Staphylococcal scalded skin syndrome

INTRODUCTION — Staphylococcal scalded skin syndrome (SSSS) is a bacterial toxin-mediated skin disorder that primarily affects young children but can also occur in older children and adults. Previous terms for SSSS in newborn infants include Ritter's disease and pemphigus neonatorum.

SSSS occurs when exotoxins produced by Staphylococcus aureus undergo hematogenous dissemination to the skin (figure 1). The characteristic clinical findings include diffuse skin pain and erythema as well as superficial blistering and desquamation (picture 1A-H). Common associated findings include fever, irritability, and poor oral intake.

Patients with SSSS typically require hospital admission for intravenous antibiotic therapy and supportive care. When adequately treated, the prognosis is excellent. Most patients recover fully within two to three weeks without significant scarring, disfigurement, or other long-term sequelae.

The clinical features, diagnosis, and management of SSSS will be reviewed here. Other cutaneous manifestations of S. aureus infection are reviewed separately.

●(See "Impetigo".)

●(See "Infectious folliculitis", section on 'Bacterial folliculitis'.)

●(See "Cellulitis and skin abscess: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

●(See "Methicillin-resistant Staphylococcus aureus infections in children: Epidemiology and clinical spectrum".)

EPIDEMIOLOGY — SSSS primarily affects young children. SSSS in adults is less frequent and usually occurs in the setting of serious illness.

SSSS in children most often occurs before the age of six and has been reported as early as the first day of life [1,2]. Estimates of the incidence of SSSS vary. An analysis of data from over 6 million pediatric hospital stays in the United States between 2008 and 2012 supports a mean annual incidence of approximately 8 cases per million children and approximately 45 cases per million children under the age of two years [3].

The major risk factors for SSSS in adults include impaired kidney function, immunosuppression, and other comorbidities that impair the immune response to bacterial infection (eg, diabetes) [4,5]. An analysis of over 32 million hospitalizations in adults in the United States between 2008 and 2012 supports an annual incidence of approximately 1 case per million adults [6]. The incidence increased with age, from 0.3 cases per million for adults between the ages of 18 and 39 years to 3.91 cases per million for adults over the age of 80 years.

Studies assessing the sex ratio in SSSS have yielded inconsistent results. Whereas a study of 399 children with SSSS in the Czech Republic found SSSS more frequent in males, a study of hospital data from the United States found SSSS more common in females [3,7].

There may be seasonal variation in the incidence of SSSS. Peak incidences in the summer and autumn for childhood SSSS have been found in some studies [3,8].

PATHOGENESIS — SSSS is caused by exotoxin-producing strains of S. aureus, with the most common subsets being phage group 2 strains 55 and 71. Less common causative strains include types 3A, 3B, 3C, and the ST121 strain.

The two pathogenic toxins produced in SSSS are exfoliative (or epidermolytic) toxin A (ETA) and exfoliative toxin B (ETB). S. aureus strains implicated in SSSS may produce ETA, ETB, or both toxins [9]. Approximately 5 percent of all S. aureus isolates and approximately 95 percent of the ST121 strain produce these toxins [10,11].

The pathogenic exotoxins serve as serine protease enzymes that cleave desmoglein 1, a desmosomal linking protein responsible for keratinocyte-to-keratinocyte adhesion in the stratum granulosum. Hematogenous dissemination of the exotoxins from the initial focus of S. aureus infection stimulates separation of epidermal keratinocytes and detachment of the superficial epidermis (figure 1). (See 'Clinical features' below.)

The frequent occurrence of prodromal symptoms resembling upper respiratory viral infections (eg, fever, irritability) has led some authors to suggest a role for viral infection as a promoter of proliferation of exotoxin-producing strains of S. aureus [9]. However, this theory has not been confirmed.

ACQUISITION — SSSS typically arises from a focus of infection with an exotoxin-producing S. aureus strain, such as may occur in impetigo, bacterial conjunctivitis, or iatrogenic wounds. SSSS may also occur in the setting of infections such as staphylococcal pneumonia, pyomyositis, septic arthritis, or endocarditis [12]. Rare reports indicate staphylococcal mastitis as a maternal source of infection for breastfed newborns [13]. The incubation period from S. aureus infection to SSSS usually ranges from 1 to 10 days [10].

