A brief discussion of a very common bacterial infection presenting as fever and skin rash following skin infection or use of tampons. Affecting adults especially women. Very helpful for medical students, ER doctors, dermatologists, nurses. References from dermatology textbook Rooks.

1. Bacterial Exanthems Part I:
Toxic Shock Syndrome:

2. Introduction:
• Exanthem is the name given to
a widespread rash that is usually accompanied
by systemic symptoms such as fever, malaise and
headache.
• It is usually caused by an infectious condition and
represents either a reaction to a toxin produced by
the organism, damage to the skin by the organism,
or an immune response.

3. Classification of Bacterial Exanthems:
• Staphylococcal toxin infections:
– Toxic shock syndrome (TSS)
– Staphylococcal scalded skin syndrome (SSSS)
• Streptococcal toxin infections:
– Scarlet fever
– Streptococcal toxic shock-like syndrome (STSS)
Exanthem of Unknown Etiology:
• Kawaski Disease

4. Toxic Shock Syndrome (TSS):

5. Definition and nomenclature:
Serious life‐threatening illness characterized by
fever, acute erythema followed by desquamation,
circulatory shock and multisystem disease
mediated by one or more bacterial toxins
elaborated by Staphylococcus aureus or
Streptococcus pyogenes.
Synonyms:
• Staphylococcal TSS
• Streptococcal TSS

6. Causative organisms:
• Staphylococcus aureus.
• Streptococcus pyogenes

8. Introduction and general description:
• Historically most cases were reported shortly after
the introduction of super‐absorbent tampons in the
1970s.
• Many menstruating women using these highly
absorbent tampons presented acutely unwell with
fever, low blood pressure and multi-organ failure
leading to a death.
• This particular type of tampon is no longer
manufactured and the number of cases has
consequently declined dramatically.

9. Epidemiology:
Incidence and prevalence
• Approximately 1–17/100 000 tampon users per annum.
Age
• Any age but is more common at the extremes of age and in
menstruating women (15–40 years).
Sex
• Historically, it was more common in females.
Ethnicity
• Black women (Aged 13-40 years) in the USA had lower
antibody titres to TSS toxin 1 (TSS‐1) than white or Hispanic
women, suggesting the former are more at risk of menstrual
TSS

10. An awareness
poster from 1985

11. Associated diseases:
• Recent chickenpox infection,
• Cellulitis
• Necrotizing fasciitis,
• Underlying HIV or
• Internal malignancy,
• Alcohol misuse and
• Diabetes

12. Pathophysiology:
(a)Predisposing factors:
• Staphylococcal infection of any
severity, at any site, at any age and in either sex may cause
TSS.
• TSS due to Tampons was the result of introduction of the
Staphylococci by hand or from perineal skin. Appropriate
conditions for Satphylococcal growth were provided in the
medium of the menstrual blood, facilitated in some way by
the tampon.
• Postpartum Women are also at risk in addition to using
internal barrier type contraception such as the diaphragm.

13. Pathophysiology Contd:
• Toxic shock syndrome toxin 1 (also called
staphylococcal enterotoxin F / pyrogenic exotoxin C
or TSS-1 toxin), is produced by S. aureus and is
believed to be the main bacterial mediator of the
disease.
• More recently, staphylococcal enterotoxin B was
also identified.
• TSS-1 Toxin is able to stimulate T‐lymphocyte
proliferation in a non‐antigen‐specific manner.
• This results in fever, inflammation and shock.
TSS Due to Streptococcus:
• May be cause by a re-emergent scarlet fever toxin A
produced by Streptococcus pyogenes.

14. Pathology:
• No specific histological features.
• A perivascular mononuclear cell infiltrate and
papillary oedema may occur in the dermis.
• In cases with blister formation the split is
subepidermal.

