Ultraviolet Phototherapy Research Articles

The case for ultraviolet light therapy in nephrogenic fibrosing dermopathy--report of two cases and review of the literature

Nephrogenic fibrosing dermopathy (NFD) is an emerging skin disease in patients with renal failure [1]. It is characterized by skin induration that affects the upper and lower extremities, and may progress to involve other areas of the body. Recent reports suggest that NFD may not be limited to the skin and could affect internal organs [2–5]. In all these patients, NFD appeared to be progressive and to affect vital organs including the heart and lungs. In one report, the patient apparently died from complications related to severe skin fibrosis involving the trunk and precluding dialysis catheter replacement [5]. Although there are no consistently effective therapies reported in the literature, ultraviolet light therapy in various forms, including photodynamic therapy and photopheresis has been recently reported to improve the disease [6–10]. Systemic lupus erythematosus was reported only recently to be a cause of renal failure in patients with NFD, and herein we extend this observation [11]. Ultraviolet light is known to exacerbate the cutaneous and perhaps even the systemic manifestations of lupus, which may deter clinicians from treating NFD with this form of therapy in lupus patients. Conversely, ultraviolet light therapy has been reported to improve lupus symptoms [12]. We report two patients with end-stage renal disease (ESRD) due to systemic lupus erythematosus who developed NFD and in whom ultraviolet light therapy, namely psoralen plus ultraviolet light A (PUVA) and extracorporeal photopheresis, resulted in significant improvement of NFD without exacerbation of their lupus symptoms. We then review the recent literature on NFD and summarize the published cases treated with the most successful therapies.

Management of psoriatic arthritis: The therapeutic interface between rheumatology and dermatology

Psoriatic arthritis is an inflammatory arthritis, which occurs in up to 30% of individuals with psoriasis. Dermatologists and other physicians treating psoriasis are in an ideal position to screen for the condition, and with rheumatologists, strategize optimal therapy. Mild skin and joint manifestations may be treated effectively with topical agents, ultraviolet light therapy, and nonsteroidal anti-inflammatory drugs. More severe manifestations of the disease, including progressive peripheral joint damage, spine disease, enthesitis, dactylitis, and severe skin changes, require systemic therapy. Traditional systemic agents include methotrexate, sulfasalazine, and cyclosporine. When these agents are not adequate or not tolerated, new biologic agents, particularly anti-tumor necrosis factor (TNF) compounds, have shown significant and enduring benefit in all disease domains, improvement in quality of life and function, and inhibition of progressive joint damage.

Ultraviolet A1-induced downregulation of human β -defensins and interleukin-6 and interleukin-8 correlates with clinical improvement in localized scleroderma

In previous studies, distinct immunological abnormalities have been reported in localized scleroderma (LS). Several pro-inflammatory cytokines have been demonstrated at increased levels in sera of patients with LS in parallel with disease activity. Human beta-defensins (hBDs) are peptides with antimicrobial activity, but have been also shown to be implicated in tissue injury, scarring and wound healing. hBD expression in LS, a condition resembling pathological scarring due to excessive stimulation of matrix synthesis and fibroblast activation, has so far not been investigated. Ultraviolet (UV) A1 phototherapy, the most recent advance in the treatment of LS, targets T-cell dermal inflammatory infiltrates via induction of various cytokines and soluble factors besides well-known effects on collagen metabolism. We sought to investigate the effects of UVA1 on the expression and modulation of hBDs and several pro-inflammatory cytokines in LS. UVA1 phototherapy was performed five times weekly for 8 weeks resulting in a total of 40 treatment sessions (single dose 20 J cm2, cumulative dose 800 J cm2). hBD-1, hBD-2 and hBD-3 mRNA as well as tumour necrosis factor-alpha, transforming growth factor-beta, interleukin (IL) -2, IL-4, IL-6 and IL-8 mRNA expression were determined by quantitative real-time reverse transcription-polymerase chain reaction in lesional and unaffected skin of patients with LS. Skin status markedly improved in all 14 patients, resulting in a significant reduction of the clinical score from baseline to the end of treatment. hBD-1, hBD-2 and hBD-3 mRNA levels were higher in lesional skin compared with unaffected skin and skin from healthy volunteers. Following UVA1 phototherapy, hBD-1 mRNA decreased in lesional, but not in unaffected skin. hBD-3 mRNA levels significantly decreased after UVA1 in lesional skin, whereas an increase of hBD-3 was observed in unaffected skin. IL-6 and IL-8 mRNA levels were significantly elevated in lesional skin and significantly decreased after UVA1 irradiation, whereas mRNA for both cytokines remained unchanged in irradiated unaffected skin. The decrease of hBD-1, hBD-3, IL-6 and IL-8 mRNA paralleled the extent of disease and response to UVA1 phototherapy. hBDs and IL-6 and IL-8, cytokines with pivotal importance in sclerotic skin diseases, are downregulated by UVA1 in the lesional skin of patients with LS. Their pathogenetic relevance with respect to clinical improvement needs further investigation.

