The differential diagnosis of SJS/TEN includes:

Erythroderma and erythematous drug eruptions - Erythematous drug reactions are

commonplace. The generalized and symmetric maculopapular erythema of a drug
eruption can mimic early SJS/TEN. However, erythematous drug eruptions lack mucosal
involvement as well as the ill-defined but prominent skin pain of TEN. Treatment of
erythematous drug reactions includes withdrawal of possible causative agents and
supportive measures (eg, antihistamines for pruritus).

Pustular drug eruptions - Pustular drug reactions, including acute generalized

exanthematous pustulosis (AGEP), may also be severe and mimic early SJS/TEN. AGEP
is an eruption consisting of non-follicularly centered pustules that often begin on the neck
and intertriginous areas. Most commonly, AGEP is caused by beta-lactam antibiotics,
occurring within a few days of ingestion. The lesions are not associated with pain, and
mucosal involvement is rare. The pustules of AGEP may coalesce and slough, but this
occurs during resolution of the disorder, and is not present during the evolving phase of
the disease. Treatment of pustular drug reactions includes withdrawal and supportive
measures.

Phototoxic eruptions - Phototoxic eruptions are caused by direct interaction of a

chemical with sunlight to yield a byproduct toxic to the skin. The most common
phototoxic reactions to be confused with SJS/TEN are those that are due to oral
ingestants. As an example, fluoroquinolones may yield a phototoxic reaction, which can
lead to widespread epidermal sloughing. Important clues to the presence of a phototoxic
eruption include recent sun exposure, known phototoxic qualities of certain medications,
and locations of the lesions on sun-exposed areas. When sloughing is marked, the patient
with a severe phototoxic reaction is managed in a burn unit, much like a patient with
SJS/TEN.

Toxic shock syndrome - Toxic shock syndrome (TSS) is classically caused by

Staphylococcus aureus, although a similar disorder can be caused by toxin-elaborating

strains of Group A streptococci. Compared to SJS/TEN, TSS presents with more

prominent

involvement

of

multiple

organ

systems.

TSS is caused by elaboration of specific bacterial toxin(s) from staphylococci or

streptococci that act as superantigens, non-specifically activating large numbers of T
lymphocytes. These disorders are described briefly here and presented in detail
elsewhere.
TSS develops acutely in healthy individuals, particularly young women, typically (but
not

always)

within

days

of

menstruation

or

surgical

procedure.

Cutaneous manifestations may include a diffuse, red, macular rash resembling sunburn
that may involve the palms and soles. This eruption may be subtle or fleeting. Petechiae,
vesicles, and bullae may develop in severe cases. Desquamation occurs one to two weeks
after the onset of illness and chiefly affects the palms and soles . Mucosal involvement in
TSS includes hyperemia of the vaginal and oropharyngeal mucosa and conjunctivalscleral suffusion and hemorrhage, Systemic signs and symptoms include fever, nonpitting
edema of the face and hands, diarrhea and vomiting, myalgias, hypotension, mental status
changes, and multi-organ failure. Early laboratory findings include elevations of
creatinine phosphokinase, elevated transaminases, and elevated creatinine. The diagnosis
of TSS is based upon clinical presentation, utilizing the CDC case definition.

Staphylococcal scalded skin syndrome (SSSS) - Staphylococcal scalded skin syndrome

(SSSS), also known as Ritter disease, is caused by epidermolytic toxins produced by
certain strains of Staphylococci. This toxin is distributed systemically and results in
dissolution of keratinocyte attachments in only the upper layer of the epidermis (stratum
granulosum). SSSS usually affects newborns and children. Adults are less commonly
affected because improved renal function allows for clearance of the toxins from the
body,

although

adults

with

renal

failure

are

more

susceptible.

SSSS presents with fever, irritability, and a generalized, erythematous, micromacular to

maculopapular rash. The exfoliative phase is heralded by perioral exudation and crusting
with large radial fissures, likened to an "unhappy clown," appearing around the mouth.
However, mucosal membranes are not involved. There is usually no history of drug

exposure. SSSS is distinguished clinically from SJS/TEN chiefly by its epidemiology and
sparing of mucous membranes. The diagnosis is supported by histologic examination,
which reveals sloughing of only the upper layers of the epidermis. Frozen section
examination of sloughing epidermis can often distinguish SSSS from TEN as histology in
TEN will reveal a subepidermal split with full thickness epidermal necrosis, while only
partial thickness epidermal sloughing and minimal keratinocyte necrosis will be noted in
SSSS.

Paraneoplastic pemphigus Paraneoplastic pemphigus (PNP) is a rare disorder that

can represent the initial presentation of a malignancy or occur in a patient with a known
neoplastic process, such as non-Hodgkin lymphoma in adults or Castleman's disease in
children. Patients may develop severe mucocutaneous disease with ocular and oral
blisters and skin lesions that resemble erythema multiforme, bullous pemphigoid, or
lichen planus.