Stem cells and alopecia: a review of pathogenesis.

Recent work has focused on the hair follicle as the main source of multipotent stem cells in the skin. The hair follicle bulge contains multipotent stem cells that can form the epidermis, hair follicles and sebaceous glands and help in repopulation of the epidermis after injury. The localization of these stem cells to the bulge area may explain why some types of inflammatory alopecia cause permanent loss of hair (cicatricial alopecia) (such as lichen planopilaris and discoid lupus erythematosus), while others (such as alopecia areata) are reversible (noncicatricial alopecia). The lack of distinctive bulge morphology in human hair follicles has hampered studies of bulge cells. To date, the best marker for bulge stem cells in human hair is cytokeratin (CK) 15; human bulge cells have been reported to express CK15 selectively throughout all stages of the hair cycle in different types of follicles. There is direct evidence in the mouse, and indirect evidence in the human, that compromising the integrity of the sebaceous gland and/or bulge is important in the development of alopecia. Several interesting studies have been done in the last few years to investigate the role of stem cells in alopecia, especially nonscarring types. This is a review about the role of stem cells in the pathogenesis of alopecia (scarring and nonscarring).

Immunohistochemistry of ultrastructural changes in scarring lupus erythematosus.

BACKGROUND: The various clinical types of lupus erythematosus (LE) show an essentially similar histological picture, and the subsets of LE cannot easily be distinguished by histology alone. However, there is an important clinical difference: lesions of discoid LE (DLE) cause scarring, particularly on the scalp, whereas lesions of subacute and acute LE heal without scarring. The focal thickening of the basement membrane zone (BMZ) in DLE lesions represents an important histopathological finding, and there is little known about the nature of these alterations at the BMZ level. AIM: To investigate BMZ alterations in the basement membrane zone (BMZ) in cutaneous LE (CLE) by immunohistochemistry. METHODS: Skin biopsies from 30 patients with CLE [DLE and subacute CLE (SCLE)] and from 10 controls were studied using antibodies to cytokeratin 5, cytokeratin 14, bullous pemphigoid (BP)180, BP230, plectin, laminin 5, collagen IV and collagen VII. Results. There was increased expression of components of the lamina lucida, lamina densa and anchoring fibrils in active DLE, whereas expression was normal in SCLE and control tissues, and in areas of scarring in DLE. In addition, higher expression of the hemidesmosome-associated antigens (BP230 and plectin) was found in active DLE. The expression of other antigens was similar in all tissues examined. CONCLUSIONS: These alterations in the BMZ suggest that the BMZ may react in a different way in active DLE than in SCLE, and that the BMZ may remodel in different ways. These immunohistochemical differences may provide a new method of histological differentiation between the various LE subtypes.

Scar classification in cutaneous lupus erythematosus: morphological description.

BACKGROUND: Scarring represents the single most debilitating aspect of discoid lupus erythematosus (DLE) in patients with cutaneous lesions alone. Despite this, there have been no studies which have attempted to classify the types of scars seen in this chronic disease. OBJECTIVES: The aim was to classify the types of scars based on morphological description. PATIENTS AND METHODS: Forty-five patients with histologically confirmed DLE were included in the study. In the assessment of the types of scars, the scars were scored initially according to their anatomical localization. Each anatomical area was assessed for the types of scars which occurred in these areas. RESULTS: Scars in patients with DLE were initially classified morphologically into six types according to the site of the scar and then each type was classified into subtypes according to the morphology of the scar. Scars were seen in the majority of the patients and scarring affected mostly areas including the scalp, other hairy areas such as the eyebrows, nonhairy areas, mucosa, fatty layers of the skin and the nails. This study demonstrated that scars may not only produce textural changes but may also produce pigmentary changes. It is possible that other types of scars may yet occur in DLE but have not so far been detected. CONCLUSIONS: Early classification and identification of the types of scars in these patients may change management towards more aggressive therapy in those with continued disease activity, and it is possible that different types of scarring require different therapies.

Basement membrane changes in lichen planopilaris.

BACKGROUND: Lichen planopilaris (LPP) is an inflammatory disease that affects the scalp and tends to produce cicatricial alopecia. The inflammatory process frequently results in the disruption of the basal cell of the external root sheath of the hair follicle. OBJECTIVES: To investigate the alterations in the basement membrane zone (BMZ) in LPP by immunohistochemistry. METHODS: Skin biopsies from six patients with LPP plus six normal controls were studied by immunohistochemistry with antibodies to the following BMZ components: cytokeratin 5, cytokeratin 14, BP230 (bullous pemphigoid), BP180, plectin, laminin 5, collagen IV and collagen VII. RESULTS: The localization and staining of the hemidesmosome, laminin and collagen components were strikingly different in the inflamed follicular epithelium when compared to the uninvolved follicles or interfollicular epithelium in active LPP lesions. The hemidesmosome-associated complexes were weakly expressed and discontinuous in involved hair follicles. The expression of laminin-5, type IV collagen and type VII collagen was disrupted and not linear along the BMZ with finger-like projections of the staining protruding into the dermis. The expression of the intermediate filaments was normal. CONCLUSION: These alterations in the BMZ in LPP may explain the abnormal healing at follicular level which leads to irreversible hair loss and scarring in this condition.

Expression of hair follicle stem cells detected by cytokeratin 15 stain: implications for pathogenesis of the scarring process in cutaneous lupus erythematosus.

BACKGROUND: Discoid lupus erythematosus (DLE) is a scarring disease. Although the scarring and deformity may affect any part of the body, such changes have been reported to be most obvious on the face and scalp. The pathogenesis behind this scarring process is not well understood. Once lesions have scarred, recurrent disease tends to occur at the edge of the scarred lesions but not within them. OBJECTIVES: The fact that inflammation in DLE generally involves the bulge area of the follicles raises the possibility that damage to the stem cells of the bulge region may be one process leading to the permanent loss of follicles. The aim of this study was to investigate the role of the hair follicle stem cells which reside in the bulge region in the scarring process in cutaneous lupus erythematosus (CLE). METHODS: We studied the reactivity of an antibody to the CD8 antigen (C8/144B), which recognizes cytokeratin (CK) 15 and preferentially immunostains hair follicle stem cells without staining the remaining hair follicle, on skin biopsies (scalp and body lesions) from patients with CLE (36 with discoid lesions and 10 with subacute lesions). Normal scalp and body biopsy specimens served as controls. The correlation between the extent of the cytotoxic inflammatory cell infiltrate (CD8+) and the presence of stem cells was investigated. Results were analysed semiquantitatively. RESULTS: The expression of CK15 in hair follicle stem cells was variable in the DLE lesions; there was normal to moderate CK15 expression at the bulge region of hair follicles when surrounded by mild or moderate inflammatory infiltrate (CD8+), but in cases of severe inflammation, CK15 expression was weak or absent. CONCLUSIONS: The bulge region appears to be involved in this disease as part of a broader involvement of the hair follicles; it is secondarily affected by the surrounding inflammatory cell infiltrate. Expression of C8/144B diminished and was then absent, indicating either damage to stem cells or differentiation to help in the repair process. Damage to follicular stem cells may help to explain the irreversible alopecia and the scarring process which characterize this disease.