INTRODUCTION — Impetigo is a contagious, superficial bacterial infection observed most frequently in children ages two to five years, although older children and adults may also be affected. It may be classified as primary impetigo (direct bacterial invasion of previously normal skin) (picture 1A-E) or secondary impetigo (infection at sites of minor skin trauma such as abrasions, minor trauma, and insect bites, or underlying conditions such as eczema (picture 2)). Pyoderma and impetigo contagiosa are sometimes used as synonyms for primary impetigo. The occurrence of secondary impetigo is sometimes referred to as "impetiginization."
The infection usually occurs in warm, humid conditions and is easily spread among individuals in close contact; risk factors include poverty, crowding, poor hygiene, and underlying scabies [1,2]. Carriage of group A Streptococcus (GAS; Streptococcus pyogenes) and Staphylococcus aureus predisposes to subsequent impetigo [3].
CLINICAL MANIFESTATIONS — Variants of impetigo include nonbullous impetigo, bullous impetigo, and ecthyma. Systemic symptoms are usually absent. Regional lymphadenitis may occur.
Nonbullous impetigo — Nonbullous impetigo is the most common form of impetigo. Lesions begin as papules that progress to vesicles surrounded by erythema. Subsequently they become pustules that enlarge and rapidly break down to form thick, adherent crusts with a characteristic golden appearance; this evolution usually occurs over approximately one week (picture 1A-B, 1F-G). Lesions usually involve the face and extremities. Multiple lesions may develop but tend to remain well localized.
Bullous impetigo — Bullous impetigo is a form of impetigo seen primarily in young children in which the vesicles enlarge to form flaccid bullae with clear yellow fluid, which later becomes darker and more turbid; ruptured bullae leave a thin brown crust (picture 1D-E, 1H) [4,5]. Usually there are fewer lesions than in nonbullous impetigo, and the trunk is more frequently affected. Bullous impetigo in an adult with appropriate demographic risk factors should prompt an investigation for previously undiagnosed HIV infection [6].
Bullous impetigo is due to strains of S. aureus that produce exfoliative toxin A, a toxin that causes loss of cell adhesion in the superficial epidermis by targeting the protein desmoglein 1 [7]. This mechanism is related to the pathophysiology of pemphigus, in which autoantibodies are directed against the same protein [8]. (See "Pathogenesis, clinical manifestations, and diagnosis of pemphigus".)
Ecthyma — Ecthyma is an ulcerative form of impetigo in which the lesions extend through the epidermis and deep into the dermis. They consist of "punched-out" ulcers covered with yellow crust surrounded by raised violaceous margins (picture 3A-B) [9].
POSTINFECTIOUS SEQUELAE
Poststreptococcal glomerulonephritis — Poststreptococcal glomerulonephritis is a potential complication of streptococcal impetigo that most often occurs within one to two weeks following infection [10]. Common clinical findings include edema, hypertension, fever, and hematuria [11,12]. (See "Poststreptococcal glomerulonephritis".)
Rheumatic fever — In Australian aboriginal communities, where acute rheumatic fever is hyperendemic, low rates of streptococcal pharyngitis and high rates of impetigo have been observed [13]. Observers have hypothesized that streptococcal skin infections such as impetigo may be protective against pharyngitis but may be followed by sequelae such as acute rheumatic fever. (See "Acute rheumatic fever: Clinical manifestations and diagnosis".)
MICROBIOLOGY — The principal pathogen is S. aureus. Beta-hemolytic streptococci (primarily group A but occasionally other serogroups, such as C and G) account for a minority of cases, either alone or in combination with S. aureus [14-16]. The relative frequency of S. aureus infections has changed with time. It was predominant in the 1940s and 1950s, after which group A Streptococcus (GAS) became more prevalent. Since the 1990s, S. aureus has become more common again [17].
