外阴硬化萎缩性苔藓与外阴鳞状细胞癌的基因研究

外阴硬化萎缩性苔藓是较为常见的一种慢性皮肤黏膜病变，部分患者可能发展为外阴鳞状细胞癌。近年来的研究发现，外阴硬化萎缩性苔藓可能与多种癌基因、抑癌基因突变及其表达异常存在着密切联系。综述与外阴硬化萎缩性苔藓和外阴鳞状细胞癌相关的十余种癌基因与抑癌基因，分析从外阴硬化萎缩性苔藓发展到外阴鳞状细胞癌的因素。     

The effect of topical corticosteroids on Ki67 and p53 expression in vulval lichen sclerosus

BACKGROUND: Topical corticosteroids have become the treatment of choice for genital lichen sclerosus (LS) and are believed to be required for long-term relief of symptoms. OBJECTIVE: To compare vulval LS that had been treated with topical corticosteroids, vulval LS that had not received topical corticosteroids, and histologically normal vulval skin. METHODS: We used immunohistochemistry to look for Ki67 expression and abnormal p53 expression. RESULTS: We found a statistically significant difference for p53 overexpression, with increased levels seen when comparing corticosteroid-treated LS with normal genital skin (P = 0.011). Ki67 expression was also significantly higher in the corticosteroid-treated group compared with normal genital skin (P = 0.001), and increased levels were also found in the treated group compared with untreated LS (P = 0.05). CONCLUSIONS: Our data suggest that topical corticosteroids have an effect on cell cycle proteins in genital skin and, in particular, genital skin with LS changes.     

Differential expression of oestrogen receptor isoforms and androgen receptor in the normal vulva and vagina compared with vulval lichen sclerosus and chronic vaginitis

BACKGROUND: Although the expression of the oestrogen receptor (ER) alpha isoform and androgen receptor (AR) has been examined in vulval lichen sclerosus (VLS), the distribution pattern of ERalpha, ERbeta and AR has not been described in chronic atrophic vaginitis nor correlated with markers of proliferation (Ki-67) in either of these diseased tissues. OBJECTIVES: To measure the levels and distribution of ERalpha, ERbeta and AR immunoreactivity in relation to Ki-67 in normal and diseased vulva and vagina. METHODS: The expression of ERalpha, ERbeta and AR in relation to the proliferation marker Ki-67 in VLS, squamous hyperplasia of the vulva and chronic atrophic vaginitis was determined by immunohistomorphometric analysis and compared with that in normal vulva and vagina. RESULTS: VLS showed similar ERalpha and ERbeta expression in the 'epidermal' and 'dermal' tissue layers to that of normal vulvae, whereas AR expression appeared to be absent in most cases. ERbeta and Ki-67 expression was correlated with ERalpha expression but only in the 'fibrovascular' layer of the vulva. ERalpha expression was absent from the 'fibromuscular' layer of diseased vulvae, while ERbeta expression was absent in normal tissues but was highly expressed in diseased vulvae. ERalpha expression was significantly correlated with AR expression in the fibrovascular layer of the vagina and inversely correlated with Ki-67 staining in the parabasal cells of the epidermis in patients with chronic atrophic vaginitis. CONCLUSIONS: These data suggest that ER expression and levels may be implicated in the aetiopathology of VLS and chronic atrophic vaginitis.     

Diagnosis and treatment of oral lichen sclerosus in a pediatric patient

Lichen sclerosus is an uncommon chronic inflammatory disease, which rarely affects the oral mucosa. Here, we describe the occurrence of oral lichen sclerosus with gingival destruction in a 12‐year‐old female patient. After diagnostic confirmation by histopathology, intralesional injection of corticosteroid was performed, producing satisfactory remission of the lesion.     

Clinical and dermoscopic changes of vulvar lichen sclerosus after topical corticosteroid treatment

With the aim to assess changes in both clinical and dermoscopic features of vulvar lichen sclerosus (VLS) after a treatment with topical corticosteroid, 29 VLS patients treated with mometasone furoate 0.1% ointment for 12 weeks were evaluated for symptoms, objective signs and dermoscopic variables at baseline and treatment completion. Numeric scores were assigned to each parameter. Mean itching and burning values had decreased significantly at the 12‐week control visit compared with baseline, as well as values referring to pallor, hyperkeratosis and purpuric lesions. Among the dermoscopic variables, the vessel score increased while the scores of patchy, structureless, whitish areas, whitish background, purpuric globules and scales decreased significantly after treatment. Scores referring to gray‐blue dots, comedo‐like openings and structures like ice slivers did not change significantly throughout the treatment. Based on these findings, dermoscopic features may change, even significantly, with topical corticosteroids and may be useful for monitoring the response to treatment.     

