Extragenital Lichen Sclerosus Research Articles

Pulsed High-Dose Corticosteroids Combined With Low-Dose Methotrexate Treatment in Patients With Refractory Generalized Extragenital Lichen Sclerosus

Lichen sclerosus (LS) is a rare, chronic inflammatory skin disease that predominantly affects the anogenital area. A few patients exhibit widespread extragenital disease that may lead to blister formation and superficial erosions. We evaluated the efficacy of pulsed high-dose corticosteroids combined with low-dose methotrexate treatment in patients with refractory generalized LS that had failed to respond to standard topical corticosteroid therapy. Observation Seven patients were included in this retrospective study, all of whom were treated with pulsed high-dose corticosteroids combined with low-dose methotrexate for at least 6 months. The outcome measure was an individual, nonvalidated clinical score. Overall, a significant decrease in the clinical score was observed, from a median score of 8 (range, 5 to 24) before treatment to 2 (range, 1 to 4) after treatment. Adverse effects observed during therapy were moderate and disappeared after the end of treatment. During the follow-up period of at least 3 months (mean, 4.7 [range, 3-8] months), none of the patients experienced a relapse of extragenital LS. Patients with severe extragenital LS benefit from pulsed high-dose corticosteroids combined with low-dose methotrexate therapy. This combination therapy should be considered in generalized disease, especially disease that is refractory to conventional treatment.

Angiokeratoma‐like changes in extragenital and genital lichen sclerosus

Hemorrhagic blisters have rarely been described developing in the background of either genital or extragenital lichen sclerosus and have invariably been designated clinically as telangiectatic, hemorrhagic or bullous lichen sclerosus. We describe three patients with extragenital and genital lichen sclerosus, who presented clinically with hemorrhagic plaques and/or papules. In addition to the classical histology of lichen sclerosus, dilated, congested and focally thrombosed vascular channels lined by flat endothelium were seen within the sclerotic dermal collagen. They were in close proximity to and even in contact with the overlying epidermis and thus mimicked an angiokeratoma. Angiokeratoma-like changes in lichen sclerosus represent secondary features because of damage to the dermis by lichen sclerosus and are characterized histologically by ectatic thin-walled vascular spaces in the papillary dermis intimately associated with the epidermis. Increased venous pressure, local trauma, degenerative changes in the elastic tissue of the vessel wall and/or surrounding supportive tissue, as well as abnormalities in the extracellular protein network, appear to be implicated in their pathogenesis.

Comparative Treatment of Extragenital Lichen Sclerosus with Methylaminolevulinic Acid Pulsed Dye Laser-Mediated Photodynamic Therapy or Pulsed Dye Laser Alone

Lichen sclerosus (LS) is a chronic inflammatory disease. Lesions are characterized by ivorywhite atrophic plaques. The anogenital areas of prepubertal and postmenopausal women are usually involved. The extragenital form of lichen sclerosus is rare, and its course is usually asymptomatic. 1 Cutaneous lesions of lichen sclerosus are better tolerated than the erosive genital form, but they lead to unaesthetic lesions that are difficult to treat. Selective treatment with laser appears to be an attractive approach for localized forms of LS. Only one genital case and one cutaneous case of LS have been reported to be successfully treated with a pulsed dye laser (PDL). 2,3 More recently photodynamic therapy mediated by PDL (PDL-PDT) has been suggested to be effective in LS. 4

Extragenital Lichen Sclerosus and Atrophicus Treated with Topical Steroids and Retinoids in a Child with Vitiligo

Lichen sclerosus and atrophicus (LSA) most commonly affects the anogenital region. Extragenital involvement is rare, and women are reported to be affected 6 to 10 times more often than men. The aetiology of LSA is unclear, but genetic, physiological and environmental factors are thought to be involved. Several lines of evidence support the hypothesis of an autoimmune basis for LSA; an increased incidence of tissue-specific antibodies and an association with autoimmune disorders such as vitiligo, alopecia areata, thyroid disease and pernicious anaemia have been reported. We describe a paediatric patient with extragenital LSA associated with vitiligo who was successfully treated with topical steroids and retinoids.

