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.     

Is there still a role for UV therapy in itch treatment?

Itching is a frequent and greatly distressing symptom related to many skin and systemic diseases. New insights into the pathophysiology of itchy skin and potentially involved mediators have increased the interest in and development of new treatments that specifically act on targets involved in the transmission and perception of itching. Phototherapy has long been known and used as an effective treatment for various kinds of chronic itching. However, despite its well‐known beneficial effects, the mechanisms behind the antipruritic effect of phototherapy are less well‐known. In addition, phototherapy requires the use of expensive equipment in dermatology offices, patients must undergo repeated treatments and no large, randomized, controlled trials have yet supported the antipruritic effect of UV. Therefore, phototherapy is rarely recommended as a treatment method for chronic pruritic diseases or only used as a last recourse. However, the wide range of pruritic conditions that can be successfully treated with phototherapy, together with its low acute side effects, extremely low frequency of interactions with other medications, possibilities to combine phototherapy with other treatment modalities and the fact that patients of almost all ages—from childhood to old age, including women during pregnancy or lactation—can be treated make UV therapy advantageous over other treatments of chronic pruritus. Thus, despite the development of new targeted therapies against pruritus, UV therapy is neither outdated nor the ‘last recourse’, but should be considered early on in the treatment of chronic pruritus.     

What is the role of field-directed therapy in the treatment of actinic keratosis? Part 2: Commonly used field-directed and lesion-directed therapies

Actinic keratosis (AK) constitutes the initial epidermal lesion in a disease continuum that may potentially progress to invasive squamous cell carcinoma (SCC). A number of treatment options are available to clear lesions and thus reduce the risk for progression to SCC. Field-directed therapies are primarily used to clear multiple AKs and subclinical lesions. Part 1 of this review explaining the role of field-directed therapy for the treatment of AK discussed the unmet needs with current therapies and the investigational agents that are being developed to fill treatment gaps. Part 2 will mainly focus on field-directed therapies that currently are available for AK, such as resurfacing procedures, patient-administered topical therapy, and photodynamic therapy (PDT), as well as lesion-directed therapy, which is used to clear discrete lesions in relatively small numbers.     

Is there a role for topically delivered eicosapentaenoic acid in the treatment of psoriasis?

The n-3 fatty acids have demonstrable biological activities and have been associated with many health improvements from child brain development to arthritis. In this review we sought to pull together the works that have examined the potential use of n-3 fatty acids in psoriasis. The rationale of using EPA and/or its metabolites is supported by findings which suggest that it has anti-inflammatory properties and plays an important role in the resolution phase of inflammation. EPA use in psoriasis has also been demonstrated in trials using oral, intravenous, and topical preparations, with generally positive outcomes. Depth profile analysis revealed that EPA and its metabolite, 15-HEPE are deposited in the epidermis, particularly in the metabolically active basal layer. This is considered advantageous in psoriasis therapy. Currently there are many unknowns about psoriasis aetiology and the effects of blocking different cytokines have on the disease progression. Furthermore not enough is known about EPA effects on cellular immunity other than via prostaglandin and leukotriene synthesis to fully understand the mode of action of EPA. However, evidence so far suggests EPA does have a potential role in the treatment of psoriasis, in particular for topical treatments either as an active anti-inflammatory agent by itself, or as a dual action permeation enhancer for other anti-psoriatic treatments. The challenges include optimising the delivery of EPA to the skin and determining the derivatives of EPA which would give maximal effects, and overcoming pharmacokinetic and formulation problems to optimally deliver EPA to its intended target cells.     

What is the role of field-directed therapy in the treatment of actinic keratosis? Part 1: overview and investigational topical agents

Actinic keratosis (AK) constitutes the initial epidermal lesion in a disease continuum that may progress to invasive squamous cell carcinoma (SCC). A number of treatment options are available to clear lesions, and thus reduce the risk for progression. Field-directed approaches are primarily used to clear multiple AKs and subclinical lesions. Current field-directed approaches still have a number of unmet needs, and a number of investigational agents are being evaluated. Topical therapy can be improved by shortening treatment periods; enhancing tolerability, compliance, and patient satisfaction; reducing recurrence rates; and lowering cost. This 2-part review will explain the role of field-directed therapy in the treatment of AK. Part 1 focuses mainly on investigational agents that are being studied for topical patient-administered, field-directed therapy.     

Is there a role for systemic targeted therapy after surgical treatment for metastases of renal cell carcinoma?

Metastatic renal cell carcinoma (mRCC) is a challenging disease. Despite the new targeted therapies, complete remissions occur only in 1%-3% of the cases, and the most effective first-line treatment drugs have reached a ceiling in overall survival (ranging from 9 to 49 mo). Metastasectomy remains to be the only curative option in most patients with mRCC. Prognostic nomograms have been recently published, so we have tools to classify patients in risk groups, allowing us to detect the cases with the higher risk of recurrence after metastasectomy. Although sparse, there is some evidence of effectiveness of neoadjuvant targeted therapy before metastasectomy; but with an increase in surgical complications due to the effects of these new drugs in tissue healing. We have aimed to answer the question: Is there a role for systemic targeted therapy after surgical treatment for metastases of renal cell carcinoma? We have made a search in Pubmed database. As far as we know, evidence is low and it’s based in case reports and small series of patients treated with adjuvant drugs after neoadjuvant therapy plus metastasectomy in cases of partial response to initial systemic treatment. Despite the limitations and high risk of bias, promising results and cases with long-term survival with this approach have been described. Two ongoing clinical trials may answer the question that concerns us.     

