Defining D-irAEs: consensus-based disease definitions for the diagnosis of dermatologic adverse events from immune checkpoint inhibitor therapy.

With an increasing number of patients eligible for immune checkpoint inhibitors, the incidence of immune-related adverse events (irAEs) is on the rise. Dermatologic immune-related adverse events (D-irAEs) are the most common and earliest to manifest, often with important downstream consequences for the patient. Current guidelines lack clarity in terms of diagnostic criteria for D-irAEs. The goal of this project is to better define D-irAE for the purposes of identification, diagnosis, and future study of this important group of diseases.The objectives of this project were to develop consensus guidance for an approach to D-irAEs including disease definitions and severity grading. Knowing that consensus among oncologists, dermatologists, and irAE subspecialists would be critical for usability, we formed a Dermatologic irAE Disease Definition Panel. The panel was composed of 34 experts, including oncologists, dermatologists, a rheumatologist, and an allergist/immunologist from 22 institutions across the USA and internationally. A modified Delphi consensus process was used, with two rounds of anonymous ratings by panelists and two virtual meetings to discuss areas of controversy. Panelists rated content for usability, appropriateness, and accuracy on 9-point scales in electronic surveys and provided free text comments. A working group aggregated survey responses and incorporated them into revised definitions. Consensus was based on numeric ratings using the RAND/UCLA Appropriateness Method with prespecified definitions.Following revisions based on panelist feedback, all items received consensus in the second round of ratings. Consensus definitions were achieved for 10 core D-irAE diagnoses: ICI-vitiligo, ICI-lichen planus, ICI-psoriasis, ICI-exanthem, ICI-bullous pemphigoid, ICI-Grover's, ICI-eczematous, ICI-eruptive atypical squamous proliferation, ICI-pruritus without rash, and ICI-erosive mucocutaneous. A standard evaluation for D-irAE was also found to reach consensus, with disease-specific exceptions detailed when necessary. Each disorder's description includes further details on disease subtypes, symptoms, supportive exam findings, and three levels of diagnostic certainty (definite, probable, and possible).These consensus-driven disease definitions standardize D-irAE classification in a useable framework for multiple disciplines and will be the foundation for future work. Given consensus on their accuracy and usability from a representative panel group, we anticipate that they can be used broadly across clinical and research settings.

Perceptions of telehealth among inpatient consultative dermatology providers and practice patterns during COVID-19.

Use of inpatient teledermatology increased during the COVID-19 pandemic. We surveyed the Society for Dermatology Hospitalists to better characterize the impact of COVID-19 on teledermatology use by inpatient dermatology providers, particularly on provider perceptions of teledermatology. Prior to the COVID-19 pandemic, 40% (8/20) of surveyed providers had used telehealth at their institution to help perform inpatient consults, while 90% (18/20) adapted use of teledermatology during the pandemic. 80% (16/20) reported that their opinion of teledermatology changed as a result of the COVID-19 pandemic, with the vast majority (87.5%, 14/16) reporting having a more positive opinion. Benefits of teledermatology included efficiency, ability to increase access safely, and ability for clinicians to focus on complex cases. Some providers expressed concerns over the potential implications regarding the perception of dermatology within medicine, limitations of inadequate photos, and breakdowns in communication with consulting teams and patients. Robust algorithms and or utilization criteria of teledermatology may help to mitigate risk, while increasing access to inpatient dermatologic evaluation.

Association of autoimmune blistering disease, and specifically, pemphigus vulgaris, with cardiovascular disease and its risk factors: a systematic review and meta-analysis.

