Key Points

  • Impetigo is a highly contagious superficial skin infection due to Staphylococcus aureus or less commonly Streptococcus pyogenes.
  • Secondary impetigo, also known as impetiginization, may occur when these bacteria enter the skin through a disrupted barrier such as in preexisting dermatoses like atopic dermatitis, scabies, superficial cuts and abrasions, and insect bites.
  • Honey-colored crusted erosions are the typical clinical morphology for lesions of impetigo contagiosa—also known as non-bullous impetigo. Superficial bullae or erosions with surrounding scale and minimal crust are the hallmarks of bullous impetigo. Finally, ulcerative and necrotic lesions with pus can occur with ecthyma, a deeper form of non-bullous impetigo primarily due to pyogenes.
  • Impetigo is mostly self-limited, though treatment should be considered when extensive involvement occurs, when deeper involvement occurs as in ecthyma, or during outbreaks.
  • An important consideration in the treatment of impetigo is the rising incidence of methicillin-resistant S. aureus (MRSA). Bacterial cultures for the determination of species and antibiotic sensitivity are recommended when treatment is being considered.
  • Bullous impetigo is due to the local production of exfoliative toxins (ETA and ETB) produced by S. aureus, phage group II.

Introduction

Impetigo is a contagious superficial skin infection most common in children, with a peak incidence between ages 2 and 5. A recent systematic review of the global epidemiology of impetigo found a median prevalence rate of 12.3% in children and 4.9% in adults. Risk factors include poor hygiene, lower socioeconomic status and warm climate.

The two major forms of impetigo, non-bullous impetigo (impetigo contagiosa) and bullous impetigo, can masquerade as noninfectious diseases, as both may lack characteristic signs of acute infection (i.e., dolor, calor, tumor, and in rare cases may not be erythematous) and because of their tendency to form dry crusts. The clustering of lesions around facial orifices and exposed areas of the body is an important diagnostic clue. A rare deeper, ulcerative form of impetigo called ecthyma most commonly occurs on the lower extremities. Impetigo, in all its forms, can complicate preexisting skin conditions such as atopic dermatitis, scabies, insect bites, and cuts and abrasions. The presence of honey-colored crusts or erosions distinguishes impetigo contagiosa from bullous impetigo, which is typified by bullous lesions or erosions with peripheral scale and minimal or no crust. Ecthyma is notable for its distinctive purplish, ulcerated appearance that may be associated with necrosis and pus.

While in the past S. pyogenes was the most commonly implicated pathogen in non-bullous impetigo, it has been replaced more recently by S. aureus. Often, the infection can be due to a combination of these two common pathogens. Bullous impetigo is due to the local production of exfoliative toxins (ETA and ETB) produced by S. aureus, phage group II species. Systemic production of these toxins is the cause of staphylococcal scalded skin syndrome. Finally, ecthyma is due almost exclusively to S. pyogenes.

Initial Evaluation

Impetigo contagiosa (non-bullous impetigo)

Bullous lesions of impetigo

Differential Diagnosis

Herpes simplex: May result in painful or burning, crusted grouped vesicles near the mouth or nares, often recurrent in the same location. Grouped (herpetiform) pustular lesions resulting in erosions with scalloped borders are suggestive of herpes.

Eczema herpeticum: Superinfection of atopic dermatitis with herpes or impetiginizing bacteria (Staphylococcus or Streptococcus) is common and can be difficult to distinguish clinically. Bacterial and viral cultures may be required to determine which infection is present.

Staphylococcal scalded skin syndrome: A variation of impetigo that is systemic, with epidermolytic toxin-producing strains of S. aureus, resulting in widespread superficial exfoliation, erosions and/or flaccid blisters.

Bullous pemphigoid: Usually a disease of elderly adult individuals, the typical lesions are tense bullae, commonly arising from urticarial plaques. Biopsy with direct immunofluorescence can be used to confirm the diagnosis.

Pemphigus vulgaris: Usually results in more widespread flaccid bullae with erosions and crusting. Mucosal involvement is common. Biopsy with direct immunofluorescence and serum indirect immunofluorescence can be used to confirm the diagnosis.

