A randomized split-face clinical trial of conventional vs indoor-daylight photodynamic therapy for the treatment of multiple actinic keratosis of the face and scalp and photoaging.

BACKGROUND: Recently, indoor daylight photodynamic therapy (idl-PDT) has been developed; however, its efficacy and tolerability remain to be assessed. OBJECTIVE: This is a not-inferiority study to compare treatment outcomes of cPDT with a red LED lamp and idlPDT with a polychromatic white LED lamp in adult patients affected by symmetrical AKs of face and/or scalp. METHODS: In this comparative, intra-patient, split-face, randomized clinical trial forty-three adult patients were enrolled. Two contralateral and symmetrical target areas of the face and/or scalp harboring at least 5 AKs were selected and randomized 1:1 to treatment with cPDT and idlPDT. The AKs number and cumulative area were assessed at baseline (T0). Efficacy and cosmetic outcome were assessed 3 months after treatment (T1). RESULTS: Total AKs number and area reduced significantly with both idlPDT (p < .0001) and cPDT (p < .0001) in comparison to baseline. cPDT was more painful (p < .0001) and induced a more severe inflammation (p < .0001). Twenty-nine patients (70.7%) gave their overall preference to idlPDT (p < .001). CONCLUSION: idlPDT may represent an alternative treatment protocol to cPDT for in-office treatment of AKs patients with better tolerability and a not inferior efficacy.

Effects of MAL-PDT, ingenol mebutate and diclofenac plus hyaluronate gel monitored by high-frequency ultrasound and digital dermoscopy in actinic keratosis - a randomized trial.

BACKGROUND: The efficacy for actinic keratosis (AK) clearance of field-directed treatments has been investigated in randomized studies against placebo, but the comparison of results is difficult for several methodological reasons. OBJECTIVES: The present study aims to compare efficacy of MAL-photodynamic therapy (MAL-PDT), ingenol mebutate gel (IMB) and diclofenac plus hyaluronate gel (DHA) on multiple AKs assessing a new performance index of efficacy, the cumulative AK area and evaluating dermoscopical and high-frequency ultrasound (HFUS) changes. METHODS: Patients with ≥5 Olsen II AKs in a 25 cm2 area of the scalp and face were enrolled and randomized to one of the treatment choices. Number of AKs and cumulative area were assessed before and after treatment. Dermoscopy and HFUS were performed on a single AK and surrounding photo-damaged skin in the treatment area. RESULTS: Cumulative AKs area reduced significantly more with PDT compared to other treatment options and with IMB in comparison to DHA. PDT was also the only treatment option that increased at a significant level the dermal density in both target AK and the surrounding skin and decreased significantly the SLEB thickness in the perilesional skin at HFUS. CONCLUSIONS: MAL-PDT is more effective than IMB and DHA for reducing the cumulative AK area which is calculated digitally from 3D pictures and should be the preferred performance index for the evaluation of the efficacy of treatments for AKs, rolling out clinical and dermoscopy evaluation. MAL-PDT improves all HFUS features of chronic photodamages of the dermis of the skin underlying and surrounding the AK spots.

Sunbeds and carcinogenesis: the need for new regulations and restrictions in Europe from the Euromelanoma perspective.

Experimental investigations have definitely assessed that ultraviolet A (UVA) as well as ultraviolet B (UVB) radiation induce mutagenic DNA photoproducts and other cell damages with a carcinogenic potential. Artificial tanning increases significantly the lifetime risk for basal cell carcinoma, squamous cell carcinoma and melanoma particularly in subjects with fair skin type, subjects with a history of skin cancer or frequent childhood sunburn or if exposures took place at an age younger than 18 years. In addition, experimental and clinical evidence indicate that UVA exposure promotes skin photoageing. Therefore we are dealing with a recreational activity (for customers) and a profitable business (for the tanning industry) with human costs, i.e. an increase in morbidity and mortality by skin cancer, and health and social costs leading to an increased expenditure by the European national health systems. In a few European countries, legislation has recently prohibited the use of sunbeds for minors, pregnant women, people with skin cancer or a history of skin cancer and individuals who do not tan or who burn easily from sun exposure. However, this legislation seems to be insufficient from a photobiological perspective, and importantly, it is largely disregarded by consumers and tanning industry. Therefore the Euromelanoma group proposes a new, more stringent regulation for the tanning industry and restrictions for customers, particularly for those individuals with constitutional and anamnestic risk factors. Finally, we ask for an enhanced commitment to increase the awareness of the general population on the risk of artificial tanning.

