Alopecia

Overview

Normal phases of hair growth

1. Anagen: 
   • Period of active growth
   • Approximately 90% of all hair follicles are in the anagen phase.
   • Lasts 2–6 years
2. Catagen: 
   • Transitory period of follicular degeneration or regression 
   •  < 1% of all hair follicles are in the catagen phase.
   • Lasts 2–3 weeks
3. Telogen: 
   • Period of rest
   • Approximately 10% of all hair follicles are in the telogen phase.
   • Lasts 2–3 months
4. After the telogen phase, hairs fall out at a rate of 50–100 scalp hairs per day.

Classification or types of alopecia

The most common classifications of hair loss are cicatricial (scarring) alopecia, non-scarring alopecia, and structural hair disorders.

Cicatricial (scarring):

The hair follicle undergoes irreversible damage, which heals through fibrosis, leading to a cessation in hair cycling and permanent hair loss.

• Secondary: caused by inflammation due to physical trauma or a condition that is not a primary scalp disease (includes tinea capitis, neoplasms, radiation therapy, and surgical scars)
• Primary: caused by inflammatory disorders of the scalp in which the hair follicle is the main target in destruction, resulting in permanent hair loss (divided into 3 subtypes: lymphocytic, neutrophilic, and mixed)

Non-scarring:

Inflammation is mild or absent so that the hair follicle is not damaged, resulting in non-permanent hair loss (divided into 3 subtypes: focal, patterned, and diffuse).

Structural hair disorders:

Structural hair disorders are inherited or acquired disorders of hair structure that result in brittle or fragile hair, which lead to hair breakage or the appearance of hair growth failure.

Diagnosis

Medical history:

• It’s important to determine the duration, rate of progression, location, pattern, and extent of hair loss along with the patient’s associated symptoms, medical disorders/events, family history of hair loss, medications, and diet/caloric intake.
• Drugs associated with hair loss: 
  • Amantadine
  • Amiodarone
  • Isotretinoin
  • Anticoagulants
  • Ketoconazole 
  • Anticonvulsants
  • Lithium
  • Captopril
  • Penicillamine
  • Statins
  • Propranolol
  • Cimetidine
  • Colchicine
• Medical conditions associated with hair loss:
  • Major illness, surgery, and/or psychologic stress
  • Significant weight loss 
  • Chronic iron deficiency
  • Thyroid disorders 
  • Childbirth
  • Poisoning from arsenic, mercury, or thallium

Physical exam:

• Visual inspection: 
  • Presence versus absence of follicular ostia (absence = scarring alopecia)
  • Distribution and density of hair
  • Pattern of hair loss
  • Use of contrasting colored paper to fully visualize hair
  • Examine other sites of hair plus nails, skin, and teeth
• Trichoscopy: dermoscopy of the hair and scalp, which allows for better visualization of the epidermis, follicular ostia, hair shafts, scale, erythema, and blood vessels
• Hair pull test: identifies active hair loss by grasping and slightly tugging 50–60 hair fibers, easy extraction of > 6 hair fibers suggests active hair loss

Additional tests:

• Microscopy: microscopic evaluation of the proximal hair ends, which is useful for determining the phase of the shedding hair
• Scalp biopsy: used in scarring forms of alopecia to distinguish inflammatory from non-inflammatory causes
• Trichograms and phototrichograms: used to evaluate non-scarring hair loss and treatment response
• Laboratory: 
  • Thyroid-stimulating hormone (TSH) to assess thyroid disorders
  • Serum iron and ferritin to assess iron deficiency
  • Rapid plasma reagin test to assess for syphilis

Androgenetic Alopecia

Definition

Androgenetic alopecia is a hereditary type of hair loss that is mediated by the presence of the androgen dihydrotestosterone (DHT) and is the most common type of alopecia.

