Incontinentia pigmenti

Nearly two-thirds of men experience hair loss during their lifetime. The condition is less common in women, yet it is extremely common in older women. Throughout history, hair loss has been associated with unattractiveness, sickness and old age, while a full head of hair has connoted youth, health and power.[1] Because of the strongly negative cosmetic and psychologic ramifications of hair loss, millions of dollars are spent each year on treatments promising to minimize hair loss.

Most cases of hair loss are caused by androgenetic alopecia (common baldness) resulting from genetic and hormonal factors. A small proportion of all cases of hair loss are secondary to pathologic causes such as drugs, diseases of autoimmunity, endocrine dysfunction, infections, trauma and stress.

Early recognition of the cause of hair loss may facilitate timely treatment, prevent further hair loss and interrupt a process that might otherwise damage self-esteem.

The Biology of Hair

Embryologically, hair follicles appear in the ninth week of gestation. At eight months of gestation, the initial fine and lightly pigmented fetal hair called lanugo is shed and vellus hairs emerge.[2] During puberty, vellus hairs are replaced by thick, pigmented terminal hairs on the scalp, beard area, axillae and pubic areas. This progression may be reversed when vellus scalp hairs replace terminal hairs in common baldness.

Sex hormones, primarily androgens, are necessary for the growth of beard, axillary, pubic and body hair. Eyelash and eyebrow hair seems to grow independently of hormonal influences.[3] Scalp hair growth is not dependent on androgens, yet, in persons with androgenetic alopecia, androgens are implicated in the manifestation of hair loss.[4] Androgen excess in women may result in both hirsutism and alopecia. Other hormone imbalances, such as hypothyroidism and hyperthyroidism, hypoparathyroidism and hypopituitary states, are also associated with alopecia.[5]

Hair follicle growth is cyclical (Figure 1).[3] During the anagen phase of the cycle, the hair follicle is actively growing. Hair length in different areas of the body varies directly with the time spent in the anagen phase. Approximately 85 to 90 percent of all scalp hairs are in the anagen phase.[4] The catagen, or involutional, phase follows and spans nearly six weeks. The telogen phase marks the final stage and lasts two to four months before the hair falls out. Shedding of telogen hair (average of 100 hairs per day) occurs when an anagen hair emerges at the beginning of a new hair cycle.

Classification of Hair Loss

Hair loss is primarily classified according to the presence or absence of scarring[6-9] (Table 1).[6] Of the common hair disorders encountered in primary care, androgenetic alopecia, anagen effluvium and telogen effluvium, and alopecia areata are clinically nonscarring. Conversely, traumatic alopecia and alopecia due to fungal infections, syphilis or lupus erythematosus may be either scarring or nonscarring. Inflammation is commonly seen clinically in patients with alopecia areata and alopecia due to fungal infections, syphilis and lupus erythematosus.

Diagnostic Evaluation

HISTORY

A thorough history may reveal the cause of the patient's alopecia. It is important to assess the duration and pattern of hair loss and identify any associated symptoms. Years of increased shedding and thinning of scalp hair in the temporal and parietal areas, particularly in conjunction with a family history of common baldness, indicate androgenetic alopecia. Rapid, diffuse hair loss suggests anagen or telogen effluvium. A history of physical or psychologic stress, drug use, systemic disease, recent childbirth, or crash dieting or other weight loss is associated with telogen effluvium.

Cold intolerance, fatigue, dry skin and constipation may indicate alopecia secondary to hypothyroidism. Easy fatigability may indicate alopecia secondary to iron deficiency anemia. Chemotherapy or exposure to radiation may induce anagen effluvium.

Psychologic factors may be implicated in trichotillomania. A review of hair care habits often reveals the cause of trauma-induced alopecia. Acute onset of hair loss on the scalp and other hair-bearing areas may signal alopecia areata. Tenderness and pruritus are frequently reported in infectious alopecia. In alopecia caused by dermatophytic fungi, the infection is frequently transmitted from another household member or pet.

