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Dermatology > BACTERIAL INFECTIONS
Staphylococcal Scalded Skin Syndrome
Article Last Updated: May 16, 2007
AUTHOR AND EDITOR INFORMATION
Section 1 of 11  
Author: Jessica H Kim, MD, Clinical Assistant Professor, Department of Medicine, Division of Dermatology, University of Washington School of Medicine, Consulting Staff, Department of Dermatology, Cascade Eye and Skin Centers
Jessica H Kim is a member of the following medical societies: American Academy of Dermatology and Washington State Medical Association
Coauthor(s):
Paul Benson, MD, Chief, Program Director, Dermatology Service, Walter Reed Army Medical Center; Associate Professor, Department of Dermatology, Uniformed Services University of the Health Sciences at Bethesda
Editors: Leonard Sperling, MD, Chair, Professor, Department of Dermatology, Uniformed Services University of the Health Sciences; Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center; Edward F Chan, MD, Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University; William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System
Author and Editor Disclosure
Synonyms and related keywords:
SSSS, exfoliative dermatitis, toxin-mediated staphylococcal syndromes, Ritter's disease, pemphigus neonatorum, Staphylococcus aureus, S aureus
Background
Staphylococcal scalded skin syndrome (SSSS) is a toxin-mediated type of exfoliative dermatitis. Toxin-mediated staphylococcal syndromes comprise a group of blistering skin diseases, ranging in severity from localized bullous impetigo to SSSS, in which superficial blistering and exfoliation follow widespread painful erythema.
Pathophysiology
The disorder is caused by toxigenic strains of Staphylococcus aureus, usually belonging to phage group 2 (types 3A, 3B, 3C, 55, or 71). Two exotoxins (ETs), epidermolytic toxin A (ET-A) and epidermolytic toxin B (ET-B), are responsible for the pathologic changes seen in SSSS. These toxins cause intraepidermal splitting through the granular layer by specific cleavage of desmoglein 1 (also the target protein in the autoimmune blistering dermatosis, pemphigus foliaceus), a desmosomal cadherin protein that mediates cell-to-cell adhesion of keratinocytes in the granular layer. Specific targeting of desmoglein 1 by ETs allows S aureus to proliferate and spread beneath the barrier of the skin. Crystal structures and amino acid sequences indicate that these toxins act as serine proteases and cleave desmoglein 1 after glutamic acid residue 381 between extracellular domains 3 and 4. The ET-A and ET-B amino acid sequences are approximately 40% identical with each other. Recently, researchers have found an additional ET family member, ET-D, by screening the genomes of S aureus isolated from patients with skin infections. They demonstrated that ET-D specifically digested desmoglein 1. However, only ET-A and ET-B have been firmly linked to human SSSS. The ET-D gene was detected mainly in isolates from patients with skin and soft-tissue infections, such as furuncles, abscesses and finger pulp infections. It has been suggested that ET-B is more frequently isolated than ET-A in children with SSSS. This link between ET-B and generalized SSSS might be due to increased virulence of ET-B or to more abundant ET-B release. Because ET-A is chromosome borne and ET-B is plasmid borne, multiple copies of the ET-B gene could possibly lead to higher ET-B production. However, levels of ET-A and ET-B are quite similar in vitro. The link between ET-B and generalized SSSS may be explained, at least in part, by lower levels of anti-ETB antibodies than anti-ETA antibodies in the general population. An asymptomatic adult carrier introduces the causative bacteria into the nursery. Asymptomatic nasal carriage of S aureus occurs in 20-40% of healthy individuals, with the organism being isolated from the hands, the perineum, and the axillae in a smaller proportion of the general population.
Frequency
United States
SSSS most commonly occurs in infants and in young children, and it tends to occur in outbreaks in neonatal nurseries or in day care nurseries. Large outbreaks of SSSS in neonatal nurseries have been described, but the occurrence of SSSS in adults as a nosocomial infection appears to be exceptional; epidemics have never been observed.
Epidemiologic data on strains of S aureus that produce ET are scarce. In a prospective clinical and bacteriologic study, 5.1% of 944 isolates of S aureus were identified as ET producers. SSSS in adults is an exceedingly rare disorder, with only 50 reported cases.
Mortality/Morbidity
Children generally do well and are not as ill as their dramatic eruptions might suggest. SSSS is usually associated with a trivial infective focus in the conjunctivae or the skin; however, severe infections, such as sepsis, do contribute to a low but appreciable fatality rate (4%).
- Morbidity in the occasional child who develops cellulitis, sepsis, and pneumonia can be significant.
- In children, the foci of staphylococcal infections are usually the nasopharynx or localized skin infections.
- Adults with SSSS often have blood cultures positive for toxigenic S aureus, and mortality rates can be high (>60%). In older patients, risk factors consisting of immunosuppression in tumor patients and underlying consumptive infectious diseases contribute to high mortality.
Race
Black children are less prone to SSSS than white children.
Sex
A male-to-female predominance exists (2:1 in sporadic cases, 4:1 in epidemics).