Male-pattern hair loss

• Epidemiology:
  • Most common alopecia in men
  • Prevalence increases with age.
  • Affects 80% of men by age 80
  • Lower prevalence in Chinese, Asian, and African Americans than in Caucasians
• Etiology:
  • Genetic predisposition (androgen-dependent trait) 
  • Related to the X chromosome
• Pathophysiology:
  1. Testosterone is converted to DHT by 5-alpha-reductase.
  2. DHT binds to the androgen receptor in hair follicles and activates genes that shorten the anagen phase.
  3. Leads to follicular miniaturization of hair follicles of the scalp (a progressive decrease in the ratio of terminal hairs to shorter, thinner vellus hairs)
• Clinical presentation:
  • Hair loss can begin any time after puberty (usually in the late 20s) and progresses over the patient’s lifetime.
  • Receding mid-temporal hairline
  • Vertex has diffuse thinning/balding with intact frontal hair.
  • Preservation of hair density in the occipital region
  • Visible reduction in hair density
• Diagnosis: based on history and exam
• Management:
  • 1st-line therapy: 
    • Oral finasteride: 5-alpha-reductase inhibitor that inhibits the conversion of testosterone to DHT and inhibits follicular miniaturization
    • Topical minoxidil: vasodilator that increases the duration of anagen, shortening telogen, and enlarging miniaturized follicles
  • Other options:
    • Hair transplant surgery
    • Low-level laser light therapy
    • Cosmetic use of hairpieces

Female-pattern hair loss

• Epidemiology: 
  • A common condition affecting 19% of Caucasian women
  • Most commonly occurs following menopause
  • Prevalence increases with age, with ⅓ of women being affected by age 70.
• Etiology: 
  • Not well understood
  • Androgen excess may play a role.
  • Genetic predisposition is suspected.
• Pathophysiology:
  • Transformation of the terminal hair follicle to a thinner vellus hair follicle via follicular miniaturization
  • Shortened anagen phase and lengthened telogen phase
• Clinical presentation:
  • Diffuse thinning of hair
  • Frontal hairline is thinned yet preserved.
  • Progressively widening midline part leading to crown thinning
  • Preservation of hair density in the occipital region
• Diagnosis: 
  • Based on history and exam
  • Laboratory: Free and total testosterone level and dehydroepiandrosterone sulfate (DHEAS) level can test for an underlying hyperandrogenic state.
• Management:
  • 1st-line therapy: topical minoxidil (vasodilator that increases the duration of anagen, shortening telogen, and enlarging miniaturized follicles)
  • 2nd-line therapies: 
    • Spironolactone: aldosterone antagonist that competitively blocks androgen receptors and inhibits androgen synthesis
    • Finasteride: 5-alpha-reductase inhibitor that inhibits the conversion of testosterone to DHT and inhibits follicular miniaturization
  • Other options:
    • The use of wigs or cosmetic camouflaging
    • Hair transplant surgery

Alopecia Areata

Definition

Alopecia areata is a chronic, relapsing, autoimmune disorder in which the body’s immune system targets anagen hair follicles and causes non-scarring hair loss.

Epidemiology

• Occurs in 1% of the population
• The lifetime risk is approximately 2%.
• Occurs at similar rates in males and females
• The average age of onset is approximately 30 years.

Etiology

• Autoimmune disease, where hair follicles are targeted and transition prematurely from the anagen growth phase to the catagen and telogen phases
• Genetic predisposition also plays a role.
• Associated disorders:
  • Other autoimmune diseases: vitiligo, lupus, psoriasis, scleroderma, thyroiditis, celiac disease, atopic dermatitis, allergic rhinitis
  • Genetic disorders: Down’s syndrome
  • Psychosocial disorders: stress, anxiety, mood disorders

Clinical presentation

• Sudden onset of hair loss over a few weeks that may relapse throughout the patient’s life
• Usually asymptomatic and not associated with pain, but occasionally may present with pruritus or burning that precedes the loss of hair
• Hair loss occurs in well-demarcated, smooth, circular patches.
• Commonly affects the scalp, but may also affect the eyebrows, eyelashes, and beard 
• Exclamation point hairs: short, broken hairs where the proximal end is narrower than the distal end
• Nail abnormalities: pitting, fissuring, red spots, or separation from the nail bed
• Types/patterns of distribution:
  • Areata: patchy areas of hair loss
  • Ophiasis: hair loss localized to the back and sides of the scalp
  • Sisaipho: sparing of the sides and back of the scalp
  • Extensive: affects > 50% of scalp
  • Totalis: total loss of scalp hair
  • Universalis: complete loss of all body hair

Diagnosis

• Exam: smooth, round, or patchy areas of non-scarring hair loss with exclamation point hairs (pathognomonic for the areata type of alopecia)
• Hair pull test: confirms active hair loss when > 6 hairs are easily extracted when 50–60 are pulled

