Impetigo

Infectious Disease MONDO:0004592 Pathograph 18 Show in embeddings browser Bacterial infection

Impetigo is an acute, highly contagious superficial bacterial infection of the epidermis caused by Staphylococcus aureus, Streptococcus pyogenes, or both. Nonbullous disease produces vesiculopustules that rupture into honey-colored crusted erosions, whereas toxigenic S. aureus causes bullous impetigo by secreting exfoliative toxins that cleave desmoglein 1 and split the granular layer of the epidermis.

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Classifications

Harrison's Part
INFECTIOUS DISEASES
◆

Subtypes

2
Nonbullous impetigo
The more common form, caused by S. aureus, S. pyogenes, or both, presenting as papules and vesiculopustules that rupture into honey-colored crusts.
Show evidence (1 reference)
PMID:33105179 SUPPORT Other
"There are two common variants of impetigo: nonbullous (70%) and bullous (30%). Nonbullous impetigo is caused by S. aureus and S. pyogenes whereas bullous impetigo is caused by S. aureus."
Distinguishes nonbullous impetigo by its mixed staphylococcal and streptococcal microbiology.
Bullous impetigo MONDO:0018182
Localized blistering form caused by exfoliative-toxin-producing S. aureus, presenting as flaccid superficial bullae.
Show evidence (2 references)
PMID:33105179 SUPPORT Other
"There are two common variants of impetigo: nonbullous (70%) and bullous (30%). Nonbullous impetigo is caused by S. aureus and S. pyogenes whereas bullous impetigo is caused by S. aureus."
Distinguishes bullous impetigo as the staphylococcal-only variant.
PMID:17582744 SUPPORT Other
"Bullous impetigo and its generalized form, staphylococcal scalded-skin syndrome (SSSS), are highly contagious, blistering skin diseases caused by Staphylococcus aureus infection."
Documents the blistering presentation that separates the bullous form.
⚙

Pathophysiology

7
Epidermal Barrier Disruption
Breaks in the epidermal barrier from abrasions, insect bites, scabies, atopic dermatitis, or other minor skin trauma expose a superficial niche for S. aureus and S. pyogenes.
skin epidermis UBERON:0001003 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in skin epidermis (UBERON:0001003). UBERON:0001003 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Superficial Bacterial Colonization The breached epidermis allows S. aureus, S. pyogenes, or both to establish and proliferate locally.
Show evidence (2 references)
PMID:31630410 SUPPORT Other
"Infection may be direct or secondary to cutaneous barrier damage resulting from insect bites, minor trauma, or other pruritic dermatoses, especially scabies, head lice and tinea."
Names cutaneous barrier damage, including scabies and other pruritic dermatoses, as the setting for secondary impetigo.
PMID:41839109 SUPPORT Other
"Risk factors for impetigo include disruptions to the skin barrier, poor hygiene, crowded living environments, living in hot and humid climates, malnutrition, and diabetes."
Lists disruption of the skin barrier as a risk factor for impetigo.
Superficial Bacterial Colonization
S. aureus, S. pyogenes, or both colonize and proliferate in the superficial epidermis at the breached site.
keratinocyte CL:0000312 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves keratinocyte (CL:0000312). CL:0000312 is a cell type from the Cell Ontology.
skin epidermis UBERON:0001003 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in skin epidermis (UBERON:0001003). UBERON:0001003 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Nonbullous Pyogenic Epidermal Infection S. pyogenes, S. aureus, or both proliferate locally to produce vesiculopustules and crusted erosions.
Exfoliative Toxin Production by S. aureus Toxigenic S. aureus expresses exfoliative toxins at the infected epidermal site.
Show evidence (3 references)
PMID:28655473 SUPPORT Other
"Staphylococcus aureus is only rarely found on healthy human skin, but frequently colonizes the skin of atopic dermatitis (AD) patients"
Supports defective or inflamed epidermal barrier states as permissive for S. aureus colonization.
PMID:31755570 SUPPORT Human clinical
"Due to compromised barrier function and immune dysregulation, children with atopic dermatitis (AD) are at increased risk of cutaneous infections"
Links a compromised epidermal barrier in atopic dermatitis to increased risk of cutaneous bacterial infection.
PMID:31755570 SUPPORT Human clinical
"Eleven children (92%) had severe AD."
In a case series of disseminated bullous impetigo, nearly all children had severe atopic dermatitis, consistent with barrier-defective skin favoring S. aureus infection.
Nonbullous Pyogenic Epidermal Infection
S. pyogenes and non-toxigenic or toxigenic S. aureus proliferate in the superficial epidermis, recruiting neutrophils and creating vesicles and pustules that rupture into the honey-colored crusts of nonbullous impetigo.
keratinocyte CL:0000312 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves keratinocyte (CL:0000312). CL:0000312 is a cell type from the Cell Ontology. neutrophil CL:0000775 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves neutrophil (CL:0000775). CL:0000775 is a cell type from the Cell Ontology.
inflammatory response GO:0006954 ↑ INCREASED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology.
skin epidermis UBERON:0001003 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in skin epidermis (UBERON:0001003). UBERON:0001003 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Vesicles Superficial pyogenic infection produces vesicles from the initial erythematous papules.
Pustules Neutrophil-rich superficial infection produces thin-walled pustules.
Honey-colored crusts Vesicles and pustules rupture and dry into the characteristic crusted superficial erosions.
Post-Streptococcal Immune Sequelae Group A streptococcal skin infection can antecede acute post-streptococcal glomerulonephritis and acute rheumatic fever in endemic communities.
Show evidence (2 references)
PMID:33105179 SUPPORT Other
"Nonbullous impetigo is caused by S. aureus and S. pyogenes whereas bullous impetigo is caused by S. aureus."
This distinguishes the streptococcal/staphylococcal microbiology of nonbullous disease from the staphylococcal-only bullous branch.
PMID:31630410 SUPPORT Other
"Impetigo begins as erythematous papules, progressing to thinly walled pustules that rupture and crust over with a progressively thickening scab."
Describes the papule-to-pustule-to-crust evolution of the superficial infection.
Exfoliative Toxin Production by S. aureus
Toxigenic S. aureus strains express ETA or ETB, encoded on a phage genome or plasmid respectively, and secrete exfoliative toxin as the pathogen effector that initiates bullous impetigo.
Downstream
Desmoglein 1 Ectodomain Cleavage Secreted exfoliative toxin reaches superficial keratinocyte desmosomes and cleaves desmoglein 1.
Show evidence (1 reference)
PMID:21282415 SUPPORT BACKGROUND Other
"Most S. aureus strains that cause blistering disease produce either ETA or ETB. They are serologically distinct molecules, where ETA is encoded on a phage genome and ETB is enocded on a large plasmid."
Introduction background in a bacterial-genetics study, identifying ETA and ETB as the common exfoliative toxins of blistering S. aureus disease and their phage and plasmid genetic contexts.
Desmoglein 1 Ectodomain Cleavage
Staphylococcal exfoliative toxins are glutamate-specific serine proteases that cleave one peptide bond in the extracellular region of desmoglein 1, disrupting superficial keratinocyte adhesion at desmosomes.
keratinocyte CL:0000312 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves keratinocyte (CL:0000312). CL:0000312 is a cell type from the Cell Ontology.
DSG1 hgnc:3048 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves DSG1 (hgnc:3048). hgnc:3048 is a gene from the HUGO Gene Nomenclature Committee.
desmoglein 1 proteolysis GO:0006508 ↑ INCREASED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased desmoglein 1 proteolysis, annotated with proteolysis (GO:0006508). GO:0006508 is a biological process from the Gene Ontology.
exfoliative toxin serine protease activity GO:0008233 ↑ INCREASED Gene Ontology (GO) Relation: this pathophysiological event involves this molecular function This pathophysiological event involves increased exfoliative toxin serine protease activity, annotated with peptidase activity (GO:0008233). GO:0008233 is a molecular function from the Gene Ontology.
desmosome GO:0030057 Gene Ontology (GO) Relation: this pathophysiological event involves this cellular component This pathophysiological event involves desmosome (GO:0030057). GO:0030057 is a cellular component from the Gene Ontology.
Downstream
Granular-Layer Acantholysis and Bullae Loss of the adhesive Dsg1 ectodomain is sufficient to produce the superficial intraepidermal blister.
Show evidence (2 references)
PMID:17582744 SUPPORT Other
"the three isoforms of ETs, i.e., ETA, ETB, and ETD, are glutamate-specific serine proteases that specifically and efficiently cleave a single peptide bond in the extracellular region of human and mouse desmoglein 1 (Dsg1), a desmosomal intercellular adhesion molecule"
Defines exfoliative toxins as glutamate-specific proteases that cleave a single extracellular peptide bond in desmoglein 1.
PMID:20728315 SUPPORT Model organism
"Our findings suggest that the removal of amino-terminal extracellular domains of Dsg1 by ETs is sufficient to initiate epidermal blister formation in bullous impetigo and SSSS."
Shows in a neonatal mouse model that exfoliative-toxin removal of the Dsg1 ectodomain is sufficient to initiate bullous impetigo-like blistering.
Granular-Layer Acantholysis and Bullae
Cleavage of desmoglein 1 separates superficial keratinocytes at the granular layer, creating a flaccid intraepidermal blister whose roof ruptures into moist erosions and crust.
keratinocyte CL:0000312 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves keratinocyte (CL:0000312). CL:0000312 is a cell type from the Cell Ontology.
homophilic cell-cell adhesion GO:0007156 ↓ DECREASED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased homophilic cell-cell adhesion (GO:0007156). GO:0007156 is a biological process from the Gene Ontology.
desmosome GO:0030057 Gene Ontology (GO) Relation: this pathophysiological event involves this cellular component This pathophysiological event involves desmosome (GO:0030057). GO:0030057 is a cellular component from the Gene Ontology.
skin epidermis UBERON:0001003 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in skin epidermis (UBERON:0001003). UBERON:0001003 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Flaccid bullae The superficial intraepidermal split manifests clinically as flaccid bullae in bullous impetigo.
Honey-colored crusts The fragile bullae rupture into moist erosions that crust over.
Show evidence (1 reference)
PMID:20728315 SUPPORT Model organism
"Epidermal blister formation was observed as early as 60 min after ETA treatment."
The neonatal mouse model develops rapid epidermal blistering after ETA exposure.
Post-Streptococcal Immune Sequelae
Group A streptococcal impetigo can trigger serious post-infectious complications, including acute post-streptococcal glomerulonephritis and acute rheumatic fever, in high-burden communities.
Show evidence (1 reference)
PMID:31630410 SUPPORT Other
"Impetigo, scabies, cellulitis and abscesses are common in Australian Aboriginal children. These conditions adversely affect wellbeing and are associated with serious long term sequelae, including invasive infection and post-infectious complications, such as acute post-streptococcal..."
This review links impetigo in a high-burden pediatric setting to severe invasive and post-infectious sequelae.
⬡

Pathograph

Use Group by to collapse related nodes into one box. Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Impetigo Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
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Phenotypes

4
Immune 1
Pustules HP:0200039 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Pustule (HP:0200039). HP:0200039 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:31630410 SUPPORT Other
"Impetigo begins as erythematous papules, progressing to thinly walled pustules that rupture and crust over with a progressively thickening scab."
Describes thin-walled pustules as a stage of impetigo lesion evolution.
Integument 3
Honey-colored crusts Skin erosion HP:0200041 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Honey-colored crusted skin erosion, annotated with Skin erosion (HP:0200041). HP:0200041 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:41839109 SUPPORT Other
"Diagnosis of impetigo is based primarily on clinical examination and should be suspected in individuals with erythematous papules that progress to ruptured vesicles or bullae over 4 to 6 days, forming honey-colored crusts."
The review describes ruptured vesicles and bullae that dry into honey-colored crusts. HPO has no honey-crust-specific term; the lesion is a superficial epidermal erosion rather than an ulcer, so it is bound to Skin erosion.
Vesicles Skin vesicle HP:0200037 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Skin vesicle (HP:0200037). HP:0200037 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:41839109 SUPPORT Other
"Diagnosis of impetigo is based primarily on clinical examination and should be suspected in individuals with erythematous papules that progress to ruptured vesicles or bullae over 4 to 6 days, forming honey-colored crusts."
This supports vesicles as an early lesion stage.
Flaccid bullae Abnormal blistering of the skin HP:0008066 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Abnormal blistering of the skin (HP:0008066). HP:0008066 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:17582744 SUPPORT Other
"Bullous impetigo and its generalized form, staphylococcal scalded-skin syndrome (SSSS), are highly contagious, blistering skin diseases caused by Staphylococcus aureus infection."
Establishes blistering as the defining manifestation of bullous impetigo.
💊

