The spectrum of histopathologic patterns secondary to the topical application of EMLA® on vulvar epithelium: clinicopathological correlation in three cases.

EMLA(®) (eutectic mixture of local anesthetics, 2.5% each of lidocaine and prilocaine in an oil and water emulsion) is used as a topical anesthetic. We report three cases of EMLA(®) -induced histopathologic changes on the vulvar epithelium. While there are some similar histopathologic features to those reported in extragenital skin, we describe additional findings on vulvar epithelium, which, to our knowledge, have not been reported previously. The patients presented with clinical signs suggestive of lichen sclerosus or erosive lichen planus (LP), but were all confirmed histopathologically as LP. The biopsy was taken after 15 min of EMLA(®) application and intradermal injection of 1% lidocaine. Blistering prior to intradermal lidocaine and the biopsy procedure was observed in two patients. The histopathologic changes observed in the epithelium included pallor of the upper epidermis, mild spongiosis, intraepidermal subcorneal and suprabasal acantholysis, congestion of the papillary dermal capillaries and extravasated erythrocytes. Basophilic granules were present, but rare, while the necrosis with multifocal clefting was more marked than in extragenital skin. It is important to be aware of these changes occurring on genital mucosa; these may occur in the absence of clinical signs and may obscure the primary underlying pathology, thus representing a diagnostic pitfall.

Management of symptomatic esophageal involvement with lichen planus.

AIM: To describe the clinical features and treatment schedules of a series of 5 patients with esophageal lichen planus (LP). To review the literature on esophageal LP. BACKGROUND: LP, a common papulosquamous dermatologic condition, can present to the gastroenterologist with esophageal involvement. This is rare and occurs in a distinct population of LP patients. Disease at this site is frequently refractory to conventional treatment. CASE SERIES: Between 2001 to 2007, 5 female patients were diagnosed with esophageal LP. They all had esophageal strictures which were treated with a combination of balloon dilatation and intralesional triamcinolone. Therapeutic intervention was covered with oral steroids before and after the procedure. Symptoms tended to recur, necessitating repeat procedures. The average interval between treatments was 8.3 months. CONCLUSIONS: Intralesional triamcinolone and balloon dilatation produced good symptomatic relief in these 5 patients with esophageal LP. This was generally maintained for several months. We reviewed 35 cases of symptomatic esophageal LP in the English literature. Esophageal LP seems to have a striking predilection for middle-aged women, particularly those with disease at other mucosal sites. A range of systemic immunosuppressants and esophageal-directed therapies has been tried.

Vulvar cancer and the need for awareness of precursor lesions.

Vulvar cancer continues to rise in incidence. In the absence of screening, attempts to reduce this cancer must focus on recognizing precursor lesions, namely, lichen sclerosus and vulvar intraepithelial neoplasia (VIN). The steep rise in human papillomavirus-repeated VIN will fall after the introduction of vaccination against human papillomavirus; in the meantime, those patients with VIN must be treated and then reviewed carefully and frequently. Lichen sclerosus has a 3% to 5% risk of progressing to vulvar cancer. Recommendations about which patients require referral to and follow-up by specialists/specialist clinics are given.

Guidelines for the follow-up of women with vulvar lichen sclerosus in specialist clinics.

It is recommended that women with vulvar lichen sclerosus be followed in specialist clinics where difficulty exists with symptom control or where there is clinical evidence of localized skin thickening. Follow-up is also recommended for women who have previously been treated for squamous cell carcinoma of the vulva (arising in lichen sclerosus or vulvar intraepithelial neoplasia) or where the pathologist expresses concern and is unable to make a definitive diagnosis of differentiated vulvar intraepithelial neoplasia.

Development of antigen-specific ELISA for circulating autoantibodies to extracellular matrix protein 1 in lichen sclerosus.

