Continuing Education Activity

Staphylococcal scalded skin syndrome (SSSS) is a systemic cutaneous infection caused by toxin-producing staphylococcal species. The condition presents with desquamation of the skin and may easily be confused with other life-threatening conditions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis. The condition usually affects children and adults with comorbid conditions. Evaluation for SSSS is mainly clinical, with adjunct studies to aid in the formal diagnosis. Management typically requires inpatient admission with fluid resuscitation and intravenous antibiotics for treatment. Monitoring for sequelae includes close observation to avoid hypothermia, hemodynamic instability, and, rarely, relapse.

This activity for healthcare professionals is designed to enhance learners' proficiency in evaluating and managing SSSS. Participants gain a deeper insight into the disorder's causes, clinical characteristics, and best diagnostic and management practices. Greater competence equips clinicians to collaborate effectively within an interprofessional team caring for patients with SSSS, improving outcomes.

Objectives:

• Identify the clinical features indicative of staphylococcal scalded skin syndrome.

• Create a clinically guided diagnostic plan for suspected cases of staphylococcal scalded skin syndrome.

• Apply evidence-based, personalized management strategies for staphylococcal scalded skin syndrome.

• Implement effective collaboration and communication among interprofessional team members to improve outcomes and treatment efficacy for patients diagnosed with staphylococcal scalded skin syndrome.

Introduction

Staphylococcal scalded skin syndrome (SSSS), also known as Ritter disease or pemphigus neonatorum, is a dangerous cutaneous infection caused by certain exotoxin-producing strains of Staphylococcus species (see Image. Staphylococcal Scalded Skin Syndrome).[1] The condition typically presents with superficial skin blistering and denudation and affects children more often than adults. SSSS in adult patients is often associated with renal dysfunction or immunocompromise.[2][3]

Skin desquamation is typically caused by exotoxins from a distant location rather than a local infection spreading via the blood.[4][5] In the pediatric population, SSSS can present as early as 48 hours after birth and becomes less frequent in children older than 6 years.[6] SSSS is a clinical diagnosis, but the diagnostic evaluation focuses on identifying bacteremia, distinguishing SSSS from mimicking conditions like bullous impetigo, and selecting appropriate management. Therapy includes antibiotics, specifically penicillinase-resistant penicillins, supportive care, and monitoring for possible sequelae, including hypothermia, hemodynamic instability, and relapse.

Etiology

Staphylococcus aureus, a gram-positive coccus, causes most cases of SSSS. Many individuals are colonized, particularly in areas such as the umbilicus, groin, buttocks, and the face, especially the nares.[7][8] Methicillin-sensitive S aureus (MSSA) is more commonly identified than methicillin-resistant S aureus (MRSA).[9] Exfoliative or epidermolytic exotoxins A and B are serine proteases released by S aureus at the primary infection site. These toxins are produced by less than 5% of Staphylococcus species, although all species produce some form of toxin.[10][11][12]

Phage group II types 3A, 3B, 3C, 55, and 71 and the strain ST121 are the most likely S aureus species implicated in producing exotoxins A and B.[13][14][15] The accumulated toxins directly target cadherin desmoglein-1 at distant sites after hematogenous dissemination, causing loss of cellular adhesion among keratinocytes in the stratum granulosum. Notably, desmoglein-3, which predominates in the lower epidermis, is not affected by the exotoxins A and B produced by S aureus.[16][17][18] However, testing for the specific phage type is often not helpful or available.

The primary source of infection is usually distant from areas of skin denudation. However, no specific source can be identified in many cases, and the organism can come from sites that include the upper respiratory tract, ears, conjunctivae, or an abscess, fistula, or joint infection.[19]

Epidemiology

The incidence of SSSS is low. A study in the Czech Republic reported an incidence of approximately 25 cases per 100,000 children younger than 1 year.[20] Most cases involve children younger than 5 years, with most cases occurring before 3 years. However, neonates are relatively protected from SSSS due to the predominance of desmoglein-3 in the epidermis, which is not targeted by staphylococcal exotoxins.[21][22] The disease is much less common in adults because of neutralizing antibodies and mature kidney function, which allow for efficient clearance of exotoxins from the bloodstream.[23] Thus, SSSS in adults typically affects individuals with immunosuppression, including people with HIV/AIDS and advanced malignancies or those with severe kidney impairment.[24]

SSSS may occur as an outbreak in daycares or nurseries. The frequent occurrence of prodromal symptoms resembling those of upper respiratory viral infections, such as fever and irritability, has led some authors to suggest a role for viral infection as a promoter of the proliferation of exotoxin-producing strains of S aureus. Viral coinfection may explain the autumnal predominance of the condition and the prodromal upper respiratory infection symptoms observed in patients with SSSS.

