Disorders of Hair Part 1

Physiology and Evaluation of Hair Growth

A basic knowledge of the hair growth cycle is needed to evaluate disorders of hair growth.1,2 Scalp hair follicles cycle independently of one another. On average, of 100,000 scalp hairs, approximately 90% are in the anagen (growing) phase and 10% in the telogen (resting) phase at any given time. Anagen lasts an average of 3 years, with a range of 1 to 7 years. Telogen usually lasts 3 months, after which the resting hairs are shed and new hairs grow in. The average rate of scalp hair growth is approximately 0.35 mm/day, or 1 cm/month (1 in. every 2 to 3 months).

An average loss of 100 hairs a day is normal, with larger numbers of hairs being lost on shampoo days. When obtaining a history, it is important to determine whether shedding is abnormal and whether the shed hairs break off or come out by the roots.3 Hair normally comes out by the roots; however, trauma or excessive fragility may cause hair to break.

Examination of the patient should include a routine check for broken-off hairs and the performance of hair-pull tests on the top, sides, and back of the scalp. The hair-pull test is performed by grasping groups of 10 to 20 hairs between the index finger and thumb and pulling steadily.4,5 Extraction of more than 20% of the grasped hairs indicates a potential for abnormal shedding, usually involving telogen hairs. Telogen hairs (club hairs) are easily recognized by their whitish club-shaped bulbs and lack of root sheaths. Anagen hairs are normally difficult to detach and have blackish, indented roots with intact root sheaths.

Androgenetic Alopecia

Androgenetic alopecia is the common type of nonscarring hair loss affecting the crown. It results from a genetically determined end-organ sensitivity to androgens. It is often referred to as common baldness, male-pattern alopecia, and female-pattern alopecia.

Epidemiology and pathogenesis

Androgenetic alopecia affects at least 50% of men by 50 years of age and 50% of women by 60 years of age.6,7 Males have more androgen than females and therefore are usually affected earlier and more severely. Male-pattern alopecia often starts between 15 and 25 years of age. Male-pattern alopecia has two characteristic components, bitemporal recession and vertex balding [see Figure 1], which in pronounced cases can progress to complete balding of the crown.6,7 Female-pattern alopecia is more likely to start between 25 and 30 years of age (or sometimes later, after menopause). It is characterized by an intact frontal hairline and an oval area of diffuse thinning over the crown [see Figure 2]. Bitem-poral recession in women is much less obvious than it typically is in men, or it can be nonexistent. In general, androgenetic alopecia in women progresses to mild, moderate, or severe thinning but not to complete baldness. The best predictor of outcome is the degree of progression in affected relatives.

Androgenetic alopecia is an autosomal dominant disorder with variable penetrance. Susceptible hairs on the crown are predisposed to miniaturize under the influence of androgens, notably dihydrotestosterone. In both sexes, miniaturization results from a shortening of the anagen cycle, from years to months or weeks. Miniaturized hairs are characterized by reduced length and diameter; this accounts for the appearance of hair loss.8 Androgenetic alopecia largely spares the back and sides of the scalp.

Diagnosis

The diagnosis of androgenetic alopecia is usually obvious from the clinical pattern of hair loss from the top of the head.9 In some men, a female pattern of alopecia (see above) causes diagnostic confusion but has no other significance. In women, a male pattern of alopecia (i.e., bitemporal recession and vertex balding) occurring with menstrual irregularities, acne, hirsutism, and a deep voice is significant. The virilism indicates significant hyper-androgenism, the cause of which must be identified and treated [see 3:III Ovary and 3:IV The Adrenal].

Scalp biopsies are rarely necessary to diagnose androgenetic alopecia. Biopsies cut horizontally are sometimes useful, however, in differentiating female-pattern alopecia from chronic telo-gen effluvium (see below).

Treatment

Depending on the severity of the condition, management of androgenetic alopecia ranges from watchful inactivity to medical and surgical treatment, or a hairpiece or wig may be used in the most refractory cases.

Topical Therapy

The Food and Drug Administration approved topical 2% mi-noxidil for use in men in 1987 and in women in 1989. Minoxidil is applied twice daily with a dropper, spread over the top of the scalp, and gently rubbed in. The drug should be tried for at least a year. Minoxidil acts by initiating and prolonging anagen. It produces visible hair growth in approximately one third of male and female patients, fine-hair growth in approximately one third, and no growth in approximately one third. It is more effective as a preventive agent, retarding hair loss in approximately 80% of patients.6

Figure 1 Bitemporal recession and vertex balding are present in this patient with male pattern androgenetic alopecia.

Figure 2 Intact frontal hairline and diffuse thinning over the crown are characteristic of female pattern androgenetic alopecia.