Potential human papillomavirus reactivation following topical corticosteroid therapy of genital lichen sclerosus and erosive lichen planus

Using a highly sensitive polymerase chain reaction (PCR) technique, based on general GP5+/GP6+ PCR primers covering 34 different human papillomavirus (HPV) types, the presence of HPV DNA was studied in paraffin-embedded penile biopsies from 20 men treated topically with corticosteroids. Clobetasol propionate was applied for 2-16 (mean 7) weeks by 19 men (age 18-73; mean 40) with lichen sclerosus. High-risk HPV was detected prior to therapy in three patients (16%) who lacked clinical or histopathological signs of HPV infection. Following therapy high-risk HPV was detected in biopsies from four men (21%), of whom three also exhibited clinical and/or light microscopic signs of HPV infection. Low-risk HPV DNA was not detected in any of these samples. Four biopsies were collected during a 5-year period from a 51-year-old man who was treated repeatedly with topical mild-moderate potent corticosteroids at intervals of up to 10 weeks for penile erosive lichen planus, followed by nine clinical outbreaks of typical condylomas that consistently showed the presence of low-risk HPV DNA only. These observations indicate that long-lasting topical corticosteroid therapy occasionally may be associated with opportunistic reactivation of a latent high- and low-risk mucosotrophic HPV type infection. The importance of clinical follow-up is underlined.     

Successful treatment of vulvar lichen sclerosus in a child with low-concentration topical tacrolimus ointment

Lichen sclerosus is a chronic inflammatory skin disorder that has a predilection for the anogenital area. Topical corticosteroid is occasionally effective; however, continuous treatment is often required and recurrence after its stoppage is frequent. Herein, we report a case of vulvar lichen sclerosus in a 5-year-old girl, which was refractory to topical corticosteroids. After 14 weeks of treatment with 0.03% tacrolimus ointment once daily, the lesions completely resolved without side-effects. Of interest, the number of milia within the plaque of lichen sclerosus was reduced in tandem with the improvement of lichen sclerosus. This is the first report of topical low-concentration tacrolimus treatment showing a dramatic effect in the treatment of childhood vulvar lichen sclerosus.     

Angiomatous reaction Kaposi-sarcoma-like as a side effect of topical corticosteroid therapy in lichen sclerosus of the penis

Lichen sclerosus (LS) is a chronic inflammatory skin condition usually located in the anogenital area. Topical corticosteroid therapy is the first choice treatment which may arrest or delay the progression of the disorder.
We report the case of a 74-year-old man presented with a 6-month history of nodular lesions localized on penis. The man had a previous history of genital lesions that had been diagnosed as LS and treated with long-term topical corticosteroid therapy. After 3 months of corticosteroid therapy, the patient observed the appearance of several nodular erythematous lesions on the penis with progressive disappearance of the clinical symptoms of LS. These purple to red asymptomatic angiomatoid nodules resembled the clinical features of Kaposi sarcoma.     

Multicentre, phase II trial on the safety and efficacy of topical tacrolimus ointment for the treatment of lichen sclerosus

BACKGROUND: Lichen sclerosus is a chronic inflammatory autoimmune disease causing significant sclerosis, atrophy and pruritus. Treatment remains unsatisfactory, with potent corticosteroids being the most effective therapy. OBJECTIVES: To conduct a multicentre, phase II trial to assess the safety and efficacy of tacrolimus ointment 0.1% for the treatment of lichen sclerosus with a follow-up period of 18 months at 10 university and teaching hospitals in Germany and Austria. METHODS: Eighty-four patients (49 women, 32 men and three girls) aged between 5 and 85 years with long-standing, active lichen sclerosus (79 with anogenital and five with extragenital localization) were treated with topical tacrolimus ointment 0.1% twice daily for 16 weeks. Computerized analysis of the lesional area was performed. The primary endpoint was clearance of active lichen sclerosus. Secondary endpoints were time to optimal response, reduction of sclerosis and duration of remission. RESULTS: The primary endpoint (clearance of active lichen sclerosus) was reached by 43% of patients at 24 weeks of treatment. Partial resolution was reached in 34% of patients. Maximal effects occurred between week 10 and 24 of therapy. Treatment led to a significant reduction of the total lesional area (P < 0.01) and to a significant decline in the total symptom score (P < 0.005). Symptoms (e.g. itching) and findings (erythema, erosions and induration) showed significant improvement. No serious adverse events were observed. There were three (9%) recurrences during the follow-up period. CONCLUSIONS: Topical tacrolimus ointment 0.1% was safe and effective for the treatment of long-standing active lichen sclerosus.     

