Vulvar diseases: Conditions in adults and children.

The most problematic vulvovaginal conditions are familiar to dermatologists but may exhibit distinct clinical features or medication management because of the anatomic location. The second article in this continuing medical education series focuses on management pearls for treating vulvar diseases. We highlight key conditions, such as lichen sclerosus, erosive lichen planus, and vulvodynia. In addition, we review conditions that dermatologists may be less familiar with, such as plasma cell vulvitis, desquamative inflammatory vaginitis, vulvar aphthae, and low estrogen states. Nearly 1 in 6 women experience undiagnosed and untreated vulvovaginal discomfort at some point in their lives. Physicians who treat vulvar disorders will improve the quality of life of countless women.

Nivolumab in chemotherapy-resistant cervical cancer: report of a vulvitis as a novel immune-related adverse event and molecular analysis of a persistent complete response.

BACKGROUND: Treatment options for advanced cervical cancer are limited and patients experiencing recurrence after first-line cisplatin-based chemotherapy and bevacizumab have a poor prognosis. A recent phase II study in advanced cervical cancer has demonstrated a disease control rate of 68.4% with the immune checkpoint inhibitor nivolumab. By blocking immune checkpoints, immunotherapy puts the immune system into a state of hyper-activation that can cause immune-related adverse events. We present the clinical, pathological and molecular data of a patient with metastatic cervical cancer and progressive disease after second-line therapy. We report on the therapeutic response under third-line immunotherapy with nivolumab, the immune-related adverse events (IRAE), and their successful management. CASE PRESENTATION: We report the case of a 62-year-old woman who was diagnosed with advanced squamous cell carcinoma of the cervix with paraaortic lymph node metastases. After an initial combined radio-chemotherapy with cisplatin, she developed local and nodal (supraclavicular) recurrence. Second-line chemotherapy with 6 cycles of carboplatin, paclitaxel, and bevacizumab resulted in a partial response for 6 months. Checkpoint inhibition with nivolumab was started due to progression, leading to persistent complete remission. Immunotherapy was well tolerated for 8 months until the patient presented with an immune-related isolated vulvitis, which was successfully managed with topical corticosteroids. CONCLUSIONS: The persistent complete response after third-line treatment for relapsed chemotherapy-resistant cervical cancer presented in this case highlights the potential of immunotherapy for patients with advanced cervical cancer impressively. To our knowledge, this is the first report of an isolated immune-related vulvitis under nivolumab. This adverse event might be underdiagnosed and mistreated, however, it is of importance due to its impact on quality of life, sexual wellbeing and compliance of patients. Successful IRAE management may enable prolonged immune checkpoint inhibitor therapy. In the future, routine molecular tumour profiling is likely to aid in the stratification of cervical cancer patients for immunotherapy. Here, we provide the methylome data of a case with complete response.

Vulvitis de Zoon: caso clínico / Zoon vulvitis: clinical case

Se presenta un caso de una paciente de 84 años con vulvitis de Zoon. Se trata de una dermatosis vulvar de etiología incierta, muy poco frecuente, que ocasiona sintomatología inespecífica de prurito y escozor vulvar de larga evolución, acompañados de una o varias lesiones focales circunscritas y eritematosas de difícil diagnóstico clínico. Se insiste en la necesidad de realización de biopsia vulvar para obtención de un diagnóstico histológico de certeza. Se comentan las opciones terapéuticas actuales descritas en la literatura aunque no existe un tratamiento de elección.

An 84 year old female patient with Zoons vulvitis case is reported. It is a rare vulvar dermatosis of unknown etiology, with unspecific symptoms such as pruritus and vulvar stinging, both developed over a long period of time, accompanied with focal erythematous injuries. As a clinical diagnosis remains difficult, it is essential that a biopsy is obtained for accurate histological diagnosis. Despite different therapeutic options available, there is no consensus on a standardized treatment.

[A woman with cayenne pepper spots]. / Een vrouw met roestbruine plekjes op de vulva.

A 52-year-old female with dyspareunia presented with red-brown maculae at the vulva.Biopsy revealed an inflammatory cell infiltrate mostly consisting of plasma cells, and the diagnosis 'vulvitis circumscripta plasmacellularis' was established.A biopsy is mandatory to confirm this rare benign inflammatory disorder of the vulva.

