Year: 2024
Type: editorial
Abstract: Over the last decade there have been considerable insights on immunotherapy and immunecheckpoint-inhibitor-therapy-induced SJS/TEN as well as novel methods to improve the diagnosis, management, and mortality risk stratification of SJS/TEN, and organ-specific pathology.Chen et al and Kurian et al (6,7) highlight SJS/TEN occurring in association with novel agents: the epidermal growth factor receptor tyrosine kinase inhibitor toripalimab and the αspecific PI3K inhibitor alpelisib. Kuo et al (8) highlight the addition of severe cutaneous immune related adverse events associated with immune checkpoint inhibitors and highlight knowledge and evidence gaps related to diagnosis and treatment. The presentation can vary from SJS mimickers such as lichenoid and autoimmune bullous disorders to presentations more in keeping with traditional SJS/TEN. In their comprehensive 40 year literature review, Wang et al identify the demographics, clinical course, and mortality risk of 379 drug culprits across four common classes associated with SJS/TEN (9).While notable recent advances in SJS/TEN have made risk prediction and prevention possible for some causative factors, many challenges still exist in the scoring and documentation of the severity of SJS/TEN, which has not been standardized to be reproducible across individual cases and treatment centers. This phenotyping is a pre-requisite for engaging in further studies, particularly clinical trials, to assess the efficacy of therapeutics and other interventions. Shareef et al (10) examine the predictive value of a random forests classifier for mortality compared with SCORTEN, the most commonly used mortality risk prediction tool. SCORTEN requires calculation of total body surface area detached, which is subject to considerable observer error and variability. In their model which used only routine laboratory information, the top five predictors of mortality were RBC count, total bilirubin, prothrombin time, WBC count and RBC count.Beyond mortality prediction, however, other novel diagnostic and staging systems include medical photography to monitor progression and treatment response. Dobry et al (11) summarize the state of current clinical assessment and scoring tools and highlight the need for standardized approaches to measure cutaneous involvement. Lehloenya (12) highlights the need for reproducible endpoints in clinical studies and consideration for innovative approaches such as use of biological markers, artificial intelligence, and imaging approaches (e.g. PET/CT scan) to monitor progression and therapeutic response.In adults, > 80% of SJS/TEN is caused by a small molecule drug. SJS/TEN is also marked by tissue specificity. Hence, "blood tests" and ex vivo/in vitro tests to define drug causality have been challenging. Copaescu et al (13) comprehensively review the current state of in vivo and ex vivo/in vitro diagnostic tools of potential use in severe cutaneous adverse drug reactions, including SJS/TEN, to aid diagnosis and drug causality. The sensitivity of both patch testing and in vitro/ex vivo testing in SJS/TEN was dependent on the culprit medication and was lower (<50%) for SJS/TEN than for drug reaction with eosinophilia and systemic (DRESS). Genetic testing has been posited in the past as a screening tool for the prevention of SJS/TEN or DRESS where this is a well-established association. However, when an HLA allele is distinct for a specific medication, genetic testing, along with patch testing and in vitro/ex vivo testing, may also aid in diagnosis.Although there is agreement on harmonized supportive care and comprehensive ophthalmological, cutaneous, and urogynecological management in an acute critical care setting, the long-term effects of acute SJS/TEN and its management on long-term complications are largely unknown. DenAdel et al (14) present a retrospective chart review of 77 biopsy-supported female patients with SJS/TEN treated at a single center. They. were able to measure a positive impact on protocolizing acute management that guided gynecological consultation and appropriate treatment of vulvovaginal disease.Although there has been much progress in SJS/TEN research, many gaps exist. In addition to genetic factors, more study is needed on the social determinants of health that can drive medication utilization and impact risk in disadvantaged populations (15,16). Further study of tissue specific responses will help define markers for earlier diagnosis and targeted treatment. A system that ensures that care does not end at hospital discharge is also crucial to providing necessary medical and psychological support and to prevent and support long-term complications such as visual impairment and blindness (17). Particularly important is documentation and a health "passport" to avoidance exposure to culprit medication(s) and ensure drug safety for the future.
Source: Frontiers in Medicine
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,295
Awards: G2508017656, G265873141, Stevens-Johnson syndrome/toxic epidermal necrolysis 2021: Collaboration, Innovation and Community, Genetic risk and long-term outcomes associated with Drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in survivors, Identification of genetic polymorphisms in Stevens Johnson syndrome and toxic epidermal necrolysis, G6771029017, Immune-mediated adverse drug reactions to HIV and TB treatments in South Africa: predict, prevent and improve long-term outcomes (IMARI SA study), NATIENS: A Phase III Randomized Double Blinded Study to Determine the Mechanisms and Optimal Management of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
OpenAlex ID: W4392552286