Crohn's disease of the vulva: A prospective study.

BACKGROUND AND AIMS: Vulval Crohn's disease (VCD) is a rare extra-intestinal cutaneous manifestation of Crohn's disease. VCD is often unrecognized and misdiagnosed and can be difficult to treat. The aim of the study was to describe the clinical presentation, associated features, and response to treatment modalities in patients with VCD. METHODS: A prospective review of patients with VCD who were referred to our specialist dermatology clinic from 2003 to 2017 was performed. Data on age at diagnosis, presenting signs, associated features, and response to treatment were collected. RESULTS: Thirty-one patients with a median age of 40 years (range 13-66 years) were identified. VCD manifested most frequently with vulval edema (77%), ulceration (35%), and fissures (39%). Eighty-one percent had active gastrointestinal disease. Oral involvement and pyoderma gangrenosum were present in 13% and 19%, respectively. Topical therapy was effective in mild VCD. Tumor necrosis factor-α inhibitors were the most effective second-line therapy, with 53% achieving complete clinical remission. Additionally, we have found compression garments and shorts to be useful adjuncts in treating vulval edema. CONCLUSIONS: Vulval Crohn's disease is a diagnostic and therapeutic challenge. We recommend consideration of tumor necrosis factor-α inhibitors at an early stage.

Vulvovaginal-gingival Lichen Planus: Association with Lichen Planopilaris and Stratified Epithelium-specific Antinuclear Antibodies.

Vulvovaginal-gingival lichen planus (VVG-LP) consists of a triad of symptoms: vulval, vaginal and gingival lichen planus lesions. The aim of this study was to analyse the prevalence of lesions in various anatomical locations in patients with VVG-LP. The study included 126 consecutive patients with lichen planus. Sixteen (12.7%) patients fulfilled the criteria of VVG-LP. In 12/16 (75%) patients with VVG-LP scalp lesions were also observed. Stratified epithelium-specific antinuclear antibodies (SES-ANA) and anti-ΔNp.3α antibodies were detected in 10/16 (75%) patients with VVG-LP and in 15/110 (13.6%) patients with other forms of lichen planus (p < 0.05). In conclusion, VVG-LP is frequently associated with lichen planopilaris. The new entity may be termed "vulvovaginal-gingival-pilar lichen planus" and our study indicates that SES-ANA is a marker of this type of lichen planus with extensive, severe and refractory-to-therapy involvement of the mucous membranes, skin and scalp.

Immunological activity of photodynamic therapy for genital warts.

BACKGROUND: An increasing body of evidence supports the usefulness of photodynamic therapy (PDT) in the treatment of non-neoplastic pathological conditions, including genital warts. In particular, PDT has demonstrated good clinical cure rates and low recurrence, and is now suggested as a safe alternative means of treating condylomata. OBJECTIVE: To confirm the suitability of aminolaevulinic acid (ALA)-PDT for the treatment of this condition and to investigate the recruitment and significance of immune cells in lesional areas by immunohistochemical analysis at different time intervals after treatment. METHODS: Fifteen subjects with histologically proven, recalcitrant condylomata acuminata of the penis, urethra, vulva or perianal area underwent several cycles of PDT following ALA application. Biopsies were taken at baseline and at different intervals during the trial, and infiltrating immune cells, CD3, CD4, CD8, CD1a and CD68, were evaluated by double immunocytochemical alkaline phosphatase antialkaline phosphatase (APAAP) staining. RESULTS: Our trial provided a complete cure rate of nine of 15 subjects after five PDT sessions. Perianal lesions showed a particularly rapid remission. While progressing towards total lesion clearance, the immunohistochemical pattern was dominated by dense CD4+ T lymphocytes infiltrating the superficial dermis, accompanied by an accumulation of Langerhans cells. Simultaneously, CD8 began to increase in the lesions of responding patients, and Langerhans cells seemed to migrate towards the dermis. CD68+ macrophages apparently did not participate in the immune inflammatory response. CONCLUSIONS: This study, to the best of our knowledge, represents the first attempt to clarify the effect of ALA-PDT on infiltrating immune cells in condylomata acuminata. Our results appear to confirm previously reported clinical data, suggesting that rapid activation of specific immunity in lesional skin, CD4+ T lymphocytes and dendritic cells could be responsible for healing.

Lipschütz genital ulceration associated with mumps.

