Sequential treatment with calcitriol and methyl aminolevulinate-daylight photodynamic therapy for patients with multiple actinic keratoses of the upper extremities.

BACKGROUND: Topical photodynamic therapy (PDT) is a widely used and effective treatment for actinic keratoses (AKs). However, cure rates are significantly reduced for AKs on acral sites. We compared the sequential regimen of topical calcitriol and methyl aminolevulinate (MAL) daylight-PDT (CAL-DL-PDT) versus placebo and MAL-DL-PDT (P-DL-PDT) on acral AKs in an intra-individual, randomized trial. METHODS: Adult patients with multiple all grade AKs of the upper extremities were treated with daily topical calcitriol or placebo for 14 days followed by 2 sessions of DL-MAL-PDT. After 3 months, patients were evaluated for lesion response rate, both overall and by AK grade, and patient ≥ 75 % clearance rate. Safety assessments included pain VAS immediately after the first DL-PDT session, side effects after calcitriol pretreatment and 7 days after the first DL-PDT session. Cosmetic outcome by the physician and patient's preference were graded at the end of the study. RESULTS: Forty-two patients were enrolled and 36/42 completed the study. After 3 months, the overall lesion response rate and patient ≥ 75 % clearance rate of CAL-DL-PDT were higher, albeit not significantly, than P-DL-PDT. According to grade, response rate of grouped AK II/III was significantly higher for CAL-DL-PDT than for P-DL-PDT while similar results were observed for grade I AKs. Mild erythema and itch were reported after calcitriol application. No significant difference was observed in pain intensity. Local skin reactions occurred more frequently on the CAL-DL-PDT-treated sides. Cosmetic outcome did not differ but overall subject's preference was slightly significantly in favor of P-DL-PDT. CONCLUSIONS: CAL-DL-PDT is more effective than P-DL-PDT for thicker "difficult to treat" AKs on the upper extremities but is associated with increased local skin reactions.

5-Aminolaevulinic acid patch photodynamic therapy for the treatment of actinic keratoses: preliminary results from an Italian study in the real-life setting.

BACKGROUND: Photodynamic therapy (PDT) is recommended for both lesion and field therapy of actinic keratoses (AKs). The 5-aminolaevulinic acid (5-ALA) patch PDT is indicated for the treatment of isolated mild AKs (≤1.8 cm) on the face and bald scalp. It was demonstrated to be effective and safe in clinical trials with a good tolerability profile. METHODS: In this retrospective multicenter real-life study, 33 patients with a total of 99 AKs of the scalp, face, ears, and/or hands and 2 actinic cheilitis were treated with one treatment session of 5-ALA patch PDT with a red light source (total dose of 37 J/cm2). RESULTS: Overall, 12 weeks after treatment, 68/99 (69%) lesions were completely cleared. Complete response was obtained in 82% of AKs on the ears, 78% on the face, 57% on the hands, and 56% on the scalp and in the two actinic cheilitis. The treatment was very effective on grade I AKs, cleared in 87% of the cases and less efficient on grade II-III lesions, cleared in 47% of the cases. 5-ALA patch PDT was well tolerated with a good to excellent cosmetic outcome in 97% of the patients and with 94% of the patients being satisfied or very satisfied with the treatment. CONCLUSIONS: Our results confirm that 5-ALA patch PDT is a good option for AK treatment in clinical practice, it is easy to use, effective and well tolerated even in difficult-to-treat-areas. Moreover, it has an excellent cosmetic outcome.

Single versus two-treatment schedule of methyl aminolevulinate daylight photodynamic therapy for actinic keratosis of the face and scalp: An intra-patient randomized trial.

BACKGROUND: Efficacy of daylight-photodynamic therapy (DL-PDT) with methyl aminolaevulinate (MAL) has been reported to gradually decrease as the severity of actinic keratosis (AK) lesions increases. Repeated treatments have been suggested to increase the efficacy of DL-PDT. Aim of our pilot study was to evaluate the efficacy and tolerability of a single versus two-treatment schedule of MAL DL-PDT for the treatment of multiple AKs of the face/scalp in a prospective, intra-patient, comparison study. METHODS: Patients with multiple AKs of the face/scalp received a single treatment of MAL DL-PDT or 2 treatments, 1 week apart, on either half-side. Weather conditions and outdoor temperature were recorded during daylight exposure. Visual analog scale for pain was assessed immediately after each session, and severity of local skin reactions after 2 days. Treatment efficacy was evaluated at 3 months. RESULTS: Thirty-one patients with multiple AKs of the face/scalp were enrolled and completed the study. No significant difference was observed between single and two-treatment schedule in the lesion complete response rate for total AKs (80.7% vs 85.6%, p = 0.28) and for AKs divided by grade (grade I: 88.5% vs 89.2%, p = 0.79; grade II: 67.3% vs 71.0%, p = 0.71; grade III: 50.0% vs 55.6%, p≈1.00). Pain was significantly higher during the second session (p = 0.04). Local skin reactions were generally mild, but more severe after the first treatment (p < 0.01). CONCLUSIONS: The two-treatment schedule did not improve significantly the efficacy of MAL DL-PDT for AKs of the face and scalp as compared to the single-treatment. Alternative strategies might be recommended to optimize the efficacy of DL-PDT.

