What is the likely diagnosis and recommended management for a solitary small vesicle on the foot of a 3‑month‑old infant who is otherwise healthy?

Likely Diagnosis and Management of Solitary Vesicle on Infant Foot

The most likely diagnosis is a solitary mastocytoma, which characteristically presents as a single lesion that can blister in friction-prone areas like the foot, and confirmation requires checking for Darier's sign (rubbing the lesion to see if it forms a wheal and erythema). 1, 2

Clinical Reasoning

Why Mastocytoma is Most Likely

• Solitary mastocytomas typically present at birth or within the first weeks of life as single lesions that can blister and form bullae, especially in interdigital or friction-prone locations on the foot. 2
• The presence of a foot lesion in an area prone to maceration and friction is a high-risk site for ulceration and bullae formation in mastocytomas. 2
• The absence of systemic symptoms (the baby is "stable and active") is consistent with solitary mastocytoma, where visceral involvement is rare. 2
• Mastocytomas can rapidly progress from a papule to a bulla, which matches the description of "one vesicle noted, may be one more very small." 2

Key Diagnostic Maneuver

Perform Darier's sign by gently rubbing the lesion—a positive test (formation of wheal and erythema) confirms cutaneous mastocytosis. 2

Critical Differential Diagnoses to Exclude

Herpes Simplex Virus (HSV)

• HSV can present with vesicular lesions on any skin surface in infants, though it more commonly affects the diaper/buttock area. 1
• At 3 months of age, this would represent primary HSV infection rather than reactivation. 1
• However, HSV typically presents with multiple grouped vesicles on an erythematous base, not a solitary lesion, and the baby would likely show systemic symptoms if disseminated. 1, 3
• If there is any concern for HSV (fever, irritability, multiple lesions, or immunocompromised state), obtain viral culture or PCR from vesicular fluid immediately. 1

Infantile Hemangioma

• Infantile hemangiomas typically appear before 4 weeks of age with maximum growth by 5 months, and interdigital/foot lesions are unusual locations. 4, 2
• Hemangiomas present as red/purple vascular lesions, not clear vesicles. 4

Friction Blister or Sucking Blister

• Sucking blisters occur on areas accessible to the infant's mouth (hands, fingers, wrists) and are present at birth or shortly after. 5
• At 3 months, the location on the foot makes this less likely unless there is clear history of trauma. 5

Recommended Evaluation

Immediate Assessment

• Examine the entire body to rule out urticaria pigmentosa (multiple mastocytomas) versus a solitary lesion. 2
• Perform Darier's sign on the lesion. 2
• Assess for symptoms of mast cell mediator release: facial flushing, pruritus, abdominal pain, diarrhea, hypotension, or respiratory symptoms. 2

If Mastocytoma is Confirmed

• No biopsy is routinely needed in young children with typical presentation. 2
• Avoid friction and trauma to the area; protect with soft bandage if needed. 2
• Use H1 antihistamines for pruritus control if present. 2
• Reassure parents that solitary mastocytomas typically resolve spontaneously before puberty and have an excellent prognosis. 2
• Educate parents that the lesion may blister with trauma but this is expected. 2

Red Flags Requiring Urgent Evaluation

• If fever, irritability, or systemic symptoms develop, immediately evaluate for disseminated HSV or other infectious causes. 1
• If multiple vesicles appear or the lesion spreads rapidly, obtain viral culture/PCR for HSV and consider empiric acyclovir while awaiting results. 1, 3
• If the infant is immunocompromised, maintain a lower threshold for hospitalization and IV acyclovir. 1

Common Pitfalls to Avoid

• Do not dismiss a solitary vesicle without examining the entire body—what appears solitary may be the first of multiple lesions in conditions like HSV or varicella. 1, 6
• Do not assume all vesicles are benign—infectious causes (HSV, varicella, bacterial) require prompt recognition and treatment. 6, 5
• Do not perform aggressive interventions (biopsy, PUVA) for typical mastocytomas in young children. 2
• Do not forget to check vaccination status for varicella, though at 3 months the infant would not yet have received this vaccine. 1