Methicillin-resistant Staphylococcus aureus (MRSA) is detected in some cases of impetigo. In a Chinese study that investigated the antimicrobial susceptibility of 984 S. aureus isolates taken from sites of impetigo in children, community-acquired MRSA (CA-MRSA) was identified in 1 percent [18]. Other studies have found higher rates of MRSA in impetigo [19-21]. As an example, a Japanese study of 136 S. aureus isolates from children with impetigo found CA-MRSA in 10 percent [19].
Bullous impetigo is caused by strains of S. aureus that produce a toxin causing cleavage in the superficial skin layer (see 'Bullous impetigo' above). Ecthyma is due to GAS.
Streptococcal colonization of intact skin precedes inoculation via breaches in the skin; bacteria may be subsequently transferred from the skin to the upper respiratory tract. The GAS virulence factor, M protein, can be encoded by one of five chromosome patterns of emm genes (denoted A through E) [22]. Pharyngeal strains usually have patterns A-C, while nearly all impetigo strains have patterns D or E [23]. The impetigo strains' patterns are rarely observed among invasive clinical isolates [24].
DIAGNOSIS — The diagnosis of impetigo often can be made on the basis of clinical manifestations. The key clinical findings of nonbullous impetigo, bullous impetigo, and ecthyma include:
●Nonbullous impetigo – Papules, vesicles, and pustules that rapidly break down to form golden adherent crusts; often located on the face or extremities (picture 1A-B, 1F-G)
●Bullous impetigo – Flaccid, fluid-filled bullae that rupture and leave a thin brown crust; often located on the trunk (picture 1D-E)
●Ecthyma – "Punched-out" ulcers with overlying crusts and raised violaceous borders (picture 3A-B)
A Gram stain and culture of pus or exudate is recommended to identify whether S. aureus and/or a beta-hemolytic Streptococcus is the cause. However, treatment may be initiated without these studies in patients with typical clinical presentations [25].
Serologic testing for streptococcal antibodies is not useful for the diagnosis of impetigo; the anti-streptolysin O (ASO) response is weak, likely because skin lipids suppress streptolysin O response [26-28]. Anti-deoxyribonuclease B (anti-DNase B) and antihyaluronidase (AHT) response are more reliable than the ASO response following group A Streptococcus (GAS) skin infections. However, serologic testing can be helpful in the setting of impetigo with subsequent presumed poststreptococcal glomerulonephritis. (See "Poststreptococcal glomerulonephritis", section on 'Serology'.)
DIFFERENTIAL DIAGNOSIS — The differential diagnosis of impetigo differs based upon the clinical presentation. Gram stain and culture are useful for confirming the etiologic diagnosis (see 'Microbiology' above):
●Nonbullous impetigo – Skin conditions that may share features with nonbullous impetigo include a variety of inflammatory conditions that may present with localized areas of inflammation. Examples include contact dermatitis (picture 4A-B), tinea infection (picture 5A-B), and eczema herpeticum and other herpes simplex virus infections (picture 6A-B). Recognition of the characteristic golden crust should raise suspicion for impetigo.
●Bullous impetigo – Bullous impetigo should be differentiated from other blistering skin conditions. Examples include autoimmune blistering diseases (table 1), acute contact dermatitis (picture 7), bullous drug eruptions, burns, bullous insect bite reactions (picture 8), varicella (picture 9), and subcorneal pustular dermatosis (picture 10). The progression from bullae to erosions with peripheral crust is characteristic of bullous impetigo. (See "Approach to the patient with cutaneous blisters".)
●Ecthyma – The differential diagnosis of ecthyma often includes other conditions that may cause localized ulcers, such as mycobacterial or deep fungal infections (picture 11A-B) or pyoderma gangrenosum (picture 12A-B). Ecthyma can be confused with ecthyma gangrenosum, a potentially life-threatening skin condition that occurs in patients with pseudomonal bacteremia. In ecthyma gangrenosum, painless erythematous or purpuric macules rapidly evolve into hemorrhagic vesicles or bullae that subsequently rupture to leave an ulcer with necrotic black eschar (picture 13A-B). Unlike ecthyma, patients with ecthyma gangrenosum are usually systemically ill. (See "Pseudomonas aeruginosa skin and soft tissue infections", section on 'Ecthyma Gangrenosum'.)
