Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)

Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) represent severe skin reactions that can be triggered by many causes, mainly by medications, and can be characterized by a spectrum of severity ranging from SJS, the milder form, to the more severe TEN. Initially considered distinct entities, they are now understood as part of a continuum. Symptoms typically begin with fever and flu-like manifestations, followed by rapid onset of skin blistering and peeling skin to severe burns, primarily affecting areas like the face and chest, then spreading across the body. The slothing of the skin and the concurrent mucous membrane damage complicates the condition, potentially leading to life-threatening outcomes due to fluid loss, infection susceptibility, and systemic complications such as pneumonia, sepsis, and organ failure.

Mortality rates vary significantly: approximately 10% for SJS and up to 50% for TEN, with survivors often facing long-term issues like skin pigmentation changes, dry skin, abnormal sweating, hair loss, and nail abnormalities. The incidence ranges from two to seven cases per million annually, with SJS more prevalent than TEN and a higher occurrence in older individuals, women, and those with HIV.

Medications implicated in triggering SJS/TEN include anticonvulsants (e.g., lamotrigine, carbamazepine), allopurinol, sulfonamides, certain antibiotics (e.g., penicillin), and others. Genetic predisposition, specifically certain human leukocyte antigen (HLA) types, increases susceptibility, underscoring the importance of familial awareness and cautious medication use.

Diagnostic evaluation employs the SCORTEN system, which assesses criteria like age, malignancy, heart rate, and biochemical markers to predict mortality risk. Management begins with discontinuing the offending agent upon suspicion or confirmation through tools like the ALDEN algorithm. Supportive care in specialized units—such as ICUs or burn units—focuses on fluid resuscitation, temperature regulation, pain control, infection prevention, and meticulous skin and mucosal care. There is an uncertainty among some treatment options, one being the use of steroids. In some cases, systemic corticosteroids may be considered, though their efficacy remains debated.

The pathophysiology involves a Type IV hypersensitivity reaction mediated by T cells, particularly CD8+ cells, triggering cytotoxicity and keratinocyte death, leading to blister formation and skin detachment. As a Type IV hypersensitivity reaction, this is seen as much more severe than a simple allergic reaction and requires quick treatment. Furthermore, early recognition within weeks of medication initiation is crucial, as prompt intervention can mitigate progression and improve outcomes.

Long-term sequelae management includes scar management, psychological support, and addressing residual physical impairments, necessitating a multidisciplinary approach. Research into adjunctive therapies like cyclosporine, intravenous immunoglobulin, and plasmapheresis continues, aiming to refine treatment strategies and enhance patient outcomes.

In conclusion, while this reaction is relatively rare and uncommon, SJS/TEN poses significant clinical challenges due to its rapid onset, potential for severe morbidity and mortality, and long-term impact on survivors. This is a painful and difficult treatment that can greatly impede on the quality of life of a person. Vigilance in medication management, early recognition, and comprehensive supportive care are paramount and absolutely necessary in mitigating the devastating effects of this complex and life-threatening condition.

Kumar, R., Das, A., & Das, S. (2018). Management of Stevens-Johnson Syndrome-Toxic Epidermal Necrolysis: Looking Beyond Guidelines!. Indian journal of dermatology, 63(2), 117–124. https://doi.org/10.4103/ijd.IJD_583_17

Marks, M. E., Botta, R. K., Abe, R., Beachkofsky, T. M., Boothman, I., Carleton, B. C., Chung, W. H., Cibotti, R. R., Dodiuk-Gad, R. P., Grimstein, C., Hasegawa, A., Hoofnagle, J. H., Hung, S. I., Kaffenberger, B., Kroshinsky, D., Lehloenya, R. J., Martin-Pozo, M., Micheletti, R. G., Mockenhaupt, M., Nagao, K., … Phillips, E. J. (2023). Updates in SJS/TEN: collaboration, innovation, and community. Frontiers in medicine, 10, 1213889. https://doi.org/10.3389/fmed.2023.1213889