Lipschütz ulcers are characterised by a first flare of non-sexually related acute genital ulcers (AGU) occurring in adolescent girls. Epstein-Barr primary infection is the most frequently reported aetiology but other infectious agents are probably implicated. We report the first case of mumps associated with an AGU in a 21-year-old girl. She presented a bilateral parotitis with genital ulcers, and serology confirmed she had mumps. As in our case, most Lipschütz ulcers heal spontaneously within a couple of weeks and the diagnosis should be reconsidered in case of recurrence.

Genital manifestation of graft-vs.-host disease: a series of case reports.

INTRODUCTION: After hematopoietic stem cell transplantation (HSCT), many patients present genital graft-vs.-host disease (GVHD) that can culminate with sexual problems, which are poorly dimensioned. AIM: We hope to draw attention to the need to perform genital biopsy to diagnose genital GVHD, and thus to call attention to the need to incorporate careful attention to sexual health in the treatment of these patients. METHODS: Five allogeneic stem cell transplant recipients complaining of coital pain after HSCT were clinically diagnosed for genital GVHD. Genital biopsies were given for histological analysis, and microphotographs of the corresponding marked field in the slide were taken. Specimens were evaluated by the site pathologist and then sent to a reference pathologist, each blinded to the histological findings. A literature search was performed in PubMed/MEDLINE (1966-2009) for cross-sectional and cohort studies or trials related to genital GVHD. Expert opinions peer reviews and case reports were also considered. MAIN OUTCOME MEASURES: HSCT, genital GVHD, genital biopsy. RESULTS: The biopsy showed evidence of dilated apoptotic cells in the basal layer and detachment of the epithelial lining of the mucosa, hyalinization and thickening of collagen fibers, capillary ectasia, and mononuclear inflammatory infiltrate of the submucosa. Three patients presented vulval lesion such as leucoplasia and ulcer on the large lip. Histological analyses showed evidence of epithelial hyperplasia and influx of inflammatory cells to the epithelial surface, intercellular edema and spongiosis, apoptotic bodies on the basal layer of the epithelium, spongiosis, and nuclear vacuolization. A common treatment based on corticotherapy resulted in complete remission of coetaneous or mucous genital lesions in all five patients. CONCLUSION: Genital biopsy is important to differentially diagnose GVHD and secondary symptoms due to hypoestrogenism. Prevention is the most important step in controlling the evolution GVHD in the vagina to prevent vaginal obstruction and sexual dysfunction.

The association of lichen sclerosus and erosive lichen planus of the vulva with autoimmune disease: a case-control study.

OBJECTIVE: To investigate the prevalence of autoimmune disease and circulating autoantibodies in women with lichen sclerosus (LS) and erosive lichen planus (LP) of the vulva and to compare these with a control population. DESIGN: Age- and sex-matched controlled study. SETTING: The vulval clinics in Oxfordshire, England, for patients with LS and LP. Healthy controls were recruited from the hospital and community. PATIENTS: A total of 190 women with the typical features of adult-onset LS of the vulva, 126 women with adult-onset erosive LP of the vulva, and 922 female controls (of whom 230 were examined). INTERVENTIONS: Personal history of autoimmune disorder for patients and controls, family history of autoimmune disorder for vulval LS and LP cohorts, and an autoantibody screen. MAIN OUTCOME MEASURES: The presence or absence of a personal or family history of autoimmune disorder, and the presence or absence of 1 or more circulating autoantibodies. RESULTS: The mean ages of patients with LS, patients with erosive LP, and control patients were 63, 61, and 61 years, respectively. The mean age of the 230 controls examined (including those who had serum autoantibodies assayed) was 62 years. Autoimmune disorders were more frequent in patients with erosive LP compared with controls (29% vs 9%; P < .001) and in those with LS compared with controls (28% vs 9%; P < .001). Circulating autoantibodies were more frequent in those with erosive LP compared with controls (41% vs 20%; P < .001). Conclusion This study demonstrates an association of autoimmune disorder and autoantibodies with erosive LP of the vulva and confirms the autoimmune associations of vulval LS.

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

Treatment of vulval Crohn's disease with infliximab.

Anti-tumour necrosis factor-alpha therapy of Crohn's disease (CD) with infliximab has proved a major advance in the treatment of patients with difficult disease. We report our experience of the use of infliximab in a patient with recalcitrant vulval CD. The introduction of infliximab has improved disease control, although a search for an optimum remittive dosing schedule is ongoing.

Cutaneous hypersensitivity to Candida albicans in idiopathic vulvodynia.

