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.

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.

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.

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.