Pain during photodynamic therapy is associated with protoporphyrin IX fluorescence and fluence rate

BACKGROUND: Pain during photodynamic therapy (PDT) is a considerable problem that needs to be studied to improve this otherwise attractive treatment of skin diseases. OBJECTIVES: To compare pain during PDT using two different fluence rates, and also to evaluate the association between pain and protoporphyrin IX (PpIX) fluorescence, lesion type, lesion preparation and lesion localization. METHODS: Twenty-six patients with actinic keratoses (AKs) in different localizations and 34 patients with facial acne vulgaris were treated with methyl aminolaevulinate-PDT. Patients with acne were illuminated using two different fluence rates. Pain score during PDT and PpIX fluorescence prior to illumination were measured. RESULTS: The study showed that pain during illumination was associated with the PpIX fluorescence in the treatment area (P = 0.0003, R(2) = 0.31). When using a fluence rate of 34 mW cm(-2) patients with acne had a pain score of 6 [interquartile range (IQR) 5-7] compared with 8 (IQR 6-10) when using a fluence rate of 68 mW cm(-2) (P = 0.018). After correcting the pain score for PpIX fluorescence no differences in pain scores were found between first and second acne treatment, locations of AK lesions or between the two types of lesions. CONCLUSIONS: Pain during PDT was correlated with the PpIX fluorescence in the treatment area prior to illumination. Pain was reduced using a lower fluence rate during PDT of acne.     

The impact of different fluence rates on pain and clinical outcome in patients with actinic keratoses treated with photodynamic therapy

Background/purpose: Literature data suggest that lower fluence rates are preferable in terms of clinical response and tolerability for treating patients with actinic keratoses (AKs). We aimed to clarify the impact of different fluence rates on pain during photodynamic therapy (PDT) for AKs, as well as on treatment outcome. Methods: Individuals with at least three discrete AKs were recruited. Each lesion was randomly allocated to 25, 50 or 75 mW/cm² of topical 5‐aminolevulinic acid (5‐ALA) PDT, using non‐coherent light source. Primary end point was pain during illumination, evaluated using a visual analogue scale (VAS). Secondary end points were clinical outcome and adverse events. Results: Fifty adults, with 150 AKs lesions were recruited in the study. Mean VAS score did not significantly differ between the groups of 25 and 50 mW/cm² (P=0.714). However, mean VAS was significantly higher at the group of 75 mW/cm² in comparison to the former ones (P=0.000). With respect to the clinical outcome and adverse events during the first year of follow‐up, no differences were observed between the three groups. Comparison between the 25 and the 50 mW/cm² (P=0.749), as well as between the former and the 75 mW/cm², did not show a dependence of complete response rate on fluence (P=0.749 and P=1.000, respectively). Conclusions: According to our observations a fluence rate between 25 and 50 mW/cm² is effective and better tolerated by patients treated with topical 5‐ALA PDT for AKs.     

Aminolevulinic acid photodynamic therapy for skin cancers

Aminolevulinic acid photodynamic therapy (ALA-PDT) is an effective and noninvasive therapy for superficial basal cell carcinoma (BCC) and Bowen's disease. It also may have a role in the treatment of nodular BCC and other cutaneous malignancies, including localized cutaneous lymphomas. ALA-PDT offers multiple advantages over traditional treatments, including little to no scarring, excellent cosmetic results, and the ability to treat multiple lesions simultaneously. It is not an effective therapy for aggressive subtypes of BCC or for invasive squamous cell carcinoma. Finally, ALA-PDT may be a useful way to prevent new skin cancers in certain high-risk patients.     

光动力疗法治疗皮肤肿瘤及转移癌的临床观察

目的观察光动力疗法(photodynamic therapy,PDT)治疗皮肤肿瘤的临床疗效及不良反应。方法对病理检查确诊的31例皮肤肿瘤患者(基底细胞癌14例,鳞状细胞癌11例,皮脂腺癌1例,汗腺癌1例,上皮样肉瘤1例,皮肤转移性腺癌3例),给予血啉甲醚5mg/kg静滴,24h、48h、72h后行632.8nm激光照射,能量密度(648.42±16.45)J/cm2。4周1个疗程,治疗3个疗程后评价疗效。结果31例患者中完全缓解率74.20%(23/31),部分缓解率12.90%(4/31),总有效率87.10%,无效率12.90%(4/31)。完全缓解患者随访19个月以上,1年后复发率26.09%(6/23),中位疾病进展时间13.2个月,再次给予光动力治疗后完全缓解。所有患者无严重不良反应。结论光动力疗法治疗皮肤肿瘤,安全有效,值得临床推广应用。     

Perspectives of photodynamic therapy for skin diseases.

