Cutaneous bacterial infections are important to recognize in pediatrics. Some may actually be emergencies. These include localized skin infections, such as methicillin-resistant Staphylococcus aureus (MRSA) infections, as well as more generalized toxin-mediated diseases, such as toxic shock syndrome (TSS) and staphylococcal scalded skin syndrome (SSSS). It is important for pediatricians to recognize and distinguish these cutaneous bacterial emergencies so treatment and appropriate infection control measures can be promptly initiated.
MRSA poses therapeutic and public health challenges because of its increasing incidence, enhanced virulence, and frequent multidrug resistance.1–3 MRSA infections most commonly involve the skin and soft tissues, typically manifesting as suppurative lesions such abscesses, furuncles, folliculitis, or cellulitis (see Figure 1, page 629).4–6 Infections may occur at any site but especially on the buttocks and lower extremities. Because pustular lesions commonly have a necrotic center, they are often confused with spider bites. Skin and soft-tissue infections caused by MRSA cannot be distinguished reliably on clinical grounds from those caused by methicillin-sensitive Staphylococcus aureus.7 Risk factors include trauma to the skin, contact with an individual infected with MRSA, rectal and/or nasal colonization, crowded households, childcare attendance, antibiotic usage in the past year, contact sports, chronic skin disease, and pets.3
Figure 1. Children with Abscesses (A) and Carbuncles (B) Typical of Methicillin-Resistant Staphylococcus aureus.
The mecA gene provides MRSA with its methicillin resistance.8 This gene encodes penicillin-binding protein 2a, a transpeptidase with very low affinity for beta-lactams. Penicillin-binding protein 2a catalyzes the transpeptidation reactions of peptidoglycan, allowing cell wall synthesis even in the presence of beta-lactams. The mecA gene may be carried on small-sized (eg, the staphylococcal cassette chromosome mec type IV or V of community-acquired MRSA) or large-sized (eg, the staphylococcal cassette chromosome mec type I, II, or III of hospital-acquired MRSA) gene cassettes. The latter can also confer resistance to many non-beta-lactam antibiotics.
An important virulence factor for MRSA is Panton-Valentine leukocidin (PVL). PVL is uncommon among non-MRSA isolates. PVL acts as a cytotoxin, causing lysis of leukocytes and tissue necrosis. In addition, PVL is more often found in MRSA strains, which contain staphylococcal cassette chromosome mec type IV or V rather than I, II, or III. PVL is encoded by the lukS-PV and lukF-PV genes. Other virulence factors for MRSA include alpha-hemolysin and phenol soluble modulins.9
When possible, incision and drainage are a critical part of initial therapy for skin and soft tissue infections suspected to be due to MRSA.10,11 Antibiotics should be considered as an adjunctive therapy, especially for cases with purulent drainage, rapid progression, large abscess size, and the presence of systemic manifestations or immunocompromise. Antibiotic therapy should be based on local resistance patterns and the results of cultures and susceptibility testing. In general, non-beta-lactam antibiotics should be used for cases that are either suspected to be due to MRSA or which do not respond to initial incision, drainage, and beta-lactam antibiotics. These agents include clindamycin, trimethoprim/sulfamethoxazole, tetracycline, linezolid, or vancomycin. Decolonization measures, such as intranasal mupirocin, dilute bleach baths, and bathing with antimicrobial soaps, can be helpful adjuncts.12
SSSS is caused by infections with epidermolytic (also known as exfoliative) toxin (ET)-producing S. aureus. SSSS preferentially affects newborns and children younger than 5 years.13 The nares, conjunctivae, perioral region, umbilicus, and perineum are common foci of infection. When involvement is localized, infections manifest as bullous impetigo. On the other hand, when hematogenous spread of ET occurs, the generalized form of SSSS develops. Cutaneous findings include widespread erythema, which may start on the head and evolve into superficial skin peeling, flaccid bullae, and denuded tender skin (see Figure 2, page 630).14
Figure 2. Child Demonstrating Superficial Skin Peeling, Denuded Tender Skin (A), Flexural Prominence, and Periorificial Crusting (B) Typical of Staphylococcal Scalded Skin Syndrome.