Vulvitis de Zoon / Zoon´s vulvitis

La vulvitis de Zoon fue descripta por primera vez por Zoon y Garnier en 1954. Se trata de una inflamación crónica de la mucosa vaginal, de baja incidencia. La etiopatogenia es desconocida y hasta la fecha no hay descripto ningún tratamiento efectivo. Las características clínicas e histopatológicas remedan su contrapartida masculina, la clásica balanitis circunscripta plasmocelular o de Zoon.

Zoon´s vulvitis was first described by Zoon and Garnier in 1954. It´s a low- prevalence, chronicinflammation of the vaginal mucosa. The etiology is unknown, and an effective standardtreatment has not yet been described. Its clinical and histophatologic features resemble the malecounterpart known as Zoon´s balanitis.

Anti-inflammatory treatment.

Inflammatory mucosal disorders are treated conventionally with potent or superpotent topical corticosteroids. For more than 20 years, topical cyclosporine has been used in the management of oral mucous membrane affections. Recently other topically applied calcineurin inhibitors, namely tacrolimus and pimecrolimus, expanded the armamentarium for the treatment of inflammatory mucosal diseases. This chapter places its main emphasis on the efficacy and safety of topical calcineurin inhibitors in the management of different oral and genital conditions, including anogenital lichen sclerosus (LS), oral and genital lichen planus, plasma cell balanitis and vulvitis, mucous membrane pemphigoid and pemphigus vulgaris, all conditions having usually a protracted course, requiring long-lasting treatment. There is current evidence for the effectiveness of both pimecrolimus and tacrolimus in the topical treatment of inflammatory oral mucosal diseases and genital dermatoses, especially oral lichen planus and genital LS.

Contact dermatitis of the vulva.

Contact dermatitis of the vulva is common, with irritant contact dermatitis occurring more frequently than allergic contact dermatitis. Patients with chronic vulvar dermatoses are at greater risk and should continually be reassessed for possible contact dermatitis. Comprehensive and specific questioning about hygiene practices and product use is necessary to elicit a history of contactant use. Patch testing is required to identify relevant contact allergens, the most common of which include medicaments, preservatives, and fragrances. Patient education and follow-up are essential in optimizing treatment and preventing recurrence of vulvar contact dermatitis.

Vulvar pyoderma gangrenosum in a child.

We present a case of a 10-year-old girl with a diagnosis of vulvar pyoderma gangrenosum. Intravenous methylprednisolone was started and on tapering the steroid regimen, the lesion showed significant enlargement and purulent discharge without any remission of fever and inflammatory activity, so she was treated with oral cyclosporin A in combination with low-dose steroid. A response to treatment was achieved after 2 weeks and clinical and laboratory follow-up at 12 months did not show any disease relapse or inflammation.

Metastatic vulval Crohn's disease and infliximab: a case report.

BACKGROUND: Metastatic vulval Crohn's disease is uncommon, and diagnosis is frequently delayed. Topical therapy is often ineffective, and systemic immunosuppressive agents are required. CASE: A 32-year-old Caucasian female with known gastrointestinal Crohn's disease presented with a 7-year history of vulvitis. Perianal biopsy demonstrated typical granulomas. Her disease was resistant to treatment with prednisone and azathioprine; however, infliximab effected good control, and she remains well on 8 weekly infusions 1 year later. CONCLUSION: Biopsy should be performed in patients with vulvitis who have Crohn's disease to rule out metastatic involvement. Infliximab was successfully used in this case to control Crohn's vulvitis.

Tacrolimus 0.1% ointment: is it really effective in plasma cell vulvitis? Report of four cases.

BACKGROUND: Plasma cell vulvitis is a clinically and histologically well-characterized chronic disease that usually relapses after various topical therapies. Considering the inflammatory nature of the disease, the new topical calcineurin inhibitors have been also employed successfully in few cases of Zoon's balanitis, the corresponding male condition. OBJECTIVE: The aim of our study is to evaluate the effectiveness of tacrolimus ointment in a small group of plasma cell vulvitis sufferers. METHODS: 4 women affected by biopsy-proved plasma cell vulvitis were enrolled, after informed consent. The topical drug was applied twice daily for 6 weeks, then tapered on the basis of the clinical results. Symptoms and objective parameters were obtained periodically at the beginning, after 6 weeks and up to the end of the topical treatment. A final biopsy was performed in 3 out of our 4 patients. The follow-up is still ongoing. RESULTS: The comparative analysis of subjective, objective and histopathological data has shown discordant and less encouraging results than those reported for the corresponding male condition. CONCLUSION: At the moment, topical tacrolimus could be considered an alternative treatment for plasma cell vulvitis only in cases resistant to conventional therapies.

