Maintenance of Investigator's Static Global Assessment Response with Once-Daily Crisaborole in Participants with Mild to Moderate Atopic Dermatitis.

INTRODUCTION: Treatments for atopic dermatitis (AD) often fail to achieve lasting disease control. In the CrisADe CONTROL phase III study (ClinicalTrials.gov: NCT04040192), participants aged ≥ 3 months with mild to moderate AD treated with once-daily (QD) crisaborole, following initial treatment success with crisaborole twice daily (BID), had longer periods of flare-free maintenance, a higher number of flare-free days, and a lower number of flares compared with those who received vehicle. The study was an exploratory analysis of data on the maintenance of response per Investigator's Static Global Assessment (ISGA; ISGA score of 0 [clear] or 1 [almost clear]) during the CrisADe CONTROL study through week 52. METHODS: Exploratory endpoints were the time to ISGA response during the open-label run-in period, and the maintenance of ISGA response and the severity and duration of flares during the double-blind maintenance period. Outcomes were stratified by age (participants aged 3 months to < 12 years and ≥ 12 years) and duration of crisaborole BID treatment (< 4 weeks or ≥ 4 weeks) during the open-label run-in period. RESULTS: During the open-label run-in period, the median time to ISGA response was 41.5 days. From week 4 to week 52 of the double-blind maintenance period, the proportion of participants who maintained ISGA response was greater with crisaborole versus vehicle, and this difference was statistically significant up to week 36 (P < 0.05). Duration of flare periods during the maintenance period were 54.1 and 54.0 days for the vehicle and crisaborole-treated groups, respectively. Numerically fewer crisaborole-treated participants experienced a flare with an ISGA score of ≥ 2 compared with vehicle-treated participants (64.8% vs. 74.4%, respectively). Findings were comparable across most subgroups. CONCLUSIONS: Adult and pediatric participants with mild to moderate AD at baseline who had achieved responder criteria (treatment success) with crisaborole BID during the run-in period maintained response per ISGA with crisaborole QD during the double-blind maintenance period through week 52. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04040192.

Atopic dermatitis is a skin disease that causes itchy, red, and dry patches of skin that can affect a person for a long time. Current treatments for atopic dermatitis often fail to keep the symptoms under control. Some creams and ointments applied to the skin (known as topical treatments) can ease the discomfort of atopic dermatitis. Crisaborole is a steroid-free ointment that has been shown to improve symptoms of atopic dermatitis in clinical studies. In a study called the CrisADe CONTROL trial, crisaborole was tested to see if it can keep atopic dermatitis symptoms under control. People who participated in the study were aged 3 months and older and they had mild-to-moderate atopic dermatitis. Participants were asked to use crisaborole on their itchy, red, and dry skin twice daily for 8 weeks. Patients were called "responders" if their symptoms became nearly clear or completely clear based on a doctor's assessment called the Investigator's Static Global Assessment, which rates atopic dermatitis between clear to severe. Some responders were asked to use crisaborole once daily for 52 weeks and another group of responders was asked to use a control (an ointment with no medicine) once daily for 52 weeks. Investigators looked at how long the skin remained nearly clear or completely clear during the 52 weeks. Results of this study showed that after initial treatment success with crisaborole twice daily, adult and pediatric participants who had mild-to-moderate atopic dermatitis were able to keep their skin nearly clear or completely clear with crisaborole once daily.

Targeting antibody-mediated complement-independent mechanism in bullous pemphigoid with diacerein.