Erythema arises abruptly, spreads rapidly, and demonstrates characteristic flexural and perioral prominence, including radial perioral fissures. There also may be a predilection for areas of mechanical stress, such as shoulders, buttocks, hands, and feet. Skin tenderness is a key feature. The Nikolsky sign, defined as extension of blistering with gentle pressure at the edge of a bulla, may be elicited. Other features include fever, malaise, irritability, purulent rhinorrhea, conjunctivitis, and poor oral intake. The primary source of infection is often around the head and neck area or circumcision site. Rarely, SSSS may result from ET derived from extracutaneous infections, such as pneumonia, pyomyositis, endocarditis, urinary tract infection, and septic arthritis.15
The predilection of SSSS for newborns and young children may be caused by decreased renal clearance of ET and/or the lack of anti-toxin antibodies. Outbreaks in nurseries and intensive care units are well described.16
Two types of ET mediate SSSS, including ET-A and ET-B, both of which are serine proteases.17,18 These two ETs target desmoglein-1, a cell adhesion protein located in desmosomes in the superficial epidermis, explaining the superficial cleavage plane within the stratum granulosum seen in lesions of SSSS. These ETs also possess superantigen activity.19 Strains of ET-producing S. aureus usually belong to phage groups 1, 2, or 3, especially group 2 strains 71 and 55. ET-A is chromosomally encoded, whereas ET-B is plasmid derived.
SSSS is a clinical diagnosis that can be confirmed by culturing S. aureus from foci of infection, such as from the nostrils, conjunctivae, umbilicus, or nasopharynx.20 Culturing exfoliative lesions and blisters is not helpful because these are induced by circulating ET and, therefore, are typically sterile, unless secondarily infected. Bacteremia is uncommon in children with SSSS. Occasionally, a skin biopsy or the painless removal and examination of blisters roofs can help to confirm a superficial cleavage plane, at the level of the stratum granulosum.
The main differential diagnosis for SSSS is toxic epidermal necrolysis (TEN), a more life-threatening blistering disease characterized by a significantly lower cleavage plane below the junction of the epidermis and dermis. TEN is discussed later in this issue. TEN involves full thickness necrosis of the epidermis. Unlike SSSS, TEN demonstrates characteristic mucosal involvement. TEN is quite unusual in infants. Other differential diagnoses may include epidermolysis bullosa, epidermolytic hyperkeratosis, thermal burns, scarlet fever, toxic shock syndrome, Kawasaki disease, and nutritional deficiencies.
Treatment of generalized SSSS includes hospitalization for most young children, with intravenous antibiotics and close monitoring of electrolytes, temperature, and hemodynamics.20,21 Typical empiric antibiotic choices should include a penicillinase-resistant penicillin, first- or second-generation cephalosporin, and clindamycin, with adjustments made based on local resistance patterns and sensitivities of obtained cultures. Skin care generally consists of bland emollients (petroleum jelly) and minimal handling of patients. Mupirocin can be used at foci of infection. Gentle cleansing may help prevent secondary infection. Removal of dried skin with bathing is not necessary initially when the skin is too tender to touch but is used an adjunct later. Other important measures include contact isolation and pain management. Corticosteriods should be avoided.
The prognosis of SSSS is usually good in children and is more guarded in infants. Complications include sepsis, secondary infections, electrolyte imbalances, fluid losses, and hypothermia. Compared with TEN, the higher blister cleavage plane in SSSS confers a better prognosis, causing less water loss and temperature instability. The mortality rate in SSSS is less than 5%. In many cases, patients respond rapidly to treatment, with complete recovery within 2 or 3 weeks. Because the cleavage plane in SSSS is superficial, lesions heal without scarring. SSSS is more life-threatening in newborns as well as adults, especially those with underlying diseases, such as immunocompromise or renal failure.22
Impetigo is a contagious, superficial skin infection that occurs in bullous or non-bullous forms.23,24 Most cases are non-bullous, caused by streptococci, staphylococci, or both. Clinically, non-bullous impetigo demonstrates the classic honey-colored crust and commonly affects the face, especially around the nose. The differential diagnosis sometimes includes herpes simplex infection. In contrast, bullous impetigo is the localized version of SSSS and is, therefore, always caused by S. aureus. Clinically, bullous impetigo presents with flaccid bullae and tender erosions, without much surrounding erythema (see Figure 3, page 630). A rim of scale may be seen at edge of erosions, where the blister has become denuded. Bullous impetigo often occurs in infancy, particularly in the diaper area. Treatment includes topical mupirocin or, for more widespread or severe cases, oral antibiotics. Similar to SSSS, bullous impetigo is characterized by a superficial cleavage plane, is mediated by the same ET-A and -B, and typically does not scar.
