How do you differentiate between molluscum contagiosum and herpes simplex (Herpes Simplex Virus) rash?

Differentiating Molluscum Contagiosum from Herpes Simplex Rash

Molluscum contagiosum presents as dome-shaped, skin-colored to pink papules with central umbilication that remain stable over weeks to months, while herpes simplex manifests as grouped vesicles on an erythematous base that rapidly progress to shallow ulcers and crust within 10 days. 1, 2

Key Clinical Distinguishing Features

Morphology of Individual Lesions

• Molluscum contagiosum appears as firm, smooth-surfaced, pearly papules 2-5 mm in diameter with a characteristic central umbilication (dell), presenting in skin-colored, whitish, pink, or yellow hues with a shiny surface 2, 3
• Early molluscum lesions may appear as simple dome-shaped papules without visible umbilication, particularly in inflamed or nascent lesions 2
• Herpes simplex begins as a patch of erythema followed by papules that rapidly evolve into grouped vesicles containing clear fluid, which then burst to form shallow ulcers or erosions that eventually crust 1

Lesion Evolution and Timeline

• Molluscum lesions develop slowly, remain stable for extended periods (6 months to 5 years), and do not spontaneously rupture or ulcerate unless traumatized 2, 4
• Herpes lesions follow a predictable rapid progression: erythema → papules → vesicles → ulcers → crusts, with each episode lasting less than 10 days 1
• Herpes recurrences typically occur at the same anatomic site with similar morphology, while molluscum can spread through autoinoculation to new sites 1, 2

Distribution Patterns

• Molluscum in children typically affects the trunk, face, and extremities, while in sexually active adults it appears on genital skin, lower abdomen, and inner thighs 2, 3
• Herpes simplex presents in characteristic locations: HSV-1 primarily affects perioral areas, while HSV-2 involves genital, buttock, and perineal regions 1
• Molluscum lesions are often scattered or grouped but discrete, whereas herpes presents as tight clusters of vesicles on an erythematous base 1, 2

Diagnostic Approach Algorithm

Step 1: Assess Lesion Characteristics

• If firm papules with central umbilication are present, molluscum contagiosum is the diagnosis 2, 3
• If vesicles on erythematous base or shallow ulcers are present, herpes simplex is the diagnosis 1
• Use dermoscopy to identify central orifices (visible in 96.68% of molluscum lesions) and specific vascular patterns including crown, radial, or the "flower pattern" that are pathognomonic for molluscum 5

Step 2: Evaluate Temporal Course

• If lesions have been stable for weeks to months without spontaneous resolution, favor molluscum contagiosum 2, 4
• If lesions appeared acutely and are progressing through vesicular to ulcerative stages within days, favor herpes simplex 1
• Ask about history of recurrent episodes at the same site, which strongly suggests herpes simplex 1

Step 3: Examine Associated Features

• Molluscum may present with perilesional eczema or inflammatory reactions, and associated conjunctivitis if lesions are near eyelids 2
• Herpes may present with dysuria, systemic symptoms during primary infection, or prodromal tingling/burning before recurrences 1
• Multiple large molluscum lesions with minimal inflammation should raise suspicion for immunocompromised state 2, 6

Critical Pitfalls to Avoid

• Do not rely solely on clinical appearance without considering temporal evolution - inflamed or excoriated molluscum lesions may lose their characteristic umbilication and mimic other conditions 2, 5
• Do not assume all genital papules are molluscum - laboratory confirmation should always be sought for genital ulcerative lesions, as HSV is the most common cause of sexually acquired genital ulceration and clinical diagnosis alone leads to both false positives and false negatives 1
• In immunocompromised patients (especially HIV), molluscum can present atypically as giant, disseminated, necrotic, or nodular forms without classic umbilication, potentially mimicking cryptococcal infection 2
• Punctiform vessels on dermoscopy are associated with inflammation and excoriation in molluscum, which may obscure the diagnosis 5

When Laboratory Confirmation is Needed

• For any genital ulcerative or vesicular lesions, laboratory testing should be performed to confirm HSV infection, as other sexually transmitted infections (Treponema pallidum, Haemophilus ducreyi) or non-infectious causes (Crohn disease, Behçet syndrome) can mimic herpes 1
• Collect vesicular fluid with a swab for viral culture or nucleic acid amplification tests (NAATs) for herpes diagnosis 1
• Dermoscopy or dermatology referral is recommended for atypical presentations or diagnostic uncertainty, particularly in immunocompromised patients 2
• Patients with molluscum contagiosum should be screened for other sexually transmitted infections 3