pain) as non-obvious causes ^[1].

A. Degenerative / Wear-and-Tear

Definition: Chronic wear and tear process involving a joint; degeneration is only one of the causes ^[3].

Aetiology ^[3]:

Primary (degenerative): More common in elderly > 70y as OA knee
Secondary: May be seen in young < 50y — must ask about previous trauma and chronic joint instability
- Defective load:
  - Force: obesity, occupational overuse
  - Area: joint dysplasia
- Defective cartilage:
  - Damage: trauma, haemophilia
  - Diseases: inflammatory (e.g., RA), metabolic (e.g., gout), infection
  - Unsupported: AVN

Pathophysiology (understanding this explains ALL the symptoms and signs):

Cartilage degradation: Chondrocytes fail to maintain the balance between synthesis and degradation of the extracellular matrix. Matrix metalloproteinases (MMPs) and aggrecanases break down type II collagen and proteoglycans → loss of cartilage resilience and shock absorption.
Subchondral bone changes: Loss of cartilage → increased stress on subchondral bone → reactive sclerosis (thickening). Microfractures in sclerotic bone allow synovial fluid intrusion → subchondral cysts. Bone at joint margins proliferates → osteophytes (the body's attempt to redistribute load over a wider area).
Synovial inflammation: Cartilage breakdown products enter synovial fluid → activate innate immune response → low-grade synovitis → effusion, warmth.
Joint capsule changes: Chronic inflammation → capsular thickening and fibrosis → reduced range of motion.
Muscle weakness: Pain → disuse → quadriceps atrophy → further loss of dynamic stability → accelerated degeneration.

Why does OA prefer weight-bearing joints? Because axial loading accelerates cartilage wear. The knee bears ~3–6× body weight during stair climbing, which is why knee pain is worse on going downstairs (patellofemoral joint involvement) ^[3].

Radiological features (LOSS) ^[3]:

Loss of joint space (earliest radiographic sign)
Osteophytes
Subchondral cysts
Subchondral sclerosis

Kellgren-Lawrence (KL) Classification ^[3]:

Grade	Description
Grade 0	No joint space narrowing (JSN)
Grade 1	Possible osteophytes, doubtful JSN
Grade 2	Definite osteophytes
Grade 3	Definite JSN
Grade 4	Bone-on-bone deformity

Radiographic views for OA knee ^[3]:

Weightbearing AP: medial vs lateral compartment
Lateral: anteromedial vs posteromedial (e.g., posterior osteophytes)
Skyline: patellofemoral joint space
Valgus stress / Varus stress: assess medial / lateral joint space
Standing scanogram: alignment
+/- Schuss view (30° flexion): more sensitive for early OA

Classification of OA progression: WOMAC (Western Ontario and McMaster Universities Arthritis Index) ^[3].

B. Traumatic / Mechanical

C. Inflammatory / Crystal Arthropathies

E. Periarticular / Soft Tissue

Key principle: In children, always think age-related causes ^[4]:

Age	Common Causes
0–5 years	Septic arthritis, transient synovitis ("irritable hip" — but child localises to knee), juvenile idiopathic arthritis (JIA), trauma (NAI?)
5–10 years	Perthes disease (idiopathic AVN of proximal femoral epiphysis, boys aged 5–10y) ^[4], transient synovitis
10–16 years	SCFE (obese boys aged 10–15y) ^[4], Osgood–Schlatter disorder ^[1], osteochondritis dissecans, patellofemoral syndrome
Adolescents	Avulsion fractures, stress fractures, bone tumours (osteosarcoma, Ewing's sarcoma) ^[4]

Osgood–Schlatter disorder ^[1]:

Traction apophysitis of the tibial tuberosity. Common in active adolescents (especially boys) during growth spurts.
Pathophysiology: Repetitive traction on the immature tibial tuberosity by the patellar tendon → micro-avulsion → inflammation and new bone formation → painful bony prominence at the tibial tuberosity.
Self-limiting — resolves when the growth plate closes.

H. Vascular

Classification

Knee pain can be classified by several frameworks:

Location	Common Causes
Anterior	Patellofemoral syndrome, patellar tendinopathy, prepatellar bursitis, Osgood-Schlatter, patellar fracture/dislocation, quadriceps tendon rupture, fat pad impingement
Medial	Medial meniscal tear, MCL injury, pes anserine bursitis, medial OA, medial plica syndrome
Lateral	ITBS (most common cause of lateral knee pain), lateral meniscal tear, LCL injury, lateral OA, proximal tibiofibular joint pathology
Posterior	Baker's cyst, PCL injury, posterior meniscal tear, popliteal artery entrapment, DVT, referred from hip/spine
Diffuse	OA (advanced), RA, septic arthritis, crystal arthropathy, fracture

By Age (see Paediatric section above)

Clinical Features

A. Symptoms (with Pathophysiological Basis)

B. Signs (with Pathophysiological Basis)

Test	What It Tests	Positive Finding	Mechanism
Lachman test	ACL	Increased anterior translation with soft/absent endpoint at 20–30° flexion	ACL is the primary restraint to anterior tibial translation
Anterior drawer	ACL	Anterior translation at 90° flexion	Same as above but less sensitive (hamstrings guard at 90°)
Pivot shift	ACL	Sudden reduction (clunk) of subluxed lateral tibial plateau during extension→flexion with valgus + internal rotation	Demonstrates dynamic rotatory instability from ACL deficiency
Posterior drawer	PCL	Posterior translation at 90° flexion	PCL prevents posterior tibial displacement
Posterior sag sign	PCL	Tibia sags posteriorly with hip and knee at 90°	Gravity pulls tibia posteriorly without PCL restraint
Valgus stress (30°)	MCL	Increased medial opening	MCL resists valgus force
Varus stress (30°)	LCL	Increased lateral opening	LCL resists varus force
McMurray test	Meniscus	Pain/click during extension from full flexion with tibial rotation	Trapped meniscal fragment is compressed between condyle and plateau
Apley grind test	Meniscus	Pain with axial compression + rotation in prone position	Compresses torn meniscus between femur and tibia
Thessaly test	Meniscus	Pain/locking at 20° flexion while rotating on single leg	Loads the meniscus dynamically
Grind test (axial compression)	Small joints: OA ^[3]	Pain with axial loading	Damaged cartilage surfaces compressed together
Patellar apprehension	Patellar instability	Patient anxiety/guarding when patella pushed laterally	Prior dislocation → fear of recurrence
Noble's test	ITBS ^[3]	Pain over lateral femoral condyle at 30° flexion	IT band tightest over lateral epicondyle at ~30°
Renne test	ITBS ^[3]	Pain with single-leg squat at 30° flexion	Same mechanism

Feature	Degenerative (OA)	Inflammatory (RA, Crystal)
Morning stiffness	< 30 min	> 30–60 min
Pain pattern	Worse with use, better with rest	May be worse at rest, improves with use
Swelling	Bony (osteophytes), intermittent effusion	Soft, boggy synovitis, persistent
Warmth	Mild or absent	Significant
Joint distribution	Weight-bearing joints	Small joints of hands/feet (RA), any (gout)
Systemic features	Absent	Present (fever, fatigue, weight loss)
Radiographic	LOSS (Loss of joint space, Osteophytes, Subchondral cysts/sclerosis)	Periarticular osteopenia, erosions, uniform joint space narrowing

High Yield Summary

OA is the commonest cause of knee pain in HK, especially in the elderly. Key radiographic features = LOSS (Loss of joint space, Osteophytes, Subchondral cysts, Subchondral sclerosis). Kellgren-Lawrence grading system classifies severity (Grade 0–4). Always assess all 3 compartments with appropriate views.
Anatomy dictates presentation: Medial meniscus tears are more common (attached to MCL); ACL injuries cause haemarthrosis within 2 hours; Baker's cysts arise from underlying joint disease and can rupture to mimic DVT.
Septic arthritis is an emergency: Hot, swollen, tender joint = septic arthritis until proven otherwise. Knee is the most common site. S. aureus is the most common organism.
Crystal arthritis: Gout (MSU crystals, negatively birefringent) vs. pseudogout (CPPD crystals, positively birefringent, chondrocalcinosis on X-ray). Always screen for metabolic causes of CPPD in young patients.
In children, always examine the hip: SCFE and Perthes disease refer pain to the knee via the obturator nerve. Know the age-related differential.
IT band syndrome: Most common cause of lateral knee pain. Pain at 30° flexion over lateral femoral condyle.
Meniscal tear management depends on zone: outer 1/3 = repair; inner 2/3 = partial meniscectomy. Bucket-handle tears and locked knees need surgery.
Masquerades: Always consider referred pain from hip/spine, depression, diabetes (Charcot arthropathy, neuropathy), and psychogenic factors.

Active Recall - Knee Pain: Definition, Epidemiology, Anatomy, Etiology, Classification, Clinical Features

Differential Diagnosis of Knee Pain

The differential diagnosis of knee pain is vast, but a structured approach prevents you from missing dangerous diagnoses while keeping the common things common. The classic framework used in clinical practice — and the one Murtagh's diagnostic strategy is built on — organises differentials by probability, seriousness, and pitfalls ^[1].

Think of it like a triage system for your differential list: What is the most likely diagnosis? What is the most dangerous diagnosis I must not miss? What are the sneaky diagnoses that get overlooked?

Structured Differential by Clinical Presentation

The single most useful bedside approach is to categorise the presentation first, then narrow the differential within that category. Let me walk you through how a senior clinician thinks.

This is the first fork in the road. Monoarthritis ( = 1 joint) and polyarthritis ( ≥ 5 joints, with 2–4 being oligoarthritis) have fundamentally different differential lists ^[11]^[12].

Acute Monoarthritis (the knee is the most common joint affected) ^[11]:

Category	Differential	Key Distinguishing Features
Septic arthritis	Bacterial (S. aureus most common in adults), mycobacterial, Lyme	Hot, swollen, tender joint = septic arthritis until proven otherwise ^[9]. Fever, ↑WBC, ↑ESR/CRP. Gonococcal: purulent mono/oligoarthritis in distal joints in sexually active young adults ± dermatitis ^[11]. Non-gonococcal: large joints, occurs in immunocompromised, IVDU, prosthetic joint ^[11]. Mycobacterial: indolent progressive monoarthritis, immunocompromised or TB contact ^[11].
Crystal-induced arthritis	Gout, pseudogout, hydroxyapatite, calcium oxalate	Gout: single joint in LL (1st MTP > knee), severe pain, redness, swelling, onset often at night, rapid to max severity ≤ 12–24h ^[5]^[13]. Pseudogout: most commonly affects knee, acute presentation mimics gout, most common in elderly women ^[6]^[11].
Trauma	Fracture, internal derangement, haemarthrosis	Usually with trauma Hx +ve, typically occurs seconds to minutes after trauma ^[11]. Haemarthrosis: rapid swelling within 2h (ACL tear in 70%).
Osteoarthritis	Flare of chronic OA	Weight-bearing joint, Hx of overuse, can present with acutely painful synovitis mimicking other d/dx ^[11].
Haemarthrosis	Traumatic or coagulopathic	May be a/w trauma (intra-articular fractures, dislocations, ligamentous sprain/tear, meniscal injury). May be a/w coagulopathies and intra-articular tumours ^[11].
Spondyloarthritis	Reactive arthritis, PsA	Classically asymmetrical oligoarthritis, usually in men < 45y ^[11]. Look for enthesitis, dactylitis, preceding infection, psoriasis.
Uncommon	PVNS, AVN, erythema nodosum, osteomyelitis, leukaemia, synovial metastasis	Joint foreign body reaction, coagulopathy with haemarthrosis ^[11].