Figure 3. Flaccid Bullae in the Diaper Area of a Newborn with Bullous Impetigo.
Staphylococcal TSS is a systemic toxin-mediated disorder that may occur in menstrual or non-menstrual forms. The menstrual form tends to occur in young, healthy women with staphylococcal vaginal infection or colonization by phage group 1 S. aureus. Historically, it was associated with the usage of superabsorbent tampons.25
Non-menstrual TSS is also caused by S. aureus, and may be associated with upper airway infections, burns, postpartum infections, cutaneous infections, surgical procedures, and nasal packing.26 Staphylococcal TSS is mediated by toxic shock syndrome toxin-1 and staphylococcal enterotoxins-A, -B, and -C. These toxins act as superantigens, directly activating T cells, resulting in massive cytokine release.27 TSS toxin-1 may also decrease clearance of endotoxins from gut flora.
Clinical features are similar for menstrual and non-menstrual TSS. It starts with the abrupt onset of high fever, abdominal distress, myalgias, and headache, followed by shock and multisystem organ failure.25,26,28–30 Within 1 to 3 days of disease onset, patients develop a widespread scarlatiniform eruption or erythema with flexural accentuation. Other common findings include pharyngitis, conjunctival and mucosal membrane hyperermia, strawberry tongue, and generalized edema, especially of the hands and feet. A pruritic, maculopapular erythema occurs within 1 to 2 weeks, with a predilection for the palms and soles, sparing the face.
One to 3 weeks after disease onset, full thickness desquamation of the palms (especially subungually), soles, and perineum occurs. Nail and hair shedding may occur later. Particularly concerning complications include respiratory distress syndrome, which is more common in children, as well as disseminated intravascular coagulation, myocardial dysfunction, and renal failure. Positive blood cultures are uncommon (< 15%), and mortality is less than 3%. Diagnosis is based on clinical criteria (see Sidebar 1, page 631).
- Temperature > 38.9°C
- Diffuse macular erythroderma
- Desquamation, 1 to 2 weeks after onset, particularly palmoplantar
- Hypotension for age
- Multisystem involvement, three or more of the following:
Central nervous system
Negative test results for the following (if obtained):
- Throat, CSF, blood cultures (although blood may be positive for S. aureus)
- Serological tests for Rocky Mountain spotted fever, measles, or leptospirosis
‘Probable’ disease: Laboratory criteria + 4 out of 5 clinical criteria
‘Confirmed’ disease: Laboratory criteria + all 5 clinical criteria (unless patient dies before desquamation)
The differential diagnosis of staphylococcal TSS includes streptococcal toxic shock syndrome, scarlet fever, Kawasaki disease, Rocky Mountain spotted fever, viral exanthems, and drug reactions, such as TEN. Unlike many of the differential diagnoses, staphylococcal TSS is always characterized by shock and multiorgan failure. Skin biopsies in staphylococcal TSS reveal non-specific findings and are usually unnecessary, but can help eliminate some conditions in the differential diagnosis, such as TEN.
The mainstay of treatment of staphylococcal TSS includes rapid identification and drainage of infections, as well as removal of foreign bodies that could harbor infection (eg, meshes, tampons, nasal packing). In addition, intravenous penicillinase-resistant antistaphylococcal antibiotics and supportive care are necessary. Antibiotics that inhibit toxin production, including clindamycin, fluoroquinolones, and rifampin, are sometimes recommended.
