What to do if a rash develops on the face after 1 week of using acyclovir (antiviral medication) for a cold sore?

Facial Rash After One Week of Acyclovir for Cold Sore

Stop the acyclovir immediately and evaluate for allergic contact dermatitis, which is the most likely diagnosis given the timing and location of the rash.

Immediate Assessment and Management

Discontinue Acyclovir

• Acyclovir should be stopped immediately as allergic contact dermatitis from topical acyclovir, though rare, is a well-documented phenomenon that typically manifests after prolonged use (often 1-3 weeks) 1, 2.
• The facial location and timing (1 week of use) are consistent with allergic contact dermatitis rather than a simple drug eruption 2.

Evaluate Rash Severity and Characteristics

• Assess whether the rash is localized to the application site or has spread systemically, as this determines whether you're dealing with contact dermatitis versus a systemic hypersensitivity reaction 1.
• Look specifically for: erythema, vesiculation, pruritus, edema, or desquamation at or around the original cold sore site 2.
• If the rash has spread beyond the application site to involve distant body areas, this suggests systemic acyclovir hypersensitivity rather than simple contact dermatitis 1.

Treatment Based on Severity

For Localized Contact Dermatitis (Mild to Moderate)

• Apply topical corticosteroids such as hydrocortisone cream or prednicarbate cream 0.02% to the affected facial area 3.
• Use gentle, soap-free cleansers and avoid alcohol-containing products on the face 3.
• Consider oral antihistamines (cetirizine, loratadine, or fexofenadine) if pruritus is present 3.

For Severe or Systemic Reactions

• If the rash is severe (extensive erythema, significant edema, or systemic spread), initiate short-term oral corticosteroids 3.
• Monitor closely for progression, as systemic reactions can worsen 1.

Critical Pitfall: Cross-Reactivity with Other Antivirals

Do not switch to valacyclovir or famciclovir, as these share the 2-aminopurine nucleus with acyclovir and will cause cross-reactions in patients with acyclovir allergy 1.

Alternative Antiviral Options

• If future antiviral therapy is needed for herpes infections, the only safe alternatives are foscarnet or cidofovir, which do not contain the 2-aminopurine core structure 1.
• These alternatives should only be considered if absolutely necessary, as they have different safety profiles and are typically reserved for resistant infections 1.

Diagnostic Confirmation

Patch Testing

• Refer to dermatology for patch testing with acyclovir 2% cream and individual excipients (propylene glycol, sodium lauryl sulfate) to confirm the diagnosis and identify the specific allergen 2.
• This is particularly important because the reaction could be to acyclovir itself or to excipients in the formulation 2.
• Patch testing should be performed after the acute reaction has resolved 2.

Follow-Up and Documentation

• Reassess the patient within 2 weeks to ensure resolution of the dermatitis 3.
• Document the acyclovir allergy prominently in the medical record to prevent future exposure 2.
• Educate the patient that this represents a true drug allergy and they should avoid all acyclovir-containing products (including oral and topical formulations) 1, 2.

Management of the Original Cold Sore

• The cold sore will likely resolve spontaneously without further antiviral treatment, as most herpes labialis episodes are self-limited 3.
• Do not attempt to restart any acyclovir-related antiviral (acyclovir, valacyclovir, or famciclovir) for this episode 1.