Cytokine alterations in lichen sclerosus: an immunohistochemical study

BACKGROUND: Although the histology of lichen sclerosus is characteristic, the precise nature of the inflammatory changes and the signals provoking them is uncertain. OBJECTIVES: To delineate the inflammatory changes in lichen sclerosus more accurately by studying cytokine changes. METHODS: An immunohistochemical study of 12 specimens of genital lichen sclerosus and one specimen of extragenital lichen sclerosus was undertaken using monoclonal antibodies to interferon (IFN)-gamma, IFN-gamma receptor, tumour necrosis factor (TNF)-alpha, interleukin (IL)-1alpha, IL-2 receptor (CD25), intercellular adhesion molecule-1 (ICAM-1) and its ligand CD11a. Control specimens were seven specimens of normal vulva obtained during gynaecological procedures, three specimens of normal skin, adjacent uninvolved thigh from three of the patients with lichen sclerosus, five specimens of nonvulval psoriasis, four specimens of nonvulval lichen planus and two specimens from chronic wounds. RESULTS: The lichen sclerosus specimens demonstrated slightly increased staining for IFN-gamma within the epidermis compared with the normal vulva and nonvulval skin. There was increased dermal staining for IFN-gamma both within the pale zone of the upper dermis and within the inflammatory zone below this. We confirmed our previous demonstration that in lichen sclerosus HLA-DR immunostaining is increased in association with vascular endothelium, the inflammatory cell infiltrate and around the keratinocytes. The areas of the epidermis with the strongest immunostaining for HLA-DR generally also had the strongest staining for IFN-gamma. In the lichen sclerosus specimens the zone of inflammation also demonstrated increased immunostaining for TNF-alpha, IL-1alpha, IFN-gamma receptor, CD25, CD11a and ICAM-1 while the zone of sclerosus demonstrated a smaller increase in immunostaining for IFN-gamma receptor, TNF-alpha, CD11a and ICAM-1, and the epidermis demonstrated increased staining for ICAM-1. CONCLUSIONS: The increased staining for IFN-gamma, TNF-alpha, IL-1alpha, IFN-gamma receptor, CD25, CD11a and ICAM-1 suggest that the cytokine response in lichen sclerosus shares characteristics of the cytokine response in lichen planus and chronic wounds.     

Alterations in distribution of tenascin, fibronectin and fibrinogen in vulval lichen sclerosus

BACKGROUND: The pathophysiology of lichen sclerosus remains uncertain. The clinical features, including increased fragility and scarring, and the histology suggest that significant reorganisation of the extracellular matrix is occurring. Tenascin, fibrinogen and fibronectin are extracellular matrix components that play a significant role in tissue remodelling, for example during wound repair. Aim: To examine the distribution of tenascin, fibrinogen and fibronectin in vulval lichen sclerosus. MATERIALS AND METHODS: Immunohistochemical staining was performed to study the distribution of tenascin, fibronectin and fibrinogen in 16 specimens of untreated vulval lichen sclerosus and 1 specimen of extragenital lichen sclerosus. Haematoxylin and eosin staining of the specimens was also performed to identify the position of the pale staining homogenous zone/zone of sclerosis and the inflammatory infiltrate below this. The control tissues studied included biopsies taken from the uninvolved thigh of 13 of the lichen sclerosus patients and 6 samples of normal vulva tissue obtained during gynaecological procedures from women of similar age to the lichen sclerosus women. RESULTS: All the lichen sclerosus specimens demonstrated increased immunostaining of tenascin in the upper dermis and comparing this with the haematoxylin and eosin staining this corresponded to the zone of sclerosis with relatively little tenascin staining associated with the inflammatory band. In 14 out of the 16 vulval lichen sclerosus specimens and the extragenital lichen sclerosus specimen fibrinogen immunostaining was increased in the upper dermis which corresponded--in haematoxylin and eosin staining --to the zone of sclerosis. There was also slightly increased fibrinogen staining in the mid dermis which corresponded to the inflammatory band. Fibronectin staining was reduced in the upper dermis of 12 of the vulval lichen sclerosus specimens and the extragenital lichen sclerosus specimen which corresponded to the zone of sclerosis. However, in 14 of the vulval lichen sclerosus specimens and the extragenital lichen sclerosus specimen, fibronectin was slightly increased in the mid and deeper dermis which corresponded to the zone of inflammatory cells and the area below this. There was also increased fibronectin staining around blood vessel walls both in the mid dermis and within the zone of sclerosis. CONCLUSION: The distribution of tenascin, fibrinogen and fibronectin is altered in lichen sclerosus and the alteration in these extracellular matrix components may be relevant to the initiation of scarring in lichen sclerosus and the associated increased skin fragility.     

