Monochromatic excimer light (308 nm) in the treatment of prurigo nodularis

Three hundred and eight nanometre excimer light has been reported to be safe and effective in the treatment of chronic skin diseases, but the range of potential applications has not been fully explored. Our objective was to assess the efficacy of monochromatic excimer light (MEL) in the treatment of prurigo nodularis (PN). Eleven patients were enrolled in this pilot study. Patients were treated weekly and an average of eight sessions of MEL was given. Follow-up was 4 months. Partial or complete clinical and histological remission was observed in all patients who completed the study (81%).     

Monochromatic excimer light 308 nm in the treatment of vitiligo: a pilot study

OBJECTIVE: To study the efficacy and safety of monochromatic excimer light (MEL) on 37 vitiligo patients referred to our clinic. METHODS: In a pilot study, 37 patients (17 males, 20 females) with acrofacial (n=21), focal (n=11), segmental (n=1), and generalized (n=4) vitiligo were treated twice weekly with MEL for a maximum period of 6 months. RESULTS: Thirty-five patients (95%) showed signs of repigmentation within the first eight treatments. The treatment resulted in good repigmentation in 16 patients, and excellent repigmentation in 18 patients. Adverse events were limited to transient erythema. In addition, some patients (n=3) not responding to prior narrow-band UVB (NB UVB) phototherapy showed good results with MEL in our series. CONCLUSIONS: Treatment with 308 nm MEL for vitiligo may be more effective in obtaining rapid repigmentation than phototherapy with NB UVB. The results in this study are similar to those recently reported with a 308 nm excimer laser, but 308 MEL could present some advantages: the possibility of treating larger areas compared to the 308 nm excimer laser, with shorter treatment times and better patient compliance. The overall good results and the early appearance of repigmentation contribute to reducing the cumulative exposure to UV radiation.     

Evaluation of 308-nm monochromatic excimer light in the treatment of psoriasis vulgaris and palmoplantar psoriasis

Background: The purpose of this study is to evaluate the efficacy and safety of 308‐nm monochromatic excimer light (MEL) in the treatment of psoriasis vulgaris and palmoplantar psoriasis. Methods: Thirty‐five patients with psoriasis vulgaris and 15 patients with palmoplantar psoriasis were recruited for this study. Thirty patients with psoriasis vulgaris completed a total of 16 treatments with 308‐nm MEL twice a week, and 15 patients palmoplantar psoriasis completed 25 treatments administered once weekly. The clinical response to therapy and adverse effects were recorded. Results: Patients with psoriasis vulgaris (n=30) showed a 74.6% improvement in the mean psoriasis area and severity index score after a total of 16 MEL treatments (2 ×/week) with 36.7% of the patients (n=11) achieving clearance. Patients with palmoplantar psoriasis (n=15) showed a 52.5% improvement in the mean severity index score after a total of 25 MEL treatments (1 ×/week) with only one patient (6.7%) achieving clearance. The MEL therapy was well tolerated with a low incidence of side effects, which included pruritus, erythema and blister formation. Conclusion: The 308‐nm MEL can be utilized as an effective and safe treatment modality for patients with mild‐to‐moderate psoriasis vulgaris and palmoplantar psoriasis.     

308nm准分子激光联合卡泊三醇软膏治疗斑块状银屑病疗效评价

目的：评价308 nm准分子激光联合卡泊三醇软膏治疗斑块状银屑病的临床疗效.方法：将93例稳定期斑块状银屑病随机分为3组,治疗组（33例） 予308 nm准分子激光照射,每周2次联合外搽卡泊三醇软膏,每日2次;对照1组（30例）外搽卡泊三醇软膏;对照2组（30例）,予308 nm准分子激光照射,方法同治疗组,2个月后判断疗效.结果：治疗组、对照1组和对照2组的有效率分别为90.91%、73.33%、63.33%.3组间疗效比较差异有统计学意义（均P〈0.05）.结论：308 nm准分子激光联合卡泊三醇软膏治疗斑块状银屑病能更好地提高疗效.     

