Factors associated with adverse COVID-19 outcomes in patients with psoriasis-insights from a global registry-based study.

BACKGROUND: The multimorbid burden and use of systemic immunosuppressants in people with psoriasis may confer greater risk of adverse outcomes of coronavirus disease 2019 (COVID-19), but the data are limited. OBJECTIVE: Our aim was to characterize the course of COVID-19 in patients with psoriasis and identify factors associated with hospitalization. METHODS: Clinicians reported patients with psoriasis with confirmed/suspected COVID-19 via an international registry, Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection. Multiple logistic regression was used to assess the association between clinical and/or demographic characteristics and hospitalization. A separate patient-facing registry characterized risk-mitigating behaviors. RESULTS: Of 374 clinician-reported patients from 25 countries, 71% were receiving a biologic, 18% were receiving a nonbiologic, and 10% were not receiving any systemic treatment for psoriasis. In all, 348 patients (93%) were fully recovered from COVID-19, 77 (21%) were hospitalized, and 9 (2%) died. Increased hospitalization risk was associated with older age (multivariable-adjusted odds ratio [OR] = 1.59 per 10 years; 95% CI = 1.19-2.13), male sex (OR = 2.51; 95% CI = 1.23-5.12), nonwhite ethnicity (OR = 3.15; 95% CI = 1.24-8.03), and comorbid chronic lung disease (OR = 3.87; 95% CI = 1.52-9.83). Hospitalization was more frequent in patients using nonbiologic systemic therapy than in those using biologics (OR = 2.84; 95% CI = 1.31-6.18). No significant differences were found between classes of biologics. Independent patient-reported data (n = 1626 across 48 countries) suggested lower levels of social isolation in individuals receiving nonbiologic systemic therapy than in those receiving biologics (OR = 0.68; 95% CI = 0.50-0.94). CONCLUSION: In this international case series of patients with moderate-to-severe psoriasis, biologic use was associated with lower risk of COVID-19-related hospitalization than with use of nonbiologic systemic therapies; however, further investigation is warranted on account of potential selection bias and unmeasured confounding. Established risk factors (being older, being male, being of nonwhite ethnicity, and having comorbidities) were associated with higher hospitalization rates.

Management of patients with atopic dermatitis undergoing systemic therapy during COVID-19 pandemic in Italy: Data from the DA-COVID-19 registry.

BACKGROUND: Few and small studies have described the management of immunomodulant/immunosuppressive therapies or phototherapy in atopic dermatitis (AD) patients during coronavirus disease 2019 (COVID-19) pandemic. METHODS: A national registry, named DA-COVID-19 and involving 35 Italian dermatology units, was established in order to evaluate the impact of COVID-19 pandemic on the management of adult AD patients treated with systemic immunomodulant/immunosuppressive medications or phototherapy. Demographic and clinical data were obtained at different timepoints by teledermatology during COVID-19 pandemic, when regular visits were not allowed due to sanitary restrictions. Disease severity was assessed by both physician- and patient-reported assessment scores evaluating itch intensity, sleep disturbances, and AD severity. RESULTS: A total of 1831 patients were included, with 1580/1831 (86.3%) continuing therapy during pandemic. Most patients were treated with dupilumab (86.1%, 1576/1831) that was interrupted in only 9.9% (156/1576) of cases, while systemic immunosuppressive compounds were more frequently withdrawn. Treatment interruption was due to decision of the patient, general practitioner, or dermatologist in 39.9% (114/286), 5.6% (16/286), and 30.1% (86/286) of cases, respectively. Fear of increased susceptibility to SARS-CoV-2 infection (24.8%, 71/286) was one of the main causes of interruption. Sixteen patients (0.9%) resulted positive to SARS-CoV-2 infection; 3 of them (0.2%) were hospitalized but no cases of COVID-related death occurred. CONCLUSIONS: Most AD patients continued systemic treatments during COVID pandemic and lockdown period, without high impact on disease control, particularly dupilumab-treated patients.

