Editing Stevens–Johnson syndrome (section)

== Causes ==
SJS is thought to arise from a disorder of the immune system.<ref name=Tigchelaar />  The immune reaction can be triggered by drugs or infections.<ref>{{cite journal | author = Tan SK, Tay YK | title = Profile and pattern of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in a general hospital in Singapore: Treatment outcomes | journal = Acta Dermato-Venereologica | volume = 92 | issue = 1 | pages = 62–6 | date = 2012 | pmid = 21710108 | doi = 10.2340/00015555-1169 | last2 = Tay| doi-access = free }}</ref> Genetic factors are associated with a predisposition to SJS.<ref name="Medscape Ref SJS" /> The cause of SJS is unknown in one-quarter to one-half of cases.<ref name="Medscape Ref SJS" /> SJS, SJS/TEN, and TEN are considered a single disease with common causes and mechanisms.<ref name=":0" />

Individuals expressing certain{{specify|date=March 2023}} [[human leukocyte antigen#Serotyping|human leukocyte antigen (i.e. HLA) serotypes]] (i.e. genetic [[alleles]]), genetical-based T cell receptors, or variations in their efficiency to [[absorption (pharmacokinetics)|absorb]], [[distribution (pharmacology)|distribute to tissues]], [[metabolism|metabolize]], or [[excrete]] (this combination is termed [[ADME]]) a drug are predisposed to develop SJS.{{cn|date=March 2023}}

=== Medications ===
{{See also|List of SJS-inducing substances}}
Although SJS can be caused by viral infections and malignancies, the main cause is medications.<ref name="Mockenhaupt_2011" /> A leading cause appears to be the use of [[antibiotic]]s, particularly [[sulfa drugs]].<ref name="Medscape Ref SJS">{{cite journal |journal= [[Medscape|Medscape Reference]] |url= http://emedicine.medscape.com/article/1197450-overview#aw2aab6b2b3 |title= Stevens-Johnson Syndrome |last1= Foster |first1= C. Stephen |first2= Rola |last2= Ba-Abbad |first3= Erik |last3= Letko |last4= Parrillo |first4= Steven J. |others= Roy, Hampton Sr. (article editor) |date= August 12, 2013 |at= Etiology |ref= {{SfnRef|Foster et al.|2013}} |display-authors= etal |url-status= live |archive-url= https://web.archive.org/web/20130122091022/http://emedicine.medscape.com/article/1197450-overview#aw2aab6b2b3 |archive-date= January 22, 2013}}</ref><ref name="pmid19874350">{{cite journal | author = Teraki Y, Shibuya M, Izaki S | title = Stevens-Johnson syndrome and toxic epidermal necrolysis due to anticonvulsants share certain clinical and laboratory features with drug-induced hypersensitivity syndrome, despite differences in cutaneous presentations | journal = Clin. Exp. Dermatol. | volume = 35 | issue = 7 | pages = 723–8 | year = 2010 | pmid = 19874350 | doi = 10.1111/j.1365-2230.2009.03718.x | last2 = Shibuya | last3 = Izaki | s2cid = 12561369 }}</ref> Between 100 and 200 different drugs may be associated with SJS.<ref name="Cooper_2012">{{cite journal | author = Cooper KL | title = Drug reaction, skin care, skin loss | journal = Crit Care Nurse | volume = 32 | issue = 4 | pages = 52–9 | year = 2012 | pmid = 22855079 | doi = 10.4037/ccn2012340 | doi-access = free }}</ref> No reliable test exists to establish a link between a particular drug and SJS for an individual case.<ref name="Mockenhaupt_2011" /> Determining what drug is the cause is based on the time interval between first use of the drug and the beginning of the skin reaction. Drugs discontinued more than 1 month prior to onset of mucocutaneous physical findings are highly unlikely to cause SJS and TEN.<ref name=":0" /> SJS and TEN most often begin between 4 and 28 days after culprit drug administration.<ref name=":0" />&nbsp;A published algorithm (ALDEN) to assess drug causality gives structured assistance in identifying the responsible medication.<ref name="Mockenhaupt_2011" /><ref>{{cite journal | author = Sassolas B, Haddad C, Mockenhaupt M, Dunant A, Liss Y, Bork K, Haustein UF, Vieluf D, Roujeau JC, Le Louet H | title = ALDEN, an algorithm for assessment of drug causality in Stevens-Johnson Syndrome and toxic epidermal necrolysis: Comparison with case-control analysis | journal = [[Clinical Pharmacology & Therapeutics]] | volume = 88 | issue = 1 | pages = 60–8 | year = 2010 | pmid = 20375998 | doi = 10.1038/clpt.2009.252 | last2 = Haddad | last3 = Mockenhaupt | last4 = Dunant | last5 = Liss | last6 = Bork | last7 = Haustein | last8 = Vieluf | last9 = Roujeau | last10 = Le Louet | s2cid = 11611291 }}</ref>