BACKGROUND: Bullous pemphigoid (BP) is an antibody-mediated blistering disease predominantly affecting the elderly. The pathogenesis involves both complement-dependent and complement-independent mechanisms. The therapeutic potential of targeting complement-independent mechanism has not yet been determined. The mainstay of treatment, corticosteroid, has many side effects, indicating the needs of better treatments. OBJECTIVE: We tempted to establish an in vitro model of BP which resembles complement-independent mechanism and to examine the therapeutic potential of a novel anti-inflammatory agent, diacerein. METHODS: Cultured HaCaT cells were treated with purified antibodies from BP patients, with or without diacerein to measure the cell interface presence of BP180, protein kinase C, and the production of proinflammatory cytokines. An open-label, randomized, phase 2 trial was conducted to compare topical diacerein and clobetasol ointments in patients with mild-to-moderate BP (NCT03286582). RESULTS: The reduced presentation of BP180 at cell interface after treating with BP autoantibodies was noticed in immunofluorescence and western blotting studies. The phenomenon was restored by diacerein. Diacerein also reduced the autoantibody-induced increase of pro-inflammatory cytokines. Reciprocal changes of BP180 and protein kinase C at the cell interface were found after treating with BP autoantibodies. This phenomenon was also reversed by diacerein in a dose-dependent manner. The phase 2 trial showed that topical diacerein reduced the clinical symptoms which were comparable to those of topical clobetasol. CONCLUSION: Diacerein inhibited BP autoantibody-induced reduction of BP180 and production of proinflammatory cytokines in vitro and showed therapeutic potential in patients with BP. It is a novel drug worthy of further investigations.

Insulin-like growth factor 2 mRNA-binding protein 3 enhanced melanoma migration through regulation of AKT1 and RELA expression.

IMP-3 expression is a poor prognostic factor of melanomas and it promotes melanoma cell migration and invasion by a pathway modulating HMGA2 mRNA expression. We tried to identify other putative targets of IMP-3. We identified putative IMP-3-binding RNAs, including AKT1, MAPK3, RB1 and RELA, by RNA immunoprecipitation coupled with next-generation sequencing. IMP-3 overexpression increased AKT and RELA levels in MeWo cells. siRNAs against AKT1 and RELA inhibited MeWo/Full-length IMP-3 cell migration. IMP-3 knockdown of A2058 cells decreased AKT1 and RELA expression and lowered migration ability. Co-transfection of A2058 cells with AKT1- or RELA-expressing plasmids with IMP-3 siRNA restored the inhibitory effects of IMP-3 knockdown on migration. HMGA2 did not influence AKT1 and RELA expression in melanoma cells. Human melanoma samples with high IMP-3 levels also showed high HMGA2, AKT1 and RELA expression. Our results show that IMP-3 enhances melanoma cell migration through the regulation of the AKT1 and RELA axis.

Management of Adult Patients With Drug Reaction With Eosinophilia and Systemic Symptoms: A Delphi-Based International Consensus.

Importance: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but potentially fatal drug hypersensitivity reaction. To our knowledge, there is no international consensus on its severity assessment and treatment. Objective: To reach an international, Delphi-based multinational expert consensus on the diagnostic workup, severity assessment, and treatment of patients with DRESS. Design, Setting, and Participants: The Delphi method was used to assess 100 statements related to baseline workup, evaluation of severity, acute phase, and postacute management of DRESS. Fifty-seven international experts in DRESS were invited, and 54 participated in the survey, which took place from July to September 2022. Main Outcomes/Measures: The degree of agreement was calculated with the RAND-UCLA Appropriateness Method. Consensus was defined as a statement with a median appropriateness value of 7 or higher (appropriate) and a disagreement index of lower than 1. Results: In the first Delphi round, consensus was reached on 82 statements. Thirteen statements were revised and assessed in a second round. A consensus was reached for 93 statements overall. The experts agreed on a set of basic diagnostic workup procedures as well as severity- and organ-specific further investigations. They reached a consensus on severity assessment (mild, moderate, and severe) based on the extent of liver, kidney, and blood involvement and the damage of other organs. The panel agreed on the main lines of DRESS management according to these severity grades. General recommendations were generated on the postacute phase follow-up of patients with DRESS and the allergological workup. Conclusions and Relevance: This Delphi exercise represents, to our knowledge, the first international expert consensus on diagnostic workup, severity assessment, and management of DRESS. This should support clinicians in the diagnosis and management of DRESS and constitute the basis for development of future guidelines.

