What are the differential diagnoses for a child presenting with a maculopapular rash and an erythematous throat?

Differential Diagnosis for Maculopapular Rash and Red Throat in Children

The most common cause is a viral exanthem, particularly enteroviral infection or Group A Streptococcus (scarlet fever), but you must immediately exclude life-threatening conditions including meningococcemia, Rocky Mountain Spotted Fever, and Kawasaki disease before attributing symptoms to a benign viral illness. 1, 2

Immediate Life-Threatening Diagnoses to Exclude First

Meningococcemia

• Presents with rapid progression from maculopapular to petechial/purpuric rash with clinical deterioration, elevated white blood cell count, and markedly elevated inflammatory markers. 2
• Administer intramuscular ceftriaxone immediately and obtain blood cultures if meningococcal disease cannot be excluded. 2
• Never dismiss a petechial component without thorough evaluation, as meningococcemia requires urgent treatment. 2

Rocky Mountain Spotted Fever (RMSF)

• Begins 2-4 days after fever onset as small (1-5 mm) blanching pink macules on ankles, wrists, or forearms, evolving to maculopapular with central petechiae, spreading to palms, soles, arms, legs, and trunk while sparing the face. 1
• Up to 40% of patients report no tick bite history, so absence of this history does not exclude the diagnosis. 1, 2
• Less than 50% have rash in the first 3 days of illness, and up to 20% never develop a rash. 1
• Case-fatality rate is 5-10%; initiate doxycycline 100 mg twice daily immediately if fever + rash + headache + tick exposure or endemic area exposure are present, without waiting for laboratory confirmation. 1
• Obtain CBC with differential (looking for leukopenia, thrombocytopenia) and comprehensive metabolic panel (looking for hyponatremia, elevated hepatic transaminases) immediately if RMSF is suspected. 1

Kawasaki Disease

• Diagnosis requires fever ≥5 days plus 4 of 5 features: bilateral conjunctival injection without exudate, oral mucosal changes (erythema/cracking of lips, strawberry tongue, diffuse injection of oral and pharyngeal mucosae), cervical lymphadenopathy ≥1.5 cm, extremity changes (erythema of palms/soles, edema, periungual peeling), and polymorphous rash. 3, 1
• The rash is typically maculopapular, extensive, involving trunk and extremities with accentuation in the perineal/groin region where early desquamation may occur. 3, 1
• Causes coronary artery aneurysms if left untreated; obtain ESR, CRP, serum albumin, and urinalysis if suspected. 1
• The pharyngeal mucosa shows diffuse injection, which explains the red throat presentation. 3

Common Viral Exanthems (Most Likely Diagnoses)

Scarlet Fever (Group A Streptococcus)

• The distinguishing feature is a sandpaper-textured maculopapular rash that appears during active fever, spreads from the upper trunk throughout the body while sparing palms and soles, accompanied by pharyngitis with tonsillar exudates and strawberry tongue. 2, 4
• The erythematous throat with exudates is a key diagnostic feature. 4
• Treat with penicillin or amoxicillin immediately upon clinical diagnosis. 4

Roseola (Human Herpesvirus 6/7)

• The key distinguishing feature is that the maculopapular rash appears AFTER resolution of high fever (3-5 days), is pink-rose colored, and spares palms, soles, and face. 2, 4
• More common in children under 3 years. 4
• The timing of rash relative to fever is the single most important distinguishing feature from other viral exanthems. 2

Enteroviral Infections

• Most common cause of viral maculopapular rashes, presenting with trunk and extremity involvement while sparing palms, soles, face, and scalp. 1
• May be associated with pharyngitis explaining the red throat. 3
• Enterovirus 71 can cause hand-foot-mouth disease with papular lesions on hands, feet, and mouth, plus brainstem involvement in severe cases. 3

Epstein-Barr Virus (EBV)

• Causes maculopapular rash, especially if the patient received ampicillin or amoxicillin. 1
• Associated with pharyngitis, tonsillar exudates, and posterior cervical lymphadenopathy. 4

Parvovirus B19 (Fifth Disease/Erythema Infectiosum)

• Characterized by "slapped cheek" appearance on face with possible truncal involvement following a viral prodrome. 1, 4
• The facial erythema is the distinguishing feature. 4

