CHAPTER 9 Alopecia, Hirsutism, and Hypertrichosis Kristine E. Keplar ALOPECIA of hair growth is the telogen, or resting, phase. This phase usually lasts 2–4 months, after which the fol- Alopecia is hair loss due to a disturbance of the licle re-enters the anagen phase. At any given time, hair growth cycle and may be manifested as com- 80–90% of the follicles of the typical scalp are in the plete or partial hair loss. Although the scalp is most anagen phase, and 10–15% of follicles are in the tel- often involved, the disorder can affect all hair- ogen phase. Hair is shed during the telogen phase; bearing areas of the body.1-3 Most cases are caused telogen follicles usually shed between 30 and 100 by androgenetic alopecia, also known as male pat- hairs daily.6,8,9 Follicles in the telogen and catagen tern baldness, secondary to hormonal and genetic phases, unlike those in the anagen phase, typically factors. A relatively small percentage of alopecia are not sensitive to noxious agents, such as cancer cases are drug-induced.4 Although drug-induced chemotherapy drugs, because of their inconsistent alopecia is not an extremely common event, it mitotic and metabolic activity.6 is quite distressing to the patient and, therefore, Androgenetic alopecia, or male pattern bald- 5 important to recognize. ness, is hair thinning that occurs in an M-shaped The three phases of hair growth are anagen, pattern, during which hair loss occurs on the crown catagen, and telogen (Figure 9-1).6-8 The anagen, or and temple areas of the head but spares the back growth, phase is the most active phase of the growth and sides of the head. It is termed androgenetic cycle and lasts from several months to years. During alopecia because it generally follows the distribu- this phase, the hair follicle produces hair continu- tion of androgen-sensitive hair follicles. Androge- ously. Intense mitotic activity occurs, and follicles netic hair loss is often familial and is thought to are highly susceptible to noxious events.6 The cata- involve a physiologic process incited in genetically gen cycle, or transition period, lasts only 1–2 weeks. predisposed hair follicles under the influences of During this phase, the inferior portion of the hair androgens. Drugs with androgenic activity can also follicle significantly thins. The third and final phase induce this type of hair loss.10-13 165 166 DRUG-INDUCED DISEASES: Prevention, Detection, and Management Return to Anagen Catagen Telogen Anagen Active Transition Resting Growth Phase Phase Hair matrix Phase Papilla forming new hair 2–6 years 1–2 weeks 2–4 months 1 2 FIGURE 9-1 Diagram of the Hair Growth Cycle During the normal hair cycle, the active growth phase (anagen) can last from 2 to 6 years. This is followed by a short transition phase (catagen), which lasts 1–2 weeks, and then by a resting phase (telogen), lasting 2–4 months. The hair is then shed, the anagen phase begins again, and a new hair is developed.6-9 Alopecia areata, an autoimmune inflammatory to 3 months after the last dose of heparin.170 disease, is another type of alopecia that includes Although unfractionated heparin has been the pri- patchy hair loss, complete loss of scalp hair, or com- mary anticoagulant linked to drug-induced alope- plete loss of scalp and body hair. Alopecia areata cia, low-molecular-weight heparins, warfarin, and has been postulated to have an autoimmune patho- direct-acting oral anticoagulants have also been genesis involving inflammatory cytokines, includ- implicated as causative agents.4,10,11,28,171-173 Warfa- ing tumor necrosis factor alpha (TNFα). Alopecia rin typically induces mild, diffuse alopecia with areata is very rare, and only a few drugs have been an onset between 3 and 20 weeks after the initia- associated with it. At this time, the precise patho- tion of therapy. Most cases of hair loss secondary genesis of drug-induced alopecia areata has not to warfarin or heparinoid drugs go unnoticed by been elucidated, but it is thought to involve the per- the patient. Only 20% of those who experience hair son’s own immune system, which attacks healthy loss associated with these drugs exhibit clinically hair follicles by mistake.13-17 evident alopecia. Scalp hair is the primary target, but eyebrows, axillary, and pubic hair also may be CAUSATIVE AGENTS affected. Total alopecia is extremely rare.19,28 The primary medications that may induce alopecia RETINOL/RETINOIDS are anticoagulants, androgenetic agents, hormone Vitamin A, or retinol, is often prescribed for the therapy, psychotropic drugs, thyroid medications, treatment of hair disorders. However, alopecia of antiretroviral drugs, and cancer chemotherapy the telogen effluvium type can occur in association agents.3,6,11,18 Drugs known to induce alopecia are with ingestion of vitamin A in doses >50,000 inter- listed in Table 9-1.18-169 national units daily (whether dietary, such as cod liver oil, or pharmaceutical) over a period of several ANTICOAGULANTS months.18 Other retinoids such as acitretin, etreti- Heparin and heparinoid drugs primarily affect nate, and isotretinoin also cause hair loss.26 Alope- scalp hairs. Hair loss usually occurs approximately cia associated with these agents usually occurs after 3 months after the initiation of treatment. In one 3–8 weeks of therapy. Alopecia may occur after report, the onset of hair loss varied from 1 week exposure to lower doses, but the onset is longer than .