Age
- The disease most commonly affects children younger than 5 years, particularly neonates. A decreased ability to achieve renal clearance of toxins and a lack of specific immunity (antibody) to the toxins make neonates the group at highest risk.
- Older children and adults may also develop the disease. In such cases, renal insufficiency or immunodeficiency (eg, HIV infection, advanced stage of cancer) appears to explain the susceptibility to the syndrome. This happens because for the development of SSSS, a massive production of toxins or deficiency in their elimination must be present. Adults who are affected range in age from 19-91 years, with one half of the cases occurring in adults older than 60 years.
History
- SSSS originates from a focus of infection that may be a purulent conjunctivitis, otitis media, or occult nasopharyngeal infection. A case of SSSS from a nasal septal abscess, presumably arising from a traumatic hematoma (a tsunami survivor), has been reported. In premature infants, a previous amniocentesis procedure and intrauterine infection have been reported as triggers for SSSS.
- It usually begins with fever, irritability, and a generalized, faint, orange-red, macular erythema with cutaneous tenderness.
- Periorificial and flexural accentuation may be observed. A positive Nikolsky sign (slippage of the superficial layer of the epithelium on gentle pressure) can often be elicited at this stage.
Physical
- Within 24-48 hours, the rash progresses from a scarlatiniform to a blistering eruption.
- Characteristic tissue paper–like wrinkling of the epidermis is followed by the appearance of large, flaccid bullae in the axillae, in the groin, and around the body orifices.
- Subsequent generalized involvement occurs elsewhere on the body, but infection spares the mucous membranes.
- As sheets of epidermis are shed, a moist erythematous base is revealed.
- Despite the dramatic clinical picture, the entire process usually subsides with superficial desquamation, and healing is usually complete within 5-7 days.
- In adults, it is frequently followed by bacteremia and pneumonia, favoring a poor prognosis.
- Cultures obtained from intact bullae are usually sterile; this finding is consistent with hematogenous dissemination of a toxin produced at a distant focus of staphylococcal infection.
- An abortive form of SSSS, known as the scarlatiniform variant, shows the early erythrodermic and final desquamative stages seen in SSSS, but the bullous stage does not occur.
- Other intermediate forms of scalded skin syndrome begin as localized bullous impetigo, but they evolve to produce regionally limited bullae and denuded areas that may or may not harbor staphylococci.
Causes
See Pathophysiology.
- ET-A and ET-B are serine proteases that specifically target desmoglein-1. They are also sources of superantigenic activity and activate macrophages to produce proinflammatory cytokines such as tumor necrosis factor-alpha and interleukin 6. ET-A with an active site mutation was shown to possess a similar inflammatory activity, indicating that the inflammatory activity of ET-A was separate from its epidermolytic activity. Systemic symptoms, particularly the characteristic rash, are very likely a direct result of the toxin.
- A small number of patients with SSSS develop low titers of immunoglobulin G antibodies specific for desmoglein-1 after binding and systemic digestion of desmoglein-1 by staphylococcal exfoliative toxins. The relevance of this finding to onset the of autoimmune diseases remains to be proven. Other genetic or environmental factors may be needed to extend the immune response to encompass pathogenic antibodies and to produce overt clinical pemphigus foliaceus.
Kawasaki Disease
Scarlet Fever
Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
Toxic Shock Syndrome
Other Problems to be Considered
Child abuse
Lab Studies
- The definitive diagnosis depends on culture and biopsy results.
- Examination of frozen sections of the lesions can easily confirm the diagnosis.
- Slide latex agglutination, double immunodiffusion, and enzyme-linked immunosorbent assay tests can identify the toxins responsible for SSSS.
- Perform culturing in all patients with suspected SSSS for identification and antibiotic sensitivities of the causative organism. S aureus may be cultured from the conjunctiva, nasopharynx, feces, or pyogenic foci on the skin. Blood cultures are almost always negative in children, but they may be positive in adults.
- Investigate the possibility of a staphylococcal carrier in the vicinity.
Histologic Findings
All forms of scalded skin syndrome are characterized by intraepidermal cleavage, with splitting that occurs beneath and within the stratum granulosum. The cleavage space may contain free-floating or partially attached acantholytic cells. The remainder of the epidermis appears unremarkable, and the dermis contains no inflammatory cells.
Medical Care
- Direct the therapy for scalded skin syndrome toward eradication of the staphylococcal focus of infection, which generally requires intravenous, penicillinase-resistant, antistaphylococcal antibiotics. The current treatment of choice is cloxacillin.
- Oral antibiotic therapy can be substituted within several days or sooner.
- Antibiotics, supportive care, and appropriate attention to fluid and electrolyte management because of disrupted epidermal barrier function usually ensure rapid recovery. Moist, denuded areas should be lubricated with a bland emollient to decrease pruritus and tenderness.
- Recognizing the potential for epidemic scalded skin syndrome in neonatal care units is important.