The impact of comorbidities, neutrophil-to-lymphocyte ratio, and drug toxicities on quality of life in lung cancer patients receiving EGFR-TKI therapy.

BACKGROUND: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are used as the standard first-line treatment for patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC). However, the impact of comorbidities and treatment toxicities on quality of life (QoL) was seldom investigated. OBJECTIVE: We aimed to investigate the association of comorbidities, adverse events (AEs), and QoL in treatment-naïve advanced NSCLC patients receiving EGFR-TKI treatments. METHODS: This multi-center prospective observational study was conducted to evaluate QoL and AEs at baseline, the 2nd, 4th, 12th, and 24th week. Clinical characteristics, comorbidities, and pre-treatment laboratory data were recorded. QoL was assessed by using the summary score of the EORTC QLQ-C30 and the dermatology life quality index. The impact of comorbidities, neutrophil-to-lymphocyte ratio (NLR), and AEs on QoL was analyzed by generalized estimating equations. RESULTS: A total of 121 patients were enrolled. Diarrhea (p = 0.033), anorexia (p < 0.001), and NLR ≥4 (p = 0.017) were significantly associated with a QoL impairment. Among skin toxicities, acneiform rash (p = 0.002), pruritus (p = 0.002), visual analogue scale for pruritus (≥3 and < 7, p = 0.006; ≥7, p = 0.001) and pain (1-3, p = 0.041) were associated with a QoL impairment. No significant association was found between comorbidities and QoL changes. CONCLUSION: Diarrhea, anorexia, skin pain, and pruritus may cause a deterioration in QoL in patients receiving EGFR-TKI therapy. NLR may be a potential predictive factor for QoL impairment. Aggressive management and close monitoring for these clinical factors are crucial to improve QoL.

Clinical practice consensus for the diagnosis and management of melanoma in Taiwan.

Melanoma is rare in Taiwan. Asian melanoma is distinct from Western melanoma because acral and mucosal melanoma accounts for the majority of melanoma cases, leading to distinct tumor behaviors and genetic profiling. With consideration of the clinical guidelines in Western countries, Taiwanese experts developed a local clinical practice consensus guideline. This consensus includes diagnosis, staging, and surgical and systemic treatment, based only on clinical evidence, local epidemiology, and available resources evaluated by experts in Taiwan. This consensus emphasizes the importance of surgical management, particularly for sentinel lymph node biopsies. In addition, molecular testing for BRAF is mandatory for patients before systemic treatment. Furthermore, immunotherapy and targeted therapy are prioritized for systemic treatment. This consensus aimed to assist clinicians in Taiwan in diagnosing and treating patients according to available evidence.

Comorbidity of Ocular and Facial Demodicosis.

PURPOSE: To determine the association between ocular and facial demodicosis, and the effect of facial treatment on ocular demodicosis. DESIGN: Prospective clinical cohort study. METHODS: Ocular demodicosis outpatients from a tertiary medical center were enrolled from April to December 2020. The diagnosis was based on epilation of 4 eyelashes from each upper eyelid. High ocular Demodex load (ODL) was defined as ≥8 mites per eye. Facial infestation was assessed by direct microscopic examination, with facial Demodex overgrowth (FDO) defined as a density >5 mites/cm2. All patients were prescribed 3 months of ocular treatment, and FDO patients received dermatologic treatment. RESULTS: Eighty-nine patients were enrolled. Among those that completed the treatment course, 39 presented high ODL. Lower cylindrical sleeve counts were found in low ODL patients (low ODL vs high ODL: 8 vs 14, P = .009). FDO was less prevalent in this group (49% vs 77%, P = .012). The Ocular Surface Disease Index score decreased in patients without FDO (20.0 ± 17.1 to 14.0 ± 16.6, P = .027) after 3 months of topical tea tree oil treatment. Topical ivermectin treatment on the facial skin provided a higher ocular Demodex eradication rate in FDO patients (76% vs 16%, P < .001). CONCLUSION: Concurrence of ocular and facial demodicosis is common, especially in cases of severe ocular demodicosis. Although ocular treatment alone is effective for patients with ocular demodicosis only, cotreatment with topical ivermectin on the facial skin enhances ocular Demodex eradication in patients with comorbid facial Demodex overgrowth.