Polyarthritis involving the knee ^[12]:

Differential	Discerning Features
Rheumatoid arthritis	Symmetrical arthritis involving small and large joints. Starts in MCP, PIP, wrists, MTP. Spares DIP. Morning stiffness > 30 min. May have swan neck/Boutonnière deformity, rheumatoid nodules in chronic cases ^[12].
Viral polyarthritis	Common associations: Hep B/C, EBV, Parvovirus B19, Dengue, Rubella, HIV. Symmetrical small joint arthritis ± rash, usually self-limiting ≤ 6 weeks ^[12].
SLE-associated arthritis	Symmetrical small joint polyarthritis but usually NOT a/w evidence of synovitis. Migratory pattern with predilection for knee, wrist, PIPJ. Non-deforming, non-erosive ^[12].
Spondyloarthritis (peripheral)	Asymmetrical oligoarthritis, predominantly LL (esp knee, ankles). Enthesitis, dactylitis, anterior uveitis ^[14]. Chronic arthritis, asymmetric in ~70%, usually oligoarthritis ^[14].
OA (polyarticular)	Symmetrical polyarthralgia affecting DIP, PIP, 1st CMCJ, weight-bearing joints and neck. Heberden's/Bouchard's nodes. Pain a/w movement, relieved by rest ^[12].
Polyarticular gout	Occurs in < 20% of gout patients, more common in later untreated flares. Distal > proximal joints, migratory/simultaneous pattern. Usually a/w palpable tophi ^[12].

Timeframe	Differential	Why?
Acute ( < 6 weeks)	Crystal arthritis, reactive arthritis, septic arthritis, viral arthritis, trauma	Acute inflammation or acute mechanical disruption ^[12]
Chronic ( > 6 weeks)	RA, spondyloarthritis, OA, connective tissue disease	Chronic immune-mediated or degenerative processes ^[12]

This is a critical distinction because it determines both the urgency and the type of investigation.

Features suggestive of inflammatory joint pain ^[12]:

Early morning stiffness > 30 min after waking (classical in RA)
Swelling, heat, redness in joints
Better with gentle exercise and worse with rest

Feature	Inflammatory	Non-inflammatory (Mechanical)
Morning stiffness	> 30–60 min	< 30 min ^[3]
Effect of rest	Worse (stiffness accumulates)	Better
Effect of activity	Improves initially	Worsens
Systemic features	Fever, malaise, weight loss	Absent
Synovial fluid WBC	> 2,000/mm³ (often > 50,000 in septic)	< 2,000/mm³
Examples	Septic arthritis, RA, gout, pseudogout	OA, meniscal tear, ligament injury

The pattern tells the story ^[12]^[15]:

Pattern	Think of...
Monoarthritis in gout and septic arthritis	Gout, septic arthritis, trauma ^[15]
Oligoarthritis (≤ 4 joints) in ankylosing spondylitis and enteropathic arthritis	Spondyloarthropathy, reactive arthritis ^[15]
Polyarthritis (≥ 5 joints) in RA and SLE	RA, SLE, viral arthritis ^[15]
RA: symmetrical, proximal joints and MCP/PIP in hands	RA ^[15]
Seronegative spondyloarthritis: asymmetrical, axial joints and PIP/DIP in hands	PsA, reactive arthritis, AS ^[15]
OA: large joints (knees), CMC/PIP/DIP in hands	OA ^[15]

Temporal pattern ^[12]:

Migratory pattern (symptoms present in certain joints for a few days then remit, reappearing in other joints): rheumatic fever, gonococcal arthritis, SLE-associated arthritis
Additive pattern (symptoms begin in some joints and persist with subsequent involvement of others): RA, SLE
Intermittent pattern (repetitive attacks with complete remission between attacks): RA, polyarticular gout, palindromic rheumatism

Anatomical location is extremely helpful, especially for soft-tissue and periarticular causes:

Location	Differential	Distinguishing Clue
Anterior	Patellofemoral syndrome, patellar tendinopathy, prepatellar bursitis, Osgood-Schlatter, patellar fracture/dislocation, fat pad impingement	PFS: worse going downstairs; bursitis: localised swelling anterior to patella; Osgood-Schlatter: adolescent + tibial tuberosity tenderness
Medial	Medial meniscal tear, MCL injury, pes anserine bursitis, medial OA, medial plica	Joint-line tenderness = meniscus; below joint line = pes anserine; valgus stress = MCL
Lateral	ITBS (most common cause of lateral knee pain) ^[3], lateral meniscal tear, LCL injury, lateral OA, proximal tibiofibular joint	ITBS: pain over lateral femoral condyle at 30° flexion ^[3]; runners/cyclists
Posterior	Baker's cyst ^[2], PCL injury, popliteal artery entrapment, DVT, posterior meniscal horn tear	Baker's cyst: posterior knee pain, stiffness, mass behind knee, a/w underlying joint disease ^[2]. Ruptured Baker's cyst mimics DVT ^[1]^[7].
Diffuse / Generalised	OA, RA, septic arthritis, crystal arthritis, fracture	Hot + swollen + systemic = think septic/crystal first

Age Group	Key Differentials	Why This Age?
Children < 5	Septic arthritis, transient synovitis, JIA, NAI	Immature immune system, haematogenous spread to metaphysis
5–10	Perthes disease, transient synovitis, JIA	AVN at the vulnerable developing femoral epiphysis
10–16	SCFE, Osgood–Schlatter ^[1], osteochondritis dissecans, bone tumours	Growth spurt stresses apophyses and physes; peak age for osteosarcoma
Young adults 16–35	ACL/meniscal tears, patellofemoral syndrome, patellar dislocation, stress fracture, reactive arthritis	High activity → trauma and overuse; sexual activity → gonococcal arthritis
Middle-aged 35–55	Degenerative meniscal tears, early OA, gout, CPPD	Cartilage senescence begins; metabolic diseases accumulate
Elderly > 55	OA (by far most common), crystal arthritis, insufficiency fractures, referred pain from hip/spine ^[1], malignancy (primary or metastatic)	Accumulated wear; osteoporotic bone; increasing cancer incidence

The "Must Not Miss" Differentials — Explained from First Principles

Differentiating Key Conditions — Side-by-Side Comparison

Feature	Gout	Pseudogout
Crystal	MSU (monosodium urate)	CPPD (calcium pyrophosphate dihydrate)
Shape	Needle-shaped ^[13]	Pleomorphic or rhomboid-shaped ^[13]
Birefringence	Strongly negative ^[13]	Weakly positive ^[13]
Joint predilection	1st MTP (podagra) > knee > ankle	Most commonly knee ^[6]^[11]
Demographics	M >> F, 4th–5th decade	↑ with age (rare < 55y), M:F ≈ 1:1 ^[6]
X-ray	Punched-out erosions with overhanging edges, tophi ^[13]	Chondrocalcinosis: irregular punctate/linear radiodensities in articular cartilage ^[6]
Secondary causes	Diuretics, CKD, alcohol, myeloproliferative	Haemochromatosis, hyperPTH, Wilson's, hypoMg ^[6]

Both present as an acutely hot, swollen, painful joint — and they can coexist! The only definitive way to distinguish them is joint aspiration ^[13]:

Feature	Septic Arthritis	Crystal Arthritis
Fever	Common (may be absent in elderly)	May be present (especially gout)
Synovial fluid WBC	Typically > 50,000/mm³ (but can be lower)	Typically 2,000–100,000/mm³
Gram stain/culture	Positive (but Gram stain only ~50% sensitive)	Negative
Crystals	Absent (unless coexisting crystal disease)	Present — MSU or CPPD
Key principle	Must always aspirate the joint to exclude infection before giving steroids ^[6]	Can coexist with infection → always send for culture even if crystals seen

Coexisting Infection and Crystals

Finding crystals does NOT exclude septic arthritis. Up to 5% of patients with septic arthritis also have crystals in the joint fluid. Always send joint fluid for Gram stain and culture regardless of crystal findings. Never give intra-articular steroids without first ruling out infection.

Feature	OA	RA
Stiffness	< 30 min ^[3]	> 30–60 min
Joint distribution	Weight-bearing: knee, hip, spine. 1st CMC and IPJ in hands ^[3]	Symmetrical: MCP, PIP, wrist, MTP. Spares DIP
Swelling	Bony (osteophytes), hard	Soft, boggy (synovitis)
X-ray	LOSS: Loss of joint space, Osteophytes, Subchondral cysts, Subchondral sclerosis ^[3]	Periarticular osteopenia, erosions, uniform joint space loss
Systemic features	None	Rheumatoid nodules, extra-articular manifestations

Both can present as leg pain with exertion, but the mechanisms are entirely different ^[16]^[17]:

Feature	Vascular claudication	Neurogenic claudication
Cause	Chronic arterial insufficiency → exercise-induced muscle ischaemia ^[17]	Prolapsed IVD or OA spine → spinal stenosis → compression on spinal arteries → lumbosacral root ischaemia ^[17]
Precipitation	Claudication distance constant	Claudication distance variable
Relief	Shop window to shop window (relief upon standing still)	Park bench to park bench (relief upon flexion of spine) ^[16]^[17]
Pain at rest	None	May be present (prefer to stand in slight flexion) ^[17]
Other complaints	Nil	Paraesthesia, numbness, weakness ^[17]
Going downstairs	Not a factor	Going downstairs > upstairs (extension narrows canal) ^[17]

When evaluating knee pain, always look beyond the joint itself. Extra-articular features and associated symptoms ^[12] can clinch the diagnosis:

Finding	Suggests
Psoriatic plaques / nail pitting	Psoriatic arthritis
Preceding urethritis / conjunctivitis / diarrhoea	Reactive arthritis (spondyloarthropathy spectrum)
Tophi on ears, olecranon, 1st MTP	Chronic tophaceous gout
Erythema migrans (target lesion)	Lyme arthritis
Malar rash, oral ulcers, photosensitivity	SLE
Subcutaneous nodules, erythema marginatum, chorea	Rheumatic fever
Uveitis, enthesitis, dactylitis	Spondyloarthropathy
Fever + new murmur	Infective endocarditis → septic embolism to joint
Weight loss + night sweats + chronic cough	TB arthritis / malignancy

Joint aspiration is the single most important investigation in the acutely swollen knee ^[13]. Here's a summary:

Parameter	Normal	Non-inflammatory	Inflammatory	Septic
Appearance	Clear, colourless	Clear, yellow	Translucent-opaque, yellow	Opaque, purulent
Viscosity	High	High	Low	Very low
WBC (/mm³)	< 200	< 2,000	2,000–100,000	> 50,000 (often > 100,000)
Neutrophils	< 25%	< 25%	> 50%	> 75%
Crystals	None	None	MSU or CPPD	None (unless coexisting)
Culture	Negative	Negative	Negative	Positive
Example	—	OA, trauma	Gout, pseudogout, RA	Bacterial arthritis

High Yield Summary - Differential Diagnosis

Murtagh's framework: Probability (OA, ligament sprains, patellofemoral syndrome, bursitis) → Serious (septic arthritis, DVT, malignancy, RA, ACL tear) → Pitfalls (referred pain from hip/spine, osteochondritis dissecans, meniscal tears, pseudogout, Baker's cyst) → Masquerades (depression, diabetes, spinal dysfunction).
Septic arthritis: Always the #1 diagnosis to exclude in a hot, swollen joint. Aspirate first, ask questions later. Can coexist with crystals.
Crystal arthritis: Gout = needle-shaped, negative birefringence; Pseudogout = rhomboid, positive birefringence. Pseudogout favours the knee. Always screen for metabolic causes of CPPD in young patients.
Inflammatory vs. mechanical: Morning stiffness > 30 min, improvement with activity, systemic features → inflammatory. Morning stiffness < 30 min, worsens with activity, no systemic features → mechanical/degenerative.
Referred pain: Hip pathology (via obturator nerve L2–L4) and lumbar spine pathology (radiculopathy, neurogenic claudication) are the most commonly missed causes of knee pain. Always examine the hip and spine.
Age-specific: Children — septic arthritis, Perthes, SCFE, Osgood-Schlatter, bone tumours. Young adults — ligament injuries, patellofemoral syndrome. Middle-aged — degenerative meniscal tears, early OA, gout. Elderly — OA, crystal arthritis, insufficiency fractures, malignancy.
Joint aspiration is the definitive investigation in acute monoarthritis — analyse for cell count, crystals, Gram stain, and culture.

