Scarring Alopecia Workup

With regard to scalp biopsy, the site chosen for the specimen is crucial for proper yield of pathologic information. Ideally, the site should be clinically active. ^[3]

The chosen biopsy site should be representative of clinically active disease, with primary morphologic features and a positive pull test (if present). Symptomatic sites are often helpful in selecting the location for obtaining the biopsy specimen. Examination of a sample taken from end-stage disease/balding areas is usually not productive. In the absence of clinical inflammation, biopsy of a hair-bearing site with a relative paucity, but not complete lack, of follicular ostia may suffice. The direction of the biopsy should be in line with the follicle course in the scalp. This will help obtain complete follicles for histologic examination.

Dermatoscope evaluation has been reported in a small series. Validation in large randomized studies is pending. At this time, findings reported are as follows ^[38] :

• Discoid lupus - White patches, branching capillaries, and keratin plugs

• Lichen planopilaris - Perifollicular scales and white dots

• Frontal fibrosing alopecia - Perifollicular scales, perifollicular erythema, and branching capillaries.

Aside from white dots, blue-grey dots were also described and may be on the spectrum of variants of inflammatory and postinflammatory changes of scarring, especially in darker-skinned patients.

All findings showed the expected reduced follicle ostia.

Scalp biopsy has been shown to be especially effective when samples are submitted for both transverse and horizontal sectioning. In nonspecific presentations, with continued progression, serial biopsies may be required. Horizontal and vertical samples and a combination called HoVert (HOrizontal VERTical) have been proposed to be of use. ^{[39, 40]}

In nonspecific presentations with continued progression, serial biopsies may be required. The current literature on histologic features of scarring alopecia only consists of small case reports or series. Features believed to be specific to one condition (eg, hair casts in traction alopecia and alopecia areata) ^[41] often occur in several other conditions.

Typical scarring alopecia demonstrates perifollicular concentric fibrosis, mild perifollicular and perivascular lymphoid cell infiltrate (if of the lymphocytic scarring type), destruction of the follicular epithelium, naked hair shafts in giant cells, and, in terminal phases, follicular dropout. Numerous end-stage fibrous tracts replaced by amorphous connective tissue, consistent with follicular scars, are seen in the subcutaneous tissue. The loss of sebaceous glands is believed to be a helpful hint to indicate scarring alopecia. ^[23]

Note one example of a histologic division of the scarring alopecias based on data from the North American Hair Research Society (NAHRS).

Lymphocytic entities are as follows:

• Chronic cutaneous lupus erythematosus

• Lichen planopilaris

• Graham-Little syndrome

• Classic pseudopelade (Brocq)

• Central centrifugal cicatricial alopecia

• Alopecia mucinosa

• Keratosis follicularis spinulosa decalvans

Neutrophilic entities are as follows:

• Folliculitis decalvans

• Dissecting cellulitis/folliculitis (perifolliculitis capitis abscedens et suffodiens)

Mixed entities are as follows:

• Folliculitis (acne) keloidalis

• Folliculitis (acne) necrotica

• Erosive pustular dermatosis

Classic histologic patterns

The following are histologic patterns that are used by many pathologists in horizontal sections of a 4-mm punch biopsy sample. Understanding the patterns and the differentials assists in diagnosis of the alopecia biopsy sample.

Normal hair biopsy findings are as follows:

• Total number of hairs - 30-45 (can be half this number in African Americans)

• Telogen hairs - Less than 15%

• Terminal hairs - Vellus hairs ratio: 2:1

• Follicular units - 12-14, each with 4-6 hairs

Lichen planopilaris

Lichenoid dermatitis is present in lichen planopilaris (and its clinical variants, regardless of presentation) at the level of the infundibulum and can easily be missed in transverse sections. These are mostly CD8 cells. Concentric lamellar perifollicular fibrosis can develop.

Staining with Verhoeff–van Gieson elastin stain may be of value in differentiating advanced cases of discoid lupus erythematosus, lichen planopilaris, and pseudopelade of Brocq, which often have overlap features on routine pathologic examination but display distinct patterns on elastic tissue staining. End-stage lichen planopilaris shows loss of elastic fibers in a superficial dermal wedge-shaped scar, which is better demarcated with elastic stain. Discoid lupus erythematosus elastin stain shows a more diffuse broad dermal scar pattern. ^[42]

Direct immunofluorescence highlights the presence of colloid bodies in the peri-infundibular area after staining with immunoglobulin M (less frequently with immunoglobulins G, A and C3). A linear band of fibrin deposition is present along the basement membrane zone of affected follicles, while the interfollicular epidermis is negative for immunoreactants.

In the frontal fibrosing variant, reports have noted histopathologic features of lichen planopilaris and some authors believe this variant preferentially affects the miniaturized secondary vellus hairs in those with androgenetic alopecia. ^[43]

No large studies have validated direct immunofluorescence results as sensitive or specific for this alopecia variant.

Central centrifugal cicatricial alopecia

The findings are variable, as this does not appear to represent a single condition and at this time may be a clinical pattern of scarring alopecia.