Transmission of exotoxin-producing strains of S. aureus can occur between individuals, including from asymptomatic, colonized individuals. Outbreaks of SSSS have occurred in newborn nurseries and intensive care units [14,15]. (See 'Prevention' below.)

The susceptibility of young children to SSSS is postulated to result from a lack of protective antibodies against staphylococcal toxins and/or insufficient ability of young children's kidneys to excrete the exotoxins [4]. Adult susceptibility appears to occur in the presence of impaired immunity, impaired renal function, or serious illness. Adult disease is often associated with a high burden of staphylococci.

CLINICAL FEATURES — SSSS is characterized by progressive, cutaneous erythema and desquamation and constitutional symptoms (picture 1A-H). The term "scalded skin" refers to the resemblance of acute burns from hot water. Mucous membrane involvement is absent.

Cutaneous findings — The earliest cutaneous signs of SSSS are macular erythema and skin pain. Initially, erythema is accentuated in the skin folds, such as the neck, axillae, inguinal folds, and gluteal cleft. The erythema may be subtle, can wax and wane, and may be especially difficult to appreciate in patients with highly pigmented skin. Generalized erythema usually develops within 48 hours.

As the disease progresses, flaccid bullae begin to appear in areas of skin erythema, resulting in a wrinkled appearance (picture 1F). Shallow erosions may also occur in sites subject to friction, such as in the perianal region. Even minor insults, such as placement of a blood pressure cuff or removal of adhesive tape, may lead to erosions. Sheet-like, superficial desquamation can develop, leaving large patches of moist, erythematous, shiny skin.

Thick crusting and radial fissuring often develops around the mouth, nose, and eyes (picture 1G). The crusting, fissuring, and associated erythema can be striking and is classically referred to as SSSS "sad face." The perioral crusting has been likened to dried oatmeal in its appearance.

Associated signs and symptoms — Common prodromal and concurrent symptoms include skin pain, fever, irritability, malaise, and poor feeding. As a result of the compromised skin barrier in SSSS, patients can also exhibit signs and symptoms related to significant fluid loss and temperature instability. (See "Clinical assessment of hypovolemia (dehydration) in children" and "Etiology, clinical manifestations, and diagnosis of volume depletion in adults".)

Primary site of infection — The site of staphylococcal infection often is not evident [10]. Findings suggestive of infection include purulent drainage at the conjunctivae and medial canthi of the eyes in conjunctivitis; impetigo-associated, honey-colored crusting of the nares, perinasal skin, or perioral skin; perianal erythema; and pustules or other crusted areas on the skin. In newborns, staphylococcal infection may appear as erosions, purulence, or crusting surrounding the umbilical stump or a recent circumcision site [16].

COURSE AND COMPLICATIONS — Cutaneous erythema and pain typically subside significantly within two to three days after the start of treatment. Erosions and crusted regions usually exhibit significant improvement within one to two weeks.

Patients can continue to have pain, erythema, and skin peeling for several days despite appropriate antibiotic treatment. The prolongation of symptoms may be due to the persistence of toxins in the blood and tends be most prolonged in neonates. This may be related to relatively inefficient renal clearance or lower immunity to staphylococcal bacteria in neonates [17].

Postinflammatory hyperpigmentation or hypopigmentation occasionally follows healing, particularly in patients with highly pigmented skin (eg, phototypes IV to VI (table 1)). Pigmentary changes usually fade within several months. Scarring typically does not occur. (See "Postinflammatory hyperpigmentation".)

Serious complications are related to the extensive loss of skin and include secondary infection, septicemia, hypovolemia, electrolyte imbalance, and death. (See 'Prognosis' below.)

HISTOPATHOLOGY — Histopathologic examination of a blister in SSSS demonstrates subcorneal cleavage. Acantholysis also may be evident. Inflammatory infiltrates in the dermis are usually absent [4]. Given the fragile nature of the blisters in SSSS, disruption of the epidermal architecture may occur during the biopsy or tissue processing. (See 'Histopathologic examination' below.)

DIAGNOSIS — The diagnosis of SSSS usually can be made based upon the history and physical findings. Bacterial cultures of sites of suspected staphylococcal infection should also be performed to confirm S. aureus infection and provide information on antibiotic susceptibility. Histopathologic examination can confirm SSSS in challenging cases.