PHYSICAL EXAMINATION

A complete cutaneous examination including all hair-bearing areas of the body is an essential part of the evaluation. The examination focuses on patterns of hair loss, inflammation, scarring and the condition of remaining hairs. Alopecia may be apparent on the scalp, face, trunk and extremities, and the distribution of hair loss is an important factor in diagnosis. Diffuse hair loss occurs in patients with an effluvium, patterned loss occurs in patients with androgenetic alopecia or traction alopecia, and focal loss occurs in patients with alopecia areata, trichotillomania or infectious alopecia. Hirsutism or the presence of excessive terminal hairs in areas that normally show vellus hairs indicates endocrine dysfunction in women.

Inflammation in the areas of hair loss may occur in association with several conditions. The presence of erythema and scaling, for example, can be a manifestation of lupus erythematosus or a fungal infection. A scarring (cicatricial) alopecia such as that related to discoid lupus erythematosus often occurs with areas of hair loss devoid of patent follicular orifices. Nonscarring disorders such as an effluvium or trichotillomania usually have intact follicular units. Broken-off hair shafts are often seen in patients with trichotillomania and fungal infections.

Other diagnostic clues on physical examination are fever and lymphadenopathy (bacterial and viral infections), skin lesions on other parts of the body (lupus erythematosus, syphilis) and nail changes (alopecia areata, lichen planus). Alopecia in association with nail and dental abnormalities may be a sign of a congenital ectodermal dysplasia, a genodermatosis. A carefully diagrammed sketch or picture is helpful in documenting physical findings.

LABORATORY DATA

Selected laboratory tests to confirm a suspected cause of hair loss include a complete blood count for identification of infection and anemia, rapid plasma reagin for syphilis, serology for lupus erythematosus, thyroid profile for thyroid dysfunction, and total testosterone and dehydroepiandrosterone sulfate for alopecia associated with androgen excess and hirsutism in women. Microbiologic studies for diagnosis of bacterial-induced alopecia include Gram stain and bacterial culture. A solution of 10 percent potassium hydroxide to prepare hair and skin scrapings for microscopic examination, along with fungal culture and Wood's lamp fluorescence of affected areas are diagnostic modalities used for fungal-induced alopecia.

DIAGNOSTIC PROCEDURES

The most commonly used clinical examination to detect hair loss is the "hair-pull" test in which eight to 10 hairs are tugged gently. Loss of up to two hairs is normal, and loss of four or more hairs is abnormal.[10] In patients who present with diffuse hair loss, a positive test suggests that the patient will have further loss of hair. A negative test indicates that those particular hairs grasped are not clinically affected.

Another valuable diagnostic procedure is the scalp biopsy. A deep 4- to 5-mm punch biopsy of the scalp is performed to include hair follicles. To obtain an adequate specimen, the biopsy may need to be performed at an angle to the skin surface in the direction of hair growth. Direct immunofluorescence microscopy of biopsy specimens to detect antibody deposition in the skin may be indicated for conditions such as lupus erythematosus.

More specialized diagnostic techniques include microscopic examination of hair shafts and bulbs.[11] Hair shaft specimens can be obtained by stroking or cutting hairs. Bulb specimens are obtained by plucking hair with forceps lined with rubber tubing. Morphologic characteristics of anagen and telogen hairs permit a gross determination of the anagen:telogen ratio. Anagen hair may be microscopically differentiated by looking at the bulb. The bulb of an anagen hair is pigmented, while the bulb of a telogen hair is not.