Clinical, histological and high-frequency ultrasonographic evaluation (50 MHz) of morphoea treated with ultraviolet A1 phototherapy.

BACKGROUND: There are few studies in the literature correlating the ultrasonographic findings, clinical scoring systems or histological findings in morphoea after ultraviolet (UV)A1 phototherapy. AIMS: To evaluate the quantitative and morphological aspects of high-frequency ultrasonography in the treatment of plaque morphoea in response to UVA1 phototherapy, and to correlate these with clinical and histological scores. METHODS: In total, 17 patients with morphoea were studied. Initially and at study end, high-frequency ultrasonography (50 MHz) was performed on the edge of a morphoea lesion treated with UVA1 phototherapy. A quantitative and qualitative analysis of dermal features was performed and compared with the features of healthy skin. Skin biopsy specimens were obtained from lesions analysed at the beginning and end of the study, assessing dermal sclerosis and dermal inflammatory infiltrate and their distribution. RESULTS: All affected skin showed a statistically significant increase in dermal thickness and hypoechogenicity, corresponding to a reduction in dermal density by ultrasonography compared with healthy skin. Morphological evaluation identified undulations of the dermis in 11 of 17 lesions (64.7%) and in 5 healthy skin areas (29.4%) (P = 0.08), while 'yoyo' figures were identified in 8 lesions (47%) but only 1 healthy skin area (5.9%) (P = 0.02). Ultrasonographic morphological analysis highlighted an improvement in dermal hyperechogenic bands and disappearance of yoyo figures after UVA1 treatment. Histology revealed a reduction in dermal sclerosis and inflammation, although this was not statistically significant. CONCLUSIONS: Ultrasonographic pattern analysis of morphoea is a suitable technique for monitoring UVA1 phototherapy response.

Cutaneous infiltration of plasmacytoid dendritic cells and T regulatory cells in skin lesions of polymorphic light eruption.

BACKGROUND: Polymorphic light eruption (PLE) is the most common autoimmune photodermatosis. Plasmacytoid dendritic cells (PDCs) are important mediators of innate antimicrobial immunity involved in the pathogenesis of many inflammatory skin diseases. In addition to PDCs, regulatory T cells (Tregs) are involved in controlling inflammation and adaptive immunity in skin by their immunosuppressive capacity. OBJECTIVE: The aim of this study was to investigate the presence of PDCs and Tregs in photoexposed skin from PLE compared to healthy skin. METHODS: Patients with PLE diagnosis and healthy controls were recruited and underwent a photoprovocative test. A 4-mm punch biopsy was taken from the site of positive photoprovocation test reaction, and immunohistochemistry for BDCA2 as marker for PDCs, CD4 and FOXP3 as markers for Tregs was performed. Double immunostain for FOXP3 and CD4 was performed as well. Absolute counts for CD4, BDCA2 and FOXP3 were performed in at least 5 High Power Fields (HPF). Percentage of CD4-, BDCA2- and CD4FOXP3-positive cells over the total inflammatory infiltrate was assessed for each case. RESULTS: We enrolled 23 patients and controls. BDCA2+ cells were present in 91.3% of PLE skin samples and 100% of healthy volunteer. Both in PLE patients and healthy controls, PDCs distribution was mainly dermic (P < 0.05). Compared to healthy controls, both epidermic and dermic BDCA2+ cells count were significantly higher in PLE patients (P < 0.05). Both in PLE patients and healthy controls, Tregs distribution was mainly dermic (P < 0.05). The presence of both CD4+ cells and FOXP3+ cells was significantly higher in the dermis of PLE patients compared to controls (P < 0.05). Relative percentages of cellular infiltrations confirmed these results. CONCLUSIONS: D-PDCS and Tregs may play a significant role in the development of PLE, and dermal distribution of PDCs in PLE skin biopsies seems to confirm a possible overlap with cutaneous lupus erythematosus (CLE).

