Alopecia

Alopecia is the loss of hair from any hair-bearing area of the body, but most often the scalp. It may be congenital or acquired, circumscribed or diffuse, and scarring or nonscarring. Androgenetic alopecia, a type of diffuse, nonscarring, acquired alopecia, is most common. Alopecia areata, an acquired, circumscribed, nonscarring alopecia, is the second most common type. Clinical diagnosis is usually possible. In ambiguous cases, diagnosis is aided by microscopic examination of the hair, trichogram, and scalp biopsy. Treatment depends on the type of alopecia and can include long-term (at least one year) use of topical minoxidil, corticosteroids (topical, intralesional, or oral), or antiandrogens. Surgery (hair transplant) or camouflaging techniques are used as ancillary treatments and/or when medical therapy is unsuccessful. The prognosis is variable and depends on the etiology and severity of hair loss.

Terminology

• Alopecia: : loss of hair (baldness)
• Effluvium : process of hair loss
• Atrichia : inherited hair loss
• Hypotrichosis : congenital sparse hair, which is usually associated with syndromes such as:
  • Netherton syndrome: autosomal recessive disorder caused by mutations in SPINK5, a gene that encodes a serine protease kinase.
  • Rothmund-Thomson syndrome: syndrome characterized by short stature, sparse hair, poikiloderma, skeletal abnormalities, and cataracts.

Phases of hair growth ^[1]

• Anagen phase: phase of active growth
• Catagen phase: phase of follicular regression
• Telogen phase: resting phase

Classification by etiology and pattern

Classification by presence of scarring ^[4]

Scarring (cicatricial) alopecia

• Brocq pseudopelade ^[6]
  • Seen mainly in women 30–50 years of age
  • Irregular areas of irreversible hair loss, which become scarred areas at a later stage
• Lichen planopilaris
• Frontal fibrosing alopecia: a progressive form of frontotemporal hair loss associated with local scarring ^[7]
• Central centrifugal cicatricial alopecia ^[7]
  • Alopecia that starts at the crown and spreads outwards
  • Occurs almost exclusively in Black women
• Skin conditions causing scarring alopecia
  • Discoid lupus erythematosus
  • Ichthyosis
  • Dyskeratosis
• Acquired scarring alopecia (e.g., via viral diseases, mycoses, burns, chemical burns)

Nonscarring alopecia

• Alopecia areata
• Telogen effluvium
• Traction alopecia ^[8]
• Temporal triangular alopecia

The diagnosis is often clear from the patient history and physical examination; however, there are several tests that help determine the type and etiology of alopecia.

Clinical evaluation ^[5]

• History that includes onset, pattern, history of inciting events, and family history
• Physical examination of the scalp, hair shaft, and hair follicles
• Evaluate for systemic symptoms suggestive of underlying medical conditions.

Diagnostic studies ^[5][9][10]

• Trichoscopy: examination of the hair and scalp using a dermatoscope to visualize hair shafts, hair follicle openings, perifollicular epidermis, and scalp blood vessels
• Hair pull test: about 50 strands of hair are lightly tugged away from the scalp; if > 5 strands are pulled out, the test is positive.
• Hair mount: a microscopic examination of the hair follicles and hair shaft to identify hair cycle disorders and structural hair shaft abnormalities
• Trichogram: ∼ 50 hairs are plucked from the scalp and microscopically examined to quantify hair follicles in different growth phases and assess for the presence of dystrophic hairs ^[11]
• Scalp biopsy: performed at sites of active disease where there are persistent hair fibers

Congenital diffuse alopecia ^[2]

• Trichorrhexis nodosa: a hair shaft deformity characterized by the development of weak points in the shaft due to physical or chemical trauma or genetic predisposition
• Pili torti: a condition in which the hair shaft is flattened and has multiple twists, resulting in fragile hair that breaks easily
• Monilethrix (beaded hair): predominantly autosomal dominant disorder in which hair shafts break easily, resulting in a beaded appearance usually a few months after birth
• Genetic syndromes: e.g., Menkes disease, Netherton syndrome

