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Introduction: Severe recurrent aphthous stomatitis (RAS) represents a therapeutic challenge because of its impact on the patient's quality of life. Additionally, no approved systemic therapies are available. Roflumilast, a phosphodiesterase-4 inhibitor, has shown promise in other inflammatory dermatological conditions. This study aimed to assess the characteristics, effectiveness, and safety of roflumilast in treating RAS in routine clinical practice., Methods: This is a single cohort ambispective observational study conducted in five Spanish centers. Twenty-two patients with RAS treated with roflumilast participated. Data collection included demographic, clinical, and outcome variables. Statistical analysis compared the outcomes of 12 weeks of roflumilast treatment with a similar prior period without treatment., Results: During treatment with roflumilast, a significant reduction in flare-ups (88%) and oral ulcers (94%) was observed compared to the untreated period. A reduction in pain (66%) and ulcer duration (63%) was observed. Adverse effects (AEs) occurred in 13 patients, predominantly headache and gastrointestinal disturbances. Most of these were self-limiting or manageable with dose adjustment. Treatment was withdrawn in three cases, mainly because of AEs., Conclusions: This study suggests that roflumilast may effectively treat RAS by reducing the number of flare-ups and ulcers, their duration, and the symptomatology produced by the ulcers. In addition, roflumilast has a good safety profile, is well tolerated at low doses, and does not require close monitoring. These characteristics and its favorable economic profile make roflumilast a promising therapeutic option in this pathology., (© 2024 The Author(s). International Journal of Dermatology published by Wiley Periodicals LLC on behalf of the International Society of Dermatology.)

Introduction: Dupilumab is approved as first-line systemic treatment for adults/adolescents with moderate-to-severe atopic dermatitis (AD) in Europe and elsewhere owing to its favourable benefit-risk profile. However, systemic non-steroidal immunosuppressants (NSISS) are often used as first-line therapy in clinical practice. Impact of prior therapy with NSISS on dupilumab's treatment effect vs. control has not been described previously. This study assessed dupilumab's efficacy vs. control in patients with moderate-to-severe AD, comparing treatment effect in patients with/without prior systemic NSISS therapy, in four phase 3 trials., Methods: This post hoc analysis included 1553 patients randomized to placebo or dupilumab (300 mg q2w) as monotherapy for 16 weeks, or with concomitant topical corticosteroids (TCS) for 16/52 weeks, from four randomized, double-blind, placebo-controlled, phase 3 trials. Patients were stratified by prior use of systemic NSISS and dupilumab-treated patients were analysed against control groups (treated with placebo or placebo + TCS)., Results: Dupilumab-treated patients, regardless of prior treatment with NSISS, achieved a significantly higher percentage reduction from baseline in Eczema Area and Severity Index (EASI), SCORing Atopic Dermatitis (SCORAD), Dermatology life Quality Index (DLQI), and Patient-Oriented Eczema Measure (POEM) vs. control; significantly more achieved EASI score ≤ 7, Peak Pruritus Numerical Rating Scale ≤ 4, POEM ≤ 7, and DLQI ≤ 5 by week 4. These rapid, significant improvements were seen with or without concomitant TCS and sustained through end-of-treatment., Conclusions: Dupilumab treatment (monotherapy or + TCS) provides rapid, significant, sustained improvements in signs, symptoms, and quality of life in patients with moderate-to-severe AD compared with control, regardless of prior systemic NSISS use., Clinical Trial Registration: LIBERTY AD SOLO 1: ClinicalTrials.gov identifier NCT02277743, EudraCT 2014-001198-15. LIBERTY AD SOLO 2: ClinicalTrials.gov identifier NCT02277769, EudraCT 2014-002619-40., Liberty Ad Chronos: ClinicalTrials.gov identifier NCT02260986, EudraCT 2013-003254-24. LIBERTY AD CAFÉ: ClinicalTrials.gov identifier NCT02755649, EudraCT 2015-002653-35., (© 2021. The Author(s).)

Background and Purpose: Current criteria to evaluate acute radiodermatitis are highly subjective so quantification of physiological parameters is needed. We describe a non-invasive method of assessing skin microcirculation in breast cancer patients treated with hypofractionated radiotherapy and correlate them with the CTCAE scale., Methods: Prospective study of 63 patients where blood flow was measured with real-time laser Doppler flowmetry (LDF) at baseline, weekly, and 3-months post-radiotherapy. Skin toxicity was assessed with the microcirculation index (MCI), a novel index based on blood flow parameters obtained via LDF., Results: MCI was positively correlated (R=0.647; p<0.001) with the dose. Changes in MCI from baseline to the end of radiotherapy and at 3-months post-radiotherapy were significant (p<0.001). All CTCAE groups experienced a significant increase in MCI values from baseline to end of radiotherapy (p<0.001 for CTCAE grades 0 and 1; and p=0.028 for the grade 2 group). Significant differences in MCI values were observed among CTCAE groups at the end of radiotherapy (p=0.016)., Conclusions: LDF is an accurate and objective measure of changes in blood flow. The comparison with the CTCAE shows the limitations of this subjective way of classifying patients. LDF is the first step for future studies of radiodermatitis treatments and prevention., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Psoriasis is a chronic inflammatory skin disease whose clinical characteristics vary from patient to patient. We aimed to analyze how comorbidities and quality of life (QoL, as per the Dermatology Life Quality Index [DLQI]) may be affected by a family history of psoriasis and by age. The ARIZONA study was a multicenter, cross-sectional study in 1022 adult patients diagnosed with moderate to severe psoriasis at least 6 months prior to inclusion. The severity of psoriasis and the proportion of patients with comorbidities were not affected by the presence of a family history. The regression analysis revealed that the presence of a family history of psoriasis was associated with the effect on the patient's QoL (P = 0.002), regardless of disease severity. The mean DLQI total score varied significantly across age groups (5.1 ± 5.3 for the 18-30-year group, 5.7 ± 6.5 for the 31-60-year group and 3.8 ± 5.1 for the >60-year group; P = 0.001). In conclusion, the presence of a family history of psoriasis appears to disrupt QoL in patients with moderate to severe psoriasis, but it hardly affected the prevalence of comorbid conditions. The effect of age on QoL was particularly noticeable in younger patients, highlighting its negative impact. As expected, older patients appeared to be burdened with a higher number of comorbidities than their younger counterparts., (© 2015 Japanese Dermatological Association.)

