Guidelines of care for the management of atopic dermatitis in adults with phototherapy and systemic therapies.

BACKGROUND: For people with atopic dermatitis (AD) refractory to topical therapies, treatment with phototherapy and systemic therapies can be considered. Multiple biologic therapies and Janus kinase (JAK)inhibitors have been approved since 2014 to treat AD. These guidelines update the 2014 recommendations for management of AD with phototherapy and systemic therapies. OBJECTIVE: To provide evidence-based recommendations on the use of phototherapy and systemic therapies for AD in adults. METHODS: A multidisciplinary workgroup conducted a systematic review and applied the GRADE approach for assessing the certainty of evidence and formulating and grading recommendations. RESULTS: The workgroup developed 11 recommendations on the management of AD in adults with phototherapy and systemic agents, including biologics, oral JAK inhibitors, and other immunomodulatory medications. LIMITATIONS: Most randomized controlled trials of phototherapy and systemic therapies for AD are of short duration with subsequent extension studies, limiting comparative long-term efficacy and safety conclusions. CONCLUSIONS: We make strong recommendations for the use of dupilumab, tralokinumab, abrocitinib, baricitinib, and upadacitinib. We make conditional recommendations in favor of using phototherapy, azathioprine, cyclosporine, methotrexate, and mycophenolate, and against the use of systemic corticosteroids.

Executive summary: Guidelines of care for the management of atopic dermatitis in adults with phototherapy and systemic therapies.

BACKGROUND: The summarized guidelines update the 2014 recommendations for the management of AD with phototherapy and systemic therapies. METHODS: A multidisciplinary workgroup conducted a systematic review and applied the GRADE approach for assessing the certainty of the evidence and formulating and grading recommendations. RESULTS: The workgroup developed 11 recommendations on the management of AD in adults with phototherapy and systemic therapies, including biologics, oral Janus Kinase inhibitors, and other immunomodulatory medications. CONCLUSIONS: The evidence supported strong recommendations for the use of dupilumab, tralokinumab, abrocitinib, baricitinib, and upadacitinib and conditional recommendations in favor of using phototherapy, azathioprine, cyclosporine, methotrexate, and mycophenolate, and against the use of systemic corticosteroids.

Derivation of a Multivariable Psoriatic Arthritis Risk Estimation Tool (PRESTO): A Step Towards Prevention.

OBJECTIVE: A simple, scalable tool that identifies psoriasis patients at high risk for developing psoriatic arthritis (PsA) could improve early diagnosis. We aimed to develop a risk prediction model for the development of PsA and to assess its performance among patients with psoriasis. METHODS: We analyzed data from a prospective cohort of psoriasis patients without PsA at enrollment. Participants were assessed annually by a rheumatologist for the development of PsA. Information about their demographics, psoriasis characteristics, comorbidities, medications, and musculoskeletal symptoms was used to develop prediction models for PsA. Penalized binary regression models were used for variable selection while adjusting for psoriasis duration. Risks of developing PsA over 1- and 5-year time periods were estimated. Model performance was assessed by the area under the curve (AUC) and calibration plots. RESULTS: Among 635 psoriasis patients, 51 and 71 developed PsA during the 1-year and 5-year follow-up periods, respectively. The risk of developing PsA within 1 year was associated with younger age, male sex, family history of psoriasis, back stiffness, nail pitting, joint stiffness, use of biologic medications, patient global health, and pain severity (AUC 72.3). The risk of developing PsA within 5 years was associated with morning stiffness, psoriatic nail lesion, psoriasis severity, fatigue, pain, and use of systemic nonbiologic medication or phototherapy (AUC 74.9). Calibration plots showed reasonable agreement between predicted and observed probabilities. CONCLUSIONS: The development of PsA within clinically meaningful time frames can be predicted with reasonable accuracy for psoriasis patients using readily available clinical variables.

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.

A description of treatment patterns of psoriasis by medical providers and disease severity in US women.

BACKGROUND: Studies on treatment patterns of psoriasis are valuable to evaluate how efficiently individuals with psoriasis are treated and may facilitate improved outcomes for these patients. OBJECTIVE: To describe treatment patterns of psoriasis among US women. METHODS: In the Nurses' Health Study II (NHS II), a prospective study of female nurses, 2107 women reported to have a diagnosis of psoriasis made by a clinician. We sent them the Psoriasis Screening Tool-2, a validated diagnostic tool for psoriasis, which queries age at diagnosis, treatments, type of psoriasis lesions, body surface area involved, and the provider who made the diagnosis. RESULTS: A total of 1382 women completed and returned the survey, with 1243 of them validated for having psoriasis. 30% of the patients were diagnosed by non-dermatologists. 79% of the patients reported mild, 17% moderate and 4% severe disease. Psoriasis phenotypes were as follows: plaque 41%, scalp 49%, inverse 27%, nail 22% and palmoplantar 15%. Treatment patterns for mild psoriasis were as follows: only topical treatment 58%, systemic therapy and/or phototherapy 16% and no treatment 26%. Treatment patterns for moderate-to-severe disease were as follows: only topical treatment 42%, systemic therapy and/or phototherapy 47% and no treatment 11%. CONCLUSION: The majority of women in NHS II with psoriasis have mild disease. A large proportion of psoriasis patients were diagnosed by non-dermatologists. More than half of people with moderate-to-severe disease received no treatment or only topical medications. A considerable percentage of people with psoriasis reported phenotypes other than chronic plaque psoriasis.

Association of Caffeine Intake and Caffeinated Coffee Consumption With Risk of Incident Rosacea in Women.