Extragenital lichen sclerosus et atrophicus

A 76-year-old woman with a history of eczematous dermatitis presented with a 9-month history of a pruritic, eczematous eruption of the trunk. This eruption responded to topical glucocorticoids but recurred on discontinuation of treatment on multiple occasions. A biopsy specimen showed extragenital lichen sclerosus et atrophicus. The diagnosis of extragenital lichen sclerosus is reviewed with a comparison to classic lichen sclerosus in terms of clinical features, histopathologic characteristics, and treatment approaches.

Significant Improvement in Extensive Lichen Sclerosus with Tacrolimus Ointment and PUVA

Lichen sclerosus is an uncommon, chronic inflammatory skin disorder of unknown origin. It is clinically characterized by sclerotic, whitish, atrophic-type lesions. The most frequent site of the lesions is generally the genital region, with about 15-20% having additional extragenital involvement. We present the case of a 62-year-old woman with a very extensive extragenital lichen sclerosus who showed great clinical and subjective improvement with 0.1% tacrolimus ointment and psoralen plus UVA (PUVA), without any topical or systemic adverse effects. Combined treatment of 0.1% tacrolimus ointment and PUVA may be a good option in extensive cases of lichen sclerosus or when other treatment options have failed, and has a good tolerability and safety profile.

Extragenital lichen sclerosus of childhood presenting as erythematous patches

Extragenital lichen sclerosus of childhood presenting as erythematous patches

Case of sequentially occurring lesions of facial lichen sclerosus following the lines of Blaschko

Extragenital lichen sclerosus (LS) is usually asymptomatic and appears as ivory- or porcelain-white macules, papules and plaques. It is most common on the neck, shoulders and upper portion of the trunk. To date, the linear form of extragenital LS corresponding to the lines of Blaschko on the trunk or limbs has been rarely reported. We describe a 25-year-old Korean woman with sequentially occurring lesions of extragenital LS confined to the face following the lines of Blaschko.

Progressive Extragenital Lichen Sclerosus Successfully Treated With Narrowband UV-B Phototherapy

A 76-year-old woman with hypertension and hepatitis C presented with a 10-year history of sclerotic, atrophic, ivory-white plaques with violaceous borders on the upper part of her trunk and on her arms, waistline, and anogenital areas (Figure 1). The plaques were gradually extending and becoming more pruritic. A biopsy revealed findings diagnostic of lichen sclerosus (LS), including an atrophic epidermis, homogenized upper dermis, and sparse chronic inflammation in the middle dermis, below the homogenized collagen. The patient experienced a modest response to topical tacrolimus therapy, followed by more substantial improvement with topical clobetasol propionate therapy. However, several months later, she returned with worsening pruritus and enlargement of the plaques on her neck, waist, and arms. The anogenital lesions were stable. A trial of calcipotriene ointment applied to the midchest region did not produce any appreciable benefit.

Cytokine alterations in lichen sclerosus: an immunohistochemical study

Although the histology of lichen sclerosus is characteristic, the precise nature of the inflammatory changes and the signals provoking them is uncertain. To delineate the inflammatory changes in lichen sclerosus more accurately by studying cytokine changes. 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. 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. 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.

UVA1 phototherapy for genital lichen sclerosus

Lichen sclerosus (LS) is characterized histologically by an inflammatory T-cell infiltrate, sclerosis and thickening of the dermis, and epidermal atrophy. Ultraviolet (UV) A1 therapy has been shown to be effective in the management of morphea and scleroderma, diseases that have some histological and clinical similarities with LS, and more recently in extragenital LS. To determine the effectiveness of UVA1 therapy for genital LS. Seven women with severe genital LS uncontrolled by ultrapotent topical corticosteroids, with a median age of 62 years (range 48-78) and disease duration of 6-47 years, were treated with UVA1 therapy from a high output source. After completion of UVA1 therapy, a clinician and the patient graded the overall response of symptoms and physical signs. Five patients improved with therapy. Three obtained moderate improvement in overall disease severity and two had minimal improvement. Of these five, one relapsed within 3 months and another after a year. Both had a further course of UVA1 therapy, resulting in minimal improvement in one and moderate improvement in the other. In the remaining three, disease severity had improved to a point where intermittent use of topical corticosteroids resulted in acceptable control. UVA1 therapy may be of benefit in the management of vulval LS, a disease that is often poorly responsive to standard therapies. The therapy is well tolerated and could provide an acceptable therapeutic option for patients with severe disease.

