Drug Eruption and Interactions - PHARMACEUTICAL REVIEW

Erythema nodosum
Erythema nodosum is a cutaneous reaction pattern characterized
by erythematous, tender or painful subcutaneous
nodules commonly distributed over the anterior aspect of
the lower legs, and occasionally elsewhere.
More common in young women, erythema nodosum is
often associated with increased estrogen levels as occurs
during pregnancy and with the ingestion of oral contraceptives.
It is also an occasional manifestation of streptococcal
infection, sarcoidosis, secondary syphilis, tuberculosis, certain
deep fungal infections, Hodgkin’s disease, leukemia,
ulcerative colitis, and radiation therapy and is often preceded
by fever, fatigue, arthralgia, vomiting, and diarrhea.
The incidence of erythema nodosum due to drugs is low
and it is impossible to distinguish clinically between erythema
nodosum due to drugs and that caused by other factors.
Some of the drugs that are known to occasion erythema
nodosum are: antibiotics, estrogens, amiodarone, gold,
NSAIDs, oral contraceptives, sulfonamides, and opiates.
Exanthems
Exanthems, commonly resembling viral rashes, represent
the most common type of cutaneous drug eruption.
Described as maculopapular or morbilliform eruptions,
these flat, barely raised, erythematous patches, from one to
several millimeters in diameter, are usually bilateral and symmetrical.
They commonly begin on the head and neck or
upper torso and progress downward to the limbs. They may
present or develop into confluent areas and may be accompanied
by pruritus and a mild fever.
The exanthems caused by drugs can be classified as
either:
Morbilliform eruptions: fingernail-sized erythematous
patches
Scarlatiniform eruptions: punctate, pinpoint, or pinheadsized
lesions in erythematous areas that have a tendency
to coalesce. Circumoral pallor and the subsequent appearance
of scaling may also be noted.
Maculopapular drug eruptions usually fade with desquamation
and, occasionally, postinflammatory hyperpigmentation,
in about 2 weeks. They invariably recur on rechallenge.
Exanthems often have a sudden onset during the first 2
weeks of administration, except for semisynthetic penicillins
that frequently develop after the first 2 weeks following the
initial dose.
The drugs most commonly associated with exanthems
are: amoxicillin, ampicillin, bleomycin, captopril,
carbamazepine, chlorpromazine, co-trimoxazole, gold,
nalidixic acid, naproxen, phenytoin, penicillamine, and
piroxicam.
DESCRIPTION OF THE 34 MOST COMMON REACTION PATTERNS 647
Exfoliative dermatitis
Exfoliative dermatitis is a rare but serious reaction pattern
that is characterized by erythema, pruritus and scaling over
the entire body (erythroderma).
Drug-induced exfoliative dermatitis usually begins a few
weeks or longer following the administration of a culpable
drug. Beginning as erythematous, edematous patches, often
on the face, it spreads to involve the entire integument. The
skin becomes swollen and scarlet and may ooze a straw-colored
fluid; this is followed in a few days by desquamation.
High fever, severe malaise and chills, along with enlargement
of lymph nodes, often coexist with the cutaneous
changes.
One of the most dangerous of all reaction patterns,
exfoliative dermatitis can be accompanied by any or all of the
following: hypothermia, fluid and electrolyte loss, cardiac
failure, and gastrointestinal hemorrhage. Death may supervene
if the drug is continued after the onset of the eruption.
Secondary infection often complicates the course of the disease.
Once the active dermatitis has receded,
hyperpigmentation as well as loss of hair and nails may ensue.
The following drugs, among others, can bring about
exfoliative dermatitis: barbiturates, captopril,
carbamazepine, cimetidine, furosemide, gold, isoniazid, lithium,
nitrofurantoin, NSAIDs, penicillamine, phenytoin,
pyrazolons, quinidine, streptomycin, sulfonamides, and
thiazides.
Fixed eruptions
A fixed eruption is an unusual hypersensitivity reaction characterized
by one or more well demarcated erythematous
plaques that recur at the same cutaneous (or mucosal) site
or sites each time exposure to the offending agent occurs.
The sizes of the lesions vary from a few millimeters to as
much as 20 centimeters in diameter. Almost any drug that is
ingested, injected, inhaled, or inserted into the body can trigger
this skin reaction.
The eruption typically begins as a sharply marginated, solitary
edematous papule or plaque – occasionally surmounted
by a large bulla – which usually develops 30 minutes to
8 hours following the administration of a drug. If the offending
agent is not promptly eliminated, the inflammation intensifies,
producing a dusky red, violaceous or brown patch that
may crust, desquamate, or blister within 7 to 10 days. The
lesions are rarely pruritic. Favored sites are the hands, feet,
face, and genitalia – especially the glans penis.
The reason for the specific localization of the skin lesions
in a fixed drug eruption is unknown. The offending drug cannot
be detected at the skin site. Certain drugs cause a fixed
eruption at specific sites, for example, tetracycline and
ampicillin often elicit a fixed eruption on the penis, whereas
aspirin usually causes skin lesions on the face, limbs and
trunk.