Importance: Caffeine is known to decrease vasodilation and have immunosuppressant effects, which may potentially decrease the risk of rosacea. However, the heat from coffee may be a trigger for rosacea flares. The relationship between the risk of rosacea and caffeine intake, including coffee consumption, is poorly understood. Objective: To determine the association between the risk of incident rosacea and caffeine intake, including coffee consumption. Design, Setting, and Participants: This cohort study included 82 737 women in the Nurses' Health Study II (NHS II), a prospective cohort established in 1989, with follow-up conducted biennially between 1991 and 2005. All analysis took place between June 2017 and June 2018. Exposures: Data on coffee, tea, soda, and chocolate consumption were collected every 4 years during follow-up. Main Outcomes and Measures: Information on history of clinician-diagnosed rosacea and year of diagnosis was collected in 2005. Results: A total of 82 737 women responded to the question regarding a diagnosis of rosacea in 2005 in NHS II and were included in the final analysis (mean [SD] age at study entry, 50.5 [4.6] years). During 1 120 051 person-years of follow-up, we identified 4945 incident cases of rosacea. After adjustment for other risk factors, we found an inverse association between increased caffeine intake and risk of rosacea (hazard ratio for the highest quintile of caffeine intake vs the lowest, 0.76; 95% CI, 0.69-0.84; P < .001 for trend). A significant inverse association with risk of rosacea was also observed for caffeinated coffee consumption (HR, 0.77 for those who consumed ≥4 servings/d vs those who consumed <1/mo; 95% CI, 0.69-0.87; P < .001 for trend), but not for decaffeinated coffee (HR, 0.80; 95% CI, 0.56-1.14; P = .39 for trend). Further analyses found that increased caffeine intake from foods other than coffee (tea, soda, and chocolate) was not significantly associated with decreased risk of rosacea. Conclusions and Relevance: Increased caffeine intake from coffee was inversely associated with the risk of incident rosacea. Our findings do not support limiting caffeine intake as a means to prevent rosacea. Further studies are required to explain the mechanisms of action of these associations, to replicate our findings in other populations, and to explore the relationship of caffeine with different rosacea subtypes.

Health Care Resource Utilization and Costs Among Adults with Atopic Dermatitis in the United States: A Claims-Based Analysis.

BACKGROUND: Data on health care resource utilization (HCRU) and costs for patients with atopic dermatitis (AD) are lacking. OBJECTIVE: The objective of this study was to determine HCRU and costs associated with AD in US adults. METHODS: This retrospective study identified patients with AD from the Truven Health Marketscan Commercial Claims and Encounters database during 2013 based on ≥2 claims with International Classification of Diseases, Ninth Revision code 691.8 (n = 10,533; first claim = index event); 1-year continuous enrollment before and after index was required. Patients were age- and gender-matched in a 1:3 ratio to controls without AD (n = 31,599). Patients with AD were further categorized into 2 groups, with treatment regimens as surrogates for increasing disease severity: claim for phototherapy or systemic immunomodulatory agents (more severe) or no claim for either (less severe). Incremental differences in resource use and costs were evaluated using multivariate analysis. RESULTS: AD was associated with higher utilization and costs across resource categories (all P < .0001); adjusted total incremental annual costs were $3,302. Resource utilization and costs were higher in the more severe group, with adjusted total incremental annual costs of $4,463. CONCLUSION: AD is associated with significant incremental health care utilization and costs, which are higher in patients with more severe disease.

When does atopic dermatitis warrant systemic therapy? Recommendations from an expert panel of the International Eczema Council.

BACKGROUND: Although most patients with atopic dermatitis (AD) are effectively managed with topical medication, a significant minority require systemic therapy. Guidelines for decision making about advancement to systemic therapy are lacking. OBJECTIVE: To guide those considering use of systemic therapy in AD and provide a framework for evaluation before making this therapeutic decision with the patient. METHODS: A subgroup of the International Eczema Council determined aspects to consider before prescribing systemic therapy. Topics were assigned to expert reviewers who performed a topic-specific literature review, referred to guidelines when available, and provided interpretation and expert opinion. RESULTS: We recommend a systematic and holistic approach to assess patients with severe signs and symptoms of AD and impact on quality of life before systemic therapy. Steps taken before commencing systemic therapy include considering alternate or concomitant diagnoses, avoiding trigger factors, optimizing topical therapy, ensuring adequate patient/caregiver education, treating coexistent infection, assessing the impact on quality of life, and considering phototherapy. LIMITATIONS: Our work is a consensus statement, not a systematic review. CONCLUSION: The decision to start systemic medication should include assessment of severity and quality of life while considering the individual's general health status, psychologic needs, and personal attitudes toward systemic therapies.

Narrowband UVB as an effective substitute for psoralen plus UVA: lessons from a psoralen shortage.

From March to August 2010, there was a shortage of encapsulated liquid 8-methoxypsoralen (8-MOP), the psoralen used for bath psoralen plus UVA (PUVA) in Toronto, Canada. Patients were forced to discontinue bath PUVA treatment and were transitioned to other therapeutic modalities, including narrowband UVB (nbUVB). A retrospective chart review was conducted of all patients who discontinued bath PUVA due to the unavailability of 8-MOP, with a focus on those who were switched to nbUVB. Sixty-three patients discontinued PUVA, 39 of whom were switched to nbUVB. Fifteen of 17 patients with mycosis fungoides (MF) who were switched to nbUVB improved, and patients with earlier-stage disease were more likely to improve. Ten of 13 (77%) psoriasis patients improved with nbUVB, including two patients whose psoriasis cleared completely. All three small-plaque parapsoriasis patients who switched to nbUVB had complete clearance of their lesions. In conclusion, nbUVB may be a suitable alternative for patients with MF, small-plaque parapsoriasis and psoriasis who cannot access PUVA therapy.