We have observed that the majority of our vulvodynia patients give a previous history of vaginal candidiasis that was treated but was followed by symptoms of chronic vulvodynia. 27 vulvodynia patients were patch-tested to a standard series of contact allergens, a customized vulvar series and commensal organisms including ultraviolet-killed Candida albicans. Comparison tests for the commensal organism were made to a group of 13 female atopic dermatitis patients and to 19 female dermatitis patients without a history of childhood flexural dermatitis who were undergoing patch test evaluation in our clinic. Patients reporting vulvodynia were significantly (P < 0.05) more likely to react to C. albicans than the dermatitis comparison group. Interestingly, lower concentrations of C. albicans caused more positive patch tests than higher concentrations. Our findings suggest that previous C. albicans infection may predispose patients to a subsequent hypersensitivity response to C. albicans that is expressed only in areas of high cutaneous peripheral fibre density. Low levels of C. albicans may also be required to elicit this response as high levels of C. albicans may actually result in decreased cutaneous inflammation and decreased intensity of C. albicans patch test responses.

Erosive lichen planus of the vulva: weak circulating basement membrane zone antibodies are present.

The objective of this study was to investigate whether circulating basement membrane zone (BMZ) antibodies are present in erosive lichen planus (LP) of the vulva. In total, 56 consecutive women with biopsy-confirmed erosive LP of the vulva were recruited from a vulval clinic in a district general hospital and teaching hospital in Oxfordshire. Indirect immunofluorescence (IgG and IgA) was performed on 56 sera, and 15 were tested to IgG subclasses (1-4). Immunoblotting was carried out on salt-split and urea-extracted epidermal skin extracts on 11. The main outcome measure was the presence or absence of staining at the BMZ. Of the 56 sera, 34 (61%) had weak (neat or 1 : 5) epidermal-binding BMZ antibodies (25 had IgG, 5 had IgA, 4 had both IgG and IgA). All 15 sera tested to IgG showed epidermal binding to one or more IgG subclasses: IgG1 (7 sera), IgG2 (7), IgG3 (7) and IgG4 (0). Immunoblotting identified IgG antibodies to bullous pemphigoid (BP)180 (10/11) and BP230 (2/11). The majority (61%) of patients with vulval erosive LP had circulating serum IgG BMZ antibodies, chiefly reacting with BP180. There was subclass restriction of the IgG response to IgG1, 2 and 3. The significance of these antibodies is uncertain, but they may be a marker for the disease.

Lack of specific immunological disease pattern in vulvar lichen sclerosus.

The literature suggests that autoantibody formations and disturbances in cellular or humoral immunities are relevant immunological events in lichen sclerosus (LS). We examined 39 patients (age range: 7-81 years) enrolled in this experimental immunopathology study and treated for vulvar LS. In the serum, we used 88 clinical immunology parameters to evaluate the immunological patterns, i.e., autoimmune phenomena, humoral immunity, cellular immunity, and inflammation. The analyses permitted direct comparison of the measured distributions of alternative data. We found that all pathological findings of single immunological events followed a random distribution without any positive or negative trend or a distribution with a negative trend. There was a lack of correlation between the majority of cases and the presence of pathological findings (confidence intervals 0.950 and 0.999). Combinations of two or more of the four patterns did not improve the outcomes (confidence intervals 0.950 and 0.999). However, abnormalities in systemic immune parameters implying system impairments might have occurred long before the patients with such a chronic disease presented to the clinic. This may be especially true of such diseases as vulvar LS, where local skin scarring might represent a local tissue response secondary to an initial insult by immune or other processes.

Vulvar susceptibility to contact irritants and allergens: a review.

Vulvar tissue differs from cutaneous epithelia in structure, morphology and biophysical characteristics. For example, the skin of the labia majora exhibits elevated hydration, occlusion and frictional properties, which may increase susceptibility to irritants and contact sensitizers. Furthermore, the nonkeratinized vulvar vestibule is likely to be more permeable than keratinized regions. These differences heighten vulvar susceptibility to topical agents. This reviews the structure and properties of vulvar tissue, emphasizing their impact on susceptibility contact irritants and allergens.

The basement membrane zone and dermal extracellular matrix in erosive lichen planus of the vulva: an immunohistochemical study demonstrating altered expression of hemidesmosome components and anchoring fibrils.

