Follicular streamers (stelae) in scarring and non-scarring alopecia

Background: Follicular streamers are residual fibrovascular tracts representing the impermanent lower third of the hair follicle below the bulge region. Streamers are generally not counted in transverse alopecia samples as they may represent catagen/telogen (CT) follicles and vellus‐like (VL) follicles, or be mistaken as follicular scars. Design: We evaluated 22 non‐scarring alopecia cases, including alopecia areata (AA) and androgenetic alopecia (AGA), and 22 scarring alopecia cases, including follicular degeneration syndrome (FDS)/central centrifugal cicatricial alopecia and other scarring alopecia (OSA) disorders. We counted terminal follicular streamers found at a deep dermal level (L2) and followed them into a mid‐dermal level at the central follicular unit (FU) to determine their precise derivation. Results: We found streamers in 8/9 AA, 11/13 AGA, 6/12 FDS and 3/10 OSA cases. We counted a total of 74 streamers at L2, including 61 in non‐scarring alopecia cases (p < 0.001). At the more superficial FU level, 72% of streamers corresponded to CT follicles, 25% to VL follicles and 3% to follicular scars. Conclusions: Follicular streamers are found predominantly in non‐scarring alopecia cases. Streamers found at deep dermal or subcutaneous levels should be followed and identified at the FU level in order to obtain accurate follicular counts and follicular ratios needed for non‐scarring alopecia diagnosis.     

'Follicular Swiss cheese' pattern--another histopathologic clue to alopecia areata

Yellow dots are the most useful dermoscopic criterion in the clinical diagnosis of alopecia areata and correspond histopathologically with dilated follicular infundibula. They are found in about 95% of alopecia areata cases and help to differentiate alopecia areata from trichotillomania, telogen effluvium and from scarring alopecias. Histopathology of alopecia areata differs with disease activity and dermatopathologist, therefore, heavily depends on other diagnostic features. Objective of the study was to determine the frequency of dilated follicular infundibula, peribulbar lymphocytic infiltrate, inflammatory infiltrates of lymphocytes and eosinophils within fibrous streamers and a shift to catagen/telogen follicles in alopecia areata. Histopathologic features of 56 specimens of 33 patients were correlated with clinical findings and alopecia areata subtype. Results: 57% of all biopsies showed dilated follicular infundibula, regardless of horizontal or vertical sectioning of the slides. Dilated follicular infundibula showed a maximum occurrence of 66% in the recovery stage of alopecia areata and were seen in 33% of alopecia areata incognita. In conclusion, dilated follicular infundibula, reminiscent of a Swiss cheese in horizontally sectioned slides, is an exceedingly useful criterion in the histopathologic diagnosis of alopecia areata and are of great help in the daily routine to recognize alopecia areata.     

'Black dots' seen under trichoscopy are not specific for alopecia areata

Background. ‘Black dots’ are macrocomedo‐like round structures localized to the follicular ostium, and are considered a specific trichoscopic feature of alopecia areata (AA). Aim. To characterize specific features of ‘black dots’, and assess their possible presence in common hair and scalp disorders. Methods. In total, 107 patients with hair loss [30 with alopecia areata (AA), 37 with androgenetic alopecia (AGA), 17 with chronic telogen effluvium (TE), 23 with other hair and scalp diseases] and 93 healthy controls were examined, using a videodermoscope with 20–70 times magnification. Results. There was a correlation between the black dots and the early acute phase of the various alopecia types with the presence of the black dots. Black dots were found in 11% (22/107) of patients with hair loss, including 53.3% (16/30) with AA; in 40% (2/5) of patients with severe chemotherapy‐induced alopecia, and in 100% of patients with dissecting cellulitis of the scalp (n = 2), hypotrichosis simplex (n = 1), and congenital aplasia cutis (n = 1). No black dots were seen in patients with AGA or TE. Conclusions. Black dots are not specific for AA, and may be present in other hair and scalp diseases.     

