Staphylococcal scalded skin syndrome

1. Pediatric Dermatology. 2020;00:1–5. wileyonlinelibrary.com/journal/pde | 1
Pediatric
Dermatology
© 2020 Wiley Periodicals LLC.
DOI: 10.1111/pde.14470
O R I G I N A L A R T I C L E
Staphylococcal scalded skin syndrome: An epidemiological and
clinical review of 84 cases
Carmen Liy-Wong MD | Elena Pope MD, MSc, FRCPC |
Miriam Weinstein MD, FRCPC | Irene Lara-Corrales MD, MSc
Division of Pediatric Medicine, Section of
Dermatology, Department of Pediatrics,
The Hospital for Sick Children, University of
Toronto, Toronto, ON, Canada
Correspondence
Irene Lara-Corrales, MD, MSc, Pediatric
Dermatology, University of Toronto,
Hospital for Sick Children, 555 University
Avenue, Toronto, ON M5G1X8, Canada.
Email: irene.lara-corrales@sickkids.ca
Abstract
Background: Staphylococcal scalded skin syndrome (SSSS) is a toxin-mediated, blis-
tering skin disorder that mainly affects infants and children. There is limited literature
regarding pediatric SSSS. The purpose of this study was to describe the epidemiol-
ogy, clinical features, and management of pediatric SSSS.
Methods: Retrospective cohort study of pediatric patients with a clinical diagnosis of
SSSS seen at the Hospital for Sick Children in Toronto, Ontario, Canada, from January
1994 to March 2016.
Results: We included 84 patients with a clinical diagnosis of SSSS; 49/84 (58%) were
male. Mean age of diagnosis was 3.1 ± 2.4 years. All patients presented with erythema
and exfoliation, while 64/84 (76%) presented with vesicles/ bullae. Skin tenderness
was the most common symptom, present in 68/84 (81%) subjects. Staphylococcus
aureus was more commonly isolated from periorificial cultures than from bullae.
Mean hospitalization was 4.7 ± 2.3 days. No difference was found in admission du-
ration between children receiving clindamycin and those that did not (3.6 ± 2.2 vs
3.9 ± 2.34 days, P = .63). Skin debridement was the only risk factor leading to more
complications and prolonged hospitalization (P = .03). Severe complications were
seen in 4 (5%) cases, and no fatalities were observed.
Conclusions: Healthcare providers should be aware of SSSS and consider it in the dif-
ferential diagnosis of infants and children with new onset erythema, exfoliation, and/
or vesiculation. Suspected culprit pathogens were more often obtained from perior-
ificial swabs; however, these isolates were not tested for exfoliative toxin to confirm
causality. Antibiotic treatment should be guided by sensitivity testing. Addition of
clindamycin as an anti-toxin agent had no effect on the duration of hospitalization,
and this should be further investigated. Surgical debridement of the skin in patients
with SSSS should be discouraged.
K E Y W O R D S
antibiotics, pediatrics, skin infections, Staphylococcal scalded skin syndrome

2. 2 | Pediatric
Dermatology
LIY-WONG et al.
1 | INTRODUCTION
Staphylococcal scalded skin syndrome (SSSS) is an exfoliative
toxin-mediated skin condition produced by certain strains of
Staphylococcus aureus (S aureus). It predominantly affects neonates
and children under 5 years of age and rarely immunocompromised
adults.1,2
Clinically, this manifests as blistering, large areas of de-
tachment and denuded skin.1,2
The most common primary sources
of S aureus producing exfoliative toxins (ETs) are the conjunctiva,
nose, throat, and perianal skin. In newborns, the umbilical stump
is also a common reservoir, and for all patients, a wound or surgi-
cal site should also be considered.1,2
Subsequent hematogenous
spread of this toxin is responsible for the development of consti-
tutional symptoms and multifocal skin involvement.1,2
The higher
incidence in children may be due to less efficient renal clearance of
the toxin and to immunological immaturity (low anti-ET antibody
titers).3
Staphylococcal scalded skin syndrome in children typically pres-
ents with a prodrome of irritability, malaise, and fever followed by
tender erythema and fragile bullae formation with epidermal de-
tachment beginning typically on the central face, neck, axillae, and
groin.1,2
The denuded skin is a source for fluid loss, dehydration, and
temperature dysregulation and also serves as a potential source for
secondary infection.
