Chapter 056. Cutaneous Drug Reactions (Part 1) potx
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Chapter 056. Cutaneous
Drug Reactions
(Part 1)
Harrison's Internal Medicine > Chapter 56. Cutaneous Drug Reactions
CUTANEOUS DRUG REACTIONS: INTRODUCTION
Cutaneous reactions are among the most frequent adverse reactions to
drugs. Every physician will see patients suffering from them. Most are benign, but
a few can be life-threatening. Prompt recognition of severe reactions, drug
withdrawal, and appropriate therapeutic interventions can minimize toxicity. This
chapter focuses on adverse cutaneous reactions to drugs other than topical agents;
it covers their incidence, patterns, and pathogenesis and provides some practical
guidelines on treatment, assessment of causality, and future utilization of drugs.
USE OF PRESCRIPTION DRUGS IN THE UNITED STATES
In the United States more than 3 billion prescriptions for over 60,000 drug
products, which include more than 2000 different active agents, are dispensed
annually. Hospital inpatients alone annually receive about 120 million courses of
drug therapy, and half of adult Americans receive prescription drugs on a regular
outpatient basis. Many additional patients use over-the-counter medicines that
may cause adverse cutaneous reactions.
INCIDENCE OF CUTANEOUS REACTIONS
Several large cohort studies established that acute cutaneous reaction to
drugs affected about 3% of hospital inpatients. Reactions usually occur a few days
to 4 weeks after initiation of therapy.
Many drugs of common use are associated with a 1–2% rate of "rashes"
during premarketing clinical trials. The risk is often higher when medications are
used in general unselected populations. The rate may reach 3–7% for amoxicillin,
sulfamethoxazole, and many anticonvulsants (Table 56-1). It may be even higher
with anti-HIV agents.
Table 56-1 Cutaneous Reactions to Drugs Received by at Least 1000
Patients (BCDSP)
a
Drug Reactio
ns, No.
Recipien
ts, No.
Rat
e, %
95
%
Confiden
ce
Interval
Amoxicillin 63 1225 5.1 3.9
–6.4
Ampicillin 215 4763 4.5 3.9
–5.1
Co-
trimoxazole
46 1235 3.7 2.7
–4.8
Semisyntheti
c penicillins
41 1436 2.9 2.0
–3.7
Red blood
cells
67 3386 2.0 1.5
–2.4
Penicillin G 68 4204 1.6 1.2
–2.0
Cephalospor
ins
27 1781 1.5 0.9
–2.1
Gentamicin 13 1277 1.0 0.5
–1.6
a
BCDSP, Boston Collaborative Drug Surveillance Program.
Source: Adapted from Bigby.
In addition to acute eruptions, a variety of skin diseases can be induced or
exacerbated by prolonged utilization of drugs, e.g., pruritus, pigmentation, nail or
hair disorders, psoriasis, and pemphigus. These chronic drug reactions are not
frequent, but neither their incidence nor their impact on public health has been
evaluated.
In a series of 48,005 inpatients over a 20-year period, morbilliform rash
(91%) and urticaria (6%) were the most frequent skin reactions. Severe reactions
are actually too rare to be detected in such cohorts. Their incidence has been
estimated to be in the range of 1 in 10,000 to 1 in 1 million users. Even though
they are rare, severe cutaneous reactions to drugs have an important impact on
health and on the risk-versus-benefit evaluation of medicines because of
significant mortality and sequelae.
Some populations are at increased risks of drug reactions: patients with
collagen vascular diseases, bone marrow graft recipients, and those with acute
Epstein-Barr virus infection. It has also been established that HIV infection
increases the risk of drug allergy (Chap. 182). This was true for many drugs but
has been evaluated mainly with sulfamethoxazole. Up to 40% of HIV-infected
patients had skin reactions when treated with high doses, and about 15% reacted to
the same dosage that induced 3–5% eruptions in non-HIV-infected populations.
How HIV promotes allergy to certain medications has not yet been explained.