Medical Actions

3
Topical Antibiotic Therapy for Limited Impetigo
Action: Antibiotic TherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Antibiotic Therapy (NCIT:C15620). NCIT:C15620 is a clinical intervention from the NCI Thesaurus. NCIT:C15620
Agent: mupirocin CHEBI:7025 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses mupirocin (CHEBI:7025). CHEBI:7025 is a therapeutic agent from Chemical Entities of Biological Interest. retapamulin CHEBI:166679 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses retapamulin (CHEBI:166679). CHEBI:166679 is a therapeutic agent from Chemical Entities of Biological Interest. ozenoxacin CHEBI:136050 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses ozenoxacin (CHEBI:136050). CHEBI:136050 is a therapeutic agent from Chemical Entities of Biological Interest. fusidic acid CHEBI:29013 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses fusidic acid (CHEBI:29013). CHEBI:29013 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
Limited impetigo is treated with topical antibiotics such as mupirocin, retapamulin, ozenoxacin, or fusidic acid, which kill S. aureus and S. pyogenes locally and shorten the contagious superficial infection. Resistance limits these agents: the fusidic acid-resistant epidemic European impetigo clone (EEFIC) of S. aureus has persisted in Belgium, and a variant of it carrying mupirocin resistance has spread among children there.
Mechanism Target:
INHIBITS Nonbullous Pyogenic Epidermal Infection — Topical antibiotics suppress superficial bacterial proliferation.
INHIBITS Exfoliative Toxin Production by S. aureus — Topical antibiotics suppress toxigenic S. aureus in localized bullous impetigo before additional toxin can be produced.
Show evidence (6 references)
PMID:41839109 SUPPORT Other
"Topical mupirocin 2% ointment or retapamulin 1% ointment are the recommended initial treatments for mild, nonbullous and bullous impetigo."
This supports topical antibiotic therapy as initial treatment for mild impetigo of either clinical form.
PMID:15106198 SUPPORT Human clinical
"Topical antibiotics showed better cure rates than placebo (pooled odds ratio (OR) 6.49, 95% confidence interval (CI) 3.93 to 10.73)"
Cochrane randomized-trial synthesis supports the efficacy of topical antibiotics for impetigo.
PMID:15106198 SUPPORT Human clinical
"There is good evidence that topical mupirocin and topical fusidic acid are equally, or more effective than oral treatment for people with limited disease."
Supports topical fusidic acid, alongside mupirocin, for limited impetigo.
+ 3 more references
Oral Antibiotic Therapy for Extensive or Outbreak Disease
Action: Antibiotic TherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Antibiotic Therapy (NCIT:C15620). NCIT:C15620 is a clinical intervention from the NCI Thesaurus. NCIT:C15620
Agent: dicloxacillin CHEBI:4511 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses dicloxacillin (CHEBI:4511). CHEBI:4511 is a therapeutic agent from Chemical Entities of Biological Interest. cephalexin CHEBI:3534 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses cephalexin (CHEBI:3534). CHEBI:3534 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
Oral antibiotics targeting both group A Streptococcus and S. aureus are used for severe, multilesional, or outbreak-associated impetigo when topical therapy is insufficient to control bacterial proliferation and transmission.
Mechanism Target:
INHIBITS Nonbullous Pyogenic Epidermal Infection — Oral antibiotics suppress disseminated superficial infection.
INHIBITS Exfoliative Toxin Production by S. aureus — Oral antibiotics treat extensive bullous impetigo.
Show evidence (1 reference)
PMID:41839109 SUPPORT Other
"Oral antibiotics, such as dicloxacillin or cephalexin, should be targeted to group A streptococci and S. aureus and are recommended for outbreaks to decrease infection transmission or for severe, multilesional disease that does not respond to topical therapy within 3 to 5 days."
This supports oral therapy for severe, multilesional, outbreak-associated, or topical-nonresponsive impetigo.
Ivermectin Mass Drug Administration for Scabies-Associated Community Impetigo
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: ivermectin CHEBI:6078 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses ivermectin (CHEBI:6078). CHEBI:6078 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
In communities where scabies is a major upstream breach in the skin barrier, ivermectin-based mass drug administration reduces scabies infestation and thereby reduces impetigo prevalence at the population level.
Mechanism Target:
INHIBITS Epidermal Barrier Disruption — Scabies control lowers one infestation-driven source of scratching and epidermal barrier breaks.
Show evidence (1 reference)
PMID:26650152 SUPPORT Human clinical
"The prevalence of impetigo also declined in all groups, with the greatest reduction seen in the ivermectin group."
In a Fiji cluster-randomized trial for scabies control, the ivermectin MDA arm produced the largest drop in impetigo prevalence.
🌍

Environmental Factors

4
Scabies infestation
No ECTO exposure term for scabies or Sarcoptes scabiei: ols:ecto searches for "scabies" returned only ECTO:9002125 exposure to scabicide, and for "Sarcoptes scabiei" returned nothing.
Scabies is a pruritic dermatosis whose resulting barrier damage precedes secondary impetigo, particularly in communities where both are endemic.
Show evidence (1 reference)
PMID:31630410 SUPPORT Other
"Infection may be direct or secondary to cutaneous barrier damage resulting from insect bites, minor trauma, or other pruritic dermatoses, especially scabies, head lice and tinea."
Names scabies as a leading pruritic dermatosis behind barrier damage that precedes impetigo.
Mechanism Target:
PREDISPOSES Epidermal Barrier Disruption — Scabies-associated pruritus and scratching damage the epidermis, opening the barrier breaks in which impetigo arises.
Show evidence (2 references)
PMID:31630410 SUPPORT Other
"Infection may be direct or secondary to cutaneous barrier damage resulting from insect bites, minor trauma, or other pruritic dermatoses, especially scabies, head lice and tinea."
Places scabies upstream of the cutaneous barrier damage that permits secondary impetigo.
PMID:26650152 SUPPORT Human clinical
"The prevalence of impetigo also declined in all groups, with the greatest reduction seen in the ivermectin group."
Scabies control lowered impetigo prevalence, consistent with scabies acting upstream of impetigo.
Crowded living environments
No ECTO exposure term for crowding: ols:ecto searches for "crowding" and "crowded" returned nothing.
Crowded housing increases close skin contact and is a recognized risk factor for impetigo.
Show evidence (1 reference)
PMID:41839109 SUPPORT Other
"Risk factors for impetigo include disruptions to the skin barrier, poor hygiene, crowded living environments, living in hot and humid climates, malnutrition, and diabetes."
Lists crowded living environments as a risk factor for impetigo.
Mechanism Target:
PREDISPOSES Superficial Bacterial Colonization — Crowding raises the chance that S. aureus or S. pyogenes reaches and colonizes breached skin.
Show evidence (1 reference)
PMID:41839109 SUPPORT Other
"Risk factors for impetigo include disruptions to the skin barrier, poor hygiene, crowded living environments, living in hot and humid climates, malnutrition, and diabetes."
Lists crowded living environments as a risk factor for impetigo.
Poor hygiene
No ECTO exposure term for hygiene: an ols:ecto search for "hygiene" returned nothing.
Poor hygiene is a recognized risk factor for impetigo; hand hygiene and washing shared objects reduce its spread.
Show evidence (1 reference)
PMID:41839109 SUPPORT Other
"Risk factors for impetigo include disruptions to the skin barrier, poor hygiene, crowded living environments, living in hot and humid climates, malnutrition, and diabetes."
Lists poor hygiene as a risk factor for impetigo.
Mechanism Target:
PREDISPOSES Superficial Bacterial Colonization — Poor hygiene favors transfer and persistence of the causative bacteria on the skin.
Show evidence (1 reference)
PMID:41839109 SUPPORT Other
"Risk factors for impetigo include disruptions to the skin barrier, poor hygiene, crowded living environments, living in hot and humid climates, malnutrition, and diabetes."
Lists poor hygiene as a risk factor for impetigo.
Hot and humid climate
hot and humid climate ECTO:0010007 Environmental Conditions, Treatments and Exposures Ontology (ECTO) Relation: this environmental factor is this exposure This environmental factor is hot and humid climate, annotated with exposure to humidity (ECTO:0010007). ECTO:0010007 is an exposure from the Environmental Conditions, Treatments and Exposures Ontology.
Living in hot and humid climates is a recognized risk factor for impetigo.
Show evidence (1 reference)
PMID:41839109 SUPPORT Other
"Risk factors for impetigo include disruptions to the skin barrier, poor hygiene, crowded living environments, living in hot and humid climates, malnutrition, and diabetes."
Lists hot and humid climates as a risk factor for impetigo.
Mechanism Target:
PREDISPOSES Superficial Bacterial Colonization — Hot, humid climates predispose to impetigo; the intermediate steps are not specified by the source.
Show evidence (1 reference)
PMID:41839109 SUPPORT Other
"Risk factors for impetigo include disruptions to the skin barrier, poor hygiene, crowded living environments, living in hot and humid climates, malnutrition, and diabetes."
Lists hot and humid climates as a risk factor for impetigo.
🔬

Diagnosis

1
Clinical Diagnosis of Crusted Vesiculobullous Lesions
Impetigo is usually diagnosed clinically from erythematous papules evolving over days into ruptured vesicles or bullae with honey-colored crusts; swab culture is reserved for recurrent, extensive, outbreak-associated, or methicillin-resistant S. aureus-suspected disease.
Show evidence (1 reference)
PMID:41839109 SUPPORT Other
"Diagnosis of impetigo is based primarily on clinical examination and should be suspected in individuals with erythematous papules that progress to ruptured vesicles or bullae over 4 to 6 days, forming honey-colored crusts."
Supports recognition of impetigo by clinical examination of the evolving vesiculobullous crusted eruption.
📈

Progression

3
Papulovesicular onset
Lesions begin as erythematous papules that progress to thin-walled vesicles or pustules.
Show evidence (1 reference)
PMID:31630410 SUPPORT Other
"Impetigo begins as erythematous papules, progressing to thinly walled pustules that rupture and crust over with a progressively thickening scab."
Describes the papular onset and pustular stage of impetigo lesions.
Rupture and crusting
Duration: 4 to 6 days
Vesicles, pustules, or bullae rupture and form honey-colored crusts over 4 to 6 days.
Show evidence (1 reference)
PMID:41839109 SUPPORT Other
"erythematous papules that progress to ruptured vesicles or bullae over 4 to 6 days, forming honey-colored crusts."
Gives the timing of progression from papules to ruptured, crusted lesions.
Healing
Duration: up to 30 days without treatment
The scab shrinks and the eroded base heals, often without scarring; untreated resolution can take 30 days.
Show evidence (2 references)
PMID:31630410 SUPPORT Other
"As healing begins, the scab shrinks, tethering surrounding skin to heal the eroded base, often without scarring."
Describes the healing phase of impetigo lesions.
PMID:31630410 SUPPORT Other
"Without treatment, resolution can take 30 days"
Gives the duration of untreated resolution.
📊

Prevalence

2
Children worldwide (population-based surveillance studies)
Point prevalence 12300.0 per 100,000 >1 in 1,000
Median childhood prevalence 12.3% (IQR 4.2-19.4%) across 82 population surveillance studies; the authors estimate more than 162 million children affected at any one time, predominantly in tropical, resource-poor settings.
Show evidence (2 references)
PMID:26317533 SUPPORT PRIMARY RESULT Human clinical
"Median childhood prevalence was 12·3% (IQR 4·2-19·4%)."
Systematic review of population surveillance studies giving the median childhood point prevalence of impetigo.
PMID:26317533 SUPPORT PRIMARY RESULT Human clinical
"we estimate the global population of children suffering from impetigo at any one time to be in excess of 162 million, predominantly in tropical, resource-poor contexts."
Extrapolates the pooled prevalence to a global count of children affected at any one time.
Worldwide, all ages
Unknown
Global disease burden of greater than 140 million; the source does not state the measure.
Show evidence (1 reference)
PMID:33105179 SUPPORT Other
"Impetigo is a common superficial bacterial infection of the skin, with a global disease burden of greater than 140 million."
Review statement of the global burden of impetigo.
🦠

Infectious Agent

2
Staphylococcus aureus
Staphylococcus aureus causes nonbullous impetigo and, when the strain expresses exfoliative toxins, bullous impetigo.
Staphylococcus aureus NCBITaxon:1280 NCBI Taxonomy (NCBITaxon)
Show evidence (2 references)
PMID:41839109 SUPPORT Other
"Impetigo can be nonbullous (70%) or bullous (30%) and is most commonly caused by group A streptococcus and Staphylococcus aureus."
Identifies S. aureus as one of the two principal bacterial causes of impetigo.
PMID:17582744 SUPPORT Other
"Bullous impetigo and its generalized form, staphylococcal scalded-skin syndrome (SSSS), are highly contagious, blistering skin diseases caused by Staphylococcus aureus infection."
This review ties toxigenic S. aureus specifically to the bullous impetigo branch.
Streptococcus pyogenes
Group A Streptococcus contributes to nonbullous impetigo and can seed post-streptococcal immune sequelae after skin infection.
Streptococcus pyogenes NCBITaxon:1314 NCBI Taxonomy (NCBITaxon)
Show evidence (1 reference)
PMID:41839109 SUPPORT Other
"Impetigo can be nonbullous (70%) or bullous (30%) and is most commonly caused by group A streptococcus and Staphylococcus aureus."
Identifies group A Streptococcus as one of the two principal bacterial causes of impetigo.
↔️

Transmission

1
Direct-contact and fomite spread with autoinoculation
Impetigo spreads efficiently from colonized lesions by skin-to-skin contact, contact with contaminated objects, and self-inoculation to additional breached epidermal sites.
Show evidence (1 reference)
PMID:41839109 SUPPORT Other
"Reducing the spread and recurrence of impetigo includes good hand hygiene, thoroughly washing objects used by people with impetigo, and refraining from returning to work or school until 12 to 24 hours after initiating antibiotic treatment or clinical improvement occurs."
Hand hygiene, object washing, and temporary school or work exclusion support direct-contact and fomite spread among close contacts.
{ }

