What are the differential diagnoses of knee pain and their typical signs and symptoms?

Differential Diagnoses of Knee Pain

The differential diagnosis of knee pain is broad and must be systematically approached by anatomic location, age, and mechanism of injury, with osteoarthritis, patellofemoral pain syndrome, and meniscal tears representing the most common etiologies in primary care. 1

Age-Stratified Approach to Common Diagnoses

Patients ≥45 Years Old

• Osteoarthritis is the most likely diagnosis when patients present with activity-related knee joint pain and less than 30 minutes of morning stiffness (95% sensitivity, 69% specificity) 1
• Clinical features include age >50 years, morning stiffness <30 minutes, crepitus, and bony enlargement (89% sensitive, 88% specific for underlying chronic arthritis) 2
• Pain is predominantly nociceptive with occasional nociplastic characteristics 3

Patients <40-45 Years Old

• Patellofemoral pain syndrome has a lifetime prevalence of approximately 25% in physically active individuals 1
• Anterior knee pain during squatting is 91% sensitive and 50% specific for this diagnosis 1
• Traumatic meniscal tears occur following acute twisting injuries in younger patients 1

Patients 40-70+ Years Old

• Degenerative meniscal tears affect approximately 12% of adults and often coexist with osteoarthritis 1
• Joint line tenderness is 83% sensitive and 83% specific for meniscal pathology 1
• McMurray test (knee rotation with extension) is 61% sensitive and 84% specific 1

Anatomic Location-Based Differential

Anterior Knee Pain

• Patellofemoral disorders: cartilage loss, subluxation/dislocation, friction syndrome 4
• Patellar tendinopathy 4
• Fat pad impingement syndromes and Hoffa's disease (enhancing synovitis >2mm in Hoffa's fat correlates with peripatellar pain) 4
• Deep infrapatellar bursitis 4
• Medial plicae 4
• Osteochondritis dissecans (OCD) 4

Medial Knee Pain

• Medial compartment osteoarthritis 4
• Medial meniscal tears 1
• Medial collateral ligament (MCL) bursitis: rare but important cause presenting as painful swelling over medial knee and proximal tibia, exacerbated by valgus stress 5

Lateral Knee Pain

• Iliotibial band syndrome 4
• Lateral meniscal tears 1
• Lateral compartment osteoarthritis 4

Posterior Knee Pain

• Popliteal (Baker's) cysts: often communicate with knee joint and may rupture 6
• Hamstring tendinopathy (general medical knowledge)

Critical Structural Pathologies

Bone and Cartilage Disorders

• Subchondral insufficiency fractures (previously termed spontaneous osteonecrosis): most commonly involve medial femoral condyle in middle-aged to elderly females, radiographs often initially normal 4
• Tibial stress fractures 4
• Osteochondritis dissecans with potential loose bodies 4
• Osteophytes 4

Soft Tissue Pathologies

• Ligamentous injuries: anterior cruciate ligament (Lachman test 74% sensitive, 95% specific), posterior cruciate ligament (81% sensitive, 95% specific) 2
• Adhesive capsulitis 4
• Discoid meniscus 4

Inflammatory and Neoplastic Conditions

• Pigmented villonodular synovitis 4
• Tumors and ganglion cysts 4
• Synovitis/effusion: bone marrow lesions and synovitis indicate origin of pain in osteoarthritis 4

Fracture Assessment

Apply Ottawa knee rules to determine need for radiography following trauma: age >55 years, tenderness at fibular head or patella, inability to bear weight for 4 steps, or inability to flex knee to 90 degrees 2

Critical Differential: Referred Pain

A major pitfall is failing to consider referred pain from the lumbar spine or hip before attributing all symptoms to knee pathology. 6, 7

• Lumbar spine pathology must be considered when knee radiographs are unremarkable and clinical evidence suggests spinal origin 6, 7
• Hip pathology can refer pain to the knee and should be evaluated if knee imaging is normal 6
• Thorough clinical examination of lumbar spine and hip should precede knee-focused imaging 6

Inflammatory Arthropathies (Must Exclude)

• Rheumatoid arthritis 3
• Spondyloarthropathies 3
• Pseudogout: plain films are neither sensitive nor specific for diagnosis 2
• Septic arthritis 3

Key Clinical Examination Findings by Diagnosis

Osteoarthritis

• Crepitus, bony enlargement, limited range of motion 2
• Morning stiffness <30 minutes 1, 2

Meniscal Tears

• Joint line tenderness (83% sensitive, 83% specific) 1, 2
• McMurray test (52% sensitive, 97% specific) 1, 2
• Mechanical symptoms (locking, catching) are not specific for surgical tears 1

Patellofemoral Pain

• Anterior knee pain with squatting 1
• Pain with patellar compression (general medical knowledge)

Ligamentous Injuries

• Lachman test superior to drawer sign for ACL tears 2
• Valgus/varus stress tests for collateral ligaments 5

Common Pitfalls to Avoid

• Do not overlook referred pain from hip or lumbar spine before attributing symptoms solely to knee pathology 6
• Avoid premature MRI: approximately 20% of patients with chronic knee pain undergo MRI without recent radiographs 6
• Not all meniscal tears are symptomatic, particularly in patients over 45 years 6
• In patients over 70 years, bilateral structural abnormalities can exist with primarily unilateral symptoms 6
• Radiographs may be initially normal in subchondral insufficiency fractures, which later show articular surface fragmentation and subchondral collapse 4