Congenital circumscribed alopecia

• Temporal triangular alopecia ^[12]
  • A well-defined oval or triangular patch of alopecia in the temporal part of the scalp
  • Onset is often before adolescence.
  • Mimics alopecia areata and is differentiated from it by the absence of exclamation point hair
  • Treatment (if necessary): hair transplant or surgical excision for improved cosmesis
• Nevus sebaceous ^[13][14]
  • A well-demarcated, hairless, velvety plaque that is typically orange or tan
  • At risk of malignant degeneration (e.g., basal cell carcinoma)
  • Treatment: surgical excision
• Aplasia cutis congenita ^[15]
  • Intra-uterine developmental disruption of one/more layers of the scalp
  • A part of the scalp is missing at birth, which, on healing, causes a scarred, hairless patch
  • Treatment: depends on size, depth, location, and tissues involved
    • Small lesions: conservative treatment with antibiotic dressings and creams
    • Large lesions: surgical excision and primary closure with help of tissue expanders and skin flaps

Telogen effluvium ^[5][16]

• Etiology
  • Endocrine: hypothyroidism, hyperthyroidism
  • Drugs: retinoids, antithyroid drugs, anticonvulsants, anticoagulants, NSAIDs, antidepressants, discontinuation of oral contraceptives
  • Nutritional: zinc deficiency, iron deficiency, riboflavin deficiency, Vitamin D deficiency, malnutrition states
  • Stress: severe febrile illness, emotional stress, hemorrhage (e.g., trauma, major surgery)
  • Infectious: typhoid, malaria, HIV, tuberculosis, syphilis
  • Other: telogen gravidarum, autoimmune (e.g., systemic lupus erythematosus)
• Mechanism: telogen (resting) phase of hair growth predominates → premature shedding of the resting hair follicles → diffuse, nonscarring hair loss
• Clinical features
  • Hair density reduces by < 50%
  • Does not progress to complete baldness
• Diagnostics ^[5]
  • Hair pull test: positive
  • Trichogram: > 25% of hairs in the telogen phase
  • Assessment for potential triggers 2–5 months prior to the onset of hair loss
  • Scalp biopsy if uncertain (rarely necessary)
• Treatment: reassurance and management of the underlying condition (e.g., stop the causative medication, nutritional supplementation)

Anagen effluvium ^[5][17]

• Etiology
  • Drugs
    • Chemotherapy-induced alopecia
    • Others: e.g., tamoxifen, allopurinol, levodopa
  • Radiation therapy to the scalp
  • Medical conditions: e.g., mycosis fungoides, pemphigus vulgaris
• Mechanism: interruption of the anagen (mitotic) phase → abrupt loss of ∼ 90% of hair (within days of exposure to the causative factor)
• Clinical features: diffuse, nonscarring hair loss days to weeks after exposure
• Diagnostics
  • Clinical diagnosis
  • Positive hair pull test ^[18]
• Treatment: Stop any triggers and treat underlying conditions.

Traction alopecia ^[8][19]

• Definition: hair loss due to chronic traction or tension on the hair follicles
• Etiology: hairstyles involving tying the hair tightly
• Clinical features: circumscribed hair loss at sites of traction, predominantly at the frontal and temporal scalp
• Treatment
  • Remove the source of traction.
  • Potential additional treatments include topical and intralesional corticosteroids and topical minoxidil.

Definition ^[20]

A progressive, nonscarring alopecia that affects the regions of the scalp with the most androgen-sensitive hair follicles, resulting in a characteristic pattern of balding (bitemporal scalp in men and vertex and frontal scalp in women)

Epidemiology ^[5]

• Most common type of alopecia
• Prevalence: increases with age ^[5]
• Sex: ♂ > ♀
• Age at onset
  • ♂: Puberty
  • ♀: Menopause
• Race: more common in White individuals

Etiology ^[20][21]

• Increased androgen sensitivity of hair follicles in genetically predisposed individuals
• Conditions that cause hyperandrogenism (less common), e.g.:
  • Polycystic ovary syndrome (PCOS)
  • Congenital adrenal hyperplasia
  • Androgen-producing tumors, e.g. Leydig cell tumor

Pathophysiology ^[20]

• Dihydrotestosterone binds to androgen receptors on hair follicles.
• Follicular miniaturization: androgens shorten the anagen phase of hair growth → vellus hair formation (thin, short hair)
• 5α-reductase, an enzyme present in hair follicles, converts testosterone into the more potent dihydrotestosterone, which is responsible for alopecia.

