What are the types, pathophysiology, diagnosis, and treatment options for primary and secondary alopecia of the scalp?

Primary and Secondary Alopecia of the Scalp: Comprehensive Medical Presentation Guide

Classification Framework

Alopecia is fundamentally divided into non-scarring (reversible) and scarring (permanent) types, with primary forms originating from hair follicles themselves and secondary forms resulting from systemic diseases, medications, or external trauma. 1

Non-Scarring Alopecias (Primary)

• Androgenetic alopecia: Pattern hair loss related to dihydrotestosterone (DHT) sensitivity, presenting as diffuse thinning at the crown with frontal hairline preservation 2
• Alopecia areata: Autoimmune T-lymphocyte-mediated attack on hair follicles causing patchy, non-scarring hair loss 2
• Telogen effluvium: Stress-induced shedding where physiologic or emotional stressors (illness, surgery, childbirth, rapid weight loss, nutritional deficiencies) push follicles prematurely into resting phase 2
• Anagen effluvium: Drug-induced (particularly chemotherapy) interruption of actively growing follicles, causing rapid and severe hair loss 2
• Trichotillomania: Compulsive hair pulling with incomplete hair loss and firmly anchored broken hairs remaining in anagen phase 2
• Loose anagen syndrome: Newly characterized condition with easily extractable anagen hairs 3

Scarring Alopecias (Primary)

These cause permanent pilosebaceous follicle destruction and require early recognition. 3

Lymphocyte-Associated

• Lichen planopilaris (including frontal fibrosing variant) 3
• Discoid lupus erythematosus 3, 4
• Pseudopelade of Brocq 3, 4
• Central centrifugal cicatricial alopecia 4
• Follicular mucinosis 3

Neutrophil-Associated

• Folliculitis decalvans 4
• Dissecting folliculitis 4

Mixed Infiltrative

• Acne keloidalis 4

Secondary Alopecias

• Infectious: Tinea capitis (fungal), secondary syphilis (moth-eaten pattern) 2
• Autoimmune: Systemic lupus erythematosus (scarring and non-scarring) 2
• Connective tissue diseases, granulomatous diseases, bullous diseases, tumors 1

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Pathophysiology by Type

Alopecia Areata

T lymphocytes target hair follicles in an autoimmune process, with approximately 20% having family history indicating genetic susceptibility. 2 The condition associates with thyroid disease, lupus, and vitiligo 2. The vitamin D receptor (VDR) plays a critical role in hair follicle cycling, explaining the strong association with vitamin D deficiency 2.

Androgenetic Alopecia

Follicular sensitivity to dihydrotestosterone (DHT) causes progressive miniaturization of hair follicles. 2 In women with signs of androgen excess (acne, hirsutism, irregular periods), consider polycystic ovary syndrome (PCOS) as an underlying mechanism 2.

Telogen Effluvium

Physiologic or emotional stressors trigger premature transition of follicles from anagen (growth) to telogen (resting) phase. 2 Triggers include illness, surgery, childbirth, severe emotional stress, rapid weight loss, and nutritional deficiencies 2. The condition resolves spontaneously in 80% of cases lasting <1 year once the trigger is eliminated 5.

Nutritional Deficiency Mechanisms

• Iron deficiency (ferritin <60 ng/mL): Most common nutritional deficiency worldwide causing chronic diffuse telogen hair loss 2, 5
• Vitamin D deficiency (<20 ng/mL): 70% prevalence in alopecia areata patients versus 25% in controls, with inverse correlation to disease severity 2
• Zinc deficiency: Impairs hair follicle function as cofactor for multiple enzymes, with lower levels in alopecia areata patients 2

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Diagnostic Approach

Clinical Examination Essentials

Dermoscopy (trichoscopy) is the single most useful non-invasive tool to differentiate alopecia types and should be performed first. 2, 6

Pathognomonic Dermoscopic Features

• Alopecia areata: Yellow dots (regularly round indicating active disease), exclamation mark hairs (short broken hairs), cadaverized hairs, black dots 2, 6
• Trichotillomania: Broken hairs firmly anchored in scalp (unlike exclamation marks), incomplete hair loss pattern 6
• Androgenetic alopecia: Absence of yellow dots and exclamation mark hairs 2

Physical Examination Findings

• Pull test: Positive at margins of expanding areas signals active disease in alopecia areata 2, 7
• Nail changes: Pitting, ridging, or dystrophy occur in approximately 10% of alopecia areata patients 2
• Scalp examination: Preserved follicular ostia in non-scarring types; follicle destruction in scarring types 7
• Hair pattern: Diffuse crown thinning with frontal preservation suggests androgenetic alopecia; patchy loss suggests alopecia areata 2

Laboratory Testing Algorithm

Most cases of alopecia areata are diagnosed clinically without laboratory workup; testing is indicated when diagnosis is uncertain, presentation is atypical, or to exclude mimicking conditions. 2

First-Line Systematic Panel (for diffuse hair loss without patches)