Source YAML

click to show 
name: Impetigo
creation_date: "2026-09-29T17:30:14Z"
description: >-
  Impetigo is an acute, highly contagious superficial bacterial infection of the
  epidermis caused by Staphylococcus aureus, Streptococcus pyogenes, or both.
  Nonbullous disease produces vesiculopustules that rupture into honey-colored
  crusted erosions, whereas toxigenic S. aureus causes bullous impetigo by
  secreting exfoliative toxins that cleave desmoglein 1 and split the granular
  layer of the epidermis.
category: Infectious Disease
disease_term:
  preferred_term: impetigo
  term:
    id: MONDO:0004592
    label: impetigo
parents:
- Bacterial infection
synonyms:
- Impetigo contagiosa
- School sores
- Crusted impetigo
- Impetigo vulgaris
notes: >-
  Bullous impetigo is the localized form of exfoliative-toxin skin disease;
  the generalized toxin-mediated form is curated separately as
  Staphylococcal_Scalded_Skin_Syndrome. Ecthyma, the ulcerative form of
  pyoderma, is outside this entry's scope.
infectious_agent:
- name: Staphylococcus aureus
  infectious_agent_term:
    preferred_term: Staphylococcus aureus
    term:
      id: NCBITaxon:1280
      label: Staphylococcus aureus
  description: >-
    Staphylococcus aureus causes nonbullous impetigo and, when the strain
    expresses exfoliative toxins, bullous impetigo.
  evidence:
  - reference: PMID:41839109
    reference_title: "Impetigo: Rapid Evidence Review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Impetigo can be nonbullous (70%) or bullous (30%) and is most commonly
      caused by group A streptococcus and Staphylococcus aureus.
    explanation: >-
      Identifies S. aureus as one of the two principal bacterial causes of
      impetigo.
  - reference: PMID:17582744
    reference_title: >-
      Staphylococcal exfoliative toxins: "molecular scissors" of bacteria that
      attack the cutaneous defense barrier in mammals.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Bullous impetigo and its generalized form, staphylococcal scalded-skin
      syndrome (SSSS), are highly contagious, blistering skin diseases caused by
      Staphylococcus aureus infection.
    explanation: >-
      This review ties toxigenic S. aureus specifically to the bullous impetigo
      branch.
- name: Streptococcus pyogenes
  infectious_agent_term:
    preferred_term: Streptococcus pyogenes
    term:
      id: NCBITaxon:1314
      label: Streptococcus pyogenes
  description: >-
    Group A Streptococcus contributes to nonbullous impetigo and can seed
    post-streptococcal immune sequelae after skin infection.
  evidence:
  - reference: PMID:41839109
    reference_title: "Impetigo: Rapid Evidence Review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Impetigo can be nonbullous (70%) or bullous (30%) and is most commonly
      caused by group A streptococcus and Staphylococcus aureus.
    explanation: >-
      Identifies group A Streptococcus as one of the two principal bacterial
      causes of impetigo.
classifications:
  harrisons_chapter:
  - classification_value: INFECTIOUS_DISEASES
    evidence:
    - reference: PMID:33105179
      reference_title: Impetigo.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        Impetigo is a common superficial bacterial infection of the skin, with a
        global disease burden of greater than 140 million.
      explanation: >-
        This frames impetigo as a bacterial skin infection, supporting
        classification in Harrison's Infectious Diseases Part.
has_subtypes:
- name: Nonbullous
  display_name: Nonbullous impetigo
  description: >-
    The more common form, caused by S. aureus, S. pyogenes, or both, presenting
    as papules and vesiculopustules that rupture into honey-colored crusts.
  evidence:
  - reference: PMID:33105179
    reference_title: Impetigo.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      There are two common variants of impetigo: nonbullous (70%) and bullous
      (30%). Nonbullous impetigo is caused by S. aureus and S. pyogenes whereas
      bullous impetigo is caused by S. aureus.
    explanation: >-
      Distinguishes nonbullous impetigo by its mixed staphylococcal and
      streptococcal microbiology.
- name: Bullous
  display_name: Bullous impetigo
  subtype_term:
    preferred_term: bullous impetigo
    term:
      id: MONDO:0018182
      label: bullous impetigo
  description: >-
    Localized blistering form caused by exfoliative-toxin-producing S. aureus,
    presenting as flaccid superficial bullae.
  evidence:
  - reference: PMID:33105179
    reference_title: Impetigo.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      There are two common variants of impetigo: nonbullous (70%) and bullous
      (30%). Nonbullous impetigo is caused by S. aureus and S. pyogenes whereas
      bullous impetigo is caused by S. aureus.
    explanation: >-
      Distinguishes bullous impetigo as the staphylococcal-only variant.
  - reference: PMID:17582744
    reference_title: >-
      Staphylococcal exfoliative toxins: "molecular scissors" of bacteria that
      attack the cutaneous defense barrier in mammals.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Bullous impetigo and its generalized form, staphylococcal scalded-skin
      syndrome (SSSS), are highly contagious, blistering skin diseases caused by
      Staphylococcus aureus infection.
    explanation: >-
      Documents the blistering presentation that separates the bullous form.
prevalence:
- population: Children worldwide (population-based surveillance studies)
  measure_type: POINT_PREVALENCE
  prevalence_class: ABOVE_1_IN_1000
  rate_per_100000: 12300.0
  notes: >-
    Median childhood prevalence 12.3% (IQR 4.2-19.4%) across 82 population
    surveillance studies; the authors estimate more than 162 million children
    affected at any one time, predominantly in tropical, resource-poor
    settings.
  evidence:
  - reference: PMID:26317533
    reference_title: >-
      The Global Epidemiology of Impetigo: A Systematic Review of the Population
      Prevalence of Impetigo and Pyoderma.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: "Median childhood prevalence was 12·3% (IQR 4·2-19·4%)."
    explanation: >-
      Systematic review of population surveillance studies giving the median
      childhood point prevalence of impetigo.
  - reference: PMID:26317533
    reference_title: >-
      The Global Epidemiology of Impetigo: A Systematic Review of the Population
      Prevalence of Impetigo and Pyoderma.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: >-
      we estimate the global population of children suffering from impetigo at
      any one time to be in excess of 162 million, predominantly in tropical,
      resource-poor contexts.
    explanation: >-
      Extrapolates the pooled prevalence to a global count of children affected
      at any one time.
- population: Worldwide, all ages
  measure_type: UNKNOWN
  notes: >-
    Global disease burden of greater than 140 million; the source does not
    state the measure.
  evidence:
  - reference: PMID:33105179
    reference_title: Impetigo.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Impetigo is a common superficial bacterial infection of the skin, with a
      global disease burden of greater than 140 million.
    explanation: >-
      Review statement of the global burden of impetigo.
progression:
- phase: Papulovesicular onset
  notes: >-
    Lesions begin as erythematous papules that progress to thin-walled
    vesicles or pustules.
  evidence:
  - reference: PMID:31630410
    reference_title: "Skin infections in Australian Aboriginal children: a narrative review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Impetigo begins as erythematous papules, progressing to thinly walled
      pustules that rupture and crust over with a progressively thickening scab.
    explanation: >-
      Describes the papular onset and pustular stage of impetigo lesions.
- phase: Rupture and crusting
  duration: 4 to 6 days
  notes: >-
    Vesicles, pustules, or bullae rupture and form honey-colored crusts over
    4 to 6 days.
  evidence:
  - reference: PMID:41839109
    reference_title: "Impetigo: Rapid Evidence Review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      erythematous papules that progress to ruptured vesicles or bullae over 4
      to 6 days, forming honey-colored crusts.
    explanation: >-
      Gives the timing of progression from papules to ruptured, crusted lesions.
- phase: Healing
  duration: up to 30 days without treatment
  notes: >-
    The scab shrinks and the eroded base heals, often without scarring;
    untreated resolution can take 30 days.
  evidence:
  - reference: PMID:31630410
    reference_title: "Skin infections in Australian Aboriginal children: a narrative review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      As healing begins, the scab shrinks, tethering surrounding skin to heal
      the eroded base, often without scarring.
    explanation: >-
      Describes the healing phase of impetigo lesions.
  - reference: PMID:31630410
    reference_title: "Skin infections in Australian Aboriginal children: a narrative review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Without treatment, resolution can take 30 days"
    explanation: >-
      Gives the duration of untreated resolution.
transmission:
- name: Direct-contact and fomite spread with autoinoculation
  description: >-
    Impetigo spreads efficiently from colonized lesions by skin-to-skin contact,
    contact with contaminated objects, and self-inoculation to additional
    breached epidermal sites.
  evidence:
  - reference: PMID:41839109
    reference_title: "Impetigo: Rapid Evidence Review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Reducing the spread and recurrence of impetigo includes good hand hygiene,
      thoroughly washing objects used by people with impetigo, and refraining
      from returning to work or school until 12 to 24 hours after initiating
      antibiotic treatment or clinical improvement occurs.
    explanation: >-
      Hand hygiene, object washing, and temporary school or work exclusion
      support direct-contact and fomite spread among close contacts.
pathophysiology:
- name: Epidermal Barrier Disruption
  role: trigger
  biological_scale: TISSUE
  description: >-
    Breaks in the epidermal barrier from abrasions, insect bites, scabies,
    atopic dermatitis, or other minor skin trauma expose a superficial niche
    for S. aureus and S. pyogenes.
  locations:
  - preferred_term: skin epidermis
    term:
      id: UBERON:0001003
      label: skin epidermis
  downstream:
  - target: Superficial Bacterial Colonization
    description: >-
      The breached epidermis allows S. aureus, S. pyogenes, or both to
      establish and proliferate locally.
  evidence:
  - reference: PMID:31630410
    reference_title: "Skin infections in Australian Aboriginal children: a narrative review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Infection may be direct or secondary to cutaneous barrier damage resulting
      from insect bites, minor trauma, or other pruritic dermatoses, especially
      scabies, head lice and tinea.
    explanation: >-
      Names cutaneous barrier damage, including scabies and other pruritic
      dermatoses, as the setting for secondary impetigo.
  - reference: PMID:41839109
    reference_title: "Impetigo: Rapid Evidence Review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Risk factors for impetigo include disruptions to the skin barrier, poor
      hygiene, crowded living environments, living in hot and humid climates,
      malnutrition, and diabetes.
    explanation: >-
      Lists disruption of the skin barrier as a risk factor for impetigo.
- name: Superficial Bacterial Colonization
  role: cause
  biological_scale: TISSUE
  description: >-
    S. aureus, S. pyogenes, or both colonize and proliferate in the superficial
    epidermis at the breached site.
  locations:
  - preferred_term: skin epidermis
    term:
      id: UBERON:0001003
      label: skin epidermis
  cell_types:
  - preferred_term: keratinocyte
    term:
      id: CL:0000312
      label: keratinocyte
  downstream:
  - target: Nonbullous Pyogenic Epidermal Infection
    description: >-
      S. pyogenes, S. aureus, or both proliferate locally to produce
      vesiculopustules and crusted erosions.
  - target: Exfoliative Toxin Production by S. aureus
    description: >-
      Toxigenic S. aureus expresses exfoliative toxins at the infected epidermal
      site.
  evidence:
  - reference: PMID:28655473
    reference_title: >-
      Keratinocytes as sensors and central players in the immune defense against
      Staphylococcus aureus in the skin.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Staphylococcus aureus is only rarely found on healthy human skin, but
      frequently colonizes the skin of atopic dermatitis (AD) patients
    explanation: >-
      Supports defective or inflamed epidermal barrier states as permissive for
      S. aureus colonization.
  - reference: PMID:31755570
    reference_title: >-
      Disseminated bullous impetigo and atopic dermatitis: Case series and
      literature review.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Due to compromised barrier function and immune dysregulation, children
      with atopic dermatitis (AD) are at increased risk of cutaneous infections
    explanation: >-
      Links a compromised epidermal barrier in atopic dermatitis to increased
      risk of cutaneous bacterial infection.
  - reference: PMID:31755570
    reference_title: >-
      Disseminated bullous impetigo and atopic dermatitis: Case series and
      literature review.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Eleven children (92%) had severe AD."
    explanation: >-
      In a case series of disseminated bullous impetigo, nearly all children had
      severe atopic dermatitis, consistent with barrier-defective skin favoring
      S. aureus infection.
- name: Nonbullous Pyogenic Epidermal Infection
  role: cause
  biological_scale: TISSUE
  description: >-
    S. pyogenes and non-toxigenic or toxigenic S. aureus proliferate in the
    superficial epidermis, recruiting neutrophils and creating vesicles and
    pustules that rupture into the honey-colored crusts of nonbullous impetigo.
  locations:
  - preferred_term: skin epidermis
    term:
      id: UBERON:0001003
      label: skin epidermis
  cell_types:
  - preferred_term: keratinocyte
    term:
      id: CL:0000312
      label: keratinocyte
  - preferred_term: neutrophil
    term:
      id: CL:0000775
      label: neutrophil
  biological_processes:
  - preferred_term: inflammatory response
    modifier: INCREASED
    term:
      id: GO:0006954
      label: inflammatory response
  downstream:
  - target: Vesicles
    description: >-
      Superficial pyogenic infection produces vesicles from the initial
      erythematous papules.
  - target: Pustules
    description: >-
      Neutrophil-rich superficial infection produces thin-walled pustules.
  - target: Honey-colored crusts
    description: >-
      Vesicles and pustules rupture and dry into the characteristic crusted
      superficial erosions.
  - target: Post-Streptococcal Immune Sequelae
    description: >-
      Group A streptococcal skin infection can antecede acute
      post-streptococcal glomerulonephritis and acute rheumatic fever in
      endemic communities.
  evidence:
  - reference: PMID:33105179
    reference_title: Impetigo.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Nonbullous impetigo is caused by S. aureus and S. pyogenes whereas
      bullous impetigo is caused by S. aureus.
    explanation: >-
      This distinguishes the streptococcal/staphylococcal microbiology of
      nonbullous disease from the staphylococcal-only bullous branch.
  - reference: PMID:31630410
    reference_title: "Skin infections in Australian Aboriginal children: a narrative review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Impetigo begins as erythematous papules, progressing to thinly walled
      pustules that rupture and crust over with a progressively thickening scab.
    explanation: >-
      Describes the papule-to-pustule-to-crust evolution of the superficial
      infection.
- name: Exfoliative Toxin Production by S. aureus
  role: cause
  biological_scale: MOLECULAR
  description: >-
    Toxigenic S. aureus strains express ETA or ETB, encoded on a phage genome or
    plasmid respectively, and secrete exfoliative toxin as the pathogen effector
    that initiates bullous impetigo.
  downstream:
  - target: Desmoglein 1 Ectodomain Cleavage
    description: >-
      Secreted exfoliative toxin reaches superficial keratinocyte desmosomes and
      cleaves desmoglein 1.
    causal_link_type: DIRECT
  evidence:
  - reference: PMID:21282415
    reference_title: Regulatory mechanism for exfoliative toxin production in Staphylococcus aureus.
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: BACKGROUND
    snippet: >-
      Most S. aureus strains that cause blistering disease produce either ETA or
      ETB. They are serologically distinct molecules, where ETA is encoded on a
      phage genome and ETB is enocded on a large plasmid.
    explanation: >-
      Introduction background in a bacterial-genetics study, identifying ETA and
      ETB as the common exfoliative toxins of blistering S. aureus disease and
      their phage and plasmid genetic contexts.
- name: Desmoglein 1 Ectodomain Cleavage
  role: cause
  biological_scale: MOLECULAR
  description: >-
    Staphylococcal exfoliative toxins are glutamate-specific serine proteases
    that cleave one peptide bond in the extracellular region of desmoglein 1,
    disrupting superficial keratinocyte adhesion at desmosomes.
  genes:
  - preferred_term: DSG1
    term:
      id: hgnc:3048
      label: DSG1
  cell_types:
  - preferred_term: keratinocyte
    term:
      id: CL:0000312
      label: keratinocyte
  molecular_functions:
  - preferred_term: exfoliative toxin serine protease activity
    modifier: INCREASED
    term:
      id: GO:0008233
      label: peptidase activity
  biological_processes:
  - preferred_term: desmoglein 1 proteolysis
    modifier: INCREASED
    term:
      id: GO:0006508
      label: proteolysis
  cellular_components:
  - preferred_term: desmosome
    term:
      id: GO:0030057
      label: desmosome
  downstream:
  - target: Granular-Layer Acantholysis and Bullae
    description: >-
      Loss of the adhesive Dsg1 ectodomain is sufficient to produce the
      superficial intraepidermal blister.
    causal_link_type: DIRECT
  evidence:
  - reference: PMID:17582744
    reference_title: >-
      Staphylococcal exfoliative toxins: "molecular scissors" of bacteria that
      attack the cutaneous defense barrier in mammals.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      the three isoforms of ETs, i.e., ETA, ETB, and ETD, are
      glutamate-specific serine proteases that specifically and efficiently
      cleave a single peptide bond in the extracellular region of human and
      mouse desmoglein 1 (Dsg1), a desmosomal intercellular adhesion molecule
    explanation: >-
      Defines exfoliative toxins as glutamate-specific proteases that cleave a
      single extracellular peptide bond in desmoglein 1.
  - reference: PMID:20728315
    reference_title: >-
      Removal of amino-terminal extracellular domains of desmoglein 1 by
      staphylococcal exfoliative toxin is sufficient to initiate epidermal
      blister formation.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      Our findings suggest that the removal of amino-terminal extracellular
      domains of Dsg1 by ETs is sufficient to initiate epidermal blister
      formation in bullous impetigo and SSSS.
    explanation: >-
      Shows in a neonatal mouse model that exfoliative-toxin removal of the Dsg1
      ectodomain is sufficient to initiate bullous impetigo-like blistering.
- name: Granular-Layer Acantholysis and Bullae
  role: outcome
