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{DRESS Syndrome
Drug Reaction with Eosinophilia and Systemic Symptoms
Define the Adverse Drug Reactions. Understand the Etiology of Adverse
Drug Reaction. Define DRESS Syndrome. Mention the Etiologic Causes. Recognize the pathophysiological
mechanism Describe the Signs & Symptoms. Demonstrate the Diagnostic
Investigations. Mention the Treatment options &
preventive methods. Describe the prognosis
OBJECTIVES
The Adverse Drug Reaction
Adverse drug reaction (ADR) is a broad term referring to unwanted, uncomfortable, or dangerous effects that a drug may have.
Side effect is an imprecise term often used to refer to a drug's unintended effects that occur within the therapeutic range.
All drugs have the potential for ADRs.
Type A reactions are pharmacological effects that are predictable and dose-dependent and consist of side effects and drug interactions.
Type B reactions are hypersensitivity reactions that are unpredictable and not dose-dependent, usually occurring at normally tolerated doses.
Etiology of ADR
Drug hypersensitivity (or DRESS) is an immune-mediated reaction to a drug.
Also called drug-induced hypersensitivity syndrome (DHS).
DRESS Syndrome
Etiology
Defect in the way the liver metabolizes
drugs
Co-infection with the human herpes virus 6
(HHV6)
Genetic predisposition to
drug hypersensitivity syndrome
{
Anti-gout drug
Allopurinol
Anti-epilepsy drugs (esp. carbamazepine, phenobarbital and phenytoin)
sulphonamide group of antibiotics.
The most common drugs to cause this reaction
Causative Drugs
Pathophysiology
2. Protein and large polypeptide
drugs
3. Most drugs act as
haptens
Carrier
1. Introduction
of drugs
Pathophysiology
2. Protein and large polypeptide
drugs
Carrier
Carrier
α3α2α1 β
3. Most drugs act as
haptens
4. Bind to peptides in
(MHC) molecules
Pathophysiology
Carrier
α3α2α1 β
4. Bind to peptides in
(MHC) molecules
5. Immunogenic
protein stimulate one
or both of
Some drugs directly stimulate
T-cell responses
A. cytokine
B. Cytotoxicit
y
Antidrug antibody
production
CD4
CD8
6. Recognition to drug protein on the MHC I
or II
A. Releasing cytokines
Inflammation
Normal cellular tissueMHC I
Drug carrier
Cytokines
Neutrophil enzymes, ROS
Neutrophil
Macrophage
Tissue injury
6. Recognition to drug protein on ONLY MHC
I
B. Cytotoxicit
y
MHC I
Drug carrier
CD8+ CTLs
Cell lysis & tissue injury
Signs and Symptoms
Symptoms and signs vary from mild to severe depending on the patient and drug
Start up to 12 weeks after initiation of drug treatment and can occur after a dose increase.
Symptoms may persist or recur for several weeks after stopping drug treatment.
Signs and Symptoms
Prominent eosinophilia Hepatitis Exanthema
Facial swelling Generalized edema
Lymphadenopathy
Sometimes direct and indirect antiglobulin assays
For hematologic drug reactions
Sometimes drug provocation testingDrug is given in escalating doses
to precipitate the reaction Is usually safe and effective
Patient's report of a reaction soon after taking a drug
Time of onset Effects of a drug, and results of a repeat drug challenge
Diagnosis
Drug discontinuation• stopping the implicated drug• most symptoms & signs clear in a few days
Supportive treatment• antihistamines• corticosteroids• epinephrine
Sometimes desensitization• if sensitivity established• if treatment is essential and no alternative• reduces sensitivity only temporarily
Treatment
Avoiding the drug
Carry identificatio
n or an alert
bracelet.
Charts should be marked.
Prevention
Hypersensitivity decreases with time.
The mortality from drug hypersensitivity syndrome is estimated at around 8%.
Prognosis
The Merck Manual 9th E. Abbas & Lichtman, Basic Immunology 3E.
http://www.dermnetnz.org/reactions/drug-hypersensitivity-syndrome.html
References
{THANKS
FATIMA ALAWADH