Photodistributed Stevens-Johnson syndrome and toxic epidermal necrolysis: a systematic review and proposal for a new diagnostic classification

Abstract

Background: Ultraviolet radiation (UVR) exposure is commonly reported as a risk factor for Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, minimal evaluation of photo-induced SJS/TEN has been conducted. Thus, this review identifies all cases of SJS/TEN that are linked to an acute exposure of UVR and outlines the unifying characteristics of these cases. Furthermore, the theoretical pathogenesis, differential diagnoses, and proposed diagnostic criteria are defined.

Methods: PubMed, Google Scholar, and other databases and websites were searched from inception to September 2021 to identify studies that met inclusion criteria. The following keywords were utilized: "Stevens-Johnson syndrome" and "toxic epidermal necrolysis" with "ultraviolet," "photodistributed," "photo-induced," "photosensitivity," and "photo." One reviewer assessed study characteristics, with confirmation by a second. The risk of bias was assessed independently by another.

Results: Thirteen patient cases were identified, all reporting ultraviolet radiation prior to rash onset and an underlying causal drug. Case classifications included 7/13 SJS and 6/13 TEN. All cases described the rash as photodistributed with UVR exposure prior to rash onset (delay of 1-3 days) and a causal drug. 10 cases provided evidence that the photodistributed rash lacked linear demarcation (as in a sunburn) with satellite target-like lesions. No cases described a flu-like prodrome.

Discussion: Mucositis, palmar and plantar rash, a positive Nikolsky sign, and a prolonged disease course can help distinguish from photosensitive reactions, while a negative direct immunofluorescence test is important to distinguish from other photo-induced disorders.

Conclusion: Physicians should be aware that UVR may precipitate SJS/TEN in patients taking susceptible drugs. After a 24-h delay from UVR exposure, a non-distinct, photodistributed rash appears with no flu-like prodrome and progresses for at least 48 h to include vesiculobullous eruptions and mucous membrane involvement. Photodistributed SJS/TEN appears to be photo-drug-induced with a unique onset and rash presentation that should be recognized as a distinct diagnosis.

Keywords: Photo induced; Photodistributed; Photosensitivity; Stevens–Johnson syndrome; Sun; Systematic Review; Toxic epidermal necrolysis; Ultraviolet.

Fig. 1

Study Selection Process to Identify Cases of Photodistributed Steven’s–Johnson Syndrome and Toxic Epidermal Necrolysis. a Focused searches were first looked at before broader results. As focused results found fewer and no unique articles to be included in the study, only broader results were computed in the analysis. b Additional registers/repositories searched: National Technical Information Service (NTIS), Social Science Research Network (SSRN), ClinicalTrials.org, Sigma Repository. c Searches that produced > 150 results, the first 150 were screened for inclusion and others removed. d USA.org did not report total results for each search, but first 150 results of each search were screened (those with > 150). TRIP  TRIP medical database. OAIster OAIster: Find the Pearls, NYAGLR   New York Academy of Medicine Grey Literature Report, SJS   Steven’s–Johnson syndrome, TEN  Toxic epidermal necrolysis, BASE   Bielefeld Academic Search Engine, Grey Matters   Grey Matters: a practical search tool for health-related grey literature, MCRP  Medicine Case Reports and Protocols, UVR   Ultraviolet radiation. Table modified from: Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71. https://doi.org/10.1136/bmj.n71

Fig. 2

Rash in photodistributed Steven’s–Johnson Syndrome and Toxic Epidermal Necrolysis [32, 35, 38]. All three images were obtained from cases in this review and demonstrate a photodistributed pattern with the sparing of skin covered by bikini swimsuits. The rash distribution is less demarcated (solid arrows) without sharp lines as is observed in a common sunburn, and with satellite lesions (dotted arrows) that are target-like and isolated from the rest of the rash in areas where the swimsuit covered the skin during the UVR exposure. The images were from patient cases of a Steven’s–Johnson syndrome from 10 days of ciprofloxacin and sun exposure at the beach [35], b toxic epidermal necrolysis from 3 years of hydroxychloroquine and sun exposure on a cruise [32], and c toxic epidermal necrolysis from 10 days of lamotrigine and tanning bed exposure [38]