A. Definitions [2,8]

1. Hair Follicles - normally, scalp contains ~100,000 hairs (>90% actively growing)
2. Alopecia - hair loss
3. Androgenic alopecia - baldness caused by miniaturization of susceptible follicles
4. Alopecia areata - hair loss in patches believed to be autoimmune
5. Permanent alopecia - caused by destruction of hair follicles
6. Anagen Effluvium (see below)
   1. Anagen hairs are those that are actively growing
   2. Abrupt shedding of hair caused by interruption of active follicle growth
   3. Cancer chemotherapy is most common cause
7. Telogen Effluvium (see below)
   1. Excessive shedding of hair caused by increased proportion of follicles entering telogen
   2. Drugs and fever are common causes
8. Severity of hair loss characterized by Ludwig classification

B. Scarring (Cicatricial) Alopecia (major causes only)

1. Inflammatory Dermatoses
   1. Cicatricial pemphigoid
   2. Lupus erythematosus - discoid and systemic
   3. Necrobiosis lipoidica diabeticorum
   4. Sarcoidosis
   5. Scleroderma
   6. Likely that most forms of alopecia have an autoimmune component
2. Infection
   1. Bacterial - pyogenic, syphlis, tuberculosis, leprosy
   2. Viral - herpes (varicella) zoster
   3. Fungal and Protozoal infections
3. Physical and Chemical Agents
4. Neoplasms
   1. Basal cell carcinoma
   2. Lymphoma
   3. Nevi and Melanoma
   4. Metastatic Disease
   5. Squamous cell carcinoma
5. Congenital Abnormalities
   1. Aplasia cutis
   2. Congenital ichthyosis
   3. Epidermolysis bullosa
   4. Hair follicle hamartoma
   5. Ichthyosiform erythroderma
   6. Keratosis pilaris atrophicans

C. Nonscarring Alopecia [8]

1. Androgenic Alopecia [7]
   1. Male common baldness
   2. Affects ~65% of men
   3. Most common form of hair loss in women
   4. In women, often associated with acne, facial hirsutism (chronic anovulatory syndrome)
   5. Common mechanism is androgen excess
   6. Primary pathologic process due to androgen excess is called miniaturization
   7. Miniaturization leads to conversion of large (terminal) hairs to small (vellus) hairs
   8. Over time, the miniaturized hair follicles produce small, finer hairs
   9. The number of follicles per unit of area remains the same
   10. Young persons with androgenic alopecia have higher levels of 5alpha-reductase, more androgen receptors, and lower levels of P450 aromatase in frontal region hair follicles
   11. Reducing androgen levels (dihydrotestosterone, DHT) can improve hair growth [3]
2. Telogen Effluvium
   1. Diverse causes with anagen arrest
   2. Hair loss (usually >50%) occurs 2-4 months after initiating event
   3. Psychologic and pathologic causes and medications are often implicated
   4. Drugs: anticoagulants, oral-contraceptive withdrawal, ß-blockers, tricyclics, ACE inhibitors, amphetamines, anti-thyroid medicines, lithium, levodopa, nicotinic acid
   5. Other: hypothyroidism, fever, infection, severe systemic disease
   6. Far more common than Anagen Effluvium
3. Anagen Effluvium
   1. Drugs - colchicine, allopurinol, cimetidine, haloperidol, Vitamin A
   2. Radiation and Chemotherapy
   3. Heavy metal poisoning
4. Traumatic Alopecia
   1. Trichotillomania - Nonscarring, patchy hair loss secondary to pulling out hair
   2. Traction alopecia - tightly wound, braided hair
5. Alopecia Areata [7]
   1. Autoimmune disease affecting ~2% of population in USA
   2. Affects men and women equally
   3. One or more asymptomatic circular to oval patches, usually sudden onset
   4. May occur in small patches that regrow spontaneously, or persistent large patches
   5. Atopy, vitiligo, and autoimmuen thyroid disease are more common in affected persons
   6. Nail pitting is often present
   7. Activated CD4+ and CD8+ T lymphocytes with reactivity to hair follicles are found
   8. HLA-D (Class II MHC) associations have been observed
   9. High levels of Tumor Necrosis Factor alpha (TNFa) have been found in lesions
6. Compulsive hair pulling (trichotillomania)
7. Infections
   1. Various severe bacterial infections
   2. Secondary syphilis
   3. Tinea capitus
8. Various hair-care practices
9. Congenital disorders
10. Many of these can eventually cause scarring

