INTRODUCTION• Superantigens are a group of microbial and viral

proteins that cause polymorphic T cell stimulation and massive release of cytokines.

• Unlike conventional antigens, superantigens:

Exert their effects as globular intact proteins.

Are not MHC restricted.

Recognize and bind to variable region of T cell receptor(Vβ).

Have a high responding frequency for T cells(20-30%) against antigens(0.01- 0.1%).

• Generate large number of T cells with skin homing receptors (Cutaneous Lymphocyte Antigen).

APC

MHC 2

Ag

T cell

Cα Cβ

Vα Vβ

APC

MHC 2

T cell

Cα Cβ

Vα vβ

S

A

IL-6

IL-1

TNFα

CLASSIFICATION

TOXIC SHOCK SYNDROME

• Inflammatory response characterized by fever, rash,

hypotension and multiorgan dysfunction

• Represents the severe end of spectrum of superantigen

mediated diseases.

• First described in 1978 in children with Staph. aureus

infection.

• 1980s…… reports of epidemics in women using highly

absorbable vaginal tampons.

CAUSES

Staphylococcus aureus

Toxic Shock Syndrome Toxin(TSST-1):

• Predominant toxin associated with menstrual related cases.

• Unique ability to cross mucosal surfaces.

• Also causes less than half of the cases of non- menstrual TSS.

Staphylococcal Enterotoxin B & C (SEB & SEC):

• Cause of half of the cases of non-menstrual TSS.

Group A Streptococcus

Streptococcal Pyrogenic Exotoxin A (SPEA):

• Accounts for majority of Streptococcal TSS cases

Streptococcal Pyrogenic Exotoxin B & C (SPEB & SPEC)

Non Group A Streptococcus

CLINICAL FEATURES OF STAPHYLOCOCCAL TSS

• Menstrual TSS ---- associated with use of highly absorbent vaginal

tampons.

• Non- menstrual TSS ---- associated with post surgical wounds,

sinusitis, osteomyelitis, influenza, intravenous drug abuse, burn

wounds and gynaecological post partum infection.

• TSS begins with symptoms of fever, sore throat, myalgia and diarrhoea

or vomiting.

• Macular rash begins on the trunk and extends to the periphery & can

involve palms and soles. Later changes to scrletiniform rash.

• Non purulent conjunctival hyperemia, pharyngeal inflammation and

strawberry tongue are invariably present.

• Hypotension, altered mentation, fainting and overt shock occur.

• Rash desqumates in 1-2 weeks.

• Blood cultures positive in 10% cases only

CLINICAL FEATURES OF STREPTOCOCCAL TSS

• Streptococcal TSS ---- result of skin infection in 80% cases.

• Wounds appear to be the most common type of causative

infections.

• Also described as a complication of Varicella and influenza A.

• Initial presentation is skin pain localized to an extremity.

• Later erythema with edema develops, then cellulitis with

necrotising fasciitis and myositis occurs with concomitant

bloodstream invasion and herald of Toxic Shock Syndrome.

• Blood cultures are positive in more than 50% cases.

DIFFERENTIAL DIAGNOSIS

• Septic shock

• Staphylococcal exfoliative syndromes

• Rocky Mountain Spotted Fever

• Viral Hemorrhagic shock

• Measles

• Leptospirosis

• Stevens Johnson syndrome

• Kawasaki syndrome

• Scarlet fever

TREATMENT

• Remove the inciting cause

• Supportive care

• β-lactamase resistant antibiotics (e.g. Nafcillin): cause bacterial lysis and cause initial rise in TSST-1, so given with clindamycin (which inhibit bacterial protein toxin production).

• Vancomycin: due to rise in MRSA cases.

• IVIG in severe and recalcitrant cases.

• Systemic corticosteroids?

PROGNOSIS

• Mortality rate in Staphylococcal TSS is

approximately 5%, mostly because majority of

cases occur in otherwise healthy young individuals.

• Mortality rate in Streptococcal TSS is more than

30%.

• Recurrences seen in upto 20% cases.

SCARLET FEVER

• ‘Scarlatina’ in older literature.

• Characterised by exudative pharyngitis, fever and rash.

• Caused by Pyrogenic exotoxin producing Group A beta hemolytic Steptococcus.

• Disease of school going children, children <2 yrsprotected by maternal antiexotoxin antibodies.