Topical 5% minoxidil, which was approved for use in men in 1997, produces visible hair growth in 45% of patients in less time than the 2% solution. Both concentrations are available over the counter. Side effects are not significant and include scalp irritation and increased facial hair.10 The medication has to be continued indefinitely.11

Systemic Therapy

Oral finasteride, at a dosage of 1 mg/day, was approved by the FDA for the treatment of male-pattern alopecia in 1997. Finasteride is a powerful type II 5a-reductase inhibitor that prevents formation of dihydrotestosterone in the prostate gland and in the hair follicle. It reduces circulating dihydrotestosterone by 65% to 70%. When administered at a dosage of 1 mg/day for 2 years to male patients with androgenetic alopecia who are between 18 and 41 years of age, finasteride grew visible hair in 66% and prevented further hair loss in 83%.12 The efficacy of finasteride was maintained in a 5-year study.13 Hair-weight studies have shown that finasteride increases hair length and diameter, producing better coverage from existing hairs.

Side effects in men are minimal and include lack of libido, lack of potency, and mild reduction in semen in approximately 0.5% of patients. These effects are reversed when the drug is stopped and often disappear as the drug is continued. A 1-year trial of finasteride at a dosage of 1 mg/day in postmenopausal women failed to show any positive effects.

Because of the likelihood of finasteride to cause severe side effects in the male fetus, the drug is contraindicated in premeno-pausal women.

Therapy for Hair Loss in Women

Topical minoxidil is currently the best available treatment for androgenetic alopecia in women.10,15 However, various antian-drogenic drugs have been used. Oral contraceptives (e.g., ethinyl estradiol-ethynodiol diacetate [Demulen], desogestrel-ethinyl estradiol [Desogen], and ethinyl estradiol-norgestimate [Ortho Tri-Cyclen]) can reduce hair loss and occasionally lead to slight hair growth.6 Oral spironolactone (Aldactone) in dosages of 75 mg/day to 200 mg/day can produce androgen blockade. Dex-amethasone in dosages of 0.125 mg/day to 0.5 mg/day can suppress adrenal overactivity. Cyproterone acetate, which is not available in the United States, is not as effective as minoxidil in female pattern hair loss unless other signs of hyperandrogenism are present.

Therapy for Refractory Cases

In patients who do not respond to the treatments listed above, the next step may be hair transplantation. Micrografts and mini-grafts can produce a good cosmetic appearance in patients who have a sufficient reserve of hair on the back and sides of the scalp.17 If all therapies fail, a hairpiece may be an option.

Diffuse Alopecia

Diffuse alopecia is generalized hair loss over the entire scalp. Because the loss is so diffuse, it is often unnoticeable until 30% to 50% of scalp hair is shed. Causes of diffuse alopecia include telo-gen effluvium, anagen arrest, drug reactions, and a number of systemic and nonsystemic conditions [see Table I].

Telogen effluvium

Telogen effluvium is the most common form of diffuse alopecia.20 It presents as a generalized shedding of telogen hairs from normal resting follicles. The basic cause of telogen effluvium is a premature interruption of anagen, leading to an increase in the number of hairs cycling into telogen. When the 3-month telogen period ends, new anagen hairs grow in and numerous telogen hairs fall out. Patients may need reassurance that this apparent loss of hair is actually a sign of regrowth.

Acute telogen effluvium can be caused by childbirth, febrile illnesses, surgery, chronic systemic diseases, crash diets, traction, severe emotional stress, and drug reactions [see Table 2]. It can also be a physiologic reaction in neonates.21

During acute telogen effluvium, pull tests are positive all over the scalp, yielding two to 10 club hairs. Telogen effluvium is often accompanied by bitemporal recession; this is a useful diagnostic sign in women [see Figure 3]. The acute form usually ends within 3 to 6 months. The diagnosis is usually made on the basis of the history of an initiating event 3 months before the onset of shedding. No treatment is needed for acute telogen effluvium, because the hair invariably regrows within a short time.

Chronic telogen effluvium has a long, fluctuating course of 6 months to 7 years or more. Very often, no identifiable cause can be found.

Diagnosis

The diagnosis of telogen effluvium is usually clinical; biopsies may be necessary to distinguish telogen effluvium from an acute onset of widespread androgenetic alopecia.22 Other causes of hair loss should be excluded by a careful drug history and tests for iron deficiency, syphilis, and disorders of the thyroid, kidney, and liver.