Comparative immunophenotypic study of lichen sclerosus: epidermotropic CD57+ lymphocytes are numerous--implications for pathogenesis

To characterize the immunophenotype of inflammatory cells in lichen sclerosus (LS), we performed a comparative case control study using one- and two-color immunohistochemistry and the nitro blue tetrazolium (NBT) reaction. Study material consisted of 100 biopsies from patients with LS or from 12 control groups consisting of inflammatory, scarring, and depigmenting cutaneous disorders. In addition, fresh tissue was sampled from four vulvectomy specimens for NBT testing. The typical inflammatory infiltrate of LS contained numerous epidermotropic CD3+, CD8+, CD57+ cells, increased intraepidermal HLA-DR+ cells, and a dermal infiltrate rich in CD8+, CD57+, HLA-DR+, and CD68+ inflammatory cells. Comparing LS to the 12 control groups, epidermotropic CD57+ lymphocytes independently predicted LS (P = 0.006, logistic regression, multivariate analysis). Among the 12 control groups, only specimens of the inflammatory stage of morphea exhibited numerous dermal CD57+ lymphocytes. Two-color immunohistochemistry confirmed the CD3+/CD8+CD57+ and CD3+/ CD8+/CD57+HLA-DR+ epidermotropic and dermal lymphocytic phenotypes and the dermal macrophage CD68+HLA-DR+ phenotype. In LS, the NBT reaction revealed evidence of superoxide production associated with CD68+HLA-DR+ cells. Expansion of CD8+CD57+lymphocytes is associated with viral infections, autoimmune disease, malignancies, and transplantation and is suspected to be the result of chronic excessive antigen challenge. In these pathologic states, CD8+CD57+ lymphocytes (as terminally differentiated, antigen-specific T cells) participate in the suppression of cytolytic activity to limit tissue damage. In LS, activated macrophages and lymphocytes indicate persistent antigen-driven inflammation. LS's numerous CD8+CD57+ lymphocytes may be either the mediators or the consequence of its hallmark sclerosis.     

Detection of perforin and granzyme B mRNA expressing cells in lichen sclerosus

Granzyme B and perforin messenger RNA (mRNA) expression has been shown to be a specific in vivo activation marker for cytotoxic cells. The aim of this study was to assess the contribution of cell-mediated cytotoxicity in the pathogenesis of lichen sclerosus. In situ hybridization and immunohistochemistry were performed on serial tissue sections of lesional skin biopsies and normal skin as control. Immunohistochemical staining showed that the cellular infiltrate of diseased skin consisted predominantly of T cells (CD3+) and some B cells (CD20+). Among T cells CD4+ and CD8+ cells were found in about equal numbers. In normal skin samples perforin and granzyme B mRNA expressing cells were only rarely found. In contrast, in biopsies from diseased skin a high percentage of infiltrating cells expressed mRNA for perforin and granzyme B. The perforin and granzyme B expressing cells were found in the dermal infiltrate and intraepidermally in close proximity to keratinocytes suggesting in situ activation of these cells. These findings provide evidence that cell-mediated cytotoxicity plays a significant role in tissue destruction in lichen sclerosus.     

Abnormal accumulation of inter-alpha-trypsin inhibitor and hyaluronic acid in lichen sclerosus

Inter-alpha-trypsin inhibitor (ITI) is a recently identified extracellular hyaluronic acid (HA)-binding protein which greatly improves extracellular HA stability. In lichen sclerosus (LS), a broad hyalinized zone of superficial dermis is the most prominent pathological change. To assess the pathogenic role of ITI in accumulation of HA in a broad hyalinized zone in LS, we examined the expression and localization of ITI and HA immunohistochemically. In LS lesional skin sections, ITI staining revealed a strong, diffuse immunoreactivity predominantly in the upper dermis, whereas no staining was detected in normal skin sections. HA staining clearly showed positive reactivity in the superficial dermis, the epidermis, and occasionally the perivascular inflammatory infiltrate in LS skin sections. In normal skin, HA was present only in the epidermis. Double staining for ITI and HA demonstrated that ITI was localized in the areas where HA was abnormally deposited in the superficial dermis of LS. Other HA-binding proteins, CD44 and versican, did not show enhanced staining in the upper dermis of LS compared to normal skin specimens. These findings strongly suggest that ITI is closely implicated in the accumulation of HA in a broad hyalinized zone of the superficial dermis of LS.     