Active Recall - Differential Diagnosis of Knee Pain

References

^[1] Lecture slides: murtagh merge.pdf (Knee pain, p64–65) ^[2] Senior notes: felixlai.md (Baker's cyst, sciatica, popliteal artery entrapment) ^[3] Senior notes: maxim.md (Osteoarthritis, IT band syndrome, meniscal tears) ^[5] Senior notes: Ryan Ho Rheumatology.pdf (p35, Gout) ^[6] Senior notes: Ryan Ho Rheumatology.pdf (p41–42, CPPD Crystal Deposition Disease) ^[7] Senior notes: Ryan Ho Haemtology.pdf (p131, DVT and Baker's cyst rupture as differential) ^[9] Senior notes: Ryan Ho Rheumatology.pdf (p67, Septic arthritis) ^[11] Senior notes: Ryan Ho Rheumatology.pdf (p28, Approach to Acute Monoarthritis) and Senior notes: Ryan Ho Fundamentals.pdf (p406, Acute Monoarthritis) ^[12] Senior notes: Ryan Ho Rheumatology.pdf (p30–31, Approach to Polyarthritis) and Senior notes: Ryan Ho Fundamentals.pdf (p408–409, Polyarthritis) ^[13] Senior notes: Ryan Ho Rheumatology.pdf (p30, Synovial fluid analysis; p37, Acute Gout Flare; p39, Chronic Gout) ^[14] Senior notes: Ryan Ho Rheumatology.pdf (p63, Peripheral SpA) ^[15] Senior notes: Ryan Ho Rheumatology.pdf (p4, Examination of Rheumatological System) and Senior notes: Ryan Ho Fundamentals.pdf (p125, Examination of Rheumatological System) ^[16] Senior notes: Ryan Ho Neurology.pdf (p174, Lumbar canal stenosis and neurogenic claudication) ^[17] Senior notes: Ryan Ho Cardiology.pdf (p205, Vascular vs neurogenic claudication comparison table)

Diagnostic Criteria for Key Conditions Causing Knee Pain

OA does not have formal laboratory diagnostic criteria because it is fundamentally a clinical-radiological diagnosis. The ACR clinical classification criteria for OA knee (1986, still widely used) combine clinical features ± laboratory ± radiology:

ACR Clinical Classification Criteria for OA Knee (sensitivity 95%, specificity 69% for clinical alone):

Knee pain plus at least 3 of the following 6:
1. Age > 50
2. Morning stiffness < 30 minutes
3. Crepitus on active motion
4. Bony tenderness
5. Bony enlargement
6. No palpable warmth

Why these criteria? Each item captures the pathophysiology: age reflects cumulative cartilage wear; brief stiffness reflects mild non-inflammatory synovial thickening (not the intense synovitis of RA); crepitus = roughened cartilage surfaces; bony tenderness = exposed subchondral bone; bony enlargement = osteophytes; no warmth = lack of significant inflammation.

Radiological severity is graded by the Kellgren-Lawrence (KL) classification ^[3]:

Grade	Description
Grade 0	No joint space narrowing (JSN)
Grade 1	Possible osteophytes, doubtful JSN
Grade 2	Definite osteophytes
Grade 3	Definite JSN
Grade 4	Bone-on-bone deformity

Radiographic views ^[3]:

Weightbearing AP: medial vs lateral compartment
Lateral: anteromedial vs posteromedial (e.g., posterior osteophytes)
Skyline: patellofemoral joint space
Valgus stress / Varus stress: assess medial / lateral joint space
Standing scanogram of bilateral LL: alignment — tibiofemoral angle (TFA), mechanical axis
+/- Schuss view (30° flexion): more sensitive for early OA

Radiological features — the LOSS mnemonic ^[3]:

Loss of joint space (earliest)
Osteophytes
Subchondral cysts
Subchondral sclerosis

OA is a Clinical-Radiological Diagnosis

There is no blood test for OA. Inflammatory markers (ESR, CRP) are typically normal or minimally elevated. Radiographs may be normal in early OA (clinical symptoms precede X-ray changes). The Schuss view at 30° flexion is more sensitive for detecting early cartilage loss because it loads the posterior femoral condyle where early wear often begins.

Entry criterion: At least 1 episode of swelling, pain, or tenderness in a peripheral joint or bursa.

Sufficient criterion (if met, classify as gout without scoring): MSU crystals in a symptomatic joint/bursa (fluid or tophus).

If no crystal confirmation, use a scoring system (threshold ≥ 8 points out of 23):

Domain	Category	Score
Pattern of joint involvement	Ankle or midfoot (mono/oligoarthritis)	1
	1st MTP	2
Characteristics of episode	Erythema, cannot bear touch/pressure, great difficulty walking	1 per feature (max 3)
Time course	Maximum within < 24h, resolution ≤ 14d, complete resolution between episodes	1 per feature (max 3) if ≥ 2 typical episodes
Clinical tophi	Present	4
Serum urate	< 4 mg/dL	-4
	6– < 8 mg/dL	2
	8– < 10 mg/dL	3
	≥ 10 mg/dL	4
Imaging: urate deposition	USG double contour sign or DECT demonstrating urate deposition	4
Imaging: gout-related joint damage	XR hands/feet showing ≥ 1 erosion	4

Key investigations for gout ^[5]^[13]:

Serum urate: can be high, normal, or low (12–43% normal/low during acute flare) → should be deferred to ≥ 2 weeks after resolution ^[13]
Joint fluid analysis — most important test ^[13]:
- MSU crystals: elongated needle-shaped, negative birefringent crystals ± engulfment by PMN ^[13]
- WBC 2–100 × 10³/mL, > 90% neutrophils ^[13]
Plain XR: typically normal in acute gout ± features of chronic gout (punched-out erosions with overhanging edges, tophi, chronic joint destruction) ^[13]
USG: double contour sign overlying surface of joint cartilage ^[13]
DECT: can specifically identify urate deposits ^[13]

While RA is typically a polyarthritis, it can present as monoarthritis with monoarticular onset ^[11]. The criteria (threshold ≥ 6/10) include:

Domain	Score
Joint involvement: 1 large joint	0
2–10 large joints	1
1–3 small joints	2
4–10 small joints	3
> 10 joints (≥ 1 small)	5
Serology: Low-positive RF or anti-CCP	2
High-positive RF or anti-CCP	3
Acute phase: Normal ESR and CRP	0
Abnormal ESR or CRP	1
Duration: < 6 weeks	0
≥ 6 weeks	1

Investigation Modalities — Detailed Guide

Key investigations to consider ^[1]:

FBE/ESR
Connective tissue antibodies
Blood culture

Test	What It Tells You	When to Order	Key Findings
FBE (CBC)	Infection (↑WBC with neutrophilia), malignancy (anaemia, cytopenias), haemophilia	Any suspected inflammatory/infectious/haematological cause	↑WBC + left shift → infection; anaemia + thrombocytopenia → marrow disease
ESR/CRP	Acute phase response — indicates inflammation but NOT specific ^[18]	Useful if joint fluid examination equivocal ^[18]; to assess treatment response	↑ in infection, crystal arthritis, RA. CRP usually normal/mildly ↑ in SLE ^[18]. OA = normal or mildly elevated
Serum urate	Hyperuricaemia supports gout diagnosis	If suspicious of gout — taken 2 weeks after resolution ^[18] as urate may be paradoxically normal/low during acute flare ^[13]	> 0.42 mmol/L (7 mg/dL) in men, > 0.36 mmol/L (6 mg/dL) in women
RF (Rheumatoid Factor)	Anti-IgG IgM antibody	If suspicious for RA ^[18]	+ve in 70% RA (not sensitive) and also positive in many other conditions (Sjögren's, SLE, infections, elderly). Specificity ~80%
Anti-CCP	Anti-citrullinated peptide antibody	If suspicious for RA ^[18]	More specific than RF (~95% specificity). High titres predict erosive disease
ANA	Antinuclear antibody screen	If suspicious for SLE ^[18]	Sensitive (~95%) but not specific. If positive, request anti-dsDNA, anti-ENA panel
Blood culture	Bacteraemia	Suspected septic arthritis with systemic sepsis	Positive in ~50% of septic arthritis cases (haematogenous spread)
Ca, P, Mg, ALP, ferritin	Screen for metabolic causes of CPPD	After confirming CPPD disease, especially if age < 55	↑Ca/PTH → hyperparathyroidism; ↑ferritin → haemochromatosis; ↓Mg → hypomagnesaemia; ↓ALP → hypophosphatasia ^[6]
LDH, ALP	Bone turnover markers	Suspected malignancy, Paget's disease	↑ALP → Paget's disease or bony metastases; ↑LDH → lymphoma, Ewing's sarcoma
Coagulation screen	Bleeding disorder	Haemarthrosis without trauma	Prolonged aPTT → haemophilia

This is the single most important investigation in the acutely swollen knee. I cannot overstate this. If you can only do one test, aspirate the joint.

Indications ^[18]:

Suspicious of septic arthritis
Suspicious of crystal-induced arthritis
Suspicious of haemarthrosis
Differentiating inflammatory vs non-inflammatory arthritis

Send for ^[18]:

Macroscopic: colour, viscosity, turbidity
Microscopy: wet films, WBC count/diff, crystal microscopy
Microbiology (if suspect septic arthritis): Gram stain (urgent if septic arthritis suspected), bacterial culture, AFB smear and culture, fungal stain (if indicated)

Synovial Fluid Interpretation Table

Parameter	Normal	Non-inflammatory	Inflammatory	Septic
Appearance	Clear, colourless	Clear, yellow (straw)	Translucent → opaque, yellow	Opaque, purulent (yellow-green)
Viscosity	High (long string)	High	Low (short string)	Very low
WBC (/mm³)	< 200	< 2,000	2,000–100,000	> 50,000 (often > 100,000)
Neutrophils	< 25%	< 25%	> 50%	> 75%
Crystals	None	None	MSU or CPPD	None (unless coexisting)
Gram stain	Negative	Negative	Negative	Positive ~50%
Culture	Negative	Negative	Negative	Positive ~80–90%
Examples	—	OA, trauma, early AVN	Gout, pseudogout, RA, reactive	Bacterial septic arthritis

Why is viscosity low in inflammatory fluid? Viscosity of synovial fluid depends on hyaluronic acid concentration. Inflamed synovium produces dilute fluid with lower hyaluronic acid → reduced viscosity → the classic "short string" test (normal fluid strings out > 3 cm between fingers; inflammatory fluid breaks quickly).

Crystal microscopy — the definitive differentiator ^[13]^[18]:

Gout: slender and needle-shaped, strongly negative birefringence under polarised light
Pseudogout: pleomorphic or rhomboid shaped, weakly positive birefringence

What does birefringence mean? Birefringence is the ability of a crystal to split light into two rays travelling at different speeds. Under compensated polarised light microscopy: Negative birefringence = crystal appears yellow when parallel to the slow axis of the red compensator (mnemonic: "Negative = Needle = yellow when North-south / parallel"). Positive birefringence = crystal appears blue when parallel (opposite direction).

Special findings:

Bloody aspirate with fat globules (lipid droplets on surface) = intra-articular fracture (fat from bone marrow mixes with blood)
Bloody aspirate without fat = haemarthrosis from soft tissue injury (ACL tear, synovial injury)
Milky-white fluid = crystal arthritis or rarely chylous effusion

Arthroscopy ^[18]:

Diagnostic: assess degree of cartilage damage, synovial biopsy for equivocal cases
Therapeutic: debridement of damaged cartilage, removal of loose bodies, drainage for pain relief

Joint Aspiration Before Steroids — Always!

Never inject intra-articular steroids without first aspirating and sending fluid for Gram stain and culture. Injecting steroid into a septic joint is catastrophic — it suppresses the local immune response and allows bacterial proliferation. Even if crystals are found, send cultures — coexistence of crystals and infection occurs in up to 5% of cases.

C. Imaging

"The best modality is the one which can answer the clinical question in the clearest, fastest, safest and cheapest way." ^[19]

First-line imaging investigation for knee pain ^[19]^[20].

Main indications: evaluation of musculoskeletal system, especially in trauma and joint-based diseases ^[20]. Most films have ≥ 2 views because fractures may be detected only in one view ^[20].