Higher cumulative dose of topical corticosteroids is associated with osteoporosis and major osteoporotic fracture: A nationwide case-control study.

BACKGROUND: Connections between long-term use of topical corticosteroids (TCSs) of varying potency and osteoporosis and major osteoporotic fracture (MOF) are unclear. Susceptibility to adverse bone effects of TCSs in different sex, age and ethnic groups is unknown too. OBJECTIVES: To demonstrate the association between cumulative dose of TCSs of varying potency and osteoporosis and MOF in Taiwanese population, with stratified analysis of sex and age. METHODS: We conducted a nationwide case-control study and obtained data from Taiwan National Health Insurance Research Database. Cumulative TCS doses in different exposure periods were calculated, and the potency of TCSs was converted to prednisolone equivalent. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for osteoporosis and MOF associated with TCS use. RESULTS: From 2017 to 2020, 129,682 osteoporosis cases and 34,999 MOF cases were selected and randomly matched with 518,728 and 139,996 controls by sex and age. We found clear dose-response relationships between long-term TCS exposure and osteoporosis and MOF. For example, compared to no TCS use, adjusted ORs of osteoporosis were 1.216 (95% CI 1.189-1.243), 1.260 (95% CI, 1.241-1.280) and 1.341 (95% CI, 1.314-1.369) for exposure to low, medium and high cumulative TCS doses, respectively, over 5 years. Adjusted ORs of MOF were 1.118 (95% CI 1.069-1.170), 1.191 (95% CI, 1.156-1.227) and 1.288 (95% CI, 1.238-1.340) for exposure to low, medium and high cumulative TCS doses, respectively, over 5 years. Stratified analysis showed women had higher ORs of osteoporosis and MOF compared to men. Younger people (<50 years) had highest OR of osteoporosis compared to other age groups. CONCLUSIONS: Higher cumulative TCS dose was associated with increased risk of osteoporosis and MOF. Long-term use of TCSs should be cautious, especially in susceptible populations such as women and young people.

Psychosocial Burden of Psoriasis: A Systematic Literature Review of Depression Among Patients with Psoriasis.

Psoriasis is associated with various comorbidities with a notable psychosocial burden. This systematic literature review explores the burden of depression in patients with psoriasis, comparing it with that experienced by patients with other chronic medical conditions. Embase via Ovid, PubMed, and Cochrane Database of Systematic Reviews via Ovid were searched for peer-reviewed studies published in English between January 1, 2016 and December 6, 2021 that reported real-world evidence or observational studies involving at least 100 adults (age ≥ 18 years) with general (unspecified) or plaque psoriasis experiencing symptoms of depression (but not restricted to patients with a clinical diagnosis). Any report of depression or suicidality was eligible for inclusion. Systematic literature reviews reporting depression/suicidality in other chronic medical conditions were also included. Statistical analysis was not performed; the study was descriptive only. A total of 1744 records were identified, and after several defined screenings by two independent reviewers for publication year, relevance, and sample size, 82 publications were included. Psoriasis was significantly associated with depression. The prevalence of depression in patients with psoriasis ranged from 0.2% to 74.6%, with incidence from 4.83 to 91.9 per 1000 person-years. The prevalence of depression was generally higher among patients with more severe psoriasis than those with less severe disease (as determined by Psoriasis Area Severity Index [PASI] scoring system) and was more prevalent among women than men with psoriasis. Depression in psoriasis significantly reduced quality of life, including factors such as sexual dysfunction, sleep difficulties, subjective well-being, and addictions. Comorbid hypertension, hyperlipidemia, psoriatic arthritis, obesity, inflammatory bowel disease, diabetes, and statin use were all associated with increased depression risk in patients with psoriasis. This systematic literature review found that the burden of depression in psoriasis is no lower than in other chronic medical conditions. Greater awareness of the psychological impact of psoriasis would improve care and management, which should incorporate psychological interventions.