Clinical assessment — The clinical assessment includes a focused history and an examination of the entire skin surface and mucous membranes. The goals are to identify findings consistent (or inconsistent) with SSSS and to detect the site of S. aureus infection. (See 'Clinical features' above.)

The patient history should review the course of skin disease, associated symptoms, and the medical history. Examples of findings supportive of SSSS include:

●Occurrence in either a young child or an older child/adult with an impaired immune system, impaired renal function, or serious illness

●Initial onset of erythema in skin folds followed by rapid progression to widespread erythema (eg, within 48 hours)

●Associated skin pain

●Prodrome or concurrent fever, irritability, or poor oral intake

Examination of the skin and mucous membranes should be performed with care to avoid unnecessary friction-induced erosions and to minimize pain. Careful inspection in a well-lit environment is essential for assessing macular erythema. Physical findings consistent with SSSS include:

●Extensive, blanchable skin erythema

●Flaccid bullae, superficial desquamation, and shallow erosions

●Absent mucous membrane involvement

●Evidence of concurrent cutaneous, conjunctival, or internal staphylococcal infection (see 'Primary site of infection' above)

●Positive Nikolsky sign

The Nikolsky sign describes blistering or sloughing of skin in response to gentle mechanical pressure. While helpful for identifying skin fragility consistent with SSSS, attempts to elicit this sign can be painful, and a positive Nikolsky sign may also occur in conditions other than SSSS. Recognition of clues, such as a history of blister and erosion formation at sites of minor skin insults, can eliminate the need to intentionally induce an erosion. (See "Approach to the patient with cutaneous blisters", section on 'Nikolsky sign' and 'Cutaneous findings' above.)

Unlike conditions associated with full-thickness detachment of the epidermis, such as toxic epidermal necrolysis (TEN), erosions in SSSS are less likely to exhibit pinpoint bleeding. This is related to the superficial level of blistering.

Histopathologic examination — Histopathologic examination is not required for diagnosis but can confirm the diagnosis through distinguishing SSSS from other causes of skin blistering or sloughing when diagnostic uncertainty remains despite a careful history and physical examination. (See 'Differential diagnosis' below.)

Options for obtaining histologic support for SSSS include sampling of the full thickness of the epidermis and superficial dermis with a shave or punch biopsy and obtaining a piece of sloughed epidermis for examination. The primary goal of both procedures is to identify the level of epidermal cleavage and differentiate SSSS from conditions in which cleavage occurs lower in the epidermis or in the subepidermal plane (eg, TEN).

The specimen can be placed in formalin and submitted for routine histologic processing or placed on saline-moistened gauze and transported immediately to a pathology laboratory for examination as a frozen section. Generally, a skin biopsy submitted for routine histologic processing is the preferred procedure, particularly when there is greater uncertainty regarding the diagnosis, as it allows for a more complete pathologic assessment than examination of sloughed skin or frozen sections. The major advantage of frozen sections is rapid availability of results, when needed.

●Shave or punch biopsy – Shave and punch biopsies should be taken from the edge of an intact vesicle or bulla. For punch biopsies, a diameter of 4 mm is usually sufficient. The classic finding is a subcorneal split in the epidermis. (See "Skin biopsy techniques".)

●Snip biopsy – A snip biopsy involves the removal of a small piece of freshly sloughed epidermis. This procedure may be preferable for small children or neonates when a full biopsy is likely to be challenging or poorly tolerated. Specimens of sloughed skin from SSSS demonstrate only the uppermost portion of the epidermis.

Bacterial cultures — Although the site of S. aureus infection cannot always be found, a culture that confirms S. aureus infection supports the diagnosis of SSSS. Because blistering in SSSS results from hematologic dissemination of staphylococcal exotoxins rather than local infection, intact blisters in SSSS are sterile, and culture of blisters will not yield the causative organism.

Cultures should be taken from cutaneous or mucosal sites of suspected primary infection (eg, areas of purulent drainage) identified during a physical examination or, in the absence of an obvious site of infection, from a common site of S. aureus colonization (eg, nares) [9]. Common sites for culture are the skin, conjunctivae, nares, ear canals, and nasopharynx. In a French retrospective study of 212 children with SSSS, toxin-producing S. aureus was isolated from skin lesions (56 percent); nose, throat, eyes, or ears (35 percent); blood (4 percent); and stool (1 percent) [9]. Antibiotic susceptibility testing should also be performed to facilitate treatment selection. (See 'Primary site of infection' above and 'Antibiotic therapy' below.)

