What is the cause of a skin rash with eruptions?

Understanding Skin Rash with Eruptions

A skin rash with eruptions is a nonspecific cutaneous manifestation that can result from multiple etiologies including drug reactions, viral infections, medication-induced toxicity (particularly EGFR inhibitors and chemotherapy), graft-versus-host disease in transplant patients, and fungal infections—requiring systematic evaluation of medication history, timing of onset, morphology, distribution, and associated systemic symptoms to determine the underlying cause. 1, 2

Algorithmic Approach to Diagnosis

Step 1: Categorize by Morphology

The first critical step is identifying the rash pattern 2:

• Maculopapular eruptions: Flat or raised lesions, most common with drug reactions and viral infections 3, 1
• Vesiculobullous: Fluid-filled lesions suggesting viral infections (VZV, HSV) or severe drug reactions 3, 2
• Pustular/papular: Follicular-based eruptions typical of EGFR inhibitor toxicity 3
• Petechial/purpuric: Non-blanching lesions indicating vascular involvement or infection 2

Step 2: Assess Timing and Medication History

The temporal relationship to drug exposure is diagnostically crucial 4, 5:

• Within 2-4 weeks of drug initiation: Consider EGFR inhibitor-induced acneiform rash (occurs in 45-100% of patients), appearing primarily on face and upper trunk 3, 6
• 7-14 days after antibiotic start: Evaluate for drug hypersensitivity versus concurrent viral infection 5
• First year post-transplant: Suspect acute graft-versus-host disease (25-45% incidence in transplant recipients) 3

Step 3: Identify High-Risk Features Requiring Urgent Action

Immediately discontinue suspected medications and hospitalize if 3:

• Body surface area involvement >50% (Grade 3) 3, 6
• Presence of vesicles, bullae, skin detachment, or mucosal ulcerations suggesting Stevens-Johnson syndrome or DRESS 3
• Systemic symptoms including fever, eosinophilia, or organ dysfunction 3, 5

Specific Clinical Contexts

EGFR Inhibitor-Induced Eruptions

For patients on cetuximab (Erbitux) or similar agents, the acneiform rash is a class effect occurring in 75-90% of patients 3, 6:

• Presents as sterile follicular papules and pustules without comedones (distinguishing it from acne vulgaris) 3
• Typically affects sebaceous gland-rich areas: face, scalp, upper chest, back 3
• Grade 1 (localized): Topical antibiotics (erythromycin, metronidazole) twice daily 6
• Grade ≥2 (diffuse <50% BSA): Add oral tetracyclines (doxycycline or minocycline) for anti-inflammatory effects 6
• Critical caveat: Rash severity correlates with improved survival outcomes; avoid premature treatment discontinuation unless Grade 3 or higher 6

Viral Infections in Immunocompromised Patients

In transplant recipients or immunosuppressed patients, herpes zoster presents as unilateral vesicular eruption with dermatomal distribution 3:

• Lesions evolve from erythematous macules to papules to vesicles over 24-72 hours 3
• High-dose IV acyclovir is mandatory treatment (oral agents reserved only for mild cases with transient immunosuppression) 3
• Without treatment, 10-20% risk of dissemination and chronic ulceration with secondary bacterial/fungal superinfection 3

Acute Graft-Versus-Host Disease

Grade I aGVHD (stage 1-2 skin involvement, <50% BSA) 3:

• Continue or restart immunosuppressive agent 3
• Apply medium-to-high potency topical steroids (triamcinolone, clobetasol) except on face where low-potency hydrocortisone is used 3, 7
• Topical tacrolimus is an alternative 3

Grades II-IV aGVHD 3:

• Systemic corticosteroids: 0.5-1 mg/kg/day methylprednisolone for Grade II; 1-2 mg/kg/day for Grades III-IV 3
• Never escalate methylprednisolone above 2 mg/kg/day 3

Drug Reaction Considerations

When rash appears during antibiotic therapy with concurrent viral symptoms 5:

• Absence of eosinophilia is an early marker suggesting viral etiology rather than DRESS syndrome 5
• Prominent midface edema with maculopapular rash appearing within days of amoxicillin intake may mimic DRESS but resolve rapidly (2-5 days) if viral 5
• Presence of eosinophilia strongly suggests true drug hypersensitivity requiring permanent antibiotic avoidance 5

Fungal Infections in Moist Areas

Candida overgrowth in intertriginous regions presents with pruritic erythematous eruptions 8:

• Use oil-in-water creams rather than occlusive ointments 8
• Apply topical azoles (clotrimazole, miconazole) twice daily 8
• Keep affected areas dry with absorbent powders 8

Common Pitfalls to Avoid

• Do not use topical corticosteroids as monotherapy for EGFR inhibitor rash; they are not generally recommended but may be beneficial only in combination with topical antibiotics 6
• Avoid administering systemic steroids to neutropenic febrile patients without careful consideration, as steroids mask infection symptoms 4
• Do not label children as "amoxicillin-allergic" based solely on rash during viral URTI; confirm true drug hypersensitivity with eosinophilia and RegiSCAR scoring 5
• Never continue EGFR inhibitor therapy if Grade 3 rash develops or if DRESS/Stevens-Johnson syndrome is suspected 3, 6