Adverse Cutaneous Reactions to Drug

Wei Qingyu
The first people’s hospital of yichang
• Adverse cutaneous reactions to drugs, also known as
drug eruptions, are unwanted or unintended cutaneous or
mucocutaneous inflammatory drug reactions.

The resulting skin lesions are caused by agents reaching the

skin either systemically (typically ingestion, inhalation,
injection, or via suppository), or through direct topical
application to the surface of the skin.
ingestion inhalation
injection direct topical application to

the surface of the skin

The drugs capable of causing drug eruptions are quite
diverse. The clinical appearances vary according to the
specific combination of drugs used and the individual’s
condition when the drugs are administered.
At times the conditions can be
serious, with involvement of a
number of systems, and can even
become life-threatening.
Etiology
There's no single mechanism for drug eruptions, but some of the factors t
hat predispose to such conditions is listed below.
1. Individual factors:
genetic factors,
enzyme deficiencies,
underlying immune status,etc.

Drugs that commonly cause drug eruptions include

2. Drug factors:
Antibiotics
antipyretics and analgesics
Sedative hypnotics and antiepileptics
Heterologous serum products and vaccines
Pathogenesis
The pathogenesis of adverse cutaneous drug reactions is quite complicated,
but can simply be divided into hypersensitivity and non-hypersensitivity, th
e former being more common.

●Hypersensitivity ●Non-hypersensitivity
Pathogenesis
• Characteristics of hypersensitivity

① They are less predictable.

②They occur in only a minority of patients receiving a

drug and can do so even with low doses.

③They usually appear after the latent period required for

an immune response.

④Chemically related drugs may cross-react.

Pathogenesis
• Characteristics of hypersensitivity

⑤The clinical manifestations of drug eruption varies

among individuals for the same drug and even varies with
time for the same patient.

⑥Anti-allergic drugs and glucocorticoids are usually

effective.
Pathogenesis
• Characteristics of non-hypersensitivity

①Some are a result of overdosage, others to the

accumulation of drugs, e.g. stretch marks from systemic
steroids.

② this type of reaction is produced by direct inducing

the drugs with the immune system effectors without inducing
an antigen-antibody reaction. (Non-immunologic activation of
immune effect pathways)
 Pathogenesis
• Characteristics of non-hypersensitivity

③The patient is unable to produce the enzymes required for

drug a metabolism, either due to genetic factors or others.

④They are often predictable.

⑤They affect many, or even all patients taking the drug at a

sufficient dosage for a sufficient time.
Clinical Manifestations

The clinical manifestations for drug eruption is complicated si

nce these eruptions may stimulate virtually any cutaneous dise
ase.
 Clinical Manifestations
1. Fixed drug reactions.

The list of reactions illu 2. Urticarial drug reactions

3. Morbilliform or Scarlatiniform drug reactions
strate the extraordinary
4. Eczematous drug reactions
diversity of cutaneous e
5. Purpuric drug reactions
xpressions of adverse d
6. Erythema multiforme drug reactions
rug reactions. 7. Epidermal necrolysis drug reactions
8. Drug reactions of exfoliative dermatitis
9. Acneiform drug reactions
10. Photosensitive drug reactions
11. Drug hypersensitivity syndrome
12. Other types
 Clinical Manifestations
1. Fixed drug reactions

Single or multiple, round,

sharply demarcated, dusky
red plaques appear soon
after drug exposure and
reappear in exactly the
same site each time the
drug is taken.

• The area often blisters and then erodes, desquamation or crusting (after
bullous lesions) follows, and brown pigmentation forms with healing.
 Tetracycline and cotrimoxazole commonly cause
lesions limited to the glans penis.
Cases of familial occurrence suggest that a genetic predisposition
might be an important causal factor.
• The lesions are generally preceded or accompanied by itching
and burning, the intensity of which is usually proportionate to
the severity of the inflammatory changes.

• Pruritus and burning may be the only manifestations of

reactivation in an old patch.

• Lesions can occur on any part of the skin or mucous

membrane, but the glans penis is the most common site.
 2. Urticarial drug reactions
• Urticaria is frequently caused by
drugs, and most drugs can induce
hives.

• Hives are itchy, red, edematous

plaques that are usually generalized
and symmetric. There is no scaling or
vesiculation.

• Aspirin, penicillin, and blood

products are the most frequent causes
of urticarial drug eruptions.
 2. Urticarial drug reactions

• Wheals vary in size from small

papules to huge plaques.

• Angioedema refers to urticarial

swelling of deep dermal and
subcutaneous tissues and mucous
membranes, the reaction may be life
threatening.
3. Morbilliform or Scarlatiniform drug reactions
(Exanthematous drug reactions)

This term describes the most common type of drug eruption,

looking sometimes like measles or scarlet fever, and sometimes
showing prominent urticarial or erythema multiforme-like
elements. Itching and fever may accompany the rash.
Culprits include antibiotics (especially ampicillin), sulphonamides
and related compounds (diuretics and hypoglycaemics), barbiturates,
phenylbutazone and para-aminosalicylate (PAS).
4. Eczematous drug reactions

①The patient usually has a history of contact dermatitis,

which has sensitized the skin to some topically administrated
penicilin, streptomycin, or sulfonamide.