An immunohistochemical study of abnormal keratinocyte proliferation in molluscum contagiosum

BACKGROUND: Molluscum contagiosum is a common cutaneous tumour that is characterized by usually spontaneous involution and self-limited spreading in immunocompetent individuals. OBJECTIVE: We aimed to investigate the apoptosis and the expression of cell-cycle proteins in molluscum contagiosum lesions. METHODS: The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL)-based apoptotic index and the expression of the cell-cycle proteins Ki-67, p53, p21WAF and Bcl-2 were investigated in molluscum contagiosum lesions obtained from the trunk of 20 immunocompetent patients and in normal skin samples from the trunk of six healthy volunteers. RESULTS: Whereas molluscum contagiosum lesions displayed a TUNEL-based apoptotic index similar to that of normal skin, they exhibited an increased Ki-67 index, which was confined to the basal and first suprabasal layers (P < 0.001). Compared with normal non-sun-exposed skin, molluscum contagiosum lesions also exhibited increased p53 staining in basal cells (P < 0.01), increased p21WAF in suprabasal cells (P < 0.001) and loss of Bcl-2 expression. CONCLUSIONS: These results indicate that molluscum contagiosum lesions exhibit an increased proliferation rate of keratinocytes, which is likely to be partially counteracted by accumulation of p53.     

Efficacy of monochromatic excimer laser radiation (308 nm) in the treatment of early stage mycosis fungoides

BACKGROUND: Various reports have recently shown the efficacy of narrowband ultraviolet (UV) B phototherapy at 311 nm in the treatment of early stage mycosis fungoides (MF). OBJECTIVES: To examine the effectiveness and tolerability of monochromatic excimer light (MEL) at 308 nm as a first treatment for early stage MF (stage IA). METHODS: Ten lesions from five patients with a clinical and histological diagnosis of MF were treated with repeated applications of MEL until complete remission was achieved or up to a maximum of 10 applications, with a cumulative dose of 308 nm UVB of between 6 and 12 J cm(-2). All patients were observed every 2 weeks for 2 months, with a 1-year follow-up. Results At present, all patients are in complete remission, with no side-effects. CONCLUSIONS: Based on these results, MEL can be considered a useful tool in the treatment of early stage MF.     

The development of a filter to enhance the efficacy and safety of excimer light (308 nm) therapy

Background: Excimer light (308 nm) therapy is a new ultraviolet (UV) B phototherapy for which the efficacy and resulting DNA damage are not well established.
Purpose: To develop an effective and safe phototherapy using the excimer lamp, we studied the effects of different light cut-off filters, A and B.
Methods: Efficacy was evaluated by measuring apoptosis using fluorescence-activated cell sorting analysis. DNA damage was evaluated by measuring cyclobutane pyrimidine dimers (CPDs). Light sources, including normal wave and short wave (SW) excimer light, broad-band (BB) UVB, and narrow-band (NB) UVB, were examined using the filters. A human skin equivalent model was also examined.
Results: The ratio of positive apoptosis to CPD formation normalized to the mean induced by NB-UVB was 5.7 using the excimer lamp without a filter, 6.3 using the excimer lamp with the A filter, 6.4 using the SW excimer lamp without a filter, and 4.2 using the BB-UVB. The A filter reduced CPD formation induced by the normal wave and SW excimer lamp. In the human skin equivalent model, the use of filters significantly decreased the amount of CPD-positive cells.
Conclusions: These findings suggest that using the A filter with the excimer lamp increases the efficacy and safety of excimer light therapy.     

Monochromatic excimer light 308 nm in monotherapy and combined with topical khellin 4% in the treatment of vitiligo: a controlled study

Vitiligo is an acquired depigmentation disorder affecting 1–4% of the world's population. Conventional therapies include steroids, photosensitive topical agents, surgical treatments, and phototherapy. The aim of the study was to evaluate the efficacy of monochromatic excimer light 308 nm (MEL), both as a monotherapy and in combination with khellin 4% ointment in vitiligo. Forty-height patients (36 male and 12 female) affected with vitiligo were enrolled in this open prospective study. Patients were selected and divided into three groups: group I included 16 patients treated with MEL 308 nm once-weekly and oral vitamin E; group II included 16 patients treated with MEL 308 nm once-weekly combined with khellin 4% ointment (MEL-K) and oral vitamin E; group III (control group) included 16 patients treated only with oral vitamin E. Efficacy was assessed at the end of 12 weeks based on the percentage of repigmentation. Group I (MEL-group) showed a moderate repigmentation in 2/16 (12.5%) patients, good repigmentation in 10/16 (62.5%), and excellent repigmentation in 4/16 (25%) patients. Group II (MEL-K group) presented moderate repigmentation in 2/16 (12.5%) patients, good repigmentation in 5/16 (31.25%), and excellent repigmentation in 9/16 (56.25%). Group III (control group) showed a moderate repigmentation in 3/16 patients (18.75%), a good repigmentation in 1/16 (6.25%) patient, while 10/16 (62.5%) patients did not show signs of repigmentation. The clinical response achieved in group I and II was higher compared with group III (control group) without showing significant differences. MEL 308 nm, alone and/or combined with khellin 4% offered encouraging results and it may be considered a valid therapeutic option worthy of consideration in the treatment of vitiligo.     

UVB 308‐nm excimer light and bath PUVA: combination therapy is very effective in the treatment of prurigo nodularis

Background Prurigo nodularis (PN) is a chronic inflammatory skin disease with nodular itching lesions. UV therapy – both PUVA and NUVB – are known to clear up PN temporarily due to the antipruritic effect of UV light. However, relapse after treatment is common in PN, which means that either long‐term therapy is necessary or the treatment protocols have to be optimized to minimize side‐effects. Objective The aim of this study was to evaluate the effect that combining bath PUVA and targeted UVB 308 nm excimer radiation has on recalcitrant nodular prurigo. Methods In a prospective trial, 22 patients with PN were treated with either PUVA alone or with a combination of PUVA and excimer UVB. The end point was complete or almost complete remission of PN. Results Adding a 308‐nm excimer UVB to the treatment of the pruritic nodules sped up the healing process; 30% less PUVA radiation was needed. Conclusion The combination of PUVA and excimer UVB in PN appears to be very efficacious. Reducing psoralen UVA doses by 30% offered long‐term benefits in phototherapy of chronic recalcitrant diseases like PN.     

Comparison between 308-nm monochromatic excimer light and narrowband UVB phototherapy (311–313 nm) in the treatment of vitiligo – a multicentre controlled study

BACKGROUND: Vitiligo is an acquired pigmentary disorder characterized by areas of depigmented skin resulting from loss of epidermal melanocytes. Recently, it has been shown that narrowband ultraviolet B (NB-UVB) phototherapy may be more effective than psoralen and ultraviolet A (PUVA) photochemotherapy in treating vitiligo, and that 308-nm monochromatic excimer light (MEL) may present some advantages as compared to NB-UVB for the treatment of vitiligo. AIM The aim of this study was to compare the effectiveness of NB-UVB phototherapy and 308-nm MEL in vitiligo patients. METHODS: The study was done in a randomized, investigator-blinded and half-side comparison design. Twenty-one subjects with symmetrical vitiligo lesions were enrolled in this study. Vitiligo lesions on one body side were treated twice weekly for 6 months with 308-nm MEL, while NB-UVB phototherapy was used to treat lesions on the opposite side. RESULTS: At the end of the study six lesions (37.5%) treated with 308-nm MEL and only one lesion (6%) treated with NB-UVB achieved an excellent repigmentation (score 4) while four lesions (25%) treated with 308-nm MEL and five lesions (31%) treated with NB-UVB showed a good repigmentation (score 3). CONCLUSIONS: It appears that 308-nm MEL is more effective than NB-UVB in treating vitiligo lesions and it induces repigmentation more rapidly.     

Evaluation of a multicentre study of synchronous application of narrowband ultraviolet B phototherapy (TL-01) and bathing in Dead Sea salt solution for psoriasis vulgaris

The synchronous application of narrowband UVB phototherapy with 311 nm lamps (Philips TL-01) and bathing in Dead Sea salt solution was evaluated in a multicentre trial (n = 60) in outpatients suffering from psoriasis vulgaris. The study design consisted of an initial therapy phase of up to 35 treatments (three to five times a week) followed by maintenance therapy with up to 35 further applications (once or twice a week). Evaluation was performed separately for patients in according-to-protocol (ATP) (n = 280) and intention-to-treat (ITT) (n = 692) groups. An overall significant improvement of the Psoriasis Area and Severity Index (PASI) score (P < 0.05) could be shown for both groups during initial therapy with 71.4% improvement for ATP and 61% for ITT patients. The mean PASI for ATP (values for ITT in parentheses) was 17.7 (18.6) at baseline, 9.5 (10.7) after 20 applications and 5.2 (7.4) at the end of initial therapy. On average, ATP patients received 3.9 (3.5) applications per week with a cumulative irradiation dose of 19.5 J cm-2 (16.2 J cm-2). The most frequent side-effect was erythema, observed in 8.7% of the patients. Subjective evaluation of the therapy by the patients (n = 168) was excellent. Seventy-nine per cent of patients preferred the new treatment strategy in comparison with other previous therapies and 88% regarded this therapy as pleasant and comfortable. In conclusion, we could demonstrate a significant effect of therapy in both the ATP and the ITT groups for this new treatment system which imitates, as far as possible, the Dead Sea climatic conditions, with no severe side-effects and a high acceptance by the patients.     

Comorbidities and health‐related quality of life in Spanish patients with moderate to severe psoriasis: A cross‐sectional study (Arizona study)

Psoriasis is a common, chronic inflammatory immunologically mediated disease of the skin, showing a high prevalence of associated comorbidities, and strongly affecting patients' health‐related quality of life (HR‐QOL), with profound impact on the psychological aspect. We aimed to establish the correlation between HR‐QOL and the associated comorbidities in patients with moderate to severe psoriasis in Spain. A cross‐sectional, observational, epidemiological study was conducted at 68 dermatology‐based centers across Spain. From October 2010 to June 2011, all adult patients diagnosed with moderate to severe psoriasis at least 6 months prior to the study visit and receiving or not receiving treatment for psoriasis were eligible for inclusion. A total of 1022 patients were included. The study population showed mean 36‐item short‐form (SF‐36) physical and mental health scores and Dermatological Life Quality Index (DLQI) of 49.7, 46.2 and 5.3, respectively. The multiple linear regression models showed that patients with moderate to severe psoriasis and a diagnosis of psoriatic arthritis (PsA), hypertension, diabetes mellitus, sleep disturbances or obesity were found to have lower SF‐36 health physical scores. Female patients with depression or anxiety disorders had lower SF‐36 health mental scores. Patients diagnosed with moderate to severe psoriatic disease and associated anxiety disorder had greater DLQI scores. Moderate to severe psoriasis has a significant burden on the HR‐QOL of patients. Regardless of sex, patients with several comorbidities such as PsA, hypertension or obesity were found to have worse scores in the physical component of the QOL questionnaire, whilst women were more affected in the mental health component than men.     

Efficacy and safety of ixekizumab treatment in Japanese patients with moderate‐to‐severe plaque psoriasis: Subgroup analysis of a placebo‐controlled,phase 3 study (UNCOVER‐1)

The present study describes a subgroup analysis of 33 Japanese patients participating in UNCOVER‐1, an international, placebo‐controlled, phase 3 study of ixekizumab in patients with moderate‐to‐severe psoriasis. Patients were randomized to a placebo (n = 13) or ixekizumab 80 mg every 4 (IXEQ4W, n = 12) or 2 (IXEQ2W, n = 8) weeks, from week 0–12. At week 12, ixekizumab‐treated patients with a static Physician Global Assessment score 0 or 1 (sPGA [0,1]; n = 16) were re‐randomized to a placebo (n = 6), ixekizumab 80 mg every 12 (IXEQ12W, n = 5) or 4 (IXEQ4W, n = 5) weeks, from week 12–60. At week 12, more ixekizumab‐treated versus placebo‐treated patients achieved sPGA (0,1) (≥66.7% vs 0%), ≥75% improvement in Psoriasis Area and Severity Index (≥75% vs 0%), and sPGA (0) or 100% improvement in Psoriasis Area and Severity Index (both ≥33.3% vs 0%), with improved symptoms and quality of life. At week 60, 100% (IXEQ4W), 40.0% (IXEQ12W) and 16.7% (placebo) had maintained sPGA (0,1). From week 0–12, treatment‐emergent adverse events were 76.9% (placebo), 75.0% (IXEQ4W) and 87.5% (IXEQ2W), and from week 12–60 were 66.7% (placebo) and 100% (IXEQ12W, IXEQ4W). Ixekizumab‐treated patients had no severe treatment‐emergent adverse events, and one serious TEAE (IXEQ4W); infection was the most frequent treatment‐emergent adverse event. In conclusion, ixekizumab for 60 weeks was effective and safe for Japanese patients with moderate‐to‐severe psoriasis, in line with the overall findings from UNCOVER‐1.     

Expression of vascular endothelial growth factor, apoptosis inhibitors (survivin and p16) and CCL27 in alopecia areata before and after diphencyprone treatment: an immunohistochemical study

BACKGROUND: Alopecia areata (AA) is a relatively common inflammatory form of nonscarring hair loss of unknown pathogenesis, but possibly of autoimmune origin. Topical immunotherapy, using a potent contact allergen such as diphencyprone (DPC), is currently considered the most effective mode of treatment. However, the way in which DPC operates on hair follicles in AA still remains to be elucidated. Vascular endothelial growth factor (VEGF), essential for angiogenesis and vascular permeability, may be responsible for maintaining proper vasculature around hair follicles, and several studies provide evidence that apoptosis is a central element in the regulation of hair follicle and vascular regression. The cutaneous lymphocyte-associated antigen (CLA) and the skin-associated chemokine CCL27 highlight an important role for epithelial cells in controlling homeostatic lymphocyte trafficking. OBJECTIVES: To determine the expression pattern of VEGF, factor (F)VIII, survivin, p16, CD4, CD8, CLA and CCL27 in alopecic skin before and after treatment with DPC. Methods Immunohistochemical staining methods were applied to skin biopsy specimens obtained from alopecic areas of 14 patients before and after DPC treatment and from five healthy subjects. Sections were incubated with monoclonal antibodies against VEGF, FVIII, survivin, p16, CCL27, CLA, CD4 and CD8, and their immunohistochemical expression was evaluated by light microscopy. RESULTS: The intensity of VEGF staining in alopecic human hair follicles was significantly lower than in healthy scalp tissue. FVIII immunostaining showed a significantly reduced development of the microvasculature in AA in comparison with healthy scalp tissue. After DPC therapy, cells of alopecic hair follicles showed a significant increase of VEGF immunopositivity, and the number of capillary vessels expressing FVIII was markedly increased in comparison with untreated scalp tissue. The increase in microvessels was associated with strong survivin expression in endothelial cells after treatment. All alopecic specimens showed expression of p16 in the hair follicle outer root sheath (ORS), with a significant increase after therapy. After treatment we observed a significantly decreased number of CD4+ cells and an increase of CD8+ cells (CD4/CD8 ratio 0.85) in alopecic skin compared with untreated scalp tissue (CD4/CD8 ratio 3.45). Most of the T lymphocytes found in inflammatory skin lesions expressed CLA antigen and after therapy we observed a significantly higher CLA positivity in hair follicles (50% or more) in comparison with untreated alopecic scalp tissue. Alopecic patients showed a CCL27 immunopositivity significantly lower than in normal scalp tissue. After DPC therapy the labelling intensity for CCL27 showed a significant increase both in the ORS and in the inner root sheath; similarly, in the basal interfollicular keratinocytes we observed a moderate increase in CCL27 expression. CONCLUSIONS: Topical immunotherapy exerts an important role in angiogenesis, upregulating VEGF in human hair follicle keratinocytes and upregulating survivin to preserve endothelial cell viability. Moreover, it considerably alters the peribulbar CD4/CD8 ratio, restoring a condition close to normal scalp skin. Our study could contribute to explaining some aspects of AA pathogenesis that are still unknown and aid understanding of how DPC could act in this complex disease.