Stevens-Johnson Syndrome/toxic epidermal necrolysis (SJS/TEN) is a severe skin reaction that is typically triggered by specific medications. While they were once considered two separate conditions, both SJS and TEN are now viewed as a part of a spectrum, with SJS representing the milder end and TEN representing the more severe end. Symptoms of SJS/TEN often initially manifest as a fever and flu-like symptoms. However, within days, the skin may begin blistering and peeling, forming painful raw areas known as erosions, resembling severe burns. Typically, these erosions appear on the face and chest before spreading to other body parts. Most individuals who suffer from SJS/TEN also often experience damage to mucous membranes, such as the mouth and airways, leading to difficulties in swallowing and breathing. Due to the severe skin and mucous membrane damage that occurs with SJS/TEN, this condition is considered life-threatening. As the skin acts as a protective barrier, extensive damage can cause fluid loss and increased risk of infection. Complications may include infection with pneumonia, sepsis, shock, organ failure and, in the worst case scenario, death. Approximately 10% of SJS cases are lethal, whereas upto 50% of TEN cases lead to death. Survivors of SJS/TEN may suffer from life-long complications such as skin pigmentation changes, xerosis, excessive sweating, alopecia, and nail abnormalities. 

SJS/TEN affects approximately two to seven individuals per million annually, with SJS being three times more common than TEN. Although it may affect anyone with a genetic predisposition, this condition is more commonly seen in older individuals and women. This condition is also notably more common in those infected with HIV, with an estimated incidence of 1 in 1000. Various medications have been implicated in triggering a SJS/TEN reaction, with the most commonly implicated drugs including anticonvulsants such as lamotrigine, carbamazepine or phenytoin, allopurinol (particularly in doses greater than 100 mg/day), sulfonamides such as sulfasalazine, and certain antibiotics such as penicillin, cephalosporins or quinolones. Genetic predisposition is also a leading factor for SJS/TEN, with certain human leukocyte antigen (HLA) allotypes increasing the risk of developing the syndrome upon exposure to aromatic anticonvulsants and allopurinol. Family members of affected individuals should be informed of the potential risk and exercise caution when taking medications associated with this condition. 

The severity of an individual’s SJS/TEN reaction is evaluated using the SCORTEN system, which assigns one point for each of the following seven criteria assessed upon admission: 

• Age greater than 40 years 

• Presence of malignancy

• Heart rate exceeding 120 beats/min

• Initial percentage of epidermal detachment greater than 10%

• Serum urea level above 10 mmol/L

• Serum glucose level above 14 mmol/L 

• Serum bicarbonate level below 20 mmol/L 

The mortality risk associated with SJS/TEN varies based on the individual’s SCORTEN score. Individuals with bicarbonate levels below 20 mmol/L have an approximated mortality rate over 40 times greater than those with normal or higher levels. The mortality rates corresponding to different SCORTEN scores are as follows: score 0-1 (3.2%), score 2 (12.1%), score 3 (35.3%), score 4 (58.3%), and score 5 (>90%). 

The management of SJS/TEN involves a comprehensive approach that begins with identifying and discontinuing the triggering agent. A detailed medical history is essential for pinpointing the causative agent, as symptoms typically emerge within 8 weeks of initiating therapy, with most cases manifesting between 4 days and 4 weeks after starting a medication. When the medical history alone is insufficient in determining the causative agent, there are a number of other causative assessment tools such as the Algorithm for Drug Causality for Epidermal Necrolysis (ALDEN) and the Liverpool Adverse Drug Reaction, both of which have demonstrated efficacy in identifying causative drugs. In addition to removal of the offending agent, supportive care is also considered the mainstay in treatment of SJS/TEN. Examples of supportive care commonly necessary for these patients include, but are not limited to, hospital admission, typically to an ICU or burn unit, administration of crystalloid fluids for adequate fluid replacement, temperature regulation through a warm environment and emergency blankets, pain management, sterile handling to prevent infection, skincare involving daily inspection of skin and mucosal surfaces, gentle removal of necrotic skin/mucosal tissue and use of antibiotics if secondary infection occurs (although prophylactic use is discouraged). Administration of systemic corticosteroids, which are often given in high doses for the first three to five days of hospitalization, may be beneficial in the treatment of SJS/TEN, however their efficacy still remains uncertain. 

