KEGAWAT

DARURATAN KULIT
1. STEVENS JOHNSON SYNDROME
2. TOXIC EPIDERMAL NECROLYSIS
3. ERYTHRODERMA
4. ERYTHEMA MULTIFORME
5. ANGIOEDEMA
6. REVERSAL REACTION
7. ERYTHEMA NODOSUM
LEPROSUM
STEVENS-JOHNSON
SYNDROME
Stevens-Johnson Syndrome

(SJS) episodic acute

mucocutaneous intolerance

reactions most often elicited by

drugs & less so by infections.

 Insidens

1- 2 per million / year.

Female twice > males.

Adult > children.

 Etiology

> 50% drug is causative

factor.

Minority infections,

vaccination or graft-versus-

host (GVHD)
 Pathogenesis

Hypersensitivity reaction

III & IV type.

 Clinical Feature

Trias sign :

1. Skin.

2. Mucous-membrane.

3. Eye.
It begins nonspecific prodrome :
Fever Malaise
Headache Rhinitis
Cough Sore throat
Chest pain Vomiting
Diarrhea Myalgia
Arthralgia.
Skin :

Erythematous (sometimes

morbiliform rash).

Vesicle.

Bullous, pustuler rarely.

Mucous membrane :
Two mucous surface minimize
Lips.
Oral cavity (palate,
buccal).
Anogenital.
Sign :
Erythema.
Edema followed blister that
rupture & transform into
extensive.
Hemorrhagic dull red erosions
coated by grayish-white
pseudomembrane or shallow
aphthous-like ulcers.
Oral lesions painful, cause
eating difficult & hyper-
salivation.

Genital painful hemorrhagic

bullous-erosive or purulent
lesions.

Anal erosi.
Eye : Conjunctiva

Inflammation & chemosis.

Vesiculation & painful

erosions.

Bilateral lacrimation.
 Purulent conjunctivitis with

photophobia &

pseudomembran.

Corneal ulceration, anterior

uveitis & panophthalmitis.

 Histopathology

Satellite-cell necrosis (early

stages) epidermal

eosinophilic necrosis of the

basal & suprabasal layers

subepidermal separation.
 Mononuclear cell infiltrate

papillary dermis.

Exocytosis epidermis.
 Laboratory

Blood sedimentation rate .

Leucocytosis.
Fluid-electrolyte imbalance.
Microalbuminuria, hypo-
proteinemia
Liver transaminase ,
anemia.
 Diagnosis

Trias sign :

Skin, mucous-membrane, eye.

< 10% or 10 30% body

surface area involvement.

 Differential Diagnosis

Erythema multiforme : < 10%

lesion of the body surface +
typical target lesion localized.
SSSS : caused by
staphylococcal epidermolisyn
toxynemia subcorneal
acantholysis.
 Macular drug eruption.

Fixed drug eruption.

Acute GVHS.

Viral exanthems.
 Complication

Toxicity, dehydration, water &

electrolyte imbalance
hemodynamic shock.

Pulmonary edema, mental

obtusion, confusion, coma &
seizure.
 Late Complication
Skin of heal : hyper and/ or
hypopigmentation.
Mucosa : scarring.
Eye :
Symblepharon, synechiae
corneal opacities or
scarring blindness.
 Treatment
According cause, type, stage &
complications.
Corticosteroid :
Not be used routinely.
Early stage of drug induced
SJS.
Prednisone 1 2 mg/kgBB/d
or dexamethasone 4 x 10
mg/d/i.v.
 Antibiotic :
Prophylactic prevention
infection.
According result culture
skin, mucous erosion.
e.g. gentamycine 2 x 60 mg <
40 kg body weight, 2 x 80 mg
> 40 kg body weight
monitoring renal function /
week.
 KCl 3 x 500 mg/d K level .

Monitoring Hm, blood gases

& fluid, electrolytes & protein

balance.
 Supportive care :
Pulmonary care (suctioning,
postural drainage, etc).
Ophthalmologic care.
High-calorie & high protein
diet.
 Topical treatment :

Sofratulle / sulfadiazine

cream.

Kenalog in orabase oral

lesion.
 Prognosis

Mortality rate severity

disease & medical care.

