What are the differential diagnoses for a non-blanchable (not fading when pressed) lesion, excluding bruise?

Differential Diagnoses for Non-Blanchable Lesions (Excluding Bruise)

Primary Differentials Based on Lesion Characteristics

The most critical non-blanchable lesions to consider are purpura/petechiae (indicating vascular bleeding into skin), Stevens-Johnson syndrome/toxic epidermal necrolysis (showing purpuric macules with epidermal detachment), and angiokeratomas (vascular malformations that appear dark red to blue-black). 1

Purpuric/Petechial Lesions

• Purpura and petechiae represent extravasated blood in the skin from vascular damage or platelet dysfunction, appearing as red-purple macules that do not blanch with pressure 1, 2
• Leukocytoclastic vasculitis presents as palpable purpura (raised, non-blanchable lesions) rather than flat purpura, caused by small vessel inflammation 1, 3
• Benign pigmented purpura (Schamberg disease) shows "cayenne pepper"-like brown macules with scattered petechiae and minute telangiectasias, often on lower extremities 4
• Cutaneous collagenous vasculopathy demonstrates ectatic papillary dermal vessels with petechiae and telangiectasias, confirmed by periodic acid-Schiff staining showing hyalinized vessel walls 4

Severe Drug Reactions

• Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) presents with widespread purpuric macules or flat atypical targets that are non-blanchable, accompanied by epidermal detachment and positive Nikolsky sign 1, 3
• The purpuric macules in SJS/TEN consist of dark red centers surrounded by pink rings, often becoming confluent to produce large areas of dusky erythema 1
• Immediate hospitalization is required if skin sloughing exceeds 30% body surface area 5

Vascular Malformations

• Angiokeratomas appear as characteristic dark red to blue-black non-blanching angiectases, most commonly found between the umbilicus and thigh, becoming larger and more numerous with age 1
• These lesions are pathognomonic for Fabry disease when present in clusters, ranging from pinhead to several millimeters in size 1

Infectious Etiologies

• Cutaneous anthrax progresses from papule to vesicles to a painless ulcer with a black eschar (non-blanchable), accompanied by surrounding edema and regional lymphadenopathy 1
• Leishmaniasis can present with nodular, verrucous, or ulcerative non-blanchable lesions, often with a necrotic appearance and surrounding edema 1
• Plague (bubonic) may show a non-blanchable skin lesion at the portal of entry, accompanied by tender regional lymphadenopathy and systemic symptoms 1

Other Inflammatory Conditions

• Sweet syndrome demonstrates tender erythematous plaques or nodules with neutrophilic infiltrate on histology, which may appear non-blanchable 1, 3
• Erythema multiforme shows classic "iris" or target lesions with three distinct concentric zones, though these may have some blanchable components in the outer ring 3

Critical Diagnostic Approach

Document lesion morphology precisely: measure size, assess for epidermal detachment, examine distribution pattern (localized vs. generalized), and inspect all mucosal surfaces for erosions or hemorrhagic crusting. 1, 3

Essential Investigations

• Skin biopsy from lesional skin is mandatory for histological evaluation, with perilesional biopsy for direct immunofluorescence to exclude immunobullous disorders 3
• Complete blood count and coagulation profile to evaluate for thrombocytopenia, coagulopathy, or hematologic malignancy 2
• Gram stain and culture of any purulent or sanguinopurulent material if infection is suspected 5, 6
• HSV PCR or serology if erythema multiforme or SJS/TEN is considered 3

Key Clinical Pitfalls

• Purulent discharge indicates bacterial superinfection, not the primary diagnosis - true purpura and petechiae lack purulent exudate unless secondarily infected 1, 5
• Localized petechiae/purpura in well-appearing infants without fever are more likely benign (tourniquet phenomenon) and may only require 4-hour observation rather than extensive workup 2
• Visual assessment alone has only moderate predictive value - always obtain tissue diagnosis for definitive classification 5
• The absence of contrast blush on CT does not exclude active bleeding in trauma settings, but this principle applies less to dermatologic lesions 1

When to Escalate Care Immediately

• Rapidly progressive purpuric lesions with systemic symptoms (fever, hypotension, altered mental status) suggest meningococcemia or other septic vasculitis requiring immediate antibiotics 1
• Epidermal detachment >10% body surface area requires burn unit or intensive care admission for SJS/TEN management 1, 5
• Suspected invasive fungal infection in neutropenic patients mandates specialist consultation and empiric echinocandin therapy 5