Bucher’s indirect comparison of daylight photodynamic therapy with methyl aminolevulinate cream versus diclofenac plus hyaluronic acid gel for the treatment of multiple actinic keratosis

Background

Actinic keratosis (AK) is a pre-cancerous condition characterised by patches of thick, scaly skin developing on sun-exposed areas of the body. When multiple AKs develop on severely photodam-aged skin, commonly used treatments include photodynamic therapy and diclofenac plus hyaluronic acid gel (DHA). Methyl aminolevulinate daylight photodynamic therapy (MAL DL-PDT) is an alternative to conventional photodynamic therapy (MAL c-PDT). Trials have indicated that MAL DL-PDT is as effective as MAL c-PDT but reduces treatment-related pain and dermatological side effects.

Objectives

To indirectly compare between MAL DL-PDT and DHA in patients with AK.

Materials and methods

A total of three randomised trials were collected using a systematic literature review. An adjusted indirect comparison was conducted on complete lesion response rate at 12 weeks.

Results

The data indicated that mild lesions, moderate lesions, and mild and moderate lesions treated with MAL DL-PDT were more than four times more likely to undergo a complete response than lesions treated with DHA at 12 weeks, with ORs ranging from 4.23 to 4.81. Results were all statistically significant.

Conclusion

This is the first indirect comparison demonstrating the effectiveness of MAL-PDT over DHA for the treatment of AK, and further research is needed to assess the long-term efficacy of these interventions (i.e. six months and beyond), as well as safety and patient-reported outcomes.

     

Is PUVA maintenance therapy necessary in patients with early‐stage mycosis fungoides? Evaluation of a treatment guideline over a 28‐month follow‐up

Background Cutaneous T‐cell lymphoma is a rare condition that represents 2% of all lymphomas and 75–80% of primary cutaneous lymphomas. The objective of the present study is to evaluate a clinical practice guideline. Methods This paper reports a prospective cohort study with a five‐year follow‐up. This is the second report to describe the analysis of data obtained during follow‐up of 28 months. To date, 40 patients diagnosed with early‐stage mycosis fungoides (stage IA, n = 20; stage IB, n = 20) have been enrolled. All patients have been treated with a minimum of 58 sessions of psoralen and long‐wave ultraviolet radiation, with complete clinical and histological clearance of lesions. Variables considered include disease duration, treatment time, treatment dose, and history of relapse. Complete physical examinations and diverse complementary examinations were performed. A tumor–node–metastasis–blood staging system was applied. The population was divided into two groups according to results consisting, respectively, of those who relapsed during follow‐up (n = 12) and those who did not (n = 28). Results History of relapse was the variable most strongly associated with future relapse (relative risk = 10.38, 95% confidence interval 2.64–40.72). No statistically significant difference between the groups according to receipt of maintenance therapy was found (P = 0.161). Conclusions Our results strongly suggest that maintenance therapy does not prevent future relapse. However, history of relapse is a strong predictor for future relapse.     

Topical aminolaevulinic acid‐based photodynamic therapy as a treatment option for psoriasis? Results of a randomized,observer‐blinded study

BACKGROUND: Topical aminolaevulinic acid-based photodynamic therapy (ALA-PDT) has recently been tried in small open studies for several inflammatory dermatoses including psoriasis. OBJECTIVES: The purpose of this randomized, within patient comparison study was to investigate whether topical ALA-based PDT using a range of light doses can induce a satisfactory response in localized psoriasis. PATIENTS AND METHODS: Twenty-nine patients with chronic plaque type psoriasis were enrolled in the study. After keratolytic pretreatment three psoriatic plaques in each patient were randomly allocated to PDT with 1% ALA and a light dose of 5 J cm(-2), 10 J cm(-2) or 20 J cm(-2), respectively. Treatment was performed twice weekly until complete clearance or for a maximum of 12 irradiations. As a measure of clinical response the psoriasis severity index (PSI) of the three target plaques was assessed separately by an observer blinded to the treatment at baseline, before each PDT treatment and 3-4 days after the last irradiation. RESULTS: Eight patients withdrew prematurely from the study. Keratolytic pretreatment alone reduced the baseline PSI in all three dose groups by about 25%. Subsequent PDT with 20 J cm(-2) resulted in a final reduction of PSI by 59%, PDT with the lower doses of 10 J cm(-2) and 5 J cm(-2) decreased the baseline PSI by 46% and 49%, respectively. The difference in clinical efficacy between 20 J cm(-2) and 10 J cm(-2) or 5 J cm(-2) was statistically significant (P = 0.003; P = 0.02), whereas no difference was found between 10 J cm(-2) and 5 J cm(-2) (P = 0.4). All patients reported some degree of PDT-induced stinging or burning during irradiation. CONCLUSIONS: The unsatisfactory clinical response and frequent occurrence of pain during and after irradiation renders topical ALA-based PDT an inadequate treatment option for psoriasis.     

Oral lichen planus and the burning mouth syndrome. Is there a role for patch testing?

There is controversy about the role of contact allergy in the pathogenesis of oral lichen planus (OLP) and the burning mouth syndrome (BMS). Patients with OLP or BMS might wish to pursue allergy testing in hopes of identifying the cause of their disease. Although patch testing in these conditions might provide useful information, one risks discovering allergens of uncertain relevance. We asked 2 experts in the field to discuss their approaches to evaluation and management of OLP and BMS, with an emphasis on the role of patch testing.