Pathophysiology

Some toxin-producing strains of Staphylococcus cause SSSS. These toxins target the desmoglein-1 complex in the zona granulosa of the epidermis, resulting in skin exfoliation. The manifestations can range from a mild localized form to exfoliation of the entire body. Individuals who have developed antibodies against the bacteria and its products are more likely to have the localized form. The resultant skin loss predisposes patients to hypothermia, large fluid volume losses, and additional or worsening infections.

Histopathology

SSSS is primarily a clinical diagnosis, rarely necessitating additional evaluation. However, a biopsy can support the diagnosis when clarity is lacking. Histopathological evaluation of a skin biopsy from a patient with SSSS typically reveals superficial intraepidermal cleavage beneath the stratum corneum.[25] Cleavage at the stratum granulosum may show sparse neutrophils or a mixed inflammatory infiltrate, complicating the diagnosis in adult patients with coexisting conditions, such as malignancy, where toxic erythema of chemotherapy may present similarly.[26]

History and Physical

SSSS initially presents with irritability, fever, and malaise, followed by the rapid development of a tender, erythematous desquamative rash on the face and flexures, such as the groin, axillae, and neck, within 24 to 48 hours. Subsequently, large, fragile, and potentially purulent blisters form bullae, exhibiting a positive Nikolsky sign. Progressive desquamation and healing without scarring occur over the next 2 weeks.[27] Adults exhibit findings similar to those seen in children.

Evaluation

SSSS is primarily a clinical diagnosis. However, further evaluation may be beneficial in certain circumstances. As with other systemic illnesses, clinicians may perform routine blood tests, including a complete blood count, urinalysis, comprehensive metabolic profile, and blood cultures. However, blood cultures and blister fluid cultures are usually negative, except in adults, who often present with sepsis from bacteremia. Adults with severe disease may require additional evaluation to identify a source of infection, such as infected fistulae in patients with renal failure, bacteremia, or septic arthritis. Testing for Staphylococcus species through nasopharyngeal and periorificial swabs may help confirm the diagnosis. Blood cultures typically provide limited information since the toxins, not the organisms, spread hematogenously.

Treatment / Management

Antibiotics effective against MSSA, such as cefazolin, nafcillin, and oxacillin, should be administered promptly. In children, nafcillin or oxacillin should be initiated at 100 to 150 mg/kg daily, divided every 6 hours. Cefazolin should be administered at 50 to 100 mg/kg daily, divided every 8 hours. Oral alternatives like cephalexin or dicloxacillin at 500 mg every 6 hours or trimethoprim/sulfamethoxazole at 160/800 mg every 12 hours may be used for mild infections.

Vancomycin should be administered if MRSA is suspected, particularly in patients with recent healthcare exposure, including those residing in a skilled nursing facility, recently hospitalized, or living in areas with a high MRSA prevalence.[28] Clindamycin should be avoided due to resistance. Topical antimicrobial therapies are generally ineffective, though they may be used for decolonization at the primary site of infection.[29] Treatment should continue for 10 days unless clinical judgment dictates a longer course.

Additional antibiotics with Pseudomonas coverage should be initiated if concern for a secondary bacterial skin infection arises. Intravenous fluids become necessary for patients showing signs of dehydration or sepsis. Some children may require intravenous immunoglobulin or fresh frozen plasma to address volume loss. Admission to an intensive care unit may be necessary, as saline-soaked gauze and wound care may be required.[30]

Emollients and nonadherent dressings should be applied to denuded areas to promote healing and reduce heat loss. Supportive care, including management of dehydration, temperature regulation, and nutrition, proves essential. Patients with significant skin involvement are prone to hypothermia and fluid deficits due to epidermal loss. The application of silver sulfadiazine should be avoided, given the potential for increased systemic absorption and resultant toxicity.[31] Acetaminophen and opioids may be needed for pain control, but nonsteroidal anti-inflammatory drugs, such as ibuprofen, should be avoided due to the risk of kidney impairment.