Streptococcal toxic shock syndrome (STSS) is caused by infection with particular toxin-producing strains of Streptococcus pyogenes, including M protein types 1, 3, 12 and 28.31 Important toxins in the pathogenesis include streptococcal pyrogenic exotoxin-A, -B, and -C, streptococcal superantigen, and mitogenic factor.27 Unlike staphylococcal TSS, STTS is more often associated with a focal tissue infection and bacteremia, as well as a more fulminant course and greater lethality (mortality of 30% to 60%).32,33
Moreover, patients with STSS typically present with severe pain, usually affecting a leg and often out of proportion to objective findings, such as edema and erythema. Necrotizing fasciitis or myonecrosis are possible.33,34 Some patients with STSS have prodromal influenza-like symptoms. Nausea and vomiting are less common than in staphylococcal TSS. Very soon after presentation, patients quickly develop shock and multiorgan failure, such as renal failure, respiratory distress syndrome, and disseminated intravascular coagulation. Bullae are uncommon and are associated with poor prognosis. Some patients demonstrate erythroderma and desquamation 1 to 2 weeks after disease onset, although this is less common than in staphylococcal TSS. A strawberry tongue is rare in STSS. More than half of cases demonstrate positive blood cultures. Clinical criteria are summarized in Sidebar 2 (see page 632).
Clinical Case Definition
- Hypotension for age/shock
- At least two of the following:
Adult respiratory distress syndrome
Generalized erythematous rash with or without desquamation
Soft-tissue necrosis (eg, necrotizing fasciitis or myositis, or gangrene)
- Isolation of group A beta-hemolytic Streptococcus
‘Probable’ disease: Clinical case definition + isolation of group A beta-hemolyticStreptococcusfrom a non-sterile site
‘Confirmed’ disease: Clinical case definition + isolation of group A beta-hemolyticStreptococcusfrom a normally sterile site
Because varicella is a risk factor for invasive S. pyogenes, clinicians treating patients with varicella should have a high index of suspicion if there is persistent or recurrent fevers (beyond day 4).35
Treatment of STSS involves supportive management in an intensive care unit, early surgical debridement, and intravenous antibiotics. Clindamycin is often used with the intent of impairing toxin production. Because of the extent of invasive infection and the required debridement, morbidity and disfigurement often occur in survivors.
Scarlet fever is caused by infection with particular S. pyogenes strains that produce streptococcal pyrogenic (erythrogenic) exotoxin-A, -B, or -C.36 Streptococcal tonsillopharyngitis is usually the source of infection. Wound infections, burns, pelvic infections, food-borne outbreaks, and cellulitis are other possible sources.37
Most patients abruptly develop fever and sore throat, followed 1 to 2 days later by a scarlatiniform rash. Headache, malaise, myalgias, vomiting, abdominal pain, lymphadenopathy, and leukocytosis are common. Erythematous macules and petechiae (Forschheimer’s spots) may be present on the palate, as well as a “white strawberry tongue” that sloughs to become a “red strawberry tongue.”38,39
The rash of scarlet fever is characterized by blanchable, confluent, erythematous macules and patches, as well as tiny papules with a dry, sandpaper-like texture (see Figure 4, page 631). Lesions often start on the upper trunk, then generalize over days, sparing the palms and soles, and involving the legs last. Pastia’s lines refer to accentuation of erythema with linear petechiae in skin folds. Accentuation is also common at dependent sites. Facial flushing with circumoral pallor is common. The rash fades within a week and is followed a week later by a superficial desquamation, especially in skin folds, on the face and in sheets from the hands and feet (may take 2 to 6 weeks). Beau’s lines (transverse nail grooves) and telogen effluvium (hair loss) may present after the illness. Early complications may include pneumonia, otitis media, bacteremia, and osteomyelitis. Later complications may include glomerulonephritis and rheumatic fever.
Figure 4. Papular, Sandpaper-Like Plaques with Streptococcal Infections.
The differential diagnosis of scarlet fever includes Kawasaki disease, SSSS, staphylococcal and streptococcal TSS, mononucleosis, fifth disease, rubella, rubeola, other viral exanthems, juvenile rheumatoid arthritis, and drug reactions. Similar rashes can also be seen with pharyngeal infections with S. aureus, Arcanobacterium haemolyticum, or Haemophilus influenzae. Cultures of infected areas should be obtained. Skin biopsies are nonspecific and are not generally helpful.
Before the discovery of antibiotics, the mortality of scarlet fever was approximately 20%.40 The antibiotic of choice for scarlet fever is penicillin. Treatment is important to relieve symptoms, to minimize spreading the infection to others, and to avoid complications, such as rheumatic fever.
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