Routine performance of blood cultures is not necessary in otherwise healthy children but may be appropriate in children at risk for bacteremia, such as a febrile neonate, immunocompromised child, or child with a serious illness. It is estimated that less than 5 percent of hospitalized pediatric patients with SSSS have bacteremia or sepsis [2,9].

In contrast to children, S. aureus bacteremia is relatively common in adults with SSSS [4,6]. Thus, blood cultures should be obtained in adults.

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of SSSS includes other infections, inflammatory conditions, and toxicities that present with extensive, cutaneous erythema or blistering.

●Burns – Chemical burns, thermal burns, or sunburn may result in erythema, blistering, and/or sloughing of the skin that can mimic SSSS (picture 2A-B). The history of an insult to the skin that corresponds to the distribution of the skin changes differentiates burns from other blistering conditions. (See "Assessment and classification of burn injury".)

●Bullous impetigo – Bullous impetigo is a superficial skin infection caused by the same toxin-producing strains of S. aureus associated with SSSS. Bullous impetigo most often occurs in young children and presents with vesicles, flaccid bullae, and erosions with collarettes of scale at sites of ruptured bullae (picture 3A-B). Intertriginous involvement is common. In contrast to SSSS, toxins are localized to the sites of skin infections rather than hematologically spread, and cultures of bullae will demonstrate S. aureus. Of note, bullous impetigo may progress to SSSS. (See "Impetigo", section on 'Bullous impetigo'.)

●Stevens-Johnson syndrome and toxic epidermal necrolysis – Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe blistering eruptions that involve the skin and mucous membranes (picture 4A-B). Targetoid skin lesions, fever, and skin pain are common associated findings. Medications are the most common cause of SJS and TEN, followed by infections. A biopsy is helpful for supporting the diagnosis; in contrast to the superficial blistering in SSSS, SJS and TEN demonstrate subepidermal blistering and full-thickness epidermal necrosis resulting in deeper erosions. In addition, mucosal involvement is present in SJS and TEN but absent in SSSS. (See "Stevens-Johnson syndrome and toxic epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis".)

●Toxic shock syndrome – Streptococcal and staphylococcal toxic shock syndromes are toxin-mediated systemic bacterial infections that can mimic SSSS. The inciting infections are usually a localized abscess, pyomyositis, or superinfection of a retained foreign body, such as tampons or surgical packing. Typical findings include widespread, blanchable, cutaneous erythema; conjunctival injection; "strawberry tongue;" fever; and hypotension (picture 5). Unlike SSSS, there is a lack of periorificial crusting on the face, absent bullae or desquamation, and a negative Nikolsky sign. Acral skin peeling or desquamation can occur but usually appears several days after the onset of symptoms [18]. (See "Staphylococcal toxic shock syndrome" and "Invasive group A streptococcal infection and toxic shock syndrome: Epidemiology, clinical manifestations, and diagnosis", section on 'Toxic shock syndrome'.)

●Scarlet fever – Scarlet fever is a bacterial infection caused by Group A Streptococcus that causes fever and a widespread cutaneous eruption and most often occurs in children in association with streptococcal pharyngitis. Affected individuals develop a "sandpaper-like" cutaneous eruption composed of diffuse, fine, pinpoint papules that are skin colored or slightly erythematous, which is followed by desquamation (picture 6A-B). The perioral crusting, skin fragility, and skin pain seen in SSSS are absent in scarlet fever. The diagnosis of scarlet fever is made based upon clinical manifestations. Confirmation of streptococcal infection supports the diagnosis. (See "Complications of streptococcal tonsillopharyngitis", section on 'Scarlet fever'.)

●Kawasaki disease – The cutaneous manifestations of Kawasaki disease are polymorphous and can include erythema accentuated in the flexural regions similar to early SSSS (picture 7). Affected patients will also typically have fever, conjunctivitis, "strawberry tongue," cervical lymphadenopathy, and swelling of their hands and feet. Kawasaki disease may manifest with superficial desquamation in localized areas (eg, inguinal folds) but does not typically have the positive Nikolsky sign, skin fragility, skin pain, or perioral crusting associated with SSSS [19]. (See "Kawasaki disease: Clinical features and diagnosis".)