Alterations induced in normal human skin by in vivo interferon-gamma

In a study of the direct effects of interferon-gamma (IFN-gamma) on normal human skin, healthy adult male volunteers received either 3 micrograms (n = 4) or 30 micrograms (n = 9) of recombinant IFN-gamma administered intradermally over 3 days. Biopsies were taken on day 6 and histopathological examination of fixed paraffin-embedded sections from sites which had received 30 micrograms IFN-gamma revealed a moderate perivascular lymphohistiocytic dermal infiltrate with mast cells. Immunophenotyping of 5 microns cryostat sections demonstrated that 3 micrograms IFN-gamma induced keratinocyte HLA-DR expression in the absence of any significant infiltrate. More intense keratinocyte HLA-DR expression was produced by 30 micrograms IFN-gamma in all specimens, with HLA-DP concurrently expressed in three biopsies. The ratio of CD4:CD8 cells within the infiltrate was approximately 3:1. CD1 + cells within the epidermis were markedly depleted by 30 micrograms IFN-gamma, while CD1-labelled cells were observed in the dermal perivascular infiltrate. Intradermal IFN-gamma induces similar immunopathological changes to those observed in many of the inflammatory dermatoses.     

Decrease in epidermal CD44 expression as a potential mechanism for abnormal hyaluronate accumulation in superficial dermis in lichen sclerosus et atrophicus

CD44 is a polymorphic integral membrane glycoprotein that serves as the principal cell surface receptor for hyaluronate, the major component of the extracellular matrix. CD44 is abundantly found in the skin and functions as a cell adhesion molecule. In a recent study we have observed a massive dermal accumulation of hyaluronate as a result of the in vivo selective suppression of CD44 in keratinocytes in mice expressing a keratin 5 promoter-driven CD44 anti-sense transgene. As the histologic features of the dorsal skin of these transgenic mice display some similarities to those of the skin lesions of lichen sclerosus et atrophicus, we explored the nature of the material accumulated in the dermis of genital and extragenital lesions of 14 patients with lichen sclerosus et atrophicus by Alcian Blue and human CD44 receptor globulin stainings, as well as the epidermal expression of CD44 protein and mRNA by immunohistochemistry and in situ hybridization. In this study we provide evidence that hyaluronate is accumulated in the superficial dermis of lichen sclerosus et atrophicus lesions, in particular by the use of human CD44 receptor globulin staining, which binds specifically to hyaluronate. In addition we show that the protein and mRNA expression of CD44 in the epidermis of the involved lichen sclerosus et atrophicus skin from genital and extragenital areas is significantly decreased, and in some cases completely lost. In contrast, keratinocyte CD44 expression was un-altered in the skin lesions of lupus erythematosus, scleroderma and reticular erythematous mucinosis, despite the presence of a mucinous material in the dermis. These results suggest that a decrease in CD44 in the keratinocytes may be correlated with an abnormal dermal accumulation of hyaluronate in the lesions of lichen sclerosus et atrophicus, and may play a pathogenetic role in this disease. J Invest Dermatol 115:1054-1058 2000     

Vulval lichen sclerosus: lack of correlation between duration of clinical symptoms and histological appearances

Background Histological criteria in lichen sclerosus have been correlated with disease duration. A progressive tendency for the inflammatory infiltrate to become more deeply placed and more sparse with long-standing disease has been described together with a tendency for collagen homogenisation in the upper dermis to become more prominent with time.
Materials and methods We performed a retrospective Wind clinico-pathological study on 20 untreated patients with lichen sclerosus. We looked at sections from five additional patients with lichen sclerosus who required serial biopsies in the course of their disease. The purpose was to observe the histological patterns at different stages of the clinical course.
Results We found a poor correlation between estimated disease duration and histological criteria for early and long-standing disease.
Conclusion We conclude that the pathological process in lichen sclerosus is a continuing process and the inflammatory component can be a persistent or recurring phenomenon which may be site-determined. The estimation of disease duration in vulval lichen sclerosus using histological criteria is unsatisfactory.     

