What are the differential diagnoses for a 6-year-old female with a 5-day history of intermittent fever, diarrhea, vomiting, maculopapular rash, and bilateral wrist swelling and tenderness?

Differential Diagnoses for a 6-Year-Old with Fever, Rash, Diarrhea, Vomiting, and Bilateral Wrist Arthritis

The most critical differential to rule out immediately is Rocky Mountain Spotted Fever (RMSF), which requires empiric doxycycline treatment without delay, as mortality reaches 5-10% if treatment is delayed. 1, 2

Life-Threatening Differentials Requiring Immediate Action

Rocky Mountain Spotted Fever (RMSF)

• Maculopapular rash appearing 2-4 days after fever onset, initially on wrists/ankles, is classic for RMSF 1
• Gastrointestinal symptoms (diarrhea, vomiting, abdominal pain) occur frequently in children with RMSF 1
• Joint pain and myalgia are common extrapulmonary manifestations 1
• Critical pitfall: Up to 20% never develop rash, and <50% have rash in first 3 days—absence of rash should NOT exclude diagnosis 1, 2
• Up to 40% report no tick bite history 2
• Children develop rash earlier than adults and more frequently 1
• Start doxycycline 2.2 mg/kg twice daily immediately if RMSF suspected, even in children <8 years old 2

Human Monocytic Ehrlichiosis (HME)

• Rash occurs in approximately 60% of children (versus 30% of adults), with variable patterns including maculopapular 1
• Gastrointestinal symptoms (nausea, vomiting, diarrhea) are prominent 1
• Arthralgia is a common feature 1
• Case-fatality rate of 3% 1, 2
• Also requires immediate doxycycline treatment 2

Meningococcemia

• Can present with fever, maculopapular rash that progresses to petechiae, and joint involvement 3
• Requires immediate ceftriaxone if petechiae develop 2

Infectious Differentials with Joint Involvement

Q Fever (Acute)

• Gastrointestinal symptoms (diarrhea, vomiting, abdominal pain) reported in 50-80% of pediatric cases 1
• Skin rash prevalence as high as 50% among children with diagnosed cases 1
• Arthralgia is a common extrapulmonary manifestation 1
• Fever lasts median 10 days in untreated patients 1
• Children typically have milder illness than adults 1

Viral Exanthems (Enterovirus)

• Enteroviruses (coxsackievirus, echovirus) commonly cause maculopapular rashes with fever 3
• Associated symptoms include headache, malaise, myalgia 3
• Can present with gastrointestinal symptoms 3
• Arthralgia may occur with certain enteroviral infections 3

Rat-Bite Fever (Streptobacillus moniliformis)

• Presents with fever, headache, and maculopapular rash affecting palms 4
• Arthritis/arthralgia is a characteristic feature 4
• Critical history: Exposure to pet rats or rodents 4
• Untreated disease can be fatal; penicillin is treatment of choice 4

Non-Infectious Differentials

Kawasaki Disease

• Fever lasting ≥5 days with rash, conjunctival injection, oral changes, extremity changes, and lymphadenopathy 3
• Can present with gastrointestinal symptoms 3
• Joint involvement occurs in some cases 3
• Requires urgent recognition to prevent coronary artery complications 3

Drug Hypersensitivity Reaction

• Can cause fever, maculopapular rash, and systemic symptoms 3
• Critical history: Recent medication exposure 3

Immediate Diagnostic Approach

History Details to Elicit

• Tick exposure or outdoor activities in past 2 weeks 1, 2
• Pet rodent exposure (rats, mice) 4
• Recent medications 3
• Travel history to endemic areas 1
• Timing: When did rash appear relative to fever onset? 1
• Rash progression: Started on wrists/ankles vs. trunk? 1

Physical Examination Focus

• Examine palms and soles for rash involvement 1
• Assess for petechial progression 1
• Evaluate for conjunctival injection 1
• Check for periorbital edema 1
• Assess joint swelling, warmth, range of motion 1

Immediate Laboratory Testing

• Complete blood count with differential (thrombocytopenia, leukopenia suggest rickettsial disease) 1, 2
• Comprehensive metabolic panel (hyponatremia, elevated transaminases) 1, 2
• Blood cultures 2
• Acute serology for R. rickettsii, E. chaffeensis, A. phagocytophilum 2
• PCR for E. chaffeensis and A. phagocytophilum if available 2

Management Algorithm

If bilateral wrist arthritis + maculopapular rash + fever + GI symptoms:

1. Start empiric doxycycline 2.2 mg/kg twice daily immediately if any suspicion for RMSF/HME 2

   • Do NOT wait for laboratory confirmation 2
   • Do NOT wait for rash to involve palms/soles 1, 2
   • Do NOT exclude diagnosis based on absent tick bite history 2

2. If petechiae present, add ceftriaxone 50-100 mg/kg/day IV for possible meningococcemia 2

3. Obtain detailed exposure history while initiating treatment 1, 2, 4

4. Expect clinical improvement within 24-48 hours if rickettsial disease 2

5. If no improvement on doxycycline, broaden differential to include Kawasaki disease, rat-bite fever, or other causes 3, 4