②A generalized eczematous eruption may then develop upon

systemic administration of the same or a across-reacting drug.
contact dermatitis (sharply demarcated)
5. Purpuric drug reactions

Thiazides, sulphonamides
phenylbutazone, barbiturates
and quinine are among the drugs
reported to cause purpura.
 5. Purpuric drug reactions

In several cases, the lesions are

accompanied by arthralgia, abdominal
pain, hematuria, blood in stool, etc.

Thrombocytopenia and coagulation

defects should be excluded.
6. Erythema multiforme drug reactions

Target-like lesions appear mainly on the extensor

aspects of the limbs, and bullae may form.
6. Erythema multiforme drug reactions

In the Stevens–Johnson syndrome, the patients are

often ill and the mucous membranes are severely
affected.

Sulphonamides, barbiturates, lamotrigine and

phenylbutazone are known offenders.
7. Epidermal necrolysis drug reactions
( Stevens-Johnson syndrome (SJS) and Toxic
epidermal necrolysis(TEN))

It’s the most severe cutaneous drug reactions.This type of

drug reaction may manifest as Stevens-Johnson syndrome
(SJS) and Toxic epidermal necrolysis(TEN), both of which
have the similar drug etiology, mechanisms, clinical and
histopathological findings.

The most important difference between SJS and TEN is

that the involved body surface area(BSA) is less than 10
percent in SJS and more than 30 percent in TEN.
7. Epidermal necrolysis drug reactions
• The onset is acute .
• The lesions at first may resemble morbilliform or scarlatiniform drug
reactions.
• But then evolved rapidly into purplish red or dark red patches overlaid
with variously sized flaccid bullae and epidermolysis on erythematous
macules that spread quickly over the entire body. Nikolsky's sign is positive

• Severe constitutional, such as high fever, nausea, diarrhea,

delirium, and even coma are likely to occur.
• Even more severe consequences from secondary infections, liver
and renal failure, electrolyte imbalance and visceral hemorrhage,
may lead to death if treatment is not begun immediately.
7. Epidermal necrolysis drug reactions

epidermolysis
7. Epidermal necrolysis drug reactions

epidermolysis
 8. Drug reactions of exfoliative dermatitis

The entire skin surface

becomes red and scaly.
This can be caused
by drugs ( particularly
phenylbutazone, para-
aminosalicylate (PAS),
isoniazid and gold), but
can also be caused by
widespread psoriasis and
eczema.
8. Drug reactions of exfoliative dermatitis
 9. Acneiform drug reactions :
Acneiform drug reactions commonly develop after long-term use of
iodides, bromides, glucocorticoids and contraceptives.
The lesions are acneiform lesions, such as follicular papules, or
papulovesicles on the face, chest and back.
The course progresses slowly, usually without general symptoms.
10. Photosensitive drug reactions

Photosensitivity eruptions represent 8% of all adverse

cutaneous drug reactions. Both systemic and topical
medications can induce photosensitivity. There are two main
types: phototoxicity and photoallergy.
10. Photosensitive drug reactions

Phototoxic reactions are related to drug concentration and

can occur in anyone.

The eruption is confined to sun-exposed areas.

The reaction can occur on first administration and subsides

when the drug is stopped.
 10. Photosensitive drug reactions

Photoallergic reactions are less common and are not

concentration related.

They occur in only a small fraction of people exposed and

may spread to involve areas that have not been exposed to
the sun, possibly from an autosensitization phenomenon.

They are a form of delayed hypersensitivity reaction and

appear within 24 to 48 hours of antigenic challenge.

On rare occasions, the reaction can persist for years, even

without further drug exposure.
11. Drug hypersensitivity syndrome:

this condition is also often referred to as drug reaction

accompanied by eosinophilia and systemic symptoms.
the most frequent causative drugs in this case are
antiepileptics and sulfonamides.

The onset is sudden and the clinical manifestations

include fever, skin rash, limphadenopathy, and internal
organ involvement.

Morbilliform lesions---later become----exfoliative

dermatitis like lesions

Facial swelling is the characteristic for this

syndrome.
12. Other types

acute generalized eruptive pustulosis,

drug-induced pigmentation,
drug-induced systemic lupus erythematosus,
lichenoid reactions, etc.
 Severe adverse cutaneous drug
reactions

• SJS

• TEN

• Exfoliative dermatitis drug eruptions

Diagnosis
The diagnosis of drug eruptions rests upon

• A positive history of drug administration

• A latent period tied to the timeline for the treatment

• Typical clinical features of the different patterns of

drug reactions

• Consistent exclusion of any other skin conditions

with similar lesions or exanthematous infections.
Differential Diagnosis

• Measles

• Scarlet fever

• Staphylococcal scalded skin syndrome

• Genital herpes

• Chancre
Treatment

The specific ways of available to physicians to treat dru

g eruption are as follows

To discontinue all suspected drugs at once,

to accelerate the excretion of the sensitizing drug,
to eliminate or avoid the drug reactions,
and quickly treat any complications.
1. Minor type of drug reactions
• Antihistamine
• VitaminC
• Prednisone treatment in moderate doses (30-60
mg/d, tapered gradually)
• Topical treatment
2. Major type of drug reactions


Glucocorticoids

Prevent and treat secondary infections

Strengthen supportive therapy

Strengthening care and topical therapy
The end !

Many thanks for your attention !