- Identification of health care workers colonized or infected with toxigenic S aureus is an integral part of managing the problem. Receiving more than one early umbilical care procedure by the same ancillary nurse was the only risk factor identified in a nosocomial outbreak in a maternity unit in France. The ancillary nurse had from chronic dermatitis on her hands that favored S aureus carriage.
- Apply control measures, including strict enforcement of chlorhexidine hand washing, administration of an oral antibiotic therapy for workers who are infected, and application of mupirocin ointment for eradication of persistent nasal carriage.
The goal of pharmacotherapy is to reduce morbidity and to prevent complications.
Drug Category: Antibiotics
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.
| Drug Name | Dicloxacillin (Dycill, Dynapen) |
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| Description | Treatment of infections caused by penicillinase-producing staphylococci. May use to initiate therapy when staphylococcal infection is suspected. |
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| Adult Dose | 125-500 mg PO q6h; 2 g/d maximum |
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| Pediatric Dose | Neonates: 4-8 mg/kg PO q6h
<40 kg: 12.5-50 mg/kg/d PO divided q6h
>40 kg: 125-500 mg PO q6h
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| Contraindications | Documented hypersensitivity |
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| Interactions | Probenecid may increase effect of penicillins; tetracyclines may decrease effect of penicillins with concurrent use; concomitant penicillin and aminoglycoside therapy has been reported to result in inactivation of the aminoglycoside both in vivo and in vitro; penicillins may alter intestinal flora which, in turn, alters the enterohepatic circulation of combination contraceptives; may reduce the anticoagulant effectiveness of warfarin |
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| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
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| Precautions | Caution in impaired renal function |
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| Drug Name | Cloxacillin (Cloxapen, Tegopen) |
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| Description | Binds to 1 or more penicillin-binding proteins, which, in turn, inhibits synthesis of bacterial cell walls. |
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| Adult Dose | 250-500 mg PO q6h |
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| Pediatric Dose | <20 kg: 50-100 mg/kg/d PO divided q6h; not to exceed 4 g/d
>20 kg: Administer as in adults |
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| Contraindications | Documented hypersensitivity |
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| Interactions | Decreases efficacy of oral contraceptives; increases effects of anticoagulants; probenecid and disulfiram may increase penicillin levels
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| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
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| Precautions | Monitor PT in patients taking anticoagulant medications; toxicity may increase in patients with impaired renal function; may aggravate agranulocytosis and myelosuppression; may cause hepatotoxicity or pseudomembranous enterocolitis; gastrointestinal diseases, such as hypermotility or malabsorption, may alter absorption |
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| Drug Name | Mupirocin (Bactroban) |
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| Description | Inhibits bacterial growth by inhibiting RNA and protein synthesis. |
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| Adult Dose | Apply thin film to affected area 2-5 times/d for 5-14 d |
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| Pediatric Dose | Apply as in adults |
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| Contraindications | Documented hypersensitivity |
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| Interactions | None reported |
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| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
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| Precautions | Prolonged use may result in the growth of nonsusceptible organisms |
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Further Inpatient Care
- Recent developments in the understanding of the exfoliative toxins should lead to new and improved diagnostic and therapeutic strategies, including the use of specific antitoxins to prevent exfoliation.
- Infusing anti-ET antibodies into mice was shown to halt progression of exfoliation in a study performed more than 2 decades ago, but this has never been applied to humans.
- A recent surge has occurred in reports of methicillin-resistant S aureus strains causing SSSS, often with a fatal outcome. These cases emphasize the need to develop alternative treatment strategies before multiple antibiotic resistance becomes a problem.
- Animal model studies have demonstrated that subinhibitory concentrations of antibiotics such as clindamycin can significantly inhibit toxin production by methicillin-sensitive and methicillin-resistant staphylococcal strains, and antiinflammatory agents such as pentoxifylline can further inhibit activation of the body's inflammatory response to these toxins. Currently, little clinical evidence supports their routine use in the management of SSSS.
- Prevention of progression of SSSS by molluscum contagiosum has been observed and indicates possible interference by a viral anticytokine molecule such as interleukin 18 binding protein. The development of drugs based on inflammatory cytokines, including interleukin 18, may be invaluable for halting the progression of severe cases.
Deterrence/Prevention
- Investigate the possibility of a staphylococcal carrier in the vicinity.
Complications
- Cellulitis, sepsis, and pneumonia are possible complications that may occur in children with SSSS.
Prognosis
- The prognosis of the disease is good in children, and the mortality rate is low if they are treated.
- In adult cases of SSSS, the mortality rate is high despite appropriate antibiotic therapy.
Medical/Legal Pitfalls
- Failure to diagnose the disorder or inadequate treatment, including fluid resuscitation, may result in liability.
- Failure to identify patients who are immunosuppressed may result in a suboptimal outcome and liability.
| Media file 1:
An infant with characteristic coloring in the skin that looks as though the child has been scalded. |
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Media type: Photo
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| Media file 2:
Staphylococcal scalded skin syndrome in an adult. |
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Media type: Photo
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Staphylococcal Scalded Skin Syndrome excerpt Article Last Updated: May 16, 2007
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