Measles (Rubeola)

• Presents with maculopapular or vesicular rash, Koplik spots (white spots on buccal mucosa), and the highly typical measles rash. 3
• Associated with conjunctivitis, coryza, and cough (the "3 Cs"). 5
• CDC recorded 764 measles cases in the most recent surveillance period, highlighting continued low but present incidence. 1

Drug Hypersensitivity Reactions

Exanthematous Drug Eruptions

• Present as fine reticular maculopapular rashes or broad, flat erythematous macules and patches, typically appearing 7-14 days after drug initiation. 1
• Common culprits include β-lactam antibiotics (amoxicillin, ampicillin), especially when given during viral infections. 6
• Absence of eosinophilia, low RegiSCAR score (2-3), confirmation of viral etiology, and rapid resolution (2-5 days) help rule out DRESS syndrome; conversely, presence of eosinophilia suggests DRESS. 6

Diagnostic Algorithm

Step 1: Assess for Life-Threatening Features

• Check for petechiae/purpura, clinical deterioration, severe headache, altered mental status, or signs of shock. 2
• If present, administer empiric ceftriaxone and/or doxycycline immediately, obtain blood cultures, CBC, comprehensive metabolic panel. 1, 2

Step 2: Determine Timing of Rash Relative to Fever

• Rash AFTER fever resolves → Roseola (HHV-6/7). 2
• Rash DURING active fever → Scarlet fever, measles, enterovirus, EBV, drug reaction. 2

Step 3: Examine Throat and Oral Cavity

• Pharyngitis with tonsillar exudates + sandpaper rash → Scarlet fever. 4
• Strawberry tongue + conjunctival injection + extremity changes → Kawasaki disease. 3
• Koplik spots (white spots on buccal mucosa) → Measles. 5
• Diffuse pharyngeal injection without exudates → Viral pharyngitis (enterovirus, EBV). 3

Step 4: Assess Rash Distribution

• Palms and soles involved → RMSF (late finding), Kawasaki disease, parvovirus B19. 1
• Palms and soles spared → Scarlet fever, roseola, most viral exanthems. 4
• "Slapped cheek" facial erythema → Parvovirus B19. 4
• Perineal/groin accentuation → Kawasaki disease. 3, 1

Step 5: Check for Associated Features

• Fever ≥5 days + conjunctival injection + lymphadenopathy ≥1.5 cm → Kawasaki disease. 3
• Recent tick exposure or endemic area travel → RMSF (but 40% have no tick bite history). 1
• Recent antibiotic use (especially amoxicillin) → Drug reaction vs. viral exanthem. 6

Common Pitfalls to Avoid

• Never rely on tick bite history to exclude RMSF, as 40% of patients have no reported bite. 1, 2
• Do not dismiss RMSF based on geography, as cases occur nationwide. 2
• Early serology for RMSF is typically negative, so negative early testing does not exclude diagnosis. 2
• Misdiagnosing viral exanthems during antibiotic therapy as drug allergy leads to unnecessary life-long exclusion of useful antibiotics. 6
• Absence of rash in the first 3 days does not exclude RMSF; up to 20% never develop a rash. 1
• In darker skin pigmentation, RMSF rash is often difficult to detect, requiring heightened clinical suspicion. 1

Management Based on Most Likely Diagnosis

If Scarlet Fever is Most Likely

• Initiate oral penicillin or amoxicillin immediately. 4
• Provide supportive care with antipyretics and adequate hydration. 2

If Viral Exanthem is Most Likely

• Provide supportive care only, including fever control with antipyretics and adequate hydration. 2
• Reassure that viral exanthems are self-limited and typically resolve within 5-14 days. 1, 2
• Monitor for clinical deterioration suggesting bacterial superinfection. 2

If RMSF Cannot Be Excluded

• Administer doxycycline 100 mg twice daily immediately without waiting for laboratory confirmation. 1, 2
• Clinical improvement is expected within 24-48 hours of initiating doxycycline. 1

If Kawasaki Disease is Suspected

• Obtain ESR, CRP, serum albumin, urinalysis, and echocardiography. 1
• Refer to pediatric cardiology urgently for IVIG and aspirin therapy. 3