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

Primary and Secondary Scarring Alopecia: Comprehensive Overview

Definition and Classification

Scarring alopecias are fundamentally divided into primary forms (where the hair follicle is the primary target of destruction) and secondary forms (where follicular destruction occurs as a bystander effect of another disease process). 1

Primary Scarring Alopecia

Primary scarring alopecia accounts for approximately 5% of all trichologic consultations and represents irreversible damage to hair epithelial stem cells residing in hair follicles. 1, 2 These disorders are classified by the North American Hair Research Society according to the predominant inflammatory cell type:

Lymphocytic Types:

• Lichen planopilaris (LPP): Shows female predominance with multifocal-interconnected pattern of hair loss 2
• Chronic cutaneous lupus erythematosus (discoid lupus, DLE): Most common in some populations (17/38 cases in one series), presents with unifocal-ragged border pattern, affects younger patients, and shows female predominance 3, 2
• Pseudopelade of Brocq (PPB): Demonstrates female predominance and affects older patients 2
• Central centrifugal cicatricial alopecia (CCCA): Shows unifocal-ragged border pattern with female predominance 2

Neutrophilic Types:

• Folliculitis decalvans (FD): Male predominance with multifocal-interconnected pattern, affects older patients 3, 2
• Dissecting cellulitis/folliculitis (DC): Most common subtype in some Asian populations (30.3%), shows male predominance, affects younger patients, with multifocal-separated pattern 2
• Acne keloidalis nuchae (AKN): Male predominance, affects younger patients 2

Mixed Types: Contain both lymphocytic and neutrophilic infiltrates 4

Secondary Scarring Alopecia

Secondary forms occur when the follicle acts as an "innocent bystander" in diseases occurring outside the follicular unit. 1 Causes include:

• Congenital defects 5
• Trauma (physical, chemical, thermal) 5
• Inflammatory conditions not primarily targeting follicles 5
• Infections (bacterial, fungal, viral) 5
• Neoplasms 5
• Rarely, drug-induced 5

Pathophysiology

The common final pathway in all scarring alopecias is destruction of the hair follicle unit with replacement by fibrous tissue, resulting in permanent hair loss. 1

Primary Scarring Alopecia Mechanisms

The pathogenesis remains incompletely understood for most primary forms, but current evidence suggests: 4

• Stem cell destruction: Irreversible damage to hair epithelial stem cells in the bulge region of the follicle 2
• Inflammatory targeting: The hair follicle itself is the primary target of the inflammatory process 3, 1
• Genetic and demographic influences: Pathogenesis appears influenced by sex, age, and genetic background, explaining different prevalence patterns across populations 2
• Progressive scarring: Inflammatory waves lead to progressive fibrosis if untreated 1

Secondary Scarring Alopecia Mechanisms

Follicular destruction occurs as collateral damage from:

• Nonfollicular scalp conditions extending to involve follicles 5
• External trauma disrupting follicular architecture 5
• Infectious processes destroying surrounding tissue including follicles 5

Biphasic Alopecias

Some initially non-scarring alopecias can progress to permanent hair loss in late phases, representing a distinct pathophysiologic category. 1

Diagnosis

Accurate diagnosis requires integration of clinical assessment, dermoscopy/trichoscopy, and histopathologic examination. 1

Clinical Evaluation

Pattern Recognition:

• Unifocal-ragged border: Suggests CCCA or DLE 2
• Multifocal-interconnected: Indicates LPP or FD 2
• Multifocal-separated: Points toward DC 2
• Location matters: AKN affects the nape, CCCA involves the vertex/crown 2

Demographic Clues:

• Male predominance: FD, DC, AKN 2
• Female predominance: CCCA, LPP, DLE, PPB 2
• Younger age: DLE, DC, AKN 2
• Older age: CCCA, LPP, PPB, FD 2

Key Clinical Features to Assess:

• Time course and completeness of hair loss 6
• Presence of scalp symptoms (itching, pain, scaling, irritation) 6
• Signs of inflammation or infection on examination 6
• Ease of hair pull-out 6
• Associated nail changes (occur in ~10% of alopecia areata, helping differentiate from scarring forms) 6, 7

Critical History Elements:

• Family history (20% of alopecia areata patients have affected relatives, helping distinguish from primary scarring forms) 6
• Autoimmune disease screening (thyroid disease, vitiligo, lupus) 6
• Medication review (chemotherapy, systemic treatments causing anagen effluvium) 6
• Recent infections or systemic illnesses 6
• Syphilis risk factors 6
• For women: menstrual irregularities, signs of androgen excess 6
• Psychological impact assessment 6

Dermoscopy/Trichoscopy

Trichoscopy serves as a simple, non-invasive bedside tool that identifies specific patterns distinguishing between conditions, guides biopsy site selection, and monitors treatment response photographically. 7