Anomalous cutaneous absorption of allergens as cause of skin prick testing adverse reactions in adult patients. Clinical and experimental evidence.

BACKGROUND: Paediatric age, active eczema and high number of allergens tested in poly-sensitized patients have been pinpointed as possible risk factors of systemic reactions by skin prick testing. As far as atopic eczema concerns, the higher penetration of the allergens into the skin because of the scraping or micro-injuries is an intuitive rationalization. Purpose of the present study is to provide documentary evidence that adverse reactions elicited by anomalous absorption of allergens can occur also in adult patients with apparently normal skin. METHODS: Report of some exemplifying clinical and experimental observations. Measuring the inoculum volume into impaired skin and its variability in relation to the variation of the chemical-physical characteristic of the solutions used for the tests by means of a method of direct assay based on the use of a gamma-camera. RESULTS: Localized impairments of the skin permeability can cause a significant increase in inoculum volume by prick-test. Critical amounts of allergens can be introduced into the skin because of the possibility of direct absorption, also without pricking, of allergy diagnostic solutions. The greater water content of the solutions used for prick-testing can significantly increase the inoculum volume. CONCLUSIONS: This study adds clinical and experimental evidences that localized impairments of permeability can occur in adult patients with apparently normal skin. Special precautions should be taken when a change of the drops' normal shape and cohesion is seen, because allergy prick-testing in such areas is potentially associated with increased risk of large local or systemic reactions.

Recurrent migratory angioedema as cutaneous manifestation in a familiar case of TRAPS: dramatic response to Anakinra.

BACKGROUND: Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS) is a hereditary autoinflammatory syndrome characterized by recurrent episodes of fever and localized inflammation. Clinical presentation can be very variable in terms of duration of fever attacks, periodicity, and accompanying manifestations. One of the most characteristic symptoms is the occurrence of migrating skin rash with myalgia that is sustained by monocytic inflammation. OBSERVATIONS: We herein present the case of a family suffering from TRAPS who had been misdiagnosed for a long period of time and whose main symptom was migrating angioedema. Skin biopsy from one of the patients documented a monocytic panniculitis. All the living patients responded dramatically to anakinra treatment. CONCLUSIONS: The classic symptom of migratory angioedema with myalgia in TRAPS can be produced by monocytic panniculitis.This manifestation is so characteristic of TRAPS that its occurrence, even in the absence of other manifestations, should prompt genetic analysis. Our patient's condition responded promptly to anakinra treatment.

Synergism between narrowband ultraviolet B phototherapy and etanercept for the treatment of plaque-type psoriasis.

BACKGROUND: Previous investigations have demonstrated that a combination of etanercept (ETN) and narrowband ultraviolet B (NB-UVB) phototherapy is more effective than ETN alone. However, it is unclear if this combination is more effective than NB-UVB phototherapy alone. OBJECTIVES: To evaluate whether the combination of NB-UVB phototherapy with ETN improves the efficacy of ETN alone in the treatment of moderate-to-severe psoriasis. METHODS: We enrolled 322 consecutive patients with moderate-to-severe plaque-type psoriasis, who were treated with NB-UVB phototherapy as the first-line treatment option. Patients who did not achieve a 75% improvement in Psoriasis Area and Severity Index (PASI 75) were treated with conventional systemic therapies for psoriasis. If they were ineligible for these, they were treated with ETN 50 mg twice weekly. If they did not achieve PASI 75 within 12 weeks, NB-UVB phototherapy was added. RESULTS: PASI 75 was achieved in 262 patients (81.4%) treated with NB-UVB phototherapy. Sixteen patients (5.0%) dropped out for personal reasons and 24 (7.5%) were treated with at least one of the conventional systemic treatments for psoriasis. Twenty patients (6.2%) were treated with ETN. The combination regimen was needed in eight patients (2.5%) with poor response to both phototherapy and ETN alone. All of these patients achieved PASI 75 and three of them had a complete remission after 14.6 ± 3.3 NB-UVB exposures. The combined treatment was well tolerated without acute adverse events. Unfortunately, all of these patients relapsed, with PASI > 10 within 2.8 ± 1.7 months. CONCLUSIONS: The combined treatment has a synergistic effect for clearing plaque-type psoriasis previously unresponsive to ETN and NB-UVB phototherapy alone. The clearance rate is very high in a very short time without short-term adverse effects. However, concerns regarding potential cocarcinogenicity remain. Therefore the number of patients who require, and could benefit from, the combined treatment is likely to be small.