• 80% children have antibodies by 10yrs

• Seen in winter & spring, associated with close contact & overcrowding.

• Transmission: Aerosol / Fomites / contaminated food.

• Combination of delayed type hypersensitivity and superantigen mediated processes.

• Usually evolves from a tonsillar/pharyngeal focus.

• 10% children with strep throat will develop scarlet fever.

• Can arise from infections of skin & soft tissue, surgical wounds(Surgical Scarlet fever) or the uterus (Puerperal Scarlet fever).

• Incubation period: 12 hours – 7 days.

• PRODROME: pharyngitis, headache, vomiting, abdominal pain & fever.

• SANDPAPER LIKE & BLANCHING RASH (1-2 days later): starts from neck, then to trunk & extremities, spares the palms & soles. ‘SUNBURN WITH GOOSE PIMPLES’

• Flushed face with CIRCUMORAL PALLOR

• PASTIA’S LINES: Confluent petechiae due to increased capillary fragility along the skin folds.

• Tonsils: edematous & erythematous

• FORCHHEIMER’S SPOTS: petechiae & red macules on soft

palate & uvula.

• WHITE STRAWBERRY TONGUE (0-2 days): White coated

tongue with red, edematous papillae.

• RED STRAWBERRY TONGUE (after 2 days): After

desquamation red tongue with prominent papillae.

• Tender anterior cervical lymphadenopathy.

• DESQUAMATIVE PHASE starting from face, involving

fingers & palms. Lasts from 1 – 4 wks.

• Diagnosis confirmed by Rapid Streptococcal Test or throat

culture.

DIFFERENTIAL DIAGNOSIS

• SSSS

• Kawasaki syndrome

• Atypical drug hypersensitivity reactions

• Staphylococcal scarlet fever

COMPLICATIONS

• Suppurative: Peritonsillar abscess, pneumonia, sinusitis, meningitis

• Non-suppurative: Acute Rheumatic fever, Glomerulonephritis

TREATMENT & PROGNOSIS

• Antibiotics: Penicillin & Erythromycin group

• Supportive Care

• Pre- antibiotic era: 20% mortality

• Presently: <1% mortality

STAPHYLOCOCCAL SCARLET FEVER

• Caused by Staphylococcal Enterotoxin B (SEB),

homologous to SPEA.

• Lack of pharyngitis.

• Scarlatiniform rash, but tender.

• Within few days, thick flakes develop & entire skin

desquamates.

• Not associated with rheumatic fever or glomerulonephritis.

• Previously considered to be a milder / abortive form of

Staphylococcal Scalded Skin Syndrome.

RECALCITRANT ERYTHEMATOUS

DESQUAMATING DISORDER(REDD)

• First described in 1992.

• Majority of patients have AIDS.

• Clinical features resemble Toxic Shock Syndrome,

but diagnostic criteria is not met

• Prolonged disease lasting for months with delayed

desquamation of diffuse, macular, erythematous

rash.

TOXIN MEDIATED ERYTHEMA

• Also called RECURRENT TOXIN

MEDIATED PERINEAL EYTHEMA.

• First described in 1996.

• Striking diffuse macular perineal

erythema within 24-48 hours of

pharyngitis with toxin producing

Group A Streptococcus or

Staphylococcus aureus.

• Clinical findings of Scarlet fever.

• Fever, hypotension and other

systemic signs of Scarlet fever /

TSS are ABSENT.

• Recurrences are common.

DISEASES INITIATED AND/OR

EXACERBATED BY SUPERANTIGENS

1. PSORIASIS

a) Guttate Psoriasis:

• Develops after Group A Stretococcal pharyngitis

• Superantigen mediated systemic activation of T cells and

resultant oligoclonal activation of keratinocytes.

b) Flaring of Psoriasis:

• Increased levels of keratinocyte MHC II expression in

patients of psoriasis, increasing cutaneous reactivity to

superantigens

2. AUTOECZEMATIZATION (ID) RESPONSE

• Because of ability of superantigens to home T cells to the skin,

superantigen producing Staphylococcus aureus or group A

Streptocoocus are believed to be the trigger for id response.

3. ATOPIC DERMATITIS

• Atopic patients have universally been found to harbor Staph.

aureus. Many atopic patients have Ig E antibodies that recognize

superantigens. Thus, they act as allergens in atopic patients and

cause disease flares.