TOXIC EPIDERMAL
NECROLYSIS
(TEN)
 DEFINITION

The disease that characterized by:

Rapidly expanding macular
rashes of more than one
mucosal site.
The rash coalesces to
widespread erythema, necrosis,
& bullous detachment of the
epidermis resembling scalding.
INCIDENCE & EPIDEMIOLOGY

1. The average incidence at 0.5 to

1.4 per million per year.

2. There is no ethnic
preponderance; females appear
to be about twice as frequently
affected as males.
3. It is most often found in
adults.

4. It typically occurs
sporadically, but epidemics
have been observed with
the mass use of drugs.
 ETIOLOGY
It is a polyetiologic reason pattern :

Drugs (the leading causative

factors).
Infection.
Vaccination.
Graft versus host disease
(GVHD).
 PATHOGENESIS

Cytotoxic immune reaction Cell T (CD4

& % CD8)
TNF

Inducing apoptosis

destruction of epidermis &
keratinocyte
CLINICAL FEATURES

TEN begins with a

nonspecific prodrome of 1

to 14 days in at least half of

patients.
 A macular at times morbiliform
rash appears first on the face,
neck, chin, & central trunk
areas & may then spread to the
extremities & the rest of the
body.
 The lesions rapidly increase in
numbers & size : maximal
disease expression is usually
reached within 4 to 5 days.
The rash is paralleled or even
preceded by mucous membrane
lesions.
 Extra cutaneous symptoms :

Constitutional sign.

Internal organ involvement.

 Toxicity, dehydration, &
water & electrolyte
imbalance may proceed to
hemodynamic shock,
pulmonary edema, coma,
etc.
 Late complications :
Skin lesions heal with transitory
hyper- and / or hypopigmentation
Scarring of mucosal lesions, which
is most serious in the eyes.
A Sjogren like syndrome( an
autoimmune disease characterized
by dryness of the mucous
membrane of eyes, nose, mouth &
vagina).
 In small minority of case,
TEN presents with primary
ill-demarcated diffuse
erythemas that are rapidly
progressive & may become
erythrodermic.
 HISTOPATHOLOGY

Erythema multiforme with

extensive eosinophilic necrosis

of the epidermis & cleavage

plane above the basement

membrane.
 LABORATORY
INVESTIGATIONS

An elevated blood

sedimentation rate.

Moderate leukocytosis,

anemia.
 Fluid-electrolyte imbalances,
microalbuminuria, hypo-
proteinemia.

A transient decrease of
peripheral CD4+ T lymphocyte
counts.
 DIAGNOSIS

Tzank preparations showing

cuboidal cells & skin biopsy can

be used to confirm the

diagnosis.
DIFFERENTIAL DIAGNOSIS

Staphylococcal scalded skin

syndrome.
Generalized fixed drug
eruption.
Burns, cauterizations, etc.
Toxic erythroderma.
 TREATMENT

Systemic glucocorticoids 80

to 120 mg of

methylprednisolone per day by

mouth until disease

progression has decreased.

 Prophylactic antibiotic

treatment should be started

right from the beginning.

Sulfonamides & antibiotics with

known sensitizing potential must

be avoided (aminopenicilline,

cephalosporins).
 Topical treatment may be
carried out with hydrocolloid or
more conservatively, with
gauze dressing.
Obviously, sulfonamide-
containing topical agents
should be avoided.
 PROGNOSIS

Severe morbidity & high

mortality.
Death is usually due to :
Sepsis.
Gastrointestinal hemorrhage.
Renal, hepatic or pulmonary
complications.
ERYTHRODERMA
 Definition

Inflammatory skin disease

characterized by erythema
which affects more than
90% of the body surface.

Usually followed by
exfoliation of scale.
 Synonym

Exfoliative dermatitis
 Etiology
Drug reaction.
Expansion of other skin
disease i.e psoriasis,
seborrhoeic dermatitis,
atopic dermatitis.
Systemic disease or
malignancy.
Unknown.
 Pathophysiology

Erythema disorder of

thermoregulation basal

hypermetabolism.

