Pathophysiology

Intact skin is usually resistant to colonization or infection by S aureus or GABHS.

These bacteria can be introduced from the environment and only transiently colonize
the cutaneous surface. Experimental studies have shown that inoculation of multiple
strains of GABHS on to the surface of subjects did not produce cutaneous disease
unless skin disruption had occurred.
The teichoic acid adhesions for GABHS and S aureus require the epithelial cell
receptor component, fibronectin, for colonization. These fibronectin receptors are
unavailable on intact skin; however, skin disruption may reveal fibronectin receptors
and allow for colonization or invasion in these disrupted surfaces. Factors that can
modify the usual skin flora and facilitate transient colonization by GABHS and S
aureus include high temperature or humidity, preexisting cutaneous disease, young
age, or recent antibiotic treatment.
Common mechanisms for disruption of skin that can facilitate bacterial colonization
or infection include the following:
Scratching
Dermatophytosis
Varicella
Herpes simplex
Scabies
Pediculosis
Thermal burns
Surgery
Trauma
Radiation therapy
Insect bites
Immunosuppression by medications (eg, systemic corticosteroids, oral retinoids,
chemotherapy), systemic diseases (eg, HIV infection, diabetes mellitus), intravenous
drug abuse, and dialysis encourages bacterial growth.
After initial infection, new lesions may be seen in areas with no apparent break in
the skin. Frequently, however, upon close examination, these lesions will
demonstrate some underlying physical damage.
GABHS colonization
If an individual is in close contact with others (eg, household members, classmates,
teammates) who have GABHS skin infection or who are carriers of the organism, the
normal skin of that individual may be colonized. Once the healthy skin is colonized,
minor trauma, such as abrasions or insect bites, may result in the development of
impetigo lesions within 1-2 weeks.
GABHS can be detected in the nose and throat of some individuals 2-3 weeks after
lesions develop, although they do not have symptoms of streptococcal pharyngitis.
This is because impetigo and pharyngitis are caused by different strains of the
bacteria. Impetigo is usually due to pattern D strains, whereas pharyngitis is due to
pattern A, B, and C strains.
Staphylococcus aureus colonization
Approximately 30% of the population is colonized in the anterior nares by S aureus.
Some individuals colonized by S aureus experience recurrent episodes of impetigo
on the nose and lip. Bacteria can spread from the nose to healthy skin within 7-14
days, with impetigo lesions appearing 7-14 days later.
Approximately 10% of individuals are colonized with S aureus in the perineum and,
more uncommonly, in the axillae, pharynx, and hands. Individuals who are
permanent carriers serve as reservoirs of the infection for other people. Most healthy
persons transiently harbor S aureus as part of their microbial flora. S aureus often
passes from one individual to another through direct hand contact, entering through
broken skin created by cutaneous diseases.
Patients with atopic dermatitis or other inflammatory skin conditions more commonly
have skin colonized by S aureus. Studies have shown a 60-90% S
aureus colonization rate in patients with atopic dermatitis. Patients with atopic
dermatitis, particularly those with a history of eczema herpeticum, are at higher risk
of developing an infection caused by MRSA.
One study found significantly lower expression of proteins related to the skin barrier
and generation of natural moisturizing factor in lesional versus nonlesional sites in
patients with atopic dermatitis. In addition, epidermal fatty acidbinding protein was
expressed at significantly higher levels in patients colonized with MRSA, and this
might perpetuate the inflammatory response through eicosanoid signaling.
[7]

Bullous impetigo
Bullous impetigo (see the image below) is commonly due to exfoliative toxins of S
aureus termed exfoliatins A and B. In 2006, exfoliative toxin D (ETD) was identified
in 10% of S aureus isolates.
[8]
These exotoxins cause a loss of cell adhesion in the
superficial dermis, which, in turn, causes blisters and skin sloughing by cleaving of
the granular cell layer of the epidermis.
One of the target proteins for exotoxin A is desmoglein I, which maintains cell
adhesion. These molecules are also superantigens that act locally and activate T
lymphocytes. Coagulase may cause these toxins to remain localized within the
upper epidermis by producing fibrin thrombi. Unlike nonbullous impetigo, the lesions
of bullous impetigo occur on intact skin.

Superficial flaccid bullae of bullous impetigo caused by Staphylococcus aureus. Courtesy of
Professor David Taplin, Department of Dermatology and Cutaneous Surgery, University of Miami
School of Medicine, Miami, Fla.

While the number of isolates of community- and hospital-acquired MRSA in lesions
of impetigo remains low, this incidence has been increasing. Community-acquired
MRSA can be differentiated from hospital-acquired MRSA. Most strains of
community-acquired MRSA contain Panton-Valentine leucocidin (P-VL), a highly
virulent, pore-forming exotoxin that causes dermal necrosis and has cytolytic activity
against neutrophils and monocytes. Destruction of leukocytes by P-VL is one of the
reasons that MRSA is more likely to produce clinical infection.
P-VL-positive S aureus strains are more frequently associated with cellulitis (38%)
and abscesses (75%). In immunodeficient or immunocompromised patients, the
toxin may disseminate hematogenously and lead to generalized staphylococcal
scalded skin syndrome.