D. Evaluation

1. History focused on duration and pattern of hair loss
2. Whether hair is shedding, which suggests alopecia areata or telogen effluvium
3. Whether hair is primarily thinning - suggests female-pattern hair loss
4. Hair falling out by the root - telogen effluvium, female-pattern hair loss, alopecia areata
5. Hair breaking off along the shafts - certain hair-care practices, trichotillomania, tinea capitis
6. Inquire about hair-care practices and about previous and current medications
7. Physical Examination
   1. Inspect scalp for inflammation, scale, erythema
   2. Scarring associated with hair loss assessed
   3. Visible follicular openings (ostia) found in non-scarring alopecia and not in scarring forms
   4. Pattern and distribution of hair loss and density of hair
   5. Quality of the hair shaft
8. Laboratory
   1. Assessment of free serum testosterone recommended for women with disease
   2. Rule out syphilis with VDRL or RPR tests
   3. Potassium hydroxide preparation of scrape if tinea is suspsected
   4. Diagnostic dilemmas may prompt a 4mm scalp punch biopsy

E. Treatments [7]

1. Finasteride (Propecia®) [4]
   1. Inhibitor of 5-alpha-reductase type 2 (converts testosterone to DHT)
   2. Reduction of DHT levels has been somewhat effective for androgenic alopecia [3]
   3. Finasteride, 1mg/day, reduces DHT levels ~65%, increases hair counts ~12%
   4. Hair count increases ~20 hairs per cubic centimeter as long as drug is taken
   5. On discontinuation, new hair is lost over 6-12 months
   6. Higher doses 5mg/day approved for prostatic hyperplasia do not appear as effective
   7. Consider finasteride in women with polycystic ovary syndrome as well
   8. Finasteride is contraindicated in women who may become or are pregnant
2. Minoxidil (Rogaine®) [4,5]
   1. Induces and prolongs anagen stage, converts vellus to terminal follicles
   2. Minoxidil is also an arteriolar vasodilator, can also improve hair counts slightly
   3. 5% and 2% solutions of minoxidil are FDA approved for promoting hair growth
   4. Treatment requires 48 weeks or more for androgenic alopecia
   5. Minoxidil (1 mL) is applied twice daily for effects
   6. 5% applied BID increases hair counts by ~19 per cubic centimeter
   7. Side effects are irritation of the scalp including dryness (increased with 5% solution)
   8. Hypertrichosis can occur in women using minoxidil
   9. No effects on blood pressure are seen
3. Psoralen plus ultraviolat A (PUVA) has shown some efficacy [4]
4. Alopecia Areata
   1. Glucocorticoids - topical or systemic
   2. Topical immunotherapy - induce contact sensitization
   3. Anthrallin
   4. Minoxidil (see above)
5. Alopecia Totalis and Universalis
   1. Relatively resistant to topical agents
   2. PUVA has shown some activity but maintenance PUVA therapy required [4]
6. Trichotillomania may respond to antidepressants
7. Hair transplantation may be required

References

1. Nielsen TA and Reichel M. 1995. Am Fam Phys. 51(6):1513
2. Paus R and Cotsarelis G. 1999. NEJM. 341(7):491
3. Finasteride. 1998. Med Let. 40(1021):25
4. Finasteride and Minoxidil. 2005. Med Let. 47(1222):95
5. Minoxidil. 1998. Med Let. 40(1021):26
6. Lebwohl M. 1997. Lancet. 349:222
7. Price VH. 1999. NEJM. 341(13):964
8. Shapiro J. 2007. NEJM. 357(16):1620