What are the differential diagnoses and initial evaluation for a 7‑month‑old infant with one‑week bilateral leg and knee swelling, no fever, and normal tibia and fibula radiographs?

Bilateral Leg and Knee Swelling in a 7-Month-Old: Differential Diagnosis and Initial Evaluation

In a 7-month-old with bilateral leg and knee swelling for one week, absent fever, and normal tibia/fibula radiographs, the priority is to rule out septic arthritis and osteomyelitis first through laboratory testing (CBC, ESR, CRP) and ultrasound of the knees, followed by consideration of inflammatory, hematologic, and metabolic causes given the bilateral presentation.

Critical Red Flags to Assess Immediately

Even without fever, serious infection remains a concern in this age group:

• Assess for "three As": Anxiety, agitation, and high analgesic requirements may indicate serious pathology even when verbal communication is impossible in infants 1
• Check weight-bearing ability: Complete refusal to bear weight or move legs raises concern for septic arthritis or osteomyelitis despite absence of fever 2, 1
• Examine for systemic signs: Irritability, poor feeding, or lethargy can indicate infection in infants who may not mount a fever response 3

Differential Diagnosis by Priority

Infectious Causes (Must Rule Out First)

• Septic arthritis: Can present without fever in young infants; bilateral involvement is rare but possible with bacteremia. Knee and hip are most commonly affected joints in this age group 3
• Osteomyelitis: Multifocal osteomyelitis occurs in 19% of cases, with over half in patients <6 years of age, particularly neonates. Early osteomyelitis (<14 days) may show normal radiographs 4

Inflammatory/Rheumatologic Causes

• Juvenile idiopathic arthritis: Can present with bilateral joint swelling; pauciarticular onset is common in young children 5, 6
• Reactive arthritis: Post-infectious inflammatory process affecting multiple joints 5

Hematologic Causes

• Leukemia: Can present with bone/joint pain and swelling; bilateral involvement is characteristic. MRI may reveal bone marrow abnormalities 4
• Hemophilia or bleeding disorders: Bilateral hemarthrosis possible with minor trauma 7

Metabolic/Developmental Causes

• Rickets: Causes metaphyseal swelling, particularly at knees and wrists; bilateral presentation is typical
• Scurvy: Rare but causes periosteal elevation and joint swelling
• Developmental dysplasia: Less likely given bilateral presentation 2

Trauma-Related

• Occult fractures: Bilateral toddler's fractures are uncommon but possible; 10% only visible on follow-up radiographs 2, 1
• Non-accidental trauma: Must consider given age and bilateral involvement

Initial Laboratory Evaluation

Order immediately:

• CBC with differential: Elevated WBC suggests infection; abnormal cell lines suggest leukemia 1, 7
• ESR and CRP: Elevated inflammatory markers increase suspicion for septic arthritis or osteomyelitis, though absence doesn't exclude infection 2, 1
• Blood cultures: Essential if any concern for bacteremia, as 43% of septic arthritis cases have positive blood or joint cultures 3

Consider based on clinical suspicion:

• Coagulation studies if bleeding disorder suspected
• Vitamin D, calcium, phosphate, alkaline phosphatase if rickets suspected
• Vitamin C level if scurvy suspected

Initial Imaging Strategy

Ultrasound of bilateral knees (perform next):

• Highly sensitive for detecting joint effusions as small as 1 mL 4
• Can identify periosteal elevation and subperiosteal collections suggesting osteomyelitis 4
• Can guide aspiration if effusion present 4

If ultrasound shows effusion:

• Image-guided aspiration is mandatory for cell count, Gram stain, and culture to distinguish septic from inflammatory arthritis 4, 3
• Septic arthritis requires intervention within hours to prevent permanent joint damage 1

Advanced Imaging if Initial Workup Negative

MRI of bilateral lower extremities:

• Sensitivity 82-100% and specificity 75-96% for osteomyelitis 4
• Can detect bone marrow abnormalities suggesting leukemia 4
• Large field-of-view MRI covering both extremities recommended, as 11% of osteomyelitis cases have contralateral findings 4
• Contrast administration improves abscess detection 4

Whole-body bone scan (if MRI unavailable or multifocal disease suspected):

• Particularly useful in children <6 years for detecting multifocal osteomyelitis 4
• Changes present within 1-2 days of symptoms, earlier than radiographic changes 4

Management Based on Initial Findings

If inflammatory markers elevated or ultrasound shows effusion:

• Urgent orthopedic and/or infectious disease consultation 2
• Empiric antibiotics after cultures obtained if septic arthritis suspected 3
• Joint aspiration for definitive diagnosis 4, 3

If initial workup negative but symptoms persist:

• Repeat clinical examination in 7-10 days 2, 8
• Consider follow-up radiographs, as occult fractures may become visible 2, 1
• Proceed to MRI if symptoms worsen or new red flags develop 2, 8

If improving with normal workup:

• Observation with close follow-up in 1-2 weeks 2, 1
• Short-course NSAIDs for symptomatic relief 1

Critical Pitfalls to Avoid

• Never assume normal radiographs exclude fracture or osteomyelitis: Early osteomyelitis (<14 days) shows normal radiographs in most cases 4; 10% of fractures only visible on follow-up films 2, 1
• Don't dismiss infection based on absence of fever alone: Young infants may not mount fever response; rely on inflammatory markers and clinical assessment 1, 3
• Don't focus only on the legs: Hip pathology presents as knee or thigh pain in up to 30% of cases, even in infants 1, 8
• Don't delay aspiration if effusion present: Septic arthritis causes permanent damage within hours; imaging cannot reliably distinguish infected from sterile effusions 4, 1
• Consider non-accidental trauma: Bilateral injuries in a 7-month-old warrant careful evaluation for abuse patterns