●Pemphigus – Pemphigus foliaceus and pemphigus vulgaris are autoimmune blistering disorders that may present with widespread blistering and erosions. Similar to SSSS, pemphigus foliaceus involves targeting of desmoglein 1, resulting in superficial blistering and an absence of mucosal involvement (picture 8). In pemphigus vulgaris, desmoglein 3 is the targeted antigen and blistering occurs lower in the epidermis, resulting in deeper erosions and characteristic mucosal erosions (picture 9A-B). A skin biopsy with direct immunofluorescence microscopy is used to confirm the diagnosis. (See "Pathogenesis, clinical manifestations, and diagnosis of pemphigus", section on 'Clinical features'.)

Examples of additional disorders that should be considered in neonates include the blistering disorders epidermolysis bullosa (picture 10), epidermolytic ichthyosis (picture 11), and bullous mastocytosis (picture 12). Unlike SSSS, these disorders are not associated with fever in the absence of secondary or unrelated infection. In addition, cutaneous candidiasis in neonates may present with widespread erythema, papules, pustules, and desquamation and should be considered in the differential diagnosis (picture 13A-B). Broader discussions of the differential diagnosis of neonatal blistering and Candida infection in neonates are available separately. (See "Vesicular, pustular, and bullous lesions in the newborn and infant", section on 'Congenital/inherited disorders' and "Clinical manifestations and diagnosis of Candida infection in neonates".)

Poisoning is an infrequent cause of SSSS-like skin changes. Ingestion or topical exposure of boric acid, an ingredient in pesticides, household cleaning agents, and some preparations of homemade slime, may cause an erythematous, desquamative rash that can mimic SSSS, toxic shock syndrome, or TEN [20-22]. Other exposures that may mimic SSSS include mercury poisoning (acral erythema and superficial peeling of skin) [23] and perianal burn-like desquamation and erythema following ingestion and excretion of sennoside-containing laxatives, particularly in diapered infants [24].

MANAGEMENT — The management of SSSS involves eradication of the causative staphylococcal infection and supportive care to promote healing, reduce discomfort, and minimize complications. Patients are typically hospitalized for treatment [2,3]. Treatment is recommended for all patients with SSSS.

Immediate interventions — Immediate interventions for SSSS generally include hospital admission, intravenous antibiotic therapy, and the initiation of supportive measures.

Admission to hospital — Children and adults with SSSS are usually treated in an inpatient setting. Patients with SSSS should be admitted to a location in which careful, appropriate skin care can be implemented. In some hospitals, this may require admission to a burn unit or intensive care unit. (See 'Supportive care' below.)

In settings where adequate skin care can be provided outside of an intensive care unit or burn unit, most children do not require admission to an intensive care unit [2]. A typical hospital stay for children lasts three to eight days [2,3]. In contrast, most adults with SSSS are seriously ill, and comorbidities or complications may warrant admission to an intensive care unit.

Antibiotic therapy — Intravenous treatment with an antistaphylococcal antibiotic should begin promptly. Patients are typically initially treated with a penicillinase-resistant penicillin, such as oxacillin or nafcillin. Initial antibiotic selection should be subsequently adjusted based upon antimicrobial susceptibility of isolates. In addition, antibiotic selection and dosing should be appropriately adjusted based upon the underlying infection. (See 'Treatment course' below and "Staphylococcus aureus in children: Overview of treatment of invasive infections".)

Alternatives for initial treatment include a first- or second-generation cephalosporin or vancomycin. As with penicillinase-resistant penicillins, treatment should be subsequently adjusted, if needed.

Clindamycin has antistaphylococcal activity but is not recommended as a primary treatment because of high rates of clindamycin resistance in SSSS [25,26]. Although some clinicians add clindamycin as an adjunct to a penicillinase-resistant penicillin or cephalosporin based upon the theory that clindamycin may decrease ribosomal production of the pathogenic staphylococcal exotoxins or from concern for resistance to antistaphylococcal penicillins [25,27], evidence to support superior efficacy of this practice is lacking. We do not typically add clindamycin to standard antibiotic therapy. We occasionally add clindamycin in the setting of a severely ill patient. (See 'Treatment course' below.)

Common intravenous antibiotic regimens for children with SSSS associated with a skin or soft tissue infection are listed below. Most SSSS isolates in children are susceptible to oxacillin or nafcillin [26].