Some authors have suggested that central centrifugal cicatricial alopecia has unique histology findings. ^[3] These findings include premature desquamation of the inner root sheath below the isthmus and eccentric thinning of the follicular epithelium. Whereas desquamation of the inner root sheath is a feature normally observed at the isthmus, its early presence below this level indicates pathology. Further, premature desquamation of the inner root sheath can be found in other inflammatory conditions of the scalp, including lichen planopilaris. Thus, to distinguish these diagnoses, it has been suggested that central centrifugal cicatricial alopecia has this finding in otherwise normal hair follicles without otherwise showing lymphocytic inflammation or structural alteration. In vertical sections, thickened dermal elastic fibers in a hyalinized dermis have been reported. ^[3]

Pseudopelade of Brocq

In advanced disease, elastin stains reveal dense elastic tissue cuffing a broad, fibrotic follicular tract, unlike the characteristic pattern seen in advanced discoid lupus erythematosus and lichen planopilaris. Other histologic findings are nonspecific; concentric lamellar fibroplasia around the upper follicle, sebaceous gland loss, and, ultimately, complete destruction of the pilosebaceous unit are noted. End-stage disease is marked by follicular longitudinal fibrous tracts extending into the subcutis, which often are found in association with hair-shaft granulomas.

Traction alopecia

In early traction alopecia, a subacute perifollicular inflammation is accompanied by mild-to-moderate hyperkeratosis. In cases of prolonged traction, decreased hair follicle and sebaceous gland density, perifollicular fibrosis, and vertical bands of follicular scarring are seen. However, blood vessels and eccrine sweat glands remain unaffected. Trichomalacia and pigment casts may be found but are not specific. Histologic pattern can be very similar to normal biopsy with variance by timeline (ie, less follicles and more streamers/telogen hairs in advanced disease).

Chemotherapy alopecia

Various patterns of inflammation have been noted. None is well proven enough to be specific to this type of permanent alopecia. ^[32]

Alopecia mucinosa

Intrafollicular mucin deposition is seen. A perivascular and perifollicular lymphocytic infiltrate is seen, often with eosinophils. Careful examination should be performed to investigate for findings of cutaneous T-cell lymphoma.

Keratosis pilaris atrophicans

A few reports have noted compact hyperkeratosis and hypergranulosis of the upper follicular epithelium. Superficial intrafollicular and perifollicular edema, as well as perivascular lymphocytes and neutrophils, may be present with acute disease or progression.

Discoid lupus

Discoid lupus erythematosus presents with vacuolar interface dermatitis, with a few dyskeratotic keratinocytes, cytoid bodies, and a variably dense periadnexal and superficial/deep perivascular lymphocytic infiltrate with dermal mucin. ^[44] Perifollicular inflammation can surround any part of the mid and upper follicle. Sebaceous glands can be atrophied or absent. Distention of follicular ostia with laminated keratin can be prominent (ie, follicular plugging histology). When stained with Verhoeff–van Gieson stain, advanced discoid lesions reveal diffuse loss of elastic fibers. This is compared with lichen planopilaris, which has a wedge-shaped scar in the area of the infundibulum that can often be found with a loss of elastic fibers only in that area.

Use of direct immunofluorescence for diagnosis and differentiation from other primary lymphocytic cicatricial alopecias can be helpful. To optimize the yield, the lesion chosen for biopsy should be untreated for at least 2-4 weeks and should be at least 3 months old. Diagnostic features of discoid lupus erythematosus on direct immunofluorescence are deposition of immunoglobulin G, immunoglobulin M, and C3 in a granular bandlike pattern at the dermal interface.

At times, differentiation of lichen planopilaris from discoid lupus erythematosus can be challenging in older lesions or those that are not fully developed. However, perieccrine inflammation, deep perivascular inflammation, and dermal mucin are not found in lichen planopilaris.

Atypical, linear presentations of lupus alopecia have also been reported. These show clinical similarity to alopecia areata but histologic findings of lupus. ^[45]

Acne keloidalis

The biopsy demonstrates scarring, ingrown hairs, and suppurative folliculitis. Many plasma cells are present in the dermis.

Acne necrotica

Histology studies show lymphocytic exocytosis, spongiosis, and sporadic necrosis of keratinocytes in the upper pilosebaceous unit. A dense perifollicular and perivascular lymphocytic infiltrate are present. ^[46] Eventually, formation of confluent necrosis of the follicular epithelium and adjacent epidermis/dermis is noted. Neutrophils may be present.

Erosive pustular dermatosis

Histology findings are nonspecific, and direct immunofluorescence results are often negative. A dense, chronic mixed inflammatory cell infiltrate and foreign body giant cells may be found but are not folliculocentric. Fibrosis and follicular unit loss eventually ensue.

Pressure alopecia

Classic diagnostic features on histology have not been determined.

Folliculitis decalvans

Histology studies show acneiform infundibular dilatation and intrafollicular and perifollicular neutrophilic infiltrate around the upper and mid follicle. With disease of long duration, the infiltrate may be mixed with neutrophils, lymphocytes, and plasma cells and extends into the deeper dermis. Abscess formation is less prominent than in perifolliculitis capitis abscedens et suffodiens and no sinus tracts are found. Granulomatous inflammation with foreign body giant cells around naked hair shafts may be seen.

Perifolliculitis capitis abscedens et suffodiens

Histology findings show infundibular acneiform distension with intrafollicular and perifollicular neutrophilic infiltration. Follicular perforation results in abscesses of neutrophils, lymphocytes, and plasma cells. The abscesses may become partially lined by squamous epithelium, forming a sinus tract.

Senescent alopecia

Telogen counts can be normal. Inflammation is often absent. Follicles are not as long or as wide as expected, but they are not miniaturized, as in androgenetic alopecia. In a 4-mm biopsy specimen, the total number of hairs would be 20-35 (normal count, 30-45). Unlike androgenetic alopecia, the terminal-to-vellus ratio is a normal 2:1. ^[30]