Hong-Wei Wang

Topical ALA PDT for the treatment of severe acne vulgaris

OBJECTIVES To evaluate the effectiveness of topical 5-aminolevulinic acid (ALA)-medicated photodynamic therapy (PDT) for the treatment of severe acne vulgaris. METHODS A total of 78 Chinese patients with Grade 4 severe facial acne were treated with 1-3 courses of ALA PDT. ALA cream (10%) was applied topically to acne lesions for 3 h. The lesions were irradiated by a LED light of 633 nm at dose levels of 50-70 J/cm(2) at 66 mW/cm(2). Clinical assessment was conducted before and after treatment up to 6 months. RESULTS 22% of patients showed excellent improvement after one-course treatment and another 34% showed excellent improvement after two-course. The rest (44%) required three-course treatment to further reduce the number and size of residual lesions. Adverse effects were minimal. The symptoms and signs in recurrent cases (14%) were much milder and responded well to conventional topical medication. CONCLUSIONS ALA PDT is a simple, safe and effective therapeutic option for the treatment of severe acne. Further studies to fully understand its mechanisms and optimize its effectiveness are needed.

Optical properties of hematoporphyrin monomethyl ether (HMME), a PDT photosensitizer

We report on some of the optical properties of Hemoporfin (hematoporphyrin monomethyl ether, HMME), a photodynamic therapy (PDT) photosensitizer that has been in clinical trials in China since the early 1990s. We characterized the photosensitizer on the basis of one- and two-photon absorption and fluorescence emission. The effects of photobleaching were probed to characterize its decay kinetics. Additionally, we determined time resolved fluorescence and thermal effects on fluorescence and absorption properties.

Combination of immunotherapy and photodynamic therapy in the treatment of Bowenoid papulosis

OBJECTIVE To investigate the feasibility and efficacy of combination of imiquimod and 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) for the treatment of genital Bowenoid papulosis (BP). MATERIALS AND METHODS A total of 27 BP patients were randomized into two groups. Fifteen (12 male and 3 female, age 22-56 years old) were treated with topical application of 5% imiquimod cream (three times a week) and ALA-PDT (100J/cm(2) at 100mW/cm(2), once a week) for 1-4 times. For comparison, other 12 (6 male and 6 female, age 29-58 years old) were treated with CO2 laser vaporization as a control. Patients were followed up for 3-12 months. Biopsies were taken from BP lesions prior to treatment and tested for HPV-16 and HPV-18 DNA. RESULTS In combined therapy group, 60% (9/15) patients showed complete remission and only one recurred (11.1%) during follow up. Local side effects included mild erythema, edema, erosion and burning and/or stinging sensation. No systemic side effect was found. In CO2 laser vaporization group, 83.3% (10/12) patients showed complete remission. However, recurrence occurred in six patients (60.0%). Local side effects included mild to moderate edema, erosion, ulceration, delayed healing, prolonged pain and scarring. The difference of recurrence rate between two groups was statistically significant (P<0.05). CONCLUSION Topical application of imiquimod cream and ALA-PDT is safe, effective and associated with low recurrence and less side effect.

Treatment of HPV Infection‐Associated Cervical Condylomata Acuminata with 5‐Aminolevulinic Acid‐Mediated Photodynamic Therapy

The aim of this study was to investigate the efficacy of 5‐aminolaevulinic acid (ALA)‐mediated photodynamic therapy (PDT) in treatment of human papillomavirus (HPV)‐associated cervical condylomata. A total of 56 patients with cervical and external condylomata lesions were recruited for this open‐label study. HPV genotyping of exfoliated cells collected from the cervix and external lesions was performed. Cervical lesions were treated with PDT by applying ALA gel (10%) to the surface of the cervix for 4 h followed by irradiating with a 635 nm laser at 100 J cm−2. PDT was repeated at 2‐week intervals if lesion and HPV infection remained. Patients were followed up for 6–24 months. Genotyping analysis revealed four HPV subtypes (HPV6, 11, 16 and 18). The overall complete remission rate of 1–4 sessions of treatments was 98.2% and the corresponding HPV clearance rate was 83.9%. Ten cases showed complete removal of cervical lesions and HPV infection after a single treatment. Recurrence rate was 3.6%. Adverse effects were minimal and no structural complications were reported. In conclusion, topical ALA PDT is safe and effective for eradicating cervical HPV infection and eliminating condylomata lesion. Its definitive role in treating cervical condylomata deserves further investigation.

