What is the differential diagnosis and treatment for impetigo (impetigo)

Differential Diagnosis of Impetigo

The differential diagnosis of impetigo includes other vesiculobullous and crusted skin conditions, most importantly tinea faciei (especially when impetigo fails to respond to antibiotics), folliculitis, herpes simplex virus infection, contact dermatitis, atopic dermatitis with secondary infection, and ecthyma. 1

Primary Differential Considerations

Fungal Infections (Critical Pitfall)

• Tinea faciei can present identically to impetigo with erythematous pustules and golden crusts, particularly when caused by Trichophyton mentagrophytes. 2
• This mimicry is clinically significant because over 50% of impetigo-like tinea faciei cases have prolonged courses due to misdiagnosis and inappropriate antibiotic treatment. 2
• Suspect fungal infection when apparent impetigo fails to respond to appropriate topical antibiotics (mupirocin) after 48-72 hours. 1, 2
• Fungal culture should be obtained in antibiotic-resistant cases, as T. mentagrophytes complex is the most common causative agent. 2

Bacterial Skin Infections

• Folliculitis differs from impetigo by being more superficial, with inflammation and pus confined to the epidermis rather than extending through the dermis. 3
• Furuncles (boils) are deeper infections of hair follicles with suppuration extending into subcutaneous tissue, presenting as inflammatory nodules rather than superficial crusted lesions. 3
• Ecthyma represents a deeper variant of impetigo itself, caused by S. aureus and/or streptococci, characterized by circular erythematous ulcers with adherent crusts rather than superficial vesicles. 3, 1

Viral Infections

• Herpes simplex virus infection can present with grouped vesicles that rupture and crust, but typically has a more localized distribution and may have a history of recurrence. 4
• The vesicles in herpes are typically smaller, more uniform, and grouped on an erythematous base. 4

Inflammatory Dermatoses

• Atopic dermatitis with secondary bacterial infection (impetiginized eczema) represents secondary impetigo superimposed on underlying eczematous lesions. 3, 4
• Contact dermatitis may present with vesicles and crusting but typically has a history of exposure and distribution pattern corresponding to the contactant. 4

Distinguishing Clinical Features of Impetigo

Nonbullous Impetigo (70% of cases)

• Caused by Staphylococcus aureus, Streptococcus pyogenes, or both, presenting as erythematous papules that rapidly evolve into vesicles, then pustules, and finally characteristic thick honey-colored crusts. 3, 1, 4
• Lesions typically occur on exposed areas, most frequently the face and extremities. 3
• Pustules gradually enlarge and break down over 4-6 days before forming crusts. 3

Bullous Impetigo (30% of cases)

• Caused exclusively by toxin-producing strains of S. aureus, characterized by fragile, thin-roofed vesicopustules that form when toxins cleave the dermal-epidermal junction. 1, 4
• Bullae initially contain clear yellow fluid that becomes darker and more turbid, often rupturing to leave thin brown crusts resembling lacquer. 3
• More likely to affect intertriginous areas compared to nonbullous impetigo. 4

Diagnostic Approach

When to Obtain Cultures

• Cultures of vesicle fluid, pus, erosions, or ulcers should be obtained in cases of treatment failure, suspected MRSA, or recurrent infections. 1, 5
• Culture is particularly important when impetigo does not respond to appropriate therapy after 48-72 hours, as this may indicate alternative diagnoses like tinea faciei. 1, 2

Clinical Diagnosis

• The diagnosis of impetigo is typically made clinically based on the characteristic appearance of honey-colored crusted lesions, though culture may be useful in atypical cases. 4, 6
• Regional lymphadenitis may occur, but systemic symptoms are usually absent. 3

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Treatment of Impetigo

For localized impetigo, topical mupirocin 2% ointment applied three times daily for 5-7 days is the first-line treatment, while extensive disease requires oral antibiotics active against both S. aureus and streptococci. 1, 7

First-Line Treatment: Topical Antibiotics

Mupirocin (Preferred)

