ultraviolet-A Therapy Research Articles

Endotracheal Application of UltravioletA Light in Critically Ill Patients with Severe Acute Respiratory Syndrome Coronavirus2: A First-in-Human Study.

IntroductionOur previous preclinical experiments show that under specific and monitored conditions, ultraviolet A (UVA) exposure reduces certain bacteria, fungi, and viruses including coronavirus-229E without harming mammalian columnar epithelial cells. The goal of this study was to evaluate the safety and effects of narrow-band UVA therapy administered by a novel device via endotracheal tube in critically ill subjects with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.MethodsNewly intubated, mechanically ventilated adults with SARS-CoV-2 infection and an endotracheal tube size of at least 7.50 mm were eligible for inclusion in the study. Subjects were treated with UVA for 20 min daily for 5 days and followed for 30 days.ResultsFive subjects were enrolled (mean age 56.60 years, three male). At baseline, all subjects scored 9/10 on the World Health Organization (WHO) clinical severity scale (10 = death), with predicted mortality ranging from 21% to 95%. Average endotracheal viral load significantly reduced from baseline to day 5 (− 2.41 log; range − 1.16 to − 4.54; Friedman p = 0.002) and day 6 (− 3.20; range − 1.20 to − 6.77; Friedman p < 0.001). There were no treatment-emergent adverse events, with no changes in oxygenation or hemodynamics during the 20-min treatments. One subject died 17 days after enrollment due to intracranial hemorrhagic complications of anticoagulation while receiving extracorporeal membrane oxygenation. The remaining subjects clinically improved and scored 2, 4, 5, and 7 on the WHO scale at day 30. In these subjects, clinical improvement correlated with reduction of viral load (Spearman’s rho = 1, p < 0.001).ConclusionsIn this first-in-human study, endotracheal narrow-band UVA therapy, under specific and monitored settings, appears to be safe and associated with a reduction in respiratory SARS-CoV-2 viral burden over the treatment period. UVA therapy may provide a novel approach in the fight against COVID-19.Clinical Trial NumberNCT04572399.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-01830-7.

SOAP PUVA.

Psoralen plus ultraviolet A (PUVA) photochemotherapy combines the use of psoralen and long-wave ultraviolet A (UVA) radiation. The phototherapeutic effects of PUVA result from photochemical reactions. PUVA therapy can be administered in various methods such as conventional UV chambers, psoralen with sunlight as source of UV light PUVASOL, bath PUVA, bath suit PUVA, soak PUVA, and turban PUVA. The advantage of using topical psoralen is that it avoids the adverse effects associated with the oral PUVA therapy and is being increasingly used in the treatment of psoriasis. However, it is known to cause increased phototoxicity, and in conditions like vitiligo, the spotty repigmentation is not cosmetically acceptable. Psoralen bath plus UVA therapy is known as bath PUVA therapy. Bath PUVA treatment for psoriasis was first reported by Fischer and Alsins in 1976. Bath PUVA is administered by mixing 37.5 mL of 1% 8-methoxypsoralen in 100 Lof water to obtain a concentration of 3.75 mg/L.[1] In bath suit PUVA, bathing suit of flannel material (stitched to suit the patient) is dipped in this solution for 5 min and worn for 15 min with a raincoat over it to prevent evaporation of the solution, and the patient is then immediately exposed to UVA in a whole-body phototherapy chamber. Bath PUVA needs plenty of water. Bath tub is not easily available and bath suit needs special suit, and treatment is cumbersome. We planned to modify the therapy by mixing psoralen with cleansing lotion and coined it as SOAP PUVA. The choice is due to the solubility factor as 8-MOP being insoluble in water. We reported a novel method of delivering 8-MOP uniformly all over the skin within a short time and on subsequent exposure to UV light. Because8-MOP was not soluble in water, we tried to dissolve it in commercially available moisturizing lotion (cetaphil) and synthetic detergent (cetaphil cleansing lotion). As it dissolved well in cleansing lotion, we decided to use it for our study [Figure 1]. As the method was new, we initially tried to standardize the procedure and determine the minimal pigmentation dose (MPD). The project was done in a single healthy subject with no existing dermatological disease requiring phototherapy. We started by using 1:100 dilution of methoxsalen that was prepared by mixing 0.1 mL of methoxsalen with 9.9 mL of cleansing lotion. The mixture was applied over the back [Figure 2]. The paste was left over for 5 min after which it was wiped with water-soaked gauze. The template cloth was worn along with goggles to protect the eyes. The area was exposed to UVA light (0–3J) with 0.5-J increments. The plan was to observe for MPD after 48 h and delayed pigmentation upto 7 days. No erythema and pigmentation was observed upto 7 days. We increased the concentration to 1:80, and the same procedure was repeated with no erythema or pigmentation. The concentration was increased to 1:60 and the same procedure was repeated. Erythema was observed at 2.5 J after 48 h [Figure 3] and pigmentation was observed after 5 days.Figure 1: Psoralen completely soluble in cleansing lotionFigure 2: Psoralen and cleansing lotion mixture applied over the backFigure 3: Erythema observed after 48 h at 2.5 JOral PUVASOL is effective but is time-consuming because the exposure to UV light occurs after 2 h and the intensity of sunlight varies. It also becomes difficult for children and working women. To overcome these issues bath PUVA was introduced, but it requires consumption of a large quantity of water. Pai and Srinivas introduced bathsuit tPUVA [2] to overcome this but the suit had to be worn for 15 min and was practically difficult. The main purpose of this study was to identify the method and use it with exposure to sunlight. The plan was to increase the concentration of psoralen rather increase the exposure time because we wanted to deliver it in a shorter period and the irradiance of sunlight was much lower than the irradiance of UV light in artificial chambers. The limitation was that it was done on a single subject, and the results might have varied. We plan to conduct further studies on a larger scale to determine the ideal dilution and use it as a viable alternative for delivering PUVA therapy. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Phototherapeutic modalities pose no significantly increased risk of oxidative damage to DNA in dark skinned individuals.

