S. aureus causes a variety of infectious diseases, ranging from superficial skin infections to severe, toxin-mediated systemic infections. SSSS is a type of systemic disorder mainly caused by coagulase-positive group II S. aureus that can cause superficial skin blistering. Skin acantholysis leads to cracks in the epidermis and characteristic skin bullae [25]. The pathophysiologic mechanisms include several steps: first, the production of exfoliative toxins (ETs). Several strains of Staphylococcus aureus (Group II) can produce epidermolytic toxins, primarily toxin A (ETA) and toxin B (ETB), which are exfoliative. These toxins have a specific affinity for skin proteins, particularly a skin protein called desmoglein-1 (Dsg-1), a desmosomal cadherin of the superficial epidermis responsible for the adhesion of skin cells (the upper layer of the skin). Thus, the epidermolytic toxins act by binding to Dsg-1 and causing cleavage of the desmosomes, leading to separation between the epidermal cells of the skin. Following the disruption of the desmosomes, epidermal cells detach from one another, causing the formation of blisters, bullae, and peeling of the skin. This process leads to the typical manifestation of skin exfoliation, which may appear like a burn [26].

The diagnosis is clinical and the consultation with a dermatologist should be considered if the diagnosis is uncertain. SSSS may resemble other exfoliative skin conditions, such as toxic epidermal necrolysis (TEN), epidermolysis bullosa (EB), Stevens–Johnson syndrome (SJS), toxic shock syndrome (TSS), and pemphigus. Differentiation is primarily based on the presence of mucosal involvement. Bullous impetigo, caused by the localized release of similar toxins, often presents with similar skin findings but is typically confined to specific areas, while SSSS causes a more widespread rash and severe symptoms due to the systemic distribution of these toxins. These conditions may occasionally be mistaken for other disorders that result in superficial blistering [27].

Our retrospective study analysed 21 cases of SSSS from 2010 to 2023 in a tertiary care Children’s Hospital IRCCS. SSSS commonly affects neonates and children younger than 5 years, with peak incidence between 2 and 3 years. It is well established that neonates and young children are at greater risk due to their immature immune system, which is unable to neutralize epidermolytic toxins and their limited renal capacity to eliminate these toxins [28, 29]. Similarly, immunocompromised adults or those with renal impairment present a higher incidence [30].

The increased frequency and severity of SSSS in neonates likely results from a combination of factors, including the reduced renal clearance of toxins and the underdeveloped structure of the neonatal epidermis. In addition to age, other predisposing conditions are recognized risk factors for SSSS, particularly in severe cases. These include atopic dermatitis, renal failure, and primary immunodeficiencies [26]. For instance, Hyper-IgE syndrome [31] and Netherton syndrome [32] have been described in children with severe SSSS. In our cohort, none of the patients presented with predisposing conditions, except one child with atopic dermatitis.

A large U.S. study on 589 children with SSSS reported an increase in incidence between 2010 and 2012 compared to 2008–2009 [7]. Similarly, Li et al. observed a rise in incidence Chinese infants, with 79,5% occurring between 2008 and 12 compared to 20,5% between 2004 and 2009 [30]. This upward trend aligns with other previous reports [33, 34]. Conversely, in Europe and regions with high hygiene standards, a decline in SSSS incidence has been noted [6]. In our study, hospital admissions remained stable over time, with an average of two cases per year.

Consistent with the literature [1, 11, 12], most of our patients (86%) were under 5 years years of age, with a slight male predominance as reported in other studies [28, 35]. However, Lyi-Wong [35], found no sex predominance.

Seasonal distribution in our series showed that SSSS was more frequent during winter, autumn, and summer, in line with prior studies [33, 35,36,37]. Some authors suggest that viral upper respiratory tract (URT) infections, particularly in autumn, may predispose colonized individuals to SSSS [5]. Previous studies have also documented preceding infections such as URT infections otitis media, conjunctivitis, omphalitis [30], pneumonia [33], pyomyositis [38], and maternal breast abscesses [39]. Similarly, we observed that eight children presented URT symptoms prior to hospitalization.

