What are the differential diagnoses for ankle redness, swelling, and tenderness?

Differential Diagnoses for Ankle Redness, Swelling, and Tenderness

The differential diagnosis for ankle redness, swelling, and tenderness includes septic arthritis, osteomyelitis, soft tissue infection (cellulitis/abscess), trauma (fracture/sprain), gout, deep venous thrombosis, and in diabetic patients with neuropathy, Charcot neuro-osteoarthropathy—with infectious and limb-threatening etiologies requiring immediate exclusion. 1, 2

Immediate Life- and Limb-Threatening Diagnoses to Exclude

Septic Arthritis

• Requires at least two of the following: local swelling/induration, erythema >0.5 cm around any wound, local tenderness/pain, local warmth, or purulent discharge 2
• Presence of fever, elevated white blood cell count, elevated erythrocyte sedimentation rate, or elevated C-reactive protein suggests infection 1
• Joint aspiration with culture is often necessary for definitive diagnosis, as imaging cannot reliably distinguish infected from noninfected joints 1

Osteomyelitis

• May present with redness, swelling, and tenderness overlying bone 1
• Early acute osteomyelitis (<14 days) may show only mild soft tissue swelling on radiographs 1
• Erosions and periosteal reaction are common findings in acute osteomyelitis, whereas bone sclerosis suggests chronic osteomyelitis 1

Soft Tissue Infection (Cellulitis/Abscess)

• Soft tissue swelling, effacement of fat planes, gas, and foreign bodies may indicate soft tissue infections 1
• Non-purulent secretions, friable granulation tissue, wound undermining, and foul odor suggest soft tissue infection 3

Charcot Neuro-Osteoarthropathy (in Diabetic Patients with Neuropathy)

• Suspect active Charcot in patients with diabetes and neuropathy presenting with a unilateral red, warm, swollen foot with intact skin and no history of ulceration 2
• Temperature difference ≥2°C between the affected and unaffected foot at the same anatomical location strongly suggests active CNO 2
• Clinical signs include hyperemia, increased foot skin temperature, and edema, with pain that may be absent or relatively mild due to sensory neuropathy 2
• Left untreated, CNO presents a high risk of bone fractures, dislocations, deformity, ulceration, infection, and amputation 2
• Initiate knee-high immobilization/offloading promptly in patients with diabetes and neuropathy while further diagnostic studies are performed—this is a strong recommendation even before imaging confirmation due to catastrophic consequences of delayed treatment 2

Other Important Differential Diagnoses

Trauma (Fracture/Sprain)

• Ankle injuries account for 4.4% of United States emergency room visits 1
• Apply Ottawa Ankle Rules to determine need for radiographs: inability to bear weight, point tenderness over the medial malleolus or posterior edge/inferior tip of lateral malleolus, or inability to ambulate for 4 steps 1, 4
• Spiral tibial fractures are the most common fractures in children <4 years presenting with nonlocalized symptoms 1

Gout

• Should be considered in patients with acute onset, severe pain, and history of hyperuricemia or prior attacks 2
• Typically presents with sudden, severe pain that may be more intense than other causes 2

Deep Venous Thrombosis

• Must be excluded with appropriate clinical assessment and D-dimer/ultrasound if indicated 2
• Presents with unilateral swelling, warmth, and tenderness 2

Other Inflammatory Conditions

• Differential diagnosis may include tumors, arthritides, metabolic conditions, cardiovascular etiologies, and venous insufficiency or thrombosis 1

Diagnostic Algorithm

Initial Clinical Assessment

• Measure skin temperature using infrared thermometry at multiple sites on both feet, comparing the highest temperature on affected foot to the same anatomic point contralaterally 2
• Palpate for point tenderness: Achilles insertion, lateral malleolus, posterior superior calcaneus, lateral calcaneal wall, and calcaneofibular ligament course 2
• Perform calcaneal compression test (medial-to-lateral squeeze) to evaluate for stress fracture 2
• Assess for systemic signs: fever >38°C or <36°C, tachycardia >90 bpm, tachypnea >20/min indicate severe infection requiring hospitalization 5
• Palpate dorsalis pedis and posterior tibial pulses bilaterally to assess for critical ischemia 5

Initial Imaging

• Obtain plain radiographs of the ankle as the first imaging study for initial evaluation 1
• Radiographs provide an excellent overview of the anatomic area and can exclude fractures and tumors as the cause of swelling or pain 1
• Radiographs help with interpretation of future imaging studies such as CT, MRI, ultrasound, and nuclear medicine scans 1

Advanced Imaging (If Initial Radiographs Normal but Symptoms Persist)

• MRI without contrast is the preferred advanced imaging modality for diagnosing active CNO, showing bone marrow edema without fractures in early stages 2
• CT with intravenous contrast can assess soft tissue and extent of infection, which can guide aspiration or surgical debridement 1
• Image-guided aspiration is ideal for confirming septic arthritis, as proper needle placement is confirmed and significantly reduces vascular complications and nerve injury 1

Critical Pitfalls to Avoid

• Never delay immobilization in diabetic patients with neuropathy and a hot swollen foot while waiting for imaging—the consequences of untreated CNO are devastating 2
• Do not assume the absence of pain rules out serious pathology in diabetic patients with neuropathy, as pain may be minimal or absent 2
• Do not rely solely on imaging to distinguish infected from noninfected joints—aspiration and culture are often needed for diagnosis 1
• The presence of ulceration and infection does not preclude underlying active Charcot—both can coexist 2
• Delayed surgery of closed ankle fractures increases the risk of soft tissue complications and prolongs hospital stay 6
• Infection after operative treatment of ankle fractures is a limb-threatening complication, especially in patients with comorbidities such as diabetes mellitus 7

When to Refer

• Immediate subspecialist referral for suspected active CNO to prevent progression to deformity and ulceration 2
• Suspected osteomyelitis requiring bone biopsy for definitive diagnosis or antibiotic sensitivity testing 2
• Suspected septic arthritis requiring urgent joint aspiration and culture 1
• No improvement after 6-8 weeks of appropriate conservative treatment for other conditions 1, 2