Approach to the Patient with Hair Loss

Peter C. Schalock

Arthur J. Sober

Alopecia may be described as the loss of hair in areas where it normally grows. The most noticeable area in which alopecia develops is the scalp, but loss of hair at other body sites may occur. Whether alopecia is a result of genetic influences, local inflammatory processes, or systemic disease, the primary care physician may be the first clinician to offer the patient a diagnosis and treatment options.

PATHOPHYSIOLOGY AND CLINICAL PRESENTATION (1, 2, 3, 4, 5, 6, 7, 8, 9, 10 and 11)

Normal Hair Growth

The follicular unit is a product of proliferating and differentiating keratinocytes in the hair bulb (otherwise known as the matrix). The hair shaft (consisting of the cuticle, cortex, and medulla) is predominately hard keratin, or trichohyalin, rich in disulfide bonds. The growth of hair is cyclical, the length of the cycle varying with the location. Scalp hair grows from 2 to 6 years (anagen), enters a transition period over 2 to 3 weeks (catagen), and then involutes over 3 months (telogen). In contrast, the anagen phase for the short hairs on the extremities is between 2 and 6 months. Moreover, the longer (or shorter) the growth period, the longer (or shorter) the hair length. In healthy young persons, about 85% to 90% of all scalp hairs are in anagen, the phase of active growth. The remainder of hairs are in telogen (10% to 15%) and catagen (<1%). The number of terminal hairs on the scalp is estimated to be 250/cm², with an average normal daily loss of 100 to 200 hairs, although there is considerable individual variation. Hairs that grow for long periods and rest briefly are the most susceptible to interruptions of the growth cycle, and variations in the ratio of the growth phase to the resting phase are most noticeable. Scalp hair grows at the rate of approximately 0.35 mm/d, or about 1 cm/mo, but multiple factors can affect the rate.

Hair Loss

Alopecia can be classified as scarring (cicatricial) or nonscarring (noncicatricial), depending on whether there is permanent injury to the bulge region (location of stem cells) located between the hair bulb and insertion of the erector pili muscle. The primary pathogenic mechanisms of hair loss are destruction of the hair matrix and stem cell bulge region by physical or chemical agents, infectious or immunologically mediated inflammation, metabolic diseases, and the administration of antimetabolites or other drugs. In general, destructive agents (physical, chemical, infectious, or autoimmune) produce scarring alopecia, whereas acute systemic illnesses and drugs usually result in nonscarring alopecia.

In noncicatricial alopecia, the follicular integrity is retained, and once the inciting process subsides, there is potential for hair regrowth. In cicatricial alopecia, hair never regrows. A few conditions that begin as nonscarring alopecia may later develop into scarring alopecia with chronicity.

Nonscarring Alopecia

Alopecia is often nonscarring, with male and female pattern baldness accounting for most patient complaints.

Male Pattern Hair Loss or Baldness (Androgenetic Alopecia).

Male pattern hair loss/baldness is symmetric, usually beginning in the frontoparietal scalp with progressive recession and vertex hair density thinning (Fig. 182-1). Its development is related to genetic predisposition and hormonal (dihydrotestosterone [DHT]) activity, and it is age related. The inheritance is polygenetic or autosomal dominant, with incomplete penetrance. Chromosome 20p11 and chromosome 7p21.1 as well as polymorphisms in the androgen receptor gene have been linked to androgenetic alopecia. The process is permanent, with pigmented scalp hairs replaced by fine, unpigmented vellus hairs. DHT inhibits the growth of scalp hair, whereas it stimulates the growth of facial hair and promotes a male pattern of pubic hair growth. When DHT is taken exogenously, laboratory investigation reveals increased levels of free testosterone, sulfated dehydroepiandrosterone (DHEA-S), or both.

Female Pattern Hair Loss.

At a population level, females may exhibit loss of hair density, cycling, and pigmentation. The mechanisms of female pattern alopecia may be similar to those of male pattern baldness, but female pattern baldness is usually more diffuse, located centrally, and, in frontal scalp areas, without complete balding. Neither an androgenetic nor a genetic cause has been proven. Some cases may be due to iron deficiency or thyroid disease. Earlyonset alopecia at puberty may be related to a strong family history, whereas onset of alopecia in older women (peri- or postmenopausal) may be due to genetic susceptibility combined with androgen sensitivity at the follicular level or systemic androgen excess.

Male Pattern Hair Loss in Women.