Lichen sclerosus is a common, acquired chronic inflammatory skin disease of unknown etiology, although circulating autoantibodies to the glycoprotein extracellular matrix protein 1 (ECM1) have been detected in most patients' sera. We have examined the nature of ECM1 epitopes in lichen sclerosus sera, developed an ELISA system for serologic diagnosis, and assessed clinicopathological correlation between ELISA titer and disease. Epitope-mapping studies revealed that lichen sclerosus sera most frequently recognized the distal second tandem repeat domain and carboxyl-terminus of ECM1. We analyzed serum autoantibody reactivity against this immunodominant epitope in 413 individuals (95 subjects with lichen sclerosus, 161 normal control subjects, and 157 subjects with other autoimmune basement membrane or sclerosing diseases). The ELISA assay was highly sensitive; 76 of 95 lichen sclerosus patients (80.0%) exhibited IgG reactivity. It was also highly specific (93.7%) in discriminating between lichen sclerosus and other disease/control sera. Higher anti-ECM1 titers also correlated with more longstanding and refractory disease and cases complicated by squamous cell carcinoma. Furthermore, passive transfer of affinity-purified patient IgG reproduced some histologic and immunopathologic features of lichen sclerosus skin. This new ELISA is valuable for the accurate detection and quantification of anti-ECM1 autoantibodies. Moreover, the values may have clinical significance in patients with lichen sclerosus.

The vulvovaginal gingival syndrome: a severe subgroup of lichen planus with characteristic clinical features and a novel association with the class II HLA DQB1*0201 allele.

BACKGROUND: The vulvovaginal gingival syndrome is an uncommon and severe variant of lichen planus characterized by erosions or desquamation of vulval, vaginal, and gingival mucosae with a predilection for scarring and stricture formation. OBJECTIVE: We sought to define the clinical, immunopathologic, and human leukocyte antigen findings in a large cohort of patients. METHODS: The clinical presentation and outcome during long-term follow-up were documented in 40 patients. In addition, human leukocyte antigen typing for class II by polymerase chain reaction and sequence-specific primers was performed. RESULTS: During a mean follow-up period of 8.7 (SD +/- 6.8) years, long-term sequelae included strictures of the esophagus, lachrymal ducts, and external auditory canal; loss of vulval architecture; vaginal stenosis; and buccal mucosal fibrosis. The DQB1( *)0201 allele was present in 80% of patients versus 41.8% of control subjects (P

Autoantibodies to extracellular matrix protein 1 in lichen sclerosus.

BACKGROUND: Lichen sclerosus is a common acquired inflammatory disorder of skin and mucous membranes. The aetiology is unknown, although HLA-subtype susceptibility and high rates of other autoimmune disorders suggest that autoantibodies to specific mucocutaneous antigens are involved. The clinicopathological similarities between lichen sclerosus and lipoid proteinosis, which results from mutations in extracellular matrix protein 1 (ECM1), suggest this protein as an autoantigen. METHODS: We analysed serum autoantibody profiles in 171 individuals (86 with lichen sclerosus, 85 healthy controls) by immunoblotting of extracts from normal human skin and lipoid proteinosis skin (lacking ECM1). We generated a full-length glutathione-S-transferase fusion protein for ECM1 to confirm specific immunoreactivity. We affinity-purified serum from patients with lichen sclerosus and did indirect immunofluorescence microscopy on normal skin with or without preabsorption with recombinant ECM1. FINDINGS: By immunoblotting, IgG autoantibodies were found in 20 (67% [95% CI 45-84]) of 30 lichen sclerosus serum samples. The highest titre was 1 in 20. The bands were not detected in ECM1-deficient substrate. These samples, and those from 56 other patients with lichen sclerosus, showed immunoreactivity to the recombinant ECM1 protein (64 of 86 positive; 74% [65-84]). Only six (7% [2-13]) of 85 control serum samples were positive. Affinity-purified IgG from serum of patients with lichen sclerosus labelled skin similarly to a polyclonal antibody to ECM1. The positive staining was blocked by preabsorption with excess recombinant ECM1 protein. INTERPRETATION: These findings provide evidence for a specific humoral immune response to ECM1 in lichen sclerosus and offer insight into disease diagnosis, monitoring, and approaches to treatment.

Squamous vulvar intraepithelial neoplasia: 2004 modified terminology, ISSVD Vulvar Oncology Subcommittee.

