Urticaria/Cutaneous Drug Reactions

Jerry Tan MD FRCP University of Western Ontario

Windsor, Ontario

Objectives

List the morphological types of cutaneous drug eruptions

Differentiate between the hypersensitivity exanthems

List types of urticaria and possible provoking factors

Contrast angioedema from urticaria

Identifying the offending drug

Potential drug triggers:

New drugs within preceding 6 wks

Drugs used intermittently

Laxatives, analgesics

Over the counter and herbal

products Any drug can cause a

cutaneous reaction.

Cutaneous drug reactions: Specific morphologies

1. Exanthematous

Simple

Hypersensitivity syndrome

2. Urticarial

Simple urticaria

Angioedema

3. Blistering

Fixed drug eruption

Erythema multiforme and variants

Drugs can induce almost

any cutaneous

morphological pattern

I. Exanthematous eruptions

(syn. morbilliform, maculopapular)

Most common cutaneous drug reaction morphology

Caused by many drugs

most commonly penicillins, sulfonamides, barbiturates,

anticonvulsants

Simple Exanthem

Patchy pruritic erythema without fever

Usually develops within 1 wk,

resolves within 7-14 days of d/c offending drug

Tx: topical steroids +/- oral antihistamines to

relieve itch

Exanthematous drug eruptions

Exanthems: Hypersensitivity Syndrome

triad of fever, skin eruption, internal organ involvement

associated lymphadenopathy, atypical lymphocytosis

and eosinophilia

cutaneous eruption in 85%:

ranges from mild erythema multiforme to potentially life-

threatening Steven-Johnson syndrome (SJS) or toxic epidermal

necrolysis (TEN)

Variants of hypersensitivity exanthems

EM minor

Target lesions or raised, edematous papules @ distal

extremities

EM major As above plus with involvement of > 1 mucous membranes;

Epidermal detachment <10% of total body surface area (TBSA).

SJS/TEN

Widespread blisters predominant @ trunk and face

> 1 mucous membrane erosions;

epidermal detachment < 10% TBSA for SJS; > 30% for TEN.

Causes: Hypersensitivity Syndrome

o Drugs (anticonvulsants, antibiotics, allopurinol, NSAIDs)

o infections,

o neoplasia,

o autoimmune disease,

…the more severe the reaction, the likelier a drug trigger

Clinical types: Hypersensitivity exanthems

1. Erythema Multiforme: target lesions

2. Stevens Johnson Syndrome (SJS) - target lesions

+ extensive mucosal erosions

3. Toxic epidermal necrolysis (TEN) - extensive

epidermal necrosis and skin detachment

•

•

often associated with hepatitis;

less frequently nephritis, pneumonitis, vasculitis

EM minor

Phenotypic variety in EM. A Edematous/urticarial; B urticarial lesions with central crusting; C Erythematous plaques with dusky centers; D classic target lesions on the palms.

Stevens-Johnson syndrome. Epidermal detachment (A) and involvement of the conjunctivae (B) and oral mucosa (above)

Toxic epidermal necrolysis (TEN)

A Detachment of large

sheets of necrolytic

epidermis (>30% body

surface area), leading to

extensive areas of

denuded skin.

B Hemorrhagic crusts with

mucosal involvement.

C Epidermal detachment of

palmar skin.

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Stevens Johnson Syndrome (SJS)

= EM + mucosal erosions

o Fever, epidermal detachment < 10% body surface area

Toxic epidermal necrolysis (TEN)

= extensive epidermal necrosis and skin detachment

o

o

Fever, epidermal detachment > 30% body surface area

Associated hepatitis, nephritis, pneumonitis, vasculitis; risk of

sepsis

Treatment for SJS and TEN

1.

2.

3.

4.

withdraw triggering factor

admit to burn unit (for TEN);

specialist consultations;

supportive therapy +/- steroids, IV

immunoglobulin, or cyclosporine

II. Urticarial eruptions

1. Urticaria

o Itchy edematous well defined wheals of varying sizes

o involves epidermis and upper dermis

2. Angioedema

o pale, poorly defined induration

o edema also involves deep dermal and subcutaneous tissues

o Potentially life threatening if involves oro-pharynx

o Associations: nausea, vomiting, diarrhea, abdo pain, laryngeal

edema, brochospasm, hypotension (anaphylaxis)

Urticarial reactions Mast cell activation and degranulation by:

type I immediate hypersensitivity (IgE mediated) or

direct non-immunologic activation of mast cells (IgE independent)

Treatment:

1. withdrawal of trigger factor(s)

2. oral antihistamines

3. for severe cases (angioedema, anaphylaxis): epinephrine

injections, systemic steroids, emergency care

Widespread urticaria

Angioedema:

• Swelling is

deeper than

urticaria

• may affect

mucosal sites

• often pale and

poorly defined.

Types of urticaria

Type Provoking factors Comments

Foods, insect stings, drugs, contact agents,Acute Duration < 6 weeks

infections, systemic diseases, idiopathic

Chronic Idiopathic, otherwise similar to acute Duration > 6 weeks

Cholinergic Heat, exercise, hot showers Tiny red wheals

Typically hands (gloves), feet (footwear), Contact Rubber latex common trigger

mouth (balloons)

aquagenic (water); adrenergic (stress); cold;

Physical heat; physical (pressure, rubbing, vibration); Discrete physical trigger factors

solar;

Tender, not itchy. Lesions last > 24 hrs. Vasculitis Primary and secondary vasculitides

Residual purpura, hyperpigmentation.

III. Blistering Eruptions

1. Fixed drug eruption

2. Erythema Multiforme (bullous type) / Stevens Johnson

syndrome / Toxic epidermal necrolysis

Fixed drug eruption

Solitary itchy dusky red macule or edematous plaque

Recurs at same site after offending drug exposure

May progressively increase with continued exposure

Common drug offenders:

phenolphthalein, NSAIDs, sulfonamides, antibiotics, barbiturates

Fixed drug eruptions

Summary

List specific morphological types of cutaneous drug eruptions

Differentiate between the hypersensitivity exanthems

List types of urticaria and possible provoking factors

Contrast angioedema from urticaria

Acknowledgements References:

Shear, Knowles and Shapiro Cutaneous Drug Reactions, Web MD Scientific American, Feb 2001.

Lebwohl, M: Cutaneous Manifestations of Systemic Diseases, WebMD Scientific American Medicine, June 2003 update.

Gawkrodger DJ. Dermatology an illustrated color text. Churchill Livingstone 2001

Illustrations: Dermatology Image Atlas: www.dermatlas.org

www.dermis.net

www.derm101.com

www.dermtext.com