Imiquimod-induced bullous pemphigoid: A case report.

A 72-year-old man treated with 3.5% imiquimod cream for scalp actinic keratoses developed the usual crusted and erosive reaction but developed bullae on the scalp, as well as the limbs and torso after several weeks into treatment. Biopsy confirmed bullous pemphigoid. He was treated with clobetasol ointment, prednisone and methotrexate, with eventual disease control. He had a severe disease course. Bullous pemphigoid is usually idiopathic, but can be induced by skin trauma, as well as by several medications; this is the first report of imiquimod as a trigger. Imiquimod is a toll-like receptor 7 agonist that induces cellular apoptosis and recruits pro-inflammatory cytokines including tumour necrosis factor-alpha and interferon-alpha, which have been implicated in autoimmunity. This case highlights an unusual but severe adverse effect from topical imiquimod.

Comparing the Hospital Frailty Risk Score and the Clinical Frailty Scale Among Older Adults With Chronic Obstructive Pulmonary Disease Exacerbation.

Importance: Frailty is associated with severe morbidity and mortality among people with chronic obstructive pulmonary disease (COPD). Interventions such as pulmonary rehabilitation can treat and reverse frailty, yet frailty is not routinely measured in pulmonary clinical practice. It is unclear how population-based administrative data tools to screen for frailty compare with standard bedside assessments in this population. Objective: To determine the agreement between the Hospital Frailty Risk Score (HFRS) and the Clinical Frailty Scale (CFS) among hospitalized individuals with COPD and to determine the sensitivity and specificity of the HFRS (vs CFS) to detect frailty. Design, Setting, and Participants: A cross-sectional study was conducted among hospitalized patients with COPD exacerbation. The study was conducted in the respiratory ward of a single tertiary care academic hospital (The Ottawa Hospital, Ottawa, Ontario, Canada). Participants included consenting adult inpatients who were admitted with a diagnosis of acute COPD exacerbation from December 2016 to June 2019 and who used a clinical care pathway for COPD. There were no specific exclusion criteria. Data analysis was performed in March 2022. Exposure: Degree of frailty measured by the CFS. Main Outcomes and Measures: The HFRS was calculated using hospital administrative data. Primary outcomes were the sensitivity and specificity of the HFRS to detect frail and nonfrail individuals according to CFS assessments of frailty, and the secondary outcome was the optimal probability threshold of the HFRS to discriminate frail and nonfrail individuals. Results: Among 99 patients with COPD exacerbation (mean [SD] age, 70.6 [9.5] years; 56 women [57%]), 14 (14%) were not frail, 33 (33%) were vulnerable, 18 (18%) were mildly frail, and 34 (34%) were moderately to severely frail by the CFS. The HFRS (vs CFS) had a sensitivity of 27% and specificity of 93% to detect frail vs nonfrail individuals. The optimal probability threshold for the HFRS was 1.4 points or higher. The corresponding sensitivity to detect frailty was 69%, and the specificity was 57%. Conclusions and Relevance: In this cross-sectional study, using the population-based HFRS to screen for frailty yielded poor detection of frailty among hospitalized patients with COPD compared with the bedside CFS. These findings suggest that use of the HFRS in this population may result in important missed opportunities to identify and provide early intervention for frailty, such as pulmonary rehabilitation.

Critical appraisal of a mHealth-assisted community-based cardiovascular disease risk screening program in rural Kenya: an operational research study.

Community health workers (CHWs) can participate in the cascade of hypertension and diabetes management in low and middle-income countries (LMICs). Their services may be enhanced with mobile health (mHealth) tools. In this operational research study, we describe the AFYACHAT mHealth-assisted cardiovascular health screening program in rural Kenya. In this study, A CHW screened a convenience sample of adults ≥ 40 years old in rural Kenya for cardiovascular disease (CVD) risk using the two-way AFYACHAT mHealth instrument. AFYACHAT analyzes a patient's age, sex, smoking, diabetes and systolic blood pressure and provides a four-tiered 10-year CVD risk score. User acceptability was assessed by an end-of-study interview with the CWH. Automated error logs were analyzed. Patient satisfaction was measured with a six-question satisfaction questionnaire. Screened participants with high CVD risk were followed-up via telephone to explore any actions taken following screening. In 24 months, one CHW screened 1650 participants using AFYACHAT. The 10-year risk of CVD was <10% for 1611 (98%) patients, 10 to <20% for 26 (1.6%), 20 to <30% in 12 (0.7%), and ≥30% for 1 (0.1%). The point prevalence of hypertension and diabetes was 27% and 1.9%, respectively. Seventy-five percent of participants with elevated CVD risk sought further medical care. There was high acceptability, a 15% miscode error rate, and high participant satisfaction with the screening program. Our operational research outlines how AFYACHAT mHealth tool can assist CHW perform rapid CVD screening; this provides a model framework for non-communicable disease screening in LMICs.

