What is the differential diagnosis (Ddx) for non-erythematous facial papules that appear umbilicated, primarily on the cheeks bilaterally?

Differential Diagnosis for Non-Erythematous Umbilicated Facial Papules on Bilateral Cheeks

The most likely diagnosis is molluscum contagiosum, which characteristically presents as shiny, dome-shaped umbilicated papules that are non-erythematous and can occur bilaterally on the face, particularly in children and immunocompromised individuals. 1

Primary Diagnosis: Molluscum Contagiosum

Molluscum contagiosum should be your first consideration given the classic umbilicated appearance and bilateral cheek distribution. 1

Clinical Features Supporting This Diagnosis:

• Appearance: Single or multiple shiny, dome-shaped umbilicated lesions that are typically 2-5 mm in size, whitish, pink, or skin-colored 1, 2
• Distribution: Can occur anywhere on the face, with bilateral presentation being common 2, 3
• Surface characteristics: Smooth, shiny surface with central umbilication (the pathognomonic feature) 1, 2
• Associated findings: May have pruritus, though lesions themselves are typically non-tender 1

Diagnostic Confirmation:

• Clinical diagnosis is usually sufficient when the classic umbilicated appearance is present 2, 3
• Dermoscopy reveals yellowish-white polylobulated structures with peripheral telangiectasia, which can confirm the diagnosis non-invasively 2, 3
• Skin biopsy is reserved for atypical presentations or diagnostic uncertainty 2

Key Populations at Risk:

• Children (most common demographic) 1, 2, 4
• Immunocompromised patients (HIV, transplant recipients, those on immunosuppressive therapy) may present with multiple, larger, or atypical lesions 1, 5
• Sexually active adults (though facial lesions are less commonly sexually transmitted) 2, 4

Alternative Differential Diagnoses to Consider

1. Cutaneous Cryptococcosis (in Immunocompromised Patients)

• Can present as umbilicated papules mimicking molluscum contagiosum 1
• Key distinguishing features: More common in severely immunocompromised patients, may have systemic symptoms 1
• Requires skin biopsy with fungal stains and culture for definitive diagnosis 1, 6

2. Disseminated Fungal Infections

• Aspergillus and other invasive fungi can cause cutaneous lesions that begin as erythematous papules but may become pustular with central ulceration 1, 6
• Critical distinction: These typically have an erythematous base and occur in neutropenic or severely immunocompromised patients 1
• Less likely given the non-erythematous presentation described 1

3. Basal Cell Carcinoma (Nodular Type)

• Can occasionally present with central umbilication 2
• Key differences: Usually solitary, occurs in older adults with sun exposure history, pearly appearance with telangiectasias 2
• Bilateral symmetric presentation on cheeks would be unusual

4. Atypical Molluscum Presentations

• Giant molluscum: Lesions >1 cm, more common in immunocompromised patients 3
• Disseminated molluscum: Multiple widespread lesions in immunosuppressed individuals 3
• Inflammatory variants: May have surrounding erythema (perilesional eczema, BOTE sign) 3

Clinical Pitfalls to Avoid

Common Diagnostic Errors:

• Assuming all umbilicated lesions are benign: In immunocompromised patients, always consider opportunistic infections including cryptococcosis and disseminated fungal infections 1, 6
• Missing immunocompromised status: Always assess immune status, as this dramatically changes the differential and management approach 1, 5
• Overlooking the need for biopsy: When lesions are atypical, rapidly progressive, or in immunocompromised patients, biopsy with histology and culture is essential 1, 6

Red Flags Requiring Immediate Further Investigation:

• Rapidly enlarging lesions (>1 cm in <24 hours) suggest aggressive infection like ecthyma gangrenosum 1
• Systemic symptoms (fever, malaise) with skin lesions in immunocompromised patients 1
• Necrotic centers developing in previously umbilicated lesions 1
• Known severe immunosuppression (neutropenia, HIV with low CD4 count, transplant recipients) 1

Management Approach

For Immunocompetent Patients with Classic Molluscum:

• Observation is reasonable as lesions typically self-resolve in 6-12 months 7, 2
• Active treatment is indicated for extensive disease, cosmetic concerns, or to prevent autoinoculation 1, 2, 5
• Treatment options include cryotherapy, curettage, or topical agents (though specific agents should be age-appropriate) 7, 2

For Immunocompromised Patients:

• Biopsy or aspiration should be performed early to obtain material for histological and microbiological evaluation 1, 6
• Consider both bacterial and fungal cultures, as well as histopathology 1, 6
• Empiric antimicrobial therapy may be necessary while awaiting culture results in severely immunocompromised patients with systemic symptoms 1