The diagnosis of late stage alopecias is challenging for both clinicians and dermatopathologists. Conventionally, the composition of the infiltrate of inflammatory cells, as well as the effects of them on follicular and infundibular epithelium, are used for diagnosis of alopecias. The number of follicles in anagen or catagen is also helpful for differentiation of some types of alopecia. But when a biopsy is taken from a late lesion of alopecia, often no follicles are encountered in the sections prepared from it. Usually, a dermatopathologist in front of such a section resigns quickly from a diagnosis with specificity and asks the clinician for a second biopsy from the margin of the alopecic area where follicles are still present, or he may "sign out" the section with a diagnosis of "pseudopelade." That term has come to be used for late stages of alopecia in which no hair follicles are visible. [1,4–6] However, various authors have suggested dropping this term because it designates a pattern seen in more than one condition, rather than it naming a specific disease. [1,6]

In the literature of dermatopathology, only few criteria can be found to differentiate between different types of alopecia at such a late stage, [1–7] and this prompted us to undertake the present study. The results of our investigation demonstrate that a specific diagnosis may sometimes be possible when attention is paid to changes in the connective tissue.

If connective tissue changes are categorized into: (1) affecting the papillary dermis, (2) affecting the reticular dermis, and (3) affecting the adventitial dermis of follicles (fibrous tracts), criteria for differential diagnosis can be summarized as follows:

(1) Papillary dermis

If the papillary dermis is normal and rete ridges are preserved, possible diagnoses are lichen planopilaris and alopecia areata. In both conditions, the epidermis is entirely spared by the pathologic process.

If the papillary dermis is flattened or absent and rete ridges are flattened as well, the two possible diagnoses are lupus erythematosus and follicuitis decalvans. If flattening of the papillary dermis is accompanied by vacuolar changes in the basal layer or by a thickened basement membrane, a diagnosis of lupus erythematosus can be made. If those changes are absent but subepidermal fibrosis is present, a diagnosis of folliculitis decalvans is likely.

A thinned epidermis with a thickened basement membrane in late lesions of alopecia in lupus erythematosus has been emphasized before by Ackerman et al. [1] and by Sperling. [6] Sperling stated, however, that at times the interfollicular zone is spared in lesions of alopecia in lupus erythematosus. This is not consistent with our own observations in which the interfollicular papillary dermis was flattened, consistently accompanied by flattening of epidermal rete ridges and accompanied with subtle signs of interface dermatitis or thickened basement membrane. Only in Weedon's textbook is it found that late lesions of folliculitis decalvans may be devoid of a papillary dermis as a result of extensive fibrosis and covered by an atrophic epidermis with flattened rete ridges. [4]

(2) Reticular dermis

The reticular dermis is largely normal in lichen planopilaris and alopecia areata. Usually, collagen bundles of the reticular dermis are also normal in late lesions of alopecia of lupus erythematosus, but mucin may still be encounetred deposited between collagen bundles.

Deposition of mucin in the reticular dermis is commonly mentioned as a criterion for lupus erythematosus, [1,2,6] but, in our opinion, is a less reliable feature in biopsies taken from alopecias. One one hand, mucin deposition may not be prominent in late lesions of lupus erythematosus. On the other hand, slight increase of interstitial mucin is sometimes encountered incidentally in lesions of other types of alopecia.

Marked alteration of the reticular dermis is seen only in late lesions of folliculitis decalvans and its analogues (perfolliculitis abscedens et suffodiens, dissecting cellulitis of the scalp, and acne keloidalis nuchae). In these conditions, the process starts with suppurative folliculitis that ruptures; contents of the follicle spill into the dermis, which invokes a foreign body response. At a late stage of the process, a scar remains. Collagen bundles in the reticular dermis are oriented horizontally, increased numbers of fibroblasts are present between bundles of collagen, and some plasma cells are also found. The overlying epidermis is flattened, just as often is the case above scars.

Ackerman et al. stated that sclerosis may be encountered in the upper part of the dermis in late lesions of alopecia of lupus erythematosus. [1] In the cases of lupus erythematosus studied by us, the collagen in the reticular dermis was normal in size and arrangement. Sperling mentioned plasma cells in the dermal infiltrate as a clue to lupus erythematosus, but that criterion works only in the absence of extensive fibrosis. If plasma cells are seen together with extensive fibrosis, the diagnosis is late stage folliculitis decalvans (or one of its analogies), a combination of findings also emphasized by Weedon [4] and Elder and colleagues. [5]

(3) Adventitial dermis of follicles (fibrous tracts)

Fibrous tracts in late stages of inflammatory alopecias show fine collagen earlier and more compact collagen later in the course. No differentiation between lupus erythematosus, lichen planopilaris, or folliculitis decalvans is possible based on the type of fibrosis in fibrous tracts alone. A helpful clue is found, however, in late stages of alopecia areata in which a thickened bluish glassy membrane is encountered as a residuum of a catagen follicle, an observation emphasized before by Ackerman et al. [1]

In conclusion, it is helpful for a dermatopathologist studying sections of alopecia not to concentrate only on the follicles or what is residual of them, but to look consciously between them. Identification of changes in the connective tissue of the papillary dermis and reticular dermis may enable a specific diagnosis, even late in the process of an inflammatory alopecia.