Therapeutic and immune effects of 5‐aminolevulinic acid photodynamic therapy on UVB‐induced squamous cell carcinomas in hairless mice

The therapeutic effects of 5‐aminolevulinic acid (ALA)‐mediated photodynamic therapy (PDT) on cutaneous squamous cell carcinoma (SCC) are not fully understood, and the usefulness of topical PDT in the treatment of SCC is still debatable. The most interesting aspect in SCC PDT is perhaps its potential in inducing antitumor immune responses. In this study, cutaneous SCCs were established by UVB irradiation of hairless mice and treated with multiple ALA PDT. Immunohistochemistry assays showed that ALA PDT could induce quick apoptosis, overexpression of TNFα and marked increases in DCs, CD4+ and CD8+ cells in tumor interstitium and subcutaneous connective tissues. However, a complete response was only achieved for small SCCs. The clinical value of ALA PDT‐induced specific antitumor immune responses in long‐term control of SCCs deserves further study.

Successful treatment of refractory facial acne using repeat short-cycle ALA-PDT: Case study.

Acne vulgaris is a common dermatological disorder. Topical photodynamic therapy (PDT)-mediated with aminolevulinic acid (ALA) or methyl aminolevulinic acid (MAL) has been successfully used in the treatment of moderate to severe acne. The purpose of this case report is to highlight the feasibility of using a repeat weekly short-cycle ALA-PDT to treat severe facial acne lesions refractory to systemic retinoid and antibiotics.

Evaluation of collagen alteration after topical photodynamic therapy (PDT) using second harmonic generation (SHG) microscopy — in vivo study in a mouse model

Topical photodynamic therapy (PDT) mediated by 5-aminolevulinic acid (ALA) has been used for the treatment of age-related skin lesions for therapeutic or cosmetic purposes. The modulation of collagen component and structure might play a significant role in influencing treatment outcomes of PDT. In this study, the effect of multi-session low dose ALA PDT on skin rejuvenation was examined in a hairless mouse model. Changes in collagen and skin texture were investigated by histological examination and in vivo second harmonic generation (SHG) microscopy. Results indicated that multi-session PDT could improve the collagen density and arrangement of skin tissue. SHG microscopy combined with quantitative collagen analysis could provide a useful tool for the evaluation of collagen alteration induced by ALA PDT.

Aminolevulinic acid (ALA)-assisted photodynamic diagnosis of subclinical and latent HPV infection of external genital region

The relatively high recurrence rate of genital warts can be attributed to the unsuccessful elimination of viruses in areas of subclinical and latent infection. Therefore, the identification and treatment of the subclinical and latent infection is a key to reduce the recurrence. The goal of this study is to investigate the usefulness of 5-aminolevulinic acid (ALA)-assisted in situ fluorescence diagnosis of subclinical lesion and latent HPV infection. A total of 30 patients with histologically confirmed genital warts (condylomata acuminata) were subjected to topical application of ALA, acetic acid test, histopathologic examination and HPV DNA subtyping. Topical application of ALA was performed by applying 20% ALA cream to the lesion plus 2-cm margin for 2h followed by fluorescence examination. Correlations between histopathologic examination, aceto-whitening test, HPV DNA subtyping and fluorescence were examined. All warty lesions and subclinical lesions (n=25) showed red fluorescence and harbored HPV DNA (HPV6 or 11). Latent HPV infections at 0.5-2 cm away from the warty lesion also showed red fluorescence. Nonspecific fluorescence was associated with mucosa, inflammatory infiltration and erosive lesion. ALA-assisted photodynamic diagnosis could be employed for the detection of the lesion and subclinical lesion of genital warts. It is also useful in detecting latent HPV infection.

Comparison of 5-aminolevulinic acid photodynamic therapy and red light for treatment of photoaging.

OBJECTIVE The aim of this pilot study was to compare the efficacy of ALA-PDT and red light alone in the treatment of photoaging. METHODS A total of 14 adults with photoaging skin were recruited. ALA-PDT or red light alone was applied to the forearm extensor. Before and after treatment, the treated sites were examined by dermoscopy, the changes in straum corneum (SC) hydration, transepidermal water loss (TEWL), and the L*a*b* values were measured, and microscopic examination of collagens and elastins was performed. RESULTS After ALA-PDT or red light illumination, the appearance of photoaging lesions improved, SC hydration increased and TEWL decreased. These changes in the ALA-PDT group were more obvious than those in the red light group. No significant change was noticed in the L*a*b* values in both groups. The signs of typical solar elastosis damage were improved in both groups. CONCLUSIONS ALA-PDT showed better skin rejuvenation effect than red light alone.

A prospective pilot study to evaluate combined topical photodynamic therapy and surgery for extramammary paget's disease.

Extramammary Pagets disease (EMPD) is a rare intra‐epithelial neoplasm. Surgical excision is the treatment of choice. The usefulness of topical photodynamic therapy (PDT) in the treatment of EMPD has been reported. The objective of this prospective pilot study was to investigate the feasibility of combined PDT and surgery in the treatment of EMPD.