Management

• ½ of the patients will experience spontaneous regrowth of hair in less than a year.
• 1st-line therapy:
  • Limited hair loss (< 3 patches or < 3 cm): 
    • Intralesional corticosteroid injections
    • Potent topical corticosteroids if unable to tolerate injections
  • Severe hair loss (alopecia totalis/universalis): 
    • Topical immunotherapy
    • Local corticosteroids
    • Systemic glucocorticoids
• 2nd-line therapy: topical anthralin (an irritant agent used as an adjunct with 1st-line therapies)
• Refractory disease:
  • Azathioprine
  • Janus kinase inhibitors
  • Methotrexate
  • Sulfasalazine

Prognosis

• Mild cases: 80% spontaneously resolve.
• Severe cases: remain chronic or relapse after treatment

Traction Alopecia

Definition

Traction alopecia is a type of non-scarring hair loss caused by repetitive or prolonged tension on the hair.

Epidemiology

• Higher prevalence in women than men due to traction hairstyles
• Most commonly associated with African American women with Afro-textured hair due to types of hairstyling

Etiology

• Long-term traction associated with any hairstyle that causes tension at the follicle (e.g., weaves, braids, tight buns, and/or ponytails) or tight headgear (e.g., caps, hats)
• Can be more severe in chemically treated hair

Pathophysiology

• Traction on hair → perifollicular inflammation → follicular miniaturization
• Initially, traction alopecia is non-scarring but persistent traction leads to scarring and irreversible damage.
• High levels of interleukin (IL) 1-alpha in the scalp sebum support the inflammatory theory.

Clinical presentation

• Early stages: 
  • Absent/limited hair loss with slightly decreased hair density
  • Traction folliculitis presenting as perifollicular erythema and pustules on the scalp
• Late stages: 
  • Decreased hair density → completely hair-free patches
  • Fringe sign: fine, residual hair retained at the margin of the anterior hairline with hair loss posteriorly
  • Hair casts: white scaling (firm cylinders ensheathing the hair shaft) that can be easily dislodged

Diagnosis and management

• Diagnosis is based on clinical evaluation.
• Management of early stages:
  • Cessation of traction hairstyles
  • Topical minoxidil to aid in hair regrowth
  • Local corticosteroids if signs of inflammation are present
  • Oral tetracycline is also used for its anti-inflammatory effects.
• Management of late stages:
  • Topical minoxidil to attempt hair regrowth, although regrowth is unlikely if the inflammation has already led to scarring
  • Hair transplant surgery
  • Cosmetic camouflage

Prognosis

• Early stages: spontaneous regrowth within 3 months
• Late stages: usually presents with scarring and may have permanent hair loss

Tinea Capitis–related Alopecia

Definition

Tinea capitis is a fungal infection of the scalp typically presenting as pruritus and scaling, leading to secondary cicatricial (scarring) alopecia.

Epidemiology

• Common in children
• More common in African American children

Etiology

• 3 forms of dermatophyte infection:
  1. Endothrix: 
     • Fungal spores are within the hair shaft.
     • Caused by Trichophyton tonsurans
     • Presents as patches of hair loss with black dots (distal ends of hairs that break at the scalp)
  2. Ectothrix: 
     • Fungal spores surround the outside of the hair shaft.
     • Caused by Microsporum canis
     • Presents as scaly patches of hair loss that enlarge centrifugally over time and have associated erythema
  3. Favus: 
     • Fungal hyphae and air spaces are found within hair shafts.
     • Caused by Trichophyton schoenleinii
     • Presents as severe hair loss with yellow cup-shaped crusts on the scalp called scutula, which surround the infected hair follicles 
• Spread through person-to-person contact, animal vectors, and fomites (e.g., combs, brushes, pillowcases, or hats)

Pathophysiology

1. Dermatophytes come in contact with the stratum corneum of the scalp.
2. Glycoproteins and keratinases produced by the fungus enable dermatophytes to invade the skin and hair, breaking down the keratin.
3. Infection spreads into the epidermis and down the hair follicle.

