How to differentiate perioral dermatitis, herpes simplex, and bullous impetigo in a patient presenting with perioral lesions?

Differentiating Perioral Dermatitis, Herpes Simplex, and Bullous Impetigo

The key to differentiating these three conditions lies in recognizing distinct morphological patterns: perioral dermatitis presents with erythematous papules and papulopustules (never vesicles or bullae) in a characteristic perioral distribution sparing the vermillion border; herpes simplex shows grouped vesicles on an erythematous base that progress to crusted erosions with pain; and bullous impetigo displays large flaccid bullae that rupture to form honey-colored crusts, typically in intertriginous areas or on the face. 1, 2, 3

Clinical Morphology: The Primary Distinguishing Feature

Perioral Dermatitis

• Lesion type: Erythematous papules, pustules, and papulovesicles—never true vesicles or bullae 1
• Distribution: Perioral region with characteristic sparing of the vermillion border (the skin immediately adjacent to the lips) 1
• Associated features: May have background erythema and scaling, often preceded by topical corticosteroid use on the face 1, 4
• Symptoms: Generally minimal pruritus or discomfort 1

Herpes Simplex Virus

• Lesion type: Grouped vesicles containing clear fluid on an erythematous base, which rupture to form shallow ulcers or erosions that eventually crust 2, 5
• Distribution: Grouped "herpetiform" pattern—this clustered arrangement is pathognomonic 5
• Progression: Patch of redness → papules → vesicles → ulcers/erosions → crusting, typically lasting less than 10 days 2
• Symptoms: Pain is characteristic, particularly in recurrent episodes 2, 6
• Timing: Incubation period of 2-10 days (up to 4 weeks) 2

Bullous Impetigo

• Lesion type: Large, flaccid bullae that rupture easily, leaving denuded areas with honey-colored crusts 3
• Distribution: More likely to affect intertriginous areas, though can occur on face and extremities 3
• Causative organism: Exclusively Staphylococcus aureus 3
• Age predilection: Most common in children 2-5 years of age 3
• Progression: Bullae are fragile and rupture quickly, leaving characteristic honey-colored crusting 3

Diagnostic Algorithm

Step 1: Assess Lesion Morphology

• If papules/papulopustules without vesicles or bullae → Consider perioral dermatitis 1
• If grouped vesicles on erythematous base → Consider herpes simplex 2, 5
• If large flaccid bullae or honey-colored crusts → Consider bullous impetigo 3

Step 2: Evaluate Distribution Pattern

• Perioral with vermillion sparing → Perioral dermatitis 1
• Grouped/clustered arrangement → Herpes simplex 5
• Intertriginous or scattered on face/extremities → Bullous impetigo 3

Step 3: Assess Symptomatology

• Pain predominant → Herpes simplex 2, 6
• Minimal symptoms → Perioral dermatitis 1
• Variable discomfort → Bullous impetigo 3

Step 4: Consider Confirmatory Testing When Diagnosis Uncertain

For suspected herpes simplex:

• Open vesicles with sterile needle and collect fluid with swab for viral culture or nucleic acid amplification tests (NAATs) 2
• Apply swab to microscope slide for immunofluorescence staining 2
• PCR is the gold standard for HSV detection, particularly important in immunocompromised patients or when oral lesions coexist with other conditions 6

For suspected bullous impetigo:

• Gram stain and culture of pus/exudates to identify S. aureus 3
• Consider methicillin-resistant S. aureus (MRSA) in the current era 3

For suspected perioral dermatitis:

• Diagnosis is primarily clinical; biopsy rarely needed 1
• History of topical corticosteroid use strongly supports diagnosis 1, 4

Critical Pitfalls to Avoid

• Do not confuse the papulovesicles of perioral dermatitis with true vesicles—perioral dermatitis never forms grouped vesicles like herpes simplex 1, 5
• Do not miss the vermillion sparing in perioral dermatitis—this is a key distinguishing feature from other perioral eruptions 1
• Do not assume all crusted perioral lesions are impetigo—herpes simplex also crusts after vesicles rupture, but the grouped pattern and pain distinguish it 2, 3
• Do not overlook the possibility of HSV infection in patients with bullous pemphigoid who have oral lesions—45% of BP patients with oral lesions may have concurrent HSV, particularly if there is pain and absence of blisters in oral lesions 6
• Do not treat perioral dermatitis with topical corticosteroids—this commonly precedes and exacerbates the condition, though there is risk of rebound when stopped 1, 4
• In the era of antibiotic resistance, do not use penicillin for impetigo—it is inadequate; consider MRSA coverage with clindamycin or trimethoprim/sulfamethoxazole if MRSA is suspected 3

Special Considerations

When Herpes Simplex Coexists with Other Conditions

In patients with bullous pemphigoid who develop oral lesions, consider HSV infection if there is inconsistent activity between oral and skin lesions, absence of blisters in oral lesions, pain, or recent high-dose glucocorticoid use (particularly 2-week accumulated dosage) 6. These patients benefit from 2-week famciclovir treatment 6.

Age-Specific Considerations

• Children under 8 years with perioral dermatitis: Avoid oral tetracyclines; use topical metronidazole or erythromycin instead 1, 4
• Children 2-5 years with honey-colored crusts: Bullous impetigo is most common in this age group 3