Alterations of Basement Membrane Zone and Cutaneous Microvasculature in Morphea and Extragenital Lichen Sclerosus

The aim of this study was to compare alterations of the basement membrane zone (BMZ) and to visualize changes within the skin vascular network in morphea and extragenital lichen sclerosus with the use of laser scanning confocal microscopy. This work was performed in eight plaques of morphea (three active and five inactive) and eight of lichen sclerosus (three of short duration and five long-lasting). Biopsy specimens from six healthy individuals served as controls. The biopsies were cut into 40-microm-thick sections, labeled with antibodies against beta4-intergin (a lamina lucida marker), collagen IV, and the N-terminal end of collagen VII (lamina densa markers) and C-terminal end of collagen VII (a sublamina densa marker) and studied using laser scanning confocal microscopy. Three-dimensional reconstruction of various regions of the BMZ showed a decreased number and size of the dermal papillae both in morphea and lichen sclerosus compared with normal skin. In morphea, the continuity of the BMZ at the level of lamina lucida, lamina densa, and sublamina densa was preserved whereas in LS numerous invaginations and holes were present in the BMZ at the level of the lamina lucida and lamina densa. Thus the alterations of the BMZ in morphea differ from those in lichen sclerosus. Three-dimensional reconstruction of the skin vascular network showed increased angiogenesis only in the early inflammatory stage of morphea, whereas in inactive morphea and lichen sclerosus various numbers of enlarged vessels were visible. The changes in the vascular network in morphea appear to be related to the activity of the disease.

Unsuccessful Treatment of Extragenital Lichen Sclerosus with Topical 1% Pimecrolimus Cream

Lichen sclerosus most commonly affects the anogenital region. Spreading into the extragenital regions is rare, and its course is most commonly asymptomatic. Women have been reported to be affected 6 to 10 times more often than men. The etiology of lichen sclerosus is still unknown. The disease is characterized by ivory-white atrophic plaques, and no treatment ensuring complete recovery is available. T-cells are also involved in its pathogenesis. Pimecrolimus is a topical inhibitor of T-cells. In the present paper, we present a male patient with lichen sclerosus located only in extragenital regions and report an unsuccessful outcome of treatment with pimecrolimus 1% cream administered topically twice a day for 16 weeks.

UVA/UVA1 phototherapy and PUVA photochemotherapy in connective tissue diseases and related disorders: a research based review.

BackgroundBroad-band UVA, long-wave UVA1 and PUVA treatment have been described as an alternative/adjunct therapeutic option in a number of inflammatory and malignant skin diseases. Nevertheless, controlled studies investigating the efficacy of UVA irradiation in connective tissue diseases and related disorders are rare.MethodsSearching the PubMed database the current article systematically reviews established and innovative therapeutic approaches of broad-band UVA irradiation, UVA1 phototherapy and PUVA photochemotherapy in a variety of different connective tissue disorders.ResultsPotential pathways include immunomodulation of inflammation, induction of collagenases and initiation of apoptosis. Even though holding the risk of carcinogenesis, photoaging or UV-induced exacerbation, UVA phototherapy seems to exhibit a tolerable risk/benefit ratio at least in systemic sclerosis, localized scleroderma, extragenital lichen sclerosus et atrophicus, sclerodermoid graft-versus-host disease, lupus erythematosus and a number of sclerotic rarities.ConclusionsBased on the data retrieved from the literature, therapeutic UVA exposure seems to be effective in connective tissue diseases and related disorders. However, more controlled investigations are needed in order to establish a clear-cut catalogue of indications.

Alterations of basement membrane zone in bullous and non-bullous variants of extragenital lichen sclerosus.