Resources: 

Frantz, R., Huang, S., Are, A., & Motaparthi, K. (2021). Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Review of Diagnosis and Management. Medicina (Kaunas, Lithuania), 57(9), 895. https://doi.org/10.3390/medicina57090895

Oakley AM, Krishnamurthy K. Stevens-Johnson Syndrome. [Updated 2023 Apr 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459323/

Stevens-Johnson syndrome/toxic epidermal necrolysis. MedlinePlus. Accessed May 3, 2024. https://medlineplus.gov/genetics/condition/stevens-johnson-syndrome-toxic-epidermal-necrolysis/.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe skin hypersensitivity reactions most often triggered by medications. Stevens-Johnson syndrome is a less severe version of toxic epidermal necrolysis. Although clinically similar, the distribution and extent of hypersensitivity allow us to differentiate between them. SJS affects less than 10% of the body surface area, whereas TEN affects more than 30% of the body surface area. Both conditions are rare but life-threatening, affecting roughly 2 people per million people each year. There are varying forms in which SJS/TEN can present itself, however, early detection is ideal upon noticing tiny maculopapular and vesicular lesions to the extent of bullous lesions. 

Several drugs can trigger such a reaction. In fact, “drugs precipitate over 50% of SJS cases and up to 95% of TEN cases”. These drugs include sulfa drugs, penicillins, fluoroquinolones, cephalosporins, anticonvulsants, NSAIDs, antiretrovirals, and others. In non-drug-induced cases, severe infections, vaccines, and graft-versus-host disease can induce a reaction. Studies have been conducted to determine typical mortality rates. In 2023, it was reported that SJS mortality rates ranged from 19.4% to 29%, and TEN mortality rates ranged from 14.8% to 48%. Once SJS progresses to TEN, massive bullae formation occurs, resulting in ruptures and peeling of the skin. An estimated 70% of individuals who heal are left with scars. 

Although the exact mechanism is unknown, it is believed that drug-induced SJS/TEN is Type IV cell mediated. The body’s T cells initiate an inflammatory response to the foreign antigen. CD8+ T cells have been identified as mediators of blister formation in TEN. It is suggested that granulysin is released from cytotoxic T cells and natural killer cells, resulting in keratinocyte death, creating blister fluid. Due to the severity of the hypersensitive reaction, it is essential to discontinue any causative agents/drugs and take the patient to a hospital. Before starting any offending agents such as carbamazepine or allopurinol, HLA genetic testing can be conducted to prevent SJS/TEN whenever possible.

Within 3 weeks of starting a causative drug, patients develop symptoms such as fever, headache, cough, and keratoconjunctivitis. This is followed by macules appearing on the face, neck, and trunk of the body. As the disorder progresses, large bullae and sloughing can be seen. The skin and mucosal membrane get damaged, affecting the body’s thermoregulatory ability. Fluid replacement is one of the key factors in treatment to regulate and maintain the body’s temperature due to its impaired ability. As several components of the body have now been damaged, each must be carefully attended to. 

Non-NSAID painkillers and oral and topical anesthetics are essential in pain management, morphine being a commonly administered, controversial drug. Mouthwashes such as chlorhexidine and topicals such as silver nitrate aid in repairing the damaged membrane and skin barrier, followed by dressing the wounds, reducing the introduction of infections. SJS/TEN treatment goes as far as providing lung care with aerosols and physiotherapy. Many patients are given psychiatric support due to the long-lasting effects of the individual's quality of life. Alongside these obvious treatments, there have been reports of patients benefiting from adjunctive treatment with cyclosporine, intravenous immunoglobulin, plasmapheresis, and systemic corticosteroids, although their roles remain controversial. An aggressive skin disorder, SJS/TEN requires patients to undergo specialized care and routine reassessments to best treat their conditions.