Anatomic mapping of acral melanocytic nevi and acral lentiginous melanomas among Taiwanese patients: A retrospective cohort study.

BACKGROUND: The early diagnosis of acral lentiginous melanoma (ALM) contributes to clinical outcomes since ALM can be mistaken for acral melanocytic nevus (AMN). ALM occurrence is reported to correlate with stress-bearing areas, which may assist in differential diagnoses. Our objective is to evaluate the distribution patterns of ALMs and AMNs on the palms and soles among Taiwanese patients. METHODS: A retrospective analysis was performed by reviewing the charts of 1400 patients diagnosed with benign and malignant pigmented lesions confirmed after excisional biopsy at our institution between 2000 and 2022 in Taiwan. Correlations between lesions and clinicopathological factors were analyzed. RESULTS: 309 AMNs and 177 ALMs were included. Mechanical stress was significantly associated with plantar ALMs (weight-bearing area: 92.65 %, arch: 7.35 %, P < 0.001). Significant differences in the distribution patterns were observed for plantar ALMs compared with all AMNs (P < 0.001) and non-atypical AMNs (P < 0.001), but were not observed between palmar AMNs and ALMs. CONCLUSION: Plantar ALMs were most commonly observed on the weight-bearing areas of the soles, distinct from the distribution of all AMNs and of non-atypical AMNs. The distribution features and anatomic mapping of ALMs may facilitate the early clinical diagnosis of ALM.

The genetic evolution of acral melanoma.

Acral melanoma is an aggressive type of melanoma with unknown origins, arising on the sole, palm, or nail apparatus. It is the most common type of melanoma in individuals with dark skin and is notoriously challenging to treat. Our study examined exome sequencing data from 139 tissue samples, spanning different progression stages, collected from 37 patients. We found that 78.4% of the melanomas displayed one or more clustered copy number transitions with focal amplifications, recurring predominantly on chromosomes 5, 11, 12, and 22. These genomic "hailstorms" were typically shared across all progression stages within individual patients. Genetic alterations known to activate TERT also arose early. By contrast, mutations in the MAP-kinase pathway appeared later during progression, often leading to different tumor areas harboring non-overlapping driver mutations. We conclude that the evolutionary trajectories of acral melanomas substantially diverge from those of melanomas on sun-exposed skin, where MAP-kinase pathway activation initiates the neoplastic cascade followed by immortalization later. The punctuated formation of hailstorms, paired with early TERT activation, suggests a unique mutational mechanism underlying the origins of acral melanoma. Our findings highlight an essential role for telomerase, likely in re-stabilizing tumor genomes after hailstorms have initiated the tumors. The marked genetic heterogeneity, in particular of MAP-kinase pathway drivers, may partly explain the limited success of targeted and other therapies in treating this melanoma subtype.

Baseline Demographics, Comorbidities, Treatment Patterns and Burden of Atopic Dermatitis in Adults and Adolescents from the GLOBOSTAD Long-Term Observational Study.