HLA-DR expression on keratinocytes is a common feature of diseased skin

Biopsy specimens from 185 patients with 52 different skin disorders were investigated by indirect immunofluorescence staining for the presence of HLA-DR bearing keratinocytes and their association with an underlying inflammatory infiltrate and in particular with activated (HLA-DR-positive, Leu-4-positive) T lymphocytes. HLA-DR expression on keratinocytes was demonstrated in 38 dermatoses, including lymphocytic vasculitis, lupus erythematosus, morphea, vitiligo, lichen planus, cutaneous T-cell lymphoma, various infectious dermatoses, allergic contact dermatitis, granulomatous dermatoses, Sweet's syndrome, lichen sclerosus and erythema nodosum. In 27 of these this had not previously been reported. Occurrence of HLA-DR on keratinocytes was invariably linked to the presence of a lymphocytic infiltrate containing numerous activated T-cells (Leu-4 +, HLA-DR +) whereas such infiltrates were not accompanied by HLA-DR expression on keratinocytes in all the dermatoses investigated, as in pseudolymphoma and erythema anulare centrifugum. However, HLA-DR positive keratinocytes were consistently absent in skin disorders lacking any significant lymphocytic infiltration (e.g. leukocytoclastic vasculitis, bullous autoimmune dermatoses, genodermatoses and mastocytosis). Although it has been suggested that HLA-DR-positive keratinocytes are involved in various immune responses of the skin, their exact functional significance is, as yet, unknown.     

Pityriasis lichenoides et varioliformis acuta in HIV-1 + patients: a marker of early stage disease

Background The high incidernce of cutaneous disease in HIV-1 + patients may be a marker of the chronic state of immune activation. In addition, specific cutaneous diseases may be related to the pattern and degree of immune dysregulation present in the patients at the time of the eruption. We have observed that HIV-1 + patients with pityriasis lichenoides et varioliformis acuta (PLEVA) were in the early to midstage of HIV-1 disease. Materials and methods To determine if there was a correlation between the phenotype of the lymphoid infiltrate and surface markers of the epidermis and the known changes in early or late-stage HIV-1 disease, we studied five HIV-1 + patients with PLEVA. Cutaneous biopsy specimens were obtained and immunohistochemical stains were used to determine the expression of ELAM-1, ICAM-1, and HLA-DR and the phenotype of the lymphoid infiltrate. Results The HIV-1 + patients showed increased expression of HLA-DR on keratinocytes as well as on the mononuclear and dendritic cell populations in the epidermis and dermis. The majority of T cells were activated CD8+ cells. Conclusions Immunophenotyping of the inflammatory infiltrate in these patients is consistent with a pattern of immune dysregulation seen only in earlier stages of HIV-1 disease. Thus, PLEVA may be useful as a marker of early to midstages of HIV-1 disease.     

Alterations in fibrillin as well as collagens I and III and elastin occur in vulval lichen sclerosus.

BACKGROUND: The clinical features of lichen sclerosus, which include atrophy, scarring, fragility and tendency to form ecchymoses with only slight trauma, suggest that there is an alteration in the extracellular matrix fibres that are responsible for the tensile strength of the dermis. However, the precise nature of these changes is poorly understood. METHODS: Biopsies from 16 patients with untreated, histologically confirmed, vulval lichen sclerosus were examined immunohistochemically using polyclonal antibodies to collagens I and III and a monoclonal antibody to elastin. Twelve of the lichen sclerosus specimens were also stained with a monoclonal antibody to fibrillin. Normal vulva tissue and patients' uninvolved thigh were used as controls. RESULTS: In the lichen sclerosus specimens, collagens I and III stained with a more homogeneous pattern than in the control tissues. Reduced numbers of elastin fibres were seen in the zone of sclerosus in 15 of the 16 lichen sclerosus specimens. In the control tissue fibrillin fibres were seen as a fine network of fibres in the upper dermis arranged at right angles to and inserting into the basement membrane and forming a fine network throughout the dermis. In the lichen sclerosus specimens, although fibrillin microfibrils were still seen inserting at right angles into the basement membrane, below this the fibrillin staining was reduced in the upper dermis in 11 of the 12 lichen sclerosus specimens. The zone of reduced fibrillin staining was greatest in those specimens where the band of inflammation was deep in the dermis. CONCLUSIONS: The distribution of collagens I and III, elastin and fibrillin are altered in lichen sclerosus and this is likely to contribute to the fragility, scarring and atrophy seen clinically in lichen sclerosus.     

