The challenges of SJS/TEN in Black and Brown skin
Lack of representation in early medication trials and genetic associations raise the risk of deadly complications (1,100 words, 5.5 minutes)
Severe reactions to medications, such as Stevens-Johnson Syndrome (SJS) or Toxic Epidermal Necrolysis (TEN), can be fatal but are thankfully rare. However, in the July 17 episode of the Skin Spectrum Summit's Summer of Dialogue podcast on dermatology concerns among patients with Brown and Black skin, Dr. Neil Shear and Dr. Bruce Carleton describe factors that may put patients with skin of colour at a higher risk.
When discussing the risk of rare adverse reactions to medication, an important consideration is that for many of the workhorse medications in use today, patients with Black and Brown skin were not included in the clinical trials, said Dr. Carleton.
“Many of these drugs were approved in the 1960s and ‘70s, from [trials conducted in] very large countries such as the United States and Canada. [The populations of those nations] are [now], in fact, different, genetically than they were in those previous decades,” he said. “We have larger numbers of immigrants from other countries now than we had before. So the makeup of patients compared to those originally used to support the licensing of a product has changed. Consequently, as immigrants from other countries move here, they marry others, and the ancestral diversity increases even further.”
Dr. Carleton is a clinician-scientist at the University of British Columbia and director of the pharmaceutical outcomes program at B.C. Children's Hospital, Vancouver.
The long-time head of dermatology at the Sunnybrook Health Sciences Centre in Toronto, Dr. Neil Shear, is Professor Emeritus at the University of Toronto.
The difference in risk of SJS or TEN in some ethnodemographic populations can be quite large, Dr. Carleton noted.
He said that Taipei-based researcher Dr. Wen-Hung Chung had identified a genetic variant in Southeast Asians that raised the risk for developing SJS in patients who had been treated with carbamazepine. Carbamazepine is common seizure-control medication. “And that risk was elevated by more than 2,500 times,” said Dr. Carleton. “That became a very powerful article in the journal Nature that caused Asian countries to evaluate how they are providing these medications.”
Other points Drs. Carleton and Shear discuss include:
How the medical community can best study conditions as rare as SJS or TEN
After a patient experiences SJS or TEN, how to protect their family members from a similar experience
The logistic steps needed to implement routine screening for genetic risk markers for SJS and TEN before prescribing medications
Innovations that may permit pre-screening of medications for safety in patients who have already experienced SJS or TEN
Listen to the complete Summer of Dialogue podcast episode here:
Have questions about SJS and TEN? Send them to our experts, Drs. Shear and Carleton, for discussion during the upcoming live Colloquium on August 21, 2021. Send them to questions@skinspectrum.net
From the literature on Stevens-Johnson Syndrome
Severe cutaneous adverse drug reactions: Incidence, clinical patterns, causative drugs and modalities of treatment in Assiut University Hospital, Upper Egypt
This study examines the incidence, causative medications, the role and side effects of systemic corticosteroids in Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), and overlap SJS/TEN. The study population included all patients with one of the conditions, presenting at a single university hospital between 2012 and 2017.
Mortality rates were high for patients treated with systemic corticosteroids—100% in TEN, 33.3% in overlap SJS/TEN, and 16.3% in SJS.
Nevirapine-induced Stevens-Johnson Syndrome in children living with HIV in South Africa
Findings from this large case series of children with nevirapine-induced Stevens-Johnson Syndrome (SJS) raises the possibility that the incidence of SJS in children may be higher than previously described. The authors say that more research is required to explore the risk factors associated with nevirapine-induced SJS in children.
Cost-effectiveness analysis of genotyping for HLA-B*15:02 in Indonesian patients with epilepsy using a generic model
This study explores whether routine screening for the HLA-B*15:02 allele would be a cost-effective strategy in Indonesia. The allele is highly prevalent in Indonesia and is strongly associated with carbamazepine-induced Stevens-Johnson Syndrome. The authors compare the cost per quality-adjusted life-year (QALY) gained for patients from routine pre-screening before carbamazepine prescription or prescribing valproic acid instead of carbamazepine. While they conclude that neither approach is cost-effective than continuing to prescribe carbamazepine without routine genomic pre-screening, they note that the improved outcomes are seen in Asian countries that have implemented such routine pre-screening make the approach desirable despite the higher cost.
Genetic markers for Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis in the Asian Indian population: Implications on prevention
This review article examines studies performed in India or involving populations originating in India to evaluate any association between individuals’ HLA type and the risk of medication-induced Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis (SJS/TEN).
The reviewed studies involved a small number of patients, the authors of the new paper note. As a result, they report, it is difficult to say if the observed associations can be extrapolated to a larger population of the same ethnicity. Similar multi-centre studies need to be conducted with a larger sample size to confirm these associations. The authors discuss how a broad understanding of these associations could be used to guide policy decisions relating to routine pre-screening for HLA type before prescribing medications that could result in SJS/TEN.
Video: Clinical syndromes, epidemiology, genomics, diagnosis and treatment - Neil Shear
At the intersection of skin and society
For the first time, Canada will officially recognize Emancipation Day nationwide on Aug. 1, 2021.
In advance of this event, the Halifax-based Delmore “Buddy” Daye Learning Institute (DBDLI) shares videos featuring interesting stories, facts, and information about Emancipation Day, Black History, and historical individuals who played important roles.
The DBDLI works with Africentric communities, government partners, and educational institutions in Nova Scotia and the rest of Canada. They aim to support learners and communities of African ancestry with educational opportunities and inform policymakers and other stakeholders on best practices to provide further educational opportunities.
Videos being shared as part of this project feature artists, entrepreneurs, journalists, politicians, community changemakers and other voices.
A new video is available each day in July, as a countdown to Emancipation Day. The full list of videos, as well as other video content from the DBDLI, is available on their YouTube channel here: https://www.youtube.com/c/DelmoreBuddyDayeLearningInstituteHalifax/videos
This Week
July 24 is International Self Care Day
Something to think about during the week ahead…
Next Week
The Summer of Dialogue: Focus on the Black and Brown Dermatology Patient continues.
The Summer of Dialogue is a summer-long podcast discussion series on Black skin health. In recognition of the persistent health gaps that BIPOC Canadians experience, this program will be dedicated to promoting and advancing medical knowledge and cultural competence. The podcast series will conclude with a live colloquium to be held on Aug. 21, 2021.
Registration for the colloquium and more information on the Summer of Dialogue is available at https://www.skinspectrum.ca/summer