SJS may be caused by the medications [[rivaroxaban]],<ref name="EMA">{{cite web |title= Scientific conclusions and grounds for the variation to the terms of the marketing authorisation(s)|url= https://www.ema.europa.eu/en/documents/scientific-conclusion/xarelto-h-c-psusa-00002653-201609-epar-scientific-conclusions-grounds-variation-terms-marketing_en.pdf |type= data sheet |publisher= [[European Medicines Agency]]|date= April 6, 2017}}</ref> [[vancomycin]], [[allopurinol]], [[valproate]], [[levofloxacin]], [[diclofenac]], [[etravirine]], [[isotretinoin]], [[fluconazole]],<ref name="NZ">{{cite web |title= Diflucan One |url= http://www.medsafe.govt.nz/profs/Datasheet/d/DiflucanOnecap.htm |type= data sheet |publisher= [[Medsafe]]; [[Ministry of Health (New Zealand)|New Zealand Ministry of Health]] |archive-url= https://web.archive.org/web/20100603131507/http://www.medsafe.govt.nz/profs/Datasheet/d/DiflucanOnecap.htm |archive-date= June 3, 2010 |date= April 29, 2008}}</ref> [[valdecoxib]], [[sitagliptin]], [[oseltamivir]], [[penicillin]]s, [[barbiturate]]s, [[Sulfonamide (medicine)|sulfonamides]], [[phenytoin]], [[azithromycin]], [[oxcarbazepine]], [[zonisamide]], [[modafinil]],<ref>{{cite web |url= https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm152701.htm |title= Provigil (modafinil) Tablets |website= [[MedWatch]] |publisher= [[Food and Drug Administration|US Food and Drug Administration]] |date= October 24, 2007 |url-status= live |archive-url= https://web.archive.org/web/20131211203820/https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm152701.htm |archive-date= December 11, 2013}}</ref> [[lamotrigine]], [[nevirapine]],<ref name=":0" /> [[pyrimethamine]], [[ibuprofen]],<ref>{{cite journal | author = Raksha MP, Marfatia YS | title = Clinical study of cutaneous drug eruptions in 200 patients | journal = [[Indian Journal of Dermatology, Venereology and Leprology]] | volume = 74 | issue = 1 | page = 80 | year = 2008 | pmid = 18193504 | doi = 10.4103/0378-6323.38431 | last2 = Marfatia | url = http://www.bioline.org.br/pdf?dv08031 | doi-access = free | hdl = 1807/48058 | hdl-access = free }}</ref> [[ethosuximide]], [[carbamazepine]], [[bupropion]], [[telaprevir]],<ref>{{cite web |url= http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/201917s007lbl.pdf |title= Incivek prescribing information |type= [[package insert]] |date= December 2012 |publisher= [[Vertex Pharmaceuticals]] |url-status= live |archive-url= https://web.archive.org/web/20130315024325/http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/201917s007lbl.pdf |archive-date= March 15, 2013}}</ref><ref>{{cite journal | author = Surovik J, Riddel C, Chon SY | title = A case of bupropion-induced Stevens-Johnson syndrome with acute psoriatic exacerbation | url= https://jddonline.com/articles/dermatology/S1545961610P1010X | journal = [[Journal of Drugs in Dermatology]] | volume = 9 | issue = 8 | pages = 1010–2 | year = 2010 | pmid = 20684153 | last2 = Riddel | last3 = Chon }}{{free access}}</ref> and [[nystatin]].<ref>{{cite journal | author = Fagot JP, Mockenhaupt M, Bouwes-Bavinck JN, Naldi L, Viboud C, Roujeau JC | title = Nevirapine and the risk of Stevens–Johnson syndrome or toxic epidermal necrolysis | journal = [[AIDS (journal)|AIDS]] | volume = 15 | issue = 14 | pages = 1843–8 | year = 2001 | pmid = 11579247 | doi = 10.1097/00002030-200109280-00014 | last2 = Mockenhaupt | last3 = Bouwes-Bavinck | last4 = Naldi | last5 = Viboud | last6 = Roujeau | last7 = Euroscar Study | s2cid = 25014092| doi-access = free }}</ref><ref>{{cite journal | author = Devi K, George S, Criton S, Suja V, Sridevi PK | title = Carbamazepine – The commonest cause of toxic epidermal necrolysis and Stevens–Johnson syndrome: A study of 7 years | journal = [[Indian Journal of Dermatology, Venereology and Leprology]] | volume = 71 | issue = 5 | pages = 325–8 | year = 2005 | pmid = 16394456 | doi = 10.4103/0378-6323.16782 | last2 = George | last3 = Criton | last4 = Suja | last5 = Sridevi| doi-access = free }}</ref>