An infective aetiology for vulval lichen sclerosus re-addressed

Although there is evidence to support an autoimmune basis for lichen sclerosus, there have also been some studies which suggest an infective aetiology. These include reports of the presence of spirochaetal forms with Steiner silver stains and purplish coccoid forms with Fite stains. We have repeated these studies on vulval biopsies obtained from 16 patients with vulval lichen sclerosus. Using the Steiner silver method we found no evidence of spirochaetal forms in any of the specimens. With the Fite stain we observed purple-staining coccoid forms within the dermis of 13 of the 16 lichen sclerosus specimens. However, these coccoid forms also stained strongly positive with toluidine blue, suggesting they were mast cell granules rather than micro-organisms. We were therefore unable to demonstrate evidence for an infective aetiology in vulval lichen sclerosus, although this cannot yet be excluded. Further work is also needed to understand the significance of mast cells in lichen sclerosus.     

CD44 and hyaluronate expression in follicular mucinosis

BACKGROUND: CD44 is a membrane glycoprotein and the major cell-surface receptor of hyaluronate (HA). Lack of CD44 expression in mouse epidermis leads to an abnormal HA accumulation in the dermis, indicating an important role of CD44 in local HA metabolism. Decrease of epidermal CD44 expression in patients of lichen sclerosus et atrophicus is potentially responsible for dermal deposition of HA in this disease. Stromal HA accumulation is associated with decreased or lost expression of CD44 in perifollicular solitary cutaneous myxoma, myxoid dermatofibroma, and dermatofibrosarcoma protuberans. METHODS: We examined the expression of CD44 and HA in the skin biopsy specimens of 10 patients with follicular mucinosis by using CD44-specific antibodies and biotinylated HA-binding protein (HABP), respectively. RESULTS: No difference of CD44 expression was observed in the follicular keratinocytes when compared with those of unaffected interfollicular epidermis. The follicular zones of mucin deposition were strongly positive for HA. A weak interkeratinocyte staining for HA was also observed in the interfollicular epidermis. However, HABP staining revealed a stronger reactivity in the follicular keratinocytes surrounding the mucin-accumulated areas compared to the interfollicular keratinocytes. CONCLUSION: Our results suggest an active secretion of HA by follicular cells in follicular mucinosis.     

Plaque psoriasis vs. atopic dermatitis and lichen planus: a comparison for lesional T-cell subsets, epidermal proliferation and differentiation

BACKGROUND: T-cell infiltration in plaque psoriasis has recently been an important subject of investigation. Interestingly, comparative analyses of the disease-specific composition of the lesional T-cell infiltrate in plaque psoriasis and other inflammatory dermatoses have only sparsely been performed. OBJECTIVES: To compare plaque psoriasis vs. atopic dermatitis and lichen ruber planus with respect to T-cell subsets, epidermal proliferation and keratinization. PATIENTS AND METHODS: Biopsies were taken from untreated lesional skin of patients, six with psoriasis, six with atopic dermatitis and six with lichen planus. T-cell subsets (CD4+, CD8+, CD45RO+, CD45RA+, CD2+, CD25+), an epidermal proliferation (Ki-67) and a keratinization marker (K10) were stained immunohistochemically and quantified using image analysis. RESULTS: The high number of CD8+ T cells (52 +/- 13 cells mm(-1)) found in the psoriatic epidermis was not found in the epidermis of atopic dermatitis (9 +/- 4), nor in the epidermis of lichen planus (34 +/- 10). The other T-cell subsets in the epidermis and dermis showed no statistically significant differences between psoriasis and atopic dermatitis. In contrast to the limited presence of CD4+, CD8+ and CD2+ in the psoriatic dermis (110 +/- 19, 27 +/- 9, 127 +/- 41, cells mm(-1), respectively), more impressive numbers of these cells were observed in the dermis of lichen planus (300 +/- 53, 144 +/- 38, 272 +/- 48, respectively). CD45RO+ memory effector T-cell counts were significantly higher in the epidermis of lichen planus (39 +/- 10) than in psoriasis (19 +/- 5). Psoriatic epidermis proved to have major keratinocyte hyperproliferation (247 +/- 26 cells mm(-1) lamina basalis), as compared with atopic dermatitis (134 +/- 15) and lichen planus (128 +/- 20). Furthermore, a marked decreased expression of keratin 10 was observed in psoriasis (41% of epidermal area) contrary to atopic dermatitis (70%). CONCLUSIONS: Psoriatic epidermis exhibits a pronounced CD8+ epidermotropism with accompanying epidermal hyperproliferation and abnormal keratinization, which changes are only minimally expressed in atopic dermatitis and lichen planus. In plaque psoriasis, substantially fewer activated CD4+ and CD8+ T cells in the dermis and less CD45RO+ T cells in the epidermis are present in comparison with lichen ruber planus.     

