Chapter 056. Cutaneous Drug Reactions (Part 3) pps

Cutaneous Drug Reactions Part 3 PIGMENTATION CHANGES Drugs, either systemic or topical, may cause a variety of pigmentary changes in the skin.. Numerous cancer chemotherapeutic agents

Chapter 056 Cutaneous

Drug Reactions

(Part 3)

PIGMENTATION CHANGES

Drugs, either systemic or topical, may cause a variety of pigmentary changes in the skin Oral contraceptives may induce melasma Long-term minocycline or pefloxacin may cause blue-gray pigmentation, while amiodarone causes a more purple coloration Long-term high-dose phenothiazine results in gray-brown pigmentation of sun-exposed areas Numerous cancer chemotherapeutic agents may be associated with pigmentation, e.g., bleomycin, busulfan, daunorubicin, cyclophosphamide, hydroxyurea, and methotrexate

Pigmentation changes may also occur in mucous membranes (busulfan), nails (zidovudine), hair, and teeth

WARFARIN NECROSIS OF SKIN

This rare reaction usually occurs between the third and tenth days of therapy with warfarin derivatives, usually in women The more common sites are breasts, thighs, and buttocks Lesions are sharply demarcated, erythematous, indurated, and purpuric and may resolve or progress to form large, irregular, hemorrhagic bullae with eventual necrosis and slow-healing eschar formation

Development of the syndrome is unrelated to drug dose, and the course is not altered by discontinuation of the drug after onset of the eruption Warfarin reactions are associated with protein C deficiency Warfarin anticoagulation in heterozygotes for protein C deficiency causes a precipitous fall in circulating levels of protein C, permitting hypercoagulability and thrombosis in the cutaneous microvasculature, with consequent areas of necrosis Similar reactions have been associated with heparin Heparin-induced necrosis may have clinically similar features but is probably due to heparin-induced platelet aggregation with subsequent occlusion of blood vessels

Warfarin-induced cutaneous necrosis is treated with vitamin K and heparin Treatment with protein C concentrates may also be helpful

DRUG-INDUCED HAIR DISORDERS

Drug-Induced Hair Loss

Medications may affect hair follicles at two different phases of their cycle

Anagen effluvium occurs within days of drug administration, whereas in telogen effluvium, the delay is 2–4 months Both present as diffuse nonscarring alopecia

most often reversible after discontinuation of the responsible agent

The prevalence and severity of alopecia depend on the drug as well as on individual predisposition A considerable number of drugs have been reported to induce hair loss These include antineoplastic agents (alkylating agents, bleomycin, vinca alkaloids, platinum compounds), anticonvulsants (carbamazepine, valproate), antihypertensive drugs (beta blockers), antidepressants, antithyroid drugs, interferons (IFNs), oral contraceptives, and hypolipidemics

Hirsutism

Hirsutism is an excessive growth of coarse hair with masculine characteristics in a female, most often on the lateral aspects of face and back Hirsutism results from androgenic stimulation of hormone-sensitive hair follicles

Anabolic steroids, oral contraceptives of the nonsteroid progesterone type, testosterone, and corticotropin can induce hirsutism

Hypertrichosis

Hypertrichosis differs from hirsutism by being located mainly on the forehead and temporal regions It is usually reversible Drugs responsible for hypertrichosis include anti-inflammatory drugs, glucocorticoids, vasodilators (diazoxide, minoxidil), diuretics (acetazolamide), anticonvulsants (phenytoin), immunosuppressive agents, psoralens, and zidovudine

Changes in hair color or structure are uncommon adverse effects from medications Hair discoloration may occur with chloroquine, IFN-α, chemotherapeutic agents, and tyrosine kinase inhibitors Changes in hair structure have been observed in patients given EGFR inhibitors

DRUG-INDUCED NAIL DISORDERS

These usually involve several or all 20 nails and need months to resolve after withdrawal of the offending agent The pathogenesis is most often toxic Drug-induced nail changes include Beau's line (transversal depression of the nail plate), onycholysis (detachment of the distal part of the nail plate), onychomadesis (detachment of the proximal part of the nail plate), pigmentation, and paronychia (inflammation of periungual skin)

Onycholysis

Onycholysis may occur as a consequence of phototoxic reactions, particularly with tetracyclines, fluoroquinolones, phenothiazines, and psoralens, as well as in persons taking NSAIDs, captopril, retinoids, sodium valproate, and many chemotherapeutic agents such as anthracyclines or taxanes including paclitaxel and docetaxel The risk of onycholysis in patients receiving cytotoxic drugs can be increased by exposure to sunlight