Acute chest syndrome (ACS) is a significant cause of morbidity and mortality in sickle cell disease (SCD), but preventive, diagnostic, and therapeutic options are limited. Further, ACS and acute vasoccclusive pain crises (VOC) have overlapping features, which causes diagnostic dilemmas. We explored changes in gene expression profiles among patients with SCD hospitalized for VOC and ACS episodes to better understand ACS disease pathogenesis. Whole blood RNA-Seq was performed for 20 samples from children with SCD at baseline and during a hospitalization for either an ACS (n = 10) or a VOC episode (n = 10). Respiratory viruses were identified from nasopharyngeal swabs. Functional gene analyses were performed using modular repertoires, IPA, Gene Ontology, and NetworkAnalyst 3.0. The VOC group had a numerically higher percentage of female, older, and hemoglobin SS participants compared to the ACS group. Viruses were detected in 50% of ACS cases and 20% of VOC cases. We identified 3004 transcripts that were differentially expressed during ACS episodes, and 1802 transcripts during VOC episodes. Top canonical pathways during ACS episodes were related to interferon signaling, neuro-inflammation, pattern recognition receptors, and macrophages. Top canonical pathways in patients with VOC included IL-10 signaling, iNOS signaling, IL-6 signaling, and B cell signaling. Several genes related to antimicrobial function were down-regulated during ACS compared to VOC. Gene enrichment nodal interactions demonstrated significantly altered pathways during ACS and VOC. A complex network of changes in innate and adaptive immune gene expression were identified during both ACS and VOC episodes. These results provide unique insights into changes during acute events in children with SCD.
With advances in drug development and our understanding of the pathophysiology of skin disease, biologic medications have emerged as powerful management tools for dermatologists. While biologics have most often been used in the management of psoriasis, they are being used off-label for the management of a variety of other immune-mediated skin diseases with overlapping molecular targets. This narrative review focuses on the novel and off-label use of biologic medications for the management of hidradenitis suppurativa (HS), pyoderma gangrenosum (PG), lichen planus (LP), and seborrheic dermatitis (SD). Review of the literature revealed that IL-17, IL-23, and tumor necrosis factor (TNF) inhibitors were being used across a variety of immune-mediated skin pathologies with variable efficacy, among other targeted biologics. While biologics were generally safe in the treatment of primary immune-mediated skin disorders, paradoxical disease eruptions were noted with biologic use and were theorized to occur owing to immune dysregulation and cytokine imbalance. While numerous case reports show promise for the use of biologics in immune-mediated skin pathologies, the variable efficacy and safety reported warrants more thorough investigations of the role of these targeted medications in comprehensive disease management.
The original version of this Article contained a typographical error in the spelling of the author Asuncion Mejias which was incorrectly given as M. Asuncion Mejias.
e13083 Background: The synergistic effects of novel combined cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) and endocrine therapy has increased their utilization for treatment of metastatic breast cancer. When compared to endocrine monotherapy, CDK4/6i may increase the risk of alopecia by nearly two-fold (Eiger D, et al. PMID: 32167397; Chan D, et al. J Clin Oncol.). The prevalence of this adverse effect underscores the importance of characterizing CDK4/6i-induced alopecia (CDKIA) and investigating therapeutic options. Methods: A retrospective cohort of 28 female patients with breast cancer and endocrine-induced alopecia (EIA) or CDKIA. Onset of alopecia was measured by time (months) between initiation of anticancer therapy and dermatology referral. Therapeutic response to minoxidil (LDOM or topical [5%] solution or foam) was assessed by both Dean Scale and qualitative clinical improvement by comparison of pre-treatment and post-treatment clinical images by 2 board certified academic dermatologists (ST and BD). Results: Androgenetic alopecia was the most common hair loss distribution (n=27, 96.4%), with CDKIA patients having preferential vertex involvement (n=7 [70.0%] CDKIA vs. n=4 [36.4%] EIA; p=0.04). Patients on CDK4/6i had shorter times to dermatology referral (mean time [months]: 44.6±37.1 for EIA vs. 9.4±13.7 CDKIA; p=0.003). After 16-24 weeks of minoxidil, moderate to significant improvement of alopecia occurred in 80% of CDKIA patients versus 94.4% of EIA patients. Despite similar baseline alopecia grade severity, significant improvement was only observed in EIA patients (mean pretreatment Dean Score – post-treatment Dean Score: -0.44; p=0.0002). Conclusions: Compared to EIA, the onset of CDKIA happened more rapidly and was more resistant to minoxidil. The preferential vertex involvement observed among patients with CDKIA may suggest combination therapy with topical or oral minoxidil and topical anti-androgens may lead to more favorable outcomes. Prompt dermatology referral should be considered for patients treated with CDK4/6i + ET. [Table: see text]
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