Characteristics ^[20]:

Most useful for structures with high-density contrasts between tissue types
Highest spatial resolution → good for fine details (e.g., fractures)
Poor contrast → poor in examining soft tissues
Plain X-ray can only tell between four densities: calcium, water (soft tissues), fat, and air
2-D representation of 3-D structures → overlapping may be present → use different angles to remedy

Standard knee views:

AP (anteroposterior): Assess alignment, joint space (medial vs lateral), bony lesions
Lateral: Assess patella position (alta/baja), posterior osteophytes, effusion (suprapatellar fat pad sign), tibial plateau
Skyline / Merchant view: Patellofemoral joint — assess patellar tilt, subluxation, patellofemoral OA
Weightbearing AP: More sensitive than supine AP for joint space narrowing (true functional loading) ^[3]
Schuss view (30° flexion weightbearing): More sensitive for early OA ^[3] — loads the posterior condylar surface where early cartilage loss occurs
Standing scanogram of bilateral LL: Full-length film for alignment assessment (mechanical axis, TFA) ^[3]
Stress views (valgus/varus): Assess collateral ligament integrity and compartmental joint space

Key X-ray findings and their meaning:

Finding	Diagnosis	Pathophysiological Basis
Loss of joint space	OA (earliest sign) ^[3]	Cartilage loss → bones approximate
Osteophytes	OA ^[3]	Reactive new bone at joint margins to redistribute load
Subchondral sclerosis	OA ^[3]	Increased stress → reactive bone thickening
Subchondral cysts	OA ^[3]	Microfractures in sclerotic bone → synovial fluid intrusion
Chondrocalcinosis	CPPD disease ^[6]	Irregular faint punctate/linear radiodensities in articular cartilage
Punched-out erosions with overhanging edges	Chronic tophaceous gout	Tophi erode bone from the outside; overhanging edge = preserved cortex overlying the erosion
Periarticular osteopenia + erosions + uniform JSN	RA	Pannus erodes bone; osteopenia from disuse + cytokine-driven bone resorption
Aggressive periosteal reaction + soft tissue mass	Malignancy (osteosarcoma)	Rapid bone destruction → sunburst pattern / Codman's triangle
Segond fracture	ACL tear (pathognomonic)	Avulsion of lateral capsular ligament off lateral tibial plateau during internal rotation + valgus
Lipohemarthrosis on lateral view	Intra-articular fracture	Fat from marrow + blood layer in suprapatellar pouch (fat-fluid level)

No radiation, cheap, excellent spatial resolution if superficial, real-time ^[19]. Operator dependent, limited penetration, cannot see through air and bone ^[19].

Applications in knee pain:

Use	Finding	Significance
Joint effusion	Anechoic or hypoechoic fluid in suprapatellar recess	Quantify effusion, guide aspiration
Baker's cyst	Well-defined fluid-filled structure in popliteal fossa between medial head of gastrocnemius and semimembranosus	Distinguish from DVT; look for underlying joint pathology
Gout	Double contour sign: hyperechoic line overlying the hypoechoic cartilage surface ^[13]	MSU crystal deposition on cartilage surface
CPPD	Thin hyperechoic band paralleling bone cortex, separated from it by hypoechoic cartilage ^[6]	CPPD crystal deposition within cartilage (cf. gout which is ON cartilage surface)
Tendinopathy	Thickened, hypoechoic tendon ± neovascularisation on Power Doppler	Patellar tendinopathy, quadriceps tendinopathy
Bursitis	Fluid-filled bursa with thickened walls	Prepatellar, infrapatellar, pes anserine
Soft tissue mass	Solid vs cystic, vascularity	Differentiate cyst from solid tumour
DVT	Non-compressibility of deep veins on compression USG (= duplex USG) ^[7]	Thrombus prevents vein from collapsing under probe pressure

Duplex USG is the first-line imaging for DVT ^[7]^[17].

Excellent anatomical differentiation especially soft tissues, no radiation ^[19]. Not readily available, very expensive, C/I pacemaker and metallic implants ^[19].

MRI is the gold standard for soft tissue evaluation of the knee — it is the investigation of choice for:

Structure	MRI Findings	Clinical Scenario
Meniscal tear	Intrameniscal signal reaching the articular surface (grade 3 signal) on T2-weighted or PD-weighted images	MRI knee: diagnostic + grading ^[3]. Determines tear pattern, location (zone), and guides surgical approach
ACL tear	Discontinuity, abnormal signal, abnormal orientation of ACL fibres; secondary signs include bone bruising (lateral femoral condyle + posterolateral tibial plateau kissing pattern), anterior tibial translation, uncovered posterior horn lateral meniscus	Suspected ACL tear after trauma with haemarthrosis
PCL tear	Loss of normal dark signal, thickening, discontinuity	Dashboard injury mechanism
MCL/LCL injury	Periligamentous oedema (grade I), partial disruption (grade II), complete disruption (grade III)	MRI: diagnostic + grading of injury ^[3]
Bone marrow oedema	High signal on T2/STIR, low on T1	Stress fracture, AVN, bone bruise, early OA
AVN/Osteonecrosis	Subchondral low signal line ("double line sign" on T2 = pathognomonic)	Suspected SONK, steroid use, SLE
Tumour	Soft tissue mass with or without bony involvement, marrow replacement	Staging, biopsy planning
Chondral damage	Focal thinning, fissuring, or defect in articular cartilage	Osteochondritis dissecans, early chondral lesions not visible on X-ray
Baker's cyst	Well-defined fluid signal collection between gastrocnemius and semimembranosus	Look for underlying meniscal/cartilage pathology

Why is MRI better than X-ray for soft tissues? MRI exploits the magnetic properties of hydrogen atoms (abundant in water and fat) to generate contrast between different soft tissue types. Ligaments, menisci, cartilage, and synovium all have different water content and produce distinct signals. X-rays only differentiate four densities (calcium, water, fat, air) and cannot distinguish between these soft tissue structures.

Excellent anatomical differentiation, allow 3D reconstruction ^[19]. Substantial radiation, not as good as MRI in soft tissues, high cost ^[19].

Applications in knee pain:

Use	Why CT Over Other Modalities?
Complex fractures (tibial plateau, distal femur)	3D reconstruction helps surgical planning; better bone detail than MRI
Loose bodies	CT detects calcified bodies that may be missed on X-ray
Pre-operative planning (total knee arthroplasty)	Rotational alignment assessment
DECT for gout	Dual energy CT can specifically identify urate deposits ^[13] — colour-codes urate crystals vs calcium

Gives specific functional information, very sensitive for certain diseases ^[19]. Radiation, poor anatomical differentiation, quite expensive ^[19].

Test	Application	Finding
Bone scintigraphy (Tc-99m)	Suspected stress fracture (negative X-ray), metastatic bone survey, infection, Paget's disease	Focal increased uptake ("hot spot") at area of ↑bone turnover
PET-CT	Staging malignancy, assessing infection extent in complex cases	FDG-avid lesions indicate high metabolic activity

Why is bone scan so sensitive? It detects areas of increased osteoblastic activity (new bone formation). Stress fractures stimulate intense bone remodeling weeks before a fracture line becomes visible on X-ray. However, it is non-specific — infection, tumour, and fracture all appear as "hot spots."

Investigation	Indication	What It Shows
Ankle-Brachial Index (ABI) ^[17]	Suspected peripheral arterial disease as cause of exertional leg/knee pain	Normal = 0.90–1.30; ≤ 0.9 = arterial occlusive disease (diagnostic); 0.40–0.90 = claudication; < 0.4 = rest pain, tissue loss; > 1.30 = calcified arteries (use TBI instead)
Nerve conduction studies / EMG	Suspected peripheral neuropathy, peroneal nerve palsy, radiculopathy	Distinguish neuropathic from musculoskeletal pain; localise nerve lesion
Lumbar MRI	Suspected referred pain from spine, neurogenic claudication	Disc herniation, spinal stenosis with "trefoil" appearance ^[16]
Hip X-ray	Suspected referred pain from hip (especially children — SCFE, Perthes)	Frog-leg lateral view for SCFE; AP pelvis for Perthes
Bone biopsy	Suspected primary bone tumour, uncertain bone lesion	Histological diagnosis; must be done at the definitive surgical centre to avoid contaminating surgical fields

Scenario	First-Line	Second-Line	Definitive
Acute hot swollen knee + fever	FBE, ESR/CRP, blood culture, urgent joint aspiration	X-ray (r/o fracture, chondrocalcinosis)	Synovial fluid: cell count, crystals, Gram stain, culture
Acute traumatic knee	X-ray (AP + lateral ± skyline)	MRI (if ligament/meniscal injury suspected clinically)	Arthroscopy (if MRI equivocal or for therapeutic intervention)
Chronic mechanical knee pain in elderly	Weightbearing AP + lateral + skyline X-ray ± Schuss view	Standing scanogram (if surgical planning)	Clinical diagnosis of OA (no blood test needed)
Suspected gout	Joint aspiration (crystals), serum urate (2 weeks post-flare)	X-ray (chronic changes), USG (double contour sign)	DECT if equivocal
Knee pain in a child	X-ray knee + X-ray hip (always!)	MRI if suspected AVN, osteochondritis dissecans	Bone biopsy if tumour suspected
Suspected DVT	Modified Wells score → D-dimer (if low probability)	Duplex USG	CT venography (if USG equivocal)
Night pain, weight loss, bone mass	X-ray, FBE, ALP, LDH, Ca	MRI (staging), CT chest/abdomen (metastatic workup)	Biopsy

High Yield Summary - Diagnosis and Investigations

Joint aspiration is the MOST IMPORTANT test in an acutely swollen knee. It differentiates septic from crystal from inflammatory from non-inflammatory causes. Always send for cell count, crystals, Gram stain, and culture simultaneously.
Crystal identification: Gout = needle-shaped, strongly negative birefringent. Pseudogout = rhomboid, weakly positive birefringent. Finding crystals does NOT exclude coexisting infection — always send cultures.
OA is a clinical-radiological diagnosis: LOSS on X-ray (Loss of joint space, Osteophytes, Subchondral cysts, Subchondral sclerosis). Kellgren-Lawrence grades 0–4. Weightbearing AP and Schuss view are more sensitive than supine films.
CPPD diagnosis = arthrocentesis + X-ray: Definite = positive birefringent crystals + chondrocalcinosis on X-ray. Always screen metabolic causes (Ca, P, Mg, ALP, ferritin) afterwards.
MRI is the gold standard for soft tissue evaluation — meniscal tears, ligament injuries, AVN, bone marrow oedema, tumours. X-ray is first-line for bony pathology and fractures.
Serum urate in gout: Check 2 weeks AFTER resolution of acute flare (12–43% are normal/low during flare).
DVT workup: Modified Wells score → D-dimer if low probability; duplex USG if high probability or positive D-dimer.
Always X-ray the hip in a child with knee pain — SCFE and Perthes refer to the knee.

Active Recall - Diagnostic Criteria, Algorithm and Investigations for Knee Pain

Condition-Specific Management

A. Osteoarthritis of the Knee

OA management follows a stepwise escalation from non-pharmacological to pharmacological to interventional to surgical. The key insight is that no treatment reverses OA — the goals are pain relief, functional improvement, and slowing progression.

Conservative management ^[3]:

Relief of weight-bearing: weight reduction, walking aids, muscle strengthening

Modality	Mechanism	Evidence
Weight loss	Every 1 kg lost reduces ~4 kg load across the knee. Adipose tissue also produces pro-inflammatory cytokines (adipokines) that accelerate cartilage degradation.	5% body weight loss → clinically meaningful pain reduction
Physiotherapy / Exercise	Quadriceps strengthening provides dynamic stability, compensating for lost cartilage cushioning. Aerobic exercise improves joint nutrition (synovial fluid circulation depends on movement) and reduces systemic inflammation.	Strong evidence for land-based exercise; aquatic therapy also beneficial
Walking aids	A contralateral cane reduces ipsilateral knee load by ~20–30%.	Simple, effective, underutilised
Orthotics / Bracing	Lateral wedge insoles for medial compartment OA (shift load laterally); unloader braces for unicompartmental OA	Modest evidence; patient compliance is the limiting factor
Patient education	Understanding the disease reduces catastrophising, improves self-management, and improves adherence to exercise	Foundation of all OA management

Why is quadriceps strengthening so important? The quadriceps acts as a "dynamic shock absorber" for the knee. In OA, pain causes reflex quadriceps inhibition (arthrogenic muscle inhibition) → atrophy → loss of dynamic stability → increased stress on cartilage → more pain → more inhibition. Breaking this vicious cycle with targeted strengthening is the single most effective non-pharmacological intervention.

Pain relief: analgesics, intra-articular steroid ^[3].