Hair Loss Disorders

ANDROGENETIC ALOPECIA (COMMON BALDNESS)

Androgenetic alopecia is the most common form of hair loss and is experienced by two out of every three men during their lifetime. It is also prevalent in older women. Androgenetic alopecia occurs in patients who have a genetic predisposition to the condition, and development of the condition depends on the presence of dihydrotestosterone.[12] The pathophysiology of this type of hair loss may be related to peripheral and central excess of androgen and androgen metabolism.[13]

In men with androgenetic alopecia, the parietal and temporal areas are predominantly affected (Figure 2). Women typically have a diffuse alopecia over the crown of the head, with retention of frontal hair (Figure 3). Early common baldness may resemble telogen effluvium, with increased shedding of hair. Examination of scalp hair reveals thinner, shorter and lighter-color hair shafts.

In women, pronounced androgenetic alopecia that is associated with hirsutism and acne may reflect an underlying endocrine abnormality. Evaluation of women with this type of alopecia is more difficult and should begin with serum total testosterone and dehydroepiandrosterone sulfate levels.[14] Late-onset adrenal hyperplasia (increased dehydroepiandrosterone sulfate), polycystic ovarian disease (increased total testosterone), and perimenopausal depletion of estrogens are all commonly associated with androgen excess, alopecia, hirsutism and other signs of masculinization in women.[14]

A recent study[15] showed that up to 50 percent of patients with common baldness had suffered psychologic problems. Men had lack of self-esteem and women had fear and anxiety about their physical appearance. These patients should be approached with empathy and sensitivity. The family physician's ability to talk openly about the patient's concerns may be as important as the medical approach to hair loss.

Treatment of androgenetic alopecia has met with limited success. In men, 2 percent topical minoxidil (Rogaine) has been widely used for the treatment of androgenetic alopecia. Before prescribing minoxidil, the cost of treatment (about $60 per month) and the results that the patient expects from treatment should be discussed with the patient. Only 20 to 40 percent of patients have clinically noticeable improvement of hair loss with use of topical minoxidil.[16] Since withdrawal of the drug commonly results in shedding of newly grown terminal hairs, 2 percent topical minoxidil may be more helpful in preventing loss of hair than in facilitating new growth. Use of 0.05 percent retinoic acid solution (Retin-A) along with 2 percent topical minoxidil solution may enhance the percutaneous absorption of minoxidil.[17] Severe androgenetic alopecia in men can be treated surgically or by alternative treatment options such as wigs or hair weaves.

Androgenetic alopecia in women may respond to treatment with 2 percent topical minoxidil. Women who have alopecia that is associated with endocrine dysfunction receive treatment for the androgen excess, which is usually of adrenal origin.[14] Other treatment options such as surgery or wigs are also available for women with androgenetic alopecia.

TELOGEN EFFLUVIUM

Telogen effluvium is a diffuse form of hair loss in which a precipitating event causes anagen arrest, and follicles rapidly cycle to the telogen phase. With regrowth of new anagen hairs, numerous telogen hairs are shed. Typically, hair loss occurs approximately two to four months after the initiating event, which reflects the length of time of the ensuing catagen and telogen phases. Telogen effluvium can be physiologic, occurring as a result of neonatal, postpartum or menstrual-related physiologic changes, or it can be pathologic, occurring in association with fever, infection, dieting, surgery or stress (Table 2).[5,18]

In patients with telogen effluvium, it is unusual to see loss of more than 50 percent of total hair. The patient's hair loss may not be evident to the clinician, since the scalp and hair shafts often appear normal. Hair growth regenerates approximately two to three months after the effluvium, but alopecia may persist indefinitely if the cause is not eliminated. Treatment involves identification of the causative factor, institution of therapy when possible, and reassurance that hair will grow back and that the patient will not become permanently bald.

ANAGEN EFFLUVIUM

Anagen effluvium is a far less common diffuse alopecia than telogen effluvium. It occurs within days to weeks after exposure to antimitotic chemotherapeutic agents or radiation therapy (Table 3).[18-20] The hair follicle matrix cells are acutely damaged, resulting in reduction of growth rate, thinning and breakage of hair shafts and loss of dystrophic anagen hairs.