Sunlight-induced Painful Skin (Sun Pain): A New Differential Diagnosis in Photodermatology.

Photodermatoses are characterized by the development of skin eruptions following exposure to ultraviolet radiation or visible light. We report here the clinical findings and results of laboratory investigations and phototesting of 6 patients who experience debilitating and excruciating pain after sun exposure ("sun pain") in the absence of any skin eruption. Phototesting with sub-erythemal doses of ultraviolet A radiation triggered localized pain in 4 patients. At follow-up, 3 female patients were found to have developed fibromyalgia, 2 male patients experienced a major depressive disorder, and another male patient had a conversion disorder. One patient also developed allodynia to tactile stimuli and one developed allodynia to thermal and tactile stimuli. Psychiatric conditions should be taken into consideration in patients presenting with excruciating and debilitating pain on exposure to ultraviolet radiation, but with absence of skin eruption. Further research is needed to evaluate whether it represents a type of allodynia triggered by exposure to ultraviolet radiation.

Cohort analysis of safety and efficacy of vismodegib in Italian patients from the Phase II, multicenter STEVIE study.

Aim: To assess safety and efficacy of vismodegib in the Italian cohort from the SafeTy Events in VIsmodEgib study. Materials & methods: Data from Italian patients with locally advanced basal cell carcinoma (laBCC) or metastatic BCC were analyzed. Results: Among 182 Italian patients, adverse events occurred with similar incidence to the overall population. Overall response rate was 67.1% in laBCC, 20% in metastatic BCC; complete response rate was 33.1% overall and 37.4% in laBCC. Median time to response was 2 months in complete responders versus 3.6 months overall. Quality of life improved from baseline. Conclusion: In the Italian cohort of STEVIE, vismodegib showed a safety profile consistent with the whole population; older age did not affect safety or efficacy. ClinicalTrials.gov registration: NCT01367665.

Are there distinct clinical and pathological features distinguishing idiopathic from drug-induced subacute cutaneous lupus erythematosus? A European retrospective multicenter study.

BACKGROUND: Clinical and pathologic criteria to distinguish drug-induced subacute lupus erythematosus (DI-SCLE) from idiopathic (I-SCLE) are controversial. OBJECTIVE: The aim of the survey was a retrospective analysis of a consistent number of iatrogenous and idiopathic SCLE cases, by means of clinical and histopathologic investigation. METHODS: Eleven European university dermatology units collected all diagnosed cases from January 2000 to December 2016. Board-certified dermatopathologists reviewed the histopathologic specimens. Statistical analysis included Student t test, exact test of goodness-of-fit, Fisher's exact test, and the Cochran-Mantel-Haenszel test for repeated measures. RESULTS: Out of 232 patients, 67 (29%) belonged to the DI-SCLE group. Patients with DI-SCLE were significantly older and reported more systemic symptoms than those with I-SCLE. No statistical differences were found for presentation pattern or serology, while histopathology showed a significant association of mucin deposition (P = .000083), direct immunofluorescence positivity for granular immunoglobulin M, and C3 deposits on the basement membrane zone (P = .0041) for I-SCLE and of leukocytoclastic vasculitis (P = .0018) for DI-SCLE. LIMITATIONS: This is a retrospective study. CONCLUSION: An integrated clinical and immunopathologic evaluation is useful to differentiate I-SCLE from DI-SCLE. Older age at onset and more frequent systemic symptoms characterize DI-SCLE. Mucin deposition and immunofluorescence findings are found in I-SCLE, and leukocytoclastic vasculitis is found in DI-SCLE.

Clinical and Spectrophotometric Evaluation of Skin Photoadaptation in Vitiligo Patients after a Short Cycle of NB-UVB Phototherapy.