Environmental risk analysis of ultraviolet phototherapy centres in Ireland

Ultraviolet (UV) radiation is commonly used in the treatment of dermatological conditions such as psoriasis. It is known that high levels of exposure to UV radiation (UVR) will increase the risk of adverse biological effects. Exposure limit values for UVR have been developed by the International Commission on Non-Ionising Radiation Protection (ICNIRP) and occupational exposure to phototherapy staff should be kept within these limits. The use of environmental controls such as warning signs, good ventilation and UV-opaque curtains will significantly reduce the risks to staff, patients and members of the public. The aim of the study is to identify hazards in phototherapy centres and present recommendations for reducing risks. An environmental risk assessment has been carried out at eleven phototherapy centres in the Republic of Ireland. The study assessed a number of areas such as patient safety, staff safety, room design and UV leakage measurements. The majority of clinics are well designed and there is consistent use of protective equipment. The results show that on the whole there is a satisfactory level of risk management in phototherapy centres. Recommendations on maintaining good safety standards are presented.

Modulation of ultraviolet (UV) transmission by emollients: relevance to narrowband UVB phototherapy and psoralen plus UVA photochemotherapy

Patients with psoriasis undergoing or about to undergo ultraviolet (UV) phototherapy and photochemotherapy often have thick scale on their plaques which can prevent the penetration of UV radiation. Emollients are used to moisturize the skin and to prevent or reduce some of the milder side-effects ('dryness', itching) sometimes experienced during UV therapy. However, emollients can alter the UV transmission of skin and thus may alter the clinical effects of phototherapy and photochemotherapy. We tested 30 of the topical emollients in the British National Formulary (BNF) using a standard in vitro technique used to test sunscreens. We also surveyed U.K. phototherapy units to establish routine practice for emollient use in phototherapy and photochemotherapy. We used a standard in vitro technique to measure the monochromatic protection factors (MPFs) of 30 non-bath emollients from the BNF. An application rate of 2 mg cm-2 was used. For the assessment of effects during narrowband UVB (TL-01) phototherapy, the mean of the protection factors at 310 and 315 nm was calculated; for psoralen plus UVA photochemotherapy the mean UVA protection factor was used. A questionnaire survey was used to assess routine practice concerning emollient use prior to phototherapies in phototherapy units throughout the U.K. In the UVA range, 17 of the 30 emollients gave protection factors of 1.2 or above. In the UVB range, 23 of 30 had an MPF of 1.2 or above. Yellow soft paraffin had the highest protection factor in the UVB range. Of 78 centres surveyed, 57 returned completed questionnaires (73%). Seventeen of 57 (30%) centres routinely used emollients immediately prior to administering phototherapy treatments. The remaining 40 of 57 (70%) did not. Forty-five (79%) responding centres recommended the use of emollients after phototherapy. This study has revealed considerable variability in the practice of emollient use before phototherapy treatments. Although the majority of centres included in this study did not routinely use emollients, almost one third did. Our in vitro measurement of 30 emollients revealed marked variation in UV transmission, with many emollients blocking sufficient UV to affect the response to therapy.

Ultraviolet phototherapy: review of options for cabin dosimetry and operation

Ultraviolet (UV) treatment dose is determined by the length of time that a patient spends in a phototherapy cabin. The output from UV fluorescent lamps declines with use and a method is needed to compensate for the change in irradiance and to identify and replace any lamps that fail. The decline in lamp output with age and the magnitudes of localized areas of low irradiance resulting from failed lamps have been measured and results used to assess different approaches to lamp replacement. In current cabin models, single failed lamps give cold spots with 7%–12% lower irradiances and replacements with new lamps give 3%–6% higher localized irradiances. However, cold spots with 30% lower irradiances may result from lamp failures in some older dual UVA/TL01 lamp cabins. The use of internal cabin detectors that can be employed to compensate for changes in irradiance level is beneficial. Cabins having pairs of internal detectors provide a reasonable reflection of the changes in irradiance that occur and the position of the patient in the cabin should not affect the treatment dose by more than ±6%. There should be a robust system to identify and replace failed lamps to minimize the risk of erythema.