Trichostasis spinulosa of the scalp mimicking Alopecia Areata black dots

Alopecia areata is a common autoimmune disorder that leads to nonscarring hair loss. Black dots, also called comedo-like cadaver hairs, can be found in almost 50% of alopecia areata patients and indicate disease activity. Trichostasis spinulosa is a follicular disorder resulting from the retention of numerous hairs surrounded by a keratinous sheath in dilated follicles. Trichostasis spinulosa is a relatively common but underdiagnosed disorder of hair follicles. Here, we describe a man with alopecia areata of the eyebrows, androgenetic alopecia and trichostasis spinulosa at the vertex and show how dermoscopy can be useful in distinguishing black dots from Trichostasis spinulosa lesions.     

Histopathologic features of alopecia areata: a new look

BACKGROUND: A peribulbar lymphocytic infiltrate is the expected histologic feature of alopecia areata, but it is absent in many scalp biopsy specimens. Other diagnostic criteria are needed. OBJECTIVE: To establish the histologic features of alopecia areata in scalp biopsy specimens taken from different types of alopecia areata, using follicular counts to relate biopsy findings to stages of the disease. METHODS: Fifty consecutive new patients with alopecia areata were studied. Four-millimeter punch biopsy specimens were taken from the scalp in areas of recent, active hair loss; old, inactive hair loss; or recent hair regrowth. Specimens were sectioned horizontally. Terminal and vellus-like hairs were counted. Inflammation and fibrosis around lower and upper follicles were rated. RESULTS: The histopathologic features of alopecia areata were not significantly affected by the sex, age, and race of the patient or by the type, percentage of hair loss, total duration, or regression of alopecia areata. The major factor affecting the histopathologic features was the duration of the current episode of alopecia areata. In the acute stage, bulbar lymphocytes surrounded terminal hairs in early episodes and miniaturized hairs in repeated episodes. In the subacute stage, decreased anagen and increased catagen and telogen hairs were characteristic. In the chronic stage, decreased terminal and increased miniaturized hairs were found, with variable inflammation. During recovery, increasing numbers of terminal anagen hairs from regrowth of miniaturized hairs and a lack of inflammation were noted. CONCLUSIONS: The histopathologic features of alopecia areata depend on the stage of the current episode. Alopecia areata should be suspected when high percentages of telogen hairs or miniaturized hairs are present, even in the absence of a peribulbar lymphocytic infiltrate.     

Patients with profuse hair shedding may reveal anagen hair dystrophy: a diagnostic clue of alopecia areata incognita

Background Several patients, especially women, seek advice because of hair loss. They may be diagnosed clinically as having telogen effluvium (TE) or androgenetic alopecia (AGA), but histopathology may reveal that a proportion of them have in fact alopecia areata incognita (AAI). Objectives To detect dystrophic anagen hairs in such patients. Methods We studied 1932 patients with hair loss and no signs of classical alopecia areata. They were submitted to the modified wash test (which counts the total number of telogen hairs lost and the percentage of vellus hairs) and divided into patients having pure TE (403), patients with AGA + TE (1235) and patients with pure AGA (294). Dystrophic hairs were detected with a low magnification microscope. Results Dystrophic hairs were observed in 13 patients with TE (3.2%), in 54 with AGA + TE (4.4%) and in none with AGA. In addition, 7 patients with TE and 32 with AGA + TE developed small patches of alopecia areata in 6 to 9 weeks. No patches developed in patients with AGA. Conclusions The presence of dystrophic hairs and the development of patches of alopecia areata (and their absence in pure AGA) provide a first evidence of the possibility that within the heterogenous condition named TE some patients have in fact AAI.     

Expression of the L-fucose moiety on infrainfundibular follicular keratinocytes of terminal follicles, its decreased expression on vellus and indeterminate follicles of androgenetic alopecia, and re-expression in drug-induced hair regrowth.