BACKGROUND: The phenomenon of photoadaptation to narrow-band ultraviolet B (NB-UVB) radiation has been previously described in vitiligo and has usually been clinically measured by the assessment of the minimal erythema dose (MED) after phototesting. OBJECTIVES: To assess the photoadaptive response in vitiligo and healthy skin after NB-UVB phototherapy not only clinically, but also by spectrophotometry. MATERIALS AND METHODS: Fourteen patients affected by generalized vitiligo underwent NB-UVB phototherapy twice weekly for 12 weeks. Before and after phototherapy, a phototesting procedure was administered on vitiligo patches and adjacent healthy skin with a solar simulated radiation (SSR). Visual assessment of the MED took place after 24 h. A spectrophotometer was used to assess the a* value and the melanin index (MI*), as signs of skin erythema and pigmentation. The photoadaptation factor (MED-PF) and the a* photoadaptation factor (a*-PF) were calculated. RESULTS: After NB-UVB phototherapy, both vitiligo and healthy skin showed an increase in MED and MI* values and a reduction of skin erythema compared to baseline (p < 0.05). MED-PF data showed a photoadaptation in 10 (71.4%) vitiligo lesions and in 12 (85.7%) healthy skin areas. The assessment of the a*-PF showed a negative mean percentage value in all affected and unaffected skin areas. CONCLUSIONS: A short cycle of NB-UVB phototherapy can induce photoadaptation in vitiligo by increasing the MED and reducing skin erythema after stimulation with SSR. This is most likely due to the physical filter function induced by ultraviolet radiation.

Prevalence of Phototherapy in the Age of Biologics.

BACKGROUND: The prevalence of narrow-band ultraviolet B (NB-UVB) use in Europe for moderate and severe psoriasis is unknown, because national registries for psoriasis do not monitor this treatment. OBJECTIVES: To quantify the use of phototherapy, biologics or conventional treatments in psoriasis, in a setting where European Medicines Agency (EMA) eligibility criteria for biologics were strictly applied, and phototherapy was included among first-line treatments. METHODS: We followed a cohort of 1,090 patients who were referred to the only centre entitled to prescribe biologics and phototherapy during a 5-year period. RESULTS: The cumulative number of treatment cycles was: 1,047 with NB-UVB phototherapy, 650 with systemic treatments and 239 with biologics; 754 patients received at least 1 course of NB-UVB phototherapy, 422 at least 1 course with a systemic treatment and 137 with a biologic; 595 patients were treated only with phototherapy. CONCLUSIONS: Regular use of NB-UVB as first-line treatment for moderate and severe psoriasis and adherence to the EMA eligibility criteria for biologics led to a relatively restricted use of biologics.

Oral Polypodium leucomotos increases the anti-inflammatory and melanogenic responses of the skin to different modalities of sun exposures: a pilot study.

BACKGROUND: The effects on the inflammatory and tanning responses of sunlight/UVR of several oral antioxidants are still unknown. OBJECTIVE: Assess intensity, time course of the inflammatory, and tanning responses to increasing dosages of solar-simulated radiation (SSR) at baseline and after oral supplementation of an extract of Polypodium leucotomos (PLE). METHODS: Ten healthy subjects underwent phototesting with SSR with a visual and spectrophotometrical assessment of the responses with or without daily oral supplementation of two tablets containing 240 mg of PLE for a total of 15 days. RESULTS: Polypodium leucotomos supplementation induced a significant increase of the minimal erythema dose (MED), a faster recovery of the inflammation following the delivery of super-erythemal doses, and no significant changes of the minimal melanogenic dose (MMD). Spectrophotometric assessment of the Δa* in test areas exposed to equally doses of SSR did not show differences. CONCLUSIONS: Polypodium leucotomos supplementation increased the MED and induced a faster recovery of the inflammation and a stronger tanning response with no changes in the melanogenic threshold.

A retrospective analysis of real-life practice of off-label photodynamic therapy using methyl aminolevulinate (MAL-PDT) in 20 Italian dermatology departments. Part 2: oncologic and infectious indications.

