What is the differential diagnosis (Ddx) for non-erythematous facial umbilicated papules on bilateral cheeks?

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

Molluscum contagiosum is the primary diagnosis to consider for non-erythematous umbilicated papules on bilateral cheeks, presenting as shiny, dome-shaped, skin-colored papules with central umbilication. 1, 2

Primary Diagnosis: Molluscum Contagiosum

Clinical Features:

• Skin-colored, whitish, or pink papules with shiny surface and characteristic central umbilication 1
• Firm, rounded, dome-shaped appearance 3, 4
• Commonly affects the face, trunk, and extremities in children 5, 1
• Typically asymptomatic, though may present with itching or occasional bacterial superinfection 1
• Lesions persist 6-12 months in immunocompetent patients but can last up to 4 years 1

Key Diagnostic Points:

• The umbilication becomes more prominent as lesions mature 1
• Diagnosis is primarily clinical based on characteristic appearance 3, 4
• Dermoscopy can be a useful diagnostic tool if clinical doubt exists 3

Critical Alternative Diagnoses in Specific Populations

Cutaneous Cryptococcosis (Immunocompromised Patients)

This is the most important alternative diagnosis that must not be missed, particularly in HIV-positive or transplant patients. 5, 2

Distinguishing Features:

• Umbilicated papules resembling molluscum contagiosum occur in AIDS patients with disseminated cryptococcosis 5
• More common in severely immunocompromised patients with systemic symptoms 2
• Skin lesions seen in up to 15% of patients with disseminated cryptococcosis, manifesting as papules, pustules, purpura, ulcers, or cellulitis 5
• In transplant recipients, cellulitis may occur without evidence of dissemination 5

Critical Action: In immunocompromised patients, early biopsy or aspiration is essential to obtain material for histological and microbiological evaluation, including both bacterial and fungal cultures 2

Basal Cell Carcinoma (Older Adults)

• Nodular type can occasionally present with central umbilication 2
• Usually solitary rather than bilateral 2
• Occurs in older adults with sun exposure history 2
• Has pearly appearance with telangiectasias 2

Clinical Approach Based on Immune Status

Immunocompetent Patients:

• Observation is reasonable as lesions typically self-resolve in 6-12 months 2
• Active treatment indicated for extensive disease, cosmetic concerns, or to prevent autoinoculation 2
• Curettage is the most efficacious treatment with lowest side effect rate (4.7%) 6
• Cantharidin is a useful bloodless alternative but has moderate complications (18.6% side effect rate) 6

Immunocompromised Patients:

• Multiple large lesions may resemble other conditions 1
• Lesions may persist longer and be more extensive 1
• Do not assume all umbilicated lesions are benign—opportunistic infections like cryptococcosis and disseminated fungal infections must be considered 2

Red Flags Requiring Immediate Investigation

The following findings mandate urgent evaluation and should not be dismissed as simple molluscum: 2

• Rapidly enlarging lesions (>1 cm in <24 hours) suggesting aggressive infection like ecthyma gangrenosum 5, 2
• Systemic symptoms (fever, malaise) accompanying skin lesions in immunocompromised patients 5, 2
• Any immunocompromised patient with umbilicated lesions requires early biopsy 2

Common Pitfalls to Avoid

• Assuming all umbilicated lesions are molluscum in immunocompromised patients without tissue diagnosis 2
• Failing to assess immune status, which dramatically changes the differential and management approach 2
• Not recognizing that cryptococcal skin lesions can be the presenting sign of disseminated disease requiring CNS evaluation 5
• Overlooking the possibility of ecthyma gangrenosum, which can present as painless erythematous papules that progress rapidly and may be caused by Pseudomonas, fungi including Candida, Aspergillus, or even HSV 5

Diagnostic Algorithm

For immunocompetent children/young adults with classic bilateral umbilicated papules:

• Clinical diagnosis of molluscum contagiosum is sufficient 3, 4
• Dermoscopy if diagnostic uncertainty 3

For immunocompromised patients or atypical presentations:

• Obtain biopsy or aspiration for histology and culture (bacterial and fungal) 2
• Rule out CNS involvement if cryptococcosis suspected 5
• Consider blood cultures and antigen detection in severely immunocompromised patients 5