Phototherapy for atopic eczema.

BACKGROUND: Atopic eczema (AE), also known as atopic dermatitis, is a chronic inflammatory skin condition that causes significant burden. Phototherapy is sometimes used to treat AE when topical treatments, such as corticosteroids, are insufficient or poorly tolerated. OBJECTIVES: To assess the effects of phototherapy for treating AE. SEARCH METHODS: We searched the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and ClinicalTrials.gov to January 2021. SELECTION CRITERIA: We included randomised controlled trials in adults or children with any subtype or severity of clinically diagnosed AE. Eligible comparisons were any type of phototherapy versus other forms of phototherapy or any other treatment, including placebo or no treatment. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. For key findings, we used RoB 2.0 to assess bias, and GRADE to assess certainty of the evidence. Primary outcomes were physician-assessed signs and patient-reported symptoms. Secondary outcomes were Investigator Global Assessment (IGA), health-related quality of life (HRQoL), safety (measured as withdrawals due to adverse events), and long-term control. MAIN RESULTS: We included 32 trials with 1219 randomised participants, aged 5 to 83 years (mean: 28 years), with an equal number of males and females. Participants were recruited mainly from secondary care dermatology clinics, and study duration was, on average, 13 weeks (range: 10 days to one year). We assessed risk of bias for all key outcomes as having some concerns or high risk, due to missing data, inappropriate analysis, or insufficient information to assess selective reporting. Assessed interventions included: narrowband ultraviolet B (NB-UVB; 13 trials), ultraviolet A1 (UVA1; 6 trials), broadband ultraviolet B (BB-UVB; 5 trials), ultraviolet AB (UVAB; 2 trials), psoralen plus ultraviolet A (PUVA; 2 trials), ultraviolet A (UVA; 1 trial), unspecified ultraviolet B (UVB; 1 trial), full spectrum light (1 trial), Saalmann selective ultraviolet phototherapy (SUP) cabin (1 trial), saltwater bath plus UVB (balneophototherapy; 1 trial), and excimer laser (1 trial). Comparators included placebo, no treatment, another phototherapy, topical treatment, or alternative doses of the same treatment. Results for key comparisons are summarised (for scales, lower scores are better): NB-UVB versus placebo/no treatment There may be a larger reduction in physician-assessed signs with NB-UVB compared to placebo after 12 weeks of treatment (mean difference (MD) -9.4, 95% confidence interval (CI) -3.62 to -15.18; 1 trial, 41 participants; scale: 0 to 90). Two trials reported little difference between NB-UVB and no treatment (37 participants, four to six weeks of treatment); another reported improved signs with NB-UVB versus no treatment (11 participants, nine weeks of treatment). NB-UVB may increase the number of people reporting reduced itch after 12 weeks of treatment compared to placebo (risk ratio (RR) 1.72, 95% CI 1.10 to 2.69; 1 trial, 40 participants). Another trial reported very little difference in itch severity with NB-UVB (25 participants, four weeks of treatment). The number of participants with moderate to greater global improvement may be higher with NB-UVB than placebo after 12 weeks of treatment (RR 2.81, 95% CI 1.10 to 7.17; 1 trial, 41 participants). NB-UVB may not affect rates of withdrawal due to adverse events. No withdrawals were reported in one trial of NB-UVB versus placebo (18 participants, nine weeks of treatment). In two trials of NB-UVB versus no treatment, each reported one withdrawal per group (71 participants, 8 to 12 weeks of treatment). We judged that all reported outcomes were supported with low-certainty evidence, due to risk of bias and imprecision. No trials reported HRQoL. NB-UVB versus UVA1 We judged the evidence for NB-UVB compared to UVA1 to be very low certainty for all outcomes, due to risk of bias and imprecision. There was no evidence of a difference in physician-assessed signs after six weeks (MD -2.00, 95% CI -8.41 to 4.41; 1 trial, 46 participants; scale: 0 to 108), or patient-reported itch after six weeks (MD 0.3, 95% CI -1.07 to 1.67; 1 trial, 46 participants; scale: 0 to 10). Two split-body trials (20 participants, 40 sides) also measured these outcomes, using different scales at seven to eight weeks; they reported lower scores with NB-UVB. One trial reported HRQoL at six weeks (MD 2.9, 95% CI -9.57 to 15.37; 1 trial, 46 participants; scale: 30 to 150). One split-body trial reported no withdrawals due to adverse events over 12 weeks (13 participants). No trials reported IGA. NB-UVB versus PUVA We judged the evidence for NB-UVB compared to PUVA (8-methoxypsoralen in bath plus UVA) to be very low certainty for all reported outcomes, due to risk of bias and imprecision. There was no evidence of a difference in physician-assessed signs after six weeks (64.1% reduction with NB-UVB versus 65.7% reduction with PUVA; 1 trial, 10 participants, 20 sides). There was no evidence of a difference in marked improvement or complete remission after six weeks (odds ratio (OR) 1.00, 95% CI 0.13 to 7.89; 1 trial, 9/10 participants with both treatments). One split-body trial reported no withdrawals due to adverse events in 10 participants over six weeks. The trials did not report patient-reported symptoms or HRQoL. UVA1 versus PUVA There was very low-certainty evidence, due to serious risk of bias and imprecision, that PUVA (oral 5-methoxypsoralen plus UVA) reduced physician-assessed signs more than UVA1 after three weeks (MD 11.3, 95% CI -0.21 to 22.81; 1 trial, 40 participants; scale: 0 to 103). The trial did not report patient-reported symptoms, IGA, HRQoL, or withdrawals due to adverse events. There were no eligible trials for the key comparisons of UVA1 or PUVA compared with no treatment. Adverse events Reported adverse events included low rates of phototoxic reaction, severe irritation, UV burn, bacterial superinfection, disease exacerbation, and eczema herpeticum. AUTHORS' CONCLUSIONS: Compared to placebo or no treatment, NB-UVB may improve physician-rated signs, patient-reported symptoms, and IGA after 12 weeks, without a difference in withdrawal due to adverse events. Evidence for UVA1 compared to NB-UVB or PUVA, and NB-UVB compared to PUVA was very low certainty. More information is needed on the safety and effectiveness of all aspects of phototherapy for treating AE.

