In vitro and in vivo comparison of two different light sources for topical photodynamic therapy

BACKGROUND: Photodynamic therapy (PDT) with 5-aminolaevulinic acid (ALA) is an effective and safe treatment option for the treatment of actinic keratosis (AK). Incoherent lamps are often used, matching the absorption maxima of ALA. OBJECTIVES: A comparative trial was performed to evaluate the efficacy of recently developed light-emitting diodes (LEDs). METHODS: Human epidermal keratinocytes were incubated for 24 h with ALA (100, 200, 300, 400 or 500 micromol L(-1)) and irradiated consecutively using either an incoherent halogen lamp (lambda(em) = 580-750 nm; 24 J cm(-2); 40 mW cm(-2)) or an LED system (lambda(em) = 633 +/- 3 nm; 3, 6, 12 or 24 J cm(-2); 40 mW cm(-2)). Topical ALA-PDT was performed on 40 patients with AK (n = 584) in a symmetrical distribution suitable for two-sided comparison. After incubation with ALA (20% in cream base) irradiation was performed with the incoherent lamp (100 J cm(-2); 160 mW cm(-2)) on one side and the LED system (40 J cm(-2); 80 mW cm(-2)) on the opposite side followed by re-evaluation up to 6 months. RESULTS: No significant differences between the LED system (3, 6, 12 or 24 J cm(-2)) and the incoherent light source (24 J cm(-2)) regarding cytotoxicity was found in vitro. The complete remission rate yielded in the in vivo investigation was also not significantly different at 6 weeks (P = 0.95), 3 months (P = 0.75) and 6 months (P = 0.61) following therapy. Six weeks following therapy complete remission rates of 84.3% (LED system) and 82.8% (incoherent lamp) were achieved. There was also no significant difference between both light sources regarding pain during light treatment (P = 0.67), patient satisfaction (P = 1.0) or cosmesis (P = 1.0) following therapy. CONCLUSIONS: These results show the efficacy of an LED system for ALA-PDT both in vitro and in vivo. ALA-PDT with the LED system showed a noninferiority regarding the clinical outcome in the treatment of AK compared with the incoherent lamp.     

Comparison of red and green light in the treatment of Bowen's disease by photodynamic therapy

BACKGROUND: A variety of protocols exist for the treatment of Bowen's disease by photodynamic therapy (PDT) using topical 5-aminolaevulinic acid (5-ALA). OBJECTIVE: To determine the optimal wavelength (red or green light) for this treatment. METHODS: A randomized comparison study of ALA-PDT using red (630 +/- 15 nm) or green (540 +/- 15 nm) light in the treatment of Bowen's disease. RESULTS: The initial clearance rate for lesions treated by red light was 94% (30 of 32) in comparison with 72% (21 of 29) for those lesions receiving green light (P = 0.002). Over the following 12 months, there were two recurrences in the red light group and seven in the green light group reducing the clearance rates to 88% and 48%, respectively. The frequency and severity of pain experienced were similar between the two treatment groups. No hyperthermia, nor significant difference in lesional temperatures, was observed between the wavelengths studied. CONCLUSION: Green light is less effective than red light, at a theoretically equivalent dose, in the treatment of Bowen's disease by topical ALA-PDT.     

Ambulatory photodynamic therapy: a new concept in delivering photodynamic therapy

BACKGROUND: Photodynamic therapy (PDT) has been shown to be effective in treating Bowen's disease, superficial basal cell carcinoma and actinic keratosis. OBJECTIVES: To investigate the feasibility of delivering PDT using a portable light-emitting diode device. METHODS: A prototype diode array, comprising 37 AlGaInP diodes cast in epoxy with a diffuser, and driven by a battery pack, was designed and constructed. A pilot study was carried out in five patients with histologically proven Bowen's disease who were referred for PDT with 5-aminolaevulinic acid. They were all treated in the hospital-based dermatology PDT suite such that each received the same level of supervision as patients receiving PDT with nonambulatory light sources. Patients recorded pain levels. In accordance with our usual practice, patients received two treatments at a 4-week interval. RESULTS: Four of five patients were clear at follow-up (range 6-13 months, median 9). Pain was classified as none or mild in 80% of treatments and moderate in the remainder. CONCLUSIONS: There are many potential benefits of ambulatory PDT, including the possibility of a much higher patient throughput, and allowing effective treatment at home. This pilot study provides early promising data of the safety and efficacy of this approach.     