In the current classification, squamous vulvar intraepithelial neoplasia (VIN) is categorized as VIN 1, 2 and 3 according to the degree of abnormality. There is neither evidence that the VIN 1-3 morphologic spectrum reflects a biologic continuum nor that VIN 1 is a cancer precursor. The VIN 2 and 3 category includes 2 types of lesion, which differ in morphology, biology and clinical features. VIN, usual type (warty, basaloid and mixed), is HPV related in most cases. Invasive squamous carcinomas of warty or basaloid type is associated with VIN, usual type. VIN, differentiated type, is seen particularly in older women with lichen sclerosus and/or squamous cell hyperplasia in some cases. Neither VIN, differentiated type, nor associated keratinizing squamous cell carcinoma is HPV related. The term VIN should apply only to histologically high grade squamous lesions (former terms, VIN 2 and VIN 3 and differentiated VIN 3). The term VIN 1 will no longer be used. Two categories should describe squamous VIN: VIN, usual type (encompassing former VIN 2 and 3 of warty, basaloid and mixed types) and VIN, differentiated type (VIN 3, differentiated type).

Lacrimal canalicular duct scarring in patients with lichen planus.

BACKGROUND: Lichen planus (LP) is a mucocutaneous inflammatory disease that affects multiple sites, including the skin, oral cavity, vulva, and vagina and can result in scarring and stricture formation. It has also been shown to cause lacrimal canalicular blockage in a series of patients attending an ophthalmology clinic. We describe a cohort of women with vulvovaginal LP who also had signs of lacrimal canalicular scarring on examination. OBSERVATIONS: We report 9 cases of LP with scarring of the conjunctiva around the lacrimal ducts. Seven of 9 women had symptoms of epiphora, and in 2 women lacrimal canalicular scarring was an incidental finding. Seven of 9 cases were diagnosed by an ophthalmologist. All women had biopsy-proven LP at 1 mucocutaneous site each. Seven of 9 women had vulvovaginalgingival syndrome, which is a subgroup of severe erosive LP. CONCLUSIONS: Given the strong association between erosive mucocutaneous LP and multisite scarring sequelae, it is not unexpected that ocular inflammation may lead to lacrimal duct stenosis. We believe that this complication has been underreported among patients with LP and that an ophthalmological history and examination of the punctum of the lacrimal duct should be sought, especially in patients with the erosive subtype of LP.

Physiological changes associated with the menstrual cycle: a review.

The cyclic hormonal changes that regulate the menstrual cycle are a significant biological influence on the female body, one with both physical and emotional ramifications. Menstruation is governed by tightly orchestrated changes in the levels of ovarian estrogen and progesterone, which produce varying responses in diverse tissues and organs. The skin, the largest organ in the body, is replete with estrogen receptors (in both dermis and epidermis) and to a lesser extent, progesterone receptors. Cyclically fluctuating levels of estrogen and progesterone influence numerous characteristics of the epidermis, including skin surface lipid secretion and sebum production, skin thickness, fat deposition, skin hydration, and barrier function. Dermal collagen content, which contributes to skin elasticity and resistance to wrinkling, is also influenced. Interestingly, estrogen levels also influence skin pigmentation and UV susceptibility, as well as resident microflora. In addition, changing hormone levels across the menstrual cycle produce measurable variations in immune function and disease susceptibility. An understanding of the profound influence that fluctuating estrogen and progesterone levels have on the biological responses of the premenopausal adult woman is critical to optimizing the efficacy of medical therapies in this population.

CO(2) laser therapy of vulval lymphangiectasia and lymphangioma circumscriptum.

BACKGROUND: Lymphangiectasia is a disorder of superficial lymphatics resulting from obstruction of previously normal deep lymphatics, while lymphangioma circumscriptum describes a deep dermal and subcutaneous lymphatic malformation with secondary superficial ectatic changes. Previous case reports have suggested the effectiveness of CO2 laser treatment. OBJECTIVE: To assess CO2 laser therapy for vulval involvement by these lymphatic disorders. METHODS: A retrospective case review at St. John's Institute of Dermatology from 1996 to 1999 identified three women with vulval lymphangiectasia and two with vulval lymphangioma circumscriptum treated with the CO2 laser. RESULTS: Patient tolerance of the procedure was good. Healing was complete within 1 month and occurred without change in skin texture. All patients reported considerable improvement in symptoms (mean follow-up 22 months, median 24 months, range 10-33 months). Focal recurrence and an area of localized persistence were noted in the two patients with lymphangioma circumscriptum. CONCLUSION: CO2 laser therapy of vulval lymphangiectasia and lymphangioma circumscription is effective and well-tolerated; the latter may possibly be more resistant to treatment than the former.