The distribution of various glycoprotein molecules on the surface of follicular keratinocytes was studied with a panel of lectins with specificity for various sugar moieties on biopsy specimens from both bald/balding scalp and normal occipital scalp, of 23 patients with androgenetic alopecia as well as on biopsies of normal forearm skin of four patients. The most significant differences between bald and normal scalp biopsy were noted with Ulex europaeus agglutinin I (UEA I). We noted an increased (91.8% +/- 3.1; mean +/- SE) expression of UEA I binding sites on the infra-infundibular follicular keratinocytes in anagen terminal scalp hairs, compared to 28.5% +/- 5.2 in the indeterminate (anagen) hairs of balding scalps, and 23.2% +/- 6.3 in the anagen follicles of vellus fore-arm hairs. By contrast, the telogen hairs demonstrated minimal UEA I staining: 4.0% +/- 0.8, mean +/- SE in telogen scalp hairs, 1.8% +/- 0.5 in telogen hairs of balding scalps (0% in completely bald scalps, in which all the hairs were in the telogen phase), and 1.9% +/- 0.2 in telogen forearm hairs. The percentage of UEA I staining correlated with the length of the infra-infundibular follicles in all cases studied. In three cases of hair regrowth after hair growth promotors, the UEA I staining increased to 80.6% +/- 6.1 in anagen hairs and correlated with increased length of infra-infundibular follicles. Our data indicate that there are 1) marked differences between anagen and telogen follicles in UEA I binding to infra-infundibular follicular keratinocytes; 2) the percentage of UEA I staining reflects the size (length) of the infra-infundibular hair follicle; and 3) the anagen follicles of balding scalps (indeterminate hairs) show UEA I staining resembling that exhibited by anagen follicles of vellus hairs.     

Hair counts from scalp biopsy specimens in Asians.

BACKGROUND: Differences in hair density have been described according to the ethnic background in whites and blacks. Asians are known to have fewer hairs than whites. OBJECTIVE: We performed this study to assess the normal values of hair counts in scalp biopsy specimens from Koreans. METHODS: A total of 35 subjects with clinically normal occipital scalps (13 patients with androgenetic alopecia, 20 with patchy alopecia areata, and 2 healthy volunteers) were included. Horizontal sections of 4-mm punch biopsy specimens from clinically normal occipital scalps were examined at various levels from the papillary dermis to the subcutis, and follicular counts of terminal/vellus hairs and anagen/telogen hairs were obtained. RESULTS: The numbers of total hairs, terminal and vellus hairs, and terminal anagen hairs were significantly lower (P <.05) in Koreans compared with the published data of whites and blacks. Percent ratio of terminal anagen and telogen hairs were similar to whites and blacks. Follicular density was significantly lower (P <.05) in Koreans than in whites and blacks. In Koreans, female subjects had a significantly higher number of terminal hairs than male subjects (P <.05). CONCLUSION: Hair density is significantly lower in Koreans than in whites or blacks. Slight sexual difference exists in follicular counts in Koreans. Our data could be used as a guideline for determining normalcy in interpreting horizontal sections of scalp biopsy specimens from Asians.     

The histopathology of noncicatricial alopecia

During the past 2 decades, the use of transverse sections in the evaluation of scalp biopsy specimens has led to a better understanding of the histopathologic changes in both cicatricial and noncicatricial alopecia. However, the technique has provided the most significant gains in the study of the latter type of alopecia, where evaluation of follicle density and follicular dynamics are integral to accurate diagnosis. This report reviews the histopathologic findings of four common types of noncicatricial alopecia: androgenetic alopecia, telogen effluvium, alopecia areata, and trichotillomania/chronic traction alopecia.     

