Review of the European Society for Photodynamic Therapy (Euro-PDT) Annual Congress 2022.

This article reviews the 2022 European Society for Photodynamic Therapy (Euro-PDT) Annual Congress. PDT has been investigated for the treatment of a broad number of oncologic, infectious and inflammatory indications. New studies confirm the potential for wider use of topical PDT for acne and photoaging, as well as several uncommon conditions including tinea capitis, Mycobacterium marinum, cutaneous alternariosis, resistant acral warts, eyelid Bowen's disease, mycosis fungoides, pseudolymphoma, and graft-versus-host disease. Hidradenitis suppurativa patients may also benefit from intra-lesional PDT. Several methods of delivering PDT have been validated, including conventional, daylight and artificial daylight PDT. Light-emitting fabrics have emerged as an innovative solution to the delivery of uniform light over the scalp as well as anatomically-challenging sites, with opportunities now to control and monitor these devices via mobile phone applications. Pre-treatment of patients with thicker, more difficult-to-treat actinic keratoses (AK) with calcitriol appears to be a practical approach to increasing efficacy, although this is associated with increased local skin reactions. Sequential treatment of AK and photoaging with daylight-PDT and injectable NASHA gel indicates that these two therapeutic approaches offer complementary effects. Potential biomarkers may help predict responsiveness of patients with field cancerization and AK receiving daylight PDT. Over-expression of the proto-oncogene, Myc, has been observed in poor responders, whilst the tumour suppressor gene, PTEN, showed under-expression. The potential for use and methods of delivery of topical PDT for dermatological indications continue to expand the enhanced choice of treatment offered to patients.

Review of the European Society for Photodynamic Therapy (Euro-PDT) Annual Congress 2020.

This article reviews the 2020 European Society for Photodynamic Therapy (Euro-PDT) Annual Congress. Cutting edge studies included assessment of immunohistochemical variables influencing response of basal cell carcinomas and Bowen's disease to PDT with p53, the only biomarker associated with good response in both conditions. A further study indicated that analysis of molecular markers, such as PIK3R1, could help select patients with actinic keratoses who demonstrate the best response to daylight PDT. Novel delivery protocols include artificial daylight, and laser-assisted and textile PDT. The meeting learnt of novel indications including antimicrobial PDT, as well as methods to optimise daylight PDT, including combination therapy for actinic keratoses. Adverse events were reviewed and options for painless and efficient PDT assessed, including the effect of reduced drug-light interval. A smartphone application was also evaluated which may be used to assist clinicians and patients in effective dosing and timing of daylight PDT via computational algorithms using data from earth observation satellites, to send light and ultraviolet dose information directly to patients' smart phones.

Daylight Photodynamic Therapy for Actinic Keratoses.

Topical photodynamic therapy (PDT) using daylight is effective in the treatment of actinic keratoses (AKs), offering the potential for treatment of large fields such as full face and balding scalp, but with minimal therapy-associated pain. Comparison with conventional PDT indicates similar efficacy for thin and moderate-thickness AKs, but with significantly less discomfort/pain, driving a patient preference for daylight-mediated PDT (DL-PDT) compared with conventional PDT using high-intensity office/hospital-based light sources. Treatment protocol involves the application of a photosensitizing agent without occlusion and subsequent exposure to ambient daylight within 30 min, with patients exposed to daylight for 1.5-2.0 h. Pivotal randomized controlled trials in Europe and Australia have confirmed the efficacy of methyl aminolevulinic acid (MAL) DL-PDT in comparison with conventional MAL-PDT for mild and moderate-thickness lesions on the face and scalp. Initial clearance rates of 70-89% are reported. DL-PDT using a nanoemulsion aminolevulinic acid (ALA) has recently been shown to be at least as effective as MAL DL-PDT in treating mild and moderate-thickness AKs. DL-PDT may offer a better-tolerated method for treating patients with extensive AK disease. There is emerging literature on the potential for field PDT to reduce the number of new AKs developing, potentially preventing/slowing skin cancer development. Conventional PDT remains established as a therapy for Bowen's disease (squamous cell carcinoma in situ), superficial and certain thin basal cell carcinomas (BCCs), and AKs. The evidence for the use of DL-PDT beyond AK is limited, although has been reported in actinic cheilitis, superficial BCC, and acne and cutaneous leishmaniasis. There is emerging interest in combination therapy for AK, using one or more field therapies such as DL-PDT as an option to complement with localized treatment for residual lesions. We review current recommendations and consider the appropriate place for DL-PDT in our treatment armamentarium.