[TABULAR DATA 3 OMITTED]

Patients with anagen effluvium have a strikingly obvious hair loss (up to 90 percent), which may take on a patchy or patterned appearance. The only hairs remaining on the scalp are normal telogen hairs not affected by the traumatic event. Alopecia usually resolves with removal of the inciting agent, but long-term exposure to an insult may result in a scarring alopecia.

TRAUMATIC ALOPECIA

Trichotillomania. Trichotillomania is a form of alopecia that is characterized by nonscarring, patchy hair loss secondary to pulling hair out. The scalp is most commonly involved, but the eyebrows or the eyelashes may be affected. In severe cases, the classic "tonsure" pattern of trichotillomania is seen as a rim of hair around the edges of the scalp (Figure 4). Although this condition may be a harbinger of serious psychologic disorders in adults, it is relatively common in otherwise healthy children. Clinically affected areas are characterized by twisted, broken-off hairs. Scalp biopsy may be diagnostic. Hair pluck usually shows characteristic findings, including an increased anagen:telogen ratio. Trichotillomania is treated by patient education and may require psychiatric consultation 21 or use of clomipramine (Anafranil), a drug useful in the treatment of obsessive-compulsive disorder.

Traction Alopecia. Traction alopecia occurs when tightly wound hair curlers are worn habitually or hair is braided too tightly. When hair is kept under traction, a pattern of alopecia may result that reflects the areas of maximum tension (Figure 5). History and clinical features are the clues to the diagnosis of this type of hair loss. Sterile folliculitis and scarring may develop in longstanding cases.[9] Treatment requires discontinuation of these hair care practices.

Hot-Comb Alopecia. Hot-Comb alopecia is most commonly seen on the vertex of the scalp in African Americans. After oil is applied to the hair, a hot comb is used to straighten it.[22] Hair shafts are damaged by the direct heat. Repeated dripping of hot oil onto hair follicles results in inflammation and scarring. Again, patient awareness is the key to resolution of the problem.

ALOPECIA AREATA

Alopecia areata may affect persons of all ages and classically has a sudden onset. Most often, alopecia areata presents as one or more asymptomatic oval patches (Figures 6 and 7), but it occasionally occurs as alopecia totalis (loss of all scalp hair) or even alopecia universalis (loss of all body hair). Inflammation may be seen in areas of recent hair loss. Alopecia areata is characterized by uniquely shaped hairs at the periphery of patches of alopecia, and it is also characterized by pitting of the nails.[23]

The disorder may occur in association with other autoimmune diseases (Figure 8) and, rarely, with Down syndrome.[24] Thyroid function tests are abnormal in up to 8 percent of patients with alopecia areata.[24] Scalp biopsy may be diagnostic. In many patients, the disease resolves on its own within months to years, but recurrences are common. Drug therapies include topical corticosteroids or, occasionally, topical anthralin (Dritho-Scalp, Drithocreme) and oral psoralens plus ultraviolet light A photochemotherapy (PUVA).[25]

FUNGAL INFECTIONS

Fungal infection of the scalp manifests as a nonscarring (noninflammatory) or scarring (inflammatory) alopecia. Noninflammatory scalp infections arise from human and animal sources. These infections are characterized by scale with an advancing border and central clearing, cause reversible hair loss and tend to recur even after treatment (Figure 9).

Inflammatory fungal infections may be passed from animals, soil and, less commonly, human sources.[26] They appear clinically as a boggy area with overlying scarring alopecia and follicular pustules. This hypersensitivity reaction to the fungus is called a kerion (Figure 10) and occurs in as many as 30 percent of fungal scalp infections in children.[9]

Diagnosis of fungal scalp infections is accomplished by using 10 percent potassium hydroxide preparation (Figure 11), Wood's lamp fluorescence (positive in only a small percentage of cases) and fungal culture.

Treatment of tinea capitis usually involves a four- to 12-week course of oral griseofulvin (Fulvicin, Grisactin, Grifulvin). Effective, but more expensive, alternatives are oral ketoconazole (Nizoral)[27] and itraconazole (Sporanox).[28] Other treatments to decrease shedding of spores and to combat secondary infection are special shampoos (2.5 percent solution of selenium sulfide [Selsun]) and antibiotics.