Other dermatologic diseases to consider in the differential diagnosis include insect bites, acute contact dermatitis, thermal burns, candidiasis, scabies, varicella, and bullous erythema multiforme. In the case of ecthyma, deep fungal infections and ecthyma gangrenosum should also be ruled out.

Treatment

Most disease is self-limited; however treatment may hasten resolution and prevent spread. Treatment should be considered when quicker resolution is desired (i.e., when in cosmetically sensitive areas) in patients with extensive disease, deeper or systemic (i.e. ecthyma) infection, or during outbreaks.  

First-line treatment: For limited skin involvement, topical antibiotic treatment is first-line and there is evidence that it may be superior to systemic therapy.

In limited cases, topical antibiotic ointment applied directly to infected lesions for three to five days is equally effective as systemic therapy. Options include mupirocin 2% ointment (such as Bactroban or Centany®) three times daily or retapamulin 1% ointment (Altabax®) twice daily. Fusidic acid may also be used however this treatment is not available in the United States. These treatments may be used safely for localized disease (less than 2% body surface area) in patients 9 months or older. Ozenoxacin (Xepi™), a topical quinolone, was approved in 2017 for the treatment of impetigo due S. aureus and S. pyogenes in adult and pediatric patients 2 months of age and older. A thin layer should be applied topically to the affected areas every 12 hours for 5 days not exceeding 2% of body surface area or 100 cm2. Over-the-counter topical antibiotics such as bacitracin, neomycin, or triple antibiotic ointment should generally be avoided as they have not been shown to improve disease course and may lead to allergic sensitization.

Systemic therapy is indicated for more generalized skin involvement, or when skin infection is associated with systemic symptoms.

First-line therapies empiric systemic for adults include:

  • Dicloxacillin 125–500 mg by mouth every 6 hours for 10 days
  • Cephalexin 250–500 mg by mouth every 6–8 hours for 10 days

Patients with documented penicillin allergy who are unable to take dicloxacillin and in whom cephalosporins (such as cephalexin) are contraindicated, can be given:

  • Clindamycin 300–450 mg by mouth every 6 hours for 10 days or
  • Carithromycin 250 mg by mouth every 12 hours for 10 days for penicillin-allergic patients

For patients with known or high suspicion for methicillin-resistant S. aureus (MRSA) infection the following treatments should be considered (note: these treatments will not supply adequate coverage for strep):

  • Doxycycline 100 mg by mouth every 12 hours for 10 days (not to be used in children under age 9 due to risk of permanent tooth staining) or
  • Trimethoprim-sulfamethoxazole double strength one tablet by mouth twice a day for 10 days (for a suspected methicillin-resistant S. aureus infection).

Ancillary therapy

  • Obtain culture and sensitivity of exudate.
  • Since methicillin-resistant S. aureus is common in both community- and hospital-acquired skin and soft tissue infections, it is prudent to obtain a culture and to determine antibiotic susceptibilities
  • Penicillin V and erythromycin are no longer recommended due to rising rates of bacterial resistance to these antibiotics.
  • Obtain nasal swabs from patients and immediate relatives in refractory/recurrent cases to rule out carriage.
  • Address any possible fomites, underlying conditions or dermatitides, as these can lead to spread of infection and recurrent infection.

Pitfalls

  • Reinfection, transmission within families, and persistent nasal bacterial carriage are common. Nasal carriage should be determined through cultures of the nares of all individuals within a household, if possible.
    • Recurrent infection therapy:
      • Apply mupirocin 2% ointment intranasal twice a day for 5 days
      • Apply mupirocin 2% cream to body folds (axillae, groin, inframammary) twice a day for 5 days
      • Bleach baths, (one-quarter to one-half cup of household bleach in a full 40- gallon tub), chlorhexidine or other antimicrobial washes (i.e., sodium hypochlorite) 2–3 times per week avoiding eyes and ears.
  • Transmission of phage group II or other epidermolytic toxin generating strains of staphylococci to susceptible individuals (neonates, immunosuppressed individuals, persons in renal failure) can result in more generalized forms such as staphylococcal scalded skin syndrome.
  • Acute post-streptococcal glomerulonephritis (associated with Anti-DNase B and antistreptolysin antibodies) may be seen in 5% of impetigo cases caused by S. pyogenes.
  • Treatment does not appear to impact the risk of developing glomerulonephritis.
  • There is no evidence to date to support a link between strep-related impetigo and rheumatic fever.