Investigation of the hair follicle inner root sheath in scarring and non-scarring alopecia

BACKGROUND: Premature desquamation of the inner root sheath (IRS) is described as a defining histologic feature of follicular degeneration syndrome/central centrifugal cicatricial alopecia (CCCA). However, IRS abnormalities have been noted in other types of alopecia. DESIGN: We evaluated the IRS in terminal hair follicles with transverse sections stained with hematoxylin-eosin and Ziehl-Neelsen stains in 22 non-scarring (7 areata and 15 androgenetic) and 21 scarring (13 CCCA, 2 lichen planopilaris, 2 lupus erythematosus, 1 folliculitis decalvans and 3 end stage) alopecia cases. In addition, we evaluated 15 normal controls with longitudinal sections to establish the level of IRS desquamation. RESULTS: The IRS was present in 99.5 +/- 0.01% (mean +/- standard error) of normal follicles at the level of the arrector pili muscle/sebaceous gland/sweat gland coil (L2) and variably present at higher levels. The IRS was present at L2 in 97.9 +/- 1.5% of alopecia areata, 87.4 +/- 5.3% of androgenetic alopecia, 59.3 +/- 7.0% of CCCA and 49.4 +/- 11.3% of other scarring alopecia follicles. CONCLUSIONS: Premature desquamation of the IRS was identified in CCCA; however, it was also noted in other scarring alopecia cases. IRS premature desquamation is a non-specific histologic feature in scarring alopecia and cannot be used alone as a defining feature of CCCA.     

Characterization of infiltrating T cells in human scalp explants from alopecia areata to SCID nude mice: possible role of the disappearance of CD8+ T lymphocytes in the process of hair regrowth

T cells may play a role in the pathogenesis of alopecia areata (AA). We attempted to elucidate the linkage between infiltrating T cells and hair regrowth processes by grafting scalp skin from the affected region of patients with AA onto severe combined immune deficiency (SCID) nude mice. When the AA scalp was grafted into the mice, the grafts were accepted, and normal hair regrowth was observed. Before grafting, CD4+ and CD8+ T cells had infiltrated into the peribulb area. After grafting, the telogen hair shifted to anagen hair, and the CD4+ and CD8+ T cell infiltrates in the bulb area decreased in all cases. CD8+ T cells had almost disappeared from all portions of the follicles. It has been suggested that CD8+ T cells play a crucial role in the pathogenesis of AA. The absence of CD8+ T lymphocytes that responded to follicular autoantigens may induce hair regrowth in the grafted skin. In addition, the CD4+ human T cells that had infiltrated or still remained in the upper-middle portions including the bulge area accompanied the HLA-DR expression after grafting. Infiltrating or surviving T cell phenotypes and locations changed during the hair cycle in the grafts. These results indicate that the location of infiltrated T cells and their phenotypes may participate not only in hair loss but also in regrowth of hair in AA.     

Histopathological investigation of clinically non‐affected perilesional scalp in alopecias detected unexpected spread of disease activities

Histopathological comparison between clinically affected and intact regions in alopecia patients has been considered to facilitate better understanding of the pathophysiology of ongoing disease. Theoretically, adjacent intact regions should provide ideal controls as they should share close histological characteristics, however, to what extent clinically non‐affected neighboring regions maintain their pathological integrity has not been fully assessed. The goal of this study is to delineate histopathological characteristics of clinically intact perilesional regions in the patients with various forms of alopecia. Transverse sections of 4‐mm punch biopsy at the levels of isthmus and suprabulbar portion were obtained from seemingly unimpaired perilesional scalp of 50 Japanese alopecia patients (16 alopecia areata [AA] multiplex, 19 scarring alopecia [SA], 15 other conditions) and subject to histopathological investigation. Initial screening detected decrease in anagen (anagen : telogen ratio = 82.4:17.6) when compared with previously reported standard hair counts in normal Asian scalp. This finding prompted further investigation. Unexpectedly, 33 (66%) specimens demonstrated some microscopic abnormalities, 10 (62.5%) AA specimens showed increase in telogen ratio, vellus hair count and miniaturization, while perifollicular inflammatory cell infiltration was detected in 5 (26.3%) SA cases. Exclusion of histologically affected specimens yielded average hair count numbers resembling those reported in Koreans, supporting the pathological integrity of selected samples and, more importantly, indicating normal hair counts in east Asians. These findings indicated a less recognized significance of histopathological investigation of clinically non‐affected perilesional scalp in alopecias for better assessment of the spread of disease activities, which should enable better management of hair loss conditions.     

