Effectiveness of a 308-nm excimer laser in treatment of vitiligo: a review

Vitiligo is a relatively common acquired disorder, characterized by progressive loss of melanocytes from the epidermis and the epidermal appendages. The disease is associated with considerable morbidity because of a major impact on the quality of life. The treatment for vitiligo is generally unsatisfactory and challenging. There are a variety of therapeutic possibilities including topical corticosteroids, topical calcineurin inhibitors, as well as phototherapy with Psoralen plus UVA (PUVA), narrow-band UVB, and a 308-nm excimer laser and/or lamps. Furthermore, surgical methods encompass grafting and transplantation while depigmentation treatments and psychological support may also be considered. The objective is to assess the effect of the 380-nm excimer laser in the treatment of vitiligo based on the available studies and case series. We searched the relevant literature about vitiligo and excimer laser published between 1990 and 2012 using the MEDLINE database. We reviewed all relevant articles about 308-nm excimer laser and light sources assessing their efficacy in the management of vitiligo as well as their side effects. The value of combination treatment methods was also analyzed. The available studies provide strong evidence that the excimer laser represents the most effective approach to treat vitiligo compared to ordinary phototherapy. Excimer laser is relatively safe and effective for localized disease. UV-sensitive areas respond best as well as a short duration of the disease. More frequent treatments achieve better results. Compared to other treatment modalities, the excimer laser most likely constitutes the treatment of choice for localized vitiligo. Its efficacy can be further improved in combination with other therapies such as corticosteroids, pimecrolimus, or tacrolimus.

Platelet-activating factor is crucial in psoralen and ultraviolet A-induced immune suppression, inflammation, and apoptosis.

Psoralen plus UVA (PUVA) is used as a very effective treatment modality for various diseases, including psoriasis and cutaneous T-cell lymphoma. PUVA-induced immune suppression and/or apoptosis are thought to be responsible for the therapeutic action. However, the molecular mechanisms by which PUVA acts are not well understood. We have previously identified platelet-activating factor (PAF), a potent phospholipid mediator, as a crucial substance triggering ultraviolet B radiation-induced immune suppression. In this study, we used PAF receptor knockout mice, a selective PAF receptor antagonist, a COX-2 inhibitor (presumably blocking downstream effects of PAF), and PAF-like molecules to test the role of PAF receptor binding in PUVA treatment. We found that activation of the PAF pathway is crucial for PUVA-induced immune suppression (as measured by suppression of delayed type hypersensitivity to Candida albicans) and that it plays a role in skin inflammation and apoptosis. Downstream of PAF, interleukin-10 was involved in PUVA-induced immune suppression but not inflammation. Better understanding of PUVA's mechanisms may offer the opportunity to dissect the therapeutic from the detrimental (ie, carcinogenic) effects and/or to develop new drugs (eg, using the PAF pathway) that act like PUVA but have fewer side effects.

Revascularisation versus medical treatment in patients with stable coronary artery disease: network meta-analysis