Scaling lost of protein

hypoalbuminemia.
 Clinical Manifestation
I. Erythroderma due to drug
reaction.
Acute, occurs within 10 days
after the suspected drug
administrated.
The eruption start as
generalized morbiliform
erythema, initially without
scale.
II. Erythroderma as an
expansion of other skin
disease.

Characterized by exfoliative
& desquamative skin
lesions.
 Psoriatic erythroderma

(most common in adults).

Leiners disease (in infant

4 - 20 weeks of age).
III. Erythroderma due to systemic
disease or malignancy.
Hodgkins disease &
mycosis fungoides / sezary
syndrome.
Universal erythema,
accompanied by scale &
severe pruritus.
 Laboratory

Type I & II : not specifically,

but occasionally found
leucocytosis & increased
serum IgE.
Type III (sezary syndrome) :
sezary cells > 1000/mm3.
 Histopathology

The histological appearances

vary depending upon the

severity an duration of

inflammatory process :
I. Acute stage (type I) :
Spongiosis.
Parakeratosis.
Non specific inflammatory
infiltrate.
II. Chronic Stage :
Acanthosis.
Elongation of rete ridges.
III. Type III :
Lymphoid infiltrate at
dermo-epidermal junction.
Atypical cerebriform
mononuclear cells.
Pautriers micro-
abscesses.
 Diagnosis

Anamnesis.

Clinical features.

Histopathology.
Differential Diagnosis

Pemphigus foliaccus.

Pityriasis Rubra Pilaris.

 Treatment

Depend on the causative factor.

1. Supportive treatment (for all

types) :
Hospitalization.
Fluid & elctrolyte balance.
High protein intake.
2. Systemic treatment :

prednisone dose.

3 - 4 x 10 mg/d type I.

4 x 10 - 15 mg/d type II

(adult).
 30 mg/d + Chlorambucyl 2

- 6 mg/d type III.

1 - 2 mg/kgBW Leiners

disease.
3. Topical treatment :

Triamcinolone acetonide

cream (Type I, II).

Psoralen + UVA (Type II).

 Potent topical steroid

cream (type II).

Nitrogen mustard cream

(Type III) .
Depend on the causative factor
Type I : Although can be
fatal at the acute phase, it
has the best prognosis if
treated with adequate
treatment. Often resolving in
2 6 weeks.
 Type II : relapses often
occur.

Type III :

Poor prognosis.

Less than 1 year Median

survival rates.
 ERYTHEMA
MULTIFORME
Erythema multiforme (EM) is a

disease spectrum that

comprises a group of acute

self limited exanthematic

intolerance reaction.
 Von Hebra descriptions EM
associated HSV.
Steven & Johnson as EM
linked SJS because the same
pathologic, differ only in
severity & term EM minor &
major.
EM major synonym SJS.
 Two main subset

1. EM - a fairly common, usually

mild & relapsing eruption that

is most often triggered by

recurrent HSV infection.

2. SJS - TEN complex an

infrequent severe muco-

cutaneus intolerance

reaction most often elicited

by drugs.
Incidence & Epidemiology

Relatively common.
Can be observer in all ages,
predominantly in adolescent
& young adult.
Rare in under 3 years olds &
over 50 years.
 Female = male.
No predominance for ethnic
groups.
Often recurrent in short
interval & reappear for many
years.
 Etiology

Triggered by HSV-1 & HSV-2.

Drugs as rare cause of EM.

 Pathogenesis

A cell mediated immune

reaction aimed at the

destruction of keratocytes

expressing HSV antigens.

 EM associated SJS-TEN is
characterized by a dense
dermal inflammatory infiltrate
that is composed chiefly of
CD4+ T lymphocyte &
monocyte the wheal-like
clinical appearance of the
typical target lesion.
Clinical Manifestation

Lesion appear within 3

days.

Up to hundred of lesion

may form.
 Symmetric, extensor surfaces

of the extremities & face

(centripetal).

Less often on palms & soles,

thigh, bottocks & trunk.

 Usually symptomless,
sometimes burning & itching.
Typically, the lesion is a highly
regular circular, wheal-like
erythematous papule or plaque
that is stable with classic target
as iris lesion.
 Target lesion consist : a
dusky central disk (blister),
more peripherally a ring of
place edema & erythematous
halo.