The Role of the TL1A/DR3 Axis in the Activation of Group 2 Innate Lymphoid Cells in Subjects with Eosinophilic Asthma.

Rationale: Group 2 innate lymphoid cells (ILC2s) are critical for type 2 inflammation. In murine models of asthma, some ILC2s remain activated in the absence of epithelial cell-derived cytokine signaling, implicating alternate stimulatory pathways. DR3 (death receptor 3), a member of the tumor necrosis factor receptor superfamily, is expressed on ILC2s. Genome-wide association studies report an association between DR3 ligand, TL1A (tumor necrosis factor-like protein 1A), and chronic inflammatory conditions.Objectives: We investigated the TL1A/DR3 axis in airway ILC2 biology in eosinophilic asthma.Methods: Stable subjects with mild asthma were subject to allergen inhalation challenge, and DR3 expression on sputum cells was assessed. We investigated cytokine regulation of DR3 expression on ILC2s and steroid sensitivity. Airway TL1A was assessed in sputum from subjects with mild asthma and subjects with prednisone-dependent severe eosinophilic asthma.Measurements and Main Results: There was a significant increase in sputum DR3+ ILC2s 24 hours after allergen challenge, and DR3 expression on ILC2s was upregulated by IL-2, IL-33, or TSLP in vitro. Stimulation with TL1A significantly increased IL-5 expression by ILC2s and was attenuated by dexamethasone, an effect that was negated in the presence of TSLP. Airway TL1A levels were increased 24 hours after allergen challenge in subjects with mild asthma but were significantly greater in those with severe eosinophilic asthma. The highest levels were detected in subjects with severe asthma with airway autoimmune responses. C1q+ immune complexes from the sputa of subjects with severe asthma with high autoantibody levels stimulated TL1A production by monocytes.Conclusions: The TL1A/DR3 axis is a costimulator of ILC2s in asthma, particularly in the airways of patients with a predisposition to autoimmune responses.

Atopic March: Collegium Internationale Allergologicum Update 2020.

In recent decades, the worldwide prevalence of allergic disease has increased considerably. The atopic march is a model aimed at explaining the apparent progression of allergic diseases from atopic dermatitis (AD) to allergic asthma (AA) and to allergic rhinitis (AR). It hypothesizes that allergic disease begins, typically in children, with the development of AD, then AA, and finally progresses to AR. This theory has been widely studied in cross-sectional and long-term longitudinal studies and it has been found that as prevalence of AD declines, prevalence of AA increases. A similar relationship is reported between AA and AR. The legitimacy of the atopic march model is, however, currently debated. Epidemiological evidence and criticism of longitudinal studies point to an overstatement of the atopic march's prevalence and incorrect mechanisms, opening a discussion for alternative models to better explain the pathophysiological and epidemiological processes that promote this progression of allergic diseases. Albeit, risk factors for the development and progression of allergic disease, particularly AD, are critical in identifying disease progression. Investigating the role of age, severity, family history, phenotype, and genetic traits may give a better indication into the progression of allergic diseases. In addition, studies following patients from infancy into adulthood and a general increase in longitudinal studies would help broaden the knowledge of allergic disease progression and the atopic march.

The role of type 2 innate lymphoid cells in eosinophilic asthma.

Eosinophilic asthma has conventionally been proposed to be a T helper 2 driven disease but emerging evidence supports a central role of type 2 innate lymphoid cells (ILC2s). These are non-T, non-B cells that lack antigen specificity and produce more IL-5 and IL-13 than CD4+ T lymphocytes, on a cell per cell basis, in vitro. Although it is clear that ILC2s and CD4+ T cells work in concert with each other to drive type 2 immune responses, kinetic studies in allergic asthma suggest that ILC2s may act locally within the airways to "initiate" eosinophilic responses, whereas CD4+ T cells act locally and systemically to "perpetuate" eosinophilic inflammatory responses. Importantly, ILC2s are increased within the airways of severe asthmatics, with the greatest number of IL-5+ IL-13+ ILC2s being detected in sputum from severe asthmatics with uncontrolled eosinophilia despite high-dose steroid therapy. Although the precise relationship between ILC2s and steroid sensitivity in asthma remains unclear, controlling the activation of ILC2s within the airways may provide an effective therapeutic target for eosinophilic inflammation in airways diseases.