What is the pathophysiology, symptoms, diagnosis, management, and differential diagnoses of molluscum contagiosum?

Molluscum Contagiosum: Comprehensive Overview

Pathophysiology

Molluscum contagiosum is caused by a poxvirus (molluscum contagiosum virus, MCV) that infects epidermal keratinocytes through direct skin-to-skin contact, fomites, or autoinoculation. 1, 2 The virus replicates within the cytoplasm of infected cells, leading to characteristic cellular proliferation and the formation of umbilicated papules. 2

• Transmission occurs through direct contact with infected individuals, sharing towels and personal items, or exposure in communal water settings like swimming pools and hot tubs. 1
• The virus remains infectious throughout the entire course of lesions, which can persist from 6 months to 5 years without treatment. 1, 2
• Self-inoculation is common, leading to spread across body surfaces through scratching or touching lesions. 1

Clinical Presentation and Symptoms

The hallmark presentation consists of skin-colored, whitish, or pink papules (2-6 mm diameter) with a shiny surface and central umbilication, most commonly affecting the trunk, face, and extremities in children. 1, 3, 2

Typical Features:

• Firm, rounded, dome-shaped papules that develop central umbilication as they mature. 3
• In children: trunk, face, and extremities are most commonly affected. 3
• In adults: genital region is predominantly involved, suggesting sexual transmission. 2
• Most lesions are asymptomatic, though pain, itching, and redness may occur. 1, 3

Associated Complications:

• Conjunctivitis when lesions are located on or near the eyelids (may be mild to severe with follicular reaction). 1, 3
• Perilesional eczema (eczematous dermatitis around lesions). 2
• Bacterial superinfection. 3, 2

Red Flags for Immunocompromised State:

• Multiple large lesions with minimal conjunctival inflammation strongly suggest immunodeficiency and warrant HIV screening. 1, 4, 5
• Atypical presentations including giant, disseminated, necrotic, polypoidal, nodular forms, pseudocysts, or abscesses. 1
• Extensive disease with prolonged course. 5

Diagnosis

Diagnosis is primarily clinical based on the characteristic appearance of umbilicated papules; dermoscopy can aid diagnosis when umbilication is not visible. 1, 2

Diagnostic Approach:

• Look for shiny, dome-shaped papules with central umbilication on typical body sites. 1
• Early lesions may appear as simple dome-shaped papules without central depression. 1
• Assess distribution pattern and look for associated findings (conjunctivitis, perilesional eczema, inflammatory reactions). 1
• White material can be expressed from lesions on compression (Henderson-Paterson bodies). 6

When Umbilication is Absent:

• Dermoscopy is useful for identifying characteristic features in early, inflamed, or atypical lesions. 1, 2
• Consider confocal microscopy or skin biopsy if diagnostic uncertainty persists. 2
• In immunocompromised patients with atypical presentations, referral to dermatology is recommended. 1

Critical Differential:

• In HIV patients, cryptococcal infection can present with umbilicated papules resembling molluscum contagiosum and must be excluded. 1, 3

Management

Physical removal methods (curettage, excision, cryotherapy) are first-line therapy for symptomatic lesions, multiple lesions, or those causing conjunctivitis, with cryotherapy achieving 93% complete response. 1, 4

Treatment Algorithm:

For Limited, Asymptomatic Disease:

• Watchful waiting is reasonable as spontaneous resolution typically occurs in 6-12 months (though can take up to 4-5 years). 1
• Consider active treatment to prevent transmission and reduce autoinoculation risk. 2

For Symptomatic, Multiple, or Periocular Lesions:

• Cryotherapy with liquid nitrogen: 93% complete response rate, applied to achieve visible freezing extending slightly beyond lesion margin. 1
• Curettage (incision and curettage, simple excision, or excision with cautery): equally effective first-line options. 1, 4
• 10% potassium hydroxide solution: similar efficacy to cryotherapy (86.6% vs 93.3% complete response) with better cosmetic results due to lower hyperpigmentation risk. 1

Critical Treatment Principles:

• Identify and treat ALL lesions, including nascent ones, during initial treatment to reduce recurrence risk. 1, 4
• Reducing viral load allows host immune response to eliminate residual virus. 1, 4
• For periocular lesions with conjunctivitis, physical removal is imperative; conjunctivitis may require several weeks to resolve after lesion elimination. 1, 4

Treatment Considerations by Modality:

Cryotherapy:

• No anesthesia is typically used as it has not shown benefit. 1
• Common adverse effects: postinflammatory hyperpigmentation (most common, may persist 6-12 months), erythema, vesicle formation, burning pain. 1
• Avoid treating sensitive areas (eyelids, lips, nose, ears) due to higher complication risk. 1

Potassium Hydroxide:

• Better cosmetic outcomes than cryotherapy, particularly for facial lesions or darker skin tones. 1

Cantharidin:

• Effective in observational studies, though randomized controlled trial evidence is limited. 1

What NOT to Use:

• Imiquimod has NOT shown benefit compared to placebo in randomized controlled trials and is NOT recommended by the American Academy of Pediatrics. 1 (Note: Despite some observational reports suggesting efficacy 7, the highest quality evidence from FDA-requested RCTs does not support its use.)

Special Populations:

Immunocompromised Patients:

• Consider screening for HIV if extensive disease with minimal inflammation is present. 1, 4
• Referral to dermatology for extensive or recalcitrant disease. 1
• Rule out cryptococcal infection in HIV patients with atypical presentations. 1

Follow-up:

• Not usually necessary unless conjunctivitis persists or new lesions develop. 1, 4
• Monitor for resolution of conjunctivitis after periocular lesion removal. 1

Patient Counseling

Transmission Prevention:

• Hand hygiene with alcohol-based disinfectant or soap and water is the most important prevention method. 1
• Avoid direct skin-to-skin contact with infected individuals. 1
• Do not share towels, clothing, personal items, or equipment. 1
• Avoid scratching lesions to prevent autoinoculation and spread. 1

Water Exposure:

• Cover all lesions with waterproof bandages if water exposure is unavoidable. 1
• Limit exposure to swimming pools associated with known outbreaks. 1
• Hot tubs present higher transmission risk than standard pools due to warmer water, closer proximity, and shared seating surfaces. 1
• Return to communal water activities only when all lesions have completely resolved and no new lesions have appeared for several weeks. 1

Natural Course:

• Lesions typically persist 6-12 months but can last up to 4-5 years without treatment. 1, 3
• Spontaneous resolution occurs in most immunocompetent individuals. 1
• Erythema around lesions may represent normal inflammatory response as the immune system clears the virus. 1
• Lesions remain infectious throughout their entire course. 1

Treatment Expectations:

• Treatment aims to reduce transmission risk, prevent complications, and address cosmetic concerns. 2
• Treating all visible lesions, including early ones, reduces recurrence risk. 1
• Some treatments may cause temporary hyperpigmentation, particularly in darker skin tones. 1

Differential Diagnoses

Primary Differentials:

• Cryptococcal infection (in HIV patients): umbilicated papules that closely mimic molluscum contagiosum. 1, 3
• Verruca vulgaris (common warts): lack central umbilication, have rough surface. 2
• Basal cell carcinoma: typically in older adults, pearly appearance, may have central ulceration rather than umbilication.
• Keratoacanthoma: rapid growth, larger size, central keratin plug.

In Immunocompromised Patients:

• Disseminated fungal infections (histoplasmosis, cryptococcosis). 1
• Cutaneous lymphoma.
• Atypical mycobacterial infections.

In Children:

• Syringomas: small, firm papules without umbilication, typically periorbital.
• Milia: smaller, white, superficial cysts without umbilication.
• Closed comedones: associated with acne, different distribution.

Common Pitfalls:

• Failing to treat nascent lesions during initial treatment is a frequent cause of recurrence. 1
• Not recognizing extensive disease with minimal inflammation as a sign of immunodeficiency. 1, 4
• Overlooking periocular lesions that require active treatment to prevent ocular complications. 1