8-oxoguanine, a major product of DNA oxidation, is considered a key parameter in measuring the carcinogenic effects of ultraviolet radiation. To assess and compare the carcinogenic potential of different photo (chemo) therapeutic modalities in photoresponsive skin diseases by measuring the levels of 8-oxoguanine in dark-skinned individuals before and after photo (chemo) therapy. A prospective, randomized controlled pilot study was conducted in 63 patients of skin types III-V with photo-responsive dermatoses including vitiligo, psoriasis and mycosis fungoides. Patients were divided into three groups; Group 1 (received narrowband ultraviolet-B), Group 2 (received psoralen plus ultraviolet-A) and Group 3 (received broadband ultraviolet-A). Biopsies were taken before and after phototherapy to measure 8-oxoguanine levels using enzyme-linked immunosorbent assay. Biopsies were also taken from the sun-protected skin in 21 controls subjects who had no dermatological disease. Regardless of the disease, a significantly higher level of 8-oxoguanine was found after treatment when compared to the pre-treatment baseline levels; however, these levels were comparable to those in control subjects. A weakly significant positive correlation was found between cumulative dose and 8-oxoguanine levels following psoralen plus ultraviolet-A therapy. In controls, comparing the 8-oxoguanine levels between skin types III and IV showed significantly lower 8-oxoguanine in skin type IV. Therapeutic doses of ultraviolet radiation are relatively safe in dark skinned patients; however, minimizing the cumulative dose of phototherapeutic modalities (particularly psoralen plus ultraviolet-A) is recommended.

Psoriatic Arthritis Complicating Systemic Sclerosis: Possible Involvement of M2 Macrophages.