Photobiology, photodermatology and sunscreens: a comprehensive overview. Part 1: damage from acute and chronic solar exposure.

Sun exposure of the skin triggers several inflammatory pathways via a multitude of photochemical and photobiological effects. Furthermore, local and systemic immune suppression develops. The main clinical effects of UV exposure can be classified schematically into immediate, including sunburn, tanning, vitamin D production and exacerbation of inherited and acquired photosensitive skin disorders and long-term, including solar ageing and skin cancer. The protection against solar radiation is afforded by a healthy behavior of reasonable sun avoidance and the use of topical sunscreens as well as topical and oral antioxidants. However, users of sunscreen products should be able to choose correctly the more convenient product according to their needs. In Europe, the sun protection factor (SPF) and the UVA-protection factor (UVA-PF) are labeled to indicate the degree of protection against UVB and UVA, respectively. However, dermatologists must be aware that the present knowledge of UV effects on human skin needs to be clarified and several regulatory issues of photo-protection remain to be clarified and standardized. Finally, much work is needed to improve water resistance, spreadability, transparency and homogeneity of the sunscreen agents.

Photobiology, photodermatology and sunscreens: a comprehensive overview. Part 2: topical and systemic photoprotection.

Sun exposure of the skin triggers several inflammatory pathways via a multitude of photochemical and photobiological effects. Furthermore, local and systemic immune suppression develops. The main clinical effects of UV exposure can be classified schematically into immediate, including sunburn, tanning, vitamin D production and exacerbation of inherited and acquired photosensitive skin disorders and long-term, including solar ageing and skin cancer. The protection against solar radiation is afforded by a healthy behavior of reasonable sun avoidance and the use of topical sunscreens as well as topical and oral antioxidants. However, users of sunscreen products should be able to choose correctly the most convenient product according to their needs. In Europe, the sun protection factor (SPF) and the UVA-protection factor (UVA-PF) are labeled to indicate the degree of protection against UVB and UVA, respectively. However, dermatologists must be aware that the present knowledge of UV effects on human skin needs to be clarified and several regulatory issues of photo-protection remain to be clarified and standardized. Finally, much work is needed to improve water resistance, spreadability, transparency and homogeneity of the sunscreen agents.

Assay of prick test inoculum volume. I. Use and reliability of a gamma camera-based method.

INTRODUCTION: In dermatology and allergy there are clinical research circumstances where very small amounts of substances introduced into the skin have to be measured "in vivo." An example is the assay of reagents injected by prick test. As injected volumes are very small, it is necessary to use indicators that can be measured at very low concentrations. In in vitro studies, gamma-emitting radioisotopes have been shown suitable for use as the indicators. In in vivo studies, except for instruments devised for specific research requirements, the measurement of small sources is taken with a common gamma camera. OBJECTIVE: The purpose of the present study is to evaluate the experimental reliability of a gamma camera-based method to measure microvolumes labeled with radioisotopes and its suitable application in vivo studies. METHODS: Using a solution of 99m Tc-pertechnetate, we prepared, with precision pipettes, some sets of scalar volumes ranging from 1 micro to 200 picoliters, which correspond to activities between some micros and some hundreds of picocuries. The volumes were measured with a gamma camera both with and without a collimator. The overall reliability of the method under different experimental conditions was evaluated for sensitivity, precision, and accuracy. Last, a blind measurement was taken as a final check on the overall reliability of the method. RESULTS: The volume-activity correlation appeared to be linear, with a Spearman coefficient higher than 0.99. The correlation straight lines of the measurements taken with and without a collimator proved that, in both cases, the linearity of the system did not change. The method showed a high degree of precision and accuracy. The maximum variation coefficient never exceeded 1.5% and the standard error 2%. The sampling error of the measured volumes was less than 8% in all the sets: up to 7% was due to the manual operations and to the technical characteristics of the micropipettes. The gamma camera measurement error ranged from 1% to 3%. The blind tests experimentally confirmed the overall reliability of the method. CONCLUSIONS: The method we studied proved highly reliable and inexpensive. Measurement errors are almost exclusively due to sampling errors. The gamma camera is a device any nuclear medicine department is equipped with, and a solution of 99m Tc-pertechnetate is readily available.