15th Annual Congress of the European Society for Photodynamic Therapy in Barcelona, Spain, February 12-13th 2016.

UNLABELLED: We provide a summary of the presentations made at the recent Euro-PDT annual Congress. Presentations covered developments in topical photodynamic therapy (PDT) pertaining to dermatological applications. Recognizing the high prevalence and chronicity of actinic keratosis, one of the approved indications for PDT, there were recommendations to pursue field therapy to treat clinical and preclinical lesions. A separate section was reserved to review the strong evidence for the use of daylight PDT for actinic keratosis and experience of use of this well tolerated form of PDT was reported from several countries. Several presentations covered the remaining approved uses of topical PDT, Bowen's disease and basal cell carcinomas, as well as considering its role in so far unapproved indications including photorejuvenation. FUNDING: Galderma.

Vaccination of patients with cutaneous melanoma with telomerase-specific peptides.

PURPOSE: A phase I study was conducted to investigate the safety, tolerability, and immunological responses to vaccination with a combination of telomerase-derived peptides GV1001 (hTERT: 611-626) and p540 (hTERT: 540-548) using granulocyte-macrophage colony-stimulating factor (GM-CSF) or tuberculin as adjuvant in patients with cutaneous melanoma. EXPERIMENTAL DESIGN: Ten patients with melanoma stages UICC IIb-IV were vaccinated 8 times intradermally with either 60 or 300 nmole of GV1001 and p540 peptide using GM-CSF as adjuvant. A second group of patients received only 300 nmole GV1001 in combination with tuberculin PPD23 injections. HLA typing was not used as an inclusion criterion. Peptide-specific immune responses were measured by delayed-type hypersensitivity (DTH) reactions, in vitro T cell proliferation assays, and cytotoxicity (51-Chromium release) assays for a selected number of clones subsequently generated. RESULTS: Vaccination was well tolerated in all patients. Peptide-specific immune response measured by DTH reactions and in vitro response could be induced in a dose-dependent fashion in 7 of 10 patients. Cloned T cells from the vaccinated patients showed proliferative responses against both vaccine peptides GV1001 and p540. Furthermore, T cell clones were able to specifically lyse p540-pulsed T2 target cells and various pulsed and unpulsed tumor cell lines. CONCLUSION: These results demonstrate that immunity to hTERT can be generated safely and effectively in patients with advanced melanoma and therefore encourage further trials.

Skin cancers in renal transplant recipients: a description of the renal transplant cohort in Bern.

BACKGROUND/AIMS: Skin tumours, in particular squamous-cell carcinomas (SCC), are the most common malignant conditions developing in transplant recipients. The aim of this study is to investigate the frequency and type of skin cancer in patients receiving immunosuppressive therapy after organ transplantation. METHODS: Multivariate logistic regression analysis was performed on data of 243 renal transplant patients who attended the dermatology outpatient clinic for the first time after transplantation in the period January 2002-October 2005. RESULTS: We found an increased risk of actinic keratosis (AK) and SCC in renal transplant recipients with a basal cell carcinoma (BCC) / SCC ratio of 1:7. Older patients had AK more frequently (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.06-1.15; p <0.0001) and SCC (OR 1.14, CI 1.07-1.22; p <0.0001) than younger patients. Men had AK (OR 0.19, CI 0.08-0.45; p = 0.0002) and SCC (OR 0.25, CI 0.07-0.89; p = 0.0332) more frequently than women. The duration of immunosuppressive therapy correlated significantly with the numbers of AKs (OR 1.15, CI 1.08-1.24; p <0.0001) and SCCs (OR 1.16, CI 1.05-1.28; p = 0.0025), and patients with fair skin had more AKs (OR 0.31, CI 0.14-1.24; p <0.0001) and SCCs (OR 0.11, CI 0.02-0.52; p = 0.0054) than darker skinned patients. We could not identify any specific immunosuppressive drug as a distinct risk factor for AK or non-melanoma skin cancer (NMSC). CONCLUSION: Skin cancers are increased in the renal transplant population. Main risk factors for skin cancers are fair skin type and long duration of immunosuppressive therapy. A follow-up programme is necessary for early detection of skin cancer and precancerous conditions. Preventive strategies should include specialist dermatological monitoring and self-examination.