When to refer to a dermatologist

  • If the diagnosis is not clear or recalcitrant to standard antibiotic protocols, the patient may need a biopsy to rule out other possible etiology.
  • If there is an underlying dermatosis or immune system condition that renders the patient at higher risk for recurrent disease.

Clinical Cases

Case 1

  • 8-year-old girl with two days’ history of erythema on the upper cutaneous lip extending onto the nose
  • No fevers, chills, malaise
  • No preceding illnesses or trauma

Initial visit

  • Obtain skin culture for bacteria; if the lesion is recurrent and unilateral, consider also obtaining a viral skin culture to rule out herpes simplex virus
  • Empiric treatment with mupirocin 2% ointment, applied three times daily for five days
  • Follow up in one week

One-week follow-up evaluation

  • Bacterial culture reveals S. aureus, methicillin-sensitive
  • Lesion resolved

Case 2

  • 7-year-old boy with a five-day history of yellow-colored crusting on the face
  • No fevers, chills, malaise
  • No preceding illness or dermatitis
  • No sick contacts

Initial visit

  • Obtain skin culture for bacteria; if the lesion is recurrent and unilateral, consider also obtaining a viral skin culture for herpes simplex virus from cells or fluid of a fresh sore
  • Empiric treatment with cephalexin 25–50 mg/kg/day by mouth divided every 12 hours for 10 days
  • Follow up in one week

One-week follow-up evaluation

  • Bacterial culture reveals S. aureus, methicillin-sensitive
  • Lesions are resolved

Case 3

  • 4-year-old boy with one week of widespread erythematous, honey-crusted annular plaques on the neck, trunk, upper arms; this is the third episode of similar eruption
  • Malaise without fevers, chills
  • Brother has had similar eruptions but not currently affected; father reports intermittent nasal crusting

Initial visit

  • Obtain skin culture for bacteria in addition to nasal cultures from patient, sibling, and father
  • Empiric treatment with cephalexin 25–50 mg/kg/day by mouth divided twice daily for 10 days
  • Follow-up in one week

One-week follow-up evaluation

  • Bacterial cultures reveal S. aureus, methicillin-resistant from both skin and nasal cultures; brother and father also have nasal carriage of the same organism
  • Lesions are not improved
  • Patient is switched to trimethoprim-sulfamethoxazole 8–12 mg TMP/kg/day divided every 12 hours for 10 days, also mupirocin 2% ointment applied twice daily to nares for 5 days
  • Brother and father also prescribed mupirocin 2% ointment applied twice times daily to nares for 5 days
  • Follow-up in one month; lesions resolved

References

Bolognia J, Schaffer JV, Cerroni L. (2018). Dermatology. Philadelphia: Elsevier Saunders.

Bowen AC, Mahé A, Hay RJ, et al. (2015). The global epidemiology of impetigo: A systematic review of the population prevalence of impetigo and pyoderma. PLoS One, 10: 1–15.

Cole C, Gazewood J. (2007). Diagnosis and treatment of impetigo. Am Fam Phys, 75(6): 859-864.

Geria A, Schwartz R. (2010). Impetigo update: new challenges in the era of methicillin resistance Cutis, 85(2): 65-70.

Koning S, Verhagen AP, van Siujilekom-Smith LW, Morris A, Butler CC, van der Wouden JC. (2004). Interventions for impetigo. Cochrane Database of Syst Rev, CD003261.

Lebwohl MG, Heymann WR, Berth-Jones J, Coulson IH. (2018). Treatment of Skin Disease Comprehensive Therapeutic Strategies. 5th ed. Philadelphia: Elsevier Saunders.

McCormick A, Fleming D, Charlton J, et al. (1995). Morbidity statistics from general practice: fourth national study 1991-1992. HMSO: London.

Stevens DL, Bryant AE. Impetigo, Erysipelas and Cellulitis. 2016 Feb 10. In: Ferretti JJ, Stevens DL, Fischetti VA, eds. Streptococcus pyogenes: Basic Biology to Clinical Manifestations. Oklahoma City (OK): University of Oklahoma Health Sciences Center, 2016. https://www.ncbi.nlm.nih.gov/books/NBK333408/. Accessed on January 3, 2017.