STEVENS JOHNSON

SYNDROME
Ward Case Presentation
By:
Airamsherlyn P. Natinga, M.D.
Pediatric Resident
General data:

- 15 year old, female
- born on April 4.1995
- Filipino, Roman Catholic
- Capul, Northern Samar
- Admitted July 4, 2010
- @ 2:44 pm
Chief Complaint:
Multiple Skin
Lesions


HISTORY OF PRESENT
ILLNESS

2 weeks PTA
- loss of consciousness for 5 min
- brought to Allen District
Hospital, admitted and managed as
Epilepsy, UTI
- Medications:
1. Phenytoin Capsule
2. Unrecalled antibiotics



- 2 days after discharged:

* noted with fever, low grade, fatigue,
associated with maculopapular rashes
on the face

- consulted to a private MD and given
Cetirizine tablet
- rashes progressed all over the body


2 days PTA
- readmitted at Allen District
Hospital for progression of
rashes/lesions
- medications:
* Cetirizine tablet
* Acyclovir
* Vit. B Complex
* Sulbactam/Ampicillin tablet
* Phenytoin capsule








Morning PTA
- referred to this center for further
evaluation and management

Admission



Personal History:

Born NSVD at home, assisted by a trained
birth attendant, with good cry and activity
- Negated any complications during the course
of pregnancy and delivery
- Breastfeed for 2 years, then to milk formula

- Growth and development: at par at age





Past Medical History
- No previous Hospitalizations
- With hx of fainting: Dec. 2009
- Non asthmatic
- No known allergies to food or
drugs
Immunization
- primary immunizations complete
c/o Barangay Health Center


Family History:
- Unremarkable

Psychosocial History:
- father: 54 year old, farmer
Barangay Tanod
- mother: 51 year old,
housewife






- 7
th
child of 9 children
- 4
th
year High School
- Average schooler
- menarche : 14 yr old
- other siblings: apparently well

Review of Systems:
General: decrease appetite
Integument: with tender lesions
HEENT: with conjunctivitis, and
eye discharges, with sore
throat
Respiratory: with occasional cough
Cardiovascular: no chest pain
GIT: no abdominal pain

GUT: with adequate output

Musculoskeletal: with body malaise
and or fatigue

Hematologic: no bleeds

Physical Examination:
General:
- awake, conscious, coherent, on wheel
chair, febrile, not in distress
Vital Signs
- RR: 24 cpm
- HR: 100 bpm
- Temp: 38
O
C
- BP: 100/60 mmHg
- Weight: 42 kg



Skin: * with dry patchy pigmented
lesions on the face,
* with bullae lesions diffusely
distributed to the different
areas of the body
HEENT: * with conjunctival
suffusion and discharges
* hyperemic tonsils
* oral lesions

Neck: * no cervical lymph adeno-
pathies
C/L: * symmetrical chest
expansion, with no
retractions, harsh breath
sounds, with no crackles, with
occasional wheeze
Heart: * adynamic precordium, no
thrills, no heaves, normal
rate and regular rhythm,
no murmur

Abdomen: * globular, normoactive
bowel sounds, soft, no
tenderness, liver not
palpable,
no organomegaly
Genitals: * with tender lesions
Anus: patent, and with lesions
Extremities: with multiple lesions,
equal, full pulses


SALIENT FEATURES:
* 15 yr old female, on Phenytoin
(Dilantin) medication
* low grade fever
* sore throat, occasional cough
* body malaise / fatigue
* tender, dry patchy lesions on
the face

* with conjunctivitis / conjunctival
suffusion,
eye discharges
* oral lesions, tender
* bullae lesions diffusely
distributed to different areas
of the body including
buccal mucosa and the
anogenital areas

ADMITTING IMPRESSION:

STEVENS JOHNSON
SYNDROME
On admission:

- placed on hypoallergenic diet
- venoclysis continued with PLR
regulated at mild x 8H
- Diagnostics requested
CBC & platelet count
Na, K, SGPT, BUN, Creatinin e
Urinalysis