References

1. Benedetti, J. (2024, February 21). Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) - dermatologic disorders. Merck Manuals Professional Edition. https://www.merckmanuals.com/professional/dermatologic-disorders/hypersensitivity-and-reactive-skin-disorders/stevens-johnson-syndrome-sjs-and-toxic-epidermal-necrolysis-ten

2. Mayo Foundation for Medical Education and Research. (n.d.). Stevens-Johnson syndrome. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/stevens-johnson-syndrome/symptoms-causes/syc-20355936

3. U.S. National Library of Medicine. (n.d.). Stevens-Johnson Syndrome/toxic epidermal necrolysis: Medlineplus Genetics. MedlinePlus. https://medlineplus.gov/genetics/condition/stevens-johnson-syndrome-toxic-epidermal-necrolysis/ 

4. Labib A, Milroy C. Toxic Epidermal Necrolysis. [Updated 2023 May 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK574530/

5. Hasegawa A, Abe R. Recent advances in managing and understanding Stevens-Johnson syndrome and toxic epidermal necrolysis. F1000Res. 2020 Jun 16;9:F1000 Faculty Rev-612. doi: 10.12688/f1000research.24748.1. PMID: 32595945; PMCID: PMC7308994.

6. Harr T, French LE. Toxic epidermal necrolysis and Stevens-Johnson syndrome. Orphanet J Rare Dis. 2010 Dec 16;5:39. doi: 10.1186/1750-1172-5-39. PMID: 21162721; PMCID: PMC3018455.

7. Lee HY, Walsh SA, Creamer D. Long-term complications of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN): the spectrum of chronic problems in patients who survive an episode of SJS/TEN necessitates multidisciplinary follow-up. Br J Dermatol. 2017 Oct;177(4):924-935. doi: 10.1111/bjd.15360. Epub 2017 Sep 22. PMID: 28144971.

SJS/ TENS

Steven Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis Syndrome (TENS) are two very serious rare skin reactions that can be life threatening. Medications are the main cause of this reaction, in fact over 80% of cases are due to medicated related adverse reactions. Furthermore, SJS can be defined as a disorder of the skin and mucous membranes. SJS presents with the initial flu-like symptoms, this is followed by a painful rash that spreads and blisters. As the reaction progresses the skin begins to shed. Overall SJS involves the loss of skin, mucosal membranes, and some systemic symptoms. TENS presents the same conditions; however, they are differentiated based on how much of the body is affected. SJS means that less than 10% of the body is infected, meanwhile TENS is more than 30% of the body is being affected. To show a statistic standpoint of how rare SJS is there are about 7 cases of SJS per million people a year. TENS is ever lower with less than 1.2 per millions of cases per year. Being able to recognize high risk medications and risk factors are essential for preventing SJS/TENS.

When looking into the epidemiology, there are not too many risk factors biological/ genetic risk factors that make a person more susceptible to SJS/TENS. Unfortunately, patients with HIV, the possibility of getting SJS/TENS is quite high compared to non-HIV patients. This is with an estimate of 1/1000 incidences.

Numerous classes of medications can cause SJS/ TENS however, as reported the most common offending medications tend to be lamotrigine, carbamazepine, phenytoin, allopurinol, sulfonamides, several classes of antibiotics, NSAIDs, and contrast media. While it is not completely known why SJS/TENS are more prominent in these drugs than others, there are inferences. The main theory is there is an interaction/binding of a drug associated antigen or metabolite with the major histocompatibility complex type 1 or cellular peptide to form an immunogenic compound. SJS/TENS is T-cell mediated.

SJS/TENS historically present as a progressive reaction. The reaction begins with nonspecific symptoms. This may include fever, malaise, upper respiratory tract symptoms like a cough and a runny nose. In the next following days blistering rashes begin to appear on the face, trunk limbs and mucosal surfaces of the body. The blisters and marks on the body may look like but not limited to erythematous, annular or purpuric macules; Flaccid bullae, large painful erosions or Nikolsky positive ( lateral pressure on the skin make the skin peel). When looking at the physical representation SJS beings to differ from TENS due to the area on the body being affected. SJS is more targetoid rashes, fewer denudation. Oppose to TENS where it is widespread tender erythroderma and erosions. Overall, the symptoms presented are extremely painful and dangerous to the patient.

