What are the differential diagnoses and initial investigations for a 9-year-old boy with a 6-month history of bilateral knee and wrist pain, intermittent fever, and a maculopapular rash, presenting with tenderness, limited range of motion, and hyperthermia (elevated body temperature)?

Differential Diagnoses and Initial Investigations

Most Likely Diagnosis: Systemic Juvenile Idiopathic Arthritis (Systemic JIA/Still's Disease)

This 9-year-old boy most likely has systemic juvenile idiopathic arthritis (systemic JIA), also known as Still's disease, based on the classic triad of high-spiking fever, polyarthritis, and salmon-pink maculopapular rash lasting 6 months. 1

Key Clinical Features Supporting Systemic JIA:

• Fever pattern: High-spiking quotidian fever (38.8°C) that characteristically peaks in late afternoon/early evening and lasts under 4 hours 2
• Arthritis: Bilateral knee and wrist involvement with morning stiffness, limited range of motion, and tenderness—knees and wrists are the most frequently affected joints (64-100% of patients) 2
• Rash: Salmon-pink maculopapular rash on trunk and extremities (back and arms) that is evanescent and often accompanies fever spikes 1
• Chronic duration: 6-month history is consistent with chronic inflammatory arthritis rather than acute infection 1

Three Differential Diagnoses:

1. Systemic Juvenile Idiopathic Arthritis (Systemic JIA/Still's Disease) - MOST LIKELY

• Presents with high-spiking fever exceeding 39°C, polyarthritis affecting knees and wrists, and characteristic salmon-pink evanescent maculopapular rash 2, 1
• Morning stiffness and worsening with movement are hallmark features of inflammatory arthritis 1
• The 6-month duration strongly supports a chronic inflammatory condition rather than acute infection 1

2. Rocky Mountain Spotted Fever (RMSF) - MUST EXCLUDE URGENTLY

• Life-threatening tickborne rickettsial disease that presents with fever and maculopapular rash 3, 4
• Rash typically begins as small blanching pink macules on ankles/wrists 2-4 days after fever onset, progressing to maculopapular with central petechiae 4, 2
• Critical caveat: Tick exposure history is absent in 40% of RMSF cases, and less than 50% have rash in first 3 days 2
• However, the 6-month chronic course makes RMSF extremely unlikely, as untreated RMSF is rapidly fatal within 8 days 3

3. Kawasaki Disease - LESS LIKELY BUT CONSIDER

• Should be considered in any young child with unexplained fever for 5 days associated with rash 3
• Presents with high-spiking fever (typically 39-40°C), polymorphous exanthem (often maculopapular), and extremity changes 3
• However, this patient lacks: bilateral conjunctival injection, oral mucosal changes (strawberry tongue, lip cracking), and cervical lymphadenopathy—making Kawasaki disease less likely 3
• The 6-month duration also argues against Kawasaki disease, which typically has acute presentation 3

Four Essential Initial Investigations:

1. Complete Blood Count (CBC) with Differential

• Look for neutrophilic leukocytosis characteristic of systemic JIA 1
• Assess for thrombocytopenia (seen in RMSF/ehrlichiosis) or normocytic normochromic anemia (seen in systemic JIA as anemia of chronic inflammation) 3, 1
• Leukocytosis with bandemia may suggest bacterial infection or systemic JIA 3, 1

2. Inflammatory Markers: Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP)

• Markedly elevated in systemic JIA and help assess disease activity 2
• Also elevated in Kawasaki disease and infectious causes 3
• Essential for monitoring treatment response in inflammatory arthritis 2

3. Comprehensive Metabolic Panel (CMP)

• Assess for hyponatremia and elevated hepatic transaminases (seen in RMSF/ehrlichiosis if infectious cause) 3, 2
• Evaluate liver function, as systemic JIA can cause hepatic abnormalities 1
• Baseline renal function important before initiating treatment 3

4. Ferritin Level

• Typically very high (often >1000 ng/mL) in systemic JIA and helps distinguish it from other causes of fever and rash 2
• Extremely elevated ferritin (>5000 ng/mL) may suggest macrophage activation syndrome, a life-threatening complication of systemic JIA 2
• Not typically elevated in infectious causes or Kawasaki disease 3

Critical Management Considerations:

Immediate Actions:

• If RMSF cannot be definitively excluded based on geographic location or any possible tick exposure: initiate empiric doxycycline 100 mg twice daily immediately without waiting for laboratory confirmation, as mortality increases dramatically with delayed treatment 2
• However, the 6-month chronic course makes acute RMSF essentially impossible 3

Diagnostic Algorithm:

• Obtain all four investigations simultaneously 3, 2
• If ferritin markedly elevated (>1000 ng/mL) with neutrophilic leukocytosis and elevated inflammatory markers, systemic JIA is confirmed 2, 1
• Consider rheumatology consultation for definitive diagnosis and treatment planning 1
• If fever persists >5 days with 4 principal Kawasaki criteria, obtain 2D echocardiography to evaluate for coronary artery involvement 3

Common Pitfalls to Avoid:

• Do not dismiss RMSF solely based on absence of tick bite history—40% of cases have no recalled exposure 2
• Do not wait for all clinical features of Kawasaki disease to appear simultaneously—they typically evolve over time 3
• Do not overlook systemic JIA because it can mimic infectious diseases and malignancy, especially when dominated by fever and systemic symptoms 1
• Recognize that the 6-month duration is the key distinguishing feature pointing away from acute infectious causes toward chronic inflammatory disease 1