Terminology

- SJS: Less severe condition: skin

detachment <10% of body surface
area
- TEN: detachment of > 30% body
surface
- SJS/TEN overlap: skin detachment
of 10-30% of body surface
 Epidemiology

- SJS is more common, outnumberig

TEN by as much as 3:1
- Incidence of SJS/TEN is much
higher among HIV-infected
individuals & patients with active
cancer
- It is more common in women than
in men with a male to female ratio
of 1:2
- The overall mortality rate of SJS is
30% ranging from 10% for SJS to up
to 50% for TEN
- Mortality continues to increase up
to one year after disease onset
 Drugs
- Medications are the leading trigger of
SJS/TEN in both adults & children
- The risk of SJS/TEN seems to be limited to
the first eight weeks of treatment
- The typical exposure period before
reaction onset is 4days-4weeks of first
continuess use of the drug
- Most common drugs include:
- Allopurinol
- Aromatic antiseizure medications and
lamotrigine
- Antibacterial sulfonamides (including
sulfasalazine)
- Nevirapine
- Oxicam nonsteroidal anti-
inflammatory drugs (NSAIDS)
- In children, the medications most often
are sulfonamide antimicrobials,
phenobarbital, carbamazepine,
lamotrigine, acetaminophen/paracetamol
 Mycloplasma pneumoniae infection

- Infections including Mycoplasma

pneumoniae infection, are the next
most common trigger of SJS/TEN

Other

- In over one third of SJS/TEN cases, no

cause can be identified
- Rarely reported causes of SJS/TEN
include vaccinations, systemic
diseases, contrast medium, external
chemical exposure, herbal medicines,
and foods
 HIV Infection

- Increased risk of drug reactions & 100-

fold higher risk of STJ/TEN
- Possible reasons: exposure to multiple
medications, immune dysregulation,
presence of concomitant infections,
polymorphisms of genes

Malignancy

- The risk is highest with hematologic

cancers
- Reason: the malignancy itself/
frequent immunocmpromised state/
increased exposure to potentially
causative medications
 Genetic Factors

- HLA-B*15:02 – increased risk for SJS/TEN

due to carbamazepine & othe aromatic
anticonvulsants
- HLA-B*15:11 – associated with
carbamazepine-induced SJS/TEN
- HLA-A*31:01 - associated with
carbamazepine-induced SJS/TEN
- HLA-A*24:02 – associated with
carbamazepine, lamotrigine, phenytoin
induced SJS/TEN
- HLA-B*13:01 – associated with dapsone
induced severe skin reactions including
SJS/TEN
- HLA-B*58:01 –associated with
allopurinol-induced STJ/TEN
- Genetic Polymorphism: polymorphism in
CYP2C19 gene
 Other Factors

- High doses of medications

- Systemic lupus erthematous
(SLE)
- Physical stimuli, such as
ultraviolet light or radiation
therapy
- Cell mediated cytotoxic reaction against
keratinocytes leading to massive
apoptosis
- Drugs can stimulate the immune system
by directly binding to MHC class I & T cell
receptor
- Drug-specific CD8+ cytotoxic T cells, along
with naural killer (NK) cells are major
inducers of keratinocyte apoptosis
- Various cytotoxic proteins & cytokines
such as soluble Fas ligand,
perforin/granzyme, TNF-alpha, and TRAIL
have been proposed as mediators for
extensive keratinocyte apoptosis in
STJ/TEN
- Granulysin, a cytolytic protein found in
cytotoxic T cells and NK cells, plays a key
role in the pathogenesis of SJS/TEN
- Serum levels of soluble IL-15 are
increased in patients with SJS/TEN and
appear to be correlated with disease
severity and in-hospital mortality
- The hallmark of SJS/TEN is the
keratinocyte necrosis, ranging from
partial to full-thickness necrosis of the
epidermis
- In early lesions, apoptotic keratinocytes
are scattered in the basal layer of the
epidermis, but in stablished lesions, full-
thickness epidermal necrosis and
subepidermal bullae may be seen
- A scant, perivascular, lymphohistiocytic,
inflammatory infiltrate containig a
variable amount of eosinophils is present
in superficial dermis
 Prodrome

- Fever, often exceeding 39ºC and

influenza-like symptoms precede by
one to three days the development of
mucocutaneous lesions
- Photophobia, conjunctval itching or
burning, and pain on swalloing may
be early symptoms of mucosal
involvement
- Malaise, myalgia, and arthralgia are
present in most patients
- In some patients, an exanthematous
eruption can be the harelding sign of
SJS/TEN
- Signs & symptoms that should alert
the clinician to the possibility of
SJS/TEN: fever>38ºC, mucositis, skin
tenderness, and blistering
 Cutaneous Lesions

- Begin with ill-defined, coalescing,

erythematous macules with purpuric
centers, although many cases of
SJS/TEN may present with diffuse
erythema
- The skin is tender to touch, skin pain
can be out of proportion to the
cutaneous findings
- Lesions start on the face and thorax
before spreading to other areas and are
symmetrically distributed
- The sculp is typically spared, and palms
and soles are rarely involved
- Atypical target lesions with darker
centers may be present
- As the disease progresses, vesicles and
bullae form, and within days the skin
begins to slough
 Cutaneous Lesions