Skin lesions are typically sterile in SSSS; cultures should be per-
formed on all possible sites of infection such as the conjunctiva,
nasopharynx, perioral, and perianal regions, and in neonates, the
umbilical stump.4
Blood cultures are typically unhelpful in diagnosis
of SSSS as they are usually negative.4
Treatment includes supportive measures such as pain control,
intravenous fluids, local skin care to avoid secondary infection and
anti-staphylococcal antibiotics/beta-lactams (ie, cloxacillin, oxacillin,
cefazolin, cephalexin, dicloxacillin) as well as clindamycin, which also
has an anti-toxin effect.1,2
In patients with SSSS due to CA- MRSA
(community-acquired, methicillin-resistant S aureus), the antibiotic
of choice is vancomycin.1,2
If treatment begins promptly, morbidity
(scarring, glomerulonephritis, pneumonia, sepsis, among others) is
minimized and mortality is rare.1,2
The primary aim of this study was to describe epidemiologic and
clinical characteristics, secondary aim was to explore and describe
management and outcomes of hospitalized children with SSSS at a
single pediatric referral center.
2 | MATERIAL AND METHODS
After institutional review board approval, a retrospective chart re-
view was performed of all patients with clinical diagnosis of SSSS
who attended the Hospital for Sick Children, Toronto, Ontario,
Canada from January 1994 to March 2016. Patients with a diagno-
sis of SSSS were identified by our health records department using
the search term “Staphylococcal scalded skin syndrome” or “Ritter
syndrome.”
Children 0-18 years of age with a clinical diagnosis of SSSS with
complete information were included. We excluded children with lo-
calized bullous forms (bullous impetigo). Epidemiologic and clinical
data obtained included the following: age, gender, prenatal history,
TA B LE 1 Clinical characteristics of 84 children with SSSS
Characteristic
Cases
n (%)
Males 49 (58)
Age of diagnosis, mean (SD), years 3.1 (2.4)
Main reasons for emergency room (ER) consultation
Skin rash 84 (100)
Pain 18 (21)
Fever 12 (14)
Irritability 12 (14)
Looks unwell 5 (6)
Not eating of drinking well 3 (4)
First symptom noticed
Skin rash 79 (94)
Fever 4 (5)
Sore throat 1 (1)
History of related symptoms
Skin tenderness 68 (81)
Fever 32 (38)
Pruritus 32 (38)
Related infections 2 wks prior diagnosis of SSSS
URTI 35 (42)
Soft tissue infection 3 (4)
Conjunctivitis 2 (2)
Pneumonia 1 (1)
Clinical signs
Skin erythema 84 (100)
Exfoliation/desquamation 84 (100)
Skin tenderness 74 (88)
Facial edema 63 (75)
Perioral crusting 61 (73)
Vesicles/ bullae 64 (76)
Periocular crusting 47 (56)
Positive Nikolsky's sign 26 (31)
Perinasal crusting 13 (15)
Conjuntivitis 9 (11)
Scarlatiniform “sand paper”-like rash 9 (11)
Mucous membrane involvement 4 (5)
Days of hospitalization 4.8 (±2.3)
Complications 4 (5)
Shock syndrome 1 (1)
Generalized bacteremia (sepsis) 3 (4)
Mortality 0
Abbreviation: SSSS, Staphylococcal scalded skin syndrome.

3. | 3
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Dermatology
LIY-WONG et al.
family history of skin related conditions, clinical features, microbio-
logical findings, management, and outcomes.
2.1 | Statistical analysis
Descriptive statistics (means, SD, percentages) were performed to
analyze continuous and categorical data. A chi-square analysis and
analysis of variance (ANOVA) were conducted to identify predictors
for hospital admission, duration of hospitalization, and complications.