Drug	Mechanism	Indication	Key Points
Paracetamol	Central inhibition of COX enzymes + serotonergic descending inhibitory pathway activation	First-line analgesic for mild-moderate OA pain	Max 4g/day in adults. Hepatotoxic in overdose. Recent evidence suggests modest efficacy vs placebo — increasingly questioned as sole analgesic ^[21]
Topical NSAIDs (e.g., diclofenac gel)	Local COX-1/2 inhibition → ↓prostaglandin synthesis at the joint → ↓inflammation and pain	Mild-moderate knee OA; preferred over oral NSAIDs in elderly	Minimal systemic absorption → fewer GI/renal/CV side effects. Apply directly over the affected joint
Oral NSAIDs (e.g., naproxen, ibuprofen, diclofenac)	Systemic COX-1/2 inhibition → ↓prostaglandin synthesis	Moderate-severe OA pain not controlled by paracetamol ± topical NSAIDs	Use lowest effective dose for shortest duration. Contraindications: active PUD, CKD (GFR < 30), heart failure, aspirin-exacerbated respiratory disease. Co-prescribe PPI for GI protection if > 65y or history of PUD
COX-2 selective inhibitors (e.g., celecoxib, etoricoxib)	Selective COX-2 inhibition → anti-inflammatory effect with less GI toxicity (COX-1 protects gastric mucosa)	Patients with GI risk factors who need oral NSAIDs	Lower GI risk but equivalent or higher CV risk compared to non-selective NSAIDs. Still need PPI in high-risk patients
Weak opioids (e.g., tramadol, codeine)	μ-opioid receptor agonism in CNS → ↓pain perception	Moderate-severe pain not responding to NSAIDs, or NSAIDs contraindicated	Risk of dependence, constipation, drowsiness. Tramadol also has serotonin/noradrenaline reuptake inhibition → risk of serotonin syndrome with SSRIs
Duloxetine	SNRI → enhances descending inhibitory pain pathways	Chronic OA pain with central sensitisation component	OARSI-recommended adjunct for patients with widespread pain or depressive comorbidity

NSAID Prescribing — The Risk Triangle

Every NSAID prescription requires you to consider three risks: GI (PUD, bleeding → co-prescribe PPI), Renal (prostaglandin-mediated afferent arteriolar dilatation maintains GFR → NSAIDs block this → AKI risk, especially in elderly, dehydrated, or CKD patients), and CV (prostaglandin I2 in endothelium is antithrombotic → COX-2 inhibition tips the balance towards thrombosis → ↑MI/stroke risk). Always check renal function before prescribing and avoid in patients with established CV disease.

Injection	Mechanism	Indication	Key Points
Intra-articular corticosteroid (e.g., triamcinolone acetonide 40 mg + 1–2 mL 1% lidocaine) ^[6]	Potent local anti-inflammatory → ↓synovitis, ↓effusion, ↓pain. Corticosteroids suppress NF-κB → ↓cytokine production → ↓neutrophil recruitment	Acute flare of OA with significant effusion; moderate-severe pain not controlled by oral medications	Effect: usually provides relief of pain/swelling ≤ 8–24h ^[6]. Duration: typically 4–12 weeks. Limit to 3–4 injections per joint per year (repeated steroid → accelerated cartilage loss). Caution: must r/o septic arthritis before injection of steroid ^[6]
Intra-articular hyaluronic acid (viscosupplementation) ^[3]	Exogenous hyaluronic acid restores synovial fluid viscosity and shock-absorbing properties. May also have anti-inflammatory and analgesic effects via CD44 receptor signalling on chondrocytes	Mild-moderate OA; patients who cannot tolerate NSAIDs or are not surgical candidates	Intra-articular hyaluronic acid / platelet-rich plasma (?evidence) ^[3]. Evidence is mixed — OARSI 2025 conditionally recommends against routine use but acknowledges some patients benefit. Effect is slow (takes 4–6 weeks) but may last 6–12 months
Platelet-rich plasma (PRP)	Concentrated growth factors (PDGF, TGF-β, VEGF) from autologous blood → promote tissue healing and modulate inflammation	Mild-moderate OA; increasingly offered in sports medicine clinics	?evidence ^[3]. RCTs show variable results. Not recommended in most international guidelines as standard of care. Not covered by public healthcare in HK

Operative management ^[3]:

Indications:
- Patient factor: age, functional status
- Disease factor: severe impairment to ADL, pain despite conservative treatment

Procedure	Indication	Mechanism	Key Details
Osteotomy	Young ( < 60y) with preservation of articular cartilage. Pre-requisite: single compartment disease ^[3]	Realigns the mechanical axis to shift load from the damaged compartment to the healthy one → reduces pain and delays need for arthroplasty	High tibial osteotomy for medial compartment OA with varus malalignment ^[3]. C/I: severe articular damage, ligament laxity, severe varus deformities ^[3]. Buys time in younger patients — bridge to eventual arthroplasty
Total knee replacement (TKR)	Older patients with progressive joint destruction ^[3]. Failed conservative management. Severe pain limiting daily activities. Radiographic KL grade 3–4	Replaces all three compartments with metal and polyethylene components → eliminates bone-on-bone contact → pain relief	Old preferred: reduced chance of revision surgery ^[3]. Prosthesis lifespan typically > 15–20 years with modern implants. 90–95% patient satisfaction
Unicompartmental knee arthroplasty (UKA)	Isolated medial or lateral compartment OA with intact ACL, correctable deformity, adequate ROM	Replaces only the affected compartment → preserves more native bone and ligaments → more physiological kinematics	Unicompartmental knee arthroplasty for medial compartment OA, higher revision rate compared to TKR ^[3]. Less invasive, faster recovery, but stricter patient selection
Arthroscopic debridement	Remove osteophytes ^[3], loose bodies	Removes mechanical irritants	Evidence for isolated debridement in OA is poor (the Moseley RCT showed no benefit over sham surgery). Primarily indicated for specific mechanical symptoms (loose bodies, locked knee)
Arthrodesis	Small joints (e.g., MCP) ^[3]. Rarely used for the knee (last resort after failed arthroplasty + infection)	Fuses the joint → eliminates pain but also eliminates movement	Gives a pain-free, stable but not mobile joint ^[21]. Functionally very limiting for the knee — patients cannot bend the knee at all

Role of surgery in joint disease ^[21]:

Aim: to achieve a joint that is (1) pain free (2) stable (3) mobile
Priority of surgical Tx: LL before UL (affects mobility); Forefoot/ankle then knee then hip (affects stability for rehab) ^[21]
Re-alignment osteotomy: used for young patients with OA knee and genu varum → ↓stress on diseased joint and delay arthroplasty. Gives pain-free, stable, and mobile joint ^[21]
Joint replacement: most reliable method to give a pain-free, stable, and mobile joint. Limited lifespan (usually > 15y) due to aseptic loosening (due to periarticular foreign body reaction resulting in osteolysis and loosening) ^[21]

This is the one condition where delay is unacceptable. Bacterial infection can destroy joint cartilage in a few days ^[9].

Management principles:

Urgent joint aspiration — both diagnostic AND therapeutic (decompresses the joint, reduces bacterial load)
Empirical IV antibiotics — immediately after aspiration (do NOT wait for culture results)
Surgical drainage / washout — arthroscopic or open, especially if no improvement in 48–72h
Serial monitoring — repeat aspirations, inflammatory markers, clinical assessment

Step	Detail
1. Aspirate	Send for Gram stain, culture + sensitivity, cell count, crystals. Decompress the joint — reduces intra-articular pressure and pain
2. Empirical IV antibiotics	Flucloxacillin 2g QDS IV (covers S. aureus, the most common organism). Add gentamicin if Gram-negative suspected (elderly, immunocompromised, IVDU). Switch to targeted therapy once culture + sensitivity available. Duration: typically 2 weeks IV then 4 weeks oral (total 6 weeks, adjusted by clinical response)
3. Surgical drainage	Arthroscopic washout is preferred for the knee — allows thorough lavage + debridement of infected tissue while preserving the joint. Open arthrotomy if arthroscopic drainage fails or is technically difficult
4. Supportive	Analgesia, splinting for comfort (short-term only — prolonged immobilisation leads to stiffness), early mobilisation once infection controlled
5. Monitor	Serial CRP/ESR (should trend downward), repeat aspiration if effusion re-accumulates, clinical assessment of fever + joint

Why IV then oral? The joint space is relatively avascular (synovial membrane has no basement membrane but cartilage is avascular). High-dose IV antibiotics achieve adequate penetration into the synovial fluid. Once clinical improvement is established and the bacteraemia is cleared, oral bioavailable antibiotics (e.g., oral flucloxacillin, clindamycin) can maintain adequate joint levels. The OVIVA trial (2019) demonstrated that oral antibiotics are non-inferior to IV for bone and joint infections after initial IV loading — early oral switch (at 1 week rather than 2) is now acceptable in stable patients.

C. Crystal Arthritis

Goals: Rapid pain relief + resolution of inflammation. Do NOT start urate-lowering therapy (ULT) during an acute flare (it can paradoxically worsen the attack by shifting the urate equilibrium and triggering further crystal shedding).

Treatment	Mechanism	Regimen	Key Points
Colchicine	Binds tubulin → inhibits microtubule polymerisation → impairs neutrophil chemotaxis, adhesion, and NLRP3 inflammasome activation → ↓IL-1β release	Low-dose: 0.5 mg TDS for 2–4 days (AGREE trial showed low-dose is as effective as high-dose with far fewer GI side effects)	Must start within 12–36h of onset for best effect. Side effects: diarrhoea, nausea, vomiting (dose-dependent). C/I: severe renal impairment (accumulates), concurrent strong CYP3A4 or P-gp inhibitors (macrolides, cyclosporine — risk of fatal toxicity)
NSAIDs	COX inhibition → ↓prostaglandin-mediated inflammation	Naproxen 500 mg BD, indomethacin 50 mg TDS. Full dose, short course (until flare resolves)	First-line if no contraindication. Co-prescribe PPI. Avoid in CKD, heart failure, PUD
Systemic corticosteroids	Broadly suppress inflammatory gene transcription via glucocorticoid receptor → ↓cytokines, ↓neutrophil recruitment	Prednisolone 30–35 mg/day for 5 days (OARSI/BSR) or equivalent methylprednisolone	Used when NSAIDs and colchicine are contraindicated (e.g., CKD + concurrent CYP3A4 inhibitor). No taper needed for short courses
Intra-articular corticosteroid injection	Same as systemic but localised → avoids systemic side effects	Triamcinolone acetonide (1 mL, 40 mg) mixed with 1–2 mL 1% lidocaine for large joints ^[6]	Thorough joint aspiration + intra-articular glucocorticoid injection if only 1–2 joints involved ^[6]. Must r/o septic arthritis before injection ^[6]. Effect: usually provides relief of pain/swelling ≤ 8–24h ^[6]
IL-1 inhibitors (e.g., anakinra, canakinumab)	Directly block IL-1β → the key cytokine in gouty inflammation	Anakinra 100 mg SC daily × 3–5 days	Third-line — reserved for refractory flares or patients who cannot take any of the above

Goal: Reduce serum urate to < 360 μmol/L ( < 6 mg/dL), or < 300 μmol/L ( < 5 mg/dL) if tophi present → dissolve existing crystals → prevent flares.

Drug	Mechanism	Indication	Key Points
Allopurinol	Xanthine oxidase inhibitor → blocks conversion of hypoxanthine → xanthine → uric acid	First-line ULT	Start low (100 mg/day, 50 mg if CKD), titrate slowly (every 2–4 weeks) to target. Must co-prescribe flare prophylaxis (colchicine 0.5 mg OD–BD or NSAID) for first 3–6 months. Serious S/E: allopurinol hypersensitivity syndrome (DRESS/SJS) — strongly associated with *HLA-B5801 (prevalent in ~6–8% HK Chinese — screen before starting!**)
Febuxostat	Non-purine selective xanthine oxidase inhibitor	Second-line if allopurinol intolerant/ineffective	More potent than allopurinol at equivalent doses. CARES trial raised concerns about CV mortality — use with caution in patients with established CVD. Does NOT require HLA-B*5801 screening
Probenecid / Benzbromarone	Uricosuric agents → block urate reabsorption in proximal tubule (URAT1 transporter) → ↑renal urate excretion	Alternative/adjunct in patients with inadequate response to xanthine oxidase inhibitors	C/I in CKD (probenecid ineffective at GFR < 50), history of urolithiasis. Ensure adequate hydration to prevent uric acid stone formation
Pegloticase	Pegylated recombinant uricase → converts uric acid to allantoin (highly soluble)	Severe refractory tophaceous gout	IV infusion Q2 weeks. Very expensive. Risk of infusion reactions and anti-drug antibodies

HLA-B*5801 Screening — Essential in HK!