Table 1 Causes of Diffuse Alopecia45

Telogen effluvium (acute and chronic)

Anagen arrest

Reactions to drugs and other chemicals

Thyroid disorder

Iron deficiency and other nutritional deficiencies

Malabsorption

Renal failure

Hepatic failure

Systemic disease

Miscellaneous causes (e.g., diffuse alopecia areata, congenital hypotrichosis) and idiopathic causes

Table 2 Categories of Drugs That Can Cause Alopecia⁵

Category	Selected Agents
Alpha blockers	Doxazosin, prazosin, terazosin
Angiotensin converting enzyme inhibitors	Captopril, enalapril
Anticancer drugs	Bleomycin, cyclophosphamide, cytarabine, dactinomycin, daunorubicin, doxorubicin, etoposide, floxuridine, fluorouracil, methotrexate, mitomycin, mitoxantrone, procarbazine, thioguanine, vinblastine, vincristine
Anticoagulant drugs	Dicumarol, heparin, warfarin
Anticonvulsant drugs	Ethotoin, mephenytoin, paramethadione, phenytoin, trimethadione, valproate sodium
Antithyroid drugs	Carbimazole, methylthiouracil, methima-zole, propylthiouracil
Beta blockers	Acebutolol, atenolol, labetalol, metoprolol, nadolol, pindolol, propranolol, timolol
Calcium channel blockers	Diltiazem, verapamil
Cholesterol reducers	Clofibrate, lovastatin
H2 receptor blockers	Cimetidine, famotidine, ranitidine
Nonsteroidal anti-inflammatory drugs	Fenoprofen, ibuprofen, indomethacin, ketoprofen, meclomen, naproxen, piroxicam, sulindac
Retinoids and retinol	Acitretin, etretinate, isotretinoin, vitamin A overdose
Tricyclic antidepressants	Amitriptyline, amoxapine, desipramine, doxepin, imipramine, nortriptyline, protriptyline, trimipramine

Treatment

As mentioned above, no treatment is needed for acute telogen effluvium because the hair invariably regrows within a short time. In chronic telogen effluvium, topical minoxidil in a 2% or 5% solution may be indicated. The patient should be reassured that telogen effluvium rarely causes permanent baldness.

Anagen arrest (anagen effluvium)

So-called anagen effluvium represents a diffuse loss of anagen hairs from growing follicles.23 The term anagen effluvium is a misnomer. Normally, hairs pass through a brief transition phase (catagen) between the anagen and telogen phases before falling out by the roots. In anagen arrest, inhibition of cell division in the hair bulb matrix leads to a progressive narrowing of the hair shaft and sometimes failure of hair formation. As the growing hair narrows near the skin surface, it may break off. The resultant shedding can occur within a few weeks, unlike in telogen effluvium, in which shedding takes 3 months to occur.

Causes of anagen arrest include reactions to cytostatic drugs and other toxic agents, radiation therapy, endocrine diseases, alopecia areata, cicatricial alopecia, trauma and pressure, and severe protein calorie malnutrition. Because 90% of scalp hairs are in anagen at any given time, this condition causes obvious and severe baldness [see Figure 4].

Diagnosis

The diagnosis of anagen arrest is easily made by the history, evidence of extensive hair loss, and hair-pull tests that yield easily broken hairs with proximal tapering.

Treatment

Treatment of anagen arrest lies in elimination of the underlying cause. Once the antimitotic influence is removed, the anagen hair will regrow promptly with a normally tapering shaft. Unbroken hairs that regrow often show the Pohl-Pinkus deformity (i.e., a constriction that results in a dumbbell shape).

Figure 3 In women, marked bitemporal recession is often a sign of telogen effluvium.

Figure 4 Anagen arrest causes severe, diffuse hair loss.

Table 3 Miscellaneous Chemicals That Can Cause Alopecia⁴⁵

Chemical	Common Source
Abrin	Plant source (Abrus precatorius [rosary pea, jequirity bean, or precatory bean])
Arsenic	Pesticides
Bismuth	Old treatment for syphilis
Boric acid	Mouthwashes, occupational exposure
Chloroprene dimers	Occupational exposure (synthetic-rubber manufacturing)
Lead	Paints
Mercury	Cosmetics, teething powders, antiseptics
Mimosine	Plant source (Leucaena glauca)
Selenocystothione	Plant source (Lecythis species)
Thallium salts	Rodenticides

Alopecia caused by drugs and chemicals

Substance-induced alopecia is relatively common but is often hard to diagnose because of the large number of drugs and chemicals that can cause hair loss [see Tables 2 and 3]. It often takes time to identify the underlying cause by trial and error: many patients are exposed to several alopecia-inducing substances, and removal of the causative agent may not result in immediate regrowth of hair.

Other causes of diffuse alopecia

Hypothyroidism and iron deficiency should be excluded in patients with diffuse hair loss [see Table 1]. Appropriate treatment may lead to hair regrowth.

Alopecia Areata

Alopecia areata is typically characterized by patchy hair loss; however, involvement can vary from a single patch on the scalp or elsewhere to total body baldness (alopecia universalis).