3 | RESULTS
We identified 109 patients from March 1994 to March 2016 with
a diagnosis of SSSS. Of those, 25 did not meet inclusion criteria (22
had localized disease and 3 had incomplete data). Data from 84 pa-
tients were analyzed. There were 49 (53%) males. The mean age at
diagnosis was 3.1 ± 2.4 years. The rest of the clinical characteris-
tics are described in Table 1. We found 67/84 (77%) of the patients
were previously healthy, 8/84 (10%) had allergies (1 to penicillin, 1 to
clarithromycin, 2 to cephalexin, and the remainder to various foods)
and 19/84 (23%) had a pre-existing skin disease: 17/84 (20%) had
atopic dermatitis, 1/84 (1%) had congenital ichthyosiform erythro-
derma, and 1/84 (1%) had alopecia areata. None of the patients had
a previous history of SSSS.
Only 5/84 (6%) of the patients had a positive family history of
skin disease (3/84 (4%) with eczema, 1/84 (1%) with eczema and
psoriasis, 1/84 (1%) with sarcoidosis). One patient (1/84 [1%]) had a
positive family history of SSSS (sibling, not part of this cohort).
The mean duration from the onset of symptoms to admission
was 2.8 ± 1.4 days. All patients presented with skin erythema and
exfoliation. The initial sites of erythema, exfoliation, and bullae are
summarized in Table 2.
A clinical diagnosis was made in 83/84 (99%) patients; only 1
case had a skin biopsy (that confirmed the diagnosis). The diagnosis
of SSSS was first established by providers from different specialties,
including dermatology in 35/84 (42%), emergency medicine in 29/85
(34%), pediatrics in 16/84 (19%), and family medicine in 4/84 (5%).
Subsequently, all patients were seen by dermatology and the diag-
nosis was confirmed clinically. Isolation and identification of patho-
genic microorganisms by blood, throat, bulla, and periorificial cultures
(perianal, perioral, periocular or nasal), as well as drug susceptibility
tests are summarized in Table 3. Periorificial cultures were performed
in 57/84 (68%) of cases; of those 42/57 (74%) were positive for S au-
reus. No testing for exfoliating toxin was completed in this cohort.
Regarding treatment, 35/84 (42%) patients received oral an-
tibiotics prior to hospitalization, 6/84 (7%) being prescribed more
than one antibiotic. Topical antibiotics were also administered in
6/84 (7%) patients prior to hospital admission. Treatment modalities
used during hospitalization are summarized in Table 4. Cephalexin
was prescribed to be completed at home after hospital discharge in
65/84 (77%) of patients.
Severe complications were seen in 4/84 (5%) of children (1 septic
shock due to MRSA and 3 cases of sepsis). All patients survived. We
found the mean duration of hospitalization was negatively affected
by performing skin debridement: 5.8 ± 4.1 days for patients with
debridement versus 3.6 ± 2.1 days without (P = .03).
4 | DISCUSSION
This is one of the largest case series reviews of pediatric SSSS. Our
study highlights the following: bacterial isolation with likely culprit
pathogens was more likely obtained from periorificial swabs; how-
ever, these isolates were not tested for exfoliative toxin to confirm
causality; surgical debridement in SSSS is associated with longer
hospitalization; and addition of clindamycin as an antitoxic agent
does not appear to impact clinical course.
4.1 | Isolation of staphylococci
Staphylococcal scalded skin syndrome is the result of exotox-
ins that are typically produced by staphylococci at a distant
site. Therefore, the blister fluid in SSSS bullae tends to be ster-
ile whereas the fluid in bullous impetigo will contain S aureus.2,4
Periorificial and nasopharyngeal cultures are the most likely to be
positive,2,4
as confirmed by our data (72% of patients). Additionally,
in contrast to adult data,2
blood cultures have a low yield in the
pediatric population.5-10
4.2 | Surgical debridement
Surgical debridement is usually employed in skin disease when
there is significant epidermal detachment in order to remove dead
TA B LE 2 Initial sites of involvement of clinical signs of 84
Children with SSSS
Clinical sign Initial site of involvement Cases n (%)
Erythema Head and neck 62/84 (74)
Trunk 12/84 (14)
Extremities 6/84 (7)
Folds 4/84 (5)
Exfoliation Head and neck 53/84 (63)
Trunk 10/84 (12)
Extremities 6/84 (7)
Bullae Head and neck 39/64 (60)
Trunk 8/64 (12)
Folds 8/64 (12)
Extremities 7/64 (5)
Genitalia 2/64 (3)
Abbreviation: SSSS, Staphylococcal scalded skin syndrome.