Long-term efficacy data for daylight-PDT.

INTRODUCTION: Conventional photodynamic therapy (c-PDT) is an established successful treatment for non-melanoma skin cancers (NMSC). Daylight PDT (DL-PDT) was introduced to overcome the main inconveniencies associated with c-PDT such as pain during illumination and long clinic visits. DL-PDT was shown to have similar short-term efficacy to c-PDT for the treatment of mild/moderate actinic keratosis (AKs) but it is associated with better tolerability. Since AKs tend to regress and reoccur over time, data on long-term efficacy of DL-PDT become crucial. EVIDENCE ACQUISITION: We performed a systematic review search up to February 2018 of available studies on DL-PDT long-term efficacy using the MEDLINE database and made a manual search of selected references. EVIDENCE SYNTHESIS: Most current studies on DL-PDT have limited follow-up periods of 3 to 6 months. Only 2 randomized, intra-individual studies provided efficacy data on AK treatment at 12 month-follow-up and supported the long-term efficacy of this novel treatment modality showing a low recurrence rate, varying from 8.7% to 13%. Current evidences for other NMSCs are limited and efficacy seems to be not as good as for AK. CONCLUSIONS: DL-PDT is a very promising treatment for mild to moderate AKs of the face and scalp. Efficacy outcomes of DL-PDT are similar to those of c-PDT in the short-term. Additional studies are required to increase our knowledge on DL-PDT long-term efficacy, as limited data are currently available.

Understanding the Molecular Genetics of Basal Cell Carcinoma.

Basal cell carcinoma (BCC) is the most common human cancer and represents a growing public health care problem. Several tumor suppressor genes and proto-oncogenes have been implicated in BCC pathogenesis, including the key components of the Hedgehog pathway, PTCH1 and SMO, the TP53 tumor suppressor, and members of the RAS proto-oncogene family. Aberrant activation of the Hedgehog pathway represents the molecular driver in basal cell carcinoma pathogenesis, with the majority of BCCs carrying somatic point mutations, mainly ultraviolet (UV)-induced, and/or copy-loss of heterozygosis in the PTCH1 gene. Recent advances in sequencing technology allowed genome-scale approaches to mutation discovery, identifying new genes and pathways potentially involved in BCC carcinogenesis. Mutational and functional analysis suggested PTPN14 and LATS1, both effectors of the Hippo-YAP pathway, and MYCN as new BCC-associated genes. In addition, emerging reports identified frequent non-coding mutations within the regulatory promoter sequences of the TERT and DPH3-OXNAD1 genes. Thus, it is clear that a more complex genetic network of cancer-associated genes than previously hypothesized is involved in BCC carcinogenesis, with a potential impact on the development of new molecular targeted therapies. This article reviews established knowledge and new hypotheses regarding the molecular genetics of BCC pathogenesis.

Staging and follow-up of cutaneous melanoma patients.

Melanoma is responsible for the greatest number of deaths caused by skin malignancies. The purpose of monitoring patients diagnosed with melanoma is to allow early detection of recurrence and any subsequent primary tumors. Several dermatological and oncological societies developed their own set of guidelines for the surveillance and management of melanoma patients depending on the stage of the disease. The object of this article is to provide a comprehensive, systematic overview that summarizes and interprets previous studies, to characterize current practices regarding progression of melanoma, division into stages of development, and subsequent surveillance. We have performed a systematic review search to December 2016 using the MEDLINE database and performed a manual search of selected references. We examined the staging system and the different surveillance programs for melanoma patients. Consistent recommendations with proven evidence are available for staging melanoma patients. Conversely, recommendations are more controversial for follow-up procedures. Given the inadequate number of randomized controlled trials, consensus on the best, universally-applicable follow-up procedure has not been reached and interpretation of the roles of imaging and laboratory tests, as well as of the appropriate frequency and duration of physical examinations, vary widely. Based on a universally-accepted staging system different surveillance procedures have been developed, which may be mainly classified in two groups: low- and high-intensity strategies.

Tinea imbricata as a clue to occult immunodeficiency.

Tinea imbricata (TI) is a geographically restricted dermatophytosis with distinctive clinical and immunologic features. We present a case of TI occurring in a native Brazilian child with previously undiagnosed human immunodeficiency virus infection. Physicians should bear in mind that diagnosis of TI may be a clinical clue to potentially serious underlying immunodeficiency.

Photoletter to the editor: Diffuse capillary malformation with overgrowth: a new and unusual case of a recent entity.

Diffuse capillary malformation with overgrowth (DCMO) has recently been proposed as an independent entity within the wide spectrum of vascular abnormalities associated with overgrowth. We present a new case of DCMO with an unusual harlequin-like appearance. Physicians should bear in mind this diagnosis because its better prognosis.