Not all lesion are typical.

 Pathology

Early :

Lymphocyte accumulation at

the dermal - epidermal

interface with exocytosis into

the epidermis.
 Scattered keratinocyte necrosis

with lymph attached to the

necrotic keratinocye (satellite-

cell necrosis).
 Spongiosis, vacuolar

degeneration of the basal

layer.

Focal junctional & sub-

epidermal cleft formation.

 Advanced : subepidermal

blister formation &

epidermal necrosis.
Differential Diagnosis
Acute annular urticaria.
Urticaria vasculitis.
Disseminated lesion of
contact dermatitis.
Bullous pemphigoid.
Linear IgA dermatosis.
Herpes gestationes.
 Treatment
Symptomatic : shake lotion,
topical steroid, analgetic &
anti histamin.

Systemic glucocorticoids :
Unnecessary & possibly
worsened.
 Because recurrent EM most
often by triggered HSV
infection the ideal
approach : prevention of HS
episodes with oral acyclovir
or derivates.
Alternatives Treatment

Dapsone.

Anti malaria.

Azathioprine.

Thalidomide.
 Prognosis
Self limited, recovery is
complete & there are no
sequelae.

Does not occur progression

to SJS-TEN.

Recurrences are common.

ANGIOEDEMA
 Introduction

Angioedema clinical

manifestations of various

immunologic & inflammatory

mechanisms.
 Epidemiology

AAE rare ; about 50 cases

reported Worldwide.

Mortality may occur laryngeal

oedema, it is more likely due to
the complications of the
associated disorder.
Race all races are affected.

Sex men & women may be

affected.

Age onset is most common

after the fourth decade of life.

A family history for hereditary

angioedema not obtained.
 Clinical Manifestation
Angioedema symptoms, on
three prominent sites :
Subcutaneous tissues.
Abdominal organs (may be as
colicky pain and mimic a
surgical emergency).
Upper airway (larynx), which
result laryngeal oedema.
Signs include overt, non
inflammatory swelling of the skin
& mucous membranes.

Occasionally erythema or mild

urticarial eruptions may precede
the oedema.
 Etiology

AAE-I most frequently related

with B-cell lymphoproliferative
disease.

Recently : one report of a T-cell

lymphoma associated with AAE-I.
AAE-II not associated with

any specific disorder, but rather

by the presence of the

autoantibody directed against

C1-INH.
Differential Diagnosis

Drug eruption.
Urticaria acute & chronic.
Urticaria, Contact syndrome.
Urticaria solar.
Urticarial vasculitis.
 ACE inhibitor-induced
angioedema.
Episodic angioedema with
angioedema.
Leukocytoclastic vasculitis.
Urticaria (Cold).
 Histopathology

Subcutaneous or submucosal

oedema without infiltrating

inflammatory cells.
 Treatment

Medical Care

Depending symptoms & site

angioedema, intensive support
may be necessary, including
intravenous fluids.
When possible underlying
disorder should be treated.

In AAE-I, treatment of the

associated lymphoproliferative
process may result in
correction of the abnormality.
Surgical Care

Intubation may be necessary in

cases of laryngeal edema.

Androgens such as danazol or
stanozolol may be beneficial in
AAE-I but are of no value in
AAE-II.

Prostate cancer and pregnancy

preclude the use of androgens.
Immunosuppressive therapy

directed toward decreasing

autoantibody production may

be of value in patients with

AAE-II.
This may be accomplished by

the use of plasmapheresis with

cyclophosphamide Danazol

(Danocrine).
REVERSAL
REACTION
(Type 1 Reaction)
 Definition

Episodes of increased

inflammatory activity in skin

lesions, peripheral nerves or both.

Occur up to 3 years starting

therapy and may occur after

treatment has stopped.

Pathology, Symptom & Sign
There are two reactions :
1. Up grading rx the immunity
was increased.
The reactions shown :
Oedema intense during the
acute phase.
Inflammatory cells.
 Nerves may under caseous
necrosis.
Neutrophils.
Increase in lymphocytes.
Langhans giant cells.
2. Down grading rections it
caused by inadequate
regular anti leprosy therapy.
It shown :
The process is incidious &
silent.
Oedema.
 Reduction in lymphocytes.

