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. . Chapter 056. Cutaneous Drug Reactions (Part 3) PIGMENTATION CHANGES Drugs, either systemic or topical, may cause a variety of pigmentary. 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. 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