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.

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.

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.

Population reference intervals for minimal erythemal doses in monochromator phototesting.

BACKGROUND/PURPOSE: Monochromator phototesting, to measure the minimal erythemal dose (MED), is useful in investigating patients with abnormal photosensitivity at different wavelengths. It relies on access to reliable, up-to-date data on the MED in normal individuals. The purpose of this study was to determine MED in normal subjects at different wavebands and compare these with historical controls. METHODS: The study group consisted of 415 normal individuals (349 males) of skin types I-III living in Scotland. Age range was 18-83 years (median 31 years). Phototesting was performed using a monochromator at prescribed wavelengths from 295 to 430 nm. All calibrations were traceable to the National Physical Laboratory. Quality systems were maintained to ISO 9001 and ISO 17025 international standards and ultraviolet (UV) measurements accredited by the United Kingdom Accreditation Service (UKAS). RESULTS: The 95% reference interval (99% confidence interval for this) ranged from 6.8 to 27 mJ/cm(2) at 295 nm to >82,000 mJ/cm(2) at 430 nm. CONCLUSIONS: Results of the current investigation are broadly in agreement with values published 25 years ago by this centre. This validates the phototesting process based on the use of monochromators with attention to careful control of conditions during UV exposure and MED reading, supported by dosimetric calibration.

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.

A double-blind, randomized assessment of the irritant potential of sunscreen chemical dilutions used in photopatch testing.

BACKGROUND: The maximum concentration of organic sunscreen filters in current usage that does not lead to irritant reactions when performing photopatch testing is not known. Such irritant reactions can be misinterpreted as positive photoallergic contact dermatitis reactions. OBJECTIVE: To determine the frequency of irritant reactions to 19 organic sunscreen filters in current use. PATIENTS/METHODS: Ninety-four healthy volunteers were photopatch tested using the European consensus methodology to three different concentrations (2%, 5%, and 10%) of 19 organic sunscreen filters at the Photobiology Unit in Dundee, UK. RESULTS: Of the 94 subjects recruited, 80 were analysed after withdrawals and exclusions. Of the 19 organic sunscreen filters studied, only 2 compounds led to irritant reactions in > or =5% subjects. Five per cent and 10% benzophenone-4 led to irritant reactions in four and six subjects, respectively. Five per cent methylene bis-benzotriazolyl tetramethylbutylphenol led to irritant reactions in six subjects, but unlike benzophenone-4, this was not in a dose-dependent fashion. CONCLUSIONS: When performing photopatch testing according to the European consensus methodology with these 19 organic sunscreen filters, a 10% concentration is suitable for all filters, except benzophenone-4, which should be tested at a concentration of 2%.

A randomized parallel study to assess the safety and efficacy of two different dosing regimens of 5% imiquimod in the treatment of superficial basal cell carcinoma.

OBJECTIVES: This study was designed to compare the safety and efficacy of two cycled dosing regimens of imiquimod 5% cream for treatment of superficial basal cell carcinoma (sBCC). METHODS: Patients (n = 32) were randomized to receive one of two treatment regimens: 8 weeks of treatment with once-daily dosing for alternate weeks (R1) and 5 weeks of once-daily dosing with a 1-week interval in the middle of the course (R2). Efficacy measures were tumour clearance at weeks 19 and 52 and measures of patients' acceptability. RESULTS: Data from 30 patients (13 females), 14 on R1 and 16 on R2, were analysed. The results revealed an initial clearance rate of 64% at week 19 for R1 and 81% for R2 (95% CI for difference: -14% to 45%, p = 0.21). However, clearance rates at week 52 were significantly different: 43% for R1 and 88% for R2 (95% CI for difference: 11% to 68%, p = 0.02). There was no difference in acceptability of treatment as measured by composite median visual analogue scores at week 8. CONCLUSION: Five weeks of 5% imiquimod cream once daily with a 1-week interval was more effective but as well tolerated as the 8-week alternate week regimen for sBCC.

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.

Dose-response and time-course characteristics of UV-A1 erythema.

OBJECTIVE: To determine the time course and dose-response characteristics of UV-A1 erythema in the Tayside region of Scotland. DESIGN: Adult volunteers (skin types I and II [n = 13] and III and IV [n = 11]) were exposed to geometric dose series of UV-A1 irradiation from a high-output source on photoprotected lower back and inner forearm skin. SETTING: Photobiology unit in a university hospital. MAIN OUTCOME MEASURES: The minimal erythema dose (MED) was recorded visually and erythema was assessed objectively by erythema meter at 4, 8, 24, and 48 hours after exposure. RESULTS: Peak erythema (lowest visual MED) was seen at 8 hours on the back and arm in 11 subjects with skin types I and II and on the back at 8 hours in 9 subjects and on the arm at 4 hours in 10 subjects with skin types III and IV. The lowest median (range) MED was 20 J/cm(2) (14-56 J/cm(2)) on the back and 42 J/cm(2) (20 to >80 J/cm(2)) on the arm at 8 hours for subjects with skin types I and II and 28 J/cm(2) (20-112 J/cm(2)) at 8 hours on the back and 56 J/cm(2) (28-80 J/cm(2)) at 4 hours on the arm for subjects with skin types III and IV. The D(0.025), an objective measure that corresponds approximately to the visual MED, demonstrated a broad peak from 8 to 24 hours. CONCLUSIONS: Our local population is more erythemally sensitive to UV-A1 radiation than reports suggest. Daily dose regimens may risk cumulative erythema. Lower starting doses should be used in this population. The wide range of MEDs highlights the need for MED testing.

Chronic actinic dermatitis in the elderly: recognition and treatment.

Chronic actinic dermatitis is a condition involving abnormal cutaneous photosensitivity to UV and, often, visible wavelengths. It is rare, but more common in the elderly than in younger populations, with an estimated prevalence of one in 2000 in the > or = 75-year-old population in Tayside, Dundee, Scotland. It usually presents as a dermatitis that maximally, but not exclusively, affects photo-exposed skin. Investigation to confirm the diagnosis and guide management includes phototesting and patch testing. The mainstay of treatment is education about the condition and advice on sunlight and allergen avoidance. Topical corticosteroids and emollients are always required, at least intermittently, and it is sometimes necessary to resort to systemic immunosuppression, usually with corticosteroids or azathioprine.