Dear Editor: Psoriatic arthritis (PsA) is a seronegative inflammatory arthritis that occurs in the presence of psoriasis. The synovial macrophages are a major source of proinflammatory cytokines1. The subset of macrophages that expresses alternatively activated macrophages (M2 macrophages) is usually greater in number in PsA synovitis than in rheumatoid arthritis synovitis2. Systemic sclerosis (SSc) is a rheumatological disorder characterized by excessive fibrosis and microvascular damage of the skin and various internal organs. The presence of macrophage infiltrates and increased numbers of M2 macrophages in fibrotic areas have been reported3. A 44-year-old Japanese man developed scaly erythema that had been present on the trunk and lower and upper extremities for 40 years. A primary care doctor had diagnosed his condition as psoriasis. His previous treatments included topical corticosteroid therapy, topical psoralen ultraviolet-A therapy, or oral cyclosporin. Sacroiliitis was also associated with the skin symptoms. For the previous 4 years, the scaly erythema had gradually improved but was then complicated by sclerodactylia. On examination, a high anti-nuclear antibody (ANA) titer with homogeneous, speckled, and nucleolar patterns (×640) was present. Detailed analysis of the ANA revealed that there was a significant increase in anti-topoisomerase I antibody (152 U/ml). Rheumatoid factor was negative. From these results, the presumptive diagnosis was SSc complicated by PsA, and the patient was admitted to our hospital. Psoriatic plaque was present on the elbows of the patient (Fig. 1A). The modified Rodnan total skin thickness score value of 22 was used to grade the degree of skin sclerosis (Fig. 1B). The levels of T helper 2 cytokines, such as interleukin (IL)-4 (17.0 pg/ml) and transforming growth factor (TGF)-β1 (15.1 ng/ml), were elevated. The serum Krebs von den Lungen-6 (1,182 U/ml) and surfactant protein D (226 ng/ml) levels were elevated, and high-resolution computed tomography revealed the presence of a bilateral consolidation of both lower lobes with peripheral ground glass opacity. Skin biopsies from the elbow and the forearm revealed the presence of markedly elongated rete ridges with parakeratosis (Fig. 1C), and sclerotic change that ascended from the lower dermis (Fig. 1D). We also performed immunostaining for CD68 (Fig. 1E, F) and CD163 (Fig. 1G, H) in lesional skin biopsy samples. Subequal infiltrated dermal cells expressed CD68, which suggested that macrophages infiltrated both types of samples of lesional skin. Furthermore, the numbers of CD163-positive cells were increased in lesional skin from SSc. This result suggests that M2 macrophages were increased in lesional skin from SSc compared with lesional skin from PsA (Fig. 1E~H). Fig. 1 Clinical and histopathological manifestations in the patient. (A) Psoriatic skin lesion affecting the elbow. (B) Widespread skin thickening, progressing from the fingers to the trunk. (C) The skin biopsy specimen from the elbow has characteristics consistent ... Polarized macrophages have been broadly classified into two groups: M1 and M2 macrophages. Tissue macrophages can exist in different activation states. They can be proinflammatory macrophages (M1; activated by interferon-γ or lipopolysaccharide) or anti-inflammatory macrophages (M2; activated by TGF-β or IL-4)4. They participate in tissue remodeling, immune modulation, parasite clearance, and tumor progression5. In this patient, M2 macrophages may be one of the key regulating cell types involved in the clinical manifestations. However, further investigations are needed for elucidating the involvement of M2 macrophages in skin disorders.

Very Severe Psoriasis Is Associated with Increased Noncardiovascular Mortality but Not with Increased Cardiovascular Risk

It has been hypothesized that severe psoriasis is an independent risk factor for cardiovascular disease (CVD). We prospectively studied patients with severe psoriasis treated with psoralens and ultraviolet-A therapy (PUVA) who enrolled in a cohort study in 1975-1976. From 1977 to 2005, 617 of the 1,376 patients (45%) died. Compared with the general population, cohort death rates were significantly higher than expected (standard mortality ratio (SMR) = 1.1, 95% confidence interval (CI) = 1.02-1.20). The number of deaths due to CVD (SMR = 1.02, 95% CI = 0.9-1.6) was nearly identical to the expected number. Deaths due to liver disease were significantly elevated (SMR = 4.04, 95% CI = 2.76-5.70). Patients with exceptionally severe psoriasis at entry (>42% body surface area (BSA)) had a significantly increased risk of death compared with less severely affected cohort members (all-cause hazard ratio (HR) = 1.42, 95% CI = 1.18-1.69) as well as for deaths because of causes other than cancer or CVD (multivariate HR 1.56, 95% CI = 1.14-2.13). Only patients with exceptionally severe psoriasis had an increased mortality risk compared with both the general population and other cohort members with less extensive but still severe psoriasis. These increases were not significant for CVD. Our data do not support the hypothesis that severe psoriasis is an independent risk factor for CVD. However, exceptionally severe psoriasis is associated with increased all-cause mortality.

2-Chlorodeoxyadenosine treatment for cutaneous T-cell lymphoma.

