Worsening Rash in a Patient With Metastatic Breast Cancer.

A 56-year-old woman with metastatic hormone receptor­positive, ERBB2-negative breast cancer presents with pruritic, erythematous, scaly macules and papules on her forearms, faces, chest, and upper back. What is your diagnosis?

Development of an artificial intelligence algorithm for the diagnosis of infantile hemangiomas.

Prompt and accurate diagnosis of infantile hemangiomas is essential to prevent potential complications. This can be difficult due to high rates of misdiagnosis and poor access to pediatric dermatologists. In this study, we trained an artificial intelligence algorithm to diagnose infantile hemangiomas based on clinical images. Our algorithm achieved a 91.7% overall accuracy in the diagnosis of facial infantile hemangiomas.

Conservation of Epithelial-to-Mesenchymal Transition Process in Neural Crest Cells and Metastatic Cancer.

Epithelial to mesenchymal transition (EMT) is a highly conserved cellular process in several species, from worms to humans. EMT plays a fundamental role in early embryogenesis, wound healing, and cancer metastasis. For neural crest cell (NCC) development, EMT typically results in forming a migratory and potent cell population that generates a wide variety of cell and tissue, including cartilage, bone, connective tissue, endocrine cells, neurons, and glia amongst many others. The degree of conservation between the signaling pathways that regulate EMT during development and metastatic cancer (MC) has not been fully established, despite ample studies. This systematic review and meta-analysis dissects the major signaling pathways involved in EMT of NCC development and MC to unravel the similarities and differences. While the FGF, TGFß/BMP, SHH, and NOTCH pathways have been rigorously investigated in both systems, the EGF, IGF, HIPPO, Factor Receptor Superfamily, and their intracellular signaling cascades need to be the focus of future NCC studies. In general, meta-analyses of the associated signaling pathways show a significant number of overlapping genes (particularly ligands, transcription regulators, and targeted cadherins) involved in each signaling pathway of both systems without stratification by body segments and cancer type. Lack of stratification makes it difficult to meaningfully evaluate the intracellular downstream effectors of each signaling pathway. Finally, pediatric neuroblastoma and melanoma are NCC-derived malignancies, which emphasize the importance of uncovering the EMT events that convert NCC into treatment-resistant malignant cells.

Targeted Inhibition of the Epidermal Growth Factor Receptor and Mammalian Target of Rapamycin Signaling Pathways in Olmsted Syndrome.

Importance: Olmsted syndrome is a rare and disabling genodermatosis for which no successful treatment is currently available. Objective: To evaluate the clinical response to the mammalian target of rapamycin (mTOR) inhibitor sirolimus and/or the epidermal growth factor receptor (EGFR) inhibitor erlotinib among patients with Olmsted syndrome. Design, Setting, and Participants: This case series focused on 4 children with treatment-refractory Olmsted syndrome. These children received treatments (initiated in 2017 and 2018) at the outpatient dermatology clinic at the Children's Hospital of Wisconsin in Milwaukee, Wisconsin; Children's National Hospital in Washington, DC; and Hospital Infantil Pequeno Príncipe, Curitiba in Paraná, Brazil. Exposures: Immunohistochemical analyses for mTOR and EGFR activation were performed on skin biopsy specimens from 2 patients. Oral sirolimus was administered to these 2 patients at a dosage of 0.8 mg/m2 twice daily, titrated to a goal trough whole-blood concentration of 10 to 15 ng/mL. Erlotinib was administered to all 4 patients at a dosage of 2 mg/kg/d. Main Outcomes and Measures: Clinical responses were assessed with visual analog scales for pruritus and pain and/or the Children's Dermatology Life Quality Index. Adverse effects were monitored throughout treatment. Results: Four patients (mean [SD] age, 7 [6] years; 2 boys and 2 girls) were analyzed. Lesional skin immunostaining showed increased phosphorylated ribosomal protein S6 (RPS6) and phosphorylated EGFR staining in the epidermis, indicating enhanced mTOR and EGFR signaling activation. Patients 1 and 2 were initially treated with sirolimus, displaying substantial clinical improvement in erythema and periorificial hyperkeratosis afterward. When switched to erlotinib, these patients showed substantial palmoplantar keratoderma (PPK) improvement. Patients 3 and 4 were treated with erlotinib only and later showed rapid and near complete resolution of PPK and substantial improvement in Children's Dermatology Life Quality Index scores. All 4 patients had sustained improvements in pruritus and pain. No severe adverse effects were reported. Conclusions and Relevance: This study's findings suggest that the EGFR-mTOR cascade may play a substantial role in the pathophysiological process of Olmsted syndrome and may serve as a major therapeutic target. Oral sirolimus and erlotinib may be a promising, life-altering treatment for pediatric patients with Olmsted syndrome.

Association of atopic dermatitis with being overweight and obese: a systematic review and metaanalysis.

BACKGROUND: Previous studies found conflicting results about whether atopic dermatitis (AD) is associated with overweight/obesity. OBJECTIVE: We sought to examine the relationship between AD and overweight/obesity by performing a systematic review and metaanalysis. METHODS: Observational studies of the relationship between AD and overweight/obesity were selected from PubMed, Embase, and the Cochrane Library. The quality of evidence was assessed using the Newcastle-Ottawa Scale. Fixed and random effects metaanalyses were performed to estimate pooled odds ratios (ORs). Sensitivity analyses were performed that compared results by location of study, study quality, and between studies in children and adults. RESULTS: In total, 30 studies were included for review. Patients who were overweight (Cochrane-Mantel-Haenszel [CMH] OR, 1.27 [95% confidence interval {CI}: 1.19-1.36]; random effects OR, 1.23 [95% CI: 1.11-1.41]), obese (CMH OR, 1.68 [95% CI: 1.54-1.84]; random effects OR, 1.47 [95% CI: 1.21-1.79]), or overweight/obese (CMH OR, 1.42 [95% CI: 1.34-1.50]; random effects OR, 1.31 [95% CI: 1.16-1.48]) had higher odds of AD than normal weight patients. In sensitivity analyses, children who were overweight (random effects OR, 1.24 [95% CI: 1.08-1.43]), obese (random effects OR, 1.44 [95% CI: 1.12-1.86]), or overweight/obese (random effects OR, 1.32 [95% CI: 1.15-1.51]) and adults who were obese (random effects OR, 1.56 [95% CI: 1.24-1.95]) or overweight/obese (random effects OR, 1.29 [95% CI: 1.05-1.59]) had higher odds of AD. The association remained significant in North America and Asia but not Europe. LIMITATIONS: Most studies were cross-sectional. CONCLUSIONS: Overweight/obesity in North America and Asia is associated with an increased prevalence of AD.