In Hong Kong, HLA-B5801 prevalence is approximately 6–8% in ethnic Chinese. This allele is strongly associated with allopurinol hypersensitivity syndrome (DRESS, SJS/TEN) — a potentially fatal drug reaction. **All patients must be screened for HLA-B5801 before starting allopurinol.** If positive, do NOT prescribe allopurinol — use febuxostat instead.

Management ^[6]:

Correction of underlying cause, e.g., hyperparathyroidism
Acute pseudogout:
- Supportive measures: ice pack, immobilisation, joint rest for 48–72h
- Thorough joint aspiration + intra-articular glucocorticoid injection if only 1–2 joints involved
- Systemic anti-inflammatory drug if > 2 joints involved

Why is there no "urate-lowering therapy equivalent" for pseudogout? There is no drug that effectively dissolves CPPD crystals once deposited. Unlike gout (where reducing serum urate dissolves MSU crystals), pyrophosphate metabolism cannot be pharmacologically targeted in a practical way. Management is therefore purely symptomatic (anti-inflammatory) plus correcting any identifiable metabolic cause.

Treatment	Detail
Joint aspiration	Both diagnostic and therapeutic — removing inflammatory fluid and crystals reduces pain
Intra-articular steroid	As for gout — triamcinolone acetonide for 1–2 joints
NSAIDs / Colchicine	Oral anti-inflammatory options for multi-joint involvement; low-dose colchicine (0.5 mg BD) effective as prophylaxis in recurrent pseudogout
Systemic corticosteroids	If NSAIDs and colchicine contraindicated
Treat underlying metabolic cause	Haemochromatosis (phlebotomy), hyperparathyroidism (parathyroidectomy), hypomagnesaemia (Mg supplementation)

D. Ligament Injuries

Management ^[3]:

Conservative: preferred for < 1 cm meniscal tear
- RICE
- Analgesics
- Rehabilitation: encourage ROM, muscle strengthening
Operative: arthroscopic surgery
- Indications: failed conservative treatment, bucket-handle tear, associated ligament injury, locked knee
- Meniscal repair with suture: indicated if outer 1/3 (good vascular supply), vertical tear ^[3]
- Partial meniscectomy: indicated if inner 1/3 (e.g., radial tear, horizontal tear) ^[3]
- Either one if middle 1/3 ^[3]

Complications of knee arthroscopy: damage to saphenous nerve and vein, peroneal nerve, popliteal vessels ^[3].

Surgical Decision	Zone	Rationale
Meniscal repair (suture)	Outer 1/3 (red-red zone)	This zone has blood supply from the perimeniscal capillary plexus → the sutured tear receives nutrients and inflammatory mediators necessary for healing
Partial meniscectomy	Inner 2/3 (white-white zone)	This zone is avascular → sutured tissue cannot heal → must excise the torn fragment. Preserve as much meniscus as possible (total meniscectomy → accelerated OA)
Either	Middle 1/3 (red-white zone)	Variable vascularity → surgeon judges intra-operatively based on tissue quality

Why preserve meniscal tissue? The meniscus absorbs ~50% of load in extension and ~85% in flexion. Total meniscectomy dramatically increases contact stress on the tibial plateau → accelerated cartilage wear → secondary OA within 10–20 years. This is why partial meniscectomy (removing only the torn fragment) and repair (whenever possible) are preferred.

F. Inflammatory Arthritis (RA, Spondyloarthropathy)

Management of RA and SpA at the knee is part of systemic disease management. The knee-specific principles are:

Component	Detail
Pharmacological — systemic	DMARDs (methotrexate as anchor drug), biologics (anti-TNF, anti-IL-6, anti-CD20), JAK inhibitors. Treat-to-target strategy: aim for remission or low disease activity
Joint-specific	Intra-articular steroid injection for isolated knee flare (triamcinolone). Physiotherapy to maintain ROM and strength
Surgery ^[21]	Aim: pain-free, stable, mobile joint. Options: Synovectomy (early disease), re-alignment osteotomy (young OA knee + genu varum), joint replacement (progressive joint destruction)

G. Periarticular Conditions

Scenario	Management
Non-septic	Conservative: activity modification (stop kneeling), ice, compression, NSAIDs. Aspiration if tense. Steroid injection if refractory (but risk of skin atrophy over patella)
Septic	Aspiration + culture. Antibiotics (oral flucloxacillin if mild; IV if systemic toxicity). Surgical drainage (incision and drainage or bursectomy) if refractory

Step	Treatment
1	Activity modification (reduce jumping/loading), relative rest
2	Eccentric decline squat protocol (the gold standard exercise) — progressively loading the tendon eccentrically promotes collagen remodeling and alignment
3	Extracorporeal shock wave therapy (ESWT) for refractory cases
4	PRP injection (emerging evidence, not standard)
5	Surgery (debridement of degenerate tissue) — last resort

Fracture	Management
Patella fracture — non-displaced, intact extensor mechanism	Conservative: Cylinder cast or knee brace in extension × 4–6 weeks. Progressive ROM exercises
Patella fracture — displaced ( > 2 mm step/gap) or disrupted extensor mechanism	Operative: ORIF (tension band wiring — converts the distractive quadriceps force into a compressive force at the fracture site, promoting healing)
Tibial plateau fracture — non-displaced	Conservative: Non-weight-bearing, hinged knee brace, early ROM
Tibial plateau fracture — displaced/depressed	Operative: ORIF with plates and screws ± bone grafting. Goals: restore articular congruity, alignment, and stability

Condition	Management
Osgood–Schlatter disorder ^[1]	Self-limiting — resolves when tibial apophysis fuses. Activity modification, ice after exercise, patellar tendon strap, hamstring/quadriceps stretching. Very rarely needs surgery
Perthes disease	Non-operative for age < 8y (do not benefit from surgery): PT (ROM exercise), activity restriction (non-weight-bearing). Operative for age > 8y: femoral/pelvic osteotomy
SCFE	Operative: percutaneous in situ fixation ± prophylactic contralateral hip fixation

Condition	First-Line	Second-Line	When to Operate
OA	Weight loss + exercise + PT	Paracetamol → topical NSAID → oral NSAID → IA steroid	Pain despite maximal conservative Rx; severe functional limitation; KL 3–4
Septic arthritis	Urgent aspiration + IV antibiotics	Arthroscopic washout	Immediately if suspected — no delay
Gout (acute)	Colchicine / NSAID / steroid	IA steroid for 1–2 joints	Not applicable (medical management)
Gout (chronic)	Allopurinol (screen HLA-B*5801 first)	Febuxostat → uricosurics → pegloticase	Not applicable
Pseudogout	Aspiration + IA steroid / NSAID	Correct metabolic cause	Not applicable
ACL tear	RICE → PT for low-demand patients	—	Active patient, instability, combined ligament injury → ACL reconstruction
Meniscal tear	RICE → PT for < 1 cm, no locking	—	Locked knee, bucket-handle, failed conservative → arthroscopic repair/meniscectomy
MCL	RICE → brace → PT	—	Grade III with distal avulsion on MRI
ITBS	Activity modification → PT → steroid injection	—	Failed conservative for 6 months → IT band release
Bursitis	Activity modification → aspiration → antibiotics if septic	—	Septic bursitis failing antibiotics → bursectomy

High Yield Summary - Management

OA management is stepwise: Non-pharmacological (weight loss, exercise, PT) → Pharmacological (paracetamol → topical NSAID → oral NSAID → weak opioid) → Injections (IA steroid, viscosupplementation) → Surgery (osteotomy for young/unicompartmental; TKR for elderly/end-stage).
Septic arthritis: Urgent aspiration + IV antibiotics + surgical drainage. Never delay. Flucloxacillin covers S. aureus. Total treatment ~6 weeks.
Gout flare: Colchicine (low-dose), NSAIDs, or corticosteroids. ULT (allopurinol) started after flare with flare prophylaxis for 3–6 months. Screen HLA-B*5801 before allopurinol in HK Chinese patients.
ACL: Reconstruction (NOT repair) for active patients. Conservative for low-demand patients. Timing: after haemarthrosis resolves.
Meniscal tears: Outer 1/3 = repair; inner 2/3 = partial meniscectomy. Preserve as much meniscus as possible. Surgery for locked knee, bucket-handle tear, or failed conservative management.
Osteotomy vs TKR: Osteotomy for young patients ( < 60) with single-compartment disease and preserved cartilage. TKR for older patients with end-stage multi-compartment disease.
Always rule out septic arthritis before injecting steroid into any joint.
Joint replacement lifespan ~15+ years — limited by aseptic loosening from periarticular foreign body reaction causing osteolysis.

Active Recall - Management of Knee Pain

A. Complications of Underlying Conditions

OA is a chronic, irreversible, progressive disease. If left untreated or inadequately managed:

Complication	Pathophysiological Mechanism
Progressive cartilage loss → bone-on-bone articulation	Ongoing imbalance between cartilage synthesis and degradation → complete loss of articular cartilage → exposed subchondral bone → bone-on-bone contact → severe pain, crepitus, loss of function
Fixed flexion deformity	Chronic inflammation → posterior capsule fibrosis and shortening → the knee cannot be passively extended beyond a certain point. Why posterior capsule? Because the knee naturally rests in slight flexion when painful (antalgic posture), and prolonged immobilisation in this position → adaptive shortening
Varus or valgus deformity	Asymmetric cartilage loss → medial compartment loss (more common) → progressive varus angulation (bow-legged). This further concentrates load on the medial side → accelerates medial wear → self-perpetuating vicious cycle
Quadriceps atrophy and weakness	Pain → reflex quadriceps inhibition (arthrogenic muscle inhibition) → disuse atrophy → loss of dynamic knee stability → functional decline → falls in elderly
Reduced mobility and systemic consequences	Immobility from knee OA → cardiovascular deconditioning, obesity (worsening the OA), depression, social isolation, increased all-cause mortality in elderly. OA is not "just a joint problem" — it is a systemic health burden
Secondary OA from other conditions	Untreated meniscal tears, ACL deficiency, crystal arthropathy, and haemophilic arthropathy all lead to secondary OA as their end-stage complication

Bacterial infection can destroy joint cartilage in a few days ^[9]. This is why septic arthritis is the most feared complication-generating condition:

Complication	Mechanism
Irreversible cartilage destruction	Neutrophil-derived proteases (MMPs, elastase) + bacterial toxins directly degrade the cartilage matrix. Cartilage is avascular → once destroyed, it cannot regenerate → permanent loss of articular surface
Osteomyelitis	Contiguous spread of infection from the joint into the subchondral bone → chronic bone infection that is extremely difficult to eradicate (bone has limited blood supply in areas of necrosis → antibiotic penetration is poor)
Secondary OA	Even with successful eradication of infection, the damaged cartilage surface leads to accelerated degenerative change
Sepsis and multiorgan failure	Bacteraemia from the infected joint → systemic inflammatory response → septic shock → organ failure. Mortality of untreated septic arthritis is significant (up to 10–15% even with treatment in elderly/immunocompromised)
Joint ankylosis	Severe inflammation → intra-articular adhesions and fibrosis → loss of motion → functional ankylosis (fibrous union)

3. Ligament Injuries — Instability and Secondary Damage

Complication	Mechanism
Locked knee	Bucket-handle tear — a large longitudinal tear where the central fragment displaces into the intercondylar notch → physically blocks knee extension. A true mechanical lock (not pseudo-locking from pain). Requires urgent arthroscopic reduction/meniscectomy ^[3]
Persistent effusion	Torn meniscal fragment irritates the synovium → chronic reactive synovitis → persistent effusion
Secondary OA	Loss of meniscal tissue (whether from the tear itself or from meniscectomy) → reduced load distribution → increased point stress on articular cartilage → accelerated degeneration. This is why meniscal preservation (repair over meniscectomy) is emphasised whenever possible