CD56 highCD16 - NK cell involvement in cutaneous lichen planus

Lichen planus is an inflammatory disease of the skin and mucous membranes characterized by vacuolization of basal keratinocytes associated with a prominent junctional lymphocyte infiltrate which comprises T?lymphocytes, NK cells, myeloid and plasmacytoid dendritic cells. Basal keratinocyte damage is considered as being a consequence of a lymphocytic cytotoxic attack, mostly mediated by perforin+CD8+ T?lymphocytes. NK cells have been described to infiltrate inflamed skin and significantly contribute to the amplification of immune-mediated skin diseases, thanks to their cytotoxic activity and the release of pro-inflammatory cytokines. Here, we investigated the characteristics and functional properties of NK lymphocytes involved in lichen planus. Double staining immunohistochemistry showed a considerable number (6.42 ± 2.2% of the total cellular infiltrate) of CD3-CD56+ cells in early lichen planus lesions, mostly distributed in the papillary dermis and at the epidermal-dermal interface. Skin NK cells isolated from lichen planus lesions belong to the CD56highCD16- subset, are highly positive for perforin and natural cytotoxic receptors NKG2D and NKp44, and, in accordance with their phenotype, are negative for KIRs receptors CD158a and CD158b. Skin CD56highCD16- NK cells display a CCR6+CXCR3+CCR5+ChemR23+ chemokine receptor asset for homing into inflamed skin. In terms of cytokine release, skin CD56highCD16- NK cells are able to secrete IFN-γ, TNF-α and hardly release IL-22, IL-17 and IL-4. Overall, our data propose a pro-inflammatory role of NK lymphocytes in lichen planus.     

Proliferative activity of CD8(+) T cells as an important clue to analyze T cell-mediated inflammatory dermatoses

Abstract To elucidate the pathogenesis of T cell-mediated inflammatory skin diseases, we examined the exact sites where CD8(+) T cells proliferate, correlating them with the localization of antigen-presenting dendritic cells. We performed CD8/Ki-67 double immunohistochemical staining and single staining for CD1a, CD68, and factor XIIIa on sections of paraffin-embedded tissue samples of inflammatory dermatoses in which T lymphocytes are thought to play a crucial role. The dermatoses were lichen planus (12 samples), acute graft-versus host disease (GVHD) (12 samples), chronic GVHD (10 samples), spongiotic dermatitis (8 samples) and psoriasis (7 samples). Labelling for Ki-67 among CD8(+) T cells was predominantly observed in the subepidermal lymphoid infiltrate, and was scanty in the epidermis. This suggested that proliferation of CD8(+) T cells occurred preferentially in the dermis. The labelling index for Ki-67 among dermal and epidermal CD8(+) cells was quite different among the different diseases studied (P < 0.05). They were rich in the subepidermal portion of the dermis of spongiotic dermatitis, acute GVHD and chronic GVHD, but rare in the dermis of psoriasis and lichen planus. A moderate infiltrate was also observed in lesional epidermis of spongiotic dermatitis, acute GVHD and chronic GVHD, whereas they was almost none in the epidermis of psoriasis and lichen planus. CD1a(+) dermal dendritic cells were densely distributed within the lymphoid infiltrate in the affected dermis of spongiotic dermatitis, psoriasis and lichen planus, whereas they were minimal in GVHD. These dermal dendritic cells are candidates as stimulators on T cells in the dermis. In conclusion, the proliferative status of T cells could be an important clue in the elucidation of the pathophysiology of T cell-mediated inflammatory dermatoses. Received: 13 December 2000 / Revised: 24 April 2001 / Accepted: 11 July 2001     

Lichen sclerosus et atrophicus, morphea, and coexistence of both diseases. Histological studies using lectins.