The clinical course of SSSS is typically characterized by a prodromal phase with fever, irritability, and anorexia. Before the onset of skin lesions, Nikolsky’s sign may already be positive. Initial dermatologic findings include widespread erythematous patches and the formation of fragile bullae, which rupture easily, leaving behind denuded, scalded-appearing skin [28, 29, 40]. Exfoliated areas crust over within 24 h, with perioral and periorbital fissures, and complete re-epithelialization generally occurs within two weeks without scarring [4]. In our series, these features were variably present and summarized in Table 1. Based on Kang et al.’s classification [24], the generalized type was most frequent (62.5%), followed by the intermediate type, while the abortive form was rare. Systemic symptoms such as poor appetite and pain were common, while fever and irritability were present in approximately one-third of cases.

In our series, complications occurred in 14.2% of patients and included sepsis, dehydration with hyponatremia, and HSV1 infection. Literature reports that SSSS severity is influenced by toxin burden and the host’s immune response. The compromised skin barrier predisposes to secondary infections, hypothermia, and fluid loss. Hence, dehydration and electrolyte imbalances, notably hyponatremia, are frequent complications, underscoring the need for careful fluid management and laboratory monitoring. Interestingly, Blyth et al. reported that fluid overload can paradoxically occur despite hypovolemia being the primary concern [41].

Although rare, other complications include pneumonia and bacteremia (sepsis). Life-threatening events such as toxic shock syndrome [35, 36], acute kidney injury, and thrombosis have also been reported [42].

Regarding laboratory findings, leukocytosis and elevated CRP levels were detected in only 28.6% of cases, indicating a mild or delayed systemic inflammatory response. Consistent with Neubauer et al., laboratory tests (WBC, ESR, CRP) showed limited prognostic value in SSSS management [36]. Zeng et al. demonstrated elevated WBC, CRP, IL-6, and PCT in both bacterial infections and SSSS compared to healthy controls, with PCT levels being notably higher in SSSS [40]. However, in our series, PCT remained negative in all patients, even at onset.

The detection rate of S.aureus was high (62%) in our study, which is consistent with prior reports [28, 43]. Blood cultures yielded no significant results, in line with the low positivity rate typically seen in pediatric populations [5, 33, 35, 44,45,46] in contrast to adult data [26].

Early diagnosis and timely administration of appropriate parenteral anti-staphylococcal antibiotics, along with supportive care, are crucial. Empirical therapy in our cohort mainly involved oxacillin, alone or in combination, reflecting current recommendations [25, 39]. The ten positive cultures (nine from skin lesions and one from throat swab) all grew MSSA.

In settings with high MRSA prevalence, vancomycin or teicoplanin should be considered upfront, particularly in severe or non-responsive cases [47]. Although no MRSA strains were isolated, six patients required teicoplanin following oxacillin failure, three of whom were critically ill. Additionally, four patients were treated with clindamycin, alone or in combination.

Despite increasing reports of clindamycin resistance [48], resistance was identified in only two isolates (10%) in our study. In contrast, Braunstein et al. reported a clindamycin resistance rate of 52% despite MSSA isolates [47]. Wang et al. also found SSSS-associated strains more frequently resistant to clindamycin but less often resistant to methicillin compared to other S. aureus infections [48].

All patients in our series survived, including those with complications, which aligns with previous studies [35]. This contrasts with larger studies reporting pediatric mortality rates between 0.3% and 5% [4, 6, 40]. In adults, mortality is significantly higher (40-63%) due to underlying comorbidities [28]. Fatal outcomes in children are primarily linked to severe complications such as pneumonia and sepsis [48].

In our cohort, the median length of stay (LOS) was 7.8 days, which is comparable to other studies reporting LOS ranging from 3 to 8 days [35, 48], and even longer among neonates [45]. No readmissions were recorded, consistent with the literature describing recurrence as exceedingly rare [10].

This case series provides insight into the clinical features, management, and outcomes of pediatric SSSS. Early diagnosis and intervention are paramount to reducing morbidity and mortality. Our data suggest a stable incidence in our setting, but results may differ in other geographic areas.

Study limitations include its retrospective design, incomplete data, small sample size, and single-center setting. Furthemore, we lacked data on S. aureus phage types and toxin profiles, limiting etiological characterization. Future studies should be prospective, multicenter investigations incorporating toxin profiling and resistance trends, as well as long-term follow-up to assess recurrence and late sequelae.