Photodynamic therapy (PDT) is largely an experimental modality for the treatment of neoplastic and selected nonneoplastic diseases. This therapeutic procedure, through a cascade of events, leads to cell killing. In the past few years, dermatology has taken advantage of PDT for the treatment of skin cancer and other skin diseases. The skin has considerable attributes over many other organs for the application of PDT. These include the accessibility to all three PDT essential requirements; the drug (photosensitizing agent), visible light and oxygen. The major benefit of experimental PDT in dermatology is the ability to assess the clinical response visually and the relative ease in obtaining biopsies for precise biochemical and histological analysis. Currently, PDT has received approval worldwide for the ablation of various tumor types. In the United States, the Food and Drug Administration has approved PDT for the treatment of advanced esophageal cancer and selected patients with lung cancer. Clinical trials, employing several types of photosensitizers for PDT, are ongoing for a variety of dermatological lesions. This review summarizes current knowledge of PDT in dermatology and highlights future perspectives of this modality for effective management of skin diseases.     

光动力疗法在感染性皮肤病中的应用

光动力疗法是通过局部或系统给予光敏剂后以特定波长光照射从而对靶组织产生选择性杀伤作用.20世纪90年代以前光动力疗法的研究主要集巾于肿瘤的诊断和治疗,随着新光敏剂的出现和应用,光动力疗法更加广泛地应用在各种疾病的治疗中,尤其是在一些局部感染性皮肤病方面表现出较好的临床疗效,局部微生物感染的光动力治疗成为新的研究热点.     

Pain caused by photodynamic therapy of skin cancer

Pain resulting from photodynamic therapy (PDT) of skin cancer was investigated. The study included 69 lesions (60 patients) with different types of skin tumours or precursors. Protoporphyrin IX, which is produced by the topical application of delta-aminolevulinic acid, was used as a photosensitizing agent. Twenty-three of the lesions (19 patients) were examined with a fluorescence imaging system which demarcates the tumour area from the healthy skin and visualizes the contrast between the fluorescence from healthy skin and that from the tumour. EMLA is used on all patients as part of our routine PDT protocol but despite this the major side-effect of PDT is pain during treatment. There is a large variation in pain intensity experienced by the patients, as measured by a visual analogue scale (VAS). Patients with actinic keratoses experienced more pain than those with Bowen's disease or basal cell carcinoma. The mean VAS score was higher when treating lesions located on the head than when treating lesions on the torso or the extremities. Also, treatment of large skin areas resulted in more pain than treatment of small areas, and men experienced more pain than women. The pain experienced by the patients did not correlate with treatment dose, Fitzpatrick skin type, age or fluorescence intensity.     

光动力治疗遗传性皮肤病相关非黑素皮肤癌的研究进展

遗传性皮肤病相关非黑素皮肤癌(non melanoma skin cancer, NMSC)是一类继发于遗传性皮肤病的皮肤恶性肿瘤,主要包括皮肤鳞状细胞癌和基底细胞癌,一般具有家族史,且呈早发、多发和易复发的特点。目前多采用手术治疗,但存在创伤大、易复发、耐受性差等缺点。光动力治疗可以靶向杀伤肿瘤和病理性增生组织,基于其破坏小、可靶向、可重复的优势,近年来已被广泛用于NMSC的治疗。本文就光动力在遗传性皮肤病相关NMSC的治疗进展进行综述。     

δ-氨基酮戊酸光动力学疗法治疗皮肤病的研究进展

δ-氨基酮戊酸光动力学疗法是一种非创伤性局部治疗技术,可特异性杀死病变细胞.近年研究表明,该疗法对靶细胞某些生物学特征的影响是重要作用机制之一.除非色素细胞性皮肤恶性肿瘤外,δ-氨基酮戊酸光动力学疗法的适应症逐渐扩展至癌前病变、病毒疣、痤疮、结缔组织病、光化性疾病等范围.升高温度、促溶剂、金属离子螫合物、电离子导入、脂质体载体等因素可促进其疗效.     

光动力与尤靖安联合治疗多发性尖锐湿疣临床疗效及其对性生活质量的影响

目的探讨光动力联合尤靖安治疗多发性尖锐湿疣的临床疗效及其对性生活质量影响。方法选取2016年1月至2017年12月广安市人民医院诊治的多发性尖锐湿疣患者120例作为研究对象。随机数字表法进行设计对照组与联合组,对照组给予常规治疗,联合组给予光动力联合尤靖安治疗,观察两组的临床治疗效果与性生活质量影响。结果联合组与对照组临床治疗总有效率(91.67%Vs80.00%),比较差异具有统计学意义(P0.05)。治疗后联合组性生活质量总评分达到(93.16±2.18)分,优于对照组的(73.67±2.66)分,差异具有统计学意义(P0.05)。结论临床中对于多发性尖锐湿疣患者应用光动力联合尤靖安治疗效果显著,提高患者的临床治疗总有效率,并且在改善性生活质量方面显著,值得临床中应用推广。     

Ultrastructural alteration of tape-stripped normal human skin after photodynamic therapy

The effect of photodynamic therapy on tape-stripped normal human skin was explored ultrastructurally. Back skin areas of 3 healthy Caucasian volunteers, 2 men and 1 woman, were tape-stripped 10 consecutive times followed by topical treatment with 5-aminolevulinic acid (20%, w/w) for 4 hours under occlusion (Tegaderm). Then the areas were irradiated for 30 minutes with Waldman PDT 1200 lamp (570-650 nm) with a total dose of 70 J/cm(2). Full-thickness punch biopsies were taken immediately after irradiation, and at 3 and 24 hours for electron microscopy examination. Photodynamic therapy caused morphological alterations mainly in the epidermis. Keratinocytes became oedematous and tonofilament bundles were split, but desmosomes remained normal. Many keratinocytes contained large intracellular vacuoles and extremely electronlucent cytoplasm implying cell damage. Although the majority of Langerhans cells were unaffected isolated Langerhans cells became apoptotic at 3 hours. The melanocytes preserved their normal morphology. The epidermal alterations recovered 24 hours after the irradiation. Inflammatory cell infiltrates were evident at 3 and 24 hours but no other dermal changes were observed. In conclusion, photodynamic therapy with 5-aminolevulinic acid affects mainly keratinocytes and can trigger apoptosis in Langerhans cells while melanocytes appear refractory, at least morphologically, to photodynamic therapy.     

Combination effect of photodynamic and sonodynamic therapy on experimental skin squamous cell carcinoma in C3H/HeN mice

We studied a combination of photodynamic therapy (PDT) and sonodynamic therapy (SDT) for improving tumoricidal effects in a transplantable mouse squamous cell carcinoma (SCC) model. Two sensitizers were utilized: the pheophorbide-a derivative PH-1126, which is a newly developed photosensitizer, and the gallium porphyrin analogue ATX-70, a commonly used sonosensitizer. Mice were injected with either PH-1126 or ATX-70 i.p. at doses of 5 or 10 mg/kg.bw. At 24 (ATX-70) or 36 hr (PH-1126) (time of optimum drug concentration in the tumor) after injection, SCCs underwent laser light irradiation (88 J/cm2 of 575 nm for ATX-70; 44J/cm2 of 650 nm for PH-1126) (PDT), ultrasound irradiation (0.51 W/cm2 at 1.0 MHz for 10 minutes) (SDT), or a combination of the two treatments. The combination of PDT and SDT using either PH-1126 or ATX-70 as a sensitizer resulted in significantly improved inhibition of tumor growth (92-98%) (additive effect) as compared to either single treatment (27-77%). The combination using PH-1126 resulted in 25% of the treated mice being tumor free at 20 days after treatment. Moreover, the median survival period (from irradiation to death) of PDT + SDT-treated mice (> 120 days) was significantly greater than that in single treatment groups (77-95 days). Histological changes revealed that combination therapy could induce tumor necrosis 2-3 times as deep as in either of the single modalities. The combination of PDT and SDT could be very useful for treatment of non-superficial or nodular tumors.     

Immunohistochemical expression of matrix metalloproteinases in photodamaged skin by photodynamic therapy

Background  Photodynamic therapy (PDT) has been described for photoageing treatment, but its mechanism of action is not clarified. Although PDT-induced matrix metalloproteinase (MMP) expression and collagen production have been studied in normal skin and in inflammatory disease, there is no report about the effect of PDT on the extracellular matrix in photodamaged skin.
Objectives  To evaluate skin remodelling induced by methyl aminolaevulinate (MAL)-PDT in photodamaged skin by histological and immunohistochemical studies.
Methods  Fourteen patients were treated with two sessions of MAL-PDT. The light source was a light-emitting diode (635 nm, 37 J cm⁻²). Skin biopsies were performed in all patients before and at 3 and 6 months after treatment. Immunohistochemical studies evaluated collagen types I and III, MMP-1, MMP-3, MMP-7, MMP-9, MMP-12 and tissue inhibitor of metalloproteinases-1.
Results  Global improvement in photodamaged skin was observed. A significant increase in expression of MMP-9 in the dermis was detected at 3 months after treatment ( P  =   0·002). Significant increases in the expression of collagen type I at 3 months ( P  =   0·002) and at 6 months after treatment ( P  =   0·001) were also observed.
Conclusions  Skin remodelling induced by MAL-PDT was demonstrated in photodamaged skin. Two sessions of MAL-PDT increases immunohistochemical expression of MMP-9 in the dermis at 3 months after treatment, and also of collagen type I.     

皮肤疾病光动力治疗的光源和照光参数选择

【摘要】 光动力治疗（PDT）是日光性角化病、尖锐湿疣和中重度寻常痤疮等难治性皮肤疾病的一线治疗方法。临床应用中照光参数和光源对PDT疗效有着重要影响。本文着重从光源波长、光源类型、照光剂量几方面阐述PDT中如何设定照光参数和选择光源,并综述新型PDT光源的研究进展。