Drug-induced cutaneous reactions

Małgorzata Sokołowska-Wojdyło, MD, MSc, PhD

Elżbieta Grubska-Suchanek MD, PhD

Department of Dermatology, Venereology and Allergology, Medical University of Gdansk

Drug hypersensitivity

Not expected consequences of medicaments ordered in therapeutic doses in right indication.

• in 2-6% of hospitalized patients

• in 8% of other patients

Drug-induced reactions

• medicaments can be applied topically or systemic

• different skin lesions; morphology depends from causal factors and mechnism of action

• in 3-4% of hospitalized patients• in 5% of other patients

Reasons of appearance the drug-induced reactions

Personal characters:• Age and sex• Genetical predisposition• Some disorders

The medicaments’ charcteristics:• Chemical structure• Additives• Long-lasting treatment, especially big doses• Long-lasting topical treatment

Dug induced reactions

Dermatoses caused only by medicaments

Toxic epidermal necrolysis (TEN), Lyell syndrome)

Erythema perstans

Acute generalised exanthematous pustulosis (AGEP)

Pseudolymphoma

Drug-induced reactions

Dermatoses with different etiology

•Utricaria•Erythema multiforme, nodosum•Purpura•Autoimmunological disorders:

- bullous diseases

- systemic lupus erythematosus

Drug-induced reactions

Morphology

•Maculo-papular eruption

•Hemorrhagic

•Lichenoidal

•Acneiforme

•Vesicular and bullous

•Pigmentous

•Morfeiform

•Necrotic

•Pruritus

•Hair and nails lesions

Maculo-papular exanthemas

1st description: 1967 (after ampicillin) - about 5% of ampicillin treated patients

Clinical morphology can imitate infectious disorders

1st symptomes: 5 days – 2 weeks after 1st tablet

Positive patch test and blastic transformation test in some cases – IV mechanism G-C (?)

Drug-induced reaction

Type of reaction Causative drug

Maculo-papular eruption

Aminopenicylines

Sulphonamides

NSAiDs

Anticonvulsants

Psuchotropics

Allopurinol

ACE inhibitors

beta-blockers

Drug-induced reaction

Type of reaction Causative drug

Urticaria

Quincke edema

Antibiotics (penicillin)

Sulphonamides

Aspirin, NSAiDs

Heterologous serum

Insulin

Contrast medium

ACE inhibitors

Opiate

Drug-induced urticaria - mechanisms

Allergic urticaria Cause

1. I mechanism G-C2. III mechanism G-C

Pnc, pirazolons, sulphonamides

Sera, pnc, cephalosporins

Nonallergic urticaria Cuase

1. Direct release of mediators

2. Idiosyncrasia

3. Inibition of inflammatory mediators inactivation

Contrast media (Iod), opiates, curara, polimyksine

Aspiryn, NSAiDs

ACE inhibitors

Angiotensines

Drug – induced reactions

Type Causative drug

Erythemas

Erythema perstans

Erythema nodosum

Erythema multiforme / Stevens-Johnson syndrome

barbituranes, paracetamol,

sulphonamides, tetracyclines

antibiotics, sulphonamides,

NSAiDs, estrogens

antibiotics, sulphonamides,

NSAiDs, barbituranes, anticonvulsants

Lyells’ syndrome (TEN)

• drugs !

• Very rare: infections, vaccines, chemical substances, graft versus host disease

• Skin, mucosa of respiratory and digestive system

• Complications: electrolites disturbances, secondary bacterial infections

Drug-induced TEN (most often causative drugs)

• anticonvulsants (fenytoin, carbamazepine)

• pirazolones’ derivatives

• sulphonamides

• beta-lactams

• chinolones

• allopurinol

Drug-induced reactions

Type cause

Haemorrhagic reaction•trombocytopathies

•trombocytopenies

•vasculitis

ASA

cytostatics

antibiotics(beta-lactams, tetracyclines, streptomycine)

sulphonamides

NSAiDs

diuretic drugs

ACE inhibitors

beta-blockers

anticonvulsants

Vasculitis

Systemic: skin, kidneys, lungs, heart, brain, digestive tract

Classifications’ criteria: - etiopathogenesis - clinical picture - vessels anatomy - histopathological picture

Allergic (leucoclastic) vasculitis

• Hierergic purpur (polymorphous lesions )

• III mechanism G-C

Causative factors: bakteria, viruses, fungi, protozoa, drugs, food

Drug-induced reactionsType Cause

Phototoxic, photoallergic

psolarens

sulphonamides

NSAiDs

tetracyclines

chinolones

thiazydes

furosemid

antimalarial

antidepressive

hormones

Photohypersensitivity

Typ reakcji Obraz kliniczny

Phototoxic

Photoallergic

Sun burn like lesions

(only on sun exposed skin),

hiperpigmentations, lichenoid exanthemas, lupus-like, PCT

Eczema-like

(can be not only on sun exposed skin)

Drug-induced reactions

Type Cause

Erythrodermia

barbiturans

carbamazepine

nitrofurantoin

NSAiDs

sulphonamides

thiazides

Caution!

• anticonvulsants

• sulphonamides

• pirazolones

• antibiotics (beta-lactams)