The aim of the study was to compare alterations of various regions of the basement membrane zone (BMZ) in lichen sclerosus (LS) using laser scanning confocal microscopy. The study included three cases of bullous LS, one case of bullous LS that developed in the course of graft-versus-host disease (GVHD), and six cases of non-bullous LS. Three cases of morphea served as a control. Biopsies from patients' skin and control biopsies from normal human skin were cut into 30-microm thick slides and labeled with antibodies against beta4-intergin (lamina lucida marker), collagen IV, and the N-terminal end of collagen VII (lamina densa markers) and the C-terminal end of collagen VII (sublamina densa marker) using routine immunofluorescence (IF). Three-dimensional (3D) reconstruction of various regions of the BMZ showed a decrease in the number and size of the dermal papillae in LS and morphea as compared with normal skin. In LS numerous invaginations and holes were present in the BMZ at the level of the lamina lucida and lamina densa. Computer animation of 3D projections revealed that the thickness of the lamina densa observed under the light microscopy is an optical artifact dependent on periodical tortion of the lamina densa along its axis. Torsions and invaginations of the BMZ are equally responsible for the phenomenon of artificial reduplication of the lamina densa observed at the ultrastructural level. IF labeling with antibody against the N-terminal end of collagen VII disclosed the presence of a large hole (up to 25 microm) in the lamina densa and the presence of granular material in deep dermis suggestive of partial degradation of lamina densa at the level of anchoring fibers. An IF mapping study showed blister formation below the lamina densa in three patients with bullous LS, whereas in a case of LS associated with GVHD, a blister formed through the basal layer of the epidermis. In morphea, there was flattening of BMZ at the level of lamina lucida, lamina densa, and sublamina densa but the continuity of BMZ was preserved. Three-dimensional reconstruction of dermal-epidermal junction in LS revealed alterations of the BMZ, most pronounced at the level of the lamina densa and sublamina densa.

Linear extragenital lichen sclerosus with underlying bony atrophy

We describe a 21-year-old male patient with linear extragenital lichen sclerosus. The lesions are confined to the left side of his body and consist of 3 long bands running along the left leg and several patchy and linear lesions on the left side of his trunk. An associated finding is a smaller diameter of the distal part of his left lower leg caused by bony atrophy of the underlying portion the tibia. This is the fifth reported case of linear lichen sclerosus.

Low-dose ultraviolet A1 phototherapy for extragenital lichen sclerosus: Results of a preliminary study

Background: Lichen sclerosus (LS) is a chronic inflammatory skin disease in which numerous therapies have been used, with only limited success. Because low-dose UVA1 phototherapy has been shown to be an effective treatment option for localized scleroderma, which shares several similar clinical and histologic features with LS, we initiated a clinical trial with this phototherapeutic modality in patients with LS. Methods: Ten patients suffering from extragenital LS were treated with low-dose UVA1 phototherapy 4 times weekly with single UVA1 doses of 20 J/cm2. Forty treatment sessions were performed within 10 weeks, resulting in a cumulative UVA1 dose of 800 J/cm2. Results: Low-dose UVA1 phototherapy resulted in a marked reduction of the clinical score and a significant (P < .05) decrease of ultrasonographically measured skin thickness as well as a highly significant (P < .001) increase of dermal density. The patients reported a remarkable softening and repigmentation of the affected skin. Conclusion: Analogous to the treatment results in localized scleroderma, low-dose UVA1 phototherapy seems to be an effective and well-tolerated treatment option for extragenital LS. (J Am Acad Dermatol 2002;46:251-5.)

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.

A case of extragenital lichen sclerosus following Blaschko's lines

<h2>Abstract</h2> Extragenital lichen sclerosus is most common on the neck, shoulders, and upper portion of the trunk. A 20-year-old Korean man had asymptomatic, well-demarcated, linear violaceous plaques on the left lateral chest, in a pattern corresponding to the lines of Blaschko. We describe a case with a pattern of extragenital lichen sclerosus following Blaschko's lines. (J Am Acad Dermatol 2000;43:903-4.)

A case of extragenital lichen sclerosus following Blaschko's lines

Extragenital lichen sclerosus is most common on the neck, shoulders, and upper portion of the trunk. A 20-year-old Korean man had asymptomatic, well-demarcated, linear violaceous plaques on the left lateral chest, in a pattern corresponding to the lines of Blaschko. We describe a case with a pattern of extragenital lichen sclerosus following Blaschko's lines. (J Am Acad Dermatol 2000;43:903-4.)