M.M. Kleinpenning

Pretreatment to Enhance Protoporphyrin IX Accumulation in Photodynamic Therapy

The response rates of photodynamic therapy (PDT) vary widely. Limited uptake of topically applied 5-aminolaevulinic acid (ALA), or its methyl ester (MAL), and suboptimal production of protoporphyrin IX (PpIX) may account for these differences. Recently, we demonstrated that hyperkeratosis is an important negative factor in ALA uptake. This review has its focus on pretreatment of the skin in order to improve the clinical outcome of ALA/MAL PDT. Pretreatment of hyperkeratosis can be achieved with keratolytics, curettage/debulking, tape stripping, microdermabrasion or laser ablation. Penetration enhancers may alter the composition or organization of the intercellular lipids of the stratum corneum. Several studies have been performed on the use of dimethyl sulfoxide, azone, glycolic acid, oleic acid and iontophoresis to increase the penetration of ALA. As PpIX production is also dominated by temperature-dependent processes, elevating skin temperature during ALA application may also improve treatment results. Another approach is the use of additives that interact with the heme biosynthetic pathway, e.g. by removing ferrous iron with iron-chelating substances such as: ethylenediaminetetraacetic acid; 3-hydroxypyridin-4-ones; 1,2-diethyl-3-hydroxypyridin-4-one-hydrochloride; and desferrioxamine. In conclusion, simple pretreatments or additions to the regular practice of PDT, aimed to optimize intralesional PpIX content, improve the clinical outcome.

Clinical and histological effects of blue light on normal skin.

Introduction: Phototherapy with visible light is gaining interest in dermatological practice. Theoretically, blue light could induce biological effects comparable to ultraviolet A (UVA) radiation.

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 Woods light.

Narrowband ultraviolet B therapy in psoriasis: randomized double-blind comparison of high-dose and low-dose irradiation regimens

Background  Ultraviolet (UV) B phototherapy is an established treatment option for psoriasis. The optimum dosage regimen still has to be determined. Within‐subject comparisons do not take into account the systemic effects of UVB phototherapy. The area of the body treated with low‐dose UVB may benefit from the systemic effects of the site treated with a higher UVB dose.

Itch and scratching as predictors of time to clearance of psoriasis with narrow-band ultraviolet B therapy.

Background  Narrow‐band ultraviolet (UV) B phototherapy is an effective treatment for psoriasis. However, there is considerable variability in the number of treatment sessions needed to achieve psoriasis clearance. While several clinical and treatment‐related factors predict time to clearance, the effect of itching and scratching on the number of irradiation sessions is insufficiently understood.

Efficacy of blue light vs. red light in the treatment of psoriasis: a double-blind, randomized comparative study.

Background  Protoporphyrin IX is present in psoriatic skin without the preceding application of aminolevulinic acid. Therefore, endogenous photosensitizers in psoriasis are a potential target for photodynamic treatment with high‐dose visible light.

Current and future treatment options for acne.

Acne is a frequent skin disease with abnormalities in the process of keratinization, sebaceous gland functioning and inflammation. In this review, our understanding of the pathogenesis of acne has been updated. An overview of efficacy and side effects of available anti‐acne treatments is presented. Based on the present overview a recommendation for the treatment of various manifestations of acne is provided, also reconciling beneficial combinations of treatments. It is attractive to speculate that the increased insight into the pathogenesis of acne will create new treatment options. Challenging new options comprise blue light, photodynamic therapy, retinoic acid metabolism blocking agents and inhibitors of Th‐1 cytokines.

The effects of keratolytic pretreatment prior to fluorescence diagnosis and photodynamic therapy with aminolevulinic acid-induced porphyrins in psoriasis

Abstract Background: Psoriasis lesions accumulate protoporphyrin IX (PpIX) with a variable distribution within plaques due to variations in hyperkeratosis causing differences in penetration of cream or light. Objectives: To study the effects of different keratolytic pretreatments in PpIX-induced fluorescence diagnosis (FDAP) and during photodynamic therapy (PDT). Methods: Two psoriasis plaques of 10 patients were treated with either topical retinoic acid or with a hydrocolloid dressing. The hydrocolloid dressing gave the best results. Subsequently, two different contralateral plaques of eight patients were pretreated with a hydrocolloid dressing or the standard pretreatment, salicylic acid in petrolatum, during the 6 weeks of PDT. Biopsies were investigated with respect to stratum corneum thickness, proliferation, differentiation and inflammation. Results: Irritation and point bleedings were noticed after retinoic acid. A hydrocolloid dressing induced the best clinical improvement. Therefore, it was used as alternative pretreatment for psoriasis prior to PDT. We observed significant clinical and immunohistochemical improvement of psoriasis in the salicylic acid as well as the hydrocolloid dressing pretreated plaques. Conclusions: Salicylic acid in petrolatum and a hydrocolloid dressing prior to FDAP and PDT induce improvement of hyperkeratosis. Thus, a hydrocolloid dressing is a good alternative to the current keratolytic pretreatment regime.

Fluorescence diagnosis in actinic keratosis and squamous cell carcinoma

Background: As different tissue types have distinct capabilities to accumulate protoporphyrin IX, fluorescence diagnosis with aminolevulinic acid‐induced porphyrins (FDAP) could be used to discriminate between different types of tissue. Previous results demonstrated higher fluorescence ratios in squamous cell carcinoma (SCC) compared with actinic keratoses (AKs).

Severe pyoderma gangrenosum unresponsive to etanercept and adalimumab

Abstract Background: A 74-year-old female with severe and therapy-resistant pyoderma gangrenosum (PG) was treated for more than 40 years with topical antibacterial ointments, topical and systemic corticosteroids, dapsone and azathioprine. Generally, immunosuppression is the mainstay of treatment of PG, but in our patient cyclosporine had to be discontinued because of significant serious side effects. An attempt was made to decrease the amount of steroids, but tapering of the prednisone dose resulted in relapses of PG. Observation: Off-label use of etanercept resulted in a temporary limited clinical improvement. After 6 months, initial clinical improvement reduced and adalimumab was started. Unfortunately, after 6 months of adalimumab no clinical improvement was seen. Therefore, systemic corticosteroids had to be continued with very good clinical results. Conclusion: In concordance with previous results of several other studies, reviews and case reports, we presume that possibly both etanercept and adalimumab could be excellent therapeutic alternatives in the treatment of PG. Unfortunately, the effectiveness of both etanercept and adalimumab were very limited in our case. Literature research revealed no other successful studies on the off-label use of other immunomodulators as an alternative treatment option for PG. However, infliximab or ustekinumab could be alternative treatment options.