4. 4 | Pediatric
Dermatology
LIY-WONG et al.
skin and prevent superinfection (eg, toxic epidermal necrolysis),
but as the detachment in SSSS is superficial affecting the granular
layer and there is no apoptosis, in contrast to TEN, debridement
should not be recommended.11
Therefore, in SSSS careful manage-
ment of the skin with minimal handling and a clean environment
is sufficient. Some patients might benefit from dressings to cover
denuded areas, but this is not necessary in a majority of patients.
Debridement risks exacerbating epidermal detachment, increasing
the affected body surface area, and increasing the risk of metabolic
disturbance and infection.1,2
In addition, debridement is painful
and requires anesthesia. In our study, the 5 patients who under-
went debridement had a longer hospital stay. No long-term data
on the patients who underwent debridement were available to as-
sess subsequent outcomes and complications (such as scarring and
dyspigmentation).
4.3 | Choice of antibiotics
Most individuals respond to oral or intravenous antibiotic therapy,
specifically penicillinase-resistant antibiotics with activity against
staphylococci. In patients with mild disease, not experiencing signifi-
cant systemic symptoms or significant pain, oral antibiotics might be
sufficient to treat SSSS. Initial antibiotic therapy may include oxacil-
lin, nafcillin, or a cephalosporin.1,2
Clindamycin is frequently used as
an anti-toxin medication due to its ability to suppress the synthesis
of bacterial toxins.12
In our cohort, 50/84 (60%) of patients received
cloxacillin as first-line therapy. The majority of our cases with a posi-
tive periorificial culture 49/50 (98%) were due to oxacillin-suscep-
tible S aureus. Only one case was caused by methicillin-resistant
S aureus; therefore, the use of the first-line agent was justified. In
areas with a high prevalence of MRSA infection, vancomycin should
be considered. Vancomycin can also be used for individuals who do
not respond to initial therapy and experience progression of disease
despite use of antibiotics.
Although most cases of SSSS are caused by methicillin-sensi-
tive organisms, resistance to clindamycin is increasing.13
We found
clindamycin resistance in 26/50 (52%) of our cases. Clindamycin
resistance in our study was similar to that reported by Braunstein
et al13
in twenty-one patients with culture-confirmed pediatric SSSS
patients in the USA. Regional differences have been reported re-
garding antibiotic resistance patterns.10,13
One retrospective study
from China found higher rates of clindamycin resistance in SSSS of
85%, but all SSSS isolates were oxacillin-susceptible.10
A more re-
cent publication by Wang et al14
also found that SSSS-associated
isolates were more likely to be clindamycin-resistant and less likely
to be methicillin-resistant in comparison to other staphylococcal in-
fections. Clindamycin is a bacteriostatic agent favored in the set-
ting of cutaneous staphylococcal infection because of excellent skin
penetration.12
Clindamycin also inhibits bacterial toxin production,
making it a preferred agent for toxin-mediated diseases like SSSS.12
In our cohort, 31/84 (40%) of the patients received a combination
of cloxacillin with clindamycin. No statistical significance was found
regarding hospital duration and complications when comparing pa-
tients who did with those who did not receive clindamycin as an
anti-toxin medication, likely due to the high rate of resistance to
clindamycin in our cohort 26/52 (50%). Given the frequency of clin-
damycin resistance in our population and others noted above, we
strongly caution against the use of clindamycin as monotherapy for
treating SSSS.10,13
TA B LE 3 Staphylococcus aureus detection susceptibility to antibiotics in 84 patients with SSSS
Type of culture
Performed
N (%)
Positive cultures
n/N (%)
Oxacillin Clindamycin Erythromycin
Sensitive
n/N (%)
Resistant
n/N (%)
Sensitive
n/N (%)
Resistant
n/N (%)
Sensitive
n/N (%)
Resistant
n/N (%)
Blood 79 (94) 3/79 3 (100) 0 2 (67) 1 (33) NA NA
Throat 31 (37) 0 — — — — — —
Bullae 28 (33) 5 (18) 5 (100) 0 5 (100) 0 5 (100) 0
Periorificial 57 (68) 42 (74) 41 (97) 1 (3) 23 (54) 19 (45) 23 (54) 19 (45)
Abbreviation: SSSS, Staphylococcal scalded skin syndrome.
