A patient with diffuse hair loss.

The most likely diagnosis in this patient with diffuse hairloss [Figure 1] is:

Figure 1

Diffuse hairloss

Telogen effluvium

Female androgenetic alopecia

Diffuse alopecia areata

Trichotillomania

Lupus

Answer: C. Diffuse alopecia areata

DISCUSSION

The biopsy demonstrates dilatation of the follicular infundibulum with a pigment cast, miniaturized dystrophic anagen follicle and pigment incontinence within the fibrous tract remnant [Figures 2 and 3]. This constellation of findings is diagnostic of alopecia areata.

Figure 2

Low power image of biopsy specimen (×40)

Figure 3

Step section demonstrates infundibular changes (×100)

The differential diagnosis of diffuse alopecia can be challenging and includes androgenetic alopecia, telogen effluvium, diffuse alopecia areata, syphilis and subtle scarring alopecia. Helpful clues to the diagnosis of diffuse alopecia areata (AA) include the presence of focal, more typical patches of complete alopecia, presence of the exclamation point hairs, sparing of white hairs and the presence of nail pits. The lack of a trigger for telogen effluvium may prompt a more thorough evaluation to include hair pull test, 1 minute hair combing or collection of shed hairs to examine for tapered fractures. Tapered fractures appear as anagen hairs with a tapered non-pigmented pencil-point fracture at the proximal end.[1]

The presence of multiple tapered fractures on a hair pull test suggests a diagnosis of AA or syphilis. In general, syphilis presents with a more moth-eaten pattern of alopecia and an accompanying exanthem. Some cases of syphilis mimic AA clinically, including circumscribed hairless patches and ophiasis pattern. If exposure history suggests the possibility of syphilis, serological studies will help establish a diagnosis. Both rapid plasma reagin and fluorescent treponemal antibody absorption tests are subject to prozone reactions and in patients with extremely high antibody titers the serum must undergo serial dilutions before a positive test is obtained.

On dermatoscopy, yellow dots, black dots (cadaverized hairs), tapered hairs (exclamation mark hairs) and clustered short vellus hairs are common findings in alopecia areata, with yellow dots and short vellus hair being 96.5% sensitive for diffuse AA.[2] Androgenetic alopecia also presents with yellow dots, but in lower frequency per surface area than diffuse AA. In androgenetic alopecia, the yellow dots represent enlarged sebaceous glands, whereas they represent follicular dilatation with laminated keratin in alopecia areata. Yellow dots, black dots and broken hairs may also be present in trichotillomania, so biopsy is often required for definitive diagnosis.[3]

If the diagnosis remains in question, a scalp biopsy will help verify the diagnosis. The most characteristic feature of AA on histopathology is the presence of sparse peribulbar lymphocytic infiltrates in a “swarm of bees” pattern.[4] Peckham et al. studied the relative frequency of histopathological findings in AA and noted that follicular miniaturization and an increase in catagen/telogen follicles was more common than the presence of a peribulbar lymphocytic infiltrate.[5] The histological findings vary by the stage of disease, with acute lesions being more likely to demonstrate lymphoid infiltrates. An increase in catagen/telogen follicles is also a feature of the acute stage of alopecia areata. In later stages, when the peribulbar infiltrates are no longer present, helpful diagnostic features include the presence of eosinophils or melanin pigment within fibrous tracts.[6]

Increased catagen/telogen phase follicles and pigment casts within the follicular channel are features shared between diffuse AA and trichotillomania, so the diagnosis should not be based solely upon these two features.[5] The presence of trichomalacia, fractured hair fibers, perifollicular and intrafollicular hemorrhage as well as the lack of follicular miniaturization, lymphocytes and eosinophils within the fibrous tract remnant can assist in differentiating trichotillomania from diffuse AA.[7]

Shared histological findings between diffuse AA and androgenetic alopecia include miniaturization and an increase in fibrous tract remnants. The presence of multiple catagen hairs, dilated follicular infundibula, a peribular infiltrate, pigment casts and pigment incontinence and eosinophils suggest a diagnosis of AA rather than androgenetic alopecia. Telogen effluvium shares an increase in the number of telogen hairs, but lacks the remaining features of AA listed above.

The prevalence of AA is 0.1-0.2%, with a lifetime risk of 1.7%.[8] Diffuse AA is the least common type, and presents with widespread apical or diffuse thinning of scalp hair, often sparing white and gray hair.[9] Patients with a predominantly apical pattern may closely mimic pattern alopecia, but the diagnosis can be established by examination of shed hairs for tapered fractures or by biopsy. The presence of focal more typical patches of complete alopecia, relative sparing of gray or white hairs, or the presence of nail pits suggest the possibility of alopecia areata.

Autoimmune injury to hair follicles is mediated initially by T cells targeting a pigment antigen, which accounts for the relative sparing of gray and white hairs and the regrowth of depigmented hair in some patients.[10] It also accounts for the presence of pigment incontinence histologically as the melanocytes in the hair bulb are damaged by the immune response. Multiple cell types are found in the anagen bulb after initiation including CD4 + and CD8 + T cell, mast cells, natural killer cells, dendritic cells, eosinophils and plasma cells.[11] All these findings overlap with those of syphilis, so careful clinical correlation is required. Patients respond to oral corticosteroids, but the response will not be maintained in patients with chronic alopecia areata. Intralesional injection is impractical in patients with widespread hair loss, but some patients will respond to topical corticosteroids, contact immunotherapy, or phototherapy (turban applications of psoralen followed by ultraviolet A light). Systemic immunosuppressive medications such as methotrexate can be effective for patients with refractory disease.