Treating SJS/TENS takes a lot of care therefore, hospitalization in a specialized unit (burn unit or ICU) is required. One of the first steps of treatment will be discontinuation of the causative drug. SJS/TENS is life threatening therefore discontinuation of the medication causing SJS/TENS is needed. The patient will require a lot of supportive care treatment. Fluid replacement, nutritional assessment, temperature control, pain relief, oxygen if needed and sterile handling. As for caring for the actual macules and blistering will require a daily examination of the skin and mucosal surfaces to see if there is infection. In particular mucosal surfaces will require careful cleansing and topical anesthetics. Gentle removal of the necrotic skin is done as well. It is unclear whether or not the use of high dose corticosteroids are effective in treating SJS/TENS. It is common for the patient to be prescribed a high dose corticosteroid for the first 5 days of treatment. Other drugs have been used as off label treatments but the effectiveness of these drugs remain controversial.

SJS/TENS is extremely dangerous and must be treated as soon as possible. There is not much research on the reaction due to it being so rare. If we can continue to study the reaction to learn more about it we may be able to expand the treatment plan for this extremely painful reaction.

References:

Oakley AM, Krishnamurthy K. Stevens-Johnson Syndrome. [Updated 2023 Apr 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459323/

Ubukata, Nanako et al. “Risk factors and drugs that trigger the onset of Stevens-Johnson syndrome and toxic epidermal necrolysis: A population-based cohort study using the Shizuoka Kokuho database.” JAAD international vol. 11 24-32. 24 Dec. 2022, doi:10.1016/j.jdin.2022.12.002

Steven Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis Syndrome (TENS) are two rare but life threatening reactions that are most often triggered by particular medications and predominantly involve the skin and mucous membranes. They can both be described as an over reaction of the immune system and are characterized by extensive exfoliation of the epidermis and mucous membrane, which may result in sepsis and death. The major difference between SJS versus TENS is that if the epidermal detachment is less than 10% of the total body surface area, it is classified as SJS, also known as erythema multiforme major. If the affected body surface area is more than 30%, then it is considered TENS. When the affected body surface area ranges from 10% to 29%, there is an overlap between the two conditions. There are 1 to 7 cases of SJS per million a year, while there are 0.4 to 1.2 cases of TENS per million a year, with the risk being higher in HIV patients.

While the main feature of SJS/TENS is the skin rash, many people describe experiencing a sense of feeling generally unwell, characterized by a headache and joint pain, often accompanied by a cough. Stinging eyes and discomfort upon swallowing has also been reported. These symptoms usually occur a few days before the skin rash. Initial areas of skin manifestation include the presternal region of the trunk and the face, as well as the palms and soles. Over 90% of patients experience involvement (such as erythema and erosions) of the buccal, genital, and/or ocular mucosa, with occasional impact on the respiratory and gastrointestinal tracts. Ocular involvement at the onset of disease is frequent as well, and can range from acute conjunctivitis, eyelid edema, erythema, crusts, and ocular discharge, to conjunctival membrane or pseduomembrane formation or corneal erosion. Furthermore, more severe cases include cicatrizing lesions, symblepharon, fornix foreshortening, and corneal ulceration. For SJS, there are more blisters and atypical target lesions involving less than 10% of the body surface area, while for TENS the blisters cover more than 30% of the body surface area accompanied with scarring. There is also erythema and massive bullae formation. 30% of people die often within 8 days after the bullae appear, while 70% heal with potential scarring in 2 weeks.

Medications that trigger this severe skin condition include certain NSAIDs (e.g. piroxicam) and anticonvulsants (e.g. carbamazepine), antipsychotics (e.g. phenothiazines), allopurinol, barbiturates, and antibiotics such as penicillins, sulfonamides, long acting sulfonamides, and fluoroquinolones, and many other medications. While treatment exists for SJS/TENS, prevention is key. