Gain with no pain? Pain management in dermatological photodynamic therapy

Pain during photodynamic therapy (PDT) is the main limiting adverse effect in its use in dermatology. Given its multifactorial nature, we reviewed both intrinsic and extrinsic factors that are involved in PDT pain. We propose a threshold theory for pain experience in PDT: it correlates positively with fluence rate and dose below a certain threshold (rate of ~60 mW cm⁻², dose of ~50 J cm⁻²); when the threshold is surpassed, pain intensity saturates. Additionally, we carefully compared recent updates on pain management strategies and we suggest that cold‐air analgesia and low‐irradiance light sources (such as variable pulsed light and daylight PDT) represent the current best analgesic options. Finally, we discuss the possible mechanisms of pain experience during PDT. Reactive oxygen species, transient receptor potential channels and inflammatory responses are key mediators in pain. Further investigation into these pathways should help with the development of more effective analgesic strategies. Taking these points together, for pain management in PDT, an individualized plan of analgesia is possible.     

Facial skin rejuvenation: Ablative laser resurfacing,chemical peels,or photodynamic therapy? Facts and controversies

Patients and cosmetic surgeons continue to develop innovative devices and techniques in search of the elusive fountain of youth. Our efforts in the past decade can be distilled to three primary approaches: refinement of existing technologies (ablative lasers); refinement of tried-and-true techniques (chemical peeling); and innovative use of new technologies (photorejuvenation). In this contribution, the authors discuss how these three approaches are used to achieve facial skin rejuvenation. Specifically, the authors compare and contrast the clinical benefits and disadvantages of the ablative fractionated and unfractionated carbon dioxide resurfacing lasers, medium-depth and deep chemical peeling, and the combination of photodynamic therapy with intense-pulsed light.     

Is the pain of topical photodynamic therapy with methyl aminolevulinate any different from that with 5‐aminolaevulinic acid?

Topical photodynamic therapy (PDT) using 5‐aminolaevulinic acid (ALA) or methyl aminolevulinate (MAL) is widely used in dermatology. It is commonly stated that MAL PDT is less painful than ALA PDT, although published data are conflicting. We report our experience of the use of ALA (4–6 h) (n = 20) and MAL (3 h) (n = 20) in 40 consecutive patients with Bowen's disease or superficial basal cell carcinoma, treated with PDT using an identical irradiation regime. Although there was a trend to higher pain scores with ALA PDT [visual analogue scale (VAS)score, median 4.50], this was not significantly different from that of MAL PDT (VAS score, median 3.55; P = 0.98), nor considered to be clinically important. Importantly, both ALA and MAL PDT regimes were fairly well tolerated in this patient cohort, supporting the use of these prodrugs in dermatological PDT.     

How realistic is cutaneous gene therapy?

Recent progress with innovative, experimental gene therapy approaches in animals, and recent improvements in our understanding and manipulation of stem cells, gene expression and gene delivery systems, have raised plenty of hopes in essentially all branches of clinical medicine that hitherto untreatable or poorly manageable diseases will soon become amenable to treatment. Few other organ systems have received such enthusiastic reviews in recent years as to the chances and prospects of gene therapy as the skin, with its excellent accessibility and its pools of--seemingly--readily manipulated epithelial stem cells (cf. Cotsarelis et al., Exp Dermatol 1999: 8: 80-88). However, as in other sectors of clinical medicine, the actual implementation of general gene therapy strategies in clinical practice has been faced with a range of serious difficulties (cf. Smith, Lancet 1999: 354 (suppl 1): 1-4; Lattime & Gerson (eds.), Gene Therapy of Cancer, Academic Press, San Diego, 1999). Thus, it is critically important to carefully distinguish unfounded hype from justified hope in this embryonal area of dermatologic therapy, to discuss in detail what can be realistically expected from cutaneous gene therapy approaches in the next few years, and importantly, what kind of promises should not be made to our patients at this time.     

Is the step‐up therapy of topical 5‐aminolevulinic acid photodynamic therapy effective and safe for the patients with recalcitrant facial flat wart?

Facial flat wart, caused by human papilloma virus type 3 and less often, type 10, 27, and 41, often brings many cosmetic problems to children and young adults. Considering the disturbing cosmetic problem, the treatment of facial flat wart is always frustrating and often unsuccessful, although there are many treatment modalities. Considering the possible serious side effects of 5‐aminolevulinic acid photodynamic therapy (ALA‐PDT), we designed step‐up therapy of ALA‐PDT on different clinical phases of facial flat wart. As a new protocol of ALA‐PDT, we found the step‐up therapy of ALA‐PDT could also receive excellent effects with the lower side effects. Meanwhile, the tolerance of patients to ALA‐PDT could improve with subsequent treatment sessions and escalating doses of ALA‐PDT.     