5. Crystal Arthritis — Chronic Joint Destruction

Complication	Mechanism
Chronic tophaceous gout	Persistent hyperuricaemia → MSU crystal deposition in periarticular tissues, tendons, bursae, subcutaneous tissue → formation of tophi (organised granulomatous aggregates of MSU crystals surrounded by macrophages). Tophi can be disfiguring, ulcerate through skin, and destroy underlying bone
Erosive arthropathy	Tophi erode bone from the periarticular surface → characteristic "punched-out" erosions with overhanging edges on X-ray → progressive joint destruction → secondary OA
Uric acid nephrolithiasis	Hyperuricaemia → supersaturation of uric acid in urine (especially in acidic urine) → stone formation. Uric acid stones are radiolucent (cannot be seen on plain X-ray but visible on CT)
Urate nephropathy	Chronic: urate crystal deposition in renal medullary interstitium → chronic tubulointerstitial nephritis → CKD. Acute: massive urate load (e.g., tumour lysis syndrome) → uric acid crystal precipitation in renal tubules → acute oliguric renal failure
Gout → patellar bursitis ^[1]	MSU crystal deposition in the prepatellar bursa → crystal-induced bursitis mimicking or coexisting with septic bursitis

Complication	Mechanism
Chronic pyrophosphate arthropathy	Chronic CPPD crystal deposition → progressive cartilage destruction resembling severe OA but with distinctive distribution (knee, wrist, MCP) → the so-called "pseudo-OA" pattern
Crowned dens syndrome	CPPD crystal deposition around the odontoid process → acute neck pain and stiffness mimicking meningitis or polymyalgia rheumatica

Tibial shaft/plateau fractures — complications ^[3]:

Compartment syndrome ^[3] — 6 Ps: Pain (out of proportion, exacerbated by passive dorsiflexion of great toe — earliest and most sensitive), Pressure, Pallor, Pulselessness, Paraesthesia, Paralysis

Compartment syndrome explained from first principles ^[22]^[23]:

Mechanism: Prolonged ischaemia when cell membrane is damaged and fluid leaks out into interstitial space in the muscle which are enclosed within a non-distensible fascial envelope ^[22]. Alternatively, post-ischaemic compartment syndrome occurs after revascularisation: ischaemic muscle → formation of oxygen free radicals → damage capillary walls → increased vascular permeability upon reperfusion → localised swelling and oedema → increased compartment pressure ^[22].

Aspect	Detail
Critical pressure	Secondary ischaemia when pressure ≥ 30 mmHg or within 30 mmHg of diastolic BP ^[23]
Most commonly affected	Anterior compartment of the leg (contains tibialis anterior, extensor hallucis longus, deep peroneal nerve) ^[22]
Most devastating	Posterior compartment involvement (contains the posterior tibial artery and tibial nerve — loss leads to foot ischaemia and sensory loss in the sole) ^[22]
Earliest symptom	Pain out of proportion to clinical situation ^[23]
Most sensitive sign	Pain with passive stretch (dorsiflexion of great toe stretches the deep posterior compartment / plantarflexion stretches the anterior compartment) ^[23]
Management	Emergent fasciotomy → lay open for oedema to resolve, then close after a few days. Consider prophylactic fasciotomy in OT if drastic ischaemia ^[23]

If untreated → ischaemia, necrosis, fibrosis → subsequent contraction of Achilles tendon ^[7] (Volkmann's ischaemic contracture equivalent in the lower limb).

Other fracture complications:

Limb ischaemia ^[3] — popliteal artery injury in knee dislocations or proximal tibial fractures
Malunion/non-union ^[3]
DVT/PE — fractures immobilise the limb → Virchow's triad (stasis + endothelial injury from fracture + hypercoagulability from trauma response) → venous thromboembolism
Infection — especially in open fractures which are common in tibial fractures due to lack of significant soft tissue protection (especially anteromedial side) ^[3]
Post-traumatic OA — articular fractures (tibial plateau) that are not anatomically reduced → step-off in the articular surface → point-loading → secondary OA

B. Complications of Treatment

Specific complications of total replacement ^[3]:

Timing	Complication	Mechanism
Immediate	Bone fracture	Intra-operative fracture during bone cuts or component impaction, especially in osteoporotic bone
Immediate	Vascular injury (popliteal artery in TKR) ^[3]	The popliteal artery lies posterior to the knee — at risk during posterior capsule release or during cementation when the knee is hyperflexed
Immediate	Nerve injury (CPN in TKR) ^[3]	The common peroneal nerve wraps around the fibular neck and can be stretched during correction of a fixed valgus or flexion deformity → foot drop. Incidence ~0.3–1.3%
Early	DVT/PE ^[3]	Virchow's triad: tourniquet use → stasis; surgical trauma → endothelial injury; post-operative immobility → stasis. All TKR patients receive thromboprophylaxis (LMWH, DOACs, or aspirin)
Early	Infection (difficult to detect and treat) ^[3]	Prosthetic joint infection (PJI) — bacteria form biofilms on the prosthetic surface → resistant to antibiotics and immune clearance. Early infection ( < 3 months): usually from intra-operative contamination (S. aureus, S. epidermidis). Presents with wound erythema, persistent drainage, fever
Late	Prosthesis infection ^[3]	Late haematogenous seeding (from dental procedures, UTI, skin infections) → biofilm formation → chronic PJI. May need two-stage revision (remove prosthesis → antibiotic spacer → 6 weeks IV antibiotics → re-implant)
Late	Patellar instability ^[3]	Malrotation of the components (internal rotation of tibial or femoral components) → patellar maltracking → subluxation or dislocation
Late	Aseptic loosening	Limited lifespan (usually > 15 years) due to aseptic loosening (due to periarticular foreign body reaction resulting in osteolysis and loosening) ^[21]. Polyethylene wear particles → macrophage phagocytosis → release of TNF-α, IL-1, IL-6 → osteoclast activation → periprosthetic bone resorption → component loosening → pain and instability → requires revision surgery
Late	Periprosthetic fracture	Bone around the prosthesis is stressed at the tip of the implant (stress riser) + osteoporotic bone → fracture adjacent to the prosthesis. Difficult to fix surgically

Why does aseptic loosening happen? Every step generates microscopic polyethylene (plastic) wear debris from the bearing surface. These particles are small enough (0.1–10 μm) to be phagocytosed by macrophages but too inert to be digested → frustrated phagocytosis → chronic inflammatory response → cytokine release → osteoclast recruitment → bone resorption around the implant → the implant becomes loose in its bony bed.

Post-op care ^[3]:

Early mobilisation (1 day after operation)
Avoid contact sports, extreme ROM of hip (angle of bed < 45°)
Survival of replacement (not requiring revision surgery): 15–20 years

Complications of knee arthroscopy: damage to saphenous nerve and vein, peroneal nerve, popliteal vessels ^[3].

Complication	Mechanism
Saphenous nerve/vein injury	Medial portal placement → the saphenous nerve and its infrapatellar branch run medially → direct injury during portal insertion. Results in medial knee/leg numbness
Common peroneal nerve injury	Lateral portal placement or manipulation near the fibular neck → nerve stretch or direct injury → foot drop
Popliteal vessel injury	Posterior meniscal work → instruments can penetrate posteriorly → popliteal artery/vein injury. Extremely rare but catastrophic
Infection	Post-arthroscopic septic arthritis (~0.1–0.4%) — lower risk than open surgery but still possible
Haemarthrosis	Damage to intra-articular vasculature → blood accumulation → pain and swelling
Arthrofibrosis	Excessive scar tissue formation post-operatively → stiffness and loss of ROM
DVT/PE	Lower risk than TKR but still possible, especially with tourniquet use

Drug Class	Complications	Mechanism
NSAIDs	GI ulceration/bleeding, AKI, cardiovascular events, hypertension, fluid retention	COX-1 inhibition → ↓protective prostaglandins in gastric mucosa → erosion + ulceration. Renal prostaglandin inhibition → ↓afferent arteriolar dilatation → ↓GFR. COX-2 inhibition → prothrombotic imbalance (↓prostacyclin, ↑thromboxane)
Colchicine	Diarrhoea (dose-dependent), bone marrow suppression (overdose), fatal toxicity with CYP3A4 inhibitors	Binds tubulin → inhibits mitotic spindle → affects rapidly dividing cells (GI mucosa, bone marrow). No antidote for overdose
Corticosteroids (systemic, prolonged)	Osteoporosis, AVN, hyperglycaemia, infection, Cushing's, adrenal suppression, myopathy	Steroids stimulate osteoclasts + inhibit osteoblasts → bone loss. AVN: mechanism uncertain but may involve fat embolism to subchondral vessels or direct lipocyte hypertrophy → increased intraosseous pressure
Corticosteroids (intra-articular, repeated)	Accelerated cartilage loss, post-injection flare, septic arthritis (if contaminated), soft tissue atrophy	Steroids are catabolic to cartilage matrix at high local concentrations → chondrocyte apoptosis. Recommended limit: 3–4 injections per joint per year
Allopurinol	Allopurinol hypersensitivity syndrome (DRESS/SJS/TEN) — associated with *HLA-B5801** (prevalent ~6–8% in HK Chinese)	Immune-mediated type IV hypersensitivity → widespread skin and organ involvement. Mortality 20–25% for SJS/TEN. *Must screen HLA-B5801 before starting**
Methotrexate (for RA)	Hepatotoxicity, myelosuppression, interstitial pneumonitis, teratogenicity	Folate antagonist → impairs DNA synthesis in rapidly dividing cells. Supplement with folic acid to reduce side effects
Biologic DMARDs (anti-TNF)	Serious infections (TB reactivation, opportunistic infections), demyelinating disease, heart failure exacerbation	TNF-α is critical for granuloma maintenance (containing TB) and defence against intracellular pathogens → inhibition → reactivation of latent infections. Screen for latent TB before starting

Complication	Mechanism
Under- or over-correction	Inaccurate pre-operative planning or intra-operative execution → residual malalignment or over-correction into opposite deformity
Non-union / delayed union	Inadequate fixation, poor blood supply, smoking → failure of osteotomy site to heal
Neurovascular injury	Peroneal nerve at risk in lateral closing-wedge high tibial osteotomy; popliteal vessels at risk posteriorly
Compartment syndrome	Oedema from surgical trauma in a tightly fascial-bound compartment
Stiffness	Post-operative immobilisation → adhesions and capsular contracture

Regardless of the cause, severe knee pain leading to immobility has its own cascade of complications — particularly in the elderly:

Complication	Mechanism
Venous thromboembolism (DVT/PE)	Immobility → venous stasis (Virchow's triad)
Muscle atrophy	Disuse → rapid quadriceps wasting (measurable within 1 week of immobilisation)
Joint contracture	Prolonged flexed position → adaptive shortening of hamstrings and posterior capsule → fixed flexion deformity
Pressure sores	Immobility + poor nutrition → skin breakdown over bony prominences
Depression and social isolation	Pain → inability to participate in activities → psychological deterioration. Depression is listed as a masquerade for knee pain ^[1] — it can both cause and result from chronic knee pain
Falls and fractures	Quadriceps weakness + impaired proprioception → balance impairment → falls → hip fractures (especially in osteoporotic elderly)
Cardiovascular deconditioning	Reduced physical activity → worsened cardiovascular fitness → increased all-cause mortality

High Yield Summary - Complications

Septic arthritis can destroy cartilage within days → irreversible joint damage, osteomyelitis, sepsis, ankylosis. This is why it is treated as an emergency.
TKR complications by timing: Immediate (fracture, popliteal artery injury, CPN palsy) → Early (DVT/PE, infection) → Late (aseptic loosening, prosthesis infection, periprosthetic fracture, patellar instability). Prosthesis survives 15–20 years; aseptic loosening from polyethylene wear particle-induced osteolysis is the main long-term failure mode.
Compartment syndrome: Pain out of proportion (earliest symptom), pain with passive stretch (most sensitive sign). Pressure ≥ 30 mmHg or within 30 mmHg of diastolic BP. Treatment: emergent fasciotomy. Anterior compartment most commonly affected; posterior compartment most devastating.
ACL deficiency → secondary meniscal and chondral damage → early OA. ACL reconstruction complications include graft failure, arthrofibrosis, and donor site morbidity.
Haemophilic arthropathy: Target joint concept — prior bleed → synovial hypertrophy → predisposes to further bleeding → progressive cartilage destruction → secondary OA.
Baker's cyst rupture mimics DVT — always differentiate with duplex USG.
Allopurinol hypersensitivity (DRESS/SJS/TEN) — screen HLA-B*5801 before prescribing in HK Chinese patients.
Immobility from knee pain itself causes DVT, contracture, atrophy, falls, depression, and cardiovascular deconditioning — a major driver of morbidity in the elderly.