Narrow-band UVB induces apoptosis in human keratinocytes

Narrow-band ultraviolet (NB-UVB) phototherapy emits mostly 311/312 nm light and is commonly used in the treatment of inflammatory skin disorders. As a source of UVB irradiation, NB-UVB causes apoptosis in T lymphocytes but its effects on keratinocytes are unknown. Herein, we have investigated the ability of NB-UVB to induce apoptosis in keratinocytes. Two types of human keratinocytes, primary and immortalized, were exposed to NB-UVB and broad-band UVB (BB-UVB; 315–280 nm) and tested for apoptosis. Both UVB light sources induced apoptosis in keratinocytes as determined by the presence of DNA ladders, although NB-UVB required approximately ten fold higher doses; NB-UVB (1000 mJ/cm 2) and BB-UVB (125 mJ/cm 2). By comparison, lower doses of NB-UVB (750 mJ/cm 2) induced apoptosis in T lymphocytes, suggesting cell type specificity for NB-UVB induced apoptosis. Approximately, 50% or more of the cells underwent apoptosis when exposed to NB-UVB or BB-UVB as revealed by TUNEL assay. Electron micrographs showed that NB-UVB irradiated keratinocytes contained marked chromatin condensation, extensive cytoplasmic vacuolization and fragmentation of the nuclear envelope. Furthermore, Western blot analysis confirmed the presence of activated products of caspase 3 in keratinocytes that received apoptotic doses of NB-UVB. This study defines conditions by which NB-UVB irradiation causes apoptosis in keratinocytes.

Ultraviolet phototherapy for pruritus

Ultraviolet-based therapy has been used to treat various pruritic conditions including pruritus in chronic renal failure, atopic dermatitis, HIV, aquagenic pruritus and urticaria, solar, chronic, and idiopathic urticaria, urticaria pigmentosa, polycythemia vera, pruritic folliculitis of pregnancy, breast carcinoma skin infiltration, Hodgkin's lymphoma, chronic liver disease, and acquired perforating dermatosis, among others. Various mechanisms of action for phototherapy have been posited. Treatment limitations, side effects, and common dosing protocols are reviewed.

Ultraviolet-A1 phototherapy modulates Th1/Th2 and Tc1/Tc2 balance in patients with systemic lupus erythematosus

Ultraviolet-A1 (UVA1) phototherapy is effective for a variety of dermatological diseases. We examined the effectiveness and reliability of low-dose UVA1 phototherapy (60 kJ/m2/treatment) in patients suffering from systemic lupus erythematosus (SLE). We studied the changes in immunological parameters. The patients received a 9-week course of phototherapy according to the following regimen: five times a week during the first 3 weeks, three times a week during the second 3 weeks and twice during the last 3 weeks. Among other things, we analysed the proportions of T helper 1 (Th1), Th2, T cytotoxic (Tc1) and Tc2 cell populations in the peripheral blood of patients by flow cytometric detection of intracytoplasmic interferon gamma (IFN-gamma) and interleukin 4 (IL-4). Our study showed the improvement of clinical symptoms determined by the subjective clinical disease activity scoring and the SLE Disease Activity Index (SLEDAI). By the end of UVA1 phototherapy, the mean value of SLEDAI had decreased from 7.2+/-5.6 to 0.9+/-1.8, which was significant (P = 0.005). Immunological investigations detected a decrease in the frequency of IFN-gamma-producing Th1 and Tc1 cells and a decrease in the Th1/Th2 and Tc1/Tc2 ratios after UVA1 therapy. According to the literature, IFN-gamma has a pathogenic role in the development of SLE. We observed a decreased proportion of IFN-gamma-secreting cells, which we think is presumably one of the beneficial effects of UVA1 therapy. On the basis of our study, UVA1 phototherapy does seem to be an effective adjuvant in the treatment of SLE patients.