TREATMENT — Treatment of impetigo is important for reducing spread of infection, hastening the resolution of discomfort, and improving cosmetic appearance [29]. Bullous and nonbullous impetigo can be treated with either topical or oral therapy. Topical therapy is used for patients with limited skin involvement, whereas oral therapy is recommended for patients with numerous lesions [25]. Unlike impetigo, ecthyma should always be treated with oral therapy [25]. In healthcare settings, contact precautions to avoid spread of impetigo are indicated until 24 hours after the start of antibiotic therapy [30].
Limited impetigo — Topical therapy for impetigo should be administered if there are a limited number of lesions.
Topical therapy — Benefits of topical therapy include fewer side effects and lower risk for contributing to bacterial resistance compared with oral therapy [29]. Mupirocin and retapamulin are first-line treatments [25]. Mupirocin is applied three times daily and retapamulin is applied twice daily. The recommended length of treatment is five days [25].
Topical fusidic acid can be effective for impetigo; however, evidence for increasing resistance of S. aureus to fusidic acid in locations where topical fusidic acid use is common has made it a less favorable option for therapy [31]. Fusidic acid is not available in the United States.
Although the components of over-the-counter triple antibiotic ointments (consisting of bacitracin-neomycin-polymyxin B) have some activity against the organisms causing impetigo, they may not be as effective for treatment [32]. Therefore, treatment of impetigo with these agents is not recommended. Bacitracin and neomycin can also cause contact dermatitis. In rare cases, bacitracin has been associated with allergic anaphylactoid reactions [33].
Ozenoxacin, a topical quinolone, was approved by the US Food and Drug Administration (FDA) in 2017 for the treatment of impetigo [34,35]. However, additional study is necessary to clarify its benefits, risks, and likelihood for promoting bacterial drug resistance relative to standard therapy prior to a recommendation for use as a primary therapy for impetigo.
Extensive impetigo and ecthyma — Oral therapy should be administered to patients with numerous impetigo lesions or ecthyma.
Systemic antibiotics — Unless cultures reveal only beta-hemolytic streptococci (usually group A Streptococcus [GAS]), the oral antibiotic prescribed for impetigo and ecthyma should be effective for the treatment of both S. aureus and streptococcal infections (table 2) (see 'Streptococcal impetigo' below). Cephalexin and dicloxacillin are appropriate treatments because S. aureus isolates from impetigo and ecthyma are usually susceptible to methicillin [25]. Although erythromycin and clindamycin can also treat impetigo, some strains of S. aureus and GAS may be resistant to these therapies [25]. Therapeutic options for impetigo are provided in a table (table 2). A seven-day course of oral antibiotic treatment is recommended [25].
Special cases — Certain scenarios warrant adjustments in the approach to treatment.
Streptococcal impetigo — If only beta-hemolytic streptococci are detected in extensive impetigo or ecthyma, oral penicillin is the preferred therapy [25]. Limited streptococcal impetigo can be treated with topical therapy. (See 'Limited impetigo' above.)
Although the efficacy of trimethoprim-sulfamethoxazole for streptococcal infections has been perceived as uncertain, the findings of an open-label, assessor-blinded randomized trial performed in 508 children in remote Australia suggest that oral trimethoprim-sulfamethoxazole is an effective alternative to injectable penicillin for the treatment of impetigo in which streptococcal infection is present [36]. In the trial, three- or five-day courses of oral trimethoprim-sulfamethoxazole and a single injection of benzathine benzylpenicillin were similarly effective for improving or healing impetigo within seven days. Ninety percent of children in the trial were culture-positive for S. pyogenes with or without concomitant S. aureus infection. Although not a first-line treatment for non-methicillin-resistant S. aureus impetigo, a short course of oral trimethoprim-sulfamethoxazole may represent an inexpensive oral alternative for staphylococcal and streptococcal impetigo in resource-limited settings.
