What is the best course of action for a patient with a severe rash covering their entire body, including the face, with unknown age, medical history, and duration of the rash?

Immediate Assessment and Management of Severe Generalized Rash

For a patient presenting with severe rash covering the entire body including the face, immediately assess for life-threatening conditions by checking for fever, mucosal involvement, petechiae/purpura, and systemic symptoms—then initiate supportive care while pursuing urgent diagnostic workup. 1

Critical Red Flags Requiring Immediate Action

• Fever with petechial/purpuric rash: Consider Rocky Mountain Spotted Fever (RMSF), meningococcemia, or other life-threatening infections requiring immediate empiric antibiotics 2
• Mucosal involvement with blistering: Suspect Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)—discontinue all potential offending medications immediately and consider ICU admission 2, 3
• Rapid progression with systemic symptoms: Drug reaction with eosinophilia and systemic symptoms (DRESS) can present with fever, hematological abnormalities, and multi-organ involvement 2, 4

Initial Diagnostic Approach

History Elements to Obtain Immediately

• Medication history: Recent medication changes (especially within 3-12 days), particularly anticonvulsants, antibiotics, or sulfonamides 2, 3
• Tick exposure: Recent outdoor activities, geographic location, tick bite within past 3-12 days 2
• Timing and progression: Sudden onset versus gradual, centripetal spread pattern, involvement of palms/soles 2
• Associated symptoms: Headache, photophobia, nausea, vomiting, abdominal pain, altered mental status, conjunctival injection 2

Physical Examination Priorities

• Rash morphology: Determine if petechial/purpuric, erythematous, maculopapular, or vesiculobullous 1, 5
• Distribution pattern: Note if palms/soles involved (suggests RMSF, drug reaction, or other serious conditions), face typically spared in RMSF 2
• Mucosal surfaces: Check for oral, ocular, or genital involvement suggesting SJS/TEN 2, 3
• Systemic signs: Vital signs, mental status, signs of end-organ damage 2

Management Algorithm Based on Clinical Presentation

If Fever + Petechial/Purpuric Rash Present

Start empiric doxycycline 100 mg twice daily immediately without waiting for confirmatory testing if RMSF suspected—delay in treatment significantly increases mortality from 5-10% to much higher rates 2

• RMSF classically presents with fever, headache, and rash appearing 2-4 days after fever onset, but only minority have classic triad initially 2
• Rash begins on ankles/wrists as blanching pink macules, spreads centrally, becomes maculopapular then petechial by days 5-6 2
• Up to 20% never develop rash or have atypical presentation—do not exclude diagnosis based on absence of rash 2
• Children develop rash earlier and more frequently than adults 2

If Suspected Drug Reaction

Immediately discontinue all non-essential medications, particularly those started within past 2-8 weeks 2, 3

• NNRTIs (especially nevirapine) cause rash in majority of patients, typically within first weeks of therapy 2
• Anticonvulsants (lamotrigine, phenytoin, carbamazepine) are high-risk for severe cutaneous reactions 3
• Do not use prophylactic corticosteroids when initiating high-risk medications—this has not proven effective and may increase rash incidence 2
• For mild-moderate drug rash without systemic symptoms: antihistamines for symptomatic relief may be considered, but discontinue drug if progression occurs 2

If EGFR Inhibitor-Related (Cancer Patients)

For grade 1 (mild scattered lesions): Continue therapy with topical antibiotics (clindamycin 2%, erythromycin 1%, or metronidazole 0.75%) and moisturizers 2

For grade 2 (moderate, localized desquamation <50% body surface): Continue therapy with intensive moisturizers, topical antibiotics, short-term topical corticosteroids (prednicarbate 0.02%), and oral doxycycline 100 mg twice daily for at least 2 weeks 2

For grade 3 (severe, ≥50% body surface involvement): Temporarily interrupt EGFR inhibitor therapy and refer to dermatology 2

If Eczematous/Inflammatory Pattern

Apply moderate-potency topical corticosteroid (clobetasone butyrate 0.05% or betamethasone valerate 0.025%) twice daily for 1-2 weeks combined with liberal emollient use 6

• Use hydrocortisone 1% for face/groin areas to avoid skin atrophy 2, 6
• Apply emollients immediately after bathing when most effective, estimated 200-400g per week needed 2, 6
• Avoid soaps—use dispersible cream as soap substitute instead 6
• For severe pruritus: sedating antihistamines (diphenhydramine, clemastine) at night; non-sedating antihistamines have little value for eczema-related itch 6

Secondary Infection Management

If crusting, weeping, or signs of bacterial superinfection present: Start flucloxacillin (or erythromycin if penicillin-allergic) for presumed Staphylococcus aureus 6

• Take bacterial swabs if no response to treatment 6
• Monitor for grouped vesicles suggesting viral superinfection 6

Common Pitfalls to Avoid

• Waiting for classic triad (fever, rash, tick bite) before treating suspected RMSF—only minority present with all three initially 2
• Assuming absence of rash excludes RMSF—up to 20% never develop rash 2
• Continuing NNRTI therapy through severe rash—permanently discontinue if Stevens-Johnson syndrome or TEN suspected 2
• Using alcohol-containing topical preparations—these worsen xerosis and should be avoided 2
• Underusing emollients due to corticosteroid fears—liberal moisturizer use is cornerstone of inflammatory rash management 2, 6
• Relying on non-sedating antihistamines for eczematous itch—these provide minimal benefit 6

Reassessment and Escalation

Reassess after 2 weeks of treatment or immediately if worsening 2, 6

Refer to dermatology if: No improvement after 2 weeks, grade 3 severity, diagnostic uncertainty, or concern for life-threatening condition 2, 6

Consider skin biopsy if diagnosis remains unclear after initial evaluation 3, 4