What is the most likely diagnosis and initial management for a red, raised, coalescing rash confined to the extremities?

Red, Raised, Coalescing Rash Limited to Extremities

The most likely diagnosis is erythema multiforme (EM), and initial management should focus on identifying HSV or Mycoplasma pneumoniae as triggers while initiating symptomatic treatment with antihistamines; however, Rocky Mountain Spotted Fever (RMSF) must be immediately excluded given its 5-10% mortality rate if treatment is delayed. 1, 2

Immediate Life-Threatening Exclusions

Before proceeding with EM diagnosis, you must rule out RMSF emergently:

• If the patient has fever, headache, tick exposure (or lives in endemic area), or any systemic symptoms, initiate doxycycline 100 mg twice daily immediately without waiting for laboratory confirmation. 2, 3
• RMSF initially presents as small (1-5 mm) blanching pink macules on ankles, wrists, or forearms 2-4 days after fever onset, then progresses to maculopapular with central petechiae spreading to palms, soles, arms, legs, and trunk while sparing the face. 2
• Critical pitfall: Up to 40% of RMSF patients report no tick bite history, and up to 20% never develop a rash—absence of these does not exclude RMSF. 2, 3
• Obtain CBC with differential (looking for thrombocytopenia, increased bands), comprehensive metabolic panel (looking for hyponatremia, elevated transaminases), and acute serology for Rickettsia rickettsii. 2, 3

Erythema Multiforme: Diagnostic Features

Once RMSF is excluded, EM becomes the primary diagnosis based on:

Lesion morphology:

• Characteristic three-zone target configuration with central dark papule/vesicle, pale zone, and erythematous halo (targetoid morphology with dusky red and white concentric rings). 1
• Lesions are raised, coalescing, and remain fixed for a minimum of 7 days (unlike urticaria which resolves within 24 hours). 1

Distribution pattern:

• Lesions typically begin on ankles, wrists, or forearms and spread to palms, soles, arms, legs, and trunk while most often sparing the face. 1
• Predominantly affects limbs and extremities with typical target lesions or raised atypical targets. 1

Identifying the Trigger

Document the following to identify the underlying cause:

• HSV infection history: EM appears approximately 10 days after viral infection through a hypersensitivity reaction with cytotoxic T lymphocytes inducing keratinocyte apoptosis. 1
• Mycoplasma pneumoniae exposure: This is a significant infectious trigger, particularly common in children, and may present with predominantly mucous membrane involvement with little or no cutaneous lesions. 1
• Recent medication use (especially anticancer agents, which can cause toxic erythema resembling EM). 1

Initial Management Algorithm

Step 1: Symptomatic relief

• Initiate second-generation nonsedating H1-antihistamines (e.g., desloratadine 5 mg once daily for adults and adolescents ≥12 years). 4, 5
• These are first-line pharmacotherapy and can be titrated to larger than standard doses if needed. 5

Step 2: Monitor lesion evolution

• Photograph and mark lesion borders to track progression or migration over 7 days. 1
• EM lesions remain fixed, distinguishing them from urticaria (which migrates and resolves within 24 hours). 1

Step 3: Histopathological confirmation if uncertain

• Consider biopsy when clinical diagnosis is uncertain—EM shows variable epidermal damage ranging from individual cell apoptosis to confluent epidermal necrosis. 1
• Histopathology helps exclude other blistering dermatoses that may mimic EM. 1

Critical Differential Diagnoses to Exclude

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN):

• Features flat atypical targets or purpuric macules with epidermal detachment and positive Nikolsky sign (not raised coalescing lesions). 1
• Usually drug-triggered with 5-30% mortality rate (versus EM which is mostly HSV-related with better prognosis). 1

Urticaria:

• Individual lesions resolve within 24 hours and are intensely pruritic, raised wheals that blanch with pressure. 6, 5
• Generalized distribution with no specific pattern (not limited to extremities). 6

Sweet's Syndrome:

• Tender, red inflammatory nodules or papules usually affecting upper limbs, face, or neck (not coalescing target lesions). 7
• Associated with IBD and responds to systemic corticosteroids. 7

When to Escalate Care

Hospitalize immediately if:

• Systemic toxicity develops (fever, altered mental status, rapidly progressive rash). 3
• Mucosal involvement suggests progression toward SJS/TEN. 1
• Clinical response to antihistamines is absent after 48 hours with worsening lesions. 5