{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