Photodynamic therapy (PDT) with methyl aminolevulinate (MAL) has been suggested as a useful treatment option in a number of skin tumors, other than approved indications, and infections. However, evidence is poor because it is mainly supported by isolated case reports or small case series, often with conflicting results. To assess the effectiveness, tolerability and safety of off-label MAL-PDT in daily clinical practice in 20 Italian hospitals, a retrospective observational study of medical records of patients treated for off-label oncologic and infectious skin conditions was carried out. In all patients standard treatment options had been either ineffective, unacceptably toxic, or medically contraindicated. Clinical data from 145 patients were analyzed. Actinic cheilitis showed a complete remission (CR) in 27 out of 43 treated patients and CR was maintained at follow-up. CR was registered in 3 of 8, 5 of 8 and 10 of 17 treated patients who were affected by extra-mammary Paget's disease (EMPD), erythroplasia of Queyrat (QD), and invasive squamous cell carcinoma (SCC), respectively. Five out of 19 patients with cutaneous T cell lymphoma had a complete remission. Cutaneous B-cell lymphoma, malignant fibrous histiocytoma, mastocytosis and nevus sebaceous were not responsive. Warts were treated in 30 patients and 15 had a complete remission. However, periungueal and plantar lesions were much more responsive than flat and common lesions. Condylomata showed a CR in 2 out of 5 male patients but treatment was painful. Bowenoid papulosis showed only a partial improvement. Atypical mycobacteriosis and chronic cutaneous leishmaniasis were successfully treated. Submammary candidal intertrigo and interdigital intertrigo with Pseudomonas aeruginosa did not improve. Among off-label oncological uses of MAL-PDT, the therapy of actinic cheilitis was the most investigated and showed the best results. In addition, MAL-PDT was used successfully in the majority of patients with QD, EMPD and invasive SCC. Treatment of specific cutaneous infections was well tolerated and gave a good therapeutic result in a few patients, but it does not seem to give substantial advantages over conventional treatment options.

A retrospective analysis of real-life practice of off-label photodynamic therapy using methyl aminolevulinate (MAL-PDT) in 20 Italian dermatology departments. Part 1: inflammatory and aesthetic indications.

Experimental investigations have demonstrated that photodynamic therapy (PDT) with methyl aminolevulinate (MAL) may be a useful treatment in several inflammatory skin disorders and aesthetic indications. To assess the effectiveness, tolerability and safety of off-label MAL-PDT in daily clinical practice in 20 Italian hospital centers, a retrospective observational study of medical records of patients treated for off-label inflammatory and aesthetic indications was carried out. In all patients standard treatment options had been either ineffective, unacceptably toxic, or medically contraindicated. Clinical data regarding 221 patients affected by 22 different diseases were collected. The most common off-label indication was acne vulgaris, with >75% improvement in 72.8% of patients. Other disorders of the sebaceous gland, i.e. acne rosacea, hidradenitis suppurativa and sebaceous hyperplasia, were less responsive. Alopecia areata did not show any improvement. Granuloma annulare and necrobiosis lipoidica showed marked or moderate response in the majority of treated patients. The rate of patients with complete remission was lower for inflammatory skin disorders with hyperkeratosis, i.e. psoriasis (6/17) and porokeratosis (3/16). The efficacy for lichenoid dermatoses was dependent on the clinical variant (erosive and scleroatrophic were more responsive than hypertrophic). Only 1 of 6 patients with Zoon balanitis had a marked improvement. MAL-PDT of venous leg ulcers, photo-aging and hypertrophic scars led to a marked remission in 3/5, 3/6 and 5/8 patients, respectively. The treatment had to be interrupted because of strong pain and burning in 24 patients. Long term adverse events were not registered. Most patients with marked improvement had lasting remission with overall excellent cosmetic outcomes. The present findings demonstrate a high interest in off-label uses of MAL-PDT for inflammatory skin disorders. According to the observed clinical responses, safety, and favorable cosmetic results, MAL-PDT seems to have a potential therapeutic role for the treatment of granulomatous dermal disorders and follicular inflammatory diseases whereas results in other conditions are less encouraging.