Ultraviolet‐free phototherapy

Ultraviolet (UV) radiation phototherapy has been used for decades in the management of common skin diseases. On the other hand, UV radiation is a complete carcinogen and as a consequence, UV phototherapy is usually not used for the long-term management of children and young adults and in combination with topical or systemic immunosuppressants. The therapeutic effectiveness of a new UV-free irradiation device in the treatment of patients with atopic hand and/or foot eczema was studied. In a single-blinded trial 10 patients with atopic hand and/or foot eczema were treated with a sham irradiation device and with the new developed UV-free irradiation device DermoDyne during the following 4 weeks. All irradiation's lasted 30 min per treatment three times weekly. UV-free irradiation was found to induce a significant clinical improvement of atopic hand and foot eczema (P = 0.0001) in marked contrast to the sham-irradiation (P = 0.39). Our studies demonstrate that visible light can be successfully used for the treatment of patients with atopic eczema.

Alefacept for the treatment of psoriasis: A review of the current literature and practical suggestions for everyday clinical use

Alefacept is the first biologic therapy approved by the United States Food and Drug Administration for the management of patients with moderate-to-severe chronic plaque psoriasis. Alefacept is a fully human fusion protein with a dual mechanism of action inhibiting T-cell activation as well as selectively reducing memory T cells. More than 2000 psoriasis patients have been treated with alefacept in clinical trials. These studies reveal an excellent clinical response, with 33% of patients achieving a Psoriasis Area Severity Index (PASI) score of 75 and 57% of patients achieving a PASI 50 after one course of alefacept. Patients achieving both PASI 75 and PASI 50 have significant improvements in their quality of life. The best responders can have long remissions, and there is a tendency toward continued improvement with subsequent courses of alefacept. The safety profile over the short and intermediate term is excellent. Preliminary data regarding alternate dosing regimens, transitioning patients from conventional systemics to alefacept, and combining alefacept with ultraviolet light therapy will be highlighted. We also will discuss our practical approach to patient selection, CD4 monitoring, management of infections while on alefacept, as well as decisions regarding retreatment and combination therapy.

Medium-dose ultraviolet A1 phototherapy in transient acantholytic dermatosis (Grover's disease)

Medium-dose ultraviolet A1 phototherapy in transient acantholytic dermatosis (Grover's disease)

Two cases of generalized lichen nitidus treated successfully with narrow‐band UV‐B phototherapy

Narrow-band ultraviolet (UV) phototherapy has not been used in the treatment of lichen nitidus. To report two cases of generalized lichen nitidus successfully treated with narrow-band UV-B phototherapy. A 7-year-old girl presented with a persisting, asymptomatic, papular eruption refractory to topical steroid for 3 months. Another 10-year-old boy presented with an asymptomatic papular eruption present for 6 months. The histopathologies of both lesions were consistent with lichen nitidus. The lesions were treated with narrow-band UV-B phototherapy. The lesions of the patients were almost completely cleared after the 30th and the 17th irradiation, respectively. Narrow-band UV-B may be an effective alternative therapy for the treatment of generalized lichen nitidus unresponsive to common therapies.

IgE-Dependent Activation of T cells by Allergen in Atopic Dermatitis: Pathophysiologic Relevance

The importance of interactions between allergen and IgE in allergen-mediated activation of T lymphocytes from patients with atopic dermatitis (AD) is unclear. A role for this interaction is implied by past evidence for IgE-facilitated presentation of allergen to T cells, but this phenomenon has only been demonstrated in specific in vitro systems biased to maximize the effect. It is therefore not known whether the process is relevant in patients. We now show that the responses to allergen of unmodified peripheral blood mononuclear cells (PBMC) from individual AD patients are significantly greater in the presence of fresh, unheated, IgE-containing autologous serum than the same serum heated under IgE-denaturing conditions or specifically depleted of IgE by immunoprecipitation. In six independent experiments, 59%-67% of the maximal in vitro PBMC response to allergen was found to be dependent upon the presence of IgE in autologous serum used at 5% final concentration. These data provide the first evidence that sufficient amounts of allergen-specific IgE and allergen-reactive T cells occur concomitantly in the blood of individual AD patients to allow IgE-enhanced T cell responses to allergen. We conclude that IgE-enhanced T cell responses are pathophysiologically relevant and a therapeutic target in AD.