Histological studies using three lectins, lens culinaris agglutinin, soybean agglutinin, and Ulex europaeus agglutinin-I, were carried out in a case of coexistent lichen sclerosus et atrophicus and morphea, five cases of morphea, and two cases of lichen sclerosus et atrophicus. The lectin staining patterns of the formaldehyde-fixed epidermis of patients with morphea were not different from those of normal epidermis, but epidermis of patients with lichen sclerosus et atrophicus showed different staining patterns. Lens culinaris agglutinin stained the basal and the spinous layers of the normal epidermis and that of patients with morphea but stained only the basal cells of the epidermis from patients with lichen sclerosus et atrophicus; epidermal Ulex europaeus agglutinin binding was observed only in the cases of lichen sclerosus et atrophicus. Moreover, in the patient with coexistent diseases, the morphea lesion showed the staining profiles of morphea and the lichen sclerosus et atrophicus lesion showed the staining patterns of lichen sclerosus et atrophicus, respectively.     

Nodular Clear Cell Hidradenoma: A Case Report with Immunohistochemistry, Cytogenetics and Flow Cytometry

CD44 is the cell surface receptor for hyaluronate (HA). We demonstrated that the lack of CD44 expression in murine keratinocytes leads to an abnormal HA accumulation in the dermis, indicating an important role of CD44 in local HA metabolism in mouse skin. We also observed a decrease in the expression of epidermal CD44 in patients of lichen sclerosus et atrophicus which is potentially responsable for the dermal deposition of HA. We also showed that HA accumulation was associated with decreased expression of CD44 in epithelial proliferations in perifollicular solitary cutaneous myxoma. In this study we examined the follicular expression of CD44 and HA in the skin biopsy specimens of seven patients with follicular mucinosis by using CD44‐specific antibodies and biotinylated HA‐binding protein (HABP), respectively. No difference of CD44 expression was observed in the follicular keratinocytes when compared with those of unaffected interfollicular epidermis. The follicular zones of mucin deposition were strongly positive for HA. A weak interkeratinocyte staining pattern for HA was also observed in the interfollicular epidermis. However, HABP staining revealed a stronger reactivity in the follicular keratinocytes surrounding the mucin‐accumulated areas compared to the interfollicular keratinocytes, indicating an active secretion of HA by follicle cells in follicular mucinosis.     

Histology of lichen sclerosus varies according to site and proximity to carcinoma.

To investigate why vulvar but not extragenital lichen sclerosus is associated with squamous cell carcinoma, we performed a histologic study of extragenital lichen sclerosus, vulvar lichen sclerosus without carcinoma, and vulvar lichen sclerosus with carcinoma adjacent to and distant from the carcinoma. We compared epidermal thickness, rete ridge length, mitotic activity, atypia, dermal collagen change, dermal inflammation, and presence of other dermatoses in 30 women in each group. Extragenital lichen sclerosus showed thinner epidermis (mean thickness of 0.13 mm versus 0.41 mm; P < 0.0005), shorter rete ridges (P = 0.0001), more dermal edema (P = 0.16), and absence of associated dermatoses of spongiotic dermatitis and lichen planus (P < 0.005) compared with vulvar lichen sclerosus. The epidermal thickening seen in vulvar lichen sclerosus was indistinguishable from lichen simplex chronicus. Vulvar lichen sclerosus without carcinoma was generally similar to that distant from carcinoma. Vulvar lichen sclerosus adjacent to carcinoma showed increased epidermal thickness (0.61 mm versus 0.26 mm; P < 0.005), more dermal fibrosis (P < 0.0005), more inflammation (P < 0.0005), and more simplex (differentiated) vulvar intraepithelial neoplasia (18 cases versus 1 case; P < 0.0005) compared with that distant from carcinoma. We concluded that (1) the classic histologic features of lichen sclerosus are seen in both vulvar and extragenital sites; (2) vulvar lichen sclerosus without associated carcinoma has a mean epidermal thickness more than three times that of extragenital lichen sclerosus; (3) the epidermal thickening is histologically indistinguishable from lichen simplex chronicus; (4) there is a tendency for vulvar lichen sclerosus to have a more sclerotic and inflamed dermis; (5) lichen sclerosus 10 mm from cancer is more similar to vulvar lichen sclerosus without carcinoma than lichen sclerosus 1 mm from carcinoma; and (6) lichen sclerosus adjacent to carcinoma tends to show exaggerated epidermis thickness, basal atypia, and loss of the edematous-hyaline layer.