{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:22:06Z","timestamp":1768569726435,"version":"3.49.0"},"posted":{"date-parts":[[2025,8,24]]},"group-title":"Dermatology","reference-count":30,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,8,24]],"date-time":"2025-08-24T00:00:00Z","timestamp":1755993600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,8,24]]},"abstract":"<jats:sec>\n                  <jats:title>Importance<\/jats:title>\n                  <jats:p>\n                    <jats:bold>S<\/jats:bold>\n                    easonal variation in adverse drug reactions has clinical and mechanistic implications for understanding disease mechanisms and risk mitigation strategies. Stevens-Johnson Syndrome\/Toxic Epidermal Necrolysis (SJS\/TEN) is a life-threatening mucocutaneous reaction with high morbidity and mortality, which may have a seasonal component.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To determine whether the reporting of SJS\/TEN to the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) follows a seasonal pattern, incorporating both traditional seasonal analyses and time-series modeling.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Cross-sectional, population-based analysis of FAERS reports from January 2010 to December 2019. Seasonal differences were assessed using Kruskal-Wallis tests and Seasonal-Trend Decomposition using Loess (STL). Seasonal autoregressive integrated moving average (SARIMA) models were used to counterfactually forecast SJS\/TEN and comparator conditions during the COVID-19 pandemic, assessing changes in reporting.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Setting<\/jats:title>\n                  <jats:p>Population-based analysis of spontaneous adverse event reports submitted to FAERS.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Participants<\/jats:title>\n                  <jats:p>All deduplicated FAERS reports with complete event dates from 2010 to 2019 were included. SJS\/TEN cases were identified using standardized MedDRA terms. Comparator analyses of known seasonal conditions \u2013 photosensitivity reactions, influenza, and respiratory syncytial virus (RSV) \u2013 served as positive controls.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Exposures<\/jats:title>\n                  <jats:p>Drug exposures as recorded in FAERS.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Main Outcomes and Measures<\/jats:title>\n                  <jats:p>The primary outcome was the monthly and seasonal proportion of unique SJS\/TEN reports, normalized using all FAERS reports during a particular interval as the denominator. Seasonality strength was quantified from STL decomposition (range 0-1). SARIMA models were applied to pre-COVID data to counterfactually forecast trends from March 2020 to December 2023. Forecast accuracy was evaluated using mean squared error (MSE), root mean squared error (RMSE), and residual diagnostics.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Among 5,900 SJS\/TEN cases reported from 2010-2019, no significant monthly or seasonal variation was detected (p &gt; 0.05), and seasonality strength was low (0.163). Positive controls (influenza, RSV, photosensitivity) showed expected strong seasonality. SARIMA forecasts indicated a mild increase in SJS\/TEN reporting during the pandemic, compared to its previous declining trend. Influenza and RSV dropped below predictions during the pandemic, while photosensitivity remained relatively consistent.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions and Relevance<\/jats:title>\n                  <jats:p>SJS\/TEN reporting to FAERS does not exhibit apparent seasonality, in contrast to positive controls. Time-series modeling confirmed these findings and highlighted the relative stability of SJS\/TEN reporting during the pandemic compared to respiratory viruses.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.08.20.25331677","type":"posted-content","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:15:14Z","timestamp":1756080914000},"source":"Crossref","is-referenced-by-count":0,"title":["Seasonality and Trends in Stevens-Johnson Syndrome\/Toxic Epidermal Necrolysis Before and During the COVID-19 Pandemic: A Pharmacovigilance Study"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8715-1378","authenticated-orcid":false,"given":"Eric Milan","family":"Mukherjee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dodie","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7589-9127","authenticated-orcid":false,"given":"Matthew