Comprehensive Lecture: Biology of Hair and Hair Disorders
Module 1: Hair Follicle Anatomy and Structure (20 minutes)
Basic Follicular Architecture
The hair follicle is a complex mini-organ embedded in the dermis that consists of distinct anatomical regions: the bulb, suprabulbar zone, isthmus, and infundibulum 1. Understanding these regions is essential for comprehending hair pathology.
- Hair follicle location and structure: The follicle is a sheath that covers and feeds the portion of hair beneath the epidermis, anchored in the dermis which extends 1.5-4 mm in thickness 2
- The hair bulb contains the hair matrix surrounding the dermal papilla, which serves as the command center for hair growth 1
- The suprabulbar zone is where the inner and outer root sheaths are well-developed during active growth 1
- The isthmus extends from the insertion of the arrector pili muscle to the sebaceous gland duct 2
- The infundibulum represents the uppermost portion connecting to the skin surface 1
Cellular Components
- Keratinocytes comprise the primary structural cells, producing the proteins that form the hair shaft 2
- Melanocytes located in the hair bulb produce pigment that determines hair color 2
- Dermal papilla cells provide critical signaling for hair follicle cycling and growth regulation 1
- Hair follicle stem cells reside in the bulge region and are regulated by Notch signaling pathways 3
Associated Structures
- Sebaceous glands connect to hair follicles (particularly on face and scalp) and secrete sebum to maintain hair and scalp health 2
- Arrector pili muscles attach to follicles and cause hair to stand erect 2
- Blood vessels supply nutrients and oxygen essential for the metabolically active hair matrix 2
- Nerve endings provide sensory innervation creating the hair follicle receptor (root hair plexus) 2
Module 2: Hair Growth Cycle and Regulation (25 minutes)
The Three Phases of Hair Growth
The most critical feature of hair follicles is their intermittent activity, cycling through anagen (growth), catagen (regression), and telogen (rest) phases 4.
Anagen Phase (Growth Phase)
- Duration varies by body region: Scalp anagen lasts 2-7 years, while eyebrow anagen lasts only 1-2 months 4
- Characterized by active hair matrix surrounding the dermal papilla with well-developed inner and outer root sheaths 1
- The length of anagen primarily determines final hair length, not growth rate, which remains relatively constant at approximately 1 cm per month on the scalp 4
- Approximately 85-90% of scalp hairs are in anagen at any given time 4
Catagen Phase (Regression Phase)
- Brief transitional phase lasting 2-3 weeks 4
- Identified by markedly thickened vitreous layer and fibrous root sheath surrounding an epithelial column 1
- The club hair begins to form above the epithelial column 1
- Represents less than 1% of scalp hairs at any time 4
Telogen Phase (Resting Phase)
- Lasts approximately 3 months on the scalp 4
- Distinguished by fully keratinized club hair surrounded by an epithelial sac 1
- Secondary hair germ and condensed dermal papilla lie dormant below, awaiting signals to initiate new anagen 1
- Approximately 10-15% of scalp hairs are in telogen normally 4
- Normal shedding of 50-100 telogen hairs daily occurs as new anagen hairs emerge 4
Molecular Regulation of Hair Cycling
Hair follicle development and cycling require interplay of several key signaling pathways: Wnt, Shh, Notch, and BMP 3.
- Wnt pathway is primarily involved in follicle induction and initiation of anagen 3
- Sonic hedgehog (Shh) is essential for early organogenesis and later cytodifferentiation stages 3
- Notch signaling governs hair follicle stem cell fate decisions 3
- BMP (bone morphogenetic protein) plays a role in cytodifferentiation and can inhibit hair growth when overexpressed 3
Hormonal Regulation
Androgens profoundly influence hair growth in specific body regions, with paradoxical effects on scalp versus body hair 4.
- Facial and body hair require high testosterone levels and conversion to 5α-dihydrotestosterone (DHT) via 5α-reductase 4
- Pubic and axillary hair require much lower androgen levels and 5α-reduction appears unnecessary 4
- Paradoxically, male pattern baldness also requires androgens for manifestation, with DHT causing progressive follicle miniaturization 4
- Androgenetic alopecia relates to DHT sensitivity in genetically predisposed follicles 5
Module 3: Hair Disorders - Classification and Pathophysiology (25 minutes)
Non-Scarring Alopecias
Alopecia Areata
Alopecia areata is an autoimmune condition mediated by T lymphocytes targeting hair follicles, characterized by patchy, non-scarring hair loss 2, 5.
