Chapter 056. Cutaneous Drug Reactions (Part 9)

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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. ...

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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.