Differential Diagnosis

The differential diagnosis for SSSS includes other blistering infections, such as:

• Bullous impetigo is typically seen in newborns and also results from cleavage of desmoglein-1. However, this condition features a large dermal inflammatory infiltrate and demonstrates a negative Nikolsky sign.[32]
• Stevens-Johnson syndrome and toxic epidermal necrolysis present with dusky areas that show necrotic keratinocytes. As opposed to clinical patterns associated with SSSS, Stevens-Johnson syndrome and toxic epidermal necrolysis are commonly linked to medications and affect older children and adults.[33]
• Acute generalized exanthematous pustulosis occurs more frequently in women. This disorder is characterized by nonfollicular pustules on flexural sites, exhibiting subcorneal pustules with eosinophilic and neutrophilic inflammation on biopsy.[34][35] 
• Toxic shock syndrome may be caused by S aureus, by a mechanism involving the toxic shock syndrome toxin-1, or by Streptococcus pyogenes. This condition presents with necrolysis of keratinocytes, fever, hypotension, and involvement of multiple organ systems.[36][37]
• Kawasaki disease affects a similar age group and is diagnosed based on criteria that include a fever lasting 5 days and at least 4 minor criteria, one of which is acral desquamation.[38][39]
• Scarlet fever, caused by S pyogenes, typically affects older children. This condition presents with flu-like symptoms followed by a characteristic sandpaper rash.[40]

A thorough clinical investigation and judicious diagnostic testing can differentiate SSSS from similar conditions, guide therapeutic strategies, and improve outcomes.

Prognosis

Pediatric patients generally do well with minimal to no scarring. Healing typically occurs within 2 weeks. The mortality rate in children is less than 5%. In contrast, adults with SSSS have a much higher mortality risk, as high as 60%.

Complications

Potential complications of SSSS include dehydration, secondary infections, electrolyte imbalance, sepsis, acute kidney injury, and scarring.[41]

Consultations

Consultation with a dermatologist should be considered if the diagnosis is uncertain. Burn centers and burn unit or critical care physicians should be consulted in severe cases. 

Deterrence and Patient Education

Preventing SSSS in children and adults involves practicing good hygiene, including regular handwashing and proper wound care. Parents and caregivers should keep the skin clean and monitor for any signs of infection, especially in children with cutaneous disorders such as eczema. Additionally, limiting exposure to infected individuals and maintaining good sanitation can help minimize the risk of transmission. Strict adherence to infection control protocols is critical to prevent outbreaks in healthcare settings.

Enhancing Healthcare Team Outcomes

SSSS cases should be approached as a team, particularly with unclear cases. Expert consultation with dermatologists can help eliminate alternative diagnoses and guide treatment. Colonized caregivers and individuals with patient contact require treatment with chlorhexidine. Nasal carriers should be treated with topical mupirocin. The mortality is relatively low in children when appropriate treatment is initiated, but it is much higher in adults, even with appropriate antibiotics and supportive therapy.[42][43] In severe cases, referral to a burn center with wound care experts should be strongly considered to reduce fluid losses and prevent scarring. 

Effective management of SSSS requires timely identification and coordinated efforts across an interprofessional healthcare team. Initial recognition typically begins with primary care providers (PCPs) and nurses, who should be trained to spot characteristic symptoms like skin redness, blistering, and peeling, especially in pediatric or immunocompromised patients. If SSSS is suspected, the PCP should quickly refer the patient to appropriate specialists, such as dermatologists and infectious disease experts, for further diagnostic support, including skin biopsies or cultures to confirm the presence of Staphylococcus aureus. Lab technicians also play a crucial role in analyzing samples, while infectious disease specialists may help guide the choice of antibiotics. Immediate referral to emergency departments ensures rapid stabilization and treatment for severe cases.

In cases requiring hospitalization, collaboration among the inpatient nursing team, pharmacists, and nutritionists is essential to manage symptoms, administer antibiotics, and address hydration and nutritional needs due to potential fluid loss from damaged skin. All team members should maintain thorough documentation in electronic health records throughout the process to support clear communication and effective care coordination. Once the patient stabilizes, discharge coordinators help arrange follow-up care and provide guidance on wound care and infection prevention. This team-based approach, supported by structured referral pathways and regular interdisciplinary communication, ensures comprehensive care for patients with SSSS, optimizing recovery and reducing the risk of complications.