Red Flags of Cold Sores
Seek immediate medical evaluation if cold sores are accompanied by systemic signs of severe infection, immunocompromised status, ocular involvement, or neurological symptoms, as these indicate potentially life-threatening complications requiring urgent intervention.
Critical Red Flags Requiring Urgent Evaluation
Systemic Inflammatory Response
- Temperature >38°C or <36°C 1
- Heart rate >90 beats/min 1
- Respiratory rate >20 breaths/min 1
- Altered mental status, confusion, or signs of encephalitis 2
These systemic signs indicate the infection may have progressed beyond simple mucocutaneous disease and requires immediate assessment for disseminated HSV or encephalitis 1, 2.
High-Risk Patient Populations
Immunocompromised patients are at substantially increased risk for severe, disseminated HSV infection 3, 2. This includes:
- Patients on immunosuppressive medications
- HIV/AIDS patients
- Transplant recipients
- Patients with malignancy
Neonates and young children (<3 years) are at higher risk for HSV encephalitis, particularly with primary infection 2. The finding of labial herpes in children with neurological symptoms may indicate primary infection with higher morbidity risk 1, 2.
Pregnant women require special consideration due to risk of transmission to the neonate 4.
Ocular Involvement
- Any eye pain, vision changes, or periorbital involvement warrants immediate ophthalmologic evaluation 3
- HSV keratitis can cause sight-threatening disease 4
Progressive or Extensive Disease
Lesions that continue to develop for >7 days suggest either:
Extensive facial involvement beyond typical perioral distribution, particularly with:
- Facial swelling or edema 3
- Erythema extending >2 cm from lesion margins 3
- Signs of deeper tissue involvement (abscess, cellulitis) 3
Neurological Warning Signs
- Severe headache, neck stiffness, or photophobia may indicate HSV encephalitis 1, 2
- Confusion or altered consciousness 3
- Children are more likely to develop encephalitis with primary HSV infection compared to adults experiencing reactivation 1, 2
Secondary Concerning Features
Signs of Secondary Bacterial Infection
- Purulent discharge (thick, opaque to white or sanguineous secretion) 3
- Increasing warmth, tenderness, or induration beyond the typical cold sore presentation 3
- Lymphangitic streaking 3
Failure to Heal
- Lesions that fail to crust over within 4-7 days 1
- Lesions that do not heal within 2 weeks despite appropriate management 5
Common Pitfalls to Avoid
Do not dismiss systemic symptoms as "just the flu" in patients with active cold sores, particularly in immunocompromised individuals or young children 1, 2. HSV can cause severe systemic disease including encephalitis.
Do not assume all perioral lesions are simple cold sores 3. Consider alternative diagnoses such as impetigo, especially if there is significant purulent drainage or if the patient is not responding to antiviral therapy 3.
Remember that viral shedding begins 1-2 days before visible lesions appear 1, so patients may be contagious before they recognize they have an outbreak.
Asymptomatic viral shedding can occur even without visible cold sores 1, which is particularly important when considering transmission risk to vulnerable populations like toddlers or immunocompromised individuals.
When to Refer
Immediate referral or emergency evaluation is warranted for:
- Any signs of systemic inflammatory response syndrome 1
- Neurological symptoms suggesting encephalitis 1, 2
- Ocular involvement 4
- Immunocompromised patients with extensive or progressive disease 3, 2
- Neonates or young children with cold sores and any systemic symptoms 2
Specialist referral (infectious disease or dermatology) should be considered for: