Chapter 056. Cutaneous Drug Reactions (Part 9) doc

Chapter 056. Cutaneous
Drug Reactions
(Part 9)

Sulfonamides
Antibacterial sulfonamides have a rather high risk of causing cutaneous
eruptions and are among the drugs most frequently implicated in SJS and TEN.
The combination of sulfamethoxazole and trimethoprim frequently induces
adverse cutaneous reactions in patients with AIDS (Chap. 182). Desensitization is
often successful in AIDS patients with morbilliform eruptions but is not
recommended in AIDS patients who manifested erythroderma or a bullous
reaction in response to their earlier sulfonamide exposure.
Reaction rates are much lower with nonantibiotic sulfonamides, including
diuretics or antidiabetic agents. Cross-reactivity between antibiotic and
nonantibiotic sulfonamides is, at most, infrequent.
Vancomycin
Vancomycin causes two unusual but recognizable cutaneous reactions:
linear IgA bullous dermatosis (a transient blistering eruption) and red man
syndrome. Red man syndrome occurs during rapid IV infusion of vancomycin.
This is thought to be a histamine-related anaphylactoid reaction characterized by
flushing, diffuse maculopapular eruption, hypotension, and, in rare cases, cardiac
arrest.
Agents Used in Cancer Chemotherapy
Since many agents used in cancer chemotherapy inhibit cell division,
rapidly proliferating elements of the skin, including hair, mucous membranes, and
appendages, are sensitive to their effects. As a result, stomatitis and alopecia are
among the most frequent dose-dependent side effects of chemotherapy. Various
nail abnormalities have been described: onycholysis, dystrophy, Beau's lines,
white lines, and pigmentation. Sterile cellulitis and phlebitis and ulceration of
pressure areas occur with many of these agents. Also reported is acral erythema,
which begins with dysesthesia followed by redness and a painful edematous

eruption of the palms and soles; it is caused by cytarabine, doxorubicin,
methotrexate, and 5-fluorouracil. Urticaria, angioedema, and exfoliative dermatitis
also have been seen, as has local and diffuse hyperpigmentation.
Hypersensitivity to carboplatin or cisplatin is not rare (with an incidence of
10–20%) among patients receiving multiple treatments with these drugs. It is
probably IgE mediated. Moderate to severe reactions including respiratory distress
and hypotension are also observed in 10–20% of patients receiving paclitaxel
regardless of premedication with glucocorticoids and histamine H(1) and H(2)
antagonists.
Glucocorticoids
Both systemic and topical glucocorticoids cause a variety of skin changes,
including acneiform eruptions, atrophy, striae, and other stigmata of Cushing's
syndrome, and in sufficiently high doses can retard wound healing. Patients using
glucocorticoids are at higher risk for bacterial, yeast, and fungal skin infections
that may be misinterpreted as drug eruptions but are instead drug side effects.
Allergy to glucocorticoids may also occur either as contact dermatitis to topical
formulations or as systemic reactions, including anaphylaxis.
Biologic Therapies
These include cytokines and monoclonal antibodies.
Injection-site reactions are the most frequent adverse event. The severity
varies from mild redness to deep inflammation and necrosis. In most cases the
treatment can be continued and the severity of reactions will decrease with time.
Like all foreign proteins, monoclonal antibodies may induce urticaria,
angioedema, anaphylactic reactions, and serum sickness.
Alopecia is a common complication of IFN-α. A nonspecific highly pruritic
"dermatitis" is frequent in patients receiving IFN and ribavirin for hepatitis C.
Induction or exacerbation of various immune-mediated disorders,
especially lupus erythematosus, has been reported with many biologicals
(interleukin 2, IFN-α, anti–tumor necrosis factor α).
Granulocyte colony-stimulating factor may induce various neutrophilic

dermatoses, including Sweet's syndrome and pyoderma gangrenosum, and can
exacerbate psoriasis.
Cetuximab is a member of a new family of antineoplastic agents that inhibit
the EGF receptor. These molecules induce acneiform eruptions after a mean
interval of 10 days in a majority of patients. The severity of the eruption was
shown to correlate with a better anticancer effect. Systemic antibiotics and topical
anti-acne treatments are helpful.
Although not usually classified as adverse drug reactions, skin infections
and skin cancer could become a major concern with long-term use of immune-
modifying biologicals.
Antimalarial Agents
Antimalarial agents are used as therapy for several skin diseases, including
the skin manifestations of lupus and polymorphous light eruption, but they can
also induce cutaneous reactions. The most frequent is pruritus, which occurs in up
to 50% of African patients receiving chloroquine and may be severe enough to
lead to discontinuation of treatment.
Pigmentation disturbances, including black pigmentation of the face,
mucous membranes, and pretibial and subungual areas, occur with antimalarials.
Quinacrine (mepacrine) causes generalized, cutaneous yellow discoloration. Less
frequent reactions include pustular eruptions (AGEP) and
hypersensitivity/DRESS.