Cost-effectiveness of biologics for moderate-to-severe psoriasis from the perspective of the Swiss healthcare system.

Treatment with biologics for moderate-to-severe psoriasis has been approved in Switzerland (2004). However, compulsory basic health insurance limits treatment in non-responders after 12 weeks; responders can continue. The study objective was to evaluate incremental cost-effectiveness ratios (ICERs) due to this regulation. Response was defined as achieving PASI 50, 75, or 90. Placebo-adjusted responder rates were gathered from randomized, controlled trials (weeks 12, 24). Total treatment costs were assessed according to Swiss prices and tariffs. Regimens investigated were infliximab (5 mg/kg IV), etanercept (50 mg SC twice weekly [tw] for 12 weeks, then 25 mg SC tw), adalimumab (80 mg SC week 0, then 40 mg every other week), efalizumab (1 mg/kg/week SC), and alefacept (15 mg/week IM, 12 weeks). Cost effectiveness was calculated as ICER per PASI 50, 75, and 90 responder. Treatment with infliximab led to the highest response rates. Infliximab demonstrated lowest ICER per PASI 90 responder of CHF 22,995 at 12 weeks. Modeling treatment changes at 12 weeks over 36-weeks-horizon resulted in lowest ICER per PASI 75 responder for adalimumab and infliximab compared to the other biologics. Hence in Switzerland, selecting the initial biologic with a high response rate evidenced best value for money.

Alopecia areata universalis elicited during treatment with adalimumab.

Adalimumab is a fully humanized recombinant anti-tumour-necrosis-factor (TNF-alpha) monoclonal antibody which has been approved for rheumatoid arthritis, active ankylosing spondylitis, psoriatic arthritis and Crohn's disease. We report a case of alopecia areata (AA) universalis occurring 6 months after administration of adalimumab monotherapy in a patient with a long-standing history of psoriatic arthritis and psoriasis. The diagnosis was confirmed by a scalp biopsy which showed a peribulbar infiltrate of both CD4+ and CD8+ T cells, CD1a+ dendritic cells as well as CD68+ and CD163+ macrophages. In addition, immunofluorescence staining for TNF-alpha was found in the mononuclear cell infiltrate. This case suggests a complex role of TNF-alpha in the induction of AA.

Wegener's granulomatosis presenting as pyoderma gangrenosum.

Half of the patients with Wegener's granulomatosis develop skin lesions due to the systemic vasculitis. Wegener's granulomatosis should be included in the differential diagnostic considerations for necrotic ulcers, including leg ulcers. We present a case which demonstrates the importance of histological evaluation of a skin biopsy from the margin of the ulcer for establishing the diagnosis. Antineutrophil cytoplasmic antibodies with antigen specificity for proteinase 3 (PR3-ANCA) were detected supporting the diagnosis of Wegener granulomatosis. Further evaluation showed involvement of the eyes and kidneys. The ulcer rapidly healed under treatment with cyclophosphamide and corticosteroids.

Efalizumab-associated papular psoriasis.

BACKGROUND: Efalizumab is a human anti-CD11a monoclonal antibody used in the treatment of patients with moderate to severe plaque psoriasis. Some of the patients develop new papular lesions during treatment, which are predominantly located in the flexural regions. OBSERVATION: Four patients with recalcitrant psoriasis undergoing treatment with efalizumab presented with erythematous, partly scaly papules and small plaques on previously unaffected areas after 4 to 10 weeks of efalizumab therapy. Tissue sections of biopsy specimens were stained with hematoxylin-eosin, and immunohistochemical staining was performed using monoclonal antibodies against CD3, CD4, CD8, T-cell-restricted intracellular antigen 1, granzyme B, neutrophil elastase, CD68, CD1a, CD11c, HLA-DR, CD25, CD20, and CD56. Histopathological and immunohistochemical examination of the lesions showed features consistent with psoriasis and activation of various leukocyte subtypes including T cells, dendritic cells, macrophages, and neutrophils. CONCLUSIONS: Papular eruptions appearing during efalizumab therapy represent new psoriatic lesions and could be referred to as efalizumab-associated papular psoriasis (EAPP). They usually do not necessitate termination of efalizumab therapy and may optionally be treated with topical corticosteroids. Dermatologists should be aware of these lesions and inform their patients accordingly.