Clinical features ^[22]

• General features: gradual, nonscarring hair loss
• Male pattern baldness
  • Bitemporal "M” pattern of recession
  • May be followed by hair loss on the vertex of the scalp
• Female pattern baldness
  • Begins at the vertex
  • Progresses to diffuse hair thinning of the entire scalp
  • Seen primarily in postmenopausal women, rarely in men
  • May be accompanied by features of hyperandrogenism

Diagnostics ^[22]

• Clinical diagnosis
• Trichoscopy: follicular miniaturization
• Negative hair pull test
• Women with hyperandrogenism: Refer to endocrinology.

Differential diagnoses

• Diffuse alopecia areata
• Telogen effluvium

Treatment ^[20][23]

Pharmacotherapy ^[5][24][25]

• Topical minoxidil 5% or minoxidil 2%
  • Direct arterial vasodilator ^[26][27]
  • First-line treatment for men and women
• Finasteride
  • 5α-reductase inhibitor
  • First-line treatment for men
  • Off-label for women ^[28]
• Oral antiandrogens, e.g., spironolactone
  • Off-label for androgenetic alopecia in women ^[23][28]
  • May be indicated for women with hyperandrogenism

Minoxidil is a direct arteriolar vasodilator and can also be used to treat resistant hypertension. ^[29]

Nonpharmacological measures ^[24]

• Camouflage: e.g., keratin fibers, hair dyes, toupées, wigs
• Low-level laser therapy (LLLT): self-administered via combs or caps
• Hair transplant surgery: Follicular units from the occipital scalp are extracted (either as small units or as a linear strip), divided into small units, and implanted into the bald areas. ^[23]

Definition ^[30]

A nonscarring circumscribed alopecia that is characterized by well-demarcated patches of hair loss due to immune-mediated inflammation of hair follicles

Epidemiology ^[30]

• Prevalence: ∼1 in 1000 people
• Age of onset: mostly < 40 years
• Sex: ♂ = ♀

Etiology

• Immune-mediated inflammation and disruption of anagen phase hair follicles → well-defined patches of nonscarring hair loss
• A trigger factor (e.g., emotional stress, infections, pregnancy) may precede some cases
• Family history in ∼ 20% of cases ^[31]

Clinical features ^[30][31]

• Abrupt onset (within weeks)
• Smooth, circular, well-defined patches of hair loss without scarring
• Nail involvement (up to 40% of cases): nail pitting, onycholysis, Beau lines
• Other autoimmune disorders may be present (e.g., vitiligo, autoimmune disorders of the thryoid).
• Patterns of hair loss
  • Ophiasis: hair loss localized to the back and sides of the scalp
  • Sisiapho: sparing of the sides and back of the scalp
  • Extensive alopecia areata: hair loss affecting > 50% of the scalp
  • Alopecia universalis: All hair-bearing sites are affected (mimics telogen effluvium).
  • Alopecia totalis: complete baldness

Diagnostics ^[5]

• Clinical diagnosis
• Trichoscopy: exclamation point hairs
• Scalp biopsy and trichogram may be performed to confirm the diagnosis.

Differential diagnosis ^[31]

• Trichotillomania: compulsive pulling out of hair resulting in ill-defined patchy hair loss and different lengths of hair
• Loose anagen syndrome: hair falling out in clumps with minimal traction due to abnormal keratinization of the hair root and poor anchoring of the hair follicle to the scalp
• Tinea capitis: Affected areas of the scalp appear scaly.
• Secondary syphilis: The scalp has a moth-eaten appearance due to patchy hair loss.
• Brocq pseudopelade: irregular areas of hair loss that become scarred in later stages

Treatment ^[5][31][32]

Treatment is guided by the patient's age, disease duration, and disease extent. Options include:

• Corticosteroids: intralesional (triamcinolone), topical, and/or systemic
• Topical immunotherapy: diphenylcyclopropenone or squaric acid dibutyl ester
• Others: anthralin, minoxidil, cyclosporine

Prognosis ^[19]

• Alopecia areata: 30–50% of patients recover within one year.
• Alopecia universalis and alopecia totalis: < 10% of patients recover.