Computerized morphometry and three-dimensional image reconstruction in the evaluation of scalp biopsy from patients with non-cicatricial alopecias

BACKGROUND: A major challenge in the histopathological examination of scalp biopsies is to perform an adequate evaluation of all the hair follicles present in the tissue. Transverse sectioning is currently the preferred technique to demonstrate every follicular structure in a punch biopsy specimen, although diagnostic accuracy is dependent on subjective evaluation of follicular morphology and hair size. OBJECTIVES: To determine if computer-based morphometry and three-dimensional (3D) image reconstruction software can be used to evaluate scalp biopsies from patients with non-cicatricial alopecias. METHODS: Nine 4-mm scalp punches were taken from nine patients with noncicatricial alopecias and step-sectioned transversely at 0.1-mm intervals from the epidermal surface to the subcutaneous fat. Each tissue section was then digitized and analysed using morphometric and 3D image reconstruction software. Morphometric data and 3D images were collated with clinical and conventional light microscopic diagnoses, as well as follow-up information. RESULTS: In four of the nine patients, results of morphometric analysis concurred with conventional clinicopathological diagnoses. In the remaining five patients, morphometry revealed a lower telogen count in one patient and higher telogen count in four patients. One of the four patients with a higher telogen count also had a low mean hair diameter and miniaturized anagen follicles in the 3D image that were suggestive of early androgenetic alopecia (AGA). 3D virtual microscopic imagery allowed the direct visualization of colour-coded, scaled hair follicles which demonstrated characteristic changes in alopecia areata, AGA and telogen effluvium. CONCLUSIONS: Our study demonstrated the feasibility of using morphometric and 3D reconstruction software to evaluate scalp biopsies. With further validation, this technique may prove to be more sensitive to detect subtle quantitative and qualitative follicular changes in non-cicatricial alopecias.     

The histopathology of alopecia areata in vertical and horizontal sections

Alopecia areata (AA) is a relatively common disease affecting 1.7% of Americans by the age of 50 years. The diagnosis is usually made on clinical grounds. In some cases the diagnosis is elusive and biopsies are necessary. In other cases biopsies are useful from a prognostic point of view to determine whether there are enough follicles left for possible future regrowth. In view of the active research being conducted into AA, biopsies provide valuable material for further investigation. The diagnosis of AA is improved by the use of horizontal sections in addition to or instead of vertical sections of scalp biopsies. The histopathologic features favoring the diagnosis of AA include peribulbar and intrabulbar mononuclear infiltrates, degenerative changes in the hair matrix, decreased numbers of terminal anagen follicles, increased numbers of terminal catagen and telogen follicles, an increased number of follicular stelae, an increased number of miniaturized vellus hair follicles, and pigment incontinence of hair bulbs and follicular stelae. Follicular counts with horizontal sections are particularly helpful in making the diagnosis of AA when the biopsy has been taken between acute episodes and the characteristic peribulbar inflammatory infiltrate is absent.     

Circumscribed alopecia areata incognita

The characteristic lesion of alopecia areata is a smooth bald patch on the scalp. When there is no bald surface it is called alopecia areata incognita. To date, all cases of alopecia areata reported as so‐called ‘incognito’ have shown a diffuse involvement of the scalp as in acute telogen effluvium. Recently, we have observed two patients who showed localised hair thinning of the scalp without bald spots. Histopathologically, the lesions were typical of alopecia areata with peribulbar lymphocytic infiltrates. The response to corticosteroid treatment and its clinical course were also compatible with alopecia areata.     

Clinical and histological challenge in the differential diagnosis of diffuse alopecia: female androgenetic alopecia,telogen effluvium and alopecia areata - Part II

Diffuse alopecia is mainly caused by telogen effluvium, diffuse androgenetic alopecia (female-pattern hair loss) and diffuse alopecia areata. Differential diagnosis between the three disorders may be difficult in several occasions. In this second part of our study, chronic telogen effluvium and diffuse alopecia areata are discussed in detail, including clinical, dermoscopic and histological aspects. A flowchart presents a practical and objective differential diagnostic approach to diffuse alopecia.     

