ABSTRACT
Raynaud's phenomenon (RP) is a medical condition characterized by vasospasm of the digital vessels in the fingers and toes. The prevalence of RP in the general population is estimated at 3-5% and can vary based on climate. It is classified into primary and secondary RP based on causality. RP has been reported in some cases diagnosed with coronavirus disease 2019 (COVID-19) infection. We report the case of a 14-year-old Caucasian female who presented during the pandemic with chief complaints of suicidal ideations and attempted suicide and had a history of attention-deficit hyperactivity disorder (ADHD) and persistent RP after a stimulant trial. After an initial failure of treatment with lisdexamfetamine, she was switched to methylphenidate hydrochloride (MPH). Within two months of starting MPH, the patient noticed skin discoloration of the lower legs and feet along with numbness. The discoloration of skin was mainly limited to her feet and gradually moved up her legs. She was advised to discontinue the MPH, but her symptoms persisted for four more months until her admission. Other etiologies were ruled out by multi-specialties and during her hospitalization. She was started on atomoxetine and buspirone with appropriate dose titration. Post-discharge from the hospital, no improvement was observed in the patient's RP at an outpatient follow-up performed within a month. The development of RP following MPH treatment and its persistence after stopping MPH is a fascinating event. Clinicians should be aware of the potential rare side effects of stimulants and stimulant-like medications, including vascular, hematological, and dermatological effects. Adolescents with ADHD may be particularly distressed by the COVID-19 pandemic and display increased behavioral issues. Stress can be a trigger for RP; therefore, minimizing stress in at-risk patients is essential.
ABSTRACT
Background: We hypothesized that the addition of receptor tyrosine kinase inhibitors (RTKis, e.g., lapatinib, erlotinib, cetuximab, bevacizumab, panitumumab) to radiotherapy-based treatment for solid tumors does not increase overall survival but may increase toxicity. Methods: Population, Intervention, Control, Outcome, Study Design; Preferred Reporting Items for Systematic Reviews and Meta-Analyses; and Meta-analysis of Observational Studies in Epidemiology methods were used to identify prospective randomized studies including patients with solid tumor cancers treated with radiotherapy with or without RTKis. Extracted variables included use of radiotherapy vs chemoradiotherapy, RTKi type (antibody vs small molecule), outcomes, and toxicities. The primary endpoint was overall survival; the secondary endpoint was grade 3+ toxicity. Random-effects meta-analyses were performed for each outcome measure. All statistical tests were 2-sided. Results: A total of 405 studies met the initial search criteria, of which 13 prospective randomized trials of radiotherapy with or without RTKi met the inclusion criteria, encompassing 5678 patients. The trials included cancers of the head and neck (6 trials, 3295 patients), esophagus (3 trials, 762 patients), lung (2 trials, 550 patients), and brain (2 trials, 1542 patients). Three studies evaluated a small molecule and radiotherapy in 949 patients, and 10 studies evaluated antibodies and radiotherapy in 4729 patients. The addition of RTKis to radiotherapy-based treatment did not improve overall survival (hazard ratio = 1.02, 95% confidence interval = 0.90 to 1.15, P = .76) but increased grade 3+ toxicity (relative risk = 1.18, 95% confidence interval = 1.06 to 1.33, P = .009). Conclusions: The addition of RTKis to radiotherapy does not improve survival and worsens toxicity.