15. Clinical features:
(a) History
In menstrual TSS, women are usually about 5 days into their menstrual bleeding when they present with
malaise and fever.
(b) Presentation
• Fever ≥ 38.9⁰C
• Rash:
– May be the presenting feature or appear within the first day.
– Appears as widespread macular erythema but scarlintiform and papulopustular eruptions also noted. Clears
within 3 days.
– Marked edema of hands and feet with blistering.
• Circulatory Shock:
– Is often rapid in onset and severity,
– Does not respond to intravenous fluid replacement
– Acute renal impairment frequently coexists.
• Multi-system Involvement: 3 or more of the following:
– Gastrointestinal: vomiting or diarrhea at onset of disease.
– Muscular: severe myalgia or creatine phosphokinase of at least twice the upper limit of normal for the laboratory
– Mucus Membrane: vaginal, bladder, oral or conjunctival hyperemia or ulceration
– Renal: Blood Urea Nitrogen or creatinine at least twice the upper limit OR Pyuria in the absence of Urinary tract
infection
– Hepatic: Total bilirubin, ALT, AST twice the upper limit of normal.
– Hematologic: Thrombocytopenia (≤100,000/mm3) causes retiform purpura in the peripheries.
– Central Nervous System: disorientation or altered consciousness without focal neurological signs when fever and
hypotension are absent.

16. Late Clinical Features:
• Towards the end of the second week, majority of patients develop a widespread, itchy,
maculopapular sometimes urticarial rash.
• Desquamation is highly characteristic occurring 10–21 days after onset. May be confined to
the fingertips, palmoplantar skin or may be generalized. (See picture below)
• Reversible patchy alopecia or telogen effluvium
• Transverse ridging and partial loss of nails.

17. Figure 1: Diffuse erythroderma, purpura, and petechiae with severe generalized
edema (A). Erythroderma, livid swelling, confluent bullae, and diffuse
desquamation of the right leg (B, C).

19. Differential diagnosis
• Septic shock
• Kawasaki disease: differentiated by prolonged fever,
cardiac involvement, generalized lymphadenopathy
and absence of peripheral shock.
• Staphylococcal Scarlatina
• Ehrlichosis
• Clostridium sordellii infection: The disease
resembles TSS syndrome except that there is no
associated rash; it may follow postpartum infections

20. Complications and co‐morbidities:
Toxic shock syndrome results in multiorgan failure
manifest as:
– Adult respiratory distress syndrome,
– Acute or chronic renal failure
– Disseminated intravascular coagulation.

21. Disease course and prognosis:
• Treatment in a high dependency unit with prompt
use of appropriate intravenous antibiotics, most
patients recover over about 3 weeks;
• Mortality rate remains at about 7%.

22. Investigations:
• Confirmation through microbiological cultures.
Microbiological swabs from wounds and from the
vagina of menstruating or postpartum females
should also be taken.
• Several sets of blood cultures should be taken.
• Routine biochemistry:
– Raised creatinine which frequently precedes
hypotension.
– Raised creatine phosphokinase
– Increased total bilirubin, ALT and AST
• Complete Blood Count:
– Thrombocytopenia

23. Management:
• Tampons if present should be removed and infected wounds debrided.
• Intensive general supportive measures are essential such as fluid resuscitation and
ventilatory support commenced.
• Patients may require noradrenaline circulatory support and dialysis.
• Low‐dose systemic corticosteroids reduced the duration and dose of vasopressor
agents in septic shock and ameliorates septic shock but does not reduce mortality
at day 28.
• Synthetic human monoclonal antibodies: against staphylococcal enterotoxin B are
protective against TSS in mice and enhance survival.
• Intravenous clindamycin (600–900 mg three times daily) should be given as first
line treatment as this is highly effective against most strains of S. aureus and S.
pyogenes, and is known to reduce toxin production.
• Some physicians give additional benzylpenicillin sodium (penicillin G, 2.4–4.8 g
daily in four divided doses) or vancomycin (1–1.5 g every 12 h) to ensure both
staphylococcal and streptococcal organisms are adequately covered.
• Intravenous antibiotics are usually continued for up to 1–2 weeks depending on
the clinical response.

24. TSS Management Flowchart:

25. Future topics to be discussed:
• Scarlet Fever
• Staphylococcal scalded skin syndrome
• Kawaski disease.
Previously Discussed Topics:
• Warts: Common warts, anogenital warts, warts in
immunocompromised patients, epidermodysplasia
verruciformis.
• Viral Exanthems: Measles, Rubella, Erythema
Infectiosum, Roseola Infantum, Cytomegalovirus,
Infectious mononucleosis.