Previous studies have found conflicting results about the association of autoimmune blistering disease (AIBD) with cardiovascular disease (CVD) risk. The objective of the study was to systematically review the relationship of AIBD, including pemphigus vulgaris (PV), and its treatment with CVD and CVD risk factors. MEDLINE, EMBASE, Cochrane, LILACS, SCOPUS, and Web of Science were searched. We included all studies of CVD and CVD risk factors in AIBD patients. Two reviewers performed title and/or abstract review and data extraction. Pooled random-effects meta-analysis was performed. Forty papers met inclusion criteria. AIBD was associated with higher odds of diabetes (DM) (odds ratio [95% confidence interval]: 1.809 [1.258-2.601]), hypertension (HTN) (1.393 [1.088-1.784]), dyslipidemia (2.177 [1.163-4.073]) and heart failure (1.919 [1.603-2.298]), but was not associated with obesity, stroke, angina, heart attack, or arrhythmia. The pooled random-effects prevalence for treatment-related adverse events (AEs) in AIBD was 13.7% for DM, 10.7% for HTN, and 17.1% for CVD. Sensitivity analysis of high-quality studies revealed similar results. AIBD patients have increased CVD risk factors and heart failure. Systemic corticosteroid treatment results in CVD-related AEs in AIBD. Increased CVD screening and prevention strategies are warranted in AIBD.

Incidence of Cutaneous Adverse Events With Phosphoinositide 3-Kinase Inhibitors as Adjuvant Therapy in Patients With Cancer: A Systematic Review and Meta-analysis.

Importance: The phosphoinositide 3-kinase (PI3K) pathway is among the most frequently activated pathways in human cancers. As the use of PI3K inhibitors for cancer treatment grows, there is increasing need for understanding the cutaneous effects associated with these therapies. Objective: To systematically review the published literature reporting incidence of cutaneous adverse events with PI3K inhibitors and to provide pooled incidence estimates using meta-analysis. Data Sources: This systematic review and meta-analysis was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. The literature search concerned entries through September 2021 in the following sources: PubMed, Cochrane registry, ClinicalTrials.gov, and evidence from the NHS UK and Trip medical database. To analyze PI3K inhibitors' cutaneous adverse events incidence, only randomized clinical trials (RCTs) were considered. The search strategy used the following keywords: (prevalence OR incidence OR epidemiology) and (phosphoinositide 3 kinase inhibitors OR PI3K inhibitors). No language restriction was applied. Analysis was conducted on July 1, 2022. Study Selection: Studies included phase 2 and phase 3 RCTs that reported incidence of cutaneous adverse events associated with use of PI3K inhibitors. Data Extraction and Measures: Data extracted included sex, medication name and class, sample size, rash incidence, and grade. The bias risk was assessed by the Cochrane tool for risk of bias assessment in RCTs. Main Outcomes and Measures: The primary outcome was incidence of PI3K inhibitor cutaneous adverse events (with 95% CIs) among the overall population and among subgroups. Between-study heterogeneity was assessed using the I2 statistic. Results: The analysis found the incidence of PI3K inhibitor cutaneous events of any grade to be 29.30% in the intervention group, translating to a pooled odds ratio (OR) for incidence of cutaneous adverse events of any grades of 2.55 (95% CI, 1.74-3.75). Incidence of severe grade (grade ≥3) of rash in the intervention group was estimated to be 6.95%, yielding a pooled Peto OR of 4.64 (95% CI, 2.70-7.97). Subgroup analyses revealed that the incidence of severe cutaneous adverse events (grade ≥3) was higher with the use of Pan-class-1 PI3K inhibitors (OR, 6.67; 95% CI, 4.28-10.38) than isoform-selective PI3K inhibitors (OR, 6.37; 95% CI, 3.25-12.48). Conclusions and Relevance: This systematic review and meta-analysis identified an overall incidence of PI3K inhibitor cutaneous adverse events of any grade to be 29.30% with a pooled OR of 2.55; (95% CI, 1.74-3.75). These findings clarify the risk of cutaneous adverse events associated with this important class of anticancer therapies.

Mycobacterium mucogenicum skin and soft tissue infection of the breast mimicking idiopathic granulomatous mastitis.

We present a case of a 28-year-old woman who came to medical attention after noticing a breast mass associated with an overlying eroded plaque of the skin. A core biopsy of the breast mass was negative for malignancy but demonstrated granulomatous inflammatory changes. Acid-fast bacilli and Gomori methenamine-silver stains were negative for microorganisms. The patient was diagnosed with presumptive idiopathic granulomatous mastitis and started on oral steroids. Her symptoms progressed. Tissue culture from a repeat biopsy grew Mycobacterium mucogenicum The patient responded well to combination oral antimicrobial therapy.