Permanent alopecia after systemic chemotherapy: a clinicopathological study of 10 cases

Anagen effluvium due to chemotherapy is usually reversible with complete hair regrowth. However, there is increased evidence that certain chemotherapy regimens can cause dose-dependent permanent alopecia. The histological features of this type of alopecia and the mechanisms of its origin are not known yet. We discuss the histological features of 10 cases of permanent alopecia after systematic chemotherapy with taxanes (docetaxel) for breast cancer (6 patients), busulfan for acute myelogenous leukemia (3 patients), and cisplatin and etoposide for lung cancer (1 patient). All patients had moderate to very severe hair thinning, which in 4 cases was more accentuated on androgen-dependent scalp regions. Patients complained that scalp hair did not grow longer than 10 cm and showed altered texture. Paired scalp biopsies from the affected scalp areas were obtained and evaluated in serial horizontal and vertical sections. The histology of all specimens was characterized by a nonscarring pattern with a preserved number of follicular units and lack of fibrosis. The hair count revealed decreased number of terminal hairs, increased telogen hairs, and increased miniaturized vellus-like hairs with a terminal to vellus and anagen to telogen ratios of 1:1 and 3.6:1, respectively. There was increased number of fibrous streamers (stelae) in both reticular dermis and subcutis. Arao-Perkins bodies were found in the subcutaneous portions of the streamers. The histological findings of permanent alopecia after chemotherapy are those of a nonscarring alopecia similar to androgenetic alopecia. Dermatopathologists should be aware of this condition as the absence of fibrosis and the presence of miniaturized hairs may be considered as features consistent with a diagnosis of androgenetic alopecia. Hence, these cases could easily be misdiagnosed in the absence of a good clinicopathological correlation.     

Clinical study on the efficacy and tolerability of a topical regenerative treatment in patients with telogen effluvium and mild androgenetic alopecia

Hair loss may change the quality of life since modern society considers hair an essential element in beauty definition. The most common causes of hair loss are androgenetic alopecia (AGA) and telogen effluvium (TE). AGA requires a lifetime use of minoxidil or finasteride (and sometimes they lose efficacy over the years), whereas TE has no standardized therapy available. Our study focuses on a novel topical regenerative preparation that, by mimicking autologous PRP, can safely and efficiently improve hair loss in patients affected by TE and AGA.     

Quantification of hair follicle parameters using computer image analysis: A comparison of androgenetic alopecia with normal scalp biopsies

Computer image analysis enables large numbers of hairs to be measured in an automated fashion. In this study, we examined horizontal scalp biopsies from 10 patients with a histological diagnosis of androgenetic alopecia and 10 normal control subjects. The density of hair follicles and the ratio of terminal to vellus hairs were determined. Hair shaft, hair canal and hair follicle diameter, inner root sheath width and outer root sheath area were measured using the Chromatic Colour Image Analysis program. This study showed a statistically significant progressive decrease in size of hair canal diameters from normal terminal hairs (85.93 ± 10.07 μm) through to androgenetic alopecia terminal (68.83 ± 13.60 μm) and vellus hairs (28.67 ± 5.60 μm). This pattern is also seen with hair follicle diameters; normal terminal (268.41 ± 24.88 μm), androgenetic alopecia terminal (236.34 ± 17.23 μm), and vellus hairs (130.88 ± 19.96 μm). Outer root sheath areas, hair shaft diameters and ratio of terminal to vellus hairs were significantly larger in normal (18500 ± 4222 μm²; 82.71 ± 13.79 μm; 36:1; respectively) compared with androgenetic alopecia scalp biopsies (8403 ± 3322 μm²; 61.11 ± 14.42 μm; 3:1; respectively), whereas inner root sheath width and density did not vary significantly. Computer image analysis can be adapted for use in clinical trials where large numbers and objectivity are critical in determining the efficacy of hair growth promoters.