Assay of prick test inoculum volume. II. Average values and individual variability.

INTRODUCTION: The amount of reagent introduced into the skin by a prick test is critical in studies on the reproducibility and standardization of the method. OBJECTIVE: The purpose of the present study was to measure the average volume and the individual variability of the inoculum performed with a prick test standardized technique. METHODS: Two hundred forty prick tests--16 inoculations per subject--were performed on the volar sides of arms of 15 healthy volunteers. The tests were performed by a skilled tester whose technical performance complied with the criteria of good reproducibility described in international guidelines. A 1-mm tip standard device and a 50% glycerosaline solution labeled with Tc99m were used for the test. The inoculum size was calculated using a direct assay method based on the gamma camera. RESULTS: The average volume of the prick test inoculum was equal to 0.016 microliters, with a remarkable dispersion of the values around the mean (median, 15906: range, 418 to 82253 picoliters). Further, we observed great variability from one subject to another and great variability in the same subject from one skin site to another. A statistical analysis of the data shows that this variability depends on the individual characteristics of the subjects examined. A skilled tester using a standardized technique is not responsible for significant variability. CONCLUSIONS: Even when performed by a skilled operator and with standardized techniques, the prick test shows great limits of reproducibility, at least as far as the size of the inoculum volume is concerned. The variability of the inoculum depends, in a statistically significant way, on the subject's individual characteristics and therefore can be reduced only within certain limits by the standardization and perfectibility of the technique.

Effect of exogenous reduced glutathione on the survival of red blood cells in hemodialyzed patients.

Reduced glutathione (GSH) is an important scavenger of free radicals in the red blood cell (RBC) membrane, and its deficiency may be a partial cause of increased hemolysis and shortened RBC survival in uremics. In this study we employed exogenous GSH (1200 mg i.v. at the end of each dialysis session for at least nine months) to treat anemia in a group of 28 hemodialyzed patients, 14 of whom were also receiving erythropoietin. RBC survival (51Cr T/2) was calculated before (26 patients) and at the end (15 pts) of GSH therapy. After the first three months anemia (RBC, hemoglobin, hematocrit, reticulocytes) improved significantly in 17 patients (60%), for as long as they were under therapy, but rapidly dropped to pre-treatment values when GSH was discontinued. The 51Cr T/2 increased significantly in responders, but not in those who did not respond. No significant differences were found between responders and non-responders as regards urea KT/V, PTH, serum iron, ferritin, dialysis membrane, dose of erythropoietin and basal 51Cr T/2. These results suggest that exogenous GSH may be a promising drug for the treatment of anemia in most hemodialyzed patients, particularly considering its low cost.

[The effect of age on early and late mortality after an acute myocardial infarct]. / Influenza dell'età sulla mortalità precoce e tardiva dopo infarto miocardico acuto.