Active Recall - Complications of Knee Pain Conditions and Treatments

High Yield Summary

OA is the commonest cause of knee pain in HK, especially in the elderly. Key radiographic features = LOSS (Loss of joint space, Osteophytes, Subchondral cysts, Subchondral sclerosis). Kellgren-Lawrence grading system classifies severity (Grade 0–4). Always assess all 3 compartments with appropriate views.
Anatomy dictates presentation: Medial meniscus tears are more common (attached to MCL); ACL injuries cause haemarthrosis within 2 hours; Baker's cysts arise from underlying joint disease and can rupture to mimic DVT.
Septic arthritis is an emergency: Hot, swollen, tender joint = septic arthritis until proven otherwise. Knee is the most common site. S. aureus is the most common organism.
Crystal arthritis: Gout (MSU crystals, negatively birefringent) vs. pseudogout (CPPD crystals, positively birefringent, chondrocalcinosis on X-ray). Always screen for metabolic causes of CPPD in young patients.
In children, always examine the hip: SCFE and Perthes disease refer pain to the knee via the obturator nerve. Know the age-related differential.
IT band syndrome: Most common cause of lateral knee pain. Pain at 30° flexion over lateral femoral condyle.
Meniscal tear management depends on zone: outer 1/3 = repair; inner 2/3 = partial meniscectomy. Bucket-handle tears and locked knees need surgery.
Masquerades: Always consider referred pain from hip/spine, depression, diabetes (Charcot arthropathy, neuropathy), and psychogenic factors.

High Yield Summary - Differential Diagnosis

Murtagh's framework: Probability (OA, ligament sprains, patellofemoral syndrome, bursitis) → Serious (septic arthritis, DVT, malignancy, RA, ACL tear) → Pitfalls (referred pain from hip/spine, osteochondritis dissecans, meniscal tears, pseudogout, Baker's cyst) → Masquerades (depression, diabetes, spinal dysfunction).
Septic arthritis: Always the #1 diagnosis to exclude in a hot, swollen joint. Aspirate first, ask questions later. Can coexist with crystals.
Crystal arthritis: Gout = needle-shaped, negative birefringence; Pseudogout = rhomboid, positive birefringence. Pseudogout favours the knee. Always screen for metabolic causes of CPPD in young patients.
Inflammatory vs. mechanical: Morning stiffness > 30 min, improvement with activity, systemic features → inflammatory. Morning stiffness < 30 min, worsens with activity, no systemic features → mechanical/degenerative.
Referred pain: Hip pathology (via obturator nerve L2–L4) and lumbar spine pathology (radiculopathy, neurogenic claudication) are the most commonly missed causes of knee pain. Always examine the hip and spine.
Age-specific: Children — septic arthritis, Perthes, SCFE, Osgood-Schlatter, bone tumours. Young adults — ligament injuries, patellofemoral syndrome. Middle-aged — degenerative meniscal tears, early OA, gout. Elderly — OA, crystal arthritis, insufficiency fractures, malignancy.
Joint aspiration is the definitive investigation in acute monoarthritis — analyse for cell count, crystals, Gram stain, and culture.

High Yield Summary - Diagnosis and Investigations

Joint aspiration is the MOST IMPORTANT test in an acutely swollen knee. It differentiates septic from crystal from inflammatory from non-inflammatory causes. Always send for cell count, crystals, Gram stain, and culture simultaneously.
Crystal identification: Gout = needle-shaped, strongly negative birefringent. Pseudogout = rhomboid, weakly positive birefringent. Finding crystals does NOT exclude coexisting infection — always send cultures.
OA is a clinical-radiological diagnosis: LOSS on X-ray (Loss of joint space, Osteophytes, Subchondral cysts, Subchondral sclerosis). Kellgren-Lawrence grades 0–4. Weightbearing AP and Schuss view are more sensitive than supine films.
CPPD diagnosis = arthrocentesis + X-ray: Definite = positive birefringent crystals + chondrocalcinosis on X-ray. Always screen metabolic causes (Ca, P, Mg, ALP, ferritin) afterwards.
MRI is the gold standard for soft tissue evaluation — meniscal tears, ligament injuries, AVN, bone marrow oedema, tumours. X-ray is first-line for bony pathology and fractures.
Serum urate in gout: Check 2 weeks AFTER resolution of acute flare (12–43% are normal/low during flare).
DVT workup: Modified Wells score → D-dimer if low probability; duplex USG if high probability or positive D-dimer.
Always X-ray the hip in a child with knee pain — SCFE and Perthes refer to the knee.

High Yield Summary - Management

OA management is stepwise: Non-pharmacological (weight loss, exercise, PT) → Pharmacological (paracetamol → topical NSAID → oral NSAID → weak opioid) → Injections (IA steroid, viscosupplementation) → Surgery (osteotomy for young/unicompartmental; TKR for elderly/end-stage).
Septic arthritis: Urgent aspiration + IV antibiotics + surgical drainage. Never delay. Flucloxacillin covers S. aureus. Total treatment ~6 weeks.
Gout flare: Colchicine (low-dose), NSAIDs, or corticosteroids. ULT (allopurinol) started after flare with flare prophylaxis for 3–6 months. Screen HLA-B*5801 before allopurinol in HK Chinese patients.
ACL: Reconstruction (NOT repair) for active patients. Conservative for low-demand patients. Timing: after haemarthrosis resolves.
Meniscal tears: Outer 1/3 = repair; inner 2/3 = partial meniscectomy. Preserve as much meniscus as possible. Surgery for locked knee, bucket-handle tear, or failed conservative management.
Osteotomy vs TKR: Osteotomy for young patients ( < 60) with single-compartment disease and preserved cartilage. TKR for older patients with end-stage multi-compartment disease.
Always rule out septic arthritis before injecting steroid into any joint.
Joint replacement lifespan ~15+ years — limited by aseptic loosening from periarticular foreign body reaction causing osteolysis.

High Yield Summary - Complications

Septic arthritis can destroy cartilage within days → irreversible joint damage, osteomyelitis, sepsis, ankylosis. This is why it is treated as an emergency.
TKR complications by timing: Immediate (fracture, popliteal artery injury, CPN palsy) → Early (DVT/PE, infection) → Late (aseptic loosening, prosthesis infection, periprosthetic fracture, patellar instability). Prosthesis survives 15–20 years; aseptic loosening from polyethylene wear particle-induced osteolysis is the main long-term failure mode.
Compartment syndrome: Pain out of proportion (earliest symptom), pain with passive stretch (most sensitive sign). Pressure ≥ 30 mmHg or within 30 mmHg of diastolic BP. Treatment: emergent fasciotomy. Anterior compartment most commonly affected; posterior compartment most devastating.
ACL deficiency → secondary meniscal and chondral damage → early OA. ACL reconstruction complications include graft failure, arthrofibrosis, and donor site morbidity.
Haemophilic arthropathy: Target joint concept — prior bleed → synovial hypertrophy → predisposes to further bleeding → progressive cartilage destruction → secondary OA.
Baker's cyst rupture mimics DVT — always differentiate with duplex USG.
Allopurinol hypersensitivity (DRESS/SJS/TEN) — screen HLA-B*5801 before prescribing in HK Chinese patients.
Immobility from knee pain itself causes DVT, contracture, atrophy, falls, depression, and cardiovascular deconditioning — a major driver of morbidity in the elderly.

Knee Pain

Knee Pain

Anatomy and Function

Etiology (Hong Kong Focus) and Pathophysiology

A. Degenerative / Wear-and-Tear

B. Traumatic / Mechanical

C. Inflammatory / Crystal Arthropathies

Septic Arthritis — A Rheumatological Emergency

E. Periarticular / Soft Tissue

H. Vascular

Classification

By Age (see Paediatric section above)

Clinical Features

A. Symptoms (with Pathophysiological Basis)

B. Signs (with Pathophysiological Basis)

Active Recall - Knee Pain: Definition, Epidemiology, Anatomy, Etiology, Classification, Clinical Features

Differential Diagnosis of Knee Pain

Structured Differential by Clinical Presentation

The "Must Not Miss" Differentials — Explained from First Principles

Differentiating Key Conditions — Side-by-Side Comparison

Active Recall - Differential Diagnosis of Knee Pain

References

Diagnostic Criteria for Key Conditions Causing Knee Pain

Investigation Modalities — Detailed Guide

Synovial Fluid Interpretation Table

C. Imaging

Active Recall - Diagnostic Criteria, Algorithm and Investigations for Knee Pain

Condition-Specific Management

A. Osteoarthritis of the Knee

C. Crystal Arthritis

D. Ligament Injuries

F. Inflammatory Arthritis (RA, Spondyloarthropathy)

G. Periarticular Conditions

Active Recall - Management of Knee Pain

A. Complications of Underlying Conditions

3. Ligament Injuries — Instability and Secondary Damage

5. Crystal Arthritis — Chronic Joint Destruction

B. Complications of Treatment

Active Recall - Complications of Knee Pain Conditions and Treatments

On this page

Knee Pain

Knee Pain

Definition

Epidemiology

Risk Factors

Anatomy and Function

Bony Anatomy

Menisci

Ligaments

Bursae

Muscles

Neurovascular

Alignment

Etiology (Hong Kong Focus) and Pathophysiology

A. Degenerative / Wear-and-Tear

1. Osteoarthritis (OA) — The Commonest Cause of Knee Pain in HK

2. Meniscal Degeneration

B. Traumatic / Mechanical

1. Meniscal Tears

2. Ligament Injuries

3. Patellar and Extensor Mechanism Injuries

4. Fractures Around the Knee

C. Inflammatory / Crystal Arthropathies

1. Gout

2. Pseudogout (CPPD Crystal Deposition Disease)

3. Rheumatoid Arthritis (RA)

4. Spondyloarthropathies

D. Infectious

Septic Arthritis — A Rheumatological Emergency

E. Periarticular / Soft Tissue

1. Iliotibial Band Syndrome (ITBS)

2. Prepatellar Bursitis ("Housemaid's Knee")

3. Pes Anserine Bursitis

4. Patellar Tendinopathy ("Jumper's Knee")

5. Baker's Cyst (Popliteal Cyst)

F. Referred Pain and Masquerades

G. Paediatric Causes (Age-Related)

H. Vascular

1. Osteonecrosis (Avascular Necrosis / AVN) [1]

2. Popliteal Artery Entrapment

I. Neoplastic

J. Other / Rare

Classification

By Anatomical Location

By Onset

By Age (see Paediatric section above)

By Mechanism

Clinical Features

A. Symptoms (with Pathophysiological Basis)

1. Pain

2. Swelling

3. Stiffness

4. Mechanical Symptoms

5. Reduced Function

6. Systemic Symptoms

B. Signs (with Pathophysiological Basis)

1. Inspection

2. Palpation

3. Range of Motion

4. Special Tests

5. Neurovascular Examination

Degenerative vs. Inflammatory Arthritis — A Key Distinction

Active Recall - Knee Pain: Definition, Epidemiology, Anatomy, Etiology, Classification, Clinical Features

References

Differential Diagnosis of Knee Pain

Murtagh's Diagnostic Strategy for Knee Pain

Structured Differential by Clinical Presentation

Step 1: Is it Monoarthritis or Polyarthritis?

Step 2: Acute vs. Chronic?

Step 3: Inflammatory vs. Non-Inflammatory (Mechanical)?

Step 4: Pattern of Joint Involvement

Step 5: Location-Based Differential

Step 6: Age-Based Differential

The "Must Not Miss" Differentials — Explained from First Principles

1. Septic Arthritis

2. DVT

3. Malignancy

4. Referred Pain from Hip or Spine

Differential Diagnosis Decision Flowchart

Differentiating Key Conditions — Side-by-Side Comparison