- Nikolsky sign (ie, the ability to extend

the area of superficial sloughing by
applying gentle lateral pressure on the
surface of the skin at an apparently
involved site) may be positive.
- The Asboe-Hansen sing or “bulla spread
sig” (a lateral extension of bullae with
pressure) may also be present
 Mucosal Lesions

- Mucosal involvement occurs in 90% of

cases: can precede or follow skin eruption
- Painful crusts and erosions may occur on
any mucosal surface
- Oral: painful hemorrhagic erosions
covered with a grayish-white membrane
- Ocular: severe conjunctivitis with a
purulant discharge, corneal ulceration,
anterior uveitis or panophthalmitis, pain
and photophobia
- No ocular involvement: 0 (none)
- Conjunctival hyperemia: 1 (mild)
- Either ocular surface epithelial defect
or pseudomembrane formation: 2
(severe)
- Both ocular suface epithelial defect
and pseudomembrane formation: 3
(very severe)
 Mucosal Lesions

- Urogenital: urethritis in two-thirds of

patients -> urinary retention, genital
erosions, vulvovaginal involvement
with erosive and ulcerative vaginitis,
vulvar bullae, vaginal synechiae,
vulvovaginal adenosis, long-term
anatomic sequelae (labial and vaginal
adhesions and stenosis, obstructed
urinary stream, urinary retention,
recurrent cystitis, hematocolpos)
- Other: pharyngeal mucosa is affected
in nearly all patients. Tracheal,
bronchial, and esophageal
membranes are less frequently
involved
 Laboratory Abnormalities

- Anemia and lymphopenia are common

- Eosinophilia is unusual
- Neutropenia is present in one-third of
patients: correlated with poor
prognosis
- Hypoalbuminemia, electolyte
imbalance, and increased blood urea
nitrogen and glucose may be noted in
severe cases, due to massive
transdermal fluid loss and
hypercatabolic state
- Serum urea nitrogen > 10mmol/L and
glucose >14 mmol/L are markers of
disease severity
- Mild elevations in serum
aminotransferase levels (2-3 times the
normal value) are present in one-half
of patients with TEN, while over
hepatitis occurs in 10%
 Clinical course

- The acute phase of SJS/TEN lasts 8-12

days and is characterized by persistent
fever, severe mucous membrane
involvement, and epidermal sloughing
that may be generalized and result in
large, raw, painful areas of denuded
skin
- Re-epithelialization may begin after
tow-four weeks
- Skin that remained attached during the
acute process may peel gradually, and
nails may be shed
 Differential Diagnosis

- Erthema multiforme: presents with

typicl target lesions, predominantly
located on the extremities
- Erythroderma and erythemous drug
eruptions: exanthematous drug
eruptions lack mucosal invlovement
and the prominent skin pain of TEN
- Acute generalized exanthematous
pustulosis
- Generalized bullous fixed drug
eruption
- Phototxic eruptions
- Staphylococcal scaled skin syndrome
- Paraneoplastic pemphigus
- Linear IgA bullous dermatosis
- Chikungunya fever
 General Priciples

- Patients with suspected SJS/TEN

require immediate in-hospital
evluation for diagnosis confirmation
and evaluation of severity, and
initiation of supportive treatment
- The evaluation of severity is done by
SCORTEN score and referral to
intensive care or burn unit should be
made
 Prompt withdrawal of Drugs

- For patients suspected of SJS/TEN

induced by drugs, ealy identification
and withdrawal of the offending agent
may improve the prognosis

Supportive Care

- Wound care: the extent of epidermal

detachment should be evaluated daily
or every few days, depending upon
the type of wound management, and
is expressed as the percentage of body
surface area involved
 Supportive Care

- Fluids and nutrition: replacement volumes

are approximately one-third lower than
those needed for burn victims
- Fluid requirement during the forst 24
hours: 2ml/kg of body weight
multiplied by percentage of body skin
area skin detachment
- Room temprature should be
increased to 30-32ºC
- Oral feeding via an Ng-tube if
necessary

Pain Control

- Mild pain (intensity<4) can be treated with

nonopioid analgesics (acetaminophen,
ibuprofen)
- Opioids are usually required for moderate
to severe pain
 Prevention and Treatment of infections

- Sterile handling
- Antiseptic solutions containing
octenidine, polyhexanide, or
chlorhexidine or silver nitrate
preparations
- Repeated cultures of the skin, as well as
blood, catheters, gastric, and urinary
tubes, should be obtained at 48-hour
intervals
- Antibiotic choice should be based upon
specific culture data whenever possible

Prevention of vulvovaginal sequelae

- Early gynecologic examination in all

females
 Ocular Management

- Saline rinses can be used to clean the

eyes and eyelids
- Multiple daily lubrication with artificial
tears
- Ophthalmic preperations containing
topical corticosteroids and broad-
spectrum antibiotic 4-6times/day in
conjunctival hyperemia
 Adjunctive Therapies

- Several immunosupressive or
immunomodulating therapies have
been used in clinical practice,
including systemic corticosteroids,
intravenous immune globulin (IVIG),
cyclosporine, plasmapheresis, and
anti-TNF monoclonal antibodies
- None of these therapies have been
studied in RCTs except thalidomide,
which as found to be harmful
- Their use is based upon clinical
experience and local guidelines