Pellagra a review exploring causes and mechanisms, including isoniazid-induced pellagra.

Pellagra is a clinical syndrome caused by a deficiency of niacin (nicotinic acid) and/or its precursor tryptophan. The cardinal manifestations are 4 D's: dermatitis, diarrhoea, dementia and in worst case death. Increased use of isoniazid prophylaxis along with antiretroviral therapy in countries where latent tuberculosis is common has been associated with increased presentations with pellagra.

Research Techniques Made Simple: Experimental UVR Exposure.

UVR exposure is a widely applied technique in clinical and preclinical studies. Such experimental conditions provide crucial information on the biological responses of skin and cell models, which may then be extrapolated and interpreted, for example, in the context of equivalent daylight exposures. It is therefore important to fully understand the characteristics of UVR and the principles behind correct and appropriate UVR exposure in experimental settings. In this Research Techniques Made Simple article, we discuss the relevant background information and the best practices for accurate, transparent, and reproducible experimentation and reporting of UVR exposure.

Ultraviolet A1 phototherapy: One center's experience.

BACKGROUND: Ultraviolet A1(UVA1) phototherapy is increasingly being used in the treatment of morphea, atopic dermatitis, lupus and some other recalcitrant dermatoses. We present a retrospective review of our experience with this modality. AIM: To evaluate the treatment response rates for various dermatoses and adverse effects of UVA1 phototherapy. METHODS: We reviewed phototherapy notes along with electronic and/or paper case records for all patients treated with UVA1 phototherapy from October 1996 to December 2008. RESULTS: A total of 269 patients (outcomes available for 247) had 361 treatment courses (treatment data available for 317 courses) over this period. We found phototherapy to be beneficial in 28 (53%) of 53 patients with atopic dermatitis and 19 (51%) of 37 patients with morphea. A beneficial outcome was recorded in all six (100%) cases of urticaria and six (85.7%) of seven patients treated for a polymorphic light eruption. Benefit was also recorded in systemic lupus erythematosus (8 (44.4%) of 18), lichen sclerosus (6 (42.9%) of 14), mastocytosis (2 (33.3%) of 6), necrobiosis lipoidica (4 (30.8%) of 13), granuloma annulare (2 (25%) of 8), scleroderma (2 (22.2%) of 9) and keloids (1 (7.7%) of 13). Overall, treatment was well tolerated with no patients having to stop treatment due to adverse effects. LIMITATIONS: This is a retrospective study with no control group. Subjective/recall bias is quite possible as a number of patients were followed up over the phone. CONCLUSIONS: Our data suggest that ultraviolet A1 can be considered for the treatment of selected dermatoses. However, long-term malignancy risk is as yet unknown.

