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. . Chapter 056. Cutaneous Drug Reactions (Part 1) Harrison's Internal Medicine > Chapter 56. Cutaneous Drug Reactions CUTANEOUS DRUG REACTIONS: INTRODUCTION Cutaneous reactions. 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. 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,