OBJECTIVE To investigate whether revascularisation improves prognosis compared with medical treatment among patients with stable coronary artery disease. DESIGN Bayesian network meta-analyses to combine direct within trial comparisons between treatments with indirect evidence from other trials while maintaining randomisation. ELIGIBILITY CRITERIA FOR SELECTING STUDIES A strategy of initial medical treatment compared with revascularisation by coronary artery bypass grafting or Food and Drug Administration approved techniques for percutaneous revascularization: balloon angioplasty, bare metal stent, early generation paclitaxel eluting stent, sirolimus eluting stent, and zotarolimus eluting (Endeavor) stent, and new generation everolimus eluting stent, and zotarolimus eluting (Resolute) stent among patients with stable coronary artery disease. DATA SOURCES Medline and Embase from 1980 to 2013 for randomised trials comparing medical treatment with revascularisation. MAIN OUTCOME MEASURE All cause mortality. RESULTS 100 trials in 93 553 patients with 262 090 patient years of follow-up were included. Coronary artery bypass grafting was associated with a survival benefit (rate ratio 0.80, 95% credibility interval 0.70 to 0.91) compared with medical treatment. New generation drug eluting stents (everolimus: 0.75, 0.59 to 0.96; zotarolimus (Resolute): 0.65, 0.42 to 1.00) but not balloon angioplasty (0.85, 0.68 to 1.04), bare metal stents (0.92, 0.79 to 1.05), or early generation drug eluting stents (paclitaxel: 0.92, 0.75 to 1.12; sirolimus: 0.91, 0.75 to 1.10; zotarolimus (Endeavor): 0.88, 0.69 to 1.10) were associated with improved survival compared with medical treatment. Coronary artery bypass grafting reduced the risk of myocardial infarction compared with medical treatment (0.79, 0.63 to 0.99), and everolimus eluting stents showed a trend towards a reduced risk of myocardial infarction (0.75, 0.55 to 1.01). The risk of subsequent revascularisation was noticeably reduced by coronary artery bypass grafting (0.16, 0.13 to 0.20) followed by new generation drug eluting stents (zotarolimus (Resolute): 0.26, 0.17 to 0.40; everolimus: 0.27, 0.21 to 0.35), early generation drug eluting stents (zotarolimus (Endeavor): 0.37, 0.28 to 0.50; sirolimus: 0.29, 0.24 to 0.36; paclitaxel: 0.44, 0.35 to 0.54), and bare metal stents (0.69, 0.59 to 0.81) compared with medical treatment. CONCLUSION Among patients with stable coronary artery disease, coronary artery bypass grafting reduces the risk of death, myocardial infarction, and subsequent revascularisation compared with medical treatment. All stent based coronary revascularisation technologies reduce the need for revascularisation to a variable degree. Our results provide evidence for improved survival with new generation drug eluting stents but no other percutaneous revascularisation technology compared with medical treatment.

Medical, psychological and socio-economic implications of chronic hand eczema: a cross-sectional study.

BACKGROUND Hand eczema (HE) is a common skin disease with major medical psychological and socio-economic implications. Onset and prognosis of HE are determined by individual as well as environmental factors. So far, most epidemiological data on HE have been reported from Scandinavian and recently German studies. OBJECTIVE To investigate the characteristics and medical care of patients with chronic HE (CHE) in Switzerland, and identify risk factors. METHODS In this cross-sectional study, data from patients with chronic HE were obtained by means of medical history, dermatological examination and patient questionnaires. Multiple logistic regression analysis was applied to identify risk factors for high severity and dermatology life quality index (DLQI). RESULTS In seven dermatology departments, 199 patients (mean age 40.4 years, 50.8% female) with CHE (mean duration 6.6 years) were enrolled. Moderate to severe HE was reported by 70.9% of patients, and was associated with age <30 or >50 years, localization of lesions and pruritus. Because of the CHE, 37.3% of patients were on sick leave over the past 12 months, 14.8% had changed or lost their job. Practically all patients applied topical therapy, 21% were treated with alitretinoin, and 21% with psoralen plus UVA light (PUVA). The effects on the health-related quality of life was moderate to large in 33.7% and 39.4% of CHE patients, respectively. Factors associated with a high impact on DLQI (mean 9.7 ± 5.8) were female sex, lesions on back of the hands and pruritus as well as mechanical skin irritation and wearing gloves. CONCLUSION In agreement with recent studies, the Swiss data demonstrate the high impact of CHE on medical well-being, patient quality of life and work ability. As it is associated with an intense use of health care services, high rate of sick leave, job loss and change, CHE may cause a high socio-economic burden.