A technology transfer journey to a model-driven access control system.

In the model-driven security domain, access control systems provide an application for handling access of persons through controlled gates. A gate, such as a door, can have a lock mechanism for securing the area from unauthorized access. Most commercial solutions for access control management offer pre-packaged software systems where customization of the authorization logic is either not allowed or subject to payment. Moreover, cross-platform development is a barrier for solution providers due to the high cost of development and maintenance that it implies. To overcome these limitations and further optimize the entire access control systems development process, we propose a model-driven approach that supports automatic code generation to enable communication between an IoT infrastructure and platforms for Facility Access Management. Specifically, the approach combines the benefits of Near-Field Communication (NFC) and Tinkerforge (i.e., an open-source hardware platform) with model-driven techniques. This allows the approach to exploit both behavioral and structural models for the modeling and the consequent code generation of part of the authorization mechanism, thus providing complete coverage of the code generated for the whole system. We implemented and evaluated our approach in a real-world case study within the premises of a fitness center with an IoT infrastructure consisting of several heterogeneous sensors by showing its practical applicability. Experimental results demonstrate the effectiveness of our approach in supporting abstraction and automation concerning traditional code-centric development through code generation features. Consequently, our approach makes the whole development process less time-consuming and error-prone, thus reducing the system's time to market.

Dermoscopic, histological and immunohistochemical evaluation of cancerous features in acquired melanocytic nevi that have been repeatedly exposed to UVA or UVB.

Previous studies have reported that repeated solar and artificial UVB (280-320 nm) and UVA (320-400 nm) exposures can modify acquired melanocytic nevi (AMN). We therefore investigated the clinical, dermoscopic, histological and immunohistochemical changes in AMN exposed to UVB and UVA radiation. Twenty healthy volunteers with at least three AMN on the trunk were enrolled in the present study and randomized into two groups to receive equally effective doses of narrow-band (NB)-UVB or UVA1. Three exposures per week were delivered for a total of 4 weeks. During exposures, one AMN was left unprotected, a second one was shielded with an opaque adhesive tape and the third nevus was covered with a commercial sunscreen. After the irradiation cycle, the AMN were surgically removed and underwent histological and immunohistochemical assessment of melanocyte/melanogenesis-related proteins (MART-1, tyrosinase, HMB-45), cell cycle activation markers (Ki-67, topoisomerase IIalpha, p53, Cdk2) and transcription factors (microphthalmia-associated transcription factor, STAT3). Nevi that were exposed to NB-UVB or UVA1 also showed statistically significant increase in size and changes in their dermoscopic features, including overall darkening, increased pigment network expression, formation of branched streaks, and increased number and size of brown globules and dots. AMN that had been covered with opaque tape or sunscreen did not show changes in size or dermoscopic features following UVA1 or NB-UVB exposure. Histological and immunohistochemical analysis did not show any significant change in exposed AMN in comparison with AMN shielded with an opaque adhesive tape or covered with the sunscreen.

Polymorphous light eruption and benign summer light eruption in Italy.

BACKGROUND/PURPOSE: Polymorphous light eruption (PLE) heterogeneity has been postulated, but the existence of benign summer light eruption (BSLE) is controversial. We studied the prevalence of the clinical patterns, criteria distinguishing BSLE from PLE, and diagnostic usefulness of phototest. METHODS: Five Italian Photodermatology Centres recruited retrospectively 346 patients with typical clinical history and/or presentation of PLE. Age, gender, skin type, family history and presence of atopy were considered. UVA and UVB MEDs and provocative phototests with UVA and UVB were obtained with a standardized procedure. Photopatch tests were applied according to the IRCDG rules. ANA were assessed by indirect immunofluorescence. RESULTS: Four criteria (predominance of women, shorter latency, uninvolvement of the face and absence of relapse during summer) identified BSLE in only 6.1% of cases. All had positive phototests, mostly with UVA. Uninvolvement of face, short latency and no seasonal relapses identified 11.7% patients, mostly with positive phototests to UVA. Short latency and no seasonal relapses in women identified 11.2% patients. Uninvolvement of face and no seasonal relapses in women identified 8.1% of patients. Uninvolvement of face and short latency in women identified 17.6% of patients. CONCLUSION: Criteria diagnosed BSLE in only a minority of patients, who were positive at phototesting, mostly with UVA.