MRSA impetigo — Patients with suspected or confirmed methicillin-resistant Staphylococcus aureus (MRSA) infections can be treated with trimethoprim-sulfamethoxazole, clindamycin, or doxycycline, provided the causative isolate is susceptible to the selected agent (table 2). (See "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Treatment of skin and soft tissue infections".)
Regarding doxycycline, although tetracyclines can cause permanent tooth discoloration in children younger than eight years, doxycycline binds less to calcium than do other tetracyclines. Therefore, short courses of doxycycline (21 days or less) can be given to children who fall within this age group [37]. Also, it is important for patients to avoid excess sun exposure due to photosensitivity associated with doxycycline.
Fluoroquinolones should not be used to treat impetigo, as MRSA resistance to this class is widespread and resistance can develop on therapy. (See "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Treatment of skin and soft tissue infections".)
Impetigo outbreaks — Oral therapy rather than topical therapy is recommended in outbreaks, including those complicated by poststreptococcal glomerulonephritis (table 2) [25].
Coinfection with scabies — Treatment of scabies in patients with impetigo is important for optimizing the response of impetigo to antibiotic therapy and reducing the prevalence of impetigo in areas of high scabies prevalence [38-42]. (See "Scabies: Management", section on 'Endemic scabies'.)
Follow-up — Crusted lesions can be washed gently. Handwashing is important for reducing spread among children, and other preventive measures employed in reducing the spread of staphylococci may also be helpful [43,44]. (See "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Prevention and control".)
Improvement in impetigo should be noted within a single course of appropriate antibiotic treatment. The possibility of resistant pathogens or an incorrect diagnosis should be considered when lesions fail to respond to antibiotic therapy. (See 'Differential diagnosis' above.)
Return to school — Children can return to school 24 hours after beginning an effective antimicrobial therapy. Draining lesions should be kept covered.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Skin and soft tissue infections".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Impetigo (The Basics)")
●Beyond the Basics topics (see "Patient education: Impetigo (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Overview – Impetigo is a contagious, superficial bacterial infection that typically involves the face and extremities with lesions that progress from papules to vesicles, pustules, and crusts (picture 1A-B). Less common manifestations include bullous impetigo and ecthyma (picture 1C-E, 3A-B). Impetigo may be complicated by poststreptococcal glomerulonephritis or rheumatic fever. (See 'Clinical manifestations' above.)
●Microbiology – The most common pathogen is Staphylococcus aureus. In contrast to skin abscess, community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is an uncommon cause of impetigo. Beta-hemolytic streptococci (primarily group A but occasionally other serogroups, such as C and G) cause a minority of cases, either alone or in combination with S. aureus. (See 'Microbiology' above.)
●Treatment:
•Patients with limited lesions – For management of impetigo with a small number of lesions, we recommend treatment with topical therapy rather than oral therapy (Grade 1A).
Topical mupirocin and topical retapamulin are options for topical therapy. Mupirocin is applied three times daily and retapamulin is applied twice daily. The recommended duration of treatment for these medications is five days. (See 'Treatment' above.)
•Patients with numerous lesions – For patients with numerous impetigo lesions, we recommend treatment with oral antibiotic therapy (Grade 1B).
The antibiotic selected should be effective for the treatment of both S. aureus and streptococcal infections; dicloxacillin and cephalexin are appropriate treatments (table 2). Oral antibiotic therapy should be given for seven days. In the setting of suspected CA-MRSA, appropriate choices include trimethoprim-sulfamethoxazole or clindamycin; doxycycline can be also used (table 2). (See 'Treatment' above.)
●Prevention – Handwashing is important for reducing spread among children, and other preventive measures employed in reducing the spread of staphylococci may also be helpful. (See "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Prevention and control".)