TA B LE 4 Treatment modalities during hospitalization in 84
patients with SSSS
Treatment modality
Cases
n=84 (%)
Systemic antibiotics 84 (100)
Cloxacillin 50 (60)
Clindamycin 48 (57)
Cefazolin 35 (42)
Vancomycin 11 (13)
Combination of cloxacillin and clindamycin 31 (40)
Pain medications 75 (89)
Acetaminophen 66 (78)
Morphine (single doses) 32 (38)
Ibuprofen 27 (33)
Morphine continuous infusion 17 (20)
Hydromorphone 3 (4)
Ketorolac 3 (4)
Ketamine 1 (1)
Combination of analgesics 17 (20)
Skin debridement 5 (6)
Abbreviation: SSSS, Staphylococcal scalded skin syndrome.

5. | 5
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4.4 | Complications and outcomes
Severe complications due to shock syndrome and sepsis in our
study group were low at 5%. The remaining patients in our study
responded completely to treatment, and no mortality was seen. The
prognosis for appropriately treated pediatric SSSS is good, with a
reported mortality of less than 5%.5-10,15-18
In contrast, the mortality
rate in adults is very high (40%-63%) despite aggressive treatment,
usually due to underlying diseases.2
Limitations of the study include the retrospective design and
heterogeneous clinical descriptions. The choice of antibiotic and
decision to debride were dependent on what team was consulted
first (medical versus surgical team). We did not have data on the
type of toxins in our population and their sensitivities or enough
data to draw conclusions on patients that developed complications.
Furthermore, the clindamycin data should be further explored as
changing patterns of resistance are emerging and the impact of its
role as an anti-toxin agent remains unclear.
5 | CONCLUSION
This is a large case series of pediatric SSSS that describes clinical
characteristics, management, including antimicrobial susceptibility
and outcomes. The 3 most common clinical signs identified in our pa-
tients were skin erythema, exfoliation, and tenderness. Periorificial
cultures (perianal, perioral, periocular, or nasal) were useful to iden-
tify possible causative organisms. Despite its toxin-reducing activ-
ity, clindamycin did not decrease duration of hospitalization in our
case series. Clindamycin-resistant isolates were identified in more
than half of our patients, suggesting clindamycin monotherapy for
SSSS should be avoided. Surgical debridement was associated with
prolonged hospitalization and more complications and should be
avoided in SSSS patients.
ETHICAL APPROVAL
This study was approved by the Research Ethics Board at the
Hospital for Sick Children in Toronto Canada.
ORCID
Carmen Liy-Wong https://orcid.org/0000-0002-4471-5281
Miriam Weinstein https://orcid.org/0000-0002-7783-1019
Irene Lara-Corrales https://orcid.org/0000-0002-3210-3413
Elena Pope https://orcid.org/0000-0002-3210-3413
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How to cite this article: Liy-Wong C, Pope E, Weinstein M,
Lara-Corrales I. Staphylococcal scalded skin syndrome: An
epidemiological and clinical review of 84 cases. Pediatr
Dermatol. 2020;00:1–5. https://doi.org/10.1111/pde.14470