INTRODUCTION: Insights into real-world treatment of atopic dermatitis (AD) are relevant to clinical decision making. The aim of this analysis was to characterize patients who receive dupilumab for AD in a real-world setting. METHODS: The GLOBOSTAD registry is an ongoing, longitudinal, prospective, observational study of patients with AD who receive dupilumab according to country-specific prescribing information. We report baseline characteristics, comorbidities and treatment patterns for patients enrolled from July 11, 2019 to March 31, 2022. Analyses are descriptive; no formal statistical comparisons were performed. RESULTS: Nine hundred fifty-two adults and adolescents were enrolled in GLOBOSTAD. Patients had a high disease burden before starting dupilumab: (mean [standard deviation]) percent body surface area affected (44.8 [24.42]), Eczema Area and Severity Index total score (24.8 [12.95]), SCORing Atopic Dermatitis total score (60.5 [16.34]), Patient-Oriented Eczema Measure total score (19.7 [6.37]) and Dermatology Life Quality Index total score (13.7 [7.02]). Overall, 741 (77.8%) patients reported ≥ 1 type 2 inflammatory comorbidities, most frequently allergic rhinitis (492 [51.7%]), asthma (323 [33.9%]), food allergy (294 [30.9%]) or another allergy (274 [28.8%]). In the previous 12 months, 310 (32.6%) patients had received systemic non-steroidal immunosuppressants and 169 (17.8%) systemic corticosteroids; 449 (47.2%) had received topical corticosteroids, most commonly potent topical corticosteroids; 141 (14.8%) had received topical calcineurin inhibitors and 32 (3.4%) ultraviolet therapy. Most (713 [74.9%]) patients started dupilumab because of prior treatment failure. CONCLUSION: Patients enrolled in GLOBOSTAD demonstrated considerable multidimensional burden of disease across AD signs, symptoms and quality of life despite previous use of systemic and non-systemic AD treatments. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03992417. Video Abstract.

A concept for integrated care pathways for atopic dermatitis-A GA2 LEN ADCARE initiative.

INTRODUCTION: The integrated care pathways for atopic dermatitis (AD-ICPs) aim to bridge the gap between existing AD treatment evidence-based guidelines and expert opinion based on daily practice by offering a structured multidisciplinary plan for patient management of AD. ICPs have the potential to enhance guideline recommendations by combining interventions and aspects from different guidelines, integrating quality assurance, and describing co-ordination of care. Most importantly, patients can enter the ICPs at any level depending on AD severity, resources available in their country, and economic factors such as differences in insurance reimbursement systems. METHODS: The GA2 LEN ADCARE network and partners as well as all stakeholders, abbreviated as the AD-ICPs working group, were involved in the discussion and preparation of the AD ICPs during a series of subgroup workshops and meetings in years 2020 and 2021, after which the document was circulated within all GAL2 EN ADCARE centres. RESULTS: The AD-ICPs outline the diagnostic procedures, possible co-morbidities, different available treatment options including differential approaches for the pediatric population, and the role of the pharmacists and other stakeholders, as well as remaining unmet needs in the management of AD. CONCLUSION: The AD-ICPs provide a multidisciplinary plan for improved diagnosis, treatment, and patient feedback in AD management, as well as addressing critical unmet needs, including improved access to care, training specialists, implementation of educational programs, assessment on the impact of climate change, and fostering a personalised treatment approach. By focusing on these key areas, the initiative aims to pave the way for a brighter future in the management of AD.

Development and Validation of a Novel Score to Predict Mortality in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: CRISTEN.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening, severe mucocutaneous adverse reactions. Severity prediction at early onset is urgently required for treatment. However, previous prediction scores have been based on data of blood tests. OBJECTIVE: This study aimed to present a novel score that predicts mortality in patients with SJS/TEN in the early stages based on only clinical information. METHODS: We retrospectively evaluated 382 patients with SJS/TEN in a development study. A clinical risk score for TEN (CRISTEN) was created according to the association of potential risk factors with death. We calculated the sum of these risk factors using CRISTEN, and this was validated in a multinational survey of 416 patients and was compared with previous scoring systems. RESULTS: The significant risk factors for death in SJS/TEN comprised 10 items, including patients' age of ≥65 years, ≥10% body surface area involvement, the use of antibiotics as culprit drugs, the use of systemic corticosteroid therapy before the onset, and mucosal damage affecting the ocular, buccal, and genital mucosa. Renal impairment, diabetes, cardiovascular disease, malignant neoplasm, and bacterial infection were included as underlying diseases. The CRISTEN model showed good discrimination (area under the curve [AUC] = 0.884) and calibration. In the validation study, the AUC was 0.827, which was statistically comparable to those of previous systems. CONCLUSION: A scoring system based on only clinical information was developed to predict mortality in SJS/TEN and was validated in an independent multinational study. CRISTEN may predict individual survival probabilities and direct the management and therapy of patients with SJS/TEN.