Medications that have traditionally been known to lead to SJS, erythema multiforme, and toxic epidermal necrolysis include [[sulfonamide (medicine)|sulfonamide]] antibiotics,<ref name=":0" /> [[penicillin]] antibiotics, [[cefixime]] (antibiotic), [[barbiturate]]s (sedatives), [[lamotrigine]], [[phenytoin]] (e.g., [[Dilantin]]) ([[anticonvulsant]]s) and trimethoprim. Combining lamotrigine with [[sodium valproate]] increases the risk of SJS.<ref>{{cite journal |pmid=17428116 | volume=8 | issue=2 | title=Stevens-Johnson syndrome due to concomitant use of lamotrigine and valproic acid | year=2007 | journal=Am J Clin Dermatol | pages=107–11 |vauthors=Kocak S, Girisgin SA, Gul M, Cander B, Kaya H, Kaya E | doi=10.2165/00128071-200708020-00007| s2cid=36720720 }}</ref>

[[Nonsteroidal anti-inflammatory drugs]] (NSAIDs) are a rare cause of SJS in adults; the risk is higher for older patients, women, and those initiating treatment.<ref name=pmid_20101062 /> Typically, the symptoms of drug-induced SJS arise within a week of starting the medication. Similar to NSAIDs, [[paracetamol]] (acetaminophen) has also caused rare cases<ref name="JPakMed">{{cite journal | author = Khawaja A, Shahab A, Hussain SA | title = Acetaminophen induced Steven Johnson syndrome-Toxic Epidermal Necrolysis overlap | journal = [[Journal of Pakistan Medical Association]] | volume = 62 | issue = 5 | pages = 524–7 | year = 2012 | pmid = 22755330 | url = http://www.jpma.org.pk/full_article_text.php?article_id=3419 | last2 = Shahab | last3 = Hussain | url-status = live | archive-url = https://web.archive.org/web/20141230130734/http://www.jpma.org.pk/full_article_text.php?article_id=3419 | archive-date = December 30, 2014}}</ref><ref name="AllergeImmuno">{{cite journal | author = Trujillo C, Gago C, Ramos S | title = Stevens-Jonhson syndrome after acetaminophen ingestion, confirmed by challenge test in an eleven-year-old patient | journal = Allergol Immunopathol (Madr) | volume = 38 | issue = 2 | pages = 99–100 | year = 2010 | pmid = 19875224 | doi = 10.1016/j.aller.2009.06.009 | last2 = Gago | last3 = Ramos }}</ref> of SJS.  People with [[systemic lupus erythematosus]] or HIV infections are more susceptible to drug-induced SJS.<ref name=Tigchelaar />

=== Infections ===
The second most common cause of SJS and TEN is infection, particularly in children. This includes [[upper respiratory infections]], [[otitis media]], [[pharyngitis]], and [[Epstein–Barr virus]], ''[[Mycoplasma pneumoniae]]'' and [[cytomegalovirus]] infections. The routine use of medicines such as [[antibiotics]], [[antipyretics]] and [[analgesics]] to manage infections can make it difficult to identify if cases were caused by the infection or medicines taken.<ref>{{cite journal|last1=Bentley|first1=John|last2=Sie|first2=David|title=Stevens-Johnson syndrome and toxic epidermal necrolysis|journal=The Pharmaceutical Journal|date=October 8, 2014|volume=293|issue=7832|url=http://www.pharmaceutical-journal.com/learning/cpd-article/stevens-johnson-syndrome-and-toxic-epidermal-necrolysis/20066728.cpdarticle|access-date=October 8, 2014|url-status=live|archive-url=https://web.archive.org/web/20141012190345/http://www.pharmaceutical-journal.com/learning/cpd-article/stevens-johnson-syndrome-and-toxic-epidermal-necrolysis/20066728.cpdarticle|archive-date=October 12, 2014}}</ref>

Viral diseases reported to cause SJS include: [[herpes simplex virus]] (possibly; is debated), AIDS, [[coxsackievirus]], [[influenza]], [[hepatitis]], and [[mumps]].<ref name="Medscape Ref SJS" />

In pediatric cases, Epstein–Barr virus and enteroviruses have been associated with SJS.<ref name="Medscape Ref SJS" />

Recent upper respiratory tract infections have been reported by more than half of patients with SJS.<ref name="Medscape Ref SJS" />

Bacterial infections linked to SJS include group A beta-hemolytic streptococci, [[diphtheria]], [[brucellosis]], [[lymphogranuloma venereum]], [[Mycobacterium|mycobacteria]], ''[[Mycoplasma pneumoniae]]'', [[Rickettsial disease|rickettsial infections]], [[tularemia]], and [[typhoid]].<ref name="Medscape Ref SJS" />

Fungal infections with [[coccidioidomycosis]], [[dermatophytosis]] and [[histoplasmosis]] are also considered possible causes.<ref name="Medscape Ref SJS" /> [[Malaria]] and [[trichomoniasis]], protozoal infections, have also been reported as causes.<ref name="Medscape Ref SJS" />