What is the best approach to evaluate a rash?

Systematic Approach to Evaluating a Rash

The best approach to evaluate a rash requires a structured algorithmic assessment that begins with determining lesion morphology and duration, followed by targeted history for specific triggers, and selective use of diagnostic testing based on clinical suspicion rather than routine screening. 1

Initial Clinical Assessment: Lesion Characteristics

Document the precise morphology of individual lesions first, as this drives your entire diagnostic algorithm 1:

• Measure body surface area involvement using the Lund and Browder chart to quantify extent 1
• Determine if lesions are raised (papules/plaques) or flat (macules) 2
• Assess individual lesion duration: wheals lasting <24 hours suggest urticaria, while lesions persisting >24 hours indicate erythema multiforme, vasculitis, or fixed drug eruption 3, 4
• Look for target-like configurations: typical targets with three distinct zones versus atypical targets with only two zones or irregular borders 1, 2
• Check for vesicles, bullae, or epidermal detachment (positive Nikolsky sign) which signals severe conditions like Stevens-Johnson syndrome/toxic epidermal necrolysis 1

Critical History Elements

Focus your history on these specific high-yield questions rather than taking an unfocused general history 1, 5:

• Medication exposure in the past 2 months, including over-the-counter drugs, supplements, and any brand switches—document exact start dates 1
• Where did the rash start and how did it spread? Initial location often reveals the diagnosis 1
• Relationship to specific products: cosmetics, topical medications, personal care products, clothing, or occupational exposures 1
• Does the rash improve away from work or on weekends? This pattern strongly suggests occupational contact dermatitis 1
• Personal or family history of atopy (childhood eczema, asthma, hay fever) 1
• Immunotherapy exposure: checkpoint inhibitors cause rash in 34-45% of patients, typically within the first few weeks 1, 6

Distribution Pattern Analysis

Map the anatomic distribution systematically 1:

• Flexural involvement (antecubital/popliteal fossae, neck) suggests atopic dermatitis 1
• Palms and soles involvement narrows the differential significantly and requires specific consideration 5
• Face and eyelid predominance suggests contact dermatitis from cosmetics or airborne allergens 1
• Sun-exposed areas indicate photosensitivity reactions 1
• Extensor versus flexor surface distribution helps distinguish psoriasis (extensors) from atopic dermatitis (flexors) 5

Mucosal Examination

Always examine all mucosal sites (eyes, mouth, nose, genitalia) as mucosal involvement dramatically changes your differential 1:

• Mucositis with skin blistering suggests Stevens-Johnson syndrome/toxic epidermal necrolysis and requires immediate escalation of care 1
• Isolated mucosal erosions without extensive skin involvement may indicate pemphigus or mucous membrane pemphigoid 1

When to Perform Diagnostic Testing

Avoid routine laboratory testing in straightforward cases, but obtain targeted investigations when specific features are present 1, 3, 4:

Skin Biopsy Indications:

• Lesions persisting >24-48 hours to rule out urticarial vasculitis 3, 4
• Suspected Stevens-Johnson syndrome/toxic epidermal necrolysis: take one biopsy from lesional skin for histopathology and a second perilesional biopsy for direct immunofluorescence 1
• Atypical distribution or treatment-refractory dermatitis to exclude alternative diagnoses 1

Patch Testing Indications:

• Chronic or persistent dermatitis not responding to standard therapy 1
• Previously well-controlled atopic dermatitis that suddenly becomes difficult to manage (suggests superimposed allergic contact dermatitis) 1
• Occupational dermatitis or patterns suggesting specific contactant exposure 1
• Unusual distribution (e.g., sides of feet, isolated facial/eyelid involvement) 1

Laboratory Testing:

• Full blood count, ESR, CRP only if wheals persist >24 hours or systemic symptoms present 3, 4
• Complement levels (C3, C4) if urticarial vasculitis suspected 3
• Mycoplasma serology in appropriate clinical context 1

Critical Pitfalls to Avoid

Do not assume all eczematous rashes are atopic dermatitis—allergic contact dermatitis occurs in 6-60% of patients with known atopic dermatitis and is clinically indistinguishable without patch testing 1

Do not perform extensive allergy testing in acute urticaria that responds to antihistamines—diagnosis is clinical and testing is unnecessary unless specific triggers are suspected 3, 4

Do not miss superimposed bacterial infection in deteriorating eczema—look for crusting, weeping, or honey-colored exudate suggesting Staphylococcus aureus 1

Do not overlook drug-induced rash in children on antibiotics during viral illness—viral exanthema mimics drug allergy in 10% of cases, and distinction during the acute phase is often impossible 7

In patients on checkpoint inhibitors, do not attribute all rashes to the immunotherapy—rule out infection, other medications, and unrelated dermatoses first 1, 6

Algorithmic Decision Points

For vesiculobullous rashes with mucosal involvement: Stop all potential culprit drugs immediately, assess body surface area involvement, and if >10% or any mucosal involvement, consider Stevens-Johnson syndrome/toxic epidermal necrolysis and escalate care urgently 1

For chronic hand/facial dermatitis: If standard topical therapy fails or disease pattern is atypical, proceed directly to patch testing rather than escalating immunosuppression 1

For urticarial rashes: If individual wheals resolve within 24 hours, treat with second-generation antihistamines and avoid extensive workup; if wheals persist >24 hours, obtain skin biopsy to exclude vasculitis 3, 4

For checkpoint inhibitor-related rash: Grade severity by body surface area—use topical corticosteroids for <10% involvement, systemic corticosteroids (0.5-1 mg/kg prednisone) for >30% involvement or grade 3+ reactions 1, 6