SYPHILIS

In up to 20 percent of patients with secondary syphilis, a patchy, diffuse, "motheaten" alopecia (Figure 12) of the scalp develops,[29] which may mimic alopecia areata or a fungal infection. Syphilitic alopecia may be preceded by a telogen effluvium. Scarring of the skin is unusual except in cases of tertiary syphilis. Diagnosis is achieved with a rapid plasma reagin or treponemal antibody, and treatment with penicillin is indicated.

LUPUS ERYTHEMATOSUS

Subacute cutaneous and systemic lupus erythematosus may cause a nonscarring alopecia characterized by erythema, scaling and broken-off hairs. In discoid lupus erythematosus, the scalp is involved in half of the cases, and in 10 percent of cases, it is the only site of involvement.[9] Discoid lesions may also be seen in patients with systemic lupus erythematosus. The early reversible stages show erythematous, scaly papules and plaques with telangiectases, edema and hair loss (Figure 13).

Diagnostic clinical findings include keratotic plugging and dilatation of follicular orifices. More advanced lesions are characterized by a peripheral violaceous border, loss of erythema, flattening of central areas, hypopigmentation with scarring, and loss of follicular units. Scalp biopsy is usually diagnostic. Direct immunofluorescence of skin biopsies may help confirm the diagnosis of systemic lupus erythematosus or discoid lupus erythematosus.

In addition to broad-spectrum photoprotection against ultraviolet A and ultraviolet B rays, discoid lupus erythematosus can be treated with topical and intralesional fluorinated corticosteroids (triamcinalone acetonide [Kenalog], although exceeding 5 mg per mL intralesionally may cause atrophy of the scalp), but permanent scarring occurs in the majority of cases. Scalp that is scarred and devoid of follicles will not regrow hair. Oral antimalarial drugs (e.g., hydroxychloroquine [Plaquenil], chloroquine [Aralen]) have been used successfully to treat discoid and subacute cutaneous lupus erythematosus.

OTHER SCARRING ALOPECIAS

Other types of scarring alopecias include other inflammatory dermatoses, deep infectious processes, neoplasms, bums, special diseases and genodermatoses that are primarily scarring in nature (Table 1). Permanent hair loss may result from these scarring processes and, once the common causes such as infection, trauma, physical or chemical irritation are ruled out, referral to a dermatologist is recommended.

Figure 1 adapted from Ackerman AB. The hair follicle. In: Histologic diagnosis of inflammatory skin diseases. Philadelphia: Lea & Febiger, 1978:50-64.

The authors thank Linda Lokys, M.D., and Chris Sartori, M.D., for their suggestions and review of the manuscript.

[Figure 1 to 13 IILLUSTRATION OMITTED]