Key to differentiate scarring from non-scarring:

• Absence of follicular openings indicates scarring 1
• Yellow dots in alopecia areata (non-scarring) appear regularly round 8, 7
• Exclamation mark hairs are pathognomonic for alopecia areata (non-scarring) 8, 7
• Black dots appear in 0-84% of alopecia areata cases 7

Trichoscopy advantages:

• Provides photographic documentation for objective treatment response evaluation 7
• Helps select optimal biopsy site when diagnosis remains uncertain 7
• May obviate unnecessary biopsies when characteristic patterns are clearly identified 7

Laboratory Testing

For suspected non-scarring conditions (to differentiate from scarring):

• Fungal culture when tinea capitis suspected 9, 6
• Serology for lupus erythematosus when systemic lupus in differential 9, 6
• Serology for syphilis when secondary syphilis suspected 9, 6
• TSH to rule out thyroid disease 8
• Serum ferritin (iron deficiency common in chronic diffuse telogen hair loss) 8
• Vitamin D levels (70% of alopecia areata patients deficient vs 25% controls) 8
• Zinc levels (tend to be lower in alopecia areata) 8

Common pitfall: Ordering excessive laboratory tests when diagnosis is clinically evident should be avoided. 8

Histopathology

Skin biopsy is essential for definitive diagnosis of primary scarring alopecia and should be performed early in the disease course. 1, 4

Biopsy technique:

• Perform at active disease margins, not end-stage scarred areas 5
• Use systematic evaluation with multiple stains 3

Staining protocol:

• Hematoxylin and eosin (H&E) 3
• Periodic acid-Schiff (PAS) 3
• Weigert stain 3

Diagnostic accuracy: This systematic approach with constellation of criteria allows accurate diagnosis in 92.3% of cases previously classified as non-specific cicatricial alopecias, even in late, pauci-inflammatory, or non-inflammatory phases. 3

Critical distinction: Detection of the underlying disorder may be difficult in end-stage lesions, emphasizing the importance of early biopsy. 5

Treatment

The primary aim of treatment is to slow or stop the progression of inflammatory waves and the scarring process at the earliest phase of involvement, as follicular destruction is irreversible. 1, 4

General Principles

• Early aggressive treatment is essential to prevent follicular destruction and permanent scarring 4
• Treatment is specific for active inflammatory conditions 5
• No treatment can reverse established scarring 1
• Recommendations are based on literature review, personal experience, expected adverse effects, cost, and patient compliance 1

Medical Management by Type

Lymphocytic Primary Scarring Alopecias:

Treatment focuses on suppressing lymphocytic inflammation:

• Topical and intralesional corticosteroids for localized disease 1
• Systemic corticosteroids for rapidly progressive disease 1
• Antimalarials (hydroxychloroquine) particularly for DLE 1
• Immunosuppressants for refractory cases 1

Neutrophilic Primary Scarring Alopecias:

Treatment targets neutrophilic inflammation and often bacterial colonization:

• Prolonged oral antibiotics (tetracyclines, rifampin combinations) for FD and DC 1
• Intralesional corticosteroids 1
• Isotretinoin for severe cases 1

Mixed Types:

Require combination approaches targeting both inflammatory pathways 1

Surgical Options

Surgery and hair transplantation are options only for:

• Localized scars after disease has been inactive for extended period 5
• End-stage stable lesions 5
• Never during active inflammatory phase 1

Monitoring and Follow-up

• Use trichoscopy with photographic documentation at each visit to objectively evaluate treatment response 7
• Assess for signs of disease activity (scalp symptoms, positive pull test, new areas of involvement) 6
• Monitor for adverse effects of systemic treatments 1

Psychological Support

Scarring alopecias have strong impact on patients' psychology and quality of life, requiring assessment for anxiety and depression and provision of psychological support when needed. 1, 6

Common Pitfalls to Avoid

• Delaying biopsy: Waiting until end-stage makes diagnosis difficult and treatment futile 5, 4
• Inadequate biopsy technique: Sampling only scarred areas rather than active margins 5
• Insufficient staining: Using only H&E without PAS and Weigert reduces diagnostic accuracy 3
• Overlooking trichoscopy: Missing this non-invasive tool that provides valuable diagnostic and monitoring information 8, 7
• Undertreating early disease: Failing to use aggressive treatment early allows irreversible follicular destruction 4
• Attempting hair transplantation during active disease: Surgery should only be considered after prolonged disease inactivity 5
• Ignoring psychological impact: Failing to assess and address the significant emotional burden of permanent hair loss 1, 6
• Confusing with non-scarring alopecias: Missing key differentiating features like exclamation mark hairs (alopecia areata) or firmly anchored broken hairs (trichotillomania) 9, 7