Nrf2 Activation Protects against Solar-Simulated Ultraviolet Radiation in Mice and Humans.

The transcription factor Nrf2 determines the ability to adapt and survive under conditions of electrophilic, oxidative, and inflammatory stress by regulating the expression of elaborate networks comprising nearly 500 genes encoding proteins with versatile cytoprotective functions. In mice, disruption of Nrf2 increases susceptibility to carcinogens and accelerates disease pathogenesis. Paradoxically, Nrf2 is upregulated in established human tumors, but whether this upregulation drives carcinogenesis is not known. Here we show that the incidence, multiplicity, and burden of solar-simulated UV radiation-mediated cutaneous tumors that form in SKH-1 hairless mice in which Nrf2 is genetically constitutively activated are lower than those that arise in their wild-type counterparts. Pharmacologic Nrf2 activation by topical biweekly applications of small (40 nmol) quantities of the potent bis(cyano enone) inducer TBE-31 has a similar protective effect against solar-simulated UV radiation in animals receiving long-term treatment with the immunosuppressive agent azathioprine. Genetic or pharmacologic Nrf2 activation lowers the expression of the pro-inflammatory factors IL6 and IL1ß, and COX2 after acute exposure of mice to UV radiation. In healthy human subjects, topical applications of extracts delivering the Nrf2 activator sulforaphane reduced the degree of solar-simulated UV radiation-induced skin erythema, a quantifiable surrogate endpoint for cutaneous damage and skin cancer risk. Collectively, these data show that Nrf2 is not a driver for tumorigenesis even upon exposure to a very potent and complete carcinogen and strongly suggest that the frequent activation of Nrf2 in established human tumors is a marker of metabolic adaptation.

Drug-induced photosensitivity.

Drug-induced photosensitivity is common. The principal mechanism of systemic drug photosensitivity is phototoxicity and the principal mechanism of topical drug photosensitivity is photoallergy. Photopatch testing is helpful to determine suspected topical agent photoallergies (eg, from ultraviolet filters in sunscreens) but generally not helpful in detecting systemic drug photosensitivity. Drug-induced photosensitivity is usually best managed by stopping the suspected drug. Other measures, including phototherapy using wavelengths that do not elicit the response, are sometimes necessary.

A randomized comparison of methods of selecting narrowband UV-B starting dose to treat chronic psoriasis.

OBJECTIVES: To compare narrowband UV-B (TL-01 lamp) phototherapy for psoriasis with individual patient starting doses based on minimal erythemal dose (MED) determination vs a standard fixed starting dose and to compare the efficacy of 70% of MED vs 50% of MED starting dose regimens. DESIGN: Single-center, randomized, double-blind, clinical trial. SETTING: Department of Dermatology, Ninewells Hospital and Medical School, Dundee, Scotland. PATIENTS: A total of 210 adult patients (207 of skin phototypes I to III) referred for narrowband UV-B to treat chronic psoriasis. The study was designed to have 90% power to detect a difference of 3 or more treatments to clearance and/or minimal residual activity (MRA) between groups. INTERVENTIONS: Narrowband UV-B phototherapy was given according to 3 standard regimens, differing only by starting dose selection method. The randomly allocated starting doses were (1) a fixed starting dose, (2) 70% of individual MED, and (3) 50% of individual MED. All patients were MED tested to ensure blinding and for safety reasons. MAIN OUTCOME MEASURES: The number of treatments to clearance and/or MRA of psoriasis was the primary efficacy outcome measure, with changes in Psoriasis Area and Severity Index and Psoriasis Disability Index scores as secondary measures. Adverse effects were recorded. RESULTS: There were no significant differences in the number of treatments to clearance and/or MRA across all 3 groups or in the percentages achieving clearance in each group. More uncomfortable erythemas occurred in the 50% of MED starting dose group (39%) than in the 70% of MED starting dose group (24%) or the fixed starting dose group (24%) (P=.07). CONCLUSIONS: The methods of determining the starting dose in this predominantly skin phototype I and II population, treated 3 times weekly, with a 20% followed by 10% incremental reduction in dose, did not significantly influence the effectiveness of treatment. Had there been a clinically important difference in efficacy, we would have expected to identify this. Thus, basing starting dose on individual MED assessments may not influence the treatment's efficacy in a skin phototype I to III population, although it remains important for patient safety. It remains possible that in populations containing individuals with a broader range of erythemal sensitivity, basing the starting dose on MED testing could have an important impact on treatment effectiveness. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN84614024.

