Drug Eruption and Interactions - PHARMACEUTICAL REVIEW

suggest an adverse reaction to light. The distribution is the
key to the diagnosis.
Initially the eruption, which consists of erythema, edema,
blisters, weeping and desquamation, involves the forehead,
rims of the ears, the nose, the malar eminences and cheeks,
the sides and back of the neck, the extensor surfaces of the
forearms and the dorsa of the hands. These reactions commonly
spare the shaded areas: those under the chin, under
the nose, behind the ears and inside the fold of the upper
eyelids. There is usually a sharp cut-off at the site of jewelry
and at clothing margins. All light-exposed areas need not be
affected equally.
There are two main types of photosensitive reactions: the
phototoxic and the photoallergic reaction.
Phototoxic reactions, the most common type of druginduced
photosensitivity, resemble an exaggerated sunburn
and occur within 5 to 20 hours after the skin has been
exposed to a photosensitizing substance and light of the
proper wavelength and intensity. It is not a form of allergy –
prior sensitization is not required – and, theoretically, could
occur in anyone given enough drug and light. Phototoxic
reactions are dose-dependent both for drug and sunlight.
Patients with phototoxicity reactions are commonly sensitive
to ultraviolet A (UVA radiation), the so-called ‘tanning
rays’ at 320–400 nm. Phototoxic reactions may cause
onycholysis, as the nailbed is particularly susceptible because
of its lack of melanin protection.
Patients with a true photoallergy (the interaction of drug,
light and the immune system), a less common form of druginduced
photosensitivity, are often sensitive to UVB radiation,
the so-called ‘burning rays’ at 290–320 nm.
Photoallergic reactions, unlike phototoxic responses, represent
an immunologic change and require a latent period of
from 24 to 48 hours during which sensitization occurs. They
are not dose-related.
If the photosensitizer acts internally, it is a photodrug
reaction; if it acts externally, it is photocontact dermatitis.
Drugs that are likely to cause phototoxic reactions are:
amiodarone, nalidixic acid, various NSAIDs, phenothiazines
(especially chlorpromazine), and tetracyclines (particularly
demeclocycline).
Photoallergic reactions may occur as a result of exposure
to systemically administered drugs such as griseofulvin,
NSAIDs, phenothiazines, quinidine, sulfonamides,
sulfonylureas, and thiazide diuretics as well as to external
agents such as para-aminobenzoic acid (found in
sunscreens), bithionol (used in soaps and cosmetics),
paraphenylenediamine, and others.
Pigmentation
Drug-induced pigmentation on the skin, hair, nails, and
mucous membranes is a result of either melanin synthesis,
increased lipofuscin synthesis, or post-inflammatory
pigmentation.
DESCRIPTION OF THE 34 MOST COMMON REACTION PATTERNS 649
Color changes, which can be localized or widespread, can
also be a result of a deposition of bile pigments (jaundice),
exogenous metal compounds, and direct deposition of elements
such as carotene or quinacrine.
Post-inflammatory pigmentation can follow a variety of
drug-induced inflammatory cutaneous reactions; fixed eruptions
are known to leave a residual pigmentation that can
persist for months.
The following is a partial list of those drugs that can cause
various pigmentary changes: anticonvulsants, antimalarials,
cytostatics, hormones, metals, tetracyclines, phenothiazine
tranquilizers, psoralens, amiodarone, etc.
Pityriasis rosea-like eruptions
Pityriasis rosea, commonly mistaken for ringworm, is a
unique disorder that usually begins as a single, large, round or
oval pinkish patch known as the ‘mother’ or ‘herald’ patch.
The most common sites for this solitary lesion are the chest,
the back, or the abdomen. This is followed in about 2 weeks
by a blossoming of small, flat, round or oval, scaly patches of
similar color, each with a central collarette scale, usually distributed
in a Christmas tree pattern over the trunk and, to a
lesser degree, the extremities. This eruption seldom itches
and usually limits itself to areas from the neck to the knees.
While the etiology of idiopathic pityriasis rosea is
unknown, we do know that various medications have been
reported to give rise to this friendly disorder. These are: barbiturates,
beta-blockers, bismuth, captopril, clonidine, gold,
griseofulvin, isotretinoin, labetalol, meprobamate,
metronidazole, penicillin, and tripelennamine.
In drug-induced pityriasis rosea, the ‘herald patch’ is usually
absent, and the eruption will often not follow the classic
pattern.
Pruritus
Generalized itching, without any visible signs, is one of the
least common adverse reactions to drugs. More frequently
than not, drug-induced itching – moderate or severe – is
fairly generalized.
For most drugs it is not known in what way they elicit pruritus;
some drugs can cause itching directly or indirectly
through cholestasis. Pruritus may develop by different
pathogenetic mechanisms: allergic, pseudoallergic (histamine
release), neurogenic, by vasodilatation, cholestatic
effect, and others.
A partial list of those drugs that can cause pruritus are as
follows: aspirin, NSAIDs, penicillins, sulfonamides,
chloroquine, ACE inhibitors, amiodarone, nicotinic acid
derivatives, lithium, bleomycin, tamoxifen, interferons, gold,
penicillamine, methoxsalen, isotretinoin, etc.