The purpose of this study is to define the importance of age as predictor of early and late mortality following acute myocardial infarction (AMI). At the same time, effects coming from the use of various therapeutic approaches are considered. We have studied 341 patients, 188 aged < 70 years and 153 > or = 70 years, consecutively admitted to the coronary care unit with diagnosis of AMI. Our findings show that age > or = 70 years, female gender, cardiogenic shock, ventricular fibrillation and early post-infarction angina are significantly connected to higher intra-hospital mortality. As for predictors of 1-year mortality, they turned out to be the age > or = 70 years, indirect signs of more extensive infarction as previous necrosis, acute heart failure, cardiogenic shock, new bundle branch blocks and pre-discharging lower ventricular ejection fraction. In patients aged > or = 70 years, especially in ultra eighty-year old men, thrombolysis, heparin, beta-blockers and aspirin are significantly less employed. All drugs used in the early hours of AMI turned out to be bound to beneficial effects with reduced mortality, except diuretics and antiarrhythmics. The only drugs correlated with an improved 1 year survival are betablockers, aspirin and thrombolysis. On the contrary, the use of diuretics and digoxin is limited to patients with a greater clinical dysfunction. These drugs are associated to a higher late mortality. The present study confirms the finding that elderly patients with AMI who are submitted to less aggressive therapeutic approaches and are more frequently represented by women, have a higher mortality.

[Prognostic significance of thallium-201 scintigraphy in patients with previous myocardial infarct]. / Valore prognostico della scintigrafia con tallio-201 nei pazienti con pregresso infarto miocardico.

With the purpose of ascertaining the predictive value of residual myocardial ischemia, in stable clinical conditions at a distance after myocardial infarction, on the incidence of late cardiac events, we evaluated 55 patients 24.2 +/- 11.4 months after myocardial infarction with thallium-201 stress test imaging. All patients were either asymptomatic or with stable effort angina pectoris, well controlled with medical treatment. In the next follow-up period, whose duration has been 22.4 +/- 14.4 months, the incidence of unfavourable cardiac events, like unstable angina, reinfarction, coronary bypass surgery, sudden cardiac death has been monitored. Thirty-one patients (56.4%) presented a reversible perfusion defect (RPD) in one or more myocardial segments; 17 of these 31 showed cardiac events during follow-up. Only 2 patients of the remaining 24 without RPD had cardiac events, with a significant difference (p less than 0.01). The patients with RPD only in peri-infarct areas had a relatively smaller number of cardiac events, with respect to those patients with RPD also or only in distant areas. Fifteen of 21 patients with RPD in 2 or more segments manifested cardiac events, compared to 2 of 10 patients with RPD in only one segment (p less than 0.01). In 10/55 patients, increased lung uptake of thallium-201 activity was observed; 8 of them presented cardiac events (p less than 0.01). This analysis confirms the high predicting value of thallium-201 RPD imaging on the incidence of cardiac events in patients controlled at a distance after myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

[Breast carcinoma. Technical problems of radiotherapy. Proposal of an algorithm as an alternative to the lack of scintigraphic visualization of the internal mammary lymph nodes]. / Carcinoma mammario. Problemi di tecnica radioterapica. Proposta di un algoritmo in alternativa alla non visualizzazione scintigrafica delle catene mammarie interne.

In early breast cancer, radiation therapy following conservative surgery needs a topographic evaluation of internal mammary lymph nodes. Three-dimensional lymphoscintigraphy (IML3D) is an useful method for this purpose. The average depth of the lymph nodes is closely correlated with the square root of the body weight/height ratio. We calculated the individual maximum depth of the lymph nodes from this function; the parameter was then verified with the experimental data from our series of cases (53 patients). Although the suggested algorithm needs to be verified on a larger number of patients, we believe the empirical maximum depth measurement to be useful when IML3D is unfeasible or the internal mammary lymph nodes are not demonstrated on scintigraphic scans.

[The recombination factor in an ionizing chamber used for dosimetry of a linear accelerator]. / Il fattore di ricombinazione in una camera a ionizzazione impiegata per la dosimetria di un acceleratore lineare.

The authors starting from the discussion of Boag address experimentally the ion recombination in an ionizing camera. They outline the fact that several basic dosimetry protocols do not highlight the importance of the used radiation sources, beam width, ionizing camera dimensions, even though they mention to take into account the recombination factor. The authors determine experimentally the recombination factor with two kinds of ionizing camera, one cylindrical and the other flat, on a linac pulsed and scanned radiation beams. As a result it ensued that it is advisable to use a Markus type ionizing camera rather than a cylindrical one, especially when scanning beams are used, to reduce the recombination phenomena.