Glutathione S-transferase M1 (GSTM1) genotype but not GSTT1 or MC1R genotype influences erythemal sensitivity to narrow band (TL-01) UVB phototherapy.

OBJECTIVES: Although a majority of psoriasis patients respond to treatment with narrow band ultraviolet B radiation (TL-01) phototherapy, it is currently not possible to predict erythemal sensitivity, or to identify treatment responders. A variety of antioxidant enzymes, including the polymorphic glutathione S-transferase GSTM1 and GSTT1 genes, protect the cell from UVR-induced oxidative challenge. GSTM1 and GSTT1 are deleted in approximately 50 and 20% of the Caucasian population, respectively, and GST null genotype has been associated with increased sunburn sensitivity and reduced minimal erythemal dose (MED) after broadband UVR exposure in healthy volunteers and with susceptibility to skin cancer. Another polymorphic determinant of UVR sensitivity is the melanocortin 1 receptor (MC1R), which protects cells from UVR-induced apoptosis and photodamage. Our aim was therefore to investigate whether GST or MC1R genotype influenced erythemal sensitivity to narrow band (TL-01) ultraviolet B radiation phototherapy in patients with psoriasis. METHODS: We used TaqMan quantitative gene copy and allelic discrimination assays to determine GST and MC1R genotypes, and looked for possible associations between genotype and threshold erythemal sensitivity (MED) and treatment outcomes in patients with psoriasis (n=256). RESULTS: We showed that GSTM1 genotype, but not GSTT1 or MC1R genotype influences erythemal sensitivity to TL-01 phototherapy, with a significantly lower MED observed in GSTM1 null individuals [χ(2 d.f.)=8.862, P=0.012]. None of the genotypes studied were associated with TL-01 treatment outcomes or relapse rates. CONCLUSION: GSTM1 genotype may have clinical utilityin the prediction of photosensitivity and/or in identifying patients at increased risk of treatment-related side effects.

Dermatomyositis presenting with symptomatic dermographism and raised troponin T: a case report.

INTRODUCTION: Dermatomyositis is an important inflammation of skin and muscles. Generalised itch is frequent in the condition; however, symptomatic dermographism has not previously been reported as a presenting feature. CASE PRESENTATION: A 32-year-old Caucasian Scottish woman was diagnosed with dermatomyositis after initial presentation with symptomatic dermographism. No underlying neoplasm was found and her condition was successfully treated with systemic corticosteroids and high-dose human immunoglobulin infusions. At presentation, her troponin T and creatine phosphokinase enzymes were highly raised. CONCLUSION: Symptomatic dermographism may be a presenting feature of dermatomyositis. Dermatomyositis is one of many conditions that can result in a raised troponin T.

Randomized comparison of Mohs micrographic surgery and surgical excision for small nodular basal cell carcinoma: tissue-sparing outcome.

BACKGROUND: Mohs micrographic surgery (MMS) is recognized globally as the criterion standard for high-risk basal cell carcinoma (BCC). The main advantage of MMS over conventional surgery is the chance of complete tumor removal, but it is also thought, based on experience, to be tissue sparing. OBJECTIVE: To determine whether MMS leaves smaller surgical defects than standard surgery. METHODS AND MATERIALS: This was a randomized trial involving 30 patients with a clinical diagnosis of BCC. Patients were randomly assigned to MMS or standard surgery. In the standard surgery group the BCCs were excised with 4-mm margins. In the MMS group, tumors were excised with 2-mm margins and subsequent stages of MMS until the tumor was completely removed. An observer unaware of the treatment allocation calculated the defect size. The main outcome measure was defect size in mm(2). RESULTS: The median area of the surgical defects in the MMS group was 116.6 mm(2), versus 187.7 mm(2) in the standard surgery group (95% confidence interval for difference=61-126, p<.001). CONCLUSIONS: This is the first randomized trial demonstrating that MMS is a tissue-sparing treatment. TRIAL REGISTRATION: http://www.clinicaltrials.gov Identifier: NCT00571363. The authors have indicated no significant interest with commercial supporters.