Medications:

- Paracetamol P.O.,15mg/kg/dose,
PRN for fever
- Hydrocortisone 4mg/kg/dose q 6H
- Ranitidine I mg/kg/dose q 8H
- Loratadine 10mg/tab OD

- Diphenhydramine 1mkd
q 8H
- Oxacillin 100mkd q 6H
- Amikacin 5mkd, OD
- I and O monitoring
- Vital signs monitoring q 6H

Laboratory Exam. Results:
CBC: Hemoglobin 126 Neutrophils 0.82
Hematocrit 0.39 Lymphocytes 0.14
RBC Count 4.11 Monocytes 0.04
WBC Count 15.2
Platelet count: 217
Urinalysis: Lt.yellow color , sl. Turbid
pH 6.0, Sp. Gr. 1.015
proteins (+), Sugar (-)
pus cells (22=30), red cells none


Serum determination:

Sodium = 135.4 mmol/L (N)
Potasium = 4.04 mmol/L (N)
BUN = 2.90 mmol/L (N)
Creatinine = 51 umol/L (N)
SGPT = 32.63 U/L (N)
COURSE IN THE WARD:

1
st
Hospital Day
Noted with fair appetite
complains pain upon eating
(+) tender bullae lesions
(+) dry pigmented lesions on all
areas of the body
adequate output


referred and seen by an
Ophthalmologist, started with
Tobr amycin +Dexamethasone
Ointment (Tobradex) to both
Eyes BID
- advised to apply Cetaphil liquid
to desquamated areas of the skin
2
nd
Hospital Day

* afebrile, still with multiple bullaes
* started with Betadine gargle
TID
* medications continued
* IVF rate decreased to 2cc/k
3
rd
, 4
th
and 5
th
Hospital days:
* afebrile, good appetite
* noted with areas of
desquamated skin
* stable vital signs
* adequate output
* medications continued
* repeat urinalysis requested
and revealed a normal result
6
th
Hospital day:
* afebrile, BP 100/60 mmHg
* adequate urine output
* Hydrocortisone decreased to
every 8 Hours
* started oral Prednisone
20mg/tab after breakfast
7
th
8
th
Hospital Day
- With areas of desquamation
- with good appetite
- afebrile
- with stable v/s, with adequate output,
full pulses
9
th
Hospital Day
- patient improved, discharged with
stable vital signs with the ff. home
medications:
1. Prednisone tablet
20mg, 1 tab after breakfast
10 mg, 1 tab after lunch
2. Ranitidine 20 mg tablet, 1 tab OD
3. Oxacillin 500 mg capsule, 1 cap
every 6 hours x 2 days
Differential Diagnosis
Toxic Epidermal Necrolysis
R/I : Hx of fever , malaise
and blisters
R/O :
scalp is not spared from
blisters
mucuos membranes are
spared



SSS
R/I : Hx of skin lesions
malaise /fatigue, fever
skin tenderness upon
palpation
R/O : (+) Nikolsky sign
not a reaction to a
drug








History
Stevens-Johnson Syndrome is
named for Albert Mason Stevens and
Fran Chamblis Johnson, American
pediatricians who in 1922 jointly
published a description of the
disorder in the American Journal of
Diseases of Children.
StevensJohnson syndrome
(SJS)

= is a life-threatening condition
affecting the skin in which cell death
causes the epidermis to separate from
the dermis.
The syndrome is thought to be a
hypersensitivity complex affecting the
skin and the mucous membranes.
majority of cases are idiopathic
the main class of known causes
is medications, followed by
infections and (rarely) cancers.
Epidemiology

Stevens-Johnson syndrome
= a rare condition,
= reported incidence of around 2.6 to 6.1
cases per million people per year. In the
United States, there are about 300 new
diagnosis per year.
= more common in adults than in children.
Women are affected more often than men,
with cases occurring at a 3:6 ratio.


