What is the best course of action for a 6-year-old female patient with a recurrent rash on her hands, fever, and sore throat, who recently completed amoxicillin (amoxicillin) for strep throat?

Recurrent Rash with Fever and Sore Throat After Recent Amoxicillin Treatment

Immediate Action: Discontinue Amoxicillin and Evaluate for Drug Reaction

This 6-year-old with recurrent rash on hands, fever, and sore throat following recent amoxicillin treatment for strep throat requires immediate discontinuation of amoxicillin and evaluation for a severe cutaneous adverse drug reaction, particularly Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome. 1

Critical Diagnostic Considerations

Rule Out Severe Drug Reactions First

• Amoxicillin can cause severe cutaneous adverse reactions (SCAR) including DRESS syndrome, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP). 1

• DRESS syndrome characteristically presents 2-3 weeks after drug initiation with rash, fever, and systemic symptoms—matching this patient's timeline. 2

• If the patient develops a skin rash while on amoxicillin, close monitoring is mandatory, and amoxicillin must be discontinued if lesions progress. 1

• The recurrent nature of this rash (appeared, resolved, then returned) with new fever suggests either a drug reaction or a new infectious process rather than simple treatment failure. 1

Evaluate for Alternative Diagnoses

• The combination of rash on hands with fever and sore throat should prompt consideration of:

  • Scarlet fever (scarlatiniform rash is a classic feature of Group A streptococcal infection) 3
  • Viral exanthem (hand rash with systemic symptoms suggests possible viral etiology) 3
  • Drug hypersensitivity reaction to amoxicillin 1, 2

• Obtain a repeat rapid strep test with backup throat culture to determine if this represents treatment failure, reinfection, or a new viral illness. 3, 4

Management Algorithm

Step 1: Immediate Assessment (Today)

• Discontinue amoxicillin immediately given the concerning rash pattern. 1

• Examine the rash carefully for progression, mucosal involvement, or bullae formation that would indicate severe SCAR. 1

• Check for lymphadenopathy, hepatosplenomegaly, and other systemic signs of DRESS syndrome. 2

• Obtain rapid antigen detection test (RADT) for Group A streptococcus with backup throat culture in this 6-year-old, as negative RADT requires culture confirmation in children. 3, 4

Step 2: If Strep Test is Positive

• This represents either treatment failure or reinfection requiring antibiotic with additional β-lactamase coverage since the child received amoxicillin within the past 30 days. 3

• Prescribe an alternative antibiotic avoiding β-lactams entirely given the concerning rash:

  • First choice: Clindamycin 7 mg/kg three times daily (maximum 300 mg per dose) for 10 days 3, 5
  • Alternative: Azithromycin 12 mg/kg once daily (maximum 500 mg) for 5 days 3, 5

• The 10-day duration is non-negotiable for preventing acute rheumatic fever, regardless of symptom resolution. 5

Step 3: If Strep Test is Negative

• Withhold antibiotics entirely as the negative test rules out streptococcal pharyngitis and treatment should be symptomatic only. 3, 4

• Provide symptomatic treatment with acetaminophen or ibuprofen for fever and sore throat. 3, 4

• The rash likely represents either a viral exanthem or a drug reaction to the recently completed amoxicillin. 3, 1

Step 4: Monitor for Drug Reaction Progression

• Instruct parents to return immediately if:

  • Rash spreads or becomes more severe
  • Mucosal involvement develops (mouth, eyes, genitals)
  • Facial swelling or respiratory symptoms occur
  • Fever persists beyond 48-72 hours 1, 2

• If DRESS syndrome is suspected based on progression, high-dose systemic corticosteroids are the treatment of choice. 2

Critical Pitfalls to Avoid

• Never prescribe another β-lactam antibiotic (including cephalosporins) until drug reaction is definitively ruled out, as cross-reactivity can occur and severe reactions are more likely in patients with prior penicillin hypersensitivity. 1

• Do not assume this is simple treatment failure and switch to amoxicillin-clavulanate—the rash pattern demands consideration of drug hypersensitivity first. 1

• Do not test or treat household contacts unless they are symptomatic, as this is not recommended even with recurrent infections. 3, 4

• Do not perform follow-up testing after completing appropriate antibiotic treatment if the child becomes asymptomatic, as this may simply reflect carrier status. 4

Special Considerations for This Case

• The timing (rash appearing after amoxicillin treatment, resolving, then recurring with new symptoms) is atypical for simple streptococcal pharyngitis and raises concern for either drug reaction or viral superinfection. 1, 2

• If symptoms persist beyond 3-4 days or worsen significantly, consider suppurative complications or alternative diagnoses including peritonsillar abscess or infectious mononucleosis. 4

• Treatment within 9 days of symptom onset still effectively prevents acute rheumatic fever, so waiting for culture results (if RADT negative) is appropriate and safe. 4, 5