This document discusses Staphylococcal Scalded Skin Syndrome (SSSS). SSSS is caused by toxins produced by Staphylococcus aureus that destroy skin cell connections. It typically affects children under 5 and presents with widespread erythema, flaccid blisters, and superficial desquamation. Diagnosis is made clinically but histology can help differentiate from other conditions. Treatment involves antibiotics to eliminate the bacterial infection and supportive care like gentle wound dressing. Prognosis is generally good but complications can include secondary infection.

1. Staphylococcal Scalded Skin Syndrome
Infections of the skin, soft tissue,
muscle and associated systems
Wilson Martín Agüero Echeverría
MD, MScID, FIDSA, FAAP
Asunción, Paraguay
2020

2. Factors controlling the skin’s microbial load
The limited amount of moisture present
Acid pH of normal skin
Surface temperature is not optimal for many pathogens
Excreted chemicals such as sebum, fatty acids and urea
Competition between different species of the normal flora

3. Infections of the skin
❖ Structural barrier
❖ Normal flora
❖ Arid areas (forearm, back): Gram-positive bacteria and yeast
❖ Moister areas (groin, armpit): Gram-negative bacteria

4. If the microorganisms breach the stratum corneum…
❖ Epidermal Langerhans cells —- cytokines
❖ Neutrophils are attracted
❖ Complement is activated via the alternative pathway

5. An immunological approach
Immune response in skin
(1) Capture of the antigen.
(2) Processing of the antigen and presentation on the surface of the APC
(3) Migration via the afferent lymphatics to the skin-draining lymph node.
(4) They present the processed antigen to naïve T-cells (CD45RA+) causing T-cell
maturation, activation and proliferation.
(5) Mature activated T-cells (CD45RO+) express CLA antigen.
(6) CLA antigen is able to bind to E-and P- selectins expressed by endothelial cells in the
dermis.
(7) This interaction stimulates T-cells to express LFA-1 and VLA-4 and endothelial cells to
produce intercellular and vascular adhesion molecules (ICAM and VCAM).
(8) The interaction of these molecules allows the activated T-cells to migrate through the
postcapillary venules into the dermis.
(9) The activated T-cells can then migrate to areas of antigen expression in the dermis or
epidermis.
(10) The activated T-cell can secrete cytokines such as IFN-γ or TNF-α and recruit other
immune effector cells, including neutrophils.

6. 3 lines of attack
❖ 1. Breach of intact skin (papillomavirus)
❖ 2. Skin manifestations of systemic
infections (blood-borne spread or direct
extension such as actinomycotic fistula)
❖ Toxin-mediated skin damage (scarlet fever,
toxic shock syndrome)

7. http://cmr.asm.org/Downloadedfrom

8. THE ROLE OF CELL DEATH IN HOMEOSTASIS AND THE CONTROL OF THE SKIN’S
IMMUNE RESPONSE
The phenomenon of cell death is intrinsically linked to the cellular life cycle and
TABLE 2 Types of cell death and causes, morphology, mechanisms, or factors that lead to
its induction
Type of skin cell death Cause
Necrosis Tuberculosis
Apoptosis Leprosy
Autophagy Zika virus infections
Pyroptosis Leishmaniasis
Ferroptosis ROS, RNS, glutathione
Necroptosis Staphylococcus aureus infection
Quaresma

9. Direct entry into skin of bacteria and fungi
Structure involved Infection Common cause
Keratinized epithelium Ringworm
Dermatophyte fungi (Trichophyton, Epidermophyton and
Microsporum)
Epidermis Impetigo Streptococcus pyogenes/Staphylococcus aureus
Dermis Erysipelas Streptococcus pyogenes
Hair follicles Folliculitis, boils, carbuncles Staphylococcus aureus
Subcutaneous fat Cellulitis Streptococcus pyogenes
Fascia Necrotizing fasciitis Anaerobes and microaerophiles, usually mixed infections
Muscle Myonecrosis gangrene Clostridium perfringens (and other clostridia)

17. Rose spots
Enteric Fever
Mary Mallon (23 September 1869 –11 November 1938)
Mary was the first person in the United States to be identified as an asymptomatic carrier of typhoid and
worked from 1900 to 1907 as a cook for affluent families. Outbreaks of typhoid occurred where she
worked and she would often then move onto a different family.
In 1906 a family hired typhoid researcher George Soper, who believed Mallon might be the source of the
outbreak, linking her to all the outbreaks but failed to convince her to provide urine and stool samples.
In 1907 she was finally arrested and quarantined for 3 years by which point she had large media attention
and the nickname ‘Typhoid Mary’ was given.
On February 1910 Mallon agreed to change her occupation and was released.
Unfortunately the provisions for a new career in a laundrette did not provide the same career satisfaction
nor pay and she returned to cooking. She was arrested again and refused to have a cholecystectomy. Her
second quarantine lasted from 1915 to 1938 when she died of stroke aged 68