Characteristic of chronic plaque psoriasis patients treated with biologics in Italy during the COVID-19 Pandemic: Risk analysis from the PSO-BIO-COVID observational study.

Background: The susceptibility of patients with chronic plaque psoriasis and the risks or benefits related to the use of biological therapies for COVID-19 are unknown. Few data about prevalence, clinical course and outcomes of COVID-19 among psoriatic patients were reported. The aims of this study were 1) to assess the prevalence and severity of COVID-19 in psoriatic patients treated with biologic agents during the first phase of the emergency (22 February to 22 April 2020) in Italy, and 2) to report the clinical outcomes of patients who have been exposed to individuals with confirmed SARS-CoV-2 infection. Methods: Patients with moderate-to-severe chronic plaque psoriasis, aged ≥18 years and undergoing treatment with biologic agents as of 22 February 2020, were eligible to be included in PSO-BIO-COVID study. Demographic and clinical characteristics of patients using any biologic for psoriasis treatment between 22 February and 22 April 2020 were registered. Results: A total of 12,807 psoriatic patients were included in the PSO-BIO-COVID study. In this cohort 26 patients (0.2%) had a swab confirmation of SARS-CoV-2 infection. Eleven patients required hospitalization and two died. Conclusion: The incidence of COVID-19 observed in our cohort of psoriatic patients (0.2%) is similar to that seen in the general population (0.31%) in Italy. However, the course of the disease was mild in most patients. Biological therapies may likely lessen 'cytokine storm' of COVID-19, which sometimes lead to multiple organ failure, ARDS, and death.

Local angioedema following sun exposures: a report of five cases.

Angioedema is a hereditary or acquired disease characterized by localized non-pitting swelling of the subcutaneous tissue which can affect either skin or mucous membranes. Acquired angioedema can often be related to a heterogeneous group of etiological factors including physical stimuli, although up to 38% of cases remain idiopathic. We describe 5 patients who developed an angioedema following sun exposures. All patients reported an intensely stinging angioedema strictly limited to face and extremities, when exposed to solar light. Urticarial wheals were never observed or reported by patients, and oral antihistamines proved to be of no help in preventing or improving the condition of lesions. Laboratory and phototesting data allowed ruling out all other acquired or inherited diseases characterized by photosensitivity. We propose that solar angioedema should be considered a novel clinical entity.

Merkel cell carcinoma arising in immunosuppressed patients treated with high-dose ultraviolet A1 (320-400 nm) phototherapy: a report of two cases.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumour of the skin. Though immunodeficiency is the most relevant risk factor, ultraviolet (UV) radiation is also involved, but as of yet we do not know the action spectrum, pattern or dose which would produce a dangerous exposure. A retrospective study of two immunosuppressed patients who developed MCC during, or soon after a treatment cycle with high dose UVA1 exposures was conducted, in order to understand wether repeated exposures to suberythemogenic UVA1 radiation may have a cancerogenic activity provoking MCC in immunosuppressed patients.

Topical tacrolimus in adult atopic dermatitis: a consensus based on a 15-year experience.