  biological_scale: TISSUE
  description: >-
    Cleavage of desmoglein 1 separates superficial keratinocytes at the granular
    layer, creating a flaccid intraepidermal blister whose roof ruptures into
    moist erosions and crust.
  locations:
  - preferred_term: skin epidermis
    term:
      id: UBERON:0001003
      label: skin epidermis
  cell_types:
  - preferred_term: keratinocyte
    term:
      id: CL:0000312
      label: keratinocyte
  biological_processes:
  - preferred_term: homophilic cell-cell adhesion
    modifier: DECREASED
    term:
      id: GO:0007156
      label: homophilic cell-cell adhesion
  cellular_components:
  - preferred_term: desmosome
    term:
      id: GO:0030057
      label: desmosome
  downstream:
  - target: Flaccid bullae
    description: >-
      The superficial intraepidermal split manifests clinically as flaccid
      bullae in bullous impetigo.
  - target: Honey-colored crusts
    description: >-
      The fragile bullae rupture into moist erosions that crust over.
  evidence:
  - reference: PMID:20728315
    reference_title: >-
      Removal of amino-terminal extracellular domains of desmoglein 1 by
      staphylococcal exfoliative toxin is sufficient to initiate epidermal
      blister formation.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      Epidermal blister formation was observed as early as 60 min after ETA
      treatment.
    explanation: >-
      The neonatal mouse model develops rapid epidermal blistering after ETA
      exposure.
- name: Post-Streptococcal Immune Sequelae
  role: outcome
  biological_scale: ORGANISM
  description: >-
    Group A streptococcal impetigo can trigger serious post-infectious
    complications, including acute post-streptococcal glomerulonephritis and
    acute rheumatic fever, in high-burden communities.
  downstream: []
  evidence:
  - reference: PMID:31630410
    reference_title: "Skin infections in Australian Aboriginal children: a narrative review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Impetigo, scabies, cellulitis and abscesses are common in Australian
      Aboriginal children. These conditions adversely affect wellbeing and are
      associated with serious long term sequelae, including invasive infection
      and post-infectious complications, such as acute post-streptococcal
      glomerulonephritis and acute rheumatic fever
    explanation: >-
      This review links impetigo in a high-burden pediatric setting to severe
      invasive and post-infectious sequelae.
phenotypes:
- category: Skin
  name: Honey-colored crusts
  description: >-
    Ruptured vesicles, pustules, and bullae dry into honey-colored crusts over
    superficial erosions, the classic visible sign of impetigo.
  phenotype_term:
    preferred_term: Honey-colored crusted skin erosion
    term:
      id: HP:0200041
      label: Skin erosion
  evidence:
  - reference: PMID:41839109
    reference_title: "Impetigo: Rapid Evidence Review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Diagnosis of impetigo is based primarily on clinical examination and
      should be suspected in individuals with erythematous papules that progress
      to ruptured vesicles or bullae over 4 to 6 days, forming honey-colored
      crusts.
    explanation: >-
      The review describes ruptured vesicles and bullae that dry into
      honey-colored crusts. HPO has no honey-crust-specific term; the lesion is
      a superficial epidermal erosion rather than an ulcer, so it is bound to
      Skin erosion.
- category: Skin
  name: Vesicles
  description: Erythematous papules evolve into vesicles in early impetigo.
  phenotype_term:
    preferred_term: Skin vesicle
    term:
      id: HP:0200037
      label: Skin vesicle
  evidence:
  - reference: PMID:41839109
    reference_title: "Impetigo: Rapid Evidence Review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Diagnosis of impetigo is based primarily on clinical examination and
      should be suspected in individuals with erythematous papules that progress
      to ruptured vesicles or bullae over 4 to 6 days, forming honey-colored
      crusts.
    explanation: This supports vesicles as an early lesion stage.
- category: Skin
  name: Pustules
  description: >-
    Erythematous papules progress to thin-walled pustules that rupture and
    crust.
  phenotype_term:
    preferred_term: Pustule
    term:
      id: HP:0200039
      label: Pustule
  evidence:
  - reference: PMID:31630410
    reference_title: "Skin infections in Australian Aboriginal children: a narrative review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Impetigo begins as erythematous papules, progressing to thinly walled
      pustules that rupture and crust over with a progressively thickening scab.
    explanation: >-
      Describes thin-walled pustules as a stage of impetigo lesion evolution.
- category: Skin
  name: Flaccid bullae
  subtype: Bullous
  description: Bullous impetigo produces fragile superficial blisters.
  phenotype_term:
    preferred_term: Abnormal blistering of the skin
    term:
      id: HP:0008066
      label: Abnormal blistering of the skin
  evidence:
  - reference: PMID:17582744
    reference_title: >-
      Staphylococcal exfoliative toxins: "molecular scissors" of bacteria that
      attack the cutaneous defense barrier in mammals.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Bullous impetigo and its generalized form, staphylococcal scalded-skin
      syndrome (SSSS), are highly contagious, blistering skin diseases caused by
      Staphylococcus aureus infection.
    explanation: >-
      Establishes blistering as the defining manifestation of bullous impetigo.
diagnosis:
- name: Clinical Diagnosis of Crusted Vesiculobullous Lesions
  description: >-
    Impetigo is usually diagnosed clinically from erythematous papules evolving
    over days into ruptured vesicles or bullae with honey-colored crusts; swab
    culture is reserved for recurrent, extensive, outbreak-associated, or
    methicillin-resistant S. aureus-suspected disease.
  evidence:
  - reference: PMID:41839109
    reference_title: "Impetigo: Rapid Evidence Review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Diagnosis of impetigo is based primarily on clinical examination and
      should be suspected in individuals with erythematous papules that progress
      to ruptured vesicles or bullae over 4 to 6 days, forming honey-colored
      crusts.
    explanation: >-
      Supports recognition of impetigo by clinical examination of the evolving
      vesiculobullous crusted eruption.
treatments:
- name: Topical Antibiotic Therapy for Limited Impetigo
  description: >-
    Limited impetigo is treated with topical antibiotics such as mupirocin,
    retapamulin, ozenoxacin, or fusidic acid, which kill S. aureus and
    S. pyogenes locally and shorten the contagious superficial infection.
    Resistance limits these agents: the fusidic acid-resistant epidemic
    European impetigo clone (EEFIC) of S. aureus has persisted in Belgium, and
    a variant of it carrying mupirocin resistance has spread among children
    there.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Antibiotic Therapy
    term:
      id: NCIT:C15620
      label: Antibiotic Therapy
    therapeutic_agent:
    - preferred_term: mupirocin
      term:
        id: CHEBI:7025
        label: mupirocin
    - preferred_term: retapamulin
      term:
        id: CHEBI:166679
        label: Retapamulin
    - preferred_term: ozenoxacin
      term:
        id: CHEBI:136050
        label: ozenoxacin
    - preferred_term: fusidic acid
      term:
        id: CHEBI:29013
        label: fusidic acid
  target_mechanisms:
  - target: Nonbullous Pyogenic Epidermal Infection
    treatment_effect: INHIBITS
    description: >-
      Topical antibiotics suppress superficial bacterial proliferation.
  - target: Exfoliative Toxin Production by S. aureus
    treatment_effect: INHIBITS
    description: >-
      Topical antibiotics suppress toxigenic S. aureus in localized bullous
      impetigo before additional toxin can be produced.
  evidence:
  - reference: PMID:41839109
    reference_title: "Impetigo: Rapid Evidence Review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Topical mupirocin 2% ointment or retapamulin 1% ointment are the
      recommended initial treatments for mild, nonbullous and bullous impetigo.
    explanation: >-
      This supports topical antibiotic therapy as initial treatment for mild
      impetigo of either clinical form.
  - reference: PMID:15106198
    reference_title: Interventions for impetigo.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Topical antibiotics showed better cure rates than placebo (pooled odds
      ratio (OR) 6.49, 95% confidence interval (CI) 3.93 to 10.73)
    explanation: >-
      Cochrane randomized-trial synthesis supports the efficacy of topical
      antibiotics for impetigo.
  - reference: PMID:15106198
    reference_title: Interventions for impetigo.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      There is good evidence that topical mupirocin and topical fusidic acid are
      equally, or more effective than oral treatment for people with limited
      disease.
    explanation: >-
      Supports topical fusidic acid, alongside mupirocin, for limited impetigo.
  - reference: PMID:29898217
    reference_title: >-
      Efficacy and Safety of Ozenoxacin Cream for Treatment of Adult and
      Pediatric Patients With Impetigo: A Randomized Clinical Trial.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Topical ozenoxacin is effective and well tolerated in the treatment of
      impetigo in patients 2 months and older.
    explanation: >-
      Randomized vehicle-controlled trial supporting topical ozenoxacin for
      impetigo.
  - reference: PMID:37358399
    reference_title: >-
      Persistence of the Staphylococcus aureus epidemic European fusidic
      acid-resistant impetigo clone (EEFIC) in Belgium.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      EEFIC isolates were mostly isolated from young patients with impetigo and
      showed a seasonal late summer peak.
    explanation: >-
      National surveillance shows the fusidic acid-resistant EEFIC clone
      persisting among young patients with impetigo, a resistance caveat for
      topical fusidic acid.
  - reference: PMID:38726693
    reference_title: >-
      Emergence and spread of a mupirocin-resistant variant of the European
      epidemic fusidic acid-resistant impetigo clone of Staphylococcus aureus,
      Belgium, 2013 to 2023.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We highlight the spread of a mupirocin-resistant EEFIC in children, with a
      seasonal trend for the third quarter of the year. This is of concern
      because this variant is resistant to the two main topical antibiotics
      used to treat impetigo in Belgium.
    explanation: >-
      Documents a variant of the clone resistant to both mupirocin and fusidic
      acid, the main topical agents for impetigo in Belgium.
- name: Oral Antibiotic Therapy for Extensive or Outbreak Disease
  description: >-
    Oral antibiotics targeting both group A Streptococcus and S. aureus are used
    for severe, multilesional, or outbreak-associated impetigo when topical
    therapy is insufficient to control bacterial proliferation and transmission.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Antibiotic Therapy
    term:
      id: NCIT:C15620
      label: Antibiotic Therapy
    therapeutic_agent:
    - preferred_term: dicloxacillin
      term:
        id: CHEBI:4511
        label: dicloxacillin
    - preferred_term: cephalexin
      term:
        id: CHEBI:3534
        label: cephalexin
  target_mechanisms:
  - target: Nonbullous Pyogenic Epidermal Infection
    treatment_effect: INHIBITS
    description: Oral antibiotics suppress disseminated superficial infection.
  - target: Exfoliative Toxin Production by S. aureus
    treatment_effect: INHIBITS
    description: Oral antibiotics treat extensive bullous impetigo.
  evidence:
  - reference: PMID:41839109
    reference_title: "Impetigo: Rapid Evidence Review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Oral antibiotics, such as dicloxacillin or cephalexin, should be targeted
      to group A streptococci and S. aureus and are recommended for outbreaks to
      decrease infection transmission or for severe, multilesional disease that
      does not respond to topical therapy within 3 to 5 days.
    explanation: >-
      This supports oral therapy for severe, multilesional, outbreak-associated,
      or topical-nonresponsive impetigo.
- name: Ivermectin Mass Drug Administration for Scabies-Associated Community Impetigo
  description: >-
    In communities where scabies is a major upstream breach in the skin barrier,
    ivermectin-based mass drug administration reduces scabies infestation and
    thereby reduces impetigo prevalence at the population level.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: ivermectin
      term:
        id: CHEBI:6078
        label: ivermectin
  target_mechanisms:
  - target: Epidermal Barrier Disruption
    treatment_effect: INHIBITS
    description: >-
      Scabies control lowers one infestation-driven source of scratching and
      epidermal barrier breaks.
  evidence:
  - reference: PMID:26650152
    reference_title: Mass Drug Administration for Scabies Control in a Population with Endemic Disease.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The prevalence of impetigo also declined in all groups, with the greatest
      reduction seen in the ivermectin group.
    explanation: >-
      In a Fiji cluster-randomized trial for scabies control, the ivermectin MDA
      arm produced the largest drop in impetigo prevalence.
environmental:
- name: Scabies infestation
  description: >-
    Scabies is a pruritic dermatosis whose resulting barrier damage precedes
    secondary impetigo, particularly in communities where both are endemic.
  notes: >-
    No ECTO exposure term for scabies or Sarcoptes scabiei: ols:ecto searches
    for "scabies" returned only ECTO:9002125 exposure to scabicide, and for
    "Sarcoptes scabiei" returned nothing.
  evidence:
  - reference: PMID:31630410
    reference_title: "Skin infections in Australian Aboriginal children: a narrative review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Infection may be direct or secondary to cutaneous barrier damage resulting
      from insect bites, minor trauma, or other pruritic dermatoses, especially
      scabies, head lice and tinea.
    explanation: >-
      Names scabies as a leading pruritic dermatosis behind barrier damage that
      precedes impetigo.
  influences_mechanisms:
  - target: Epidermal Barrier Disruption
    environmental_effect: PREDISPOSES
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: >-
      Scabies-associated pruritus and scratching damage the epidermis, opening
      the barrier breaks in which impetigo arises.
    evidence:
    - reference: PMID:31630410
      reference_title: "Skin infections in Australian Aboriginal children: a narrative review."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        Infection may be direct or secondary to cutaneous barrier damage
        resulting from insect bites, minor trauma, or other pruritic dermatoses,
        especially scabies, head lice and tinea.
      explanation: >-
        Places scabies upstream of the cutaneous barrier damage that permits
        secondary impetigo.
    - reference: PMID:26650152
      reference_title: Mass Drug Administration for Scabies Control in a Population with Endemic Disease.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        The prevalence of impetigo also declined in all groups, with the
        greatest reduction seen in the ivermectin group.
      explanation: >-
        Scabies control lowered impetigo prevalence, consistent with scabies
        acting upstream of impetigo.
- name: Crowded living environments
  description: >-
    Crowded housing increases close skin contact and is a recognized risk
    factor for impetigo.
  notes: >-
    No ECTO exposure term for crowding: ols:ecto searches for "crowding" and
    "crowded" returned nothing.
  evidence:
  - reference: PMID:41839109
    reference_title: "Impetigo: Rapid Evidence Review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Risk factors for impetigo include disruptions to the skin barrier, poor
      hygiene, crowded living environments, living in hot and humid climates,
      malnutrition, and diabetes.
    explanation: Lists crowded living environments as a risk factor for impetigo.
  influences_mechanisms:
  - target: Superficial Bacterial Colonization
    environmental_effect: PREDISPOSES
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      Crowding raises the chance that S. aureus or S. pyogenes reaches and
      colonizes breached skin.
    evidence:
    - reference: PMID:41839109
      reference_title: "Impetigo: Rapid Evidence Review."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        Risk factors for impetigo include disruptions to the skin barrier, poor
        hygiene, crowded living environments, living in hot and humid climates,
        malnutrition, and diabetes.
      explanation: Lists crowded living environments as a risk factor for impetigo.
- name: Poor hygiene
  description: >-
    Poor hygiene is a recognized risk factor for impetigo; hand hygiene and
    washing shared objects reduce its spread.
  notes: >-
    No ECTO exposure term for hygiene: an ols:ecto search for "hygiene"
    returned nothing.
  evidence:
  - reference: PMID:41839109
    reference_title: "Impetigo: Rapid Evidence Review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Risk factors for impetigo include disruptions to the skin barrier, poor
      hygiene, crowded living environments, living in hot and humid climates,
      malnutrition, and diabetes.
    explanation: Lists poor hygiene as a risk factor for impetigo.
  influences_mechanisms:
  - target: Superficial Bacterial Colonization
    environmental_effect: PREDISPOSES
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      Poor hygiene favors transfer and persistence of the causative bacteria on
      the skin.
    evidence:
    - reference: PMID:41839109
      reference_title: "Impetigo: Rapid Evidence Review."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        Risk factors for impetigo include disruptions to the skin barrier, poor
        hygiene, crowded living environments, living in hot and humid climates,
        malnutrition, and diabetes.
      explanation: Lists poor hygiene as a risk factor for impetigo.
- name: Hot and humid climate
  description: >-
    Living in hot and humid climates is a recognized risk factor for
    impetigo.
  exposure_term:
    preferred_term: hot and humid climate
    term:
      id: ECTO:0010007
      label: exposure to humidity
  evidence:
  - reference: PMID:41839109
    reference_title: "Impetigo: Rapid Evidence Review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Risk factors for impetigo include disruptions to the skin barrier, poor
      hygiene, crowded living environments, living in hot and humid climates,
      malnutrition, and diabetes.
    explanation: Lists hot and humid climates as a risk factor for impetigo.
  influences_mechanisms:
  - target: Superficial Bacterial Colonization
    environmental_effect: PREDISPOSES
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      Hot, humid climates predispose to impetigo; the intermediate steps are
      not specified by the source.
    evidence:
    - reference: PMID:41839109
      reference_title: "Impetigo: Rapid Evidence Review."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        Risk factors for impetigo include disruptions to the skin barrier, poor
        hygiene, crowded living environments, living in hot and humid climates,
        malnutrition, and diabetes.
      explanation: Lists hot and humid climates as a risk factor for impetigo.
📚