S.","family":"Krantz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1888-4188","authenticated-orcid":false,"suffix":"Jr.","given":"Cosby A.","family":"Stone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1526-9569","authenticated-orcid":false,"given":"Michelle","family":"Martin-Pozo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7623-3383","authenticated-orcid":false,"given":"Elizabeth","family":"Phillips","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025082614000557000_2025.08.20.25331677v1.1","doi-asserted-by":"publisher","DOI":"10.1007\/s40257-024-00889-6"},{"key":"2025082614000557000_2025.08.20.25331677v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2018.04.027"},{"key":"2025082614000557000_2025.08.20.25331677v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2022.12.005"},{"key":"2025082614000557000_2025.08.20.25331677v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2024.09.045"},{"key":"2025082614000557000_2025.08.20.25331677v1.5","doi-asserted-by":"publisher","DOI":"10.1007\/s40801-016-0081-6"},{"key":"2025082614000557000_2025.08.20.25331677v1.6","doi-asserted-by":"publisher","DOI":"10.1007\/s40257-025-00924-0"},{"key":"2025082614000557000_2025.08.20.25331677v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2009.08.036"},{"key":"2025082614000557000_2025.08.20.25331677v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2008.11.884"},{"key":"2025082614000557000_2025.08.20.25331677v1.9","doi-asserted-by":"publisher","DOI":"10.4103\/idoj.idoj_510_21"},{"key":"2025082614000557000_2025.08.20.25331677v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.burns.2023.08.003"},{"key":"2025082614000557000_2025.08.20.25331677v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.burns.2023.06.016"},{"key":"2025082614000557000_2025.08.20.25331677v1.12","doi-asserted-by":"publisher","DOI":"10.1155\/2024\/2131098"},{"key":"2025082614000557000_2025.08.20.25331677v1.13","doi-asserted-by":"publisher","DOI":"10.3390\/v15010223"},{"key":"2025082614000557000_2025.08.20.25331677v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2024.106944"},{"key":"2025082614000557000_2025.08.20.25331677v1.15","doi-asserted-by":"publisher","DOI":"10.1101\/2025.03.05.25323441"},{"key":"2025082614000557000_2025.08.20.25331677v1.16","doi-asserted-by":"publisher","DOI":"10.2147\/CCID.S422928"},{"key":"2025082614000557000_2025.08.20.25331677v1.17","unstructured":"Hyndman RJ , Athanasopoulos G. Forecasting: Principles and Practice. Otexts; 2021."},{"key":"2025082614000557000_2025.08.20.25331677v1.18","doi-asserted-by":"publisher","DOI":"10.1007\/s10618-005-0039-x"},{"key":"2025082614000557000_2025.08.20.25331677v1.19","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2020.34273"},{"key":"2025082614000557000_2025.08.20.25331677v1.20","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.16642"},{"key":"2025082614000557000_2025.08.20.25331677v1.21","unstructured":"WHO Director-General\u2019s opening remarks at the media briefing on COVID-19 - 11 March 2020. Accessed July 14, 2025. https:\/\/www.who.int\/director-general\/speeches\/detail\/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19-11-march-2020"},{"key":"2025082614000557000_2025.08.20.25331677v1.22","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-022-00807-9"},{"key":"2025082614000557000_2025.08.20.25331677v1.23","doi-asserted-by":"publisher","DOI":"10.1080\/028418500127345532"},{"key":"2025082614000557000_2025.08.20.25331677v1.24","doi-asserted-by":"publisher","DOI":"10.1111\/ctr.14852"},{"key":"2025082614000557000_2025.08.20.25331677v1.25","doi-asserted-by":"publisher","DOI":"10.1111\/1346-8138.17692"},{"key":"2025082614000557000_2025.08.20.25331677v1.26","doi-asserted-by":"publisher","DOI":"10.3390\/jpm11050383"},{"key":"2025082614000557000_2025.08.20.25331677v1.27","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.588063"},{"key":"2025082614000557000_2025.08.20.25331677v1.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2024.02.029"},{"key":"2025082614000557000_2025.08.20.25331677v1.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.burns.2023.08.004"},{"key":"2025082614000557000_2025.08.20.25331677v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2025.02.006"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.08.20.25331677","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:43:50Z","timestamp":1768509830000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2025.08.20.25331677"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,24]]},"references-count":30,"URL":"https:\/\/doi.org\/10.1101\/2025.08.20.25331677","relation":{},"subject":[],"published":{"date-parts":[[2025,8,24]]},"subtype":"preprint"}}