Stevens - Johnson syndrome

is a rare, serious disorder of your skin and mucous membranes. It's usually a reaction
to a medication or an infection.
Often, Stevens-Johnson syndrome begins with flu-like symptoms, followed by a
painful red or purplish rash that spreads and blisters. Then the top layer of the
affected skin dies and sheds.
Stevens-Johnson syndrome is a medical emergency that usually requires
hospitalization.
Treatment focuses on eliminating the underlying cause, controlling symptoms and
minimizing complications.
Recovery after Stevens-Johnson syndrome can take weeks to months, depending on
the severity of the condition.
If it was caused by a medication, you'll need to permanently avoid that drug and
others closely related to it.

SIGNS AND SYMPTOMS

o Facial swelling
o Tongue swelling
o Hives
o Skin pain
o A red or purple skin rash that spreads within hours to days
o Blisters on your skin and the mucous membranes of your mouth, nose, eyes and
genitals
o Shedding of your skin
If you have Stevens-Johnson syndrome, several days before the rash develops you may
experience:
o Fever
o Sore mouth and throat
o Fatigue
o Cough
o Burning eyes
CAUSES
Medication and therapy causes
Drugs that can cause Stevens-Johnson syndrome include:
o Anti-gout medications, such as allopurinol
o Pain relievers such as acetaminophen (Tylenol, others), ibuprofen (Advil, Motrin IB,
others) and naproxen sodium (Aleve)
o Medications to fight infection, such as penicillin
o Medications to treat seizures or mental illness (anticonvulsants and antipsychotics)
o Radiation therapy
Infectious causes
Infections that can cause Stevens-Johnson syndrome include:
o Herpes (herpes simplex or herpes zoster)
o Pneumonia
o HIV
o Hepatitis
RISK FACTORS
Factors that increase your risk of developing Stevens-Johnson syndrome include:
o Viral infections. Your risk of Stevens-Johnson syndrome may be increased if you
have an infection caused by a virus, such as herpes, viral pneumonia, HIV or
hepatitis.
o Weakened immune system. If you have a weakened immune system, you may have
an increased risk of Stevens-Johnson syndrome. Your immune system can be
affected by an organ transplant, HIV/AIDS and autoimmune diseases, such as lupus.
o A history of Stevens-Johnson syndrome. If you've had a medication-related form
of this condition, you are at risk of a recurrence if you use that drug again.

A family history of Stevens-Johnson syndrome. If an immediate family member

has had Stevens-Johnson syndrome or a related condition called toxic epidermal
necrolysis, you may be more susceptible to developing Stevens-Johnson syndrome
too.
Having a certain gene. If you have a gene called HLA-B 1502, you have an
increased risk of Stevens-Johnson syndrome, particularly if you take certain drugs for
seizures or mental illness. Families of Chinese, Southeast Asian or Indian descent
are more likely to carry this gene.

COMPLICATIONS

Secondary skin infection (cellulitis). Cellulitis can lead to life-threatening

complications, including sepsis.

Blood infection (sepsis). Sepsis occurs when bacteria from an infection enter your
bloodstream and spread throughout your body. Sepsis is a rapidly progressing, lifethreatening condition that can cause shock and organ failure.

Eye problems. The rash caused by Stevens-Johnson syndrome can lead to

inflammation in your eyes. In mild cases, this may cause irritation and dry eyes. In severe
cases, it can lead to extensive tissue damage and scarring that results in blindness.

Damage to internal organs. It's unusual for this condition to affect internal organs.
But it may cause inflammation of the lungs, heart, kidneys or liver.

Permanent skin damage. When your skin grows back following Stevens-Johnson
syndrome, it may have abnormal bumps and coloring. And you may have scars. Lasting
skin problems may cause your hair to fall out, an
TESTS AND DIAGNOSIS

Physical exam. Doctors often can identify Stevens-Johnson syndrome based on

your medical history, a physical exam, and the disorder's signs and symptoms.

Skin test. To confirm the diagnosis, your doctor may remove a sample of skin for
laboratory testing (biopsy).
TREATMENT AND DRUGS
Stevens-Johnson syndrome requires hospitalization, often in an intensive care unit or
burn unit.
Stopping nonessential medications
The first and most important step in treating Stevens-Johnson syndrome is to discontinue any
medications that may be causing it. Because it's difficult to determine exactly which drug may
be causing the problem, your doctor may recommend that you stop taking all nonessential
medications.
Supportive care
Supportive care you're likely to receive while hospitalized includes:
o Fluid replacement and nutrition. Because skin loss can result in significant loss of
fluid from your body, replacing fluids is an important part of treatment. You may
receive fluids and nutrients through a tube placed through your nose and advanced
into your stomach (nasogastric tube).
o Wound care. Cool, wet compresses will help soothe blisters while they heal. Your
health care team may gently remove any dead skin and place a medicated dressing
over the affected areas.
o Eye care. You may also see an eye specialist (ophthalmologist).
Medications
Medications commonly used in the treatment of Stevens-Johnson syndrome include:
o Pain medication to reduce discomfort
o Medication to relieve itching (antihistamines)
o Antibiotics to control infection, when needed
o Medication to reduce skin inflammation (topical steroids)
If the underlying cause of Stevens-Johnson syndrome can be eliminated and the skin reaction
stopped, new skin may begin to grow over the affected area within several days. In severe
cases, full recovery may take several months.