Histopathology demonstrates disruption of the basal layer of the epidermis in lichen planus (LP) and altered expression of basement membrane zone (BMZ) components occurs in cutaneous and oral LP. This is the first study in erosive LP of the vulva to investigate the expression of components of the BMZ and extracellular matrix by indirect immunofluorescence. Six biopsies from lesional vulval erosive LP were compared with two biopsies from normal vulva and five biopsies from normal skin. In erosive vulval LP there was widespread disruption of several BMZ components compared to normal skin. The hemidesmosome antigens were disrupted and attenuated, or absent. Expression of lamina lucida proteins and anchoring filaments also showed some alteration. Lamina densa components were altered and in particular there was very marked thickening, streaking and fragmentation of the anchoring fibrils. Some dermal extracellular matrix proteins were increased. This study has demonstrated widespread damage to the BMZ in erosive LP of the vulva, in particular the hemidesmosomes (alpha6beta4 integrin, BP230, BP180) and anchoring fibrils (collagen VII). This suggests an alteration in antigenic expression in the BMZ that may lead to exposure of epitopes and thus make these proteins vulnerable to attack by autoantibodies.

Discoid lupus erythematosus of the vulva.

Genital involvement is a rare manifestation in discoid lupus erythematosus (DLE) and systemic lupus erythematosus (SLE), and there are few reports on vulvar clinical features. We describe a 41-year old Caucasian woman with bilateral vulvar DLE. Although vulvar lesions in lupus are probably more common than is realized, the present report is the first case of genital DLE documented in a female.

[Langerhans' cell histiocytosis of the vulva (Case report)]. / Histiocitosis de células de langerhans de la vulva. (Reporte de un caso)

Langerhans' cell histiocytosis (LCH) is a proliferative disease that most often affects children. Presentation of vulvar lesion alone in adults is rare. We report a case of a 69-year-old woman with a vulvar lesion of 6 years of evolution. HE stain and immunohistochemical study using CTK, ACL, HMB 45, VIM, S 100, LN 5 y CD 1a were performed. CLH, although unusual presentation, it is must keep in mind when appear vulvar lesions in older woman simulating infection or proliferative neoplastic lesions of skin since is necessary rule out systemic engagement and periodical control of patients.

Histiocitosis de células de langerhans de la vulva (Reporte de un caso) / Langerhans' cell histiocytosis of the vulva (case report)

La histiocitosis de células de Langerhans (HCL) es una enfermedad proliferativa que afecta habitualmente a niños. La forma localizada en vulva de un adulto es de presentación rara. Reportamos un caso de una mujer de 69 años con una lesión vulvar de 6 años de evolución. Se realizó coloración con HE para microscopia óptica y estudio inmunohistoquímico con CTK, ACL, HMB 45, VIM, S 100, LN 5 y CD la. La HCL, aunque de aparición inusual, se debe tener en cuenta cuando aparecen lesiones en vulva en pacientes añosas que simulan infecciones o lesiones proliferativas neoplásicas de piel, ya que es necesario descartar compromiso sistémico y controlar periódicamente los pacientes.

Histiocitosis de células de langerhans de la vulva (Reporte de un caso) / Langerhans cell histiocytosis of the vulva (case report)

La histiocitosis de células de Langerhans (HCL) es una enfermedad proliferativa que afecta habitualmente a niños. La forma localizada en vulva de un adulto es de presentación rara. Reportamos un caso de una mujer de 69 años con una lesión vulvar de 6 años de evolución. Se realizó coloración con HE para microscopia óptica y estudio inmunohistoquímico con CTK, ACL, HMB 45, VIM, S 100, LN 5 y CD la. La HCL, aunque de aparición inusual, se debe tener en cuenta cuando aparecen lesiones en vulva en pacientes añosas que simulan infecciones o lesiones proliferativas neoplásicas de piel, ya que es necesario descartar compromiso sistémico y controlar periódicamente los pacientes. (AU)

Evaluation of contact sensitization in vulvar lichen simplex chronicus. A proposal for a battery of selected allergens.

OBJECTIVE: To determine the role of contact sensitization in vulvar lichen simplex chronicus and to select appropriate batteries of allergens to test. STUDY DESIGN: Between 1993 and 2000, 61 women affected by vulvar lichen simplex chronicus were enrolled to evaluate the role of contact hypersensitivity. All the patients underwent patch tests with the Italian standard series and with a wide battery of allergens (preservatives, perfumes, emulsifiers, medicaments) and products they used routinely. RESULTS: Of the women, 47.5% had at least one positive patch test, and relevant positivities were observed in 26%. The relevant allergens were usually medicaments and preservatives. CONCLUSION: It would be acceptable to reduce the number of allergens tested, in particular omitting the perfume series. Patch tests are a helpful diagnostic tool in vulvar lichen simplex chronicus and improve prescribing practice.