Clinical presentation

• Usually presents as pruritic scaly patches with alopecia and/or broken hair shaft (black dots) 
• May develop postauricular lymphadenopathy
• Kerion: 
  • Severe form due to an intense inflammatory immune response
  • Inflammatory plaques with pustules, thick crusting, and/or pus drainage develop.
  • Pain and tenderness are present.
• Favus:
  • Erythematous follicles progress to cup-shaped yellow crusts that coalesce to form adherent masses.
  • Severe, extensive alopecia develops.
  • Associated with an unpleasant odor

Diagnosis

• Physical exam: 
  • Patches with hair loss, scaling, or black dots on a child
  • Wood’s light shows the presence of spores.
• Dermoscopy: 
  • C-shaped/corkscrew hairs
  • Black dots with Trichophyton tonsurans infection
  • Yellow scales 
• Potassium hydroxide (KOH) preparation shows the presence of branching hyphae.
• Fungal cultures are used to confirm cases with high suspicion but a negative KOH preparation.

Management

• 1st-line therapy is systemic antifungals: 
  • Oral griseofulvin
  • Oral terbinafine
• Alternatives:
  • Oral fluconazole
  • Oral itraconazole 
• Adjunctives:
  • Shampoo with antifungal properties
  • Care not to spread to others, management for the family if the spread has already occurred

Prognosis

• Hair regrowth usually occurs after treatment.
• If scarring is present, the patient may have permanent damage, which is particularly likely in kerion and favus infections.

Telogen Effluvium

Definition

Telogen effluvium is defined as the premature transition of hair follicles into the resting state (telogen) after a physiologic or psychologic stressor, which leads to diffuse, non-scarring alopecia.

Epidemiology

• No predilection for any race or ethnic group
• Women are more commonly affected than men.

Etiology

• Psychosocial stressor (e.g., death of a family member, loss of a job)
• Extreme weight loss
• Severe acute illness
• General anesthesia
• Childbirth
• Hypo- and hyperthyroidism
• Iron deficiency
• Beginning or discontinuing hormonal contraceptive 
• Medications (e.g., lithium, valproate, fluoxetine, heparin, beta blockers, angiotensin-converting enzyme (ACE) inhibitors, retinoids, antituberculosis medications, antiretrovirals, androgens)

Pathophysiology

• Not completely understood
• Underlying etiology/stressor → insult to the anagen bulb → follicular cycling changes, such as immediate and/or delayed anagen release

Clinical presentation

• Diffuse reduction of scalp hair density that may be most noticeable in bitemporal, frontal, and vertex areas
• The daily loss of hair increases to 100–300 hair strands.
• Acute:
  • Develops within 1–3 months of trigger
  • Lasts 2–4 months
  • Reversible 
• Chronic:
  • Idiopathic or with no noticeable trigger
  • Lasts > 6 months

Diagnosis

• Physical examination: a tiny club-shaped bulb at the proximal end of the fallen hairs, with greater than 10% of hairs in the telogen phase
• Positive hair pull test

Management

• 1st-line therapy: 
  • Removal or treatment of any reversible causes
  • Cosmetic measures
  • Psychologic support
• Adjunctive therapy:
  • Topical minoxidil: promotes hair growth
  • Iron supplementation for possible iron deficiency anemia

Prognosis

• Acute cases: spontaneous regrowth usually within 6 months 
• Chronic cases: persistent hair loss for > 6 months

Differential Diagnosis

The following are other conditions that can cause alopecia:

• Trichotillomania: a type of patterned, non-scarring alopecia due to deliberate hair pulling, plucking, or twisting to relieve stress or anxiety. Most common in young females with family or psychosocial stress. Characterized by a wide variation in lengths of the remaining hair. Trichotillomania usually affects the scalp, eyebrows, and eyelashes.
• Nevus sebaceous: a sporadic, congenital, hairless plaque on the face or scalp due to benign growth of excess sebaceous glands resulting in loss of hair follicles in that area. Plaque is usually single, circular, linear, or irregular in shape. Surgical intervention may be necessary due to slight malignant potential.
• Secondary syphilis: a sexually transmitted infectious disease caused by the bacterium Treponema pallidum. If left untreated, primary syphilis becomes secondary syphilis approximately 4–10 weeks after the primary infection. Symptoms include fever, malaise, lymphadenopathy, moth-eaten patchy alopecia, confusion, condyloma lata, and a generalized papulosquamous eruption on palms and soles.
• Seborrheic dermatitis: a common chronic papulosquamous dermatosis with distinct infantile and adult forms. Presents as erythematous, well-demarcated plaques with greasy yellow scales in areas with hair and oily skin, such as the scalp, face, chest, and back. Seborrheic dermatitis prevents hair growth in the affected area.