A case of idiopathic granulomatous cheilitis and vulvitis.

A 36-year-old woman presented with chronic recurring dermatitis of the vulva, perineum, and lips. The genital lesions had a 3-year history and were associated with slight pruritus and occasional pain. The lesions of the upper lip had a history of 6 months. The patient had been treated with cycles of antimycotics and topical steroids which only partially controlled the symptoms during treatment. Dermatologic examination showed erythematous, infiltrative dermatitis with edema of the labia majora and persistent edema of the upper lip (Fig. 1a,b). Routine blood chemistry, urine analysis, and chest X-ray were normal. Microscopic examination and cultures of vaginal swabs did not reveal any pathogenic bacteria or fungi. Histologic examination of a biopsy of vulval lesional skin showed lichenoid lymphocytic infiltration of the papillary dermis and small, nonnecrotic epithelioid granulomas in the deep dermis (Fig. 1c,d). No microorganisms, including acid-fast bacilli or fungi, were identified. Culture was negative for fungi. Polymerase chain reaction was negative for the mycobacterial genome. Histologic examination of a biopsy from the upper lip showed similar results. The pathology reports of both regions were compatible with a diagnosis of granulomatous cheilitis and vulvitis. To investigate concomitant asymptomatic inflammatory bowel disease, the patient underwent colonoscopy with retrograde ileoscopy and gastroscopy, which were both negative. The patient refused radiographic examination of the small intestine with a barium meal. The patient was treated with systemic metronidazole (500 mg/day). After 6 months of therapy, the upper lip showed significant improvement and erythema and desquamation in the genital area showed slight improvement, but genital edema was unaffected.

Medical treatment of vulvar squamous cell hyperplasia.

OBJECTIVE: To evaluate symptomatic response and recurrence rates of graduated topical fluorinated corticosteroid in patients with vulvar squamous cell hyperplasia. METHODS: Nine hundred seventy-six patients with biopsy-proven vulvar squamous cell hyperplasia from 1990 to 2003 were reviewed in this retrospective study. All patients were treated with graduated topical fluorinated corticosteroid. Data were obtained from hospital records. Symptomatic remission and recurrence rates were noted following six months local therapy. RESULTS: The mean age was 42.55+/-10.93 (15-85). The remission rate was 93.8% in six months. The remission rate was non-significantly higher in postmenopausal patients than that in their premenopausal counterpart (94.9% vs 93.0%, p=0.15). The disease recurred in 6.9% of patients. Of the patients that suffered recurrence 47.5% had persistent disease initially. The patients with following factors older ages (>40 years), postmenopausal period had significantly higher recurrence rates. Four patients with recurrent disease and six patients with persistent disease in the form of vulvar intraepithelial neoplasia I-II or atypical squamous hyperplasia, were treated with skinning vulvectomy. CONCLUSION: Corticosteroid in the treatment of vulvar squamous cell hyperplasia yielded excellent response rates. In the evaluation of patients without symptomatic relief, the first step should be a vulvar biopsy to exclude the presence of atypical components.

[Rosacea fulminans, pyostomatitis and pyovulvitis in Crohn's disease: dapsone as key factor in combination therapy]. / Rosacea fulminans, pyostomatitis und pyovulvitis bei morbus Crohn: dapson als entscheidender wirkstoff einer erfolgreichen kombinationstherapie?

Rosacea fulminans (also known as pyoderma faciale) has been reported to occur in association with Crohn's disease. It is still unclear whether the papulopustules and confluent nodules of rosacea fulminans represent a manifestation of mucocutaneous Crohn's disease or whether this association is a mere coincidence. A 46-year-old woman presented with the spontaneous outbreak of rosacea fulminans and pyostomatitis/pyovulvitis. Complete remission of the mucocutaneous symptoms was achieved with 2 months combination therapy with methylprednisolone, isotretinoin and dapsone. The patient's Crohn's disease, already diagnosed for 3 years, did not flare during this period.

A case of vulvitis granulomatosa.

Merkersson-Rosenthal syndrome (MRS) is characterized by cheilitis or pareitis granulomatosa, facial palsy, and fissured tongue. Sometimes the forehead, eyelids and chin are involved, and occasionally genital lesions are present. A vulval lesion of MRS is named vulvitis granulomatosa. Tranilast has been described as an effective treatment for cases of MRS, granulomatous cheilitis, and granulomatous blepharitis. Herein we report a successful treatment with tranilast of an adult female patient with vulvitis granulomatosa.