●Intravenous nafcillin or oxacillin – 100 to 150 mg/kg per day in divided doses every six hours; maximum daily dose of 12 g per day. Weight-based dosing for neonates differs and is reviewed separately. (See "Nafcillin: Pediatric drug information" and "Oxacillin: Pediatric drug information".)

●Intravenous cefazolin – 50 to 100 mg/kg per day in divided doses every eight hours; usual maximum daily dose of 6 g. (See "Cefazolin: Drug information".)

●Intravenous vancomycin – 45 mg/kg per day in divided doses every eight hours; usual maximum daily dose of 2 g. Weight-based dosing for neonates differs and is reviewed separately. (See "Vancomycin: Pediatric drug information".)

Supportive care — Supportive care is a critical component of management. Adequate hydration should be ensured, and trauma to the skin should be minimized.

●Prevention of dehydration – Fluid loss through the skin can be significant in SSSS, and many patients have decreased oral intake of fluids due to irritability, fatigue, and perioral pain. Intravenous hydration is frequently necessary to prevent dehydration and secondary electrolyte abnormalities. (See "Fluid and electrolyte therapy in newborns" and "Treatment of hypovolemia (dehydration) in children in resource-abundant settings" and "Maintenance intravenous fluid therapy in children" and "Maintenance and replacement fluid therapy in adults".)

●Gentle skin care – Because even minor trauma to the skin can induce blistering, desquamation, and pain, measures should be taken to minimize direct insults to the skin. Minimal use of adhesives, tourniquets, compression devices, and tape is imperative.

Bathing is often avoided for the first 48 hours because of discomfort. Once bathing is resumed, use of a gentle, unscented cleanser is preferred and abrasive scrubbing of the skin should be avoided. After bathing, skin should be patted rather than rubbed dry to minimize skin shearing.

●Wound care – Wound dressings may induce friction and trauma to the skin upon removal and should be limited. For small erosions, frequent application of petroleum jelly is sufficient. Nonadherent dressings, such as petroleum jelly-embedded gauze or self-adherent foam dressings coated with a thick layer of sterile petroleum jelly, can be used to protect large erosions.

Dressings should be changed daily. Dressing changes can be painful, and administration of an analgesic prior to dressing changes may be necessary. Children may derive additional benefit from distraction techniques, music therapy, and psychologic support (eg, child-life services).

Treatment course — After the start of therapy, culture and antibiotic susceptibility results and the response to treatment should be followed closely. If culture and susceptibility testing reveal an S. aureus strain that is not susceptible to initial therapy (eg, methicillin-resistant Staphylococcus aureus [MRSA]), antibiotic therapy should be adjusted accordingly.

The prevalences of MRSA and clindamycin-resistant S. aureus vary based upon location. Reported rates of MRSA-induced SSSS and clindamycin-resistant S. aureus in SSSS range from 0 to 69 percent and 26 to 86 percent, respectively [8,25,26,28]. In the author's personal experience in New Jersey and Philadelphia, MRSA-induced SSSS has seemed to account for a minority of cases.

Once patients demonstrate clinical improvement and are tolerating oral intake, oral antibiotic therapy can replace intravenous antibiotic therapy. The oral antibiotic should be selected based upon the results of antibiotic susceptibility testing.

The total duration of intravenous and oral treatment with an appropriate antibiotic is typically 10 days. We occasionally extend treatment to 14 days for patients with slow responses (eg, persistent erythema, fever, and progression of skin disease after 7 to 10 days of treatment), such as may occur in young infants. In this scenario, we also optimize intravenous hydration to facilitate removal of toxins. Reassessment to ensure the correct diagnosis is always prudent when patients have poor responses to therapy. (See 'Course and complications' above.)

Other therapies — Treatment with an antibiotic selected based upon antibiotic susceptibility and supportive measures is typically sufficient, and additional therapy beyond supportive care is not necessary for most patients. Case reports describe rapid improvement following the addition of intravenous immune globulin or plasma exchange in patients with severe disease; however, data are insufficient to confirm efficacy of these therapies [29,30].

PROGNOSIS — Despite the significant morbidity of SSSS, mortality may be low among children hospitalized for treatment [2,3,6-8,25]. A review of data from pediatric and adult hospitalizations in the United States between 2008 and 2012 found a mortality rate for children of 0.3 percent [3].