- Approximately 20% have family history, indicating genetic predisposition involving MHC genes, cytokine genes, and genes regulating immune responses 2
- The hair follicle is an immunologically privileged tissue, and failure of this immune privilege plays a key role in pathogenesis 2
- Clinical presentation: Well-demarcated patches of complete hair loss with exclamation mark hairs (short broken hairs 3-4mm long) at expanding margins 2
- Prognosis varies significantly: 34-50% recover within one year, but 14-25% progress to alopecia totalis or universalis with recovery rates <10% 2
- Disease severity at presentation is the strongest predictor: Patients with <25% hair loss initially have 68% chance of being disease-free long-term, versus only 8% for those with >50% initial loss 2
- Associated with other autoimmune diseases including thyroid disease, vitiligo, and lupus 5
Telogen Effluvium
Telogen effluvium is stress-induced shedding where physiologic or emotional stressors push hair follicles prematurely into telogen phase 2, 5.
- Triggers include: Severe illness, surgery, childbirth, rapid weight loss, severe emotional stress, high fever, and nutritional deficiencies 5
- Characterized by shedding of club hairs 2-3 months after the triggering event 4
- Diffuse hair thinning rather than discrete patches 2
- Generally reversible once the triggering factor is addressed 5
Anagen Effluvium
Anagen effluvium occurs when medications (particularly chemotherapy) interrupt actively growing hair follicles 2, 5.
- More rapid and severe than telogen effluvium because it affects the 85-90% of hairs in active growth 5
- Hair loss begins within days to weeks of exposure 5
- Chemotherapy is the most common cause, but other toxic exposures can trigger it 5
Androgenetic Alopecia
Male pattern baldness and female diffuse alopecia involve gradual shortening of anagen periods and progressive follicle miniaturization 4.
- Requires androgens for manifestation, specifically DHT sensitivity in genetically predisposed follicles 4, 5
- Progressive transformation of terminal hairs to vellus-like hairs over years 4
- In women, presents as diffuse thinning with widening of the central part 4
Infectious Causes
Tinea Capitis
Tinea capitis causes patchy hair loss with scalp inflammation, though signs may be subtle 2, 5.
- Requires fungal culture for diagnosis when suspected 2
- Treatment requires oral antifungal therapy; topical agents are insufficient 5
- Can cause scarring if not treated promptly 2
Behavioral Disorders
Trichotillomania
Trichotillomania is compulsive hair pulling that mimics alopecia areata but is distinguished by incomplete hair loss and firmly anchored broken hairs remaining in anagen phase 2, 5.
- May coexist with alopecia areata in some cases, complicating diagnosis 2
- Broken hairs are firmly anchored unlike the easily extractable exclamation mark hairs of alopecia areata 2
- Irregular, bizarre patterns of hair loss are typical 2
Systemic Disease-Related Hair Loss
- Systemic lupus erythematosus can cause both scarring and non-scarring alopecia 2, 5
- Secondary syphilis presents with patchy "moth-eaten" hair loss 2, 5
- Thyroid disease (both hypo- and hyperthyroidism) causes diffuse hair thinning 5
Module 4: Diagnostic Approach to Hair Disorders (20 minutes)
Clinical Examination
The diagnosis of alopecia areata is usually straightforward clinically, and investigations are unnecessary in most cases 2.
Key Clinical Features to Identify
- Pattern of hair loss: Patchy versus diffuse, localized versus generalized 2
- Exclamation mark hairs: Short broken hairs (3-4mm) with tapered proximal ends at margins of alopecia areata patches 2
- Scalp inflammation: Present in tinea capitis, absent in alopecia areata 2
- Hair pull test: Easily extractable hairs suggest active alopecia areata or telogen effluvium 2
- Nail changes: Present in approximately 10% of alopecia areata patients 2
Dermoscopy
Dermoscopy aids diagnosis of alopecia areata by revealing characteristic features not visible to naked eye 2.
- Yellow dots (regular round dots) are commonly seen and indicate active disease progression 2
- Exclamation mark hairs (dystrophic hairs with fractured tips) are highlighted 2
- Cadaverized hairs (hairs fractured before emergence from scalp) are visible 2
- These findings are absent in trichotillomania, triangular alopecia, and scarring conditions 2
Laboratory Testing - When and What to Order
Laboratory testing should be reserved for cases where diagnosis is uncertain, presentation is atypical, or systemic disease is suspected 2, 5.
