Drug reaction with eosinophilia and systemic symptoms

Done by: Bayan Al-Ghadeer

Group ( 2)Block 1.2

King Faisal University College of Medicine

rug

eaction

osinophilia

ystamic

ymptoms

Learning Objectives

Adverse drug reaction

DRESS Overview Etiology and risk factors

Pathophysiology

Clinical presentation

 

Diagnosis

Treatment

Complication

Prognosis

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Introduction to the topic

Adverse drug reaction How to identify adverse drug reactions

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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 unrecognized.

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How to identify adverse drug reactions ?

The patient may tell you about symptoms they have experienced since taking a new medicine.

ADR criteria

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

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Overview

Definition Which type of hypersensitivity is it based on ?

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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, lung)

Drug hypersensitivity syndrome

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Which type of hypersensitivity is DRASS ?

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Delayed hypersensitivity reactions

Or type IV hypersensitivity reactions.

inflammatory reactions initiated a secondary cellular response by mononuclear leukocytes .

Lymphocytes (T cells )

monocytes/macrophages

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Etiology and risk factors

Causes side effects of “ Carbamazepine (Tegretol)” side effects of “Diazepam” Who may develops DERSS ?

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What could cause DRESS ?Antiepileptic agents e.g. carbamazepine

drugs associated with DRESS

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Carbamazepine

Antiepileptic drug

Common side effects may include:• feeling dizzy• drowsy, or unsteady• Nausea• vomiting

• diarrhea• constipation• stomach pain

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Serious side effect such as:• pale skin and skin pain

• feeling light-headed

• rapid heart rate,

• trouble concentrating

• Fever

• Chills

• sore throat

• mouth and throat ulcers

• easy bruising or bleeding,

• urinating less than usual• Jaundice

(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 and peeling.

• severe tingling• numbness• pain and muscle weakness• Confusion• agitation• vision problems• hallucinations• feeling short of breath• swelling of your ankles or feet

Cont…

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It is often used in stress and anxiety.

Side effects: • drowsiness, tired feeling

• memory problems

• dizziness, spinning sensation

• feeling restless or irritable

• muscle weakness

• nausea, constipation

• drooling or dry mouth, slurred speech

Diazepam

• 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

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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.

Carbamazepine Diazepam

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Who may develops DRESS ?

Children

adults without sex predilection

*most cases occur in adults

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Pathophysiology

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Pathophysiology

A defect in the way the liver metabolizes drugs may be responsible.

immunological imbalance

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

pathophysiology of DRESS syndrome remains unclear

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Clinical presentation

Signs & symptoms

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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.

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Prominenteosinophilia

Hepatitis

Exanthema

Lymphadenopathy

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Facial swelling

Generalized edema

Fever

Multi-organ failure

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Diagnosis

Investigations ( exclude & prove ) The most useful test

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Investigations

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 of DRESS.  

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Cont...

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 liver involvement.

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 hepatitis .

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Cont...

Serum creatinine and urinalysis 

A moderate increase in creatinine level, low grade proteinuria, and abnormal urinary sediment with occasional eosinophils indicate kidney involvement.

Skin biopsy  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.

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Cont...

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

Imaging studies 

 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

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Which drug is responsible ?

Patch test• 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.

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Treatment

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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 )

Antihistamine

Corticosteroids

epinephrine if needed

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Complication & Prognosis

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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.

death

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Summary

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.

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References

http://www.dermnetnz.org/reactions/drug-hypersensitivity-syndrome.htmlhttp://www.rxlist.com/tegretol-side-effects-drug-center.htm

http://www.rxlist.com/valium-side-effects-drug-center.htm

http://treato.com/Carbamazepine,Diazepam/?a=s

http://www.uptodate.com/contents/drug-reaction-with-eosinophilia-and-systemic-symptoms-dress

http://dermnetnz.org/reactions/drug-hypersensitivity-syndrome.html

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