Classification
StevensJohnson syndrome (SJS)
= considered a milder form of Toxic
Epidermal Necrolysis (TEN). First
recognized in 1922.
= Both diseases can be mistaken for
Erythema Multiforme. Erythema
multiforme is sometimes caused by a
reaction to a medication but is more often
a type IV hypersensitivity reaction to an
infection (caused most often by Herpes
simplex) and is relatively benign.
Although both SJS and TEN can
also be caused by infections, they
are most often adverse effects of
medications. Their consequences
are potentially more dangerous
than those of erythema
multiforme.
Pathogenesis

Carbamazepine- and Phenytoin-induced
SJS is strongly associated with HLA-
B*1502 (HLA-B75), an HLA-B serotype of
the broader serotype HLA-B15.
A study in Europe suggested that the
gene marker is only relevant for East
Asians.

Cutaneous lesions in Stevens-
Johnson syndrome
initially of erythematous macules
that rapidly and variably develop
central necrosis to form vesicles,
bullae, and areas of denudation on
the face, trunk, and extremities.


Signs and Symptoms:
SJS usually begins with fever, sore throat,
and fatigue, which is misdiagnosed and
usually treated with antibiotics.
Ulcers and other lesions begin to appear
in the mucous membranes, almost always
in the mouth and lips but also in the genital
and anal regions. Those in the mouth are
usually extremely painful and reduce the
patient's ability to eat or drink.
Conjunctivitis of the eyes occurs
in about 30% of children who
develop SJS.
A rash of round lesions about an
inch across which arises on the
face, trunk, arms and legs, and
soles of the feet, but usually not
the scalp.
Lesions may be preceded by a
flu-like upper respiratory
illness.
Pain from mucosal ulceration
is often severe, but skin
tenderness is minimal to
absent, in contrast to Toxic
Epidermal Necrolysis.
Disseminated cutaneous bullae
and erosions may result in
increased insensible fluid loss and
a high risk of bacterial
superinfection and sepsis.
New lesions occur in crops, and
complete healing may take 46 wk;
ocular scarring, visual impairment,
and strictures of the esophagus,
bronchi, vagina, urethra, or anus
may remain.
Causes
SJS is thought to arise from a disorder of
the immune system.
Infections
It can be caused by infections (usually
following infections such as herpes
simplex virus, influenza, mumps, cat-
scratch fever, histoplasmosis, Epstein-Barr
virus, mycoplasma pneumoniae or
similar).


Medication/drugs
It can be caused by adverse effects of
drugs (allopurinol, diclofenac, etravirine,
Isotretinoin aka Accutane, fluconazole,
valdecoxib, sitagliptin oseltamivir,
penicillins, barbiturates, sulfonamides,
phenytoin, azithromycin, oxcarbazepine,
zonisamide, modafinil, lamotrigine,
nevirapine, pyrimethamine, ibuprofen,
ethosuximide, carbamazepine, nystatin,
and gout medications).
Although StevensJohnson Syndrome can
be caused by viral infections, malignancies
or severe allergic reactions to medication,
the leading cause appears to be the use of
antibiotics and sulfa drugs.
Has also been consistently reported as an
uncommon side effect of herbal
supplements containing ginseng may also
caused SJS and also cocaine usage.


Diagnostics
Nonspecific laboratory
abnormalities in Stevens-Johnson
syndrome include Leukocytosis,
elevated Erythrocyte
Sedimentation Rate, and,
occasionally, increased liver
transaminase levels and decreased
serum albumin values.
Treatment
Management of Stevens-Johnson
syndrome is supportive and
symptomatic.
Potentially offending drugs must be
discontinued as soon as possible.
Ophthalmologic consultation is
mandatory because ocular sequelae
such as corneal scarring can lead to
vision loss.

Topical steroids may reduce ocular
morbidity. Oral lesions should be
managed with mouthwashes and
glycerin swabs.
Antibiotic therapy is appropriate for
documented secondary bacterial
infection.
Vaginal lesions should be observed
closely and treated to prevent vaginal
stricture or fusion.