The effect of an iron chelating agent on protoporphyrin IX levels and phototoxicity in topical 5-aminolaevulinic acid photodynamic therapy

BACKGROUND: In 5-aminolaevulinic acid (ALA)-photodynamic therapy (PDT), the prodrug ALA is endogenously converted to the active sensitizer protoporphyrin IX (PpIX), while further conversion of PpIX to haem requires iron. OBJECTIVES: To explore the potential of the iron chelator desferrioxamine (DFO) to enhance PpIX levels and phototoxicity in ALA-PDT. METHODS: A series of six doses of 2% ALA solution was iontophoresed into the healthy skin of each ventral forearm of 10 volunteers. One arm was pretreated with 20% DFO in aqueous cream, while the control arm received aqueous cream alone, for 16 h. At 5 h following iontophoresis, skin-surface PpIX fluorescence was measured, following which the forearms were simultaneously irradiated with 100 J cm-2 broadband red light. The phototoxic reaction was assessed at 24 h postirradiation as the minimal phototoxic dose (MPD) and with quantification of erythema. Next, eight patients with two superficial basal cell carcinomas or two plaques of Bowen's disease of similar appearance received 20% ALA topically to one lesion and 20% ALA with 20% DFO to the other, for 3 h. Skin-surface PpIX fluorescence was measured at 5 h, following which lesions were irradiated with 100 J cm-2 broadband red light. RESULTS: In healthy skin, PpIX fluorescence increased with increasing ALA dose at DFO-treated and untreated sites (P < 0.0005); PpIX fluorescence peak values were consistently higher in DFO-treated compared with control sites (P < 0.02). Erythema also correlated with ALA dose (P < 0.0005), but a significant difference between active and control sites occurred only at low ALA dose (P < 0.05). The median MPD appeared lower at the DFO-treated sites, at 6 mC vs. 12 mC (P = 0.06). In contrast, in lesional skin there was no consistent difference in PpIX fluorescence levels between those treated with and without DFO. CONCLUSIONS: While iron chelation augmented ALA-PDT phototoxicity in normal skin, this occurred only at low ALA dose. Addition of DFO does not appear to confer additional benefit in ALA-PDT of nonmelanoma skin cancers.     

Guidelines for topical photodynamic therapy: report of a workshop of the British Photodermatology Group

Topical photodynamic therapy (PDT) is effective in the treatment of certain non-melanoma skin cancers and is under evaluation in other dermatoses. Its development has been enhanced by a low rate of adverse events and good cosmesis. 5-Aminolaevulinic acid (ALA) is the main agent used, converted within cells into the photosensitizer protoporphyrin IX, with surface illumination then triggering the photodynamic reaction. Despite the relative simplicity of the technique, accurate dosimetry in PDT is complicated by multiple variables in drug formulation, delivery and duration of application, in addition to light-specific parameters. Several non-coherent and coherent light sources are effective in PDT. Optimal disease-specific irradiance, wavelength and total dose characteristics have yet to be established, and are compounded by difficulties comparing light sources. The carcinogenic risk of ALA-PDT appears to be low. Current evidence indicates topical PDT to be effective in actinic keratoses on the face and scalp, Bowen's disease and superficial basal cell carcinomas (BCCs). PDT may prove advantageous where size, site or number of lesions limits the efficacy and/or acceptability of conventional therapies. Topical ALA-PDT alone is a relatively poor option for both nodular BCCs and squamous cell carcinomas. Experience of the modality in other skin diseases remains limited; areas where there is potential benefit include viral warts, acne, psoriasis and cutaneous T-cell lymphoma. A recent British Photodermatology Group workshop considered published evidence on topical PDT in order to establish guidelines to promote the efficacy and safety of this increasingly practised treatment modality.     

Treatment of Darier's disease with photodynamic therapy

BACKGROUND: Photodynamic therapy (PDT) using topical 5-aminolaevulinic acid (5-ALA) as a photosensitizer has been reported in the treatment of both neoplastic and benign cutaneous disorders. OBJECTIVES: To evaluate the efficacy of photodynamic therapy in selected patients with Darier's disease (keratosis follicularis). METHODS: Six patients with Darier's disease were assessed before and after treatment with PDT using 5-ALA and mean fluence rates of 110-150 mW cm-2. RESULTS: Of the six patients, one was unable to tolerate the treatment. Of the remaining five, all experienced an initial inflammatory response that lasted two to three weeks. In four of the five patients, this was followed by sustained clearance or improvement over a followup period of six months to three years. Three of these four patients were on systemic retinoids and the fourth had discontinued acitretin prior to PDT. In the fifth patient partial improvement was followed by recurrence after etretinate therapy was discontinued. Biopsy specimens taken immediately after the procedure in two patients demonstrated a mild inflammatory cell infiltrate in the dermis. A biopsy obtained eighteen months after PDT from a successfully treated area showed no signs of Darier's disease and a subtle increase of collagen in the upper dermis. CONCLUSIONS: Photodynamic therapy can be viewed as a potential adjunctive modality for Darier's disease but should not be considered as a substitute for retinoids in patients who require systemic treatment.     

Calcitriol treatment improves methyl aminolaevulinate-based photodynamic therapy in human squamous cell carcinoma A431 cells

Background  Photodynamic therapy (PDT) using methyl aminolaevulinate (MAL) provides a new, approved method for treatment of skin cancer and its precursors. However, MAL-based PDT is not very efficient for poorly differentiated skin carcinoma. Thus, novel strategies to enhance the PDT effect are needed.
Objectives  In order to improve the efficacy of MAL-based PDT, we investigated the effect of adding calcitriol, a prodifferentiation hormone, to human squamous cell carcinoma A431 cells in vitro .
Methods  A short course (24 h) of calcitriol pretreatment was applied in A431 cells, and, subsequently, MAL-induced protoporphyrin IX (PpIX) was measured.
Results  Calcitriol pretreatment of the cells elevated their PpIX levels. Furthermore, the cell damage after exposure to blue light was significantly higher in calcitriol-treated cells. Increased photoinactivation correlated with higher levels of PpIX in the calcitriol-pretreated cells.
Conclusions  Calcitriol enhances MAL-based PDT in A431 cells.     

Topical 5-aminolaevulinic acid photodynamic therapy for cutaneous lesions: outcome and comparison of light sources

BACKGROUND: Topical 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) is increasingly used for superficial non-melanoma skin cancers and their precursors. METHODS: We report our 3-year experience of topical ALA-PDT, with a preliminary comparison of the effects of broadband and laser light sources. RESULTS: We performed 688 treatments on 483 lesions in 207 patients. Complete clearance was achieved in 222/239 lesions of Bowen's disease (BD), superficial basal cell carcinoma (sBCC) and actinic keratosis (AK) (93%) - 117/129 BD (91%), 84/87 sBCC (97%) and 21/23 AK (91%), with a median follow up of 48 weeks. Broadband and laser light sources were of similar efficacy. Recurrences have occurred in 10.3% BD, 4.8% sBCC and 4.8% AK. Adverse effects from PDT were uncommon but included pigmentary change (2%) and minor scarring (2%). How-ever, severe pain was experienced in 16-21% of treatments using the high-output broadband and laser sources, but in only 2% with the low-output xenon arc source. CONCLUSION: Topical ALA-PDT is effective for BD, sBCC and AK and has been an invaluable addition to our dermatology service. Efficacy is similar for broadband and laser light sources, although treatment at higher surface irradiance may be painful, and excellent cosmetic results can be achieved.     

Variable pulsed light is less painful than light-emitting diodes for topical photodynamic therapy of actinic keratosis: a prospective randomized controlled trial

BACKGROUND: Photodynamic therapy (PDT) of actinic keratosis (AK) using methylaminolaevulinate (MAL) is an effective and safe treatment option, but the procedure is painful. OBJECTIVES: To evaluate the efficacy and pain associated with variable pulsed light (VPL), a prospective, randomized, controlled split-face study was performed. METHODS: Topical MAL-PDT was conducted in 25 patients with AK (n = 238) who were suitable for two-sided comparison. After incubation with MAL, irradiation was performed with a light-emitting diode (LED) (50 mW cm(-2); 37 J cm(-2)) vs. VPL (80 J cm(-2), double pulsed at 40 J cm(-2), pulse train of 15 impulses each with a duration of 5 ms, 610-950 nm filtered hand piece) followed by re-evaluation up to 3 months. RESULTS: The pain during and after therapy was significantly lower with VPL irradiation [t (d.f. = 24) = 4.42, P < 0.001]. The overall mean +/- SD infiltration and keratosis score at 3 months after treatment was 0.86 +/- 0.71 (LED system) vs. 1.05 +/- 0.74 (VPL device) (no statistically significant difference; P = 0.292). Patient satisfaction following both treatment modalities did not significantly differ at the 3-month follow up (P = 0.425). CONCLUSIONS: VPL used for MAL-PDT is an efficient alternative for the treatment of AK that results in complete remission and cosmesis equivalent to LED irradiation but causes significantly less pain.     

Single-episode photodynamic therapy and vulval intraepithelial neoplasia type III resistant to conventional therapy

BACKGROUND: Photodynamic therapy (PDT) using topical 5-aminolaevulinic acid (5-ALA) has been suggested as an effective and tissue-conserving method of treating carcinoma in situ of the vulva. OBJECTIVES: To evaluate PDT in patients with vulval intraepithelial neoplasia type III (VIN III). METHODS: Topical PDT was performed in six patients with VIN III. Five of the six patients had persistent disease following treatment with other modalities including 5-fluorouracil cream, cryotherapy, carbon dioxide laser ablation and excision. Each patient was treated once with a fluence of 150 J cm-2 using a broad-band light source (580-740 nm) 4 h after topical application of 20% 5-ALA. Patients were reviewed clinically at 1 month and 6 months after treatment. RESULTS: All of the patients developed initial erythema of treated sites, three with subsequent erosions. All patients had clinically evident persistent VIN III at 1-month review. Five patients have subsequently undergone surgical treatment and one is regularly reviewed. CONCLUSIONS: This small uncontrolled study indicates that, as currently administered, a single episode of topical PDT is not effective in the management of treatment-resistant VIN III.     

A placebo-controlled randomized study on the clinical effectiveness, immunohistochemical changes and protoporphyrin IX accumulation in fractionated 5-aminolaevulinic acid-photodynamic therapy in patients with psoriasis

BACKGROUND: Topical 5-aminolaevulinic acid (ALA)-photodynamic therapy (PDT) for the treatment of psoriasis has been evaluated in a few studies. In these studies different treatment parameters were used, there was a variable clinical response, and a nonhomogeneous fluorescence was seen after irradiation with Wood's light. OBJECTIVES: To study the clinical effectiveness, immunohistochemical changes and protoporphyrin IX accumulation in ALA-PDT in patients with psoriasis. Eight patients with stable plaque psoriasis with symmetrical involvement were included in the study. Two symmetrical plaques were randomly allocated to PDT either with 10% ALA or with placebo. Irradiation consisted of 2 and 8 J cm(-2) with a dark interval of 2 h (Waldmann PDT 1200 L, 600-750 nm, 40 mW cm(-2)) once weekly for 4 weeks. Before, during and after irradiation, fluorescence diagnosis was performed. Biopsies were taken at baseline, week 1 and week 6 for immunohistochemical assessment. Psoriatic plaques were clinically assessed using the plaque severity (sum) score. Fluorescence diagnosis was performed and expression of immunohistochemical markers for proliferation, differentiation and T-cell infiltration [Ki67, keratin 10 (K10), CD4, CD8 and CD45RO] was assessed. RESULTS: From week 1 up to week 6, ALA-PDT gave a significant reduction in the number of Ki67+ nuclei, while the K10 expression increased. After 6 weeks significant improvement was observed for CD8 and CD45RO. These changes were absent in the placebo-treated lesions. The sum scores were also significantly lower in the ALA-treated plaques. Heterogeneity of macroscopic fluorescence was observed during treatment despite keratolytic treatment. CONCLUSIONS: The present study shows that clinical improvement during fractionated ALA-PDT in psoriasis parallels histological improvement as seen in normalization of epidermal proliferation, differentiation and infiltration of relevant T-cell subsets. Optimizing the current treatment protocol may increase clinical efficacy further.     

Relationship of protoporphyrin IX synthesis to photodynamic effects by 5-aminolaevulinic acid and its esters on various cell lines derived from the skin

Background  5-Aminolaevulinic acid (ALA) and its esters act as precursors to the fluorescent photosensitizer protoporphyrin IX (PpIX) in photodynamic therapy (PDT). There is little information about how ALA and its esters induce PpIX synthesis and photodynamic effects in cell lines derived from the skin.
Objectives  We compared the amount of PpIX synthesis induced by ALA and its esters in skin cell lines, and evaluated the relationship of PpIX synthesis to photodynamic effects by ALA and its esters in vitro .
Methods  Four cell lines, including human epidermal keratinocytes (HEK), human dermal fibroblast (hF), A431, and TXM13 were used. Cell survival was evaluated by the MTT assay. Fluorescence spectroscopy was used to measure the amount of PpIX synthesis induced by ALA and its esters. Flow cytometry measured cell death induced by ALA- and its esters-mediated PDT.
Results  ALA and its esters were not toxic at concentrations lower than 2 mmol L⁻¹ in all cell lines. PpIX synthesis was dose-dependent at low doses (0·01–0·1 mmol L⁻¹), and ALA esters were more effective than ALA. Cell death occurred from necrosis rather than apoptosis just after light irradiation illumination on both ALA and its esters-treated cells. Cell death related more to PpIX synthesis than the irradiation light dose.
Conclusions  PpIX production by ALA and its esters was induced on both normal and malignant cell lines derived from the skin, and cell death of PDT responses is closely related to the amount of PpIX synthesis rather than to the irradiation dose.     

Guidelines for topical photodynamic therapy: update

Multicentre randomized controlled studies now demonstrate high efficacy of topical photodynamic therapy (PDT) for actinic keratoses, Bowen's disease (BD) and superficial basal cell carcinoma (BCC), and efficacy in thin nodular BCC, while confirming the superiority of cosmetic outcome over standard therapies. Long-term follow-up studies are also now available, indicating that PDT has recurrence rates equivalent to other standard therapies in BD and superficial BCC, but with lower sustained efficacy than surgery in nodular BCC. In contrast, current evidence does not support the use of topical PDT for squamous cell carcinoma. PDT can reduce the number of new lesions developing in patients at high risk of skin cancer and may have a role as a preventive therapy. Case reports and small series attest to the potential of PDT in a wide range of inflammatory/infective dermatoses, although recent studies indicate insufficient evidence to support its use in psoriasis. There is an accumulating evidence base for the use of PDT in acne, while detailed study of an optimized protocol is still required. In addition to high-quality treatment site cosmesis, several studies observe improvements in aspects of photoageing. Management of treatment-related pain/discomfort is a challenge in a minority of patients, and the modality is otherwise well tolerated. Long-term studies provide reassurance over the safety of repeated use of PDT.     

The characteristics of erythema induced by topical 5-aminolaevulinic acid photodynamic therapy

BACKGROUND: Topical photodynamic therapy (PDT) is increasingly used to treat superficial non-melanoma skin cancers. Knowledge of the characteristics of 5-aminolaevulinic acid (ALA)-induced phototoxicity will increase our understanding of PDT and may facilitate optimisation of treatment regimes. METHODS: We examined the characteristics of ALA-induced erythema in 10 healthy subjects and investigated the effect of light source and body site. RESULTS AND CONCLUSIONS: Maximal erythema occurred within 1-2 h of PDT and inter-individual variation in ALA-induced phototoxicity was seen. No detectable differences were seen in the phototoxicity on back or leg sites or between coherent and non-coherent light sources. These data provide further information to allow us to optimise topical PDT regimes.     

Penetration enhancement of two topical 5‐aminolaevulinic acid formulations for photodynamic therapy by erbium:YAG laser ablation of the stratum corneum: continuous versus fractional ablation

Please cite this paper as: Penetration enhancement of two topical 5‐aminolaevulinic acid formulations for photodynamic therapy by erbium:YAG laser ablation of the stratum corneum: continuous versus fractional ablation. Experimental Dermatology 2010; 19 : 806–812. Abstract: 5‐Aminolaevulinic acid (ALA) is used in photodynamic therapy (PDT). Response rates of PDT vary widely, which may be because of the limited uptake of topically applied photosensitisers. We investigated skin penetration and fluorescence induction of protoporphyrin IX (PpIX) after applying either 20% ALA cream or 20% aminolaevulinic acid solution on laser‐stripped stratum corneum (SC) in an ex vivo full‐thickness porcine skin model. Both formulations are used in clinical practice. To enhance the skin penetration of ALA, we used two different 2940‐nm erbium:yttrium–aluminium–garnet (Er:YAG) laser systems to partially ablate the SC: continuous and fractional ablation. Different fluences were applied ranging from 0.5 to 1.5 J/cm² (continuous ablation) and from 4 to 24 J/cm² (fractional ablation). Fluorescence microscopy was used for detecting PpIX‐induced fluorescence. Compared to skin without laser pretreatment, mean fluorescence intensity (MFI) of PpIX was enhanced 13.8‐fold after continuous ablation with 1.0 J/cm² and 7.3‐fold after fractional ablation with 4 J/cm²; each laser procedure was followed by 4‐h incubation with lipophilic ALA cream. Optimal parameters for continuous ablation without damage to the epidermis were 1 J/cm² for both formulations, fractional ablation was best with 4 J/cm². Histological evaluations of laser‐treated skin showed necrosis and apoptosis, depending on light dose. In laser‐stripped skin, PpIX fluorescence was detected earlier and reached deeper epidermal layers than in untreated skin. Continuous laser ablation induced higher PpIX fluorescence levels than fractional ablation. This method offers a promising new tool for enhancing ALA penetration in PDT without damaging the underlying tissue.     

Topical application of 5-aminolaevulinic acid, methyl 5-aminolaevulinate and hexyl 5-aminolaevulinate on normal human skin

BACKGROUND: 5-Aminolaevulinic acid (ALA) and its ester derivatives are used in photodynamic therapy. Despite extensive investigations, the differences in biodistribution and pharmacokinetics of protoporphyrin IX (PpIX) induced by ALA and its derivatives are still not well understood, notably for humans. OBJECTIVES: To study porphyrin accumulation after topical application of ALA and two of its ester derivatives in normal human skin. METHODS: Creams containing 0.2%, 2% and 20% (w/w) of ALA, methyl 5-aminolaevulinate (MAL) and hexyl 5-aminolaevulinate (HAL) were applied on normal human skin of six volunteers. The amount and distribution of porphyrins formed in the skin was investigated noninvasively by means of fluorescence spectroscopy. RESULTS: Fluorescence emission and excitation spectra exhibited similar spectral shapes for the all drugs, indicating that mainly PpIX was formed. Low concentrations (0.2% and 2%) of MAL induced considerably less PpIX in normal human skin than similar concentrations of ALA and HAL. A high concentration (20%) of ALA gave higher PpIX fluorescence in normal human skin than was found for MAL and HAL. CONCLUSIONS: The concentrations inducing half of the maximal PpIX fluorescence are around 2% for ALA, 8% for MAL and 1% for HAL.     

Topical photodynamic therapy with 5-aminolaevulinic acid does not induce hair regrowth in patients with extensive alopecia areata

BACKGROUND: Photodynamic therapy (PDT) is a new modality involving the administration of a photosensitizer, or photosensitizer precursor, followed by its activation with light to generate a therapeutic effect. 5-Aminolaevulinic acid (ALA) is a photosensitizer precursor that is transformed by cells into protoporphyrin IX (PpIX), which can in turn be activated by red light. OBJECTIVES: To investigate the effect of PDT in alopecia areata (AA). METHODS: In six patients with extensive AA, topical ALA lotion at 5%, 10% and 20% as well as the vehicle lotion alone were applied separately to different scalp areas, followed 3 h later by exposure to red light at each treatment session. RESULTS: No significant hair growth was observed after 20 twice-weekly treatment sessions. A significant increase in erythema and pigmentation was observed for the three concentrations of ALA lotion vs. the vehicle, implying that a phototoxic PDT effect was achieved in the skin. In vivo fluorescence spectroscopy in one patient showed an increase in red PpIX fluorescence 3 h after ALA application followed by a decrease after light exposure. On fluorescence microscopy, bright red fluorescence was present in the epidermis and sebaceous glands, but not in the inflammatory infiltrate surrounding the hair follicle following ALA application. CONCLUSIONS: PDT was ineffective in the treatment of AA.     

Methylaminolaevulinate-based photodynamic therapy of Bowen's disease and squamous cell carcinoma

Background  Photodynamic therapy (PDT) with methylaminolaevulinate (MAL) is an approved noninvasive treatment option for actinic keratosis and Bowen's disease (BD), two precursors of invasive squamous cell carcinoma (SCC).
Objectives  To assess efficacy, prognostic features, tolerability and cosmetic outcome of MAL-PDT for the treatment of BD and SCC.
Methods  In total, 112 biopsy-proven lesions of BD and SCC in 55 subjects were treated in an outpatient setting. MAL cream (160 mg g⁻¹) was applied for 3 h prior to illumination with a light-emitting diode source (wavelength range 635 ± 18 nm; light dose 37 J cm⁻²). A second MAL-PDT session was given 7 days later. Complete response rate at 3 months after the last treatment, recurrence rate at the 24-month follow-up, and cosmetic outcome were recorded.
Results  The overall complete response rates were 73·2% at 3 months and 53·6% at 2 years. Clinical thickness, atypia and lesion depth were significant predictors of the response at 3 months when using a univariate analysis ( P  <   0·001). A multivariate logistic regression model, with robust variance estimation, showed that cell atypia was the only statistically significant independent predictor of the treatment outcome at 3 months.
Conclusions  MAL-PDT may represent a valuable, effective and well tolerated treatment option with good cosmetic outcome for superficial, well-differentiated (Broders' scores I and II) BD and microinvasive SCC. In contrast, its use for superficial SCCs with a microinvasive histological pattern and for nodular, invasive lesions, particularly if poorly differentiated keratinocytes are present (Broders' scores III and IV), should be avoided.     

Warty and clear-cell Bowen's disease successfully treated with photodynamic treatment

Clear cell Bowen's disease (BD) is a rare histopathological subtype of BD, characterized by epidermal atypical keratinocytes with clear-cell changes exceeding 80% of the tumor population. Warty and clear cell Bowen's disease (WCCBD) is a recently described variant of clear cell BD, with verrucous and hyperkeratotic surface changes in addition to pathological features consisting of an extremely acanthotic epidermis, hyperkeratosis and clear-cell changes. Herein we present a 72-year-old man with a 1-year history of tumoral lesion located on the left cheek with a diagnosis of WCCBD, in whom we achieved excellent result with photodynamic treatment. To the best of our knowledge, this is the second reported case of this entity.