Increasing of macrophages.

Langhans giant cells

sometimes.
 COMPLICATION
1. Neuritis :
Occur together or indepently
with the skin changes.
Common in men with BT
leprosy.
 Loss of function with

sudden paralysis of the

muscles.

Anaesthesia.
2. Systemic illness:
Malaise.
Low grade fever.
Anorexia.
Generalized oedema
especially of the hands, feet
& face.
 MANAGEMENT
Four principles:

1. Control acute neuritis in

order to prevent

anaesthesia, paralysis &

contracture.
2. Halt eye damage & prevent

blindness.

3. Control pain.

4. Kill the bacilli & prevent

extension of disease.
The treatment :
Corticosteroids : 60 80 mg
prednison / day.
Tappering of over 2 3 months.
Clofazimine: 300 mg/day until
controlled of corticosteroid then
tappering of 100/day.
 Prognosis

Depend on :
Determined.
Treatment.
Immune response.
ERYTHEMA NODOSUM
LEPROSUM
 Also known as Lepromatous

Lepra Reaction or Type 2

reaction (Jopling 1971).

 Type 2 reactions occur in

patients with multibacillary

disease & cause acute

inflammation in any organ or

tissue where M.leprae are

found.
 In the skin, type 2 reactions

cause erythema nodosum

leprosum (ENL).
 Incidence

Over one half of LL & one

quarter of BL patients will

experience type 2 reaction.

 Commonest in patients who
have had enough treatment
(second & third years
treatment), to reduce the
morphological index under
5%.
Fig. 1 Liability to reactions

ENL

REVERSAL

TT BT BB BL LL
 Predilection Sites

The most common site are

face & extensor surfaces of
the limbs, but may also be
seen elsewhere.
Lesions tend to recur at a
same sites.
 Sign

Painful red nodules

superficial or deep in the
dermis, dome shaped with ill
defined margins, shiny &
tender ulcerate thick
yellow pus contain
polymorphs & degenerate acid-
fast bacilli, but sterile on
culture.
 They appear in crops, new

ones appearing as old ones

subside over the course of a

few days.
 If not resolve completely
painful panniculitis develops
for month or year inflamed
skin & subcutaneous tissue
become fixed to underlying
fascia, muscle & bone
immobilize a hand or foot or
even the face.
This tissue is poorly

vascularized & may ulcerate

with the slightest trauma.

 Simptoms

Generalized illness.
Temperature rises to 40oC
daily, usually in the late
afternoon, & remits.
Patient becomes exhausted &
prostrated by pain, headache,
anorexia, insomnia &
depression.
 Following manifestations may
appear :
Iridocyclitis (may be the
only sign of reaction).
Orchitis.
Dactylitis.
Tender enlargement of all
peripheral nerves & tender
lymphadenopathy.
 Less commonly, muscles

may be tender & joints may

be painful or even swollen, &

there may be epistaxis &

proteinuria.
Differential Diagnosis

Neurofibromatosis.

Sarcoidosis.

Drug eruption.

Dermal leishmaniasis.
 Treatment

Continue the antileprosy

medication (MDT).
Mild cases bed rest,
symptomatic : aspirin,
sedation & nonsteroidal anti-
inflammatory.
 Severe cases

prednisone 40-60 mg daily

tapered slowly over

months or year.
 Chronic cases :
Prednisone 20-30 mg daily +
clofazimine 300 mg daily (if no
gastrointestinal intervening)
dose gradually lowered to 100
mg daily, & increasing it again
if reaction exacerbates.
Continue clofazimine until

bacterial negativity, since the

reaction sometimes recurs if

the drug is discontinued

sooner.
 Thalidomide is also the

treatment of choice for ENL.

Starting dose 100 mg 3-4 times

daily reaction controlled

tapered if possible

discontinued within 3-4 weeks.

 Other alternatives are
chloroquine :
Chloroquine starting dose 250
mg 3 times daily for a week
(reaction controlled) & then
lowered to 250 mg twice daily
for a week, followed by 250 mg
daily.
 Prognosis

Early diagnosis & treatment &

energetic management of

reactional states prevent the

development of all disabilities.