van der Linden Michelle, Meeuwis Kim, van Hees Colette, van Dorst Eleonora, Bulten Johan, Bosse Tjalling, IntHout Joanna, Boll Dorry, Slangen Brigitte, van Seters Manon, van Beurden Marc, van Poelgeest Mariëtte, de Hullu Joanne
Department of Obstetrics and Gynaecology, Radboud University Medical Center, Nijmegen, Netherlands.
Department of Dermatology, Radboud University Medical Center, Nijmegen, Netherlands.
JMIR Res Protoc. 2017 Sep 6;6(9):e178. doi: 10.2196/resprot.7503.
Vulvar Paget disease is a rare skin disorder, which is most common in postmenopausal Caucasian women. They usually present with an erythematous plaque that may show fine or typical "cake icing" scaling or ulceration that may cause itching, pain, irritation, or a burning sensation. Although most cases are noninvasive, vulvar Paget disease may be invasive or associated with an underlying vulvar or distant adenocarcinoma. The histological evidence of so-called "Paget cells" with abundant pale cytoplasm in the epithelium confirms the diagnosis. The origin of these Paget cells is still unclear. Treatment of choice is wide local excision with negative margins. Obtaining clear surgical margins is challenging and may lead to extensive and mutilating surgery. Even then, recurrence rates are high, ranging from 15% to 70%, which emphasizes the need for new treatment options. A number of case reports, retrospective case series, and one observational study have shown promising results using the topical immune response modifier imiquimod.
This study aims to investigate the efficacy, safety, and immunological response in patients with noninvasive vulvar Paget disease using a standardized treatment schedule with 5% imiquimod cream.
Topical 5% imiquimod cream might be an effective and safe treatment alternative for vulvar Paget disease. The Paget Trial is a multicenter observational cohort study including eight tertiary referral hospitals in the Netherlands. It is ethically approved by the Medical-Ethical Committee of Arnhem-Nijmegen and registered in the Central Committee on Research Involving Human Subjects (CCMO) Register by as NL51648.091.14. Twenty patients with (recurrent) noninvasive vulvar Paget disease will be treated with topical 5% imiquimod cream three times a week for 16 weeks. The primary efficacy outcome is the reduction in lesion size at 12 weeks after end of treatment. Secondary outcomes are safety, immunological response, and quality of life. Safety will be assessed by evaluation of adverse events and tolerability of treatment. To evaluate the immunological response, various immunological markers will be tested on biopsy specimens taken before, during, and after treatment. Quality of life will be assessed with three questionnaires taken before, during, and after treatment.
First results are expected in the summer of 2018.
ClinicalTrials.gov NCT02385188; https://clinicaltrials.gov/ct2/show/NCT02385188 (Archived by WebCite at http://www.webcitation.org/6sXygHuhP).
外阴佩吉特病是一种罕见的皮肤疾病，在绝经后白种女性中最为常见。患者通常表现为红斑性斑块，可能出现细微或典型的“蛋糕糖衣”样鳞屑或溃疡，可引起瘙痒、疼痛、刺激感或烧灼感。虽然大多数病例为非侵袭性，但外阴佩吉特病可能是侵袭性的，或与潜在的外阴或远处腺癌相关。上皮中存在具有丰富淡染细胞质的所谓“佩吉特细胞”的组织学证据可确诊该病。这些佩吉特细胞的起源仍不清楚。治疗的首选方法是进行切缘阴性的广泛局部切除。获得切缘阴性的手术具有挑战性，可能导致广泛且致残的手术。即便如此，复发率仍很高，在15%至70%之间，这凸显了对新治疗方案的需求。一些病例报告、回顾性病例系列研究以及一项观察性研究表明，使用局部免疫反应调节剂咪喹莫特可取得有前景的结果。
本研究旨在使用5%咪喹莫特乳膏的标准化治疗方案，调查非侵袭性外阴佩吉特病患者的疗效、安全性和免疫反应。
局部使用5%咪喹莫特乳膏可能是外阴佩吉特病一种有效且安全的治疗选择。佩吉特试验是一项多中心观察性队列研究，纳入了荷兰的八家三级转诊医院。该研究已获得阿纳姆 - 奈梅亨医学伦理委员会的伦理批准，并在涉及人类受试者的中央委员会（CCMO）注册，注册号为NL51648.091.14。20例（复发性）非侵袭性外阴佩吉特病患者将接受局部5%咪喹莫特乳膏治疗，每周三次，共16周。主要疗效指标是治疗结束后12周时病变大小的减小。次要指标包括安全性、免疫反应和生活质量。安全性将通过评估不良事件和治疗耐受性来评估。为评估免疫反应，将在治疗前、治疗期间和治疗后采集的活检标本上检测各种免疫标志物。生活质量将通过治疗前、治疗期间和治疗后使用的三份问卷进行评估。
预计2018年夏季得出初步结果。
ClinicalTrials.gov NCT02385188；https://clinicaltrials.gov/ct2/show/NCT02385188（由WebCite存档于http://www.webcitation.org/6sXygHuhP）