The presence of male pattern hair loss in a female patient should provoke concern about androgen excess, manifested by hirsutism (growth of hair in a male distributed pattern) in mild cases and virilization (coarsening of facial features, voice deepening, and clitoral enlargement) in more serious cases. Polycystic ovary disease (Stein-Leventhal syndrome), androgen-producing ovarian and adrenal tumors (see Chapter 98), hyperprolactinemia, contraceptive pills or anabolic steroids, hepatic disease, and tumor production of ectopic androgens (usually carcinoid, choriocarcinoma, or metastatic lung cancer) are some causes of androgen excess and hirsutism.

Figure 182-1 Male pattern alopecia in the typical “bald spot” on the occipital scalp.

Figure 182-2 Alopecia areata on the temporal scalp, partially in the “ophiasis” distribution.

Systemic Disease, Metabolic Abnormalities, and Medications.

Nonscarring alopecia is often associated with systemic disease, a metabolic abnormality, or the use of medications. Alopecia areata, a condition that is believed to be an autoimmune attack on the hair follicle, results in relatively rapid hair loss in distinct, well-defined round or oval patches (Fig. 182-2). Less common variants of alopecia areata include ophiasis (a band-like pattern involving the occiput and bilateral temporal regions) and generalized patterns, where one encounters generalized thinning rather than distinct patches of hair loss. Alopecia totalis is the progressive loss of all scalp hair; alopecia universalis manifests as complete facial and body hair loss.

Presumed autoimmune diseases like vitiligo, Hashimoto thyroiditis, and inflammatory bowel disease are associated with the onset of alopecia areata. The course of alopecia areata is unpredictable. Some persons have one episode, in which the development of one or several bald spots is followed by spontaneous regrowth. In others, new areas of alopecia may develop, and they become totally bald. Onset before puberty is associated with a poorer prognosis.

Diffuse hair thinning may occur in thyroid disease and iron deficiency. Less commonly, hypopituitarism and parathyroid disease produce hair loss. Alopecia is a manifestation of connective tissue diseases, notably systemic lupus erythematosus, subacute cutaneous lupus erythematosus, and dermatomyositis. Occasionally, hair loss is self-induced, a condition known as trichotillomania. Such patients may not be aware that they are plucking hairs, and the condition may indicate significant psychiatric disturbance.

Secondary syphilis, HIV infection, superficial folliculitis, and tinea capitis also produce nonscarring alopecia. Commonly used medications that can cause alopecia include β-blockers, tricyclic antidepressants, anticonvulsants, systemic retinoids, warfarin and heparin anticoagulants, allopurinol, antithyroid drugs, quinine, verapamil, indomethacin, sulfasalazine, haloperidol, and vitamin A in excessive doses (see Table 182-1). Antineoplastic agents such as 5-fluorouracil, paclitaxel, cyclophosphamide, and methotrexate predictably produce hair loss.

Physiologic Alterations in Follicular Cycling.

Alterations in the cycling of the follicular unit may produce nonscarring hair loss, a process known as telogen effluvium, by altering the relation between the growing and resting phases of hair follicles. High fever due to illness, surgery, postpartum, medications (such as oral contraceptives), and even seasonal changes may result in rapid hair loss 2 to 4 months after the insult. However, a more chronic telogen effluvium, such as that seen in middle-aged women, may present insidiously. During pregnancy, fewer hairs are shed (due to prolonged anagen), so that fewer telogen hairs are produced. Postpartum, the percentage of telogen hairs increases substantially and hair is lost diffusely over several subsequent months. Postpartum alopecia resolves within 18 months, but about half of women feel they have less hair after childbirth than they did before pregnancy.

TABLE 182-1 Differential Diagnosis of Hair Loss

Nonscarring Alopecia
	Androgenic
		Male pattern
		Female pattern
	Alopecia areata
	Post febrile infection
	Folliculitis (mild)
	Tinea capitis (ectothrix)
	Human immunodeficiency virus infection
	Hypothyroidism
	Iron deficiency
	Systemic lupus erythematosus
	Syphilis
	Medications
		Antineoplastics
		Antimetabolites
		Propylthiouracil
Scarring Alopecia
	Physical trauma
		Burns
		Radiation
		Chronic traction
	Infection
	Bacterial folliculitis (severe)
	Fungal (endothrix)
	Antidepressants
	Anticonvulsants
	Anticoagulants
	Allopurinol, probenecid
	β-Blockers
	Quinine
	High-dose vitamin A, isotretinoin
	Oral contraceptives
	Discontinuation of corticosteroids
	Psychiatric
		Trichotillomania
	Telogen effluvium
	Crash diets
	Postpregnancy
	Discoid lupus erythematosus
	Morphea
	Lichen planopilaris
	Pseudopelade
	Neoplasms
	Granulomatous disease
	Factitial