REFERENCES

[1.] Kligman AM, Freeman B. History of baldness. From magic to medicine. Clin Dermatol 1988;6:83-8. [2.] Burke KE. Hair loss. What causes it and what can be done about it. Postgrad Med 1989;85(6):52-8,67-73,77. [3.] Ackerman AB. The hair follicle. In: Histologic diagnosis of inflammatory skin diseases. Philadelphia: Lea & Febiger, 1978:50-64. [4.] Ebling FJ. The biology of hair. Dermatol Clin 1987;5(3):467-81. [5.] Spencer LV, Callen JR Hair loss in systemic disease. Dermatol Clin 1987;5(3):565-70. [6.] Bertolino AP, Freedberg IM. Disorders of epidermal appendages and related disorders. In: Fitzpatrick TB, et al., eds. Dermatology in general medicine. 4th ed. New York: McGraw-Hill, 1993:671-96. [7.] Modly CE, Wood CM, Burnett JW. Evaluation of alopecia: a new algorithm. Cutis 1989;43:148-52. [8.] Aldridge RD. Hair loss. Br Med J [Clin Res] 1984; 289:985-9. [9.] Newton RC, Hebert AA, Freese TW, Solomon AR. Scarring alopecia. Dermatol Clin 1987;5(3):603-18. [10.] Hordinsky MK. General evaluation of the patient with alopecia. Dermatol Clin 1987;5(3):483-9. [11.] Sperling LC. Hair anatomy for the clinician. J Am Acad Dermatol 1991;25(1 Pt 1):1-17. [12.] Sawaya ME, Hordinsky MK. Advances in alopecia areata and androgenetic alopecia. Adv Dermatol 1992;7:211-26. [13.] Sperling LC, Heimer WL 2d. Androgen biology as a basis for the diagnosis and treatment of androgenic disorders in women. I. J Am Acad Dermatol 1993;28(5 Pt 1):669-83. [14.] Redmond GP, Bergfeld WE Diagnostic approach to androgen disorders in women: acne, hirsutism, and alopecia. Cleve Clin J Med 1990;57:423-7. [15.] de Koning EB, Passchier J, Dekker FW. Psychological problems with hair loss in general practice and the treatment policies of general practitioners. Psychol Rep 1990;67(3 Pt 1):775-8. [16.] Katz HI. Topical minoxidil: review of efficacy and safety. Cutis 1989;43:94-8. [17.] Ferry JJ, Forbes KK, Vanderlugt JT, Szpunar GJ. Influence of tretinoin on the percutaneous absorption of minoxidil from an aqueous topical solution. Clin Pharmacol Ther 1990;47:439-46. [18.] Brodin MB. Drug-related alopecia. Dermatol Clin 1987;5(3):571-9. [19.] Crounse RG. Toxic and physiologic alopecia. In: Demis DJ, ed. Clinical dermatology. Philadelphia: Lippincott, 1990:1-6. [20.] Steck WD. The clinical evaluation of pathologic hair loss with a diagnostic sign in trichotillomania. Cutis 1979;24:293-5,298-301. [21.] Muller SA. Trichotillomania. Dermatol Clin 1987; 5(3):595-601. [22.] O'Donoghue MN. Hair cosmetics. Dermatol Clin 1987;5:619-26. [23.] Alopecia areata symposium. Pediatr Dermatol 1987;4:136-58. [24.] Mitchell AJ, Balle MR. Alopecia areata. Dermatol Clin 1987;5(3):553-62. [25.] Fiedler VC. Alopecia areata. A review of therapy, efficacy, safety and mechanism [Editorial]. Arch Dermatol 1992;128:1519-29. [26.] Sauer GC. Manual of skin diseases. 6th ed. Philadelphia: Lippincott, 1991:215-20. [27.] Hebert AA. Tinea capitis. Current concepts. Arch Dermatol 1988;124:1554-7. [28.] Elewski BE. Tinea capitis: itraconazole in Trichophyton tonsurans infection. J Am Acad Dermatol 1994;31:65-7. [29.] Hira SK, Patel JS, Bhat SG, Chilikima K, Mooney N. Clinical manifestations of secondary syphilis. Int J Dermatol 1987;26:103-7.

TIMOTHY A. NIELSEN, M.D. is chief resident in dermatology at Ohio State University College of Medicine, Columbus. He received his medical degree from the University of South Florida College of Medicine, Tampa, and completed an internship in internal medicine at the University of Miami School of Medicine.

MARTIN REICHEL, M.D. is assistant professor of dermatology at the Columbia University College of Physicians and Surgeons, New York, N.Y., and is serving a fellowship in dermatopathology at the New York (N.Y.) University Medical Center. He completed his medical degree at Albert Einstein College of Medicine of Yeshiva University, Bronx, New York. Dr. Reichel served an internship in internal medicine at Montefiore Medical Center, Bronx, and served a residency in dermatology at the University of California, Davis, School of Medicine.

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