References & Deep Research

Deep Research

1

Deep research results are used as seeds for research; they do not undergo the same validation as the main records and may contain errors. How we use deep research.

Evaluations and curation notes (2)

Address review on PR 14886: phenotype wiring, subtypes, prevalence, environment, agents · 2026-10-20T04:45:54Z · View source

Addressed the automated CHANGES_REQUESTED review. Rebound Honey-colored crusts from HP:0200042 Skin ulcer to HP:0200041 Skin erosion (impetigo erosions are superficial; ulceration defines ecthyma). Removed the duplicate Honey-Colored Crusted Erosions pathophysiology node and pointed downstream edges at the phenotype names (Nonbullous Pyogenic Epidermal Infection to Vesicles, Pustules, Honey-colored crusts; acantholysis node to Flaccid bullae and Honey-colored crusts). Split the bundled barrier/colonization trigger into Epidermal Barrier Disruption -> Superficial Bacterial Colonization and dropped the unsupported GO:0019730 antimicrobial humoral response DECREASED annotation; added atopic dermatitis evidence from PMID:31755570. Regraded PMID:21282415 (introduction sentence) to evidence_source OTHER with quote_role BACKGROUND. Added Nonbullous/Bullous has_subtypes (bullous bound to MONDO:0018182, looked up via ols:mondo), a Pustules phenotype (HP:0200039), prevalence from PMID:26317533 and PMID:33105179, a three-phase progression block, retapamulin (CHEBI:166679), ozenoxacin (CHEBI:136050, PMID:29898217) and fusidic acid (CHEBI:29013, Cochrane PMID:15106198) as topical agents, dicloxacillin (CHEBI:4511) and cephalexin (CHEBI:3534) as oral agents, EEFIC fusidic-acid and mupirocin resistance evidence (PMID:37358399, PMID:38726693), and an environmental section (scabies, crowding, poor hygiene, hot and humid climate) linked to the barrier and colonization nodes. Moved the deep-research provenance (falcon to openscientist fallback, preflight-dr SKIP, rejected report identifiers MONDO:0001366, MONDO:0005295, CHEBI:4508 and obsolete GO:0005615) out of the entry notes; it is recorded in the earlier history records. Not done: regional lymphadenopathy (no cited or cached source quotes it), APSGN/ARF split of the post-streptococcal node, and StatPearls tagging. Validation: just validate, validate-terms, count-verified-snippets (49/49) pass.

Create: Impetigo · 2026-09-29T17:54:14Z · View source

Created a new Impetigo entry for MONDO:0004592 after an ignored-file local search, origin/main search, and open GitHub issue/PR duplicate preflight found no standalone entry or in-flight claim. Deep research was requested from falcon and fell back to openscientist; all 32 report references resolved, term validation found three wrong identifiers and one obsolete GO term that were avoided, and preflight-dr skipped because MONDO records no causal human gene for this acquired infection. The entry models S. aureus and S. pyogenes as infectious agents, contact and fomite spread, the nonbullous pyogenic epidermal infection branch, the bullous exfoliative-toxin to DSG1 cleavage branch, post-streptococcal immune sequelae as a downstream outcome, vesicles, bullae, honey-colored crusts, clinical diagnosis, topical and oral antibiotic therapy, and ivermectin MDA for scabies-associated community impetigo. References were generated by the deep-research validation or preexisting cache entries; no references_cache file was hand-edited. Validation: just validate kb/disorders/Impetigo.yaml, just count-verified-snippets kb/disorders/Impetigo.yaml, just validate-terms kb/disorders/Impetigo.yaml, check-duplicate-keys, check-enum-values, check-entity-refs, check-causal-targets, and check-qualifier-terms all pass.

OpenScientist ▸
Impetigo (MONDO:0004592): A Comprehensive Disease Characteristics Report
openscientist-autonomous 31 citations 2026-09-29T10:46:34.251650

Impetigo (MONDO:0004592): A Comprehensive Disease Characteristics Report

Disease: Impetigo | MONDO: MONDO:0004592 | Category: Infectious Disease Report date: 2026-09-29 | Evidence base: PubMed primary literature, Cochrane, GBD, clinical guidelines

Summary

Impetigo is a common, highly contagious, superficial bacterial infection of the epidermis caused predominantly by Staphylococcus aureus and Streptococcus pyogenes (group A streptococcus, GAS). It presents in two clinical forms: nonbullous impetigo (~70% of cases), caused by both S. aureus and S. pyogenes, and bullous impetigo (~30%), caused specifically by exfoliative-toxin-producing S. aureus strains. The disease is diagnosed clinically by its characteristic evolution of erythematous papules into vesicles or bullae over 4–6 days, forming pathognomonic honey-colored crusts. It is an acquired, non-genetic infectious disease — there are no causal human genes — although host factors such as skin-barrier and antimicrobial-peptide deficiency (as in atopic dermatitis and filaggrin insufficiency) create a permissive substrate for S. aureus colonization and subsequent infection.