Prepared by:
Denisse Audrey D. Leonar
BSN - 4

Safety update allopurinol

Published in Health News and Evidence
Date published: 14 February 2013About this date
Allopurinol in current practice | How does allopurinol hypersensitivity occur? | Use caution
when selecting allopurinol as a gout prophylactic agent | Other suspects | Routine testing
for HLA-B*5801 is not recommended | References

Summary
Allopurinol lowers plasma urate level and is commonly used as first-line therapy in long-term
gout prophylaxis.1 Some patients may develop allopurinol hypersensitivity (AH), commonly
characterised by rash but sometimes causing systemic symptoms. 2 AH can occur as severe
cutaneous adverse reactions (SCAR), which includes StevensJohnson syndrome (SJS) or
toxic epidermal necrolysis (TEN).3,4 These reactions have a low incidence but have a mortality
rate
of
15%
for
SJS,
and
2530%
for
TEN. 3
Genetic susceptibility factors, in particular, human leukocyte antigen (HLA) alleles, have been
identified as risk factors for hypersensitivity reactions. Susceptibility to AH has been linked
specifically to the HLA-B*5801 gene allele.410 This allele occurs in high frequency in people
from certain ethnic groups, particularly those with Han-Chinese ancestry. 6 While the allele
confers risk, being a carrier does not necessarily cause the development of AH 6 and routine
testing
for HLA-B*5801 is
not
recommended.
Use caution when selecting allopurinol for gout prophylaxis in populations with a strong
association with, or if the patient is a known carrier of, HLA-B*5801.3 In all patients taking
allopurinol it is important to monitor for signs and symptoms of SCAR. 11 Do not use in people
with a known hypersensitivity.12

Allopurinol in current practice

Allopurinol lowers plasma urate level by inhibiting its production; it is commonly used and
recommended as first-line therapy in long-term prophylaxis for gout. 1
Australian guidelines recommend:

introducing allopurinol in people who experience recurrent gout attacks despite

minimising potential contributing factors to hyperuricaemia, such as diuretics and
alcohol.1 Start treatment in the interval between attacks, as initiating allopurinol or
changing the dose during an acute attack may lead to exacerbation. 1
starting at a low dose in patients with chronic gout and resolving the inflammation if
possible with concurrent NSAID and/or colchicine. 1 With chronic gout there is no
asymptomatic period in which to start urate-lowering therapy.1
measuring plasma urate concentration monthly during the titration phase, adjusting
the dose with the aim to bring the plasma urate concentration down to 0.3 mmol/L. 1

How does allopurinol hypersensitivity occur?

General agreement among clinicians and researchers is that AH is immune mediated. 13,14
However, the pathophysiological mechanisms of AH are not well understood. The term
hypersensitivity is used when an agent results in an increased or exaggerated immune
response.15

AH can occur as severe cutaneous adverse reactions

StevensJohnson syndrome or toxic epidermal
necrolysis which have high mortality rates 3,4
SJS and TEN have a low annual incidence, with about one person in 56,000 developing
allopurinol-induced SCAR.16 AH also includes less serious skin and systemic hypersensitivity
reactions drug-induced hypersensitivity syndrome (DIHS) and drug reaction with rash,
eosinophilia and systemic symptoms (DRESS). 17 Less is known about the mechanism behind
these reactions.17

Genetic factors have been identified as predisposing to

AH410
Because of the serious morbidity and mortality related to SCAR 2 there has been a sustained
effort to find markers that can predict individual susceptibility to these conditions. 9 AH has
been linked to the HLA-B*5801 allele of the HLA gene locus, a key immune modulation
protein.39The prevalence of HLA-B*5801 varies among ethnic populations.2
Abacavir and carbamazepine hypersensitivity have also been linked to polymorphisms in the
HLA locus.6 Studies confirming the sensitivity of certain DNA markers as predictive of
phenotype offer an opportunity to examine the association of certain alleles with rare skin
reactions.4

Strong association between HLA-B*5801 and AH in the

Han-Chinese population
Han-Chinese constitute about 91.5% of the population of the People's Republic of China
(mainland China).18 A recent study found the HLA-B*5801 allele to be strongly associated with
AH in the Han-Chinese population, but 20 (15%) of 135 allopurinol-tolerant patients had
theHLA-B*5801 allele, which indicates that factors other than presence of this allele must be
involved in AH.5 The association of HLA-B*5801 with the diagnosis of less severe
DIHS/DRESS has only been reported in the Han-Chinese population. 6,17
More research is required to clarify the role of this allele in AH. A major limitation of the current
evidence stems from the low incidence of SCAR, which generates observational studies with
relatively small sample sizes and insufficient power, making it difficult to establish the strength
of association of HLA-B*5801.11