EACTS expert consensus statement for surgical management of pleural empyema

Pleural infection is a frequent clinical condition. Prompt treatment has been shown to reduce hospital costs, morbidity and mortality. Recent advances in treatment have been variably implemented in clinical practice. This statement reviews the latest developments and concepts to improve clinical management and stimulate further research. The European Association for Cardio-Thoracic Surgery (EACTS) Thoracic Domain and the EACTS Pleural Diseases Working Group established a team of thoracic surgeons to produce a comprehensive review of available scientific evidence with the aim to cover all aspects of surgical practice related to its treatment, in particular focusing on: surgical treatment of empyema in adults; surgical treatment of empyema in children; and surgical treatment of post-pneumonectomy empyema (PPE). In the management of Stage 1 empyema, prompt pleural space chest tube drainage is required. In patients with Stage 2 or 3 empyema who are fit enough to undergo an operative procedure, there is a demonstrated benefit of surgical debridement or decortication [possibly by video-assisted thoracoscopic surgery (VATS)] over tube thoracostomy alone in terms of treatment success and reduction in hospital stay. In children, a primary operative approach is an effective management strategy, associated with a lower mortality rate and a reduction of tube thoracostomy duration, length of antibiotic therapy, reintervention rate and hospital stay. Intrapleural fibrinolytic therapy is a reasonable alternative to primary operative management. Uncomplicated PPE [without bronchopleural fistula (BPF)] can be effectively managed with minimally invasive techniques, including fenestration, pleural space irrigation and VATS debridement. PPE associated with BPF can be effectively managed with individualized open surgical techniques, including direct repair, myoplastic and thoracoplastic techniques. Intrathoracic vacuum-assisted closure may be considered as an adjunct to the standard treatment. The current literature cements the role of VATS in the management of pleural empyema, even if the choice of surgical approach relies on the individual surgeon's preference.

Molecular mechanism of PUVA-induced apoptosis in mouse epidermal cells

A combination of psoralens and ultraviolet-A radiation referred to as PUVA, is widely used in the treatment of psoriasis. PUVA therapy is highly effective in killing hyperproliferative cells, but its mechanism of action has not been fully elucidated. Psoralen binds to DNA, and upon photoactivation by UVA, it forms monofunctional adducts and interstrand cross-links. PUVA treatment has been shown to be mutagenic and to produce tumors in animals. In addition, epidemiological studies have reported a 10 to 15 percent increased risk of developing squamous cell carcinoma in individuals treated chronically with PUVA. However, it remains a treatment for skin disorders such as psoriasis because its benefits outweigh its risks. The widespread use of PUVA therapy and its associated cancer risk requires us to understand the molecular mechanisms by which PUVA induces cell death. Immortalized JB6 mouse epidermal cells, p53−/− mice, and Fas Ligand−/− (gld) mice were used to investigate the molecular mechanism by which PUVA kills cells. Treatment of JB6 cells with 10 μg/ml 8-methoxypsoralen followed by irradiation with 20 kJ/m2 UVA resulted in cell death. The cells exhibited morphological and biochemical characteristics of apoptosis such as chromatin condensation, DNA ladder formation, and TUNEL-positivity. PUVA treatment stabilized and phosphorylated p53 leading to its activation, as measured by nuclear localization and induction of p21Waf/Cip1, a transcriptional target of p53. Subsequent in vivo studies revealed that there was statistically significantly less apoptosis in p53 −/− mice than in p53+/+ mice at 72 hours after PUVA. In addition, immunohistochemical analysis revealed more Fas and FasL expression in p53+/+ mice than in p53−/− mice, suggesting that p53 is required to transcriptionally activate Fas, which in turn causes the cells to undergo apoptosis. Studies with gld mice confirmed a role for Fas/FasL interactions in PUVA-induced apoptosis. There was statistically significantly less apoptosis in gld mice compared with wild-type mice 24, 48, and 72 hours after PUVA. These results demonstrate that PUVA-induced apoptosis in mouse epidermal cells requires p53 and Fas/FasL interactions. These findings may be important for designing effective treatments for diseases such as psoriasis without increasing the patient's risk for skin cancer. ^