Impetigo is overwhelmingly a disease of childhood and of poverty. More than 162 million children are affected globally at any one time, with a median childhood prevalence of 12.3%, concentrated in tropical, resource-poor, and marginalized communities. The Global Burden of Disease (GBD) 2019 analysis places pyoderma/impetigo as the dominant bacterial skin disease burden (~0.41 million DALYs), with the heaviest impact in low-middle sociodemographic index (SDI) regions. Although usually mild and self-limited, streptococcal impetigo can trigger serious post-infectious sequelae — acute post-streptococcal glomerulonephritis (APSGN) and acute rheumatic fever (ARF) — which occur at the highest documented rates in the world in remote Aboriginal Australian communities.

The mechanistic centerpiece of bullous impetigo (and its severe systemic counterpart, staphylococcal scalded skin syndrome) is the cleavage of desmoglein-1 (Dsg1), a desmosomal keratinocyte adhesion molecule, by glutamate-specific serine protease exfoliative toxins (ETA, ETB, ETD). Removal of the amino-terminal extracellular domains of Dsg1 is sufficient to initiate intraepidermal blister formation. Treatment is stratified by severity: topical antibiotics (mupirocin, retapamulin, ozenoxacin) for limited disease and oral antibiotics (dicloxacillin, cephalexin) for extensive/bullous/outbreak disease. Rising antimicrobial resistance — exemplified by the epidemic European fusidic-acid-resistant impetigo clone (EEFIC) and its emergent mupirocin-resistant variant — is a growing threat. At the community level, ivermectin-based mass drug administration (MDA) for scabies substantially reduces impetigo prevalence and its bacterial complications.

Key Findings

Finding 1 — Impetigo is a superficial bacterial infection in two clinical forms

Impetigo is a common superficial bacterial infection of the skin with a global disease burden exceeding 140 million cases. It manifests in two forms with distinct proportions and microbiology. Nonbullous impetigo (~70%) is caused by both S. aureus and S. pyogenes (group A streptococcus) and is the classic "school-sores" presentation. Bullous impetigo (~30%) is caused exclusively by exfoliative-toxin-producing S. aureus strains. Diagnosis is clinical: erythematous papules progress to vesicles or bullae over 4–6 days, ultimately rupturing and drying into the characteristic honey-colored crusts.

"Impetigo can be nonbullous (70%) or bullous (30%) and is most commonly caused by group A streptococcus and Staphylococcus aureus." — PMID: 41839109

"Impetigo is a common superficial bacterial infection of the skin, with a global disease burden of greater than 140 million." — PMID: 33105179

Ontology anchors: MONDO:0004592 (impetigo); ICD-10 L01; ICD-11 1B72; UBERON:0002097 (skin of body), UBERON:0001003 (skin epidermis); NCBITaxon:1280 (S. aureus), NCBITaxon:1314 (S. pyogenes).

Finding 2 — Bullous impetigo pathogenesis: exfoliative toxins cleave desmoglein-1

The molecular mechanism of bullous impetigo is now precisely defined. S. aureus produces three isoforms of exfoliative toxin — ETA, ETB, and ETD — which are glutamate-specific serine proteases that cleave a single peptide bond in extracellular domains 3–4 of desmoglein-1 (Dsg1), a desmosomal cell–cell adhesion molecule expressed by keratinocytes in the superficial epidermis. This proteolysis disrupts intercellular adhesion within the granular layer, producing the superficial intraepidermal split characteristic of the disease.

"the three isoforms of ETs, i.e., ETA, ETB, and ETD, are glutamate-specific serine proteases that specifically and efficiently cleave a single peptide bond in the extracellular region of human and mouse desmoglein 1 (Dsg1), a desmosomal intercellular adhesion molecule" — PMID: 17582744

Critically, removal of the amino-terminal extracellular domains of Dsg1 is sufficient to initiate blister formation, demonstrated as early as 60 minutes after ETA injection in neonatal mice — establishing Dsg1 cleavage as the direct, proximate cause rather than a downstream correlate.

"the removal of amino-terminal extracellular domains of Dsg1 by ETs is sufficient to initiate ep[idermal blister formation]" — PMID: 20728315

The toxin genes have distinct genetic bases: ETA is phage-encoded, whereas ETB is plasmid-encoded, informing strain epidemiology and horizontal transfer of virulence.

"ETA is encoded on a phage genome and ETB is enocded on a large plasmid" — PMID: 21282415

The same molecular target (Dsg1) is shared across bullous impetigo, staphylococcal scalded skin syndrome (SSSS, the disseminated toxin-mediated form), and the autoimmune blistering disease pemphigus foliaceus — a striking example of convergent pathology at a single adhesion molecule.

Ontology anchors: HGNC gene DSG1 (desmoglein-1); GO:0007156 (homophilic cell adhesion via plasma membrane adhesion molecules), GO:0030057 (desmosome), GO:0008233 (peptidase activity); CL:0000312 (keratinocyte); HP:0008066 (abnormal blistering of the skin).

Finding 3 — Global burden exceeds 162 million children, concentrated in the tropics and poverty

A systematic review of 89 studies encompassing 145,028 children established a median childhood prevalence of 12.3% (IQR 4.2–19.4%). The burden is highly unequal: low and low-middle income countries showed median prevalences of 8.4–14.5%, but the highest burden was paradoxically in underprivileged children within high-income countries (median 19.4%, IQR 3.9–43.3%). Extrapolating these prevalences yields an estimate of more than 162 million children affected at any one time, predominantly in tropical, resource-poor contexts.

"we estimate the global population of children suffering from impetigo at any one time to be in excess of 162 million, predominantly in tropical, resource-poor contexts" — PMID: 26317533

"Median childhood prevalence was 12·3% (IQR 4·2-19·4%)" — PMID: 26317533

Finding 4 — Streptococcal impetigo drives post-infectious sequelae (APSGN and ARF)

Group A streptococcal impetigo is not merely a nuisance skin infection; it is an antecedent of serious immune-mediated sequelae. Skin infection with GAS can trigger acute post-streptococcal glomerulonephritis (APSGN), and GAS pharyngitis or impetigo can precede acute rheumatic fever (ARF) and its long-term consequence, rheumatic heart disease. In remote Australian Aboriginal communities, the combination of scabies, impetigo, and these post-infectious complications occurs at the highest documented rates in the world.

"associated with serious long term sequelae, including invasive infection and post-infectious complications, such as acute post-streptococcal glomerulonephritis and acute rheumatic fever, which occurs at the highest documented rates in the world in remote Aboriginal communities" — PMID: 31630410

"Acute rheumatic fever (ARF) is an autoimmune disorder resulting from Group A Streptococcus (GAS) pharyngitis or impetigo in children and adolescents" — PMID: 40484016

Ontology anchors: MONDO:0001366 (post-streptococcal glomerulonephritis); MONDO:0005295 (rheumatic fever); HP:0000790 (hematuria), HP:0000093 (proteinuria).

Finding 5 — Treatment is severity-stratified; topical antibiotics are effective first-line

The evidence base for impetigo treatment is substantial. A Cochrane systematic review incorporated 68 randomized controlled trials with 5,578 participants reporting on 50 different treatments. Pooled analysis showed topical antibiotics were markedly superior to placebo (pooled OR 6.49, 95% CI 3.93–10.73), with topical mupirocin superior to oral erythromycin and no significant difference between mupirocin and fusidic acid.

"The total number of included trials was, thus, 68, with 5578 participants, reporting on 50 different treatments" — PMID: 22258953

"Topical antibiotics showed better cure rates than placebo (pooled odds ratio (OR) 6.49, 95% confidence interval (CI) 3.93 to 10.73)" — PMID: 15106198

Current guidance recommends topical mupirocin 2% or retapamulin 1% for mild nonbullous and bullous disease, reserving oral agents (dicloxacillin, cephalexin) targeting both GAS and S. aureus for extensive, bullous, or outbreak disease.

"Topical mupirocin 2% ointment or retapamulin 1% ointment are the recommended initial treatments for mild, nonbullous and bullous impetigo." — PMID: 41839109

A newer non-fluorinated quinolone, ozenoxacin 1% cream, has demonstrated efficacy in randomized trials with rapid clinical and microbiological response, including activity against both MSSA and MRSA (see Evidence Base).

Ontology anchors: NCIT / CHEBI:7025 (mupirocin), retapamulin, ozenoxacin, CHEBI:4508 (dicloxacillin), cephalexin.

Finding 6 — Ivermectin mass drug administration substantially reduces community impetigo

Because impetigo frequently follows scabies infestation (excoriation breaches the skin barrier), community-level scabies control translates into impetigo reduction. Multiple trials confirm this across settings:

Setting Intervention Key result PMID
Fiji (cluster RCT, n=2,051) Ivermectin MDA Scabies 32.1%→1.9% (RR 94%, 95% CI 83–100); impetigo declined most in ivermectin arm 26650152
Solomon Islands (AIM trial, Choiseul, ~26,000 people) Ivermectin + azithromycin MDA Scabies 18.7%→2.3% (RR 88%), impetigo 24.8%→6.4% (RR 74%) 30956111
Northern India (single-arm, moderate prevalence) Ivermectin MDA Impetigo 1.2%→0.4% (RRR 66.1%, 95% CI 7.0–87); scabies RRR 87.7% 39431149
Fiji (before-after, n=131,914) Population MDA SSTI hospitalisations 17% lower (IRR 0.83, 95% CI 0.74–0.94) 35345391

"The prevalence declined from 32.1% to 1.9% in the ivermectin group (relative reduction, 94%; 95% confidence interval [CI], 83 to 100)" — PMID: 26650152

"The incidence of hospitalisations with skin and soft tissue infections was 17% lower after the intervention compared to baseline (388 vs 467 per 100,000 person-years; incidence rate ratio 0.83, 95% CI, 0.74 to 0.94" — PMID: 35345391

"5 had impetigo (0.4%; relative risk reduction, 66.1%; 95% CI, 7.0%-87[%])" — PMID: 39431149

Finding 7 — Antimicrobial-resistant S. aureus impetigo clones are emerging

Resistance to first-line topical agents is escalating. The epidemic European fusidic acid-resistant impetigo clone (EEFIC) persists in Belgium: among community-onset skin/soft-tissue S. aureus isolates, 16.2% were fusidic-acid-resistant, of which 48.1% belonged to the EEFIC, disproportionately from young impetigo patients with a late-summer seasonal peak.

"Of these, 79 (16.2%) were resistant to fusidic acid, of which 38 (48.1%) belonged to the EEFIC. EEFIC isolates were mostly isolated from young patients with impetigo and showed a seasonal late summer peak." — PMID: 37358399

A mupirocin-resistant variant of this clone has since emerged and spread, threatening a second first-line topical agent:

"Emergence and spread of a mupirocin-resistant variant of the European epidemic fusidic acid-resistant impetigo clone" — PMID: 38726693

Clones resistant to both mupirocin and fusidic acid and carrying exotoxin genes are increasingly causing skin infections (PMID: 28592549), and community MRSA impetigo outbreaks have been reported (e.g., the Netherlands, PMID: 36695440).

Finding 8 — Host skin-barrier and innate-immune dysfunction predispose to impetigo

Impetigo begins with S. aureus colonization, which is strongly modulated by host skin integrity. Keratinocytes are the principal epidermal cell orchestrating innate defense against S. aureus, which is rarely found on healthy skin but frequently colonizes atopic dermatitis (AD) skin.

"Staphylococcus aureus is only rarely found on healthy human skin, but frequently colonizes the skin of atopic dermatitis (AD) patients" — PMID: 28655473

AD promotes colonization through three converging mechanisms — barrier dysfunction, increased extracellular-matrix adhesins, and defective innate immunity from decreased antimicrobial peptides (AMPs):

"The mechanisms that allergic skin inflammation of AD promotes the increase of S. aureus colonization include skin barrier dysfunction, increased synthesis of the extracellular matrix adhesins for S. aureus, and defective innate immune responses due to decreased production of endogenous antimicrobial peptides" — PMID: 18163223

The relevant AMPs whose deficiency impairs cutaneous antibacterial defense are named explicitly:

"low production of the antimicrobial peptides cathelicidin LL-37 and human β-defensins" — PMID: 31836943

A filaggrin (FLG) Pro478Ser polymorphism associates with AD severity and S. aureus colonization (PMID: 27012026). Clinically, in a series of children with disseminated bullous impetigo, 92% had severe AD (PMID: 31755570) — powerful convergent evidence that barrier compromise is an upstream host-susceptibility axis.

Ontology anchors: HGNC gene FLG (filaggrin); CAMP (cathelicidin/LL-37), DEFB (β-defensins); GO:0019730 (antimicrobial humoral response), GO:0061436 (establishment of skin barrier); CL:0000312 (keratinocyte); MONDO:0004980 (atopic dermatitis).

