Chapter 056. Cutaneous Drug Reactions (Part 8) potx

Chapter 056. Cutaneous
Drug Reactions
(Part 8)

DRUGS OF SPECIAL INTEREST
Allopurinol
Together with sulfonamides and antiepileptics, allopurinol is one of the
"usual suspects" that induce frequently mild maculopapular eruptions (in at least
3% of users) and may also cause more severe reactions including
hypersensitivity/DRESS and SJS/TEN. Because of increasing utilization it is one
of the most frequent causes of life-threatening reactions.
Anti-HIV Medications
In clinical trials, combinations of highly active antiretroviral treatments
were frequently associated with ≥10% "drug eruptions." Two drugs, nevirapine
and abacavir, have been associated with specific risks.
Nevirapine has both a high risk of maculopapular eruptions and a very high
risk (about 1 in 1000) of SJS or TEN. Progressive escalation of daily doses has
been shown to decrease the risk of mild eruption but does not abrogate the risk of
severe reactions.
Abacavir is associated with a 4–5% risk of a hypersensitivity reaction,
which is remarkable because of the association of symptoms suggesting a type I
reaction (dyspnea, diarrhea, low blood pressure, shock on rechallenge) and signs
of delayed hypersensitivity (rash, late onset, hepatitis). The risk is lower in
patients of African ancestry and strongly correlated with HLAB*5701.
Penicillin
The utilization rate of penicillin has decreased markedly since it has been
the subject of many investigations and a model for "drug allergy." Incidence of
cutaneous reactions is about 1%. About 85% of cutaneous reactions to penicillin
are morbilliform, and about 10% are urticaria or angioedema. Anaphylaxis and
serum sickness appear to be due to IgE antibodies in serum.
Delayed reactions, mainly maculopapular eruptions, are much more

common with aminopenicillins, involving 4–7% of users. The question of cross-
reactivity between β-lactam antibiotics and preventing the risk of anaphylaxis is
discussed below ("Management of a Patient with a Drug Eruption").
Nonsteroidal Anti-Inflammatory Drugs
Most NSAIDs, including aspirin, cause immediate allergy-like symptoms
in susceptible individuals. Approximately 1% of persons experience urticaria or
angioedema, and about half as many (0.5%) experience rhinosinusitis and asthma.
Urticaria/angioedema may be delayed up to 24 h and may occur at any age.
The rhinosinusitis-asthma syndrome generally develops within 1 h of drug
administration. Recurrences are frequent and can be complicated by nasal and
sinus infection, polyposis, bloody discharge, and nasal eosinophilia. In many
individuals with this syndrome, asthma that can be life-threatening eventually
ensues whenever NSAIDs are subsequently ingested. Proof of the association of
symptoms and NSAID use requires either clear-cut history of symptoms following
drug ingestion or an oral challenge. That procedure must be conducted only in a
hospital setting by experienced personnel. Cross-reactivity between NSAIDs that
inhibit cyclooxygenase (COX) 1 is common, while reactivity to COX-2 inhibitors
is less frequent. The reaction is pharmacologic, and patients who are sensitive to
NSAIDs cannot be identified by assessment of IgE antibody to aspirin,
lymphocyte sensitization, or in vitro immunologic testing.
Other reactions can also occur with NSAIDs, including phototoxicity with
many agents, a pattern of pseudoporphyria being often related to naproxen,
hypersensitivity/DRESS (oxicam derivatives, COX-2 inhibitors), and SJS or TEN
(phenylbutazone, oxicam derivatives, diclofenac).
Radiocontrast Media
Large numbers of patients are exposed to radiocontrast agents. High-
osmolality radiocontrast media were about five times more likely to induce
urticaria (1%) or anaphylaxis than were newer low-osmolality media. Severe
reactions are rare with either type of contrast media. About one-third of those with
mild reactions to previous exposure re-react on re-exposure. In most cases, these

reactions are probably not immunologic. Pretreatment with prednisone and
diphenhydramine reduces reaction rates. Persons with a reaction to a high-
osmolality contrast media should be given low-osmolality media if later contrast
studies are required.
Anticonvulsants
Along with sulfonamide antibiotics, phenobarbital, phenytoin, and
carbamazepine among the older anticonvulsants, and lamotrigine among the
newer, are associated with many types of severe reactions and a high incidence of
less severe reactions, particularly in children. These drugs have among the highest
risk of SJS, TEN, and hypersensitivity syndrome in immunologically normal
patients. The aromatic anticonvulsants can induce a pseudolymphoma syndrome
and induce gingival hyperplasia.