Other suspects
AH may present differently among patients 2, making it difficult to diagnose and identify a
causative mechanism. Other risk factors include:

chemical exposures, mycoplasma pneumonia, viral infections, and immunisations 19

chronic renal impairment6,11

recent starting of treatment and high doses ( 200 mg/day) when starting treatment,
as seen in a multinational casecontrol surveillance of HLA-B in SCAR (the EuroSCAR
study).20

HLA molecules they may be functionally involved in the pathogenesis of the

disease, as there is a strong association between them and severe adverse drug
reactions.3,5,21
Further research on environmental contributors to AH is required. Patients with chronic renal
impairment have a higher risk association. 6,11 However, data from 120 patients with gout
receiving allopurinol shows dose adjustment according to creatinine clearance rate has no
significant effect on reducing AH.22

Use caution when selecting allopurinol as a gout

prophylactic agent
Do
not
use
allopurinol
in
people
with
a
known
hypersensitivity. 12
If AH does not develop within 2 months of starting of allopurinol treatment, it is unlikely to
occur.17
Only consider allopurinol if the benefits exceed the risks in a person who is a known
carrier of HLA-B*5801.22
Extra vigilance for signs of hypersensitivity syndrome or SJS/TEN is required. Inform the
patient of the need to stop treatment immediately at the first appearance of symptoms. 22
Monitor
for
signs
and
symptoms
of
SCAR. 11
Discontinue allopurinol at the first appearance of skin rash or other signs that may indicate an
allergic reaction.12
SJS/TEN reactions normally occur 5 days to 3 weeks after starting allopurinol. 23
When clinically evaluating a suspected reaction, check for the sentinel signs or symptoms that
warn of a potentially severe eruption or serious systemic drug reaction. Two or more sentinel
signs or symptoms are early indicators of multi-organ reactions and/or precede skin blistering
in many individuals who develop SJS or TEN. These symptoms may precede, coincide with or
follow skin eruption onset by several days: 23

high fever

sore throat/pharyngitis

gritty eyes, photophobia

mouth or genital ulcers

swollen tender lymph glands, and/or head and neck swelling or puffy eyes

malaise, myalgia, arthralgia and/or arthritis

headache, neck stiffness

dyspnoea, cough, rhinorrhoea and/or ear pain

skin tenderness.
Alternative hypouricaemic drugs are available. 17
Probenecid may be a safer alternative to allopurinol in patients at risk of developing AH. 17 It is
not as effective as allopurinol at reducing plasma urate levels. 1
Reduce unnecessary use of allopurinol.
The incidence of AH can be reduced by carefully evaluating whether allopurinol is indicated.
For example, asymptomatic hyperuricemia is not an indication for allopurinol treatment. 1,3

Administer with caution in patients with renal impairment and monitor carefully.12
Reduce the dose in these patients to avoid toxicity from accumulation of allopurinol,
oxypurinol and other metabolites. 6,12 Testing these patients for the HLA-B*5801 allele may be
more effective than dose adjustment to avoid allopurinol-induced SCAR. 6
After recovery from mild reactions, reintroduce allopurinol at low dose (e.g. 50 mg/day)
and gradually increase.12
If the rash recurs, allopurinol should be permanently withdrawn, as more severe
hypersensitivity reactions may occur.12

Routine
testing
recommended

for HLA-B*5801 is

not

HLA-B*5801 has a high prevalence in certain populations (e.g. Han-Chinese). 17 While the
allele confers risk, being a carrier does not necessarily cause the development of AH. 6
HLA-B*5801 testing alone is not an effective population screening test due to the low overall
incidence of AH and the weak association between presence of the allele and AH in some
populations.6,24 Screening at a population level may unnecessarily exclude some people from
allopurinol treatment. Testing does not eliminate all risk of developing SCAR, and monitoring
patients for signs and symptoms is still a priority.4
In contrast, between 5% and 9% of patients taking abacavir develop abacavir hypersensitivity,
and the presence of HLA-B*5701 is highly predictive of this reaction. 25 The Prospective
Randomized Evaluation of DNA Screening in a Clinical Trial (PREDICT-1) study evaluated
use of HLA screening for abacavir hypersensitivity prevention; results were in favour of its
use.26 In Australia, genetic screening is routinely administered before starting abacavir and is
subsidised through Medicare.25 For more information on genetic-based tests with clinical utility
for personalised medicine see the NPS Direct article Genetic testing in the genomics era
the new frontier of personalised medicine for information on other genetic based tests