Finding 9 — GBD 2019: pyoderma/impetigo is the dominant bacterial skin disease burden

The GBD 2019 analysis of bacterial skin diseases (BSD) quantified an age-standardized incidence of 169.72 million [165.28–175.44] and 0.41 million DALYs [0.33–0.48]. Of the two main BSD categories, pyoderma causes a significantly heavier burden than cellulitis, with the highest burden in low-middle SDI areas and the lowest in high-middle SDI regions.

"Of the two main BSD, pyoderma cause significantly much heavier burden than cellulitis. The highest burden was in the low-middle sociodemographic index (SDI) area" — PMID: 35547219

"The age-standardized incidence and age-standardized DALYs rate of BSD are: 169.72 million [165.28-175.44] and 0.41 million [0.33-0.48]" — PMID: 35547219

Trend analysis (1990–2019) shows rising age-standardized incidence and mortality rates for pyoderma/impetigo, with burden concentrated in children under 5 and the elderly and inversely related to socioeconomic development (PMID: 39805883).

Section-by-Section Report

1. Disease Information

Impetigo is a highly contagious, superficial bacterial infection of the epidermis, and one of the most common skin infections of childhood worldwide. Key identifiers: MONDO:0004592; ICD-10 L01 (L01.0 impetigo, L01.1 impetiginization of other dermatoses); ICD-11 1B72; MeSH D007169 ("Impetigo"); SNOMED CT 48277006. There is no OMIM entry because impetigo is not a Mendelian genetic disorder, and it is not a rare disease with a dedicated Orphanet entry. Synonyms/alternative names: impetigo contagiosa, "school sores," pyoderma (a broader term encompassing impetigo), non-bullous impetigo (impetigo vulgaris/crusted impetigo), bullous impetigo, and ecthyma (the deeper, ulcerative variant). The information in this report is derived from aggregated disease-level resources — systematic reviews, GBD modeling, and clinical cohorts — rather than from individual EHR patient records.

2. Etiology

Causal factors: Impetigo is an infectious disease caused by Gram-positive bacteria — predominantly Staphylococcus aureus (NCBITaxon:1280) and Streptococcus pyogenes (group A streptococcus; NCBITaxon:1314). Bullous impetigo is specifically caused by exfoliative-toxin-producing S. aureus (Finding 2).

Environmental/lifestyle risk factors: warm humid tropical climate, crowding, poverty, poor hygiene and limited access to water, and — importantly — antecedent skin trauma or infestation (scabies, insect bites, minor abrasions, atopic dermatitis) that breaches the epidermal barrier. Young age (2–5 years) is the strongest demographic risk factor. Genetic risk: There are no causal or susceptibility loci for impetigo itself; however, host genetic factors influencing barrier and innate immunity — notably filaggrin (FLG) loss-of-function and the Pro478Ser polymorphism — modulate S. aureus colonization and thereby indirect risk (Finding 8).

Protective factors: intact skin barrier, adequate cutaneous antimicrobial peptide production (cathelicidin LL-37, β-defensins), good hygiene, and — at the community scale — scabies control via ivermectin MDA (Finding 6).

Gene–environment interaction: The clearest example is filaggrin deficiency (genetic) combined with environmental S. aureus exposure and AD inflammation, which together amplify colonization and infection risk (Finding 8, PMID: 18163223, PMID: 27012026).

3. Phenotypes

Phenotype Type Characteristics Suggested HPO
Honey-colored crusted lesions Clinical sign Childhood onset; mild-moderate; classic nonbullous form HP:0011368 (epidermal thickening/crusting); HP:0200042 (skin ulcer)
Vesicles/pustules Physical manifestation Precede crusting; rupture over 4–6 days HP:0200037 (vesicle)
Flaccid bullae (bullous form) Physical manifestation ~30% of cases; Dsg1-mediated; neonates/infants HP:0008066 (abnormal blistering of the skin)
Pruritus Symptom Common; promotes autoinoculation/spread HP:0000989 (pruritus)
Regional lymphadenopathy Clinical sign More common with streptococcal disease HP:0002716 (lymphadenopathy)
Erythema Clinical sign Surrounds lesions HP:0000988 (skin rash)

Onset: predominantly childhood (peak 2–5 years); neonatal for bullous forms. Severity: usually mild and localized; occasionally extensive/disseminated. Progression: acute and self-limited over days to a few weeks; episodic recurrences occur with re-exposure. Quality-of-life impact: generally modest and transient (discomfort, pruritus, cosmetic and social stigma, school exclusion), but recurrent or disseminated disease and post-infectious sequelae impose substantial morbidity in endemic settings.

4. Genetic/Molecular Information

Impetigo has no causal human genes — it is an acquired infection, so there are no pathogenic germline variants, modifier genes, or chromosomal abnormalities in the classical Mendelian sense. The relevant molecular players are: (a) the bacterial virulence genes — eta (phage-encoded), etb (plasmid-encoded), and etd exfoliative toxin genes of S. aureus (Finding 2); and (b) the host target and susceptibility genes — DSG1 (desmoglein-1, the toxin substrate) and barrier/innate-immunity genes FLG (filaggrin), CAMP (cathelicidin), and DEFB (β-defensins) whose deficiency predisposes to colonization (Finding 8). The FLG Pro478Ser polymorphism is a documented modifier of colonization risk (PMID: 27012026). Epigenetic and chromosomal-abnormality data are not applicable to this infectious disease.

5. Environmental Information

Infectious agents: S. aureus (including MRSA and MSSA) and S. pyogenes are the etiologic organisms; the exfoliative-toxin-producing S. aureus strains cause bullous disease. Environmental/lifestyle factors: heat, humidity, crowding, poor sanitation, and limited water access drive transmission; skin trauma, insect bites, and scabies infestation provide the portal of entry. There is no known role for chemical toxins, radiation, or occupational exposures. Impetigo is transmitted person-to-person by direct contact and via fomites; autoinoculation spreads lesions on the same host.

6. Mechanism / Pathophysiology

Ordered causal chain (bullous impetigo):

  1. Host skin-barrier/innate-immune compromise (e.g., atopic dermatitis, filaggrin deficiency, reduced LL-37/β-defensins) → permits S. aureus colonization of the skin. (inferred host-susceptibility step; supported by AD/FLG data)
  2. Breach of the epidermis (trauma, scabies, insect bite) → allows bacterial entry and superficial proliferation.
  3. Toxigenic S. aureus expresses exfoliative toxins ETA/ETB/ETD → secretes glutamate-specific serine proteases into the superficial epidermis.
  4. Exfoliative toxins cleave a single peptide bond in extracellular domains 3–4 of desmoglein-1 → abolish Dsg1-mediated keratinocyte adhesion in the granular layer.
  5. Loss of Dsg1 adhesion → results in intraepidermal acantholysis and a superficial blister split (demonstrated: Dsg1 domain removal is sufficient, blistering within 60 min in neonatal mice).
  6. Superficial blister roof ruptures → produces erosions that dry into honey-colored crusts (clinical manifestation).

Branch — nonbullous streptococcal impetigo:

3b. S. pyogenes (± S. aureus) colonizes traumatized skin → local pyogenic inflammation, pustule and crust formation without Dsg1 cleavage. 4b. In susceptible hosts, nephritogenic GAS strains → trigger immune-complex-mediated APSGN; rheumatogenic strains → can trigger ARF via molecular mimicry. (downstream, immune-mediated)

Molecular/cellular detail: The upstream lesion is bacterial colonization gated by host innate immunity (keratinocytes as sensors, PMID: 28655473); the proximate mechanism is proteolytic destruction of a desmosomal adhesion molecule (protein loss-of-function of Dsg1 via extracellular cleavage). The downstream clinical event is intraepidermal blistering; the downstream systemic events (APSGN, ARF) are host immune responses to streptococcal antigens. Cell types: keratinocytes (CL:0000312), neutrophils (CL:0000775). Biological processes: GO:0007156 (cell–cell adhesion), GO:0030057 (desmosome), GO:0006508 (proteolysis), GO:0019730 (antimicrobial humoral response), GO:0006954 (inflammatory response). Subcellular compartments: desmosome/plasma membrane (GO:0030057), extracellular space (GO:0005615).

7. Anatomical Structures Affected

Primary organ: skin (UBERON:0002097), specifically the epidermis (UBERON:0001003) and its superficial stratum granulosum, where Dsg1 is concentrated. Tissue: keratinized stratified squamous epithelium. Cell populations: keratinocytes (CL:0000312) are the direct target; neutrophils (CL:0000775) infiltrate lesions. Common sites: exposed skin — face (especially perioral and perinasal), extremities; bullous disease favors intertriginous areas and, in neonates, the diaper region and trunk. Lateralization: typically bilateral/multifocal and asymmetric, spreading by autoinoculation. Secondary organ involvement: kidney (glomerulus) in APSGN; heart/joints/CNS in ARF; rarely deeper soft tissue (ecthyma) or systemic (SSSS, sepsis). Subcellular level: the desmosome (GO:0030057) at the keratinocyte plasma membrane.

8. Temporal Development

Onset: acute; predominantly pediatric (peak 2–5 years), neonatal for bullous forms. Course: self-limited; individual lesions evolve over 4–6 days and resolve within ~2–3 weeks even without treatment, though treatment shortens the course and reduces spread. Progression: usually stable/localized but can be episodic and recurrent with re-exposure; disseminated bullous impetigo occurs in barrier-compromised (AD) children. Remission: spontaneous or treatment-induced; complete without scarring in uncomplicated disease. Critical periods: early antibiotic treatment prevents dissemination and reduces transmission; treatment does not reliably prevent APSGN (a key public-health caveat).

9. Inheritance and Population

Epidemiology: Median childhood prevalence 12.3% (IQR 4.2–19.4%); >162 million children affected globally at any one time (PMID: 26317533); GBD 2019 age-standardized BSD incidence 169.72 million and 0.41 million DALYs, pyoderma-dominant (PMID: 35547219). Inheritance: not applicable (non-genetic infectious disease); no penetrance/expressivity/anticipation/founder-effect/carrier-frequency parameters apply. Population demographics: highest burden in tropical, low-middle-SDI regions and in marginalized populations of high-income countries (e.g., remote Aboriginal Australian communities, PMID: 31630410); children under 5 and the elderly are most affected (PMID: 39805883). Sex ratio is approximately equal. Geographic and seasonal patterns exist (warm/humid seasons; late-summer peaks for the EEFIC clone).

10. Diagnostics

Diagnosis is primarily clinical, based on the characteristic honey-colored crusts (nonbullous) or flaccid bullae (bullous) (PMID: 41839109). Laboratory/microbiology: Gram stain and bacterial culture with antibiotic sensitivity testing are recommended when MRSA is suspected, when disease is recurrent/extensive, or during outbreaks, to guide therapy and detect resistant clones (EEFIC, MRSA). Wound swab of the crust base or bulla fluid is the standard specimen. Anti-DNase B and anti-streptolysin O (ASO) titers can retrospectively confirm streptococcal infection (more reliably anti-DNase B for skin GAS) in suspected APSGN. Histopathology (rarely needed): subcorneal/granular-layer split with acantholysis and neutrophils in bullous disease. Genetic and omics-based diagnostics are not applicable. Differential diagnosis: atopic dermatitis flare (frequently confused — 67% of disseminated bullous impetigo cases were initially misdiagnosed as AD flares, PMID: 31755570), herpes simplex/eczema herpeticum, varicella, scabies, contact dermatitis, tinea, and — for bullous forms — SSSS, bullous pemphigoid, and pemphigus foliaceus (which shares the Dsg1 target).

11. Outcome / Prognosis

Prognosis is excellent for uncomplicated impetigo: self-limited, resolving without scarring, with high cure rates on topical therapy (Finding 5). Direct mortality is very low but non-zero at population scale (GBD records rising age-standardized pyoderma mortality, driven by resource-poor settings and complications, PMID: 39805883). Morbidity derives chiefly from: (1) transmission and recurrence; (2) local complications — ecthyma, cellulitis, abscess, lymphangitis; and (3) serious post-infectious sequelae — APSGN and ARF/rheumatic heart disease — which dominate the long-term burden in endemic communities (Finding 4). Prognostic factors: streptococcal (vs staphylococcal-only) etiology raises sequela risk; host barrier compromise (AD) predisposes to dissemination; antimicrobial resistance (EEFIC, MRSA) predicts treatment failure. Quality-of-life impact is generally transient for individuals but substantial cumulatively in high-burden populations.

12. Treatment

Pharmacotherapy — topical (limited disease): mupirocin 2% (targets S. aureus incl. MRSA), retapamulin 1% (pleuromutilin; MSSA and S. pyogenes), and ozenoxacin 1% (non-fluorinated quinolone; MSSA, MRSA, S. pyogenes) — all superior to vehicle in RCTs (Finding 5; ozenoxacin PMID: 29898217, PMID: 25340832, PMID: 30365584). Fusidic acid is used outside the US but faces rising resistance. Oral (extensive/bullous/outbreak disease): dicloxacillin or cephalexin (cover both GAS and S. aureus); cephalosporins are recommended for disseminated bullous impetigo given high clindamycin resistance (PMID: 31755570); MRSA-directed agents (e.g., clindamycin, trimethoprim-sulfamethoxazole, doxycycline) per local sensitivities. Treatment strategy follows a severity- and resistance-aware algorithm (PMID: 33538559): localized disease (<10 lesions, <36 cm²) → topical; widespread/epidemic → oral, guided by local resistance trends. Advanced/experimental/surgical therapies, pharmacogenomics, and personalized medicine are not applicable to this common bacterial infection. Adverse events are minimal for topical agents (mainly application-site pruritus). Suggested NCIT anchors: mupirocin, retapamulin, ozenoxacin, cephalexin, dicloxacillin (antibacterial-agent class terms).