Background: Identifying patients likely to have very good or bad results from systemic psoriasis therapy could improve efficiency of therapy., Objective: To develop prognostic models for good or bad response to classic systemic drugs, anti-TNFs, and ustekinumab in psoriasis., Methods: Multivariable logistic regression of a prospective multicenter cohort of psoriatic patients in clinical practice (6449 person-years of follow-up). We used as possible predictors demographic characteristics, comorbidities, characteristics of the psoriasis (type, PASI, arthritis), history of past therapy at entry in the cohort, and history of response to previous cycles while in the cohort. We defined good response to a treatment cycle as either cycle end due to disease remission or a cycle longer than 2 years that does not end later due to inefficacy in the follow-up period. Bad response to a treatment cycle was defined as a cycle that is finished due to inefficacy, based on the physician judgment, after more than 3 months of treatment., Results: Patients with fewer previous therapies, lower body mass index, older at start of therapy, and with previous history of good responses to therapy are more likely to have positive results of therapy. However, the predictive characteristics of models are poor., Conclusion: Predictive models of clinical response to systemic drugs in psoriasis with the studied variables do not seem to outperform drug selection by a dermatologist.

Objective: To describe the use of systemic therapy for psoriasis (biologic and nonbiologic [classic] drugs) in patients not adequately represented in randomized controlled trials (RCTs) and the risk of serious adverse events (SAEs) in these patients., Design: A registry inception cohort was used., Setting: Thirteen dermatology departments in Spain participated., Patients: A consecutive sample of patients treated with biologics and a systematic sample of patients treated with classic systemic therapy were evaluated. A total of 1042 patients (2179 person-years) were included., Exposure: Inadequate representation in trials was defined as the presence of any of the following factors: elderly age (>70 years); type of psoriasis other than chronic plaque psoriasis; history of infection caused by hepatitis B, hepatitis C, or human immunodeficiency virus; history of cancer (excluding nonmelanoma skin cancer); and chronic renal or hepatic disease., Main Outcome Measures: Serious adverse events as defined by the International Conference on Harmonization were evaluated., Results: In all, 29.8% of patients receiving systemic therapy for psoriasis would not have been eligible for RCTs. These individuals had an increased risk of SAEs (incidence rate ratio, 2.7; 95% CI, 1.5-4.7). Patients exposed to biologics had an adjusted increased risk of SAEs (incidence rate ratio, 2.3; 95% CI, 1.1-4.8) that was similar in patients eligible and ineligible for RCTs., Conclusions: Patients ineligible for RCTs are an important proportion (30%) of those receiving systemic therapy for psoriasis. These patients have a higher risk of SAEs and should be closely monitored. Patients exposed to biologics (whether these patients are eligible for RCTs or ineligible) are susceptible to the same increase in risk of SAEs, but biologics add to a higher baseline risk in patients who are ineligible for RCTs. The risk-benefit ratio in ineligible patients receiving biologics might be different from the ratio in eligible patients.

Conventional systemic treatments for patients with psoriasis are associated with multiple adverse effects that require continuous monitoring. The introduction of new biological agents such as etanercept, a fully human fusion protein, has permitted individualisation of patients' treatment according to disease stage. The drug is a competitive inhibitor of tumour necrosis factor-alpha (TNFalpha) that prevents interaction between this cytokine and its cell surface receptors. Etanercept also modulates the activity of other inflammatory cytokines and does not induce complement-mediated cell lysis in vitro. The main source of information regarding etanercept safety comes from studies in patients with rheumatoid arthritis. The most common adverse effect during drug administration is mild injection site reactions. There is no increase in the overall incidence of infections compared with placebo, although there have been several reports of infections caused by intracellular organisms (Mycobacterium tuberculosis, Listeria monocytogenes, and Mycobacterium avium intracellulare). Therefore, combination of this drug with corticosteroids must be carefully monitored and should be avoided in patients with established sepsis. There are no data showing that treatment with etanercept results in an increase in the occurrence of malignant neoplasms. However, caution is recommended in use of etanercept in patients with a current or past history of demyelinating disease. Etanercept must be used with extreme caution in patients with heart failure because of several reports indicating a worsening or de novo occurrence of congestive heart failure while receiving the drug. Monitoring of autoantibodies is not currently considered necessary as they do not predict response, toxicity or autoimmune events. The presence of non-neutralising antibodies to the TNF receptor fragment or other protein components of etanercept has not been related to a decrease in drug response or adverse reactions. Etanercept does not generally modify the course of inflammatory bowel disease. When combined with other systemic therapies for psoriasis, current data do not show an increase in adverse events. In patients with hepatitis C viral infection, etanercept does not increase transaminase levels or viral load and in some instances has allowed the concomitant use of interferon which had previously been discontinued because of a worsening of psoriasis. Etanercept is rated as a US FDA category B drug in pregnancy. However, its use is not recommended in pregnant women unless the benefit-risk ratio greatly favours its use. Etanercept is not recommended for use in lactating women. Etanercept represents a relevant treatment for psoriasis, efficacious over many weeks and safe but special care should be taken to avoid the potential risks.