Evaluation of photodynamic therapy using topical aminolevulinic acid hydrochloride in the treatment of condylomata acuminata: a comparative, randomized clinical trial

Objectives: To determine the safety and efficacy of photodynamic therapy (PDT) with topical application of 20% wt/vol aminolevulinic acid hydrochloride (ALA) in the treatment of condylomata acuminata (CA). Study design: Patients with CA were randomly allocated into the ALA‐PDT group and the CO₂ laser group in an allocation ratio of 3 : 1. The treatment was repeated weekly if necessary, but no more than 3 times. The primary efficacy endpoint was the wart clearance rate 1 week after the last treatment. The recurrence rate was evaluated at weeks 4, 8 and 12 after the treatment ended. The clinical response to therapy and adverse effects were recorded. Results: A total of 91 patients with CA were enrolled in the clinical trial. Of these 90 (98.9%) patients completed the trial (67 in the ALA‐PDT group, and 23 in CO₂ laser group). By 1 week after the last treatment, the complete clearance rate was 95.93% in the ALA‐PDT group and 100% in CO₂ laser group (P>0.05). The clearance rate of CA at male urethral orifice was100% in the ALA‐PDT group and 100% in the CO₂ laser group (P>0.05). The overall recurrence rate calculated by the end of the entire follow‐up period was significantly lower in the ALA‐PDT group than that in the CO₂ laser group (9.38% vs 17.39%, P<0.05). Moreover, there was no systemic adverse event in either group. The proportion of patients with adverse effects in the ALA‐PDT group (8.82%) was also significantly lower than that in the CO₂ laser group (100%, P<0.05). The side‐effects in patients treated with ALA‐PDT mainly included mild burning and/or stinging restricted to the illuminated area. Conclusion: The results confirmed that topical application of ALA‐PDT is a simpler and as effective therapy with a lower incidence of adverse effects in the treatment of CA compared with conventional CO₂ laser therapy.     

Prospective study of topical 5‐aminolevulinic acid photodynamic therapy for the treatment of severe adolescent acne in Chinese patients

Acne vulgaris is one of the most common skin diseases in adolescents. In the present study, we aimed to evaluate the effectiveness and safety of topical 5‐aminolevulinic acid (ALA)‐mediated photodynamic therapy (PDT) for the treatment of severe acne in Chinese adolescent patients. Twenty‐one Chinese adolescent patients aged 12–18 years with Pillsbury III–IV severe facial acne were treated with three courses of ALA‐PDT. A 5% ALA lotion was applied topically for 60 min followed by irradiation with light‐emitting diode light at 633 nm with a light intensity of 75–80 mW/cm² and a light dose of 90–96 J/cm². Clinical assessment was conducted before and after each treatment, and at each follow‐up session. The total effective rates were 85.71%, 90.48%, and 95.23% after the three PDT sessions, and at the 4‐ and 8‐week follow ups, respectively. ALA‐PDT is an effective treatment for severe adolescent acne vulgaris, and is associated with mild and reversible side‐effects.     

Photodynamic therapy for inoperable vulval Paget's disease using δ-aminolaevulinic acid: successful management of a large skin lesion

A 74-year-old woman with extensive inoperable vulval extramammary Paget's disease who had lymph node and pulmonary metastases, was treated with etoposide (VP16) 100 mg and 5000 cGy electron beam irradiation, which reduced the lesion by 60%. Following these interventions, the residual lesion was successfully treated with repeated photodynamic therapy using delta-aminolaevulinic acid, which achieved a nearly complete remission.     