Association Between the Use of Topical Calcineurin Inhibitors and the Risk of Cancer Among Patients with Atopic Dermatitis: A Nationwide, Population-Based, Retrospective Cohort Study.

IMPORTANCE: The cancer risks associated with treatment with topical calcineurin inhibitors (TCIs) in patients with atopic dermatitis (AD) remain controversial, and limited evidence exists regarding the cancer risks among patients with AD treated with TCIs in Asian populations. OBJECTIVES: This study identified the association between TCI use and the risks of developing all cancers, lymphoma, skin cancers, and other cancers. DESIGN: This study was a nationwide, population-based, retrospective cohort study. SETTING: Taiwan's National Health Insurance Research Database. PARTICIPANTS: Patients diagnosed at least twice with ICD-9 code 691 or at least one time with ICD-9 codes 691 or 692.9 within 1 year between 1 January 2003 and 31 December 2010 were included and followed until 31 December 2018. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using the Cox proportional hazard ratio model. EXPOSURES: Patients using tacrolimus or pimecrolimus were identified in the National Health Insurance Research Database and compared with patients using topical corticosteroids (TCSs). MAIN OUTCOMES AND MEASURES: The main outcomes were hazard ratios (HRs) of cancer diagnoses and associated outcomes obtained from the Taiwan Cancer Registry database. RESULTS: After propensity score (PS) matching, the final cohort included 195,925 patients with AD, including 39,185 who were initial TCI users and 156,740 who were TCS users. Propensity score matching was performed according to age, sex, index year, and Charlson Comorbidity Index using a ratio of 1:4. Except for leukemia, HR and 95% CI showed no significant associations between TCI use and the risk of developing all cancer, lymphoma, skin cancers, and other cancers. Sensitivity analysis showed that the lag time HRs for every cancer subtype continued to show no significant association between TCI use and cancer risk, except for leukemia. CONCLUSIONS AND RELEVANCE: Our study found no evidence to support an association between TCI use and the risks of almost all cancers compared with TCS use in patients with AD, but physicians should be aware of potentially higher risks of leukemia with TCI use. This study represents the first population-based study focused on the cancer risk of TCI use among patients with AD in an Asian population.

Cotrimoxazole as a Preventative Intervention for Pneumocystis Pneumonia in Pemphigus Patients Treated with Rituximab: A Retrospective Study.

INTRODUCTION: Pneumocystis jirovecii pneumonia (PJP) is a severe, life-threatening complication in patients treated with rituximab. However, there is no consensus on the primary prophylaxis for it in rituximab-treated pemphigus patients. Therefore, we sought to investigate the prophylactic efficacy and safety profile of cotrimoxazole for reducing the risk of developing PJP in pemphigus patients receiving rituximab. METHODS: This single-center retrospective study investigated 148 pemphigus patients undergoing a first cycle of rituximab between 2008 and 2021 at a tertiary referral center in northern Taiwan. Patients were divided into the prophylaxis group (N = 113) and the control group (N = 35) according to whether or not cotrimoxazole was administered. The primary outcome was the 1-year incidence of PJP in the two groups, while the secondary outcome was the incidence of cotrimoxazole-related adverse events. RESULTS: Of the 148 patients enrolled in this study, three patients, all in the control group, developed PJP during the 1-year follow-up. The incidence of PJP (8.6%) in the control group was significantly higher than that in the prophylaxis group (0%) (p = 0.012). The incidence of cotrimoxazole-related adverse events was 2.7%, and none of the cases were associated with life-threatening conditions. In addition, the cumulative prednisolone dose was associated with a trend of a higher risk of PJP (p = 0.0483). CONCLUSIONS: Prophylactic cotrimoxazole significantly reduces the risk of PJP in a certain high-risk population and has a tolerable safety profile.