Vulvar Majocchi granuloma and kerion formation in an immunocompetent female.

We report a rare case of vulvar Majocchi granuloma and kerion formation secondary to Trichophyton in an immunocompetent woman. The patient responded well to oral terbinafine and a short course of oral corticosteroids with a slow taper. Resolution of deep dermatophytosis requires prompt pathogen identification and treatment to avoid scarring and hair loss. Herein, we aim to increase clinical awareness and early recognition of this atypical presentation of a Majocchi granuloma with kerion formation.

Cutaneous Involvement in a Case of Intravascular T-Cell Lymphoma With a γδ Phenotype.

Intravascular lymphomas (IVL) are uncommon variants of extranodal non-Hodgkin which are usually difficult to diagnose because of their lack of clinical uniformity. Most cases are of B-cell differentiation followed by natural killer/T-cell differentiation and underlying CD30 lymphoproliferative conditions. Epstein-Barr virus is pathogenically related in most of the natural killer/T-cell variants, and the skin is a common site of presentation noted in approximately 40% of cases. Recently, cases with uncommon phenotypes have been described, expanding our understanding of the pathogenesis of this condition. In this report, we describe a 67-year-old man with a 3-month history of constitutional symptoms associated with linear purpuric macules on the trunk, pancytopenia, and high levels of serum lactate dehydrogenase. He had been followed for longstanding adenopathy and hepatosplenomegaly. Skin biopsy demonstrated a intravascular lymphocytic proliferation with positivity for CD3, CD2, CD5, and γδ T-cell receptor marker; in situ hybridization Epstein-Barr virus RNA was negative. The patient was subsequently treated with chemotherapy and allogenic stem cell transplant. He remains in complete remission 6 months posttransplant. Although the presence of hepatosplenomegaly led to consideration of a hepatosplenic T-cell lymphoma, it was pre-existing for several years making the diagnosis doubtful. To our knowledge, this is the first case report of an IVL γδ T-cell lymphoma.

Decreased respiratory quotient in relation to resting energy expenditure in HIV-infected and noninfected subjects.

The purpose of this study was to evaluate the relationship of respiratory quotient (RQ), a surrogate marker of substrate oxidation, as well as body composition and dietary intake to resting energy expenditure (REE) among HIV-infected patients in the current era of highly active antiretroviral therapy and among non-HIV-infected control subjects. Resting energy expenditure is increased in HIV-infected patients; but little is known regarding the potential contribution of altered substrate metabolism, body composition, and dietary intake to increased energy expenditure in this population. Respiratory quotient, REE, body composition, and dietary intake parameters were assessed in 283 HIV-infected patients and 146 community-derived HIV-negative controls who were evaluated for metabolic studies between 1998 and 2005. Respiratory quotient was lower (0.83 +/- 0.00 vs 0.85 +/- 0.01, P = .005), whereas REE adjusted for fat-free mass (FFM) was higher (31.8 +/- 0.3 vs 29.8 +/- 0.3 kcal/[d kg], P < or = .0001), in HIV-infected compared with control subjects. In multivariate modeling among HIV-infected patients, including age, sex, and parameters of immune function, FFM (beta = 24.811334, P < .0001), visceral adiposity (beta = .7182746, P = .008), and total body fat (beta = 8.0506839, P = .041) were positively associated with REE, whereas RQ was negatively associated with REE (beta = -528.4808, P = .024). Overall r(2) was equal to 0.705 and P was less than .0001 for the model. In control subjects, by contrast, only visceral adiposity (beta = 1.0612073, P = .004), total body fat (beta = 15.805547, P = .010), and FFM (beta = 22.613005, P < .0001) were significant predictors of REE; and there was no relationship with RQ. Overall r(2) was equal to 0.825 and P was less than .0001 for the model. These data suggest that alterations in substrate metabolism may contribute to increased REE in HIV-infected patients compared with control subjects.