Atopic dermatitis (AD) is one of the most common cutaneous inflammatory diseases both in adults and in children. It is a chronic, remitting-relapsing dermatitis, primarily managed by dermatologists, but also by allergists and primary care physicians. Due to coexistence of comorbidities, often a multidisciplinary team is required. Topical calcineurin inhibitors (TCIs - i.e. tacrolimus and pimecrolimus) are a class of steroid-sparing, anti-inflammatory agents that have been shown to be efficacious for the treatment of AD acute flares and in maintenance therapy. In particular, the application of tacrolimus ointment twice daily reduces AD severity and pruritus. Moreover, maintenance therapy with an intermittent application of tacrolimus to recurrent skin sites (proactive therapy) decreases frequency and severity of relapses. Many studies have also assessed the efficacy of TCIs in disorders other than AD. Although US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) issued a "black box warning" regarding the possible cancerogenic activity of these drugs, there is currently no strong evidence of an increased rate of malignancy in treated patients, and observational data from postmarketing surveillance studies have shown no safety concerns. A panel of dermatologists have thoroughly discussed the use of tacrolimus in AD after 15-year experience. The experts focused on AD flare treatment, maintenance therapy and management of side effects. Consensus was reached on some areas of interest, namely the stages of AD in which tacrolimus is recommended, the amount of drug to be applied, how to manage side effects, and how to improve patient's compliance. Moreover, the panel of experts recommended to perform randomized clinical trials to confirm the efficacy of tacrolimus off-label use, which led to successful outcomes in other skin diseases.

Clinical and molecular epidemiology of erythropoietic protoporphyria in Italy.

BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare inherited disease associated with heme metabolism, characterized by severe life-long photosensitivity and liver involvement. OBJECTIVE: To provide epidemiological data of EPP in Italy. MATERIALS & METHODS: Prospective/retrospective data of EPP patients were collected by an Italian network of porphyria specialist centres (Gruppo Italiano Porfiria, GrIP) over a 20-year period (1996-2017). RESULTS: In total, 179 patients (79 females) with a clinical and biochemical diagnosis of EPP were assessed, revealing a prevalence of 3.15 cases per million persons and an incidence of 0.13 cases per million persons/year. Incidence significantly increased after 2009 (due to the availability of alfa-melanotide, which effectively limits skin photosensitivity). Mean age at diagnosis was 28 years, with only 22 patients (12.2%) diagnosed ≤10 years old. Gene mutations were assessed in 173 (96.6%) patients; most (164; 91.3%) were FECH mutations on one allele in association with the hypomorphic variant, c.315-48C, on the other (classic EPP), and nine (5.2%) were ALAS2 mutations (X-linked EPP). Only one case of autosomal recessive EPP was observed. Of the 42 different FECH mutations, 15 are novel, three mutations collectively accounted for 45.9% (75/164) of the mutations (c.215dupT [27.2%], c.901_902delTG [11.5%] and c.67 + 5G > A [7.2%]), and frameshift mutations were prevalent (33.3%). A form of light protection was used by 109/179 (60.8%) patients, and 100 (56%) had at least one α-melanotide implant. Three cases of severe acute liver involvement, requiring OLT, were observed. CONCLUSION: These data define, for the first time, the clinical and molecular epidemiology of EPP in Italy.

Cutaneous Photoprotective Activity of a Short-term Ingestion of High-Flavanol Cocoa: A Nutritional Intervention Study.

In vivo and in vitro studies have shown that prolonged oral administration of flavanol-rich cocoas extracts have photoprotective effects. The aim of the present study was to assess the photoprotective activity of short-time administration of a new variety of naturally selected cocoa extract rich in bioactive compounds. We selected a cocoa powder particularly rich in polyphenols, flavanols, caffeine, theobromine and theophylline. We then investigated, in 10 healthy subjects, the photoprotective effects of one week of daily oral administration of two doses of such powder. Phototesting with solar simulated radiation was performed at baseline and after cocoa supplementation. Visual assessment of the minimal erythema dose and spectrophotometric measurement of the "a" parameter were done after 24 h from the irradiation. Oral daily supplementation of 1 g of high-flavanol cocoa was not effective but a one-week administration of 4-6 g of cocoa induced a statistically significant increase in the visual erythema threshold and a significant reduction in the "a" parameter. We demonstrated that a new variety of naturally selected cocoa extract, even when administered for a short time, retains a dose-dependent photoprotective effect. These results are also indicative of the fact that topical sunscreens could be supplemented by a specific diet.