NOTE:DRASS also called Drug hypersensitivity syndromeEruption = طفح جلدي
You know that we have 4 type of hypersensitivity reactions. Anaphylaxis, cytotoxic, immune complex, delayed type . Interesting point and for you to remember these names if U take first later from each, you will end up with the word “acid”. So let’s go back to DRESS, which type of these that DRASS based on ?
80% of cases are reported as a hypersensitivity reaction to certain drugs
The cause in the case was because of carbamazepine whichthe latency between drug exposure and onset of symptoms is considerably long may be reach more than 6 months
Which will affect the patient in one way or another because that will lead to changing of drug concentration in the body
may occur in children, but most cases occur in adults without sex predilectionsex predilection = with no susceptible gender more than the another
It have been believed that
Diagnose such a case is not easy, because the symptoms may relate to other conditions. So the investigations in DRESS depend on the aim of exclude other conditions and prove DRESS therefore the following test should be done.
Spongiosis is mainly intercellular edema (abnormal accumulation of fluid) in the epidermis
Testing for herpesvirus infection to avid farther complicationThe Epstein–Barr virus (EBV), Each test can support the diagnosis but not prove it ! And the combination of supportive results can be a strong evidence to diagnose a case with DRESS
The most useful test to determine which drug is
Drug reaction with eosinophilia
and systemic symptoms
Done by: Bayan Al-Ghadeer
Group ( 2)
King Faisal University College
Adverse drug reaction
Etiology and risk factors
to the topic
Adverse drug reaction
How to identify adverse drug reactions
What is Adverse drug reaction ?
(ADR) is an unwanted or harmful reaction
experienced following the administration
of a drug or combination of drugs under
normal conditions of use, which is suspected
to be related to the drug.
The reaction may be a known side effect of the
drug or it may be new and previously
How to identify adverse drug reactions ?
The patient may tell you about symptoms they have experienced
since taking a new medicine.
Abnormal clinical measurements while on drug therapy
(e.g. temperature, pulse, blood pressure, blood glucose, body weight)
Abnormal biochemical or haematological laboratory results
while on drug therapy
Which type of hypersensitivity is it based on ?
What is DRESS ?
is a rare, potentially life-threatening, drug-induced severe,
unexpected hypersensitivity reaction that includes skin eruption,
hematologic abnormalities (eosinophilia, atypical lymphocytosis),
lymphadenopathy, and internal organ involvement (liver, kidney,
Drug hypersensitivity syndrome
Delayed hypersensitivity reactions
Or type IV hypersensitivity reactions.
inflammatory reactions initiated a secondary cellular response
by mononuclear leukocytes .
Lymphocytes (T cells )
side effects of “ Carbamazepine (Tegretol)”
side effects of “Diazepam”
Who may develops DERSS ?
What could cause DRESS ?
Antiepileptic agents e.g. carbamazepine
drugs associated with DRESS
Common side effects may include:
drowsy, or unsteady
• stomach pain
Serious side effect such as:
pale skin and skin pain
rapid heart rate,
mouth and throat ulcers
easy bruising or bleeding,
pain and muscle weakness
feeling short of breath
swelling of your ankles or feet
• urinating less than usual
(yellowing of the skin or eyes)
• severe skin reaction
• swelling in face or tongue
• burning in eyes
• a red or purple skin rash
that spreads (especially in
the face or upper body)
and causes blistering
It is often used in stress and anxiety.
• drowsiness, tired feeling
• memory problems
• dizziness, spinning sensation
• feeling restless or irritable
• muscle weakness
• nausea, constipation
• blurred vision, double vision
• mild skin rash, itching
• loss of interest in sex
new or worsening seizures
weak or shallow breathing
feeling like you might pass out
muscle twitching, tremor
• drooling or dry mouth, slurred speech
If the patient takes diazepam with tegretol
decrease levels of diazepam
by increasing the elimination of diazepam
by liver enzymes.
increase level of carbamazepine
by decreasing the elimination of carbamazepine
by liver enzymes.
Who may develops DRESS ?
adults without sex predilection
*most cases occur in adults
pathophysiology of DRESS syndrome remains unclear
A defect in the way the liver metabolizes drugs may be responsible.
Another theory is that co-infection with the human herpes virus 6 (HHV6)
is important to initiate the syndrome.
Genetic may play a role. Pharmacogenetic studies have found a relation
between certain population and certain antiepileptic in developing DRESS
Signs & symptoms
Symptoms and signs vary from mild to severe depending on
the patient and drug
Start up to 12 weeks or more after initiation of drug
treatment and can occur after a dose increase .
e.g. the onset of carbamazepine’s side effects
considerably long and may be reach more than 6 months !
Symptoms may persist or recur for several weeks after
stopping drug treatment.
Investigations ( exclude & prove )
The most useful test
CBC with differential and peripheral blood smear
eosinophilia >700/microL suggests the diagnosis of DRESS.
In some patients, lymphocytosis
• And/or the finding of atypical lymphocytes on
peripheral smear also support the diagnosis
Liver function tests
• Serum alanine aminotransferase (ALT)
greater than twice the upper limit of normal values
• and/or alkaline phosphatase greater than 1.5 times the
upper limit of normal values on at least two different dates indicate
If Liver function tests were positive
Serology for viral hepatitis
(hepatitis A IgM antibody, hepatitis B surface antigen, hepatitis B core IgM
antibody, hepatitis C viral RNA) may be useful in excluding acute viral
Serum creatinine and urinalysis
A moderate increase in creatinine level, low grade
proteinuria, and abnormal urinary sediment
with occasional eosinophils indicate kidney involvement.
The histologic findings of mild spongiosis and
a lymphocytic infiltrate in the superficial dermis,
predominantly perivascular, with eosinophils
and dermal edema, although not specific,
supports the diagnosis of DRESS.
Testing for herpes-virus infection
The search for active infection with human herpes-virus testing for
EBV, HHV-6, or HHV-7 is increasingly performed in patients with DRESS, since
viral infection reactivation may be a marker of prolonged course and increased
risk of complications
In patients presenting with nonspecific symptoms of pulmonary involvement
(eg, cough, tachypnea/dyspnea), chest radiograph or CT scan may provide
evidence of interstitial pneumonitis and/or pleural effusion
Which drug is responsible ?
• helps identify which substances
may be causing a reaction in a patient.
• A patch test relies on the principle of
a type IV hypersensitivity reaction.
• Allergic substance will exhibit
inflammation in the skin
• Useful for detecting an ADR with
carbamazepine and other drugs but not all.
How to treat DRESS?
Stopping all doses of suspected medication causing the symptoms
Keeping the symptoms under control
follow up to avoid relapse
Supportive therapy ( replacement of causative medication )
epinephrine if needed
Prognosis & complication
Most patients with DRESS recover completely in weeks to months after
stop replace the drug
Autoimmune diseases have been reported in some patients months or
years after the resolution of the drug reaction.
In rare cases, patients developed chronic renal failure and lymphoma.
Adverse drug reaction
Adverse drug reaction could be fatal and a special care should
be provide for the patient.
DRESS in detail
If you as a doctor suspect of drug hypersensitivity reaction, it is
important to take a proper medication history with considering
the side effects.