Reported mortality rates in adults tend to be higher, likely related to the frequent presence of serious comorbidities. A review of data from adult hospitalizations in the United States between 2008 and 2012 found a mortality rate of 4 percent [6]. Higher mortality has also been suggested; a 1994 review of published cases of SSSS found that 19 of 32 adults died soon after diagnosis despite appropriate antibiotic therapy [31]. Mortality is typically related to complications of SSSS, such as sepsis or electrolyte imbalance, or a concurrent disease, such as pneumonia.

Recurrence of SSSS is rare but does occur, particularly in neonates and young infants [17].

PREVENTION — Prevention of SSSS involves minimizing risk for transmission of exotoxin-producing strains of S. aureus to others, particularly young children and other at-risk individuals. These measures are particularly important in newborn nurseries, neonatal intensive care units, and in settings with ill individuals, such as long-term care and inpatient facilities.

Examples include hand hygiene, trimming nails, and adherence to appropriate precautions in health care settings. The United States Centers for Disease Control and Prevention (CDC) recommends use of both standard and contact precautions for the duration of illness for the care of patients with SSSS [32]. (See "Infection prevention: Precautions for preventing transmission of infection".)

S. aureus colonization is common, with up to 40 percent of adults as asymptomatic carriers of S. aureus [33]. In some settings, screening of health care workers and caretakers has been performed to detect the source of SSSS outbreaks [14,15].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Management of Staphylococcus aureus infection".)

SUMMARY AND RECOMMENDATIONS

●Overview – Staphylococcal scalded skin syndrome (SSSS) is a skin disorder that results from infection with exotoxin-producing strains of Staphylococcus aureus. The skin lesions result from hematologic dissemination of exotoxins from the site of infection to the skin. (See 'Pathogenesis' above and 'Acquisition' above.)

●Epidemiology – Young children are most susceptible to SSSS. SSSS in adults usually occurs in the setting of renal impairment, immunosuppression, or other comorbidities that reduce the immune response to bacterial infection. (See 'Epidemiology' above.)

●Pathogenesis – The causative strains of S. aureus produce exfoliative toxin A and/or exfoliative toxin B, exotoxins capable of cleaving desmoglein 1, a protein responsible for keratinocyte-to-keratinocyte adhesion in the superficial epidermis. Cleavage of desmoglein 1 leads to skin fragility and the formation of superficial blisters and erosions (figure 1). (See 'Pathogenesis' above.)

●Clinical features – SSSS typically manifests with rapidly progressive, extensive, cutaneous erythema that begins in intertriginous areas. The cutaneous findings progress to include flaccid, sterile bullae; erosions; and sheet-like desquamation. Patients also often develop thick crusting and radial fissuring around the mouth, nose, and eyes, as well as skin pain, fever, irritability, and poor feeding (picture 1A-H). Mucosal involvement is absent. (See 'Clinical features' above.)

●Diagnosis – The diagnosis of SSSS usually can be made based upon the history and physical examination. Bacterial cultures of sites of suspected S. aureus infection (eg, purulent areas) should be performed to support the diagnosis and provide information on antibiotic susceptibility for treatment. If the diagnosis remains uncertain, a skin biopsy or pathologic examination of a frozen section of freshly sloughed skin can be helpful. (See 'Diagnosis' above.)

●Management – The initial management of SSSS typically involves hospitalization of the patient, intravenous antibiotic therapy, and supportive measures. We suggest intravenous, rather than oral, administration of an antistaphylococcal antibiotic for initial therapy (Grade 2C). A penicillinase-resistant penicillin, such as nafcillin or oxacillin, is usually given as initial therapy. Cephalosporins and vancomycin are alternative treatments. Culture and antibiotic susceptibility testing should be followed to detect the presence of S. aureus strains resistant to the selected therapy. Once clinical improvement occurs, patients may be transitioned to oral antibiotic therapy. (See 'Antibiotic therapy' above and 'Treatment course' above.)

●Prognosis – With appropriate treatment, signs and symptoms of SSSS usually resolve completely within two to three weeks without long-term sequelae. Potential complications include secondary infection, hypovolemia, electrolyte imbalances, sepsis, and rarely death. Recurrence of SSSS is rare. (See 'Prognosis' above.)