What is the approach to diagnosing and managing target lesions on the skin?

Diagnosis of Target Lesions on Skin

Target lesions on the skin require immediate differentiation between erythema multiforme (EM) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), as the latter represents a life-threatening emergency requiring urgent hospitalization while EM is typically self-limited. 1, 2

Immediate Clinical Assessment

Examine the morphology of the target lesions themselves:

• Classic "iris" or typical target lesions with three distinct concentric zones (central dusky area, pale edematous middle ring, outer erythematous ring) strongly suggest erythema multiforme 2, 3
• Flat atypical targets or purpuric macules with only two zones or poorly defined borders indicate SJS/TEN 1, 2
• Raised versus flat lesions help distinguish EM (typically raised, palpable) from SJS/TEN (flat, macular) 3, 4

Assess for epidermal detachment:

• Perform Nikolsky sign testing by applying lateral pressure to normal-appearing skin 1, 2
• A positive Nikolsky sign (skin sloughing with gentle pressure) indicates SJS/TEN, not EM 1, 2
• Document the percentage of body surface area with erythema and epidermal detachment separately using a Lund and Browder chart 1

Examine all mucosal surfaces systematically:

• Inspect the mouth, eyes, nose, genitalia, and perianal skin for erosions, blisters, and hemorrhagic crusting 1, 2
• Severe mucosal involvement with extensive erosions favors SJS/TEN over EM 1, 2
• Within 24 hours of suspected SJS/TEN diagnosis, arrange ophthalmology examination by a specialist experienced in ocular surface diseases 1

Critical Historical Elements

Document medication exposure meticulously:

• Record all medications taken and vaccinations received over the preceding 2 months, including over-the-counter and complementary therapies 1
• Note the date treatments were initiated, any dose escalations, when drugs were stopped, and any brand switches or medication errors 1
• Use the ALDEN (ALgorithm of Drug causality in Epidermal Necrolysis) online tool to predict likely causality of suspected drug reactions 1
• Immediately discontinue any potential culprit drug causing SJS/TEN 1

Identify infectious triggers:

• Document fever, malaise, and respiratory symptoms that may precede SJS/TEN by 1-3 days 1, 2
• Herpes simplex virus (HSV) is the most common trigger for EM, followed by Mycoplasma pneumoniae 2, 4
• SJS/TEN is predominantly drug-induced rather than infection-related 2, 4

Assess the distribution pattern:

• EM typically shows symmetric distribution on extremities, particularly dorsal hands and extensor surfaces 4
• SJS/TEN often begins on the trunk and face before spreading 1

Essential Diagnostic Investigations

Obtain skin biopsies:

• Perform a full-thickness skin biopsy from lesional skin just adjacent to a blister and send for routine histopathology 1
• Take a second biopsy from perilesional skin and send unfixed for direct immunofluorescence to exclude immunobullous disorders (pemphigus vulgaris, mucous membrane pemphigoid, bullous pemphigoid, linear IgA bullous dermatosis) 1, 2

Order infectious disease screening:

• HSV PCR or serology from skin swabs and conjunctival swabs 1, 2
• Mycoplasma and Chlamydia serology 1, 2
• Bacterial swabs from lesional skin for culture and sensitivity 1
• Chest X-ray if respiratory symptoms are present 1

Obtain baseline laboratory studies:

• Full blood count, C-reactive protein, urea and electrolytes, liver function tests, coagulation studies 1
• Glucose, magnesium, phosphate, bicarbonate, base excess, lactate 1

Document with standardized photographs:

• Take photographs of the skin showing lesion type and extent of involvement 1

Additional Differential Diagnoses to Consider

Immunobullous disorders:

• Direct immunofluorescence distinguishes these from EM and SJS/TEN by showing specific antibody deposition patterns 1, 2

Vasculitic conditions:

• Leukocytoclastic vasculitis presents with palpable purpura rather than true target lesions 2
• Sweet syndrome shows tender erythematous plaques or nodules with neutrophilic infiltrate on histology 2

Risk Stratification and Disposition

Calculate SCORTEN for prognostic assessment in suspected SJS/TEN:

• This scoring system helps predict mortality risk and guide intensity of care 1

Identify high-risk patients requiring immediate intensive care:

• Those with likely drug trigger and underlying diseases (malignancy, previous stem cell transplant) 1
• Patients with respiratory symptoms, airway involvement, or extensive epidermal detachment 1
• Assess airway patency by a pediatric/adult anesthetist and consider intubation if clinical signs support this, especially if transfer is planned 1

Critical Pitfalls to Avoid

• Do not delay discontinuation of suspected culprit drugs in SJS/TEN, as continued exposure worsens outcomes 1, 2
• Do not assume EM based solely on the presence of target lesions, as atypical targets occur in SJS/TEN 2, 3
• Do not miss mucosal involvement, which significantly impacts morbidity and helps distinguish SJS/TEN from EM 1, 2
• Do not fail to assess for epidermal detachment, as underestimating extent leads to inadequate treatment 1
• Do not overlook infectious triggers, particularly HSV in recurrent EM cases 1, 2, 4