Detection of perforin and granzyme B mRNA expressing cells in lichen sclerosus.

Granzyme B and perforin messenger RNA (mRNA) expression has been shown to be a specific in vivo activation marker for cytotoxic cells. The aim of this study was to assess the contribution of cell-mediated cytotoxicity in the pathogenesis of lichen sclerosus. In situ hybridization and immunohistochemistry were performed on serial tissue sections of lesional skin biopsies and normal skin as control. Immunohistochemical staining showed that the cellular infiltrate of diseased skin consisted predominantly of T cells (CD3+) and some B cells (CD20+). Among T cells CD4+ and CD8+ cells were found in about equal numbers. In normal skin samples perforin and granzyme B mRNA expressing cells were only rarely found. In contrast, in biopsies from diseased skin a high percentage of infiltrating cells expressed mRNA for perforin and granzyme B. The perforin and granzyme B expressing cells were found in the dermal infiltrate and intraepidermally in close proximity to keratinocytes suggesting in situ activation of these cells. These findings provide evidence that cell-mediated cytotoxicity plays a significant role in tissue destruction in lichen sclerosus.

Guidelines on the use of photodynamic therapy for nonmelanoma skin cancer: an international consensus. International Society for Photodynamic Therapy in Dermatology, 2005.

Topical photodynamic therapy (PDT) is used to treat nonmelanoma skin cancers, such as actinic keratoses, Bowen's disease, and basal cell carcinoma (superficial and nodular). This article presents up-to-date, practical, evidence-based recommendations on the use of topical PDT using 5-aminolevulinic acid or methyl aminolevulinate for the treatment (and prevention) of nonmelanoma skin cancers. A systematic literature review was conducted (using MEDLINE), and recommendations were made on the basis of the quality of evidence for efficacy, safety/tolerability, cosmetic outcome, and patient satisfaction/preference. Topical PDT is highly effective in the treatment of actinic keratoses, Bowen's disease, superficial and thin nodular basal cell carcinomas, with cosmesis typically superior to that achieved with existing standard therapies. PDT may also be a means of preventing certain nonmelanoma skin cancers in immunosuppressed patients.

Hypersensitivity reaction against patent blue during sentinel lymph node removal in three melanoma patients.

BACKGROUND: In order to identify the sentinel lymph node (SLN) in melanoma patients intradermal injection of a radiocolloid tracer and a blue dye are commonly used. Life-threatening side effects such as allergic reactions to the injected dye have been described. We report 3 cases with systemic allergic reactions. METHODS: Three patients suffering from systemic reactions such as hypotension and rash during SLN biopsy were tested for sensitisation against patent blue and methylene blue with skin prick, scratch, and intradermal test. RESULTS: All 3 patients showed positive skin tests to patent blue confirming allergic reaction to the injected dye. In addition, all patients showed positive skin tests with methylene blue indicating immunologic cross-reactivity between patent blue and methylene blue. CONCLUSIONS: Although allergic reactions to blue dye during SLN biopsy are rare, they may be life threatening. It is important that the attending anesthetist is aware of this.

Benefits from the use of a pimecrolimus-based treatment in the management of atopic dermatitis in clinical practice. Analysis of a Swiss cohort.

BACKGROUND: Controlled studies established the efficacy and good tolerability of pimecrolimus cream 1% for the treatment of atopic dermatitis but they may not reflect real-life use. OBJECTIVE: To evaluate the efficacy, tolerability and cosmetic acceptance of a pimecrolimus-based regimen in daily practice in Switzerland. METHODS: This was a 6-month, open-label, multicentre study in 109 patients (55% > or = 18 years) with atopic dermatitis. Pimecrolimus cream 1% was incorporated into patients' standard treatment protocols. RESULTS: The pimecrolimus-based treatment was well tolerated and produced disease improvement in 65.7% of patients. It was particularly effective on the face (improvement rate: 75.0%). Mean pimecrolimus consumption decreased from 6.4 g/day (months 1-3) to 4.0 g/day (months 3-6) as disease improved. Most patients (74.1%) rated their disease control as 'complete' or 'good' and 90% were highly satisfied with the cream formulation. CONCLUSION: The use of a pimecrolimus-based regimen in everyday practice was effective, well tolerated and well accepted by patients.