• Serum ferritin: Target >60 ng/mL; lower levels in women with alopecia areata and androgenetic alopecia 2, 5
• TSH: Screen for thyroid disease (common cause of diffuse alopecia); if abnormal, add free T4 and TPO antibodies 2, 5
• Vitamin D: Deficiency defined as <20 ng/mL; supplement according to international guidelines 2, 5
• Zinc: Serum levels tend to be lower in alopecia areata, particularly resistant disease >6 months 2, 5
• Complete blood count: Assess for anemia 5

Second-Line Testing (when indicated by clinical features)

• Hormonal panel (if signs of androgen excess present): Total or free/bioavailable testosterone, SHBG, prolactin, 2-hour oral glucose tolerance test, fasting lipid profile 2, 5
• Fungal culture: Mandatory when tinea capitis suspected; most common cause of treatment failure is incorrect clinical diagnosis 2, 7
• Lupus serology: When systemic lupus in differential 2
• Syphilis serology: When secondary syphilis suspected 2

Scalp Biopsy Indications

Biopsy is recommended for difficult cases, early scarring alopecia, diffuse alopecia areata challenging to diagnose, or when diagnosis remains uncertain after dermoscopy and laboratory testing. 2 Trichoscopy guides optimal biopsy site selection 6, 1. Both vertical and horizontal sections should be obtained for comprehensive histopathological evaluation 1, 4.

Practical Diagnostic Algorithm

1. Perform dermoscopy first, looking specifically for yellow dots and exclamation mark hairs 2
2. If characteristic dermoscopic features present: Diagnose alopecia areata clinically without biopsy 2
3. If dermoscopy inconclusive: Obtain targeted laboratory tests (ferritin, TSH, vitamin D, zinc, CBC) to exclude telogen effluvium triggers and nutritional deficiencies 2, 5
4. If diagnosis remains uncertain: Perform scalp biopsy for definitive histopathologic diagnosis 2

Common Diagnostic Pitfalls to Avoid

• Ordering excessive laboratory tests when diagnosis is clinically evident 2
• Failing to perform dermoscopy, which provides valuable non-invasive diagnostic information 2
• Making clinical diagnosis of tinea capitis without fungal culture confirmation 2
• Overlooking psychological impact: Alopecia areata causes considerable psychological and social disability warranting assessment for anxiety and depression 2

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Treatment Strategies

Alopecia Areata

Limited Patchy Disease (<25% scalp involvement)

Intralesional corticosteroid injections are first-line treatment with the strongest evidence (Strength of recommendation B, Quality of evidence III). 2 Consider observation as reasonable option since 34-50% recover within one year without treatment 2.

Extensive Patchy Disease

Contact immunotherapy is the best-documented treatment, though response rates are lower in severe cases. 2

Nutritional Supplementation

• Vitamin D: Supplement if levels <20 ng/mL according to general international adult recommendations with maintenance therapy due to chronicity 2
• Iron: Supplement if ferritin <60 ng/mL; reassess at 3 months 5
• Zinc: Consider supplementation when deficient, particularly in resistant disease 2

Note: No double-blind trials have yet examined oral vitamin D supplementation as a treatment strategy for alopecia areata, despite strong association with deficiency. 2

Androgenetic Alopecia

Treatment varies by gender and includes topical minoxidil, oral finasteride (men), oral spironolactone (women), and addressing underlying hormonal abnormalities like PCOS 2.

Telogen Effluvium

Primary strategy is identifying and eliminating the triggering factor; 80% of short-duration cases (<1 year) resolve spontaneously. 5 Address nutritional deficiencies (iron, vitamin D, zinc) and thyroid dysfunction 2.

Tinea Capitis

Requires oral antifungal therapy; topical treatment alone is insufficient. 2 Fungal culture must confirm diagnosis before initiating treatment 2.

Scarring Alopecias

Treating the underlying condition is the single most important strategy, but topical treatments for alopecia are also applied. 1 Early diagnosis and treatment are critical to prevent permanent follicle destruction 8, 4.

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Prognostic Factors

Alopecia Areata

• Favorable prognosis: <25% initial hair loss (68% disease-free at follow-up), adult onset, limited patchy disease 6
• Poor prognosis: >50% initial hair loss (only 8% disease-free at follow-up), childhood onset, ophiasis pattern (scalp margin involvement), progression to total or universal alopecia 2, 6
• Natural history: 34-50% recover within one year; 14-25% progress to total scalp or body hair loss 2

Disease Monitoring

Trichoscopy provides photographic documentation at each follow-up visit to objectively evaluate treatment response. 6 Disease severity at presentation, assessed clinically and trichoscopically, is the strongest predictor of long-term outcome 6.

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Key Clinical Pearls

• Alopecia areata may coexist with trichotillomania in some cases 2
• White hairs may be spared in alopecia areata; initial regrowth may be nonpigmented 7
• Onychomycosis in elderly patients warrants treatment due to risk of serious complications including cellulitis, particularly with diabetes or peripheral vascular disease 2
• Consider medication review: Chemotherapy, anticoagulants, and beta-blockers can cause hair loss 2
• Adequate tissue sampling and appropriate laboratory processing, combined with pertinent clinical information, provide the key to diagnosis in all primary alopecias 4