• Topical mupirocin 2% ointment applied three times daily for 5-7 days is FDA-approved and guideline-recommended as first-line treatment for localized impetigo. 1, 7
• Clinical efficacy rates of 71-93% have been demonstrated in controlled trials, with pathogen eradication rates of 94-100%. 7
• Mupirocin is effective against both S. aureus and S. pyogenes. 7

Alternative Topical Agents

• Retapamulin 1% ointment applied twice daily for 5 days is an effective alternative for limited impetigo. 8, 4
• Fusidic acid (where available) has similar efficacy to mupirocin, with no clear superiority of either agent. 1, 9

Evidence for Topical Superiority

• Topical antibiotics are superior to placebo (RR 2.24,95% CI 1.61-3.13) and equal or superior to oral antibiotics for localized disease. 9
• Topical mupirocin was slightly superior to oral erythromycin (RR 1.07,95% CI 1.01-1.13) in pooled analysis. 9

Indications for Oral Antibiotics

Oral antibiotics should be used when impetigo is extensive, involves multiple sites, topical therapy is impractical, treatment with topical antibiotics has failed, or systemic symptoms are present. 1, 8, 5

For Methicillin-Susceptible S. aureus (MSSA)

• Dicloxacillin 250 mg four times daily for adults or cephalexin 250-500 mg four times daily for adults are recommended first-line oral agents. 1, 8, 5
• Oral antibiotic dosing should be adjusted by weight for children. 1, 8

For Methicillin-Resistant S. aureus (MRSA)

• Clindamycin 300-450 mg three times daily, trimethoprim-sulfamethoxazole (TMP-SMX), or doxycycline (not for children under 8 years) are recommended for MRSA coverage. 1, 8, 5
• Clindamycin proves helpful in suspected MRSA infections. 4
• TMP-SMX covers MRSA but is inadequate for streptococcal infection alone. 4

For Streptococcal Infections

• When streptococci alone are the cause, penicillin is the drug of choice, and for penicillin-allergic patients, a macrolide or clindamycin is recommended. 1
• However, penicillin was inferior to erythromycin (RR 1.29,95% CI 1.07-1.56) and cloxacillin (RR 1.59,95% CI 1.21-2.08) in comparative trials. 9

Critical Treatment Pitfalls

Avoid Penicillin Monotherapy

• Penicillin alone is not effective for impetigo as it lacks adequate coverage against S. aureus, which is present in the majority of cases. 8, 5, 4

Avoid Topical Disinfectants

• Topical disinfectants are inferior to antibiotics (RR 1.15,95% CI 1.01-1.32) and should not be used as primary treatment. 6, 9

Recognize Treatment Failure

• Re-evaluate if no improvement after 48-72 hours of therapy, as this may indicate MRSA, resistant organisms, or alternative diagnoses like tinea faciei. 1, 8, 2

Treatment Duration and Supportive Care

• Topical treatment should be used for 5-7 days. 1, 8, 5
• Oral antibiotics should be administered for 5-10 days. 1, 8, 5
• Lesions should be kept covered with clean, dry bandages and good personal hygiene maintained to prevent spread. 1, 8

Special Clinical Situations

Recurrent Impetigo

• Application of mupirocin ointment twice daily in the anterior nares for the first 5 days each month can reduce recurrences by approximately 50%. 5
• Clindamycin 150 mg daily for 3 months may decrease subsequent infections by approximately 80% in cases of persistent or recurrent nasal impetigo with nasal colonization. 5

Outbreak Settings

• Systemic antimicrobials should be used during outbreaks of poststreptococcal glomerulonephritis to help eliminate nephritogenic strains of Streptococcus pyogenes. 1

Pediatric Considerations

• Tetracyclines (doxycycline, minocycline) should not be used in children under 8 years of age. 1, 8, 5
• Pediatric dosing should be weight-based for all oral antibiotics. 1, 8

Antibiotic Resistance Considerations

• Bacteria causing impetigo show growing resistance rates for commonly used antibiotics, including methicillin-resistant S. aureus, macrolide-resistant streptococcus, and mupirocin-resistant streptococcus. 4, 10
• Empiric treatment should account for local resistance patterns, particularly MRSA prevalence. 4
• Fusidic acid, mupirocin, and retapamulin cover methicillin-susceptible S. aureus and streptococcal infections. 4