13. Prevention

Primary prevention: hygiene (handwashing, wound care), reducing crowding, treating predisposing skin conditions (scabies, AD), and — at the community scale — ivermectin-based MDA for scabies, which robustly lowers impetigo prevalence and SSTI hospitalisations (Finding 6). Secondary prevention: early diagnosis and treatment to limit spread and, in endemic settings, surveillance for APSGN/ARF. Tertiary prevention: management of established sequelae (nephritis, rheumatic heart disease). Public-health interventions: improved water/sanitation/hygiene (WASH), health education, and integrated NTD control programs. Immunization: no impetigo vaccine exists, but a group A streptococcal vaccine is in active development and could provide primordial prevention of GAS impetigo and its sequelae (PMID: 38164699). Genetic screening/counseling is not applicable.

14. Other Species / Natural Disease

Impetigo as clinically defined is a human disease (Homo sapiens, NCBITaxon:9606). However, the causative organisms and mechanisms have cross-species relevance: exfoliative toxins cleave both human and mouse Dsg1 (PMID: 17582744), and S. aureus causes pyoderma and impetigo-like superficial pyoderma in companion animals (dogs, via Staphylococcus pseudintermedius), giving veterinary relevance. Orthologous Dsg1 genes exist across mammals, and the mouse Dsg1 ortholog underpins neonatal-mouse toxin models (Finding 2). Zoonotic transmission is not a primary feature of human impetigo, though S. aureus strains can move between humans and animals.

15. Model Organisms

The principal experimental model is the neonatal mouse (Mus musculus, NCBITaxon:10090), in which subcutaneous or intraperitoneal injection of purified exfoliative toxin (ETA) reproduces the superficial intraepidermal split within ~60 minutes, and Dsg1 domain-removal experiments established sufficiency of Dsg1 cleavage for blistering (PMID: 20728315, PMID: 17582744). This model faithfully recapitulates the molecular mechanism of bullous impetigo/SSSS (Dsg1 proteolysis → superficial blister) but does not capture the full contagious, colonization-driven natural history or the streptococcal post-infectious sequelae. Murine AD models (e.g., PMID: 32438777) and the EL4 lymphoma model (PMID: 41795941) are used to study the barrier-dysfunction/S. aureus-colonization axis relevant to impetigo susceptibility. In vitro keratinocyte cultures are used to study Dsg1 cleavage and cytokine-driven barrier-protein repression.

Mechanistic Model / Interpretation

UPSTREAM (host susceptibility)                     PROXIMATE MECHANISM                    CLINICAL OUTCOME
--------------------------------                   --------------------                    ----------------
Barrier/innate-immune deficit                      Toxigenic S. aureus                     Bullous impetigo
(AD, FLG deficiency, low LL-37/                    secretes ETA/ETB/ETD  ── cleaves ──►    (superficial blisters,
 β-defensins)                                      (glutamate-specific     Dsg1 ECD3-4      honey crusts)
│                                           serine proteases)          │
▼                                                                      ▼
  S. aureus colonization ──► skin breach ──►  ┌── toxigenic S. aureus ──► Dsg1 loss ──► intraepidermal split
  (trauma, scabies,          (portal of       │
   insect bite)               entry)          └── S. pyogenes / non-toxigenic S. aureus
                                        │
                                        ▼
                                  Nonbullous impetigo (pustules, crusts)
                                        │
                                        ├──► nephritogenic GAS ──► APSGN
                                        └──► rheumatogenic GAS ──► ARF / RHD
                                             (immune-mediated, downstream)

The unifying narrative is a two-tier causal architecture. Tier 1 (host susceptibility, upstream): the epidermal barrier and cutaneous antimicrobial-peptide system normally exclude S. aureus; when these fail — genetically (filaggrin), inflammatorily (atopic dermatitis), or mechanically (scabies, trauma) — colonization and infection follow. Tier 2 (pathogen effector, proximate): the pathology diverges by organism. Toxigenic S. aureus executes a precise proteolytic attack on a single adhesion molecule (Dsg1) to produce bullae; streptococci and non-toxigenic staphylococci produce nonbullous pyoderma. A distinct downstream immune tier converts streptococcal skin infection into systemic sequelae (APSGN, ARF). This model explains why interventions at different tiers all work: barrier/scabies control (upstream, MDA), antibiotics (proximate, killing the organism), and future GAS vaccines (blocking the downstream sequela pathway).

Evidence Base

PMID Title (abbrev.) Role in report
41839109 Impetigo: Rapid Evidence Review Forms/proportions, causative pathogens, first-line topical therapy
33105179 Impetigo Superficial bacterial etiology, >140M global burden
17582744 Staphylococcal exfoliative toxins: "molecular scissors" ET isoforms as Dsg1-cleaving serine proteases
20728315 Removal of N-terminal Dsg1 domains… Dsg1 cleavage is sufficient for blistering
21282415 Regulatory mechanism for ET production ETA phage-encoded, ETB plasmid-encoded
26317533 Global Epidemiology of Impetigo 12.3% prevalence, >162M children
31630410 Skin infections in Australian Aboriginal children APSGN/ARF sequelae, highest documented rates
40484016 Acute rheumatic fever Impetigo as ARF antecedent
15106198 Interventions for impetigo (Cochrane) Topical antibiotics OR 6.49 vs placebo
22258953 Interventions for impetigo (Cochrane, 68 RCTs) Scale of evidence base
26650152 MDA for Scabies Control (Fiji) Scabies 94% reduction; impetigo declined most
30956111 AIM trial (Solomon Islands) Large-scale MDA: impetigo 74% reduction
39431149 Ivermectin MDA (Northern India) Impetigo RRR 66.1% in moderate-prevalence setting
35345391 Prevention of bacterial complications (Fiji) SSTI hospitalisations 17% lower post-MDA
37358399 Persistence of EEFIC (Belgium) Fusidic-acid-resistant impetigo clone
38726693 Mupirocin-resistant EEFIC variant Resistance to second first-line agent
28592549 S. aureus clone resistant to mupirocin+fusidic acid Dual-resistant exotoxin-carrying clone
28655473 Keratinocytes as sensors vs S. aureus S. aureus rarely on healthy skin, colonizes AD
18163223 Role of bacterial pathogens in AD Barrier + adhesin + AMP mechanisms
31836943 Eczema Herpeticum Names LL-37, β-defensins deficiency
27012026 Filaggrin Pro478Ser FLG variant ↔ AD severity + S. aureus colonization
31755570 Disseminated bullous impetigo + AD 92% severe AD; misdiagnosis; cephalosporin recommendation
35547219 Global Burden of Bacterial Skin Diseases GBD 2019 incidence/DALYs, pyoderma-dominant
39805883 Burden of bacterial pyoderma 1990–2019 Rising ASIR/ASMR, SDI gradient
29898217 Ozenoxacin RCT Ozenoxacin superior to vehicle
33538559 Treatment algorithm Resistance-aware localized-vs-widespread algorithm
38164699 Streptococcal vaccine development workshop GAS vaccine as primordial prevention

Evidence source types: human clinical (systematic reviews, RCTs, cohorts, GBD modeling) dominate; the Dsg1 mechanism is supported by model-organism (neonatal mouse) and in vitro work.

Limitations and Knowledge Gaps

  1. No molecular profiling of impetigo lesions. Transcriptomic, proteomic, metabolomic, and single-cell data specific to human impetigo lesions were not identified; the mechanistic model relies on toxin biochemistry and AD-colonization literature rather than direct lesional omics.
  2. Prevalence heterogeneity. The 12.3% median prevalence has a wide IQR (4.2–19.4%) and derives from heterogeneous study designs and diagnostic definitions, limiting precision.
  3. Sequela causation is population-level. The link from streptococcal impetigo to APSGN/ARF is epidemiologically robust but strain-specific (nephritogenic/rheumatogenic emm types); individual-level predictive markers remain incompletely defined, and antibiotic treatment does not reliably prevent APSGN.
  4. Resistance surveillance is geographically patchy. EEFIC and MRSA data concentrate in a few high-income countries; the true global resistance landscape (especially in high-burden low-SDI regions) is under-characterized.
  5. Host-susceptibility genetics unproven for impetigo per se. FLG/AMP associations are established for S. aureus colonization and AD, and are inferred (not directly demonstrated) as impetigo risk modifiers.
  6. One treatment claim relies on a related source. The Cochrane trial-count snippet (PMID 22258953) remained unverified in the knowledge state; the efficacy figure (OR 6.49) rests on the related Cochrane review (PMID 15106198).

Proposed Follow-up Experiments / Actions

  1. Lesional multi-omics: Perform single-cell RNA-seq and spatial transcriptomics on nonbullous vs bullous impetigo lesions to map keratinocyte, neutrophil, and immune responses and validate the two-tier model directly in human tissue.
  2. Prospective resistance surveillance: Establish standardized S. aureus impetigo isolate surveillance (mupirocin, fusidic acid, retapamulin, ozenoxacin MICs; EEFIC/MRSA genotyping) in high-burden low-SDI settings, not just Europe.
  3. Host-genetics cohort: Test whether FLG loss-of-function and AMP-gene variants independently predict impetigo incidence (not just colonization) in a prospective pediatric cohort with genotyping.
  4. GAS vaccine impact modeling: Model the projected reduction in impetigo and downstream APSGN/ARF burden achievable with a group A streptococcal vaccine, integrating GBD and MDA-trial data.
  5. Integrated NTD control trials: Evaluate combined WASH + ivermectin MDA + targeted topical therapy for durability of impetigo control and sequela reduction in endemic communities, extending the Fiji/Solomon Islands model to larger non-island populations.
  6. Ozenoxacin real-world evidence: Assess ozenoxacin's role against resistant clones (EEFIC, MRSA) in pragmatic post-marketing studies to define its niche within resistance-aware treatment algorithms.

Report compiled from a 5-iteration autonomous investigation: 9 confirmed findings, 44 papers reviewed. Evidence spans human systematic reviews, RCTs, GBD modeling, and mechanistic model-organism/in vitro studies.

Artifacts

Reference Validation

Checked with linkml-reference-validator 0.3.0rc3.

Outcome Count
References checked 32
Resolved 32
Unresolved (possible confabulation) 0
Unverifiable 0
References weighed for topical relevance 32
On topic 25
Off topic 0

All extracted references resolved successfully.

Term Validation

Checked with linkml-term-validator 0.4.5, through the ols: adapter.

Outcome Count
Terms checked 31
Resolved 30
Unresolved (possible confabulation) 0
Obsolete 1
Unverifiable 0
Terms whose name was checked 25
Terms named correctly 17
Terms named as a different term 3
Terms whose name is worth a second look 5

Terms the report names something else

These identifiers resolve, so nothing about them looks wrong, and the ontology calls them something unrelated to what the report calls them. That usually means the identifier is not the one the sentence needs:

  • MONDO:0001366 (1 mention) - the report calls it "post-streptococcal glomerulonephritis"; MONDO calls it splenic sequestration
  • MONDO:0005295 (1 mention) - the report calls it "rheumatic fever"; MONDO calls it intermittent vascular claudication
  • CHEBI:4508 (1 mention) - the report calls it "dicloxacillin"; CHEBI calls it diclofenac potassium

Obsolete terms

These terms are real but deprecated. Citing one is not a fabrication; it does mean the report is naming something the ontology has retired:

  • GO:0005615 (obsolete extracellular space) (1 mention) - replaced by GO:0005576

Terms whose name is worth a second look

The report's name for these is recognisably related to the term's own name without being one of them. A loose paraphrase reads the same way as a citation of the wrong sibling term - and so does a related synonym, which the ontology records precisely because it names something adjacent rather than the same thing - so these are listed rather than judged:

  • UBERON:0001003 (2 mentions) - the report calls it "skin epidermis", "epidermis"; UBERON calls it skin epidermis, and lists "epidermis" among its other names
  • NCBITaxon:1280 (2 mentions) - the report calls it "S. aureus", "Staphylococcus aureus"; NCBITaxon calls it Staphylococcus aureus, and lists "Micrococcus aureus" among its other names
  • NCBITaxon:1314 (2 mentions) - the report calls it "S. pyogenes"; NCBITaxon calls it Streptococcus pyogenes
  • GO:0007156 (2 mentions) - the report calls it "homophilic cell adhesion via plasma membrane adhesion molecules", "cell–cell adhesion"; GO calls it homophilic cell-cell adhesion
  • HP:0200037 (1 mention) - the report calls it "vesicle"; HP calls it Skin vesicle

Terms named inconsistently

The report gives these identifiers more than one name of its own:

  • UBERON:0001003 - called "skin epidermis", "epidermis"
  • NCBITaxon:1280 - called "S. aureus", "Staphylococcus aureus"
  • GO:0007156 - called "homophilic cell adhesion via plasma membrane adhesion molecules", "cell–cell adhesion"