Topical anesthetics (diphenhydramine,
dyclonine, and viscous lidocaine) may
provide relief from pain, particularly
when applied before eating.
Denuded skin lesions can be cleansed
with saline or Burow solution
compresses
Intravenous immunoglobulin (1.52.0
g/kg/day 3 days) has also been used
and believed by many to be effective.

An ophthalmologist should be
consulted immediately, as SJS
frequently causes the formation of
scar tissue inside the eyelids, leading
to corneal vascularization, impaired
vision and a host of other ocular
problems. Also, an extensive physical
therapy program ensues after the
patient is discharged from the
hospital.

Prognosis

SJS proper (with less than 10% of
body surface area involved) has a
mortality rate of around 5%. The risk
for death can be estimated using the
SCORTEN scale, which takes a
number of prognostic indicators into
account. Other outcomes include
organ damage/failure, cornea
scratching and blindness.


Phenytoin sodium is a commonly used
antiepileptic. Phenytoin (fen-i-TOE-in) acts
to suppress the abnormal brain activity
seen in seizure by reducing electrical
conductance among brain cells by
stabilizing the inactive state of voltage-
gated sodium channels. Aside from
seizures, it is an option in the treatment of
trigeminal neuralgia in the event that
carbamazepine is deemed inappropiate.
History
Phenytoin (diphenylhydantoin) was first
synthesized by German chemist Heinrich
Biltz in 1908. Biltz sold his discovery to
Parke-Davis, which did not find an
immediate use for it. In 1938, outside
scientists including H.
Dilantin made an appearance in the 1962
novel One Flew Over the Cuckoo's Nest by
Ken Kesey, both as an anticonvulsant and
as a mechanism to control inmate
behavior.
In autoimmune disease
Phenytoin has been known to cause drug-
induced lupus.
[11]

Phenytoin therapy has been linked to the
life-threatening skin reactions Stevens-
Johnson syndrome (SJS) and toxic
epidermal necrolysis (TEN). These
conditions are significantly more common
in patients with a particular HLA-B allele,
HLA-B*1502.
[12]
This allele occurs almost
exclusively in patients with ancestry across
broad areas of Asia, including South Asian
Indians.

Good afternoon
Side-effects
Neurologic
At therapeutic doses, phenytoin produces
horizontal gaze nystagmus, which is
harmless but occasionally tested for by
police as a marker for alcohol intoxication
At toxic doses, patients experience
sedation, cerebellar ataxia, and
ophthalmoparesis, as well as
paradoxical
[clarification needed]
seizures.
Idiosyncratic side-effects of phenytoin, as
with other anticonvulsants, include rash
and severe allergic reactions.

Phenytoin may accumulate in the cerebral
cortex over long periods of time, as well
as causing atrophy of the cerebellum
when administered at chronically high
levels. Despite this, the drug has a long
history of safe use, making it one of the
more popular anti-convulsants prescribed
by doctors, and a common "first line of
defense" in seizure cases.
Hematologic
It has been suggested that phenytoin
causes a reduction in folic acid levels,
predisposing patients to megaloblastic
anemia. Folic acid is presented in foods as
polyglutamate, which is then converted
into monoglutamates by intestinal
conjugase. Phenytoin acts by inhibiting
this enzyme, thereby causing folate
deficiency.
[4]
Other side effects may
include: agranulocytosis, aplastic anemia,
leukopenia, thrombocytopenia.

Teratogenicity
Phenytoin is a known teratogen. The
syndrome consists of craniofacial
anomalies (broad nasal bridge, cleft lip
and palate, microcephaly) and a mild form
of mental retardation (average IQ=71).
[5]

This syndrome resembles the well-
described Fetal Alcohol Syndrome
[6]
and
has also been called the "fetal hydantoin
syndrome".

Gingival
Phenytoin has been associated with drug
induced gingival enlargement
(hyperplasia) in the oral cavity probably
due to above mentioned folate defiency.
Dermatologic
Hypertrichosis, rash, exfoliative dermatitis,
pruritis.