Efficacy of photodynamic therapy with topical 5‐aminolevulinic acid using intense pulsed light for Bowen’s disease

Photodynamic therapy (PDT) with topical 5‐aminolevulinic acid (ALA) is reported to be an effective and safe treatment for superficial non‐melanoma skin cancers. We have developed an photodynamic therapy with topical δ‐aminolevulinic acid (ALA‐PDT) protocol using intense pulsed light (IPL) for treating Bowen’s disease (BD). Three patients diagnosed with BD by skin biopsy were recruited in this study. They received IPL treatment after 3 h of occlusive dressing with application of ALA. This protocol was repeated every 2 weeks for a total of five sessions. The treated areas did not show any signs of BD for more than 1 year; therefore, it appeared that the affected areas showed improvement in all the patients. No patients withdrew from the study because of side‐effects. ALA‐PDT with IPL as a light source is well tolerated by patients and is beneficial for treating BD.     

Complete resolution of a squamous cell carcinoma of the skin using intralesional 5-aminolevulinic acid photodynamic therapy intralesional PDT for SCC

We present an 82-year-old female patient with a 2-year history of an infiltrative squamous cell carcinoma (SCC) on her right cheek. The patient was treated with one intralesional photodynamic therapy (PDT) session using 10% 5-aminolevulinic acid solution. We used red light by a non-coherent light source at a light dose of 100 J/cm2 and a fluency rate of 100 mW/cm2. Complete clinical and histological response was achieved 3 months after the treatment procedure. Cosmetic outcome was evaluated as fair. The patient remains disease free with the absence of any clinical sign of recurrence 16 months after PDT. Long-term follow-up is needed for assessment of recurrences. Optimization of the therapeutic protocol, as well as justification of our results in larger studies are needed in order to elicit safe conclusions.     

5-氨基酮戊酸光动力治疗面部鳞状细胞癌一例

患者,男,94岁.左颞部粉红色斑块2年.组织病理示:鳞状细胞癌.共接受光动力治疗3次(功率90 mW/cm2,照射时长25 min,间隔7日),治疗后面部皮损恢复良好,定期随访未见复发.     

Effective photodynamic therapy of actinic keratoses on the head and face with a novel, self-adhesive 5-aminolaevulinic acid patch

Background:  Photodynamic therapy (PDT) is increasingly used for the treatment of actinic keratosis (AK).
Objectives:  To investigate both the efficacy of different application times and the safety of a novel patch (PD P 506 A) containing aminolaevulinic acid in the PDT of mild to moderate AK.
Methods:  Applications of PD P 506 A for 0.5, 1, 2 and 4 h were compared in a multicentre, randomized, blinded-observer, parallel-group study. After patch removal, study lesions were illuminated with red light ( λ _em ≈ 630 nm; 37 J/cm²). Study lesions were not pretreated (e.g. by curettage) prior to PDT. Efficacy was evaluated 4 and 8 weeks after treatment. Safety and tolerability were determined through laboratory analyses and documentation of both local reactions and adverse events.
Results:  A total of 149 patients were initially enrolled. Of these, 140 patients (520 lesions) completed the study according to protocol. Eight weeks after treatment, 86% of the AK lesions (74% of the patients) treated with 4-h patch application showed complete clearance. The complete clearance rates of lesions (patients) for the 2-, 1- and 0.5-h treatment arms were 73% (47%), 72% (50%) and 51% (24%), respectively. Statistically, the 4-h application was identified as the 'best treatment'. Patients with clearance seemed to experience local reactions to a greater extent than patients without clearance. Local reactions to study treatments did not exceed the expected range.
Conclusions:  The results of this first clinical efficacy study suggest excellent therapeutic outcomes with a single PD P 506 A PDT with a 4-h application.     

5-氨基酮戊酸光动力疗法在感染相关皮肤性病中的研究进展

  5-氨基酮戊酸光动力疗法(ALA PDT)作为一种新型疗法已被应用于感染相关皮肤病性病中。基础研究已证实ALA-PDT对多种致病细菌、真菌、病毒等微生物均有明显的抑制或杀伤作用。临床研究结果表明：ALA-PDT对于寻常痤疮、尖锐湿疣、皮肤肉芽肿等感染相关皮肤性病具有肯定的疗效,且其安全性好、可重复治疗、抗菌谱广、不会诱导耐药。然而, 其临床应用受到ALA-PDT治疗深度有限、疼痛等不良反应的限制,不同感染相关皮肤性病相匹配的PDT参数需进行大规模样本的深入研究。 本文从基础研究和临床应用两方面对近年来ALA-PDT在感染相关皮肤性病中的研究进展作一综述,以期为临床诊疗提供更多依据。