Nutritional Assessment
- Serum ferritin: Iron deficiency is the most common nutritional deficiency worldwide and causes chronic diffuse telogen hair loss; levels are lower in women with alopecia areata and androgenetic alopecia 5
- Vitamin D levels: 70% of alopecia areata patients have deficiency (<20 ng/mL) versus 25% of controls, with inverse correlation between levels and disease severity 5
- Serum zinc: Levels tend to be lower in alopecia areata patients, particularly those with resistant disease >6 months duration 5
- Folate levels: May contribute to hair loss when deficient 5
Hormonal Assessment (for women with signs of androgen excess)
- Total testosterone or bioavailable/free testosterone and sex hormone binding globulin (SHBG) in women with acne, hirsutism, irregular periods 5
- TSH to rule out thyroid disease, which commonly causes hair loss 5
- TPO antibodies if biochemical hypothyroidism is confirmed 5
- Prolactin if hyperprolactinemia is suspected 5
- Two-hour oral glucose tolerance test if PCOS, diabetes, or insulin resistance is suspected 5
Infectious/Inflammatory Workup
- Fungal culture when tinea capitis is suspected 2
- Serology for lupus erythematosus when systemic lupus is in differential 2
- Serology for syphilis when secondary syphilis is suspected 2
Skin Biopsy
- Indicated for: Difficult cases, early scarring alopecia, or diffuse alopecia areata that is challenging to diagnose clinically 2
- Can be sectioned vertically or transversely to evaluate follicular architecture 1
Common Diagnostic Pitfalls to Avoid
- Ordering excessive laboratory tests when diagnosis is clinically evident wastes resources and delays treatment 5
- Failing to consider psychological impact of alopecia areata, which may cause considerable psychological and social disability warranting assessment for anxiety and depression 5
- Overlooking dermoscopy as a non-invasive diagnostic tool that provides valuable information 5
- Not recognizing that many alopecia areata cases are self-limited, with 34-50% recovering within one year without treatment 5
Module 5: Treatment Principles and Nutritional Considerations (20 minutes)
Treatment of Alopecia Areata
Intralesional corticosteroid injections represent first-line treatment for limited patchy alopecia areata 5.
- Strongest evidence supports intralesional corticosteroids for limited disease (Strength of recommendation B, Quality of evidence III) 5
- Contact immunotherapy is best-documented treatment for extensive patchy alopecia areata, though response rates are lower in severe cases 5
- Hair follicles are preserved in alopecia areata, maintaining potential for recovery even in longstanding disease 2
Nutritional Supplementation
Vitamin D supplementation is recommended for patients with levels <20 ng/mL, though no double-blind trials have examined oral supplementation as treatment strategy for alopecia areata 5.
- Vitamin D receptor (VDR) plays critical role in hair follicle cycling 5
- Zinc supplementation may contribute to hair health when deficient, particularly in alopecia areata and telogen effluvium 5
- Iron supplementation should be considered when ferritin is low, as iron deficiency causes chronic diffuse telogen hair loss 5
Prognosis Counseling
Disease severity at presentation is the strongest predictor of long-term outcome 2.
- Patients with <25% hair loss initially: 68% chance of being disease-free at long-term follow-up 2
- Patients with 25-50% hair loss initially: 32% chance of being disease-free 2
- Patients with >50% hair loss initially: Only 8% chance of being disease-free 2
- Childhood onset and ophiasis pattern (scalp margin involvement) carry poorer prognoses 5
- Full recovery from alopecia totalis/universalis is unusual (<10%) 2
- Almost all patients experience more than one episode of disease 2
Key Clinical Pearls
- Hair follicle anatomy varies by growth phase: Anagen hairs have active matrix and well-developed root sheaths; catagen hairs show thickened vitreous layer; telogen hairs have keratinized clubs 1
- Hair length is determined primarily by anagen duration, not growth rate 4
- Androgens have paradoxical effects: They stimulate facial/body hair but cause scalp hair miniaturization in androgenetic alopecia 4
- Alopecia areata diagnosis is clinical in most cases; dermoscopy aids diagnosis by revealing yellow dots and exclamation mark hairs 2
- Nutritional deficiencies (vitamin D, iron, zinc) associate strongly with hair loss and should be assessed when clinically appropriate 5
- Spontaneous remission occurs in 34-50% of alopecia areata patients within one year, making watchful waiting reasonable for limited disease 2, 5