Laser and novel light source treatments for psoriasis.

There are many treatment modalities for psoriasis including topical therapy, ultraviolet light therapy, systemic agents, and more recently the advent of the biologic agents. In addition, selective treatment using lasers and light sources that target the individual psoriatic plaques have also been employed. This article will highlight and review the employment of laser-assisted devices in the treatment of plaque psoriasis.

Treating Vitiligo with Melanocyte Cultures

Many patients with vitiligo fail to repigment after ultraviolet light therapy. Surgical alternatives include skin grafts (split or punch) and cell

Spatial distribution of the light emitted by an excimer lamp used for ultraviolet-B photo-therapy: Experiment and modeling

The availability of excimer lamps, which emit ultraviolet (UV) noncoherent but narrow-bandwidth radiation, allowed a drastic reduction of the costs of the UV photo-therapy that has so far been accomplished by using excimer lasers. The main goal of this work is the measurement of the spatial distribution of the radiation intensity emitted by a commercial excimer lamp, to check the uniformity of the dose delivered to the target when changing either the distance from the lamp or the surface to be irradiated. The results show that a good uniformity of the delivered dose is achieved within a limited area and that when changing by only 1 cm the distance between the lamp and the target, the dose delivered to the target noticeably changes its value. The experimental data are in good agreement with the analytical results achieved by approximating the lamp by a uniform two-dimensional source.

A 12-week open-label followed by 4-week double-blind study to determine the safety and efficacy of an extended course of alefacept (LFA-3/igg1 fusion protein) in subjects with chronic plaque psoriasis

Psoriasis is a common dermatologic disorder both in Europe and the United States, affecting approximately 2% of the population. Over one million of these patients require ultraviolet (UV) light or systemic therapies, all of which are associated with substantial risks. Activation of T lymphocytes has been implicated as part of the pathologic process in psoriasis. Cell surface expression levels of both CD2 and LFA-3 have a regulatory role in activating and inducing proliferation of T lymphocytes. Alefacept, a fusion protein consisting of the Fc portion of human IgG1 linked to LFA-3, has been recently approved by the United States Food and Drug Administration for the treatment of psoriasis. Previous studies with Alefacept have provided experience with the efficacy, tolerability, and immunogenicity of single and multiple 12-week courses of therapy. To date, studies, as well as the FDA-approved labeling for weekly intramuscular or intravenous injection, have been confined to treatment courses of 12 weeks. The purpose of this present study is to determine the safety and efficacy of an extended course of alefacept when administered to subjects with chronic plaque psoriasis.

Vitiligo Treated with Autologous Cell Suspension

Patients with segmental or focal vitiligo are good candidates for surgical intervention, as their lesions are limited in size and they often have an unsatisfactory response to ultraviolet light therapy. In this retrospective study from India, 49 patients with segmental vitiligo and 15 patients with focal vitiligo underwent autologous, noncultured melanocyte-keratinocyte cell-suspension transplantation of some vitiliginous patches. …

A study of the correction factor for ultraviolet phototherapy dose measurements made by the indirect method.

Optimization of ultraviolet (UV) phototherapy for treatment of psoriasis and other skin conditions requires accurate dosimetry. One factor involved in whole body treatments is the correction that needs to be applied to radiometer measurements of irradiance made remotely without a person in the phototherapy cabin. To evaluate the correction factor for cabins of different design and to consider whether different factors should be used for different phototherapy cabins and radiometers. An automated UV dosimetry system capable of recording irradiances at positions around the circumference of a circle equating to a human trunk has been developed. The system has been combined with a phantom to derive values for the ratio between irradiance measurements made by the direct method with a person in a cabin, and indirect measurements recorded remotely. In addition, values for the ratio in UVA cabins have been derived from comparisons between measurements made directly by persons in a cabin and indirect measurements. Variations in direct to indirect ratio (DIR) with cabin type were less than between individual sets of measurements. The mean DIR obtained for cabins with TL01 lamps was 0.85 +/- 0.02, while that for UVA cabins was 0.80 +/- 0.05. The DIR for dual lamp (TL01/UVA) cabins, when TL01 lamps were illuminated, was higher (0.92). The DIR should be applied to any measurements made using radiometers without a person or equivalent phantom in a cabin. It is proposed that standard values are appropriate for groups of cabins with a single type of lamp and similar reflectors.