Photosensitizers and light sources for photodynamic therapy of the Bowen’s disease

Bowen’s disease is a neoplastic skin disease, known as squamous cell carcinoma in situ. The treatment options for Bowen’s disease are: cryotherapy, curettage, surgery, topical therapy and radiotherapy. In the past recent years, photodynamic therapy was used as a new treatment method. The purpose of this paper is to summarize the results of clinical and research studies with respect to the photodynamic therapy of Bowen’s disease. A search of three databases was conducted using specific keywords and explicit inclusion and exclusion criteria for the study of photosensitizers, light sources and their efficacy in photodynamic therapy of Bowen’s disease. Two photosensitizers have been used mainly for photodynamic therapy of Bowen’s disease therapy: δ-aminolevulinic acid and methyl aminolevulinate. These photosensitizers have been activated with both coherent (lasers) and non-coherent (lamps and LEDs) light sources. Fluence has been set in a large domain (10–240 J/cm²) and irradiance was 0.23–100 mW/cm². All these light sources have the same efficacy. The high response rates were obtained using methyl aminolevulinate and light emitting diode as light source. These results have demonstrated that photodynamic therapy using methyl aminolevulinate as photosensitizer could be considered as one of the first therapeutic options for Bowen’ disease.     

Where does the antigen of cutaneous sarcoidosis come from?

Background: The antigen pathway of cutaneous sarcoidosis remains obscure. We have investigated topographic involvement of inflammatory cells and lymphatic vessels. Methods: Eleven cutaneous biopsies from eight patients were studied, along with controls from other granulomatous disorders and various skin lesions. Markers for lymphocytes, dendritic cells (DCs), and lymphatic vessel endothelial cells were detected using immunohistochemistry. Results: S100⁺ and CD1a⁺ immature DCs (Langerhans cells) occurred more frequently within the epidermis, whereas S100⁺, fascin⁺, or CD83⁺ maturing DCs occurred more frequently beneath the epithelium in cutaneous sarcoidosis cases than in controls (e.g. CD83, cutaneous sarcoidosis vs. other granulomatous disorders: r = 0.557, p = 0.011). Fascin⁺ and CD83⁺ mature DCs were often closely attached to CD3⁺ T‐lymphocytes around dermal granulomas. D2‐40⁺ lymphatic vessels were often found surrounding dermal granulomas, especially those located in the deeper dermis, in contrast to fascin⁺ blood vessels. Conclusions: Antigen‐capturing by immature DCs seems to take place initially in the epidermis, followed by maturation of DCs. These mature DCs may present the processed antigen to T‐lymphocytes that cause dermal granulomas either in the interstitium of the upper dermis, or in or around lymphatic vessels of the lower dermis. Environmental antigen could be verified by skin test. Kurata A, Terado Y, Izumi M, Fujioka Y, and Franke FE. Where does the antigen of cutaneous sarcoidosis come from?     

Pathogenesis and therapy of cutaneous lymphomas – Progress or impasse?

The cutaneous environment hosts a number of hematopoietic neoplasms that are dominated by primary cutaneous (PC) T-cell lymphomas. Recent progress in molecular biology and immunology has provided tools to investigate the pathogenesis and the biology of these neoplasms. This review highlights newest findings concerning the immune biology of CD4+ CD56+ hematodermic neoplasms, and PC T-cell and B-cell lymphomas, speculating how these can be translated into more sophisticated, biology-based treatment approaches in the near future.     

Are melanocortin peptides future therapeutics for cutaneous wound healing?

Cutaneous wound healing is a complex process divided into different phases, that is an inflammatory, proliferative and remodelling phase. During these phases, a variety of resident skin cell types but also cells of the immune system orchestrate the healing process. In the last year, it has been shown that the majority of cutaneous cell types express the melanocortin 1 receptor (MC1R) that binds α‐melanocyte‐stimulating hormone (α‐MSH) with high affinity and elicits pleiotropic biological effects, for example modulation of inflammation and immune responses, cytoprotection, antioxidative defense and collagen turnover. Truncated α‐MSH peptides such as Lys‐Pro‐Val (KPV) as well as derivatives like Lys‐d ‐Pro‐Thr (KdPT), the latter containing the amino acid sequence 193‐195 of interleukin‐1β, have been found to possess anti‐inflammatory effects but to lack the pigment‐inducing activity of α‐MSH. We propose here that such peptides are promising future candidates for the treatment of cutaneous wounds and skin ulcers. Experimental approaches in silico, in vitro, ex vivo and in animal models are outlined. This is followed by an unbiased discussion of the pro and contra arguments of such peptides as future candidates for the therapeutic management of cutaneous wounds and a review of the so‐far available data on melanocortin peptides and derivatives in wound healing.