The primary cutaneous lymphomas are often indolent but difficult to treat. In the early stages psoralen and ultraviolet-A therapy is the standard treatment whereas at the tumor stage chemotherapy (e.g. pegylated doxorubicin) is often used for debulking. The purine analog 2-chlorodeoxyadenosine (2CdA) acts in non-Hodgkin’s lymphoma and has been used in our center for the treatment of advanced primary cutaneous T-cell lyphomas (CTCL). Here, we report on the efficacy and side effects of 2CdA in six patients with CTCL. One patient died owing to myelosuppression. Partial responses were seen in four cases but full remission was observed in only one case. We concluded that 2CdA has a limited usefulness in the management of advanced CTCL.

Current and emerging therapy for the management of vitiligo

Vitiligo is an acquired cutaneous disorder of pigmentation, with an incidence of 0.5% to 2% worldwide. There are three major hypotheses for the pathogenesis of vitiligo that are not exclusive of each other: biochemical/cytotoxic, neural and autoimmune. Recent data provide strong evidence supporting an autoimmune pathogenesis of vitiligo. As vitiligo can have a major effect on quality of life, treatment can be considered and should preferably begin early when the disease is active. Current treatment modalities are directed towards stopping progression of the disease and achieving repigmentation. Therapies include corticosteroids, topical immunomodulators, photo(chemo)therapy, surgery, combination therapies and depigmentation of normally pigmented skin. Topical class 3 corticosteroids can be used for localized vitiligo. The use of topical immunomodulators (TIMs) in vitiligo seems to be equally effective as topical steroids, especially when used in the face and neck region. In photo(chemo)therapy, narrowband ultraviolet-B therapy (NB-UVB) seems to be superior to psoralen ultraviolet-A therapy (PUVA) and broadband UVB. In surgical techniques, split-thickness grafting and epidermal blister grafting were shown to be effective methods, although the non-cultured epidermal suspension technique has many advantages and seems to be a promising development. Depigmentation therapy can be considered if vitiligo affects more than 60% to 80% of the body. Complementary therapies such as Polypodium leucotomos show promising results in combination with UVB therapy. No causative treatment for vitiligo is currently available. More randomized controlled trials on the treatment of vitiligo are necessary.

Protective Effect of Epigallocatechin Gallate and Esculetin on Oxidative DNA Damage Induced by Psoralen Plus Ultraviolet-A Therapy

We examined antioxidants exhibiting no effects on DNA cross-linking, which is the basis of psoralen and ultraviolet-A therapy for skin diseases, and suppressing oxidative DNA damage incidental to the therapy. Epigallocatechin gallate and esculetin effectively suppressed oxidative DNA damage with little effect on the formation of DNA cross-linking. These antioxidants might be useful in suppressing the adverse reaction induced by this therapy.

UVA solarium versus UVB phototherapy of atopic dermatitis: a paired-comparison study

In a paired-comparison study, 21 patients suffering from atopic dermatitis were treated with fluorescent tubes radiating mainly ultraviolet A (UVA) on one half of the body and with tubes radiating mainly UVB on the other. Treatment was given three times a week for up to 8 weeks. Eight variables reflecting disease status were recorded and the sum of these comprised the total score. The total score and the overall evaluation score were better with UVA therapy (P less than 0.02 and P = 0.01, respectively). No statistically significant difference for the pruritus score was found. The reduction in extent of dermatitis, seen with both therapies, was more pronounced with UVA (P less than 0.05). Differences in the healing score were not statistically significant. Treatment with UVA resulted in healing or considerable improvement in 15 patients and 13 patients showed improvement when treated with UVB. A better result was found with UVA in 10 subjects and with UVB in two subjects. Equal results occurred with both UVA and UVB in nine of the patients although most preferred UVA treatment.

Photo-onycholysis Secondary to Psoralen Use

<h3>To the Editor.—</h3> I was interested in the report of Rau and his colleagues, in the MarchArchives, on photo-onycholysis occurring from sun exposure during psoralen treatment (114:448, 1978). They state that there are no reports of this in the medical literature. However, the association was described in two cases by Zala etal.¹These patients were treated with methoxsalen and sun exposure for vitiligo. My colleague, Vella Briffa, and I reported a case of a patient undergoing psoralen -ultraviolet-A therapy for mycosis fungoides.²Rau and his colleagues list many other causes of photo-onycholysis, one they do not mention is porphyria. Recently, a woman with porphyria variegata came to me for treatment of photo-onycholysis of all her fingernails. Common to all the conditions in which photo-onycholysis has been described is the ability of long-wave ultraviolet light to penetrate the nail plate, whereas the shorter wavelength ultraviolet light does