19. Staphylococcal infections
❖ Self-inoculation or acquired by contact
❖ Nasal carriers, recurrent boils
❖ Intense inflammatory response
❖ Influx of neutrophils
❖ Walled off by fibrin

20. S. aureus needs drainage and antibiotics
❖ Isolation and further characterization in hospital patients and staff
❖ MSSA: beta-lactamase producers
❖ MRSA: vancomycin, linezolid, quinupristin-dalfopristin, daptomycin
❖ Mupirocin creams
❖ Triclosan soaps

21. Ritter’s disease (newborn) or Lyell’s disease
❖ Staphylococcal scalded skin syndrome (SSSS) or toxic epidermal necrosis
❖ Ritter’s disease or penfigo neonatorum
❖ Sporadically or in outbreaks
❖ Scalded skin syndrome toxin or exfoliatin
❖ Destruction of intercellular connections
❖ Large blisters that are destroyed in 1-2 days

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33. SSSS
❖ More frequent under 5 yo
❖ Incidence in USA: 8 - 45 cases/million children = 1/million adults
❖ 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

34. SSSS
❖ Exotoxins —- serine protease —— desmoglein 1 —- keratinocyte-to-
keratinocyte adhesion in the stratum granulosum.
❖ Hematogenous dissemination of the exotoxins from —— impetigo, bacterial
conjunctivitis, iatrogenic wounds, staphylococcal pneumonia, pyomyositis,
septic arthritis, endocarditis, etc

38. Prodromes
❖ Rare reports indicate staphylococcal mastitis as a maternal source of infection
for breastfed newborns
❖ The incubation period from S. aureus infection to SSSS usually ranges from 1
to 10 days.
❖ Staphylococcal scalded skin syndrome in a breast-fed infant. Katzman DK, Wald ER. Pediatr Infect Dis J. 1987;6(3):295
❖ Staphylococcal-scalded skin syndrome: evaluation, diagnosis, and management. Leung AKC, Barankin B, Leong KF. World J Pediatr. 2018;14(2):116. Epub 2018 Mar 5.

39. SSSS susceptibility
❖ The susceptibility of young children 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
❖ Staphylococcal scalded skin syndrome: diagnosis and management in children and adults.Handler MZ, Schwartz RS.
J Eur Acad Dermatol Venereol. 2014;28(11):1418

40. Cutaneous findings
❖ The earliest: macular erythema and skin pain, initially accentuated in the skin
folds.
❖ The erythema may be subtle, can wax and wane.
❖ Generalized erythema usually develops within 48 hours.
❖ Flaccid bullae begin to appear in areas of skin erythema, resulting in a wrinkled
appearance.

41. Cutaneous findings
❖ Shallow erosions may also occur in sites subject to friction, such as in the perianal region.
❖ Sheet-like, superficial desquamation with large patches of moist, erythematous, shiny skin.
❖ Thick crusting and radial fissuring around the mouth, nose, and eyes.
❖ The crusting, fissuring, and associated erythema is classically referred to as SSSS "sad face."
❖ The perioral crusting has been likened to dried oatmeal in its appearance.

42. SSSS clinical picture
❖ Associated signs and symptoms:
❖ Skin pain
❖ Fever
❖ Irritability
❖ Malaise
❖ Poor feeding
❖ Temperature instability.

43. Complications
❖ Cutaneous erythema and pain typically subside in 2-3 days.
❖ Erosions and crusted regions improve in 1-2 weeks.
❖ Postinflammatory hyperpigmentation or hypopigmentation.
❖ Scarring typically does not occur.
❖ Secondary infection, septicemia, hypovolemia, electrolyte imbalance, and death

44. Diagnosis
❖ Clinical assessment
❖ Histopathologic findings
❖ Bacterial cultures of the infectious focus

45. 1. Clinical assessment
❖ History
❖ Young children/adult with an impaired immune system or impaired renal function
❖ Initial onset of erythema in skin folds followed by rapid progression(eg, within 48
hours)
❖ Associated skin pain
❖ Prodrome or concurrent fever, irritability, or poor oral intake

46. 1. Clinical assessment
❖ Physical findings
❖ Extensive, blanchable skin erythema
❖ Flaccid bullae, superficial desquamation, and shallow erosions
❖ Absent mucous membrane involvement
❖ Evidence of concurrent cutaneous, conjunctival, or internal staphylococcal infection
❖ Positive Nikolsky sign❖

47. 1. Clinical assessment
❖ SSSS versus toxic epidermal necrolysis (TEN)
❖ SSSS is less likely to exhibit pinpoint bleeding, due to the more superficial
lesion.

48. 2. Histopathologic examination
❖ It is necessary when diagnostic uncertainty remains despite a careful history
and physical examination.
❖ The primary goal is to identify the level of epidermal cleavage and
differentiate SSSS from conditions such as TEN.

49. 3. Cultures
❖ Intact blisters in SSSS are sterile.
❖ Cultures should be taken from cutaneous or mucosal sites of suspected primary infection.
❖ Blood cultures may be appropriate in children at risk for bacteremia (a febrile neonate, an
immunocompromised child, or child with a serious illness).
❖ S. aureus bacteremia is relatively common in adults with SSSS

50. Differential diagnosis - Burns
❖ Chemical burns, thermal
burns, or sunburn
❖ The history of an insult
❖ Distribution of the skin
changes

51. Differential diagnosis - Bullous impetigo
❖ Caused by the same toxin-producing strains of S. aureus associated with SSSS.
❖ Collarettes of scale at sites of ruptured bullae
❖ Intertriginous involvement is common.
❖ In contrast to SSSS, cultures of bullae will demonstrate S. aureus.
❖ It may progress to SSSS.

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54. Differential diagnosis - Stevens-Johnson syndrome
❖ Targetoid skin lesions, fever, and skin pain.
❖ Causes: medications, followed by infections.
❖ A biopsy is helpful.
❖ Subepidermal blistering and full-thickness epidermal necrosis resulting in deeper erosions.
❖ Mucosal involvement is present (but absent in SSSS).

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57. Differential diagnosis - Toxic shock syndrome
❖ Toxin-mediated systemic bacterial infections
❖ The inciting infections: localized abscess, pyomyositis, or superinfection of a retained foreign body.
❖ Widespread, blanchable, cutaneous erythema
❖ Conjunctival injection
❖ "Strawberry tongue”
❖
❖ Fever
❖ Hypotension
❖ Lack of periorificial crusting
❖ Absent bullae or desquamation
❖ Negative Nikolsky sign.

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60. Differential diagnosis - Scarlet fever
❖ Group A Streptococcus
❖ Fever and a widespread cutaneous eruption
❖ Association with streptococcal pharyngitis.
❖ A "sandpaper-like" cutaneous eruption
❖ The perioral crusting, skin fragility, and skin pain seen in SSSS are absent in scarlet fever.

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63. Pastia’s lines

64. Filatow’s sign

65. Differential diagnosis - Kawasaki disease
❖ The cutaneous manifestations include erythema in flexural folds.
❖ Fever, conjunctivitis, "strawberry tongue," cervical lymphadenopathy, and
swelling of their hands and feet.
❖ Does not typically have the positive Nikolsky sign, skin fragility, skin pain, or
perioral crusting

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67. Differential diagnosis - Pemphigus foliaceus/ vulgaris
❖ Autoimmune blistering disorders
❖ Pemphigus foliaceus involves targeting of desmoglein 1
❖ In pemphigus vulgaris, desmoglein 3 is the targeted antigen and blistering occurs lower
in the epidermis, resulting in deeper erosions and characteristic mucosal erosions
❖
❖ A skin biopsy with direct immunofluorescence microscopy is used to confirm the diagnosis.

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71. Differential diagnosis - miscellanea
❖ Epidermolysis bullosa
❖ Epidermolytic ichthyosis
❖ Bullous mastocytosis
❖ Cutaneous candidiasis in neonates

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77. Management
❖ Eradication of the causative staphylococcal infection
❖ Supportive care
❖ Healing
❖ Reduce discomfort
❖ Minimize complications.

78. Management
❖ 1. Admission
❖ PICU
❖ Burns unit

79. Management - Antibiotics
❖ Intravenous treatment
❖ Oxacillin
❖ Cefazolin
❖ Cefuroxime
❖ Clindamycin: not recommended (high R tases)
❖ Vancomycin.

80. Management - Supportive care
❖ Prevention of dehydration
❖ Gentle skin care:
❖ Minimal use of adhesives, tourniquets, compression devices, and tape is imperative.
❖ Bathing is often avoided for the first 48 hours
❖ After bathing, skin should be patted rather than rubbed dry
❖ Wound care:
❖ Petroleum jelly, nonadherent dressings
❖ Dressings should be changed daily, and administration of an analgesic prior to dressing
changes may be necessary

81. Prognosis
❖ 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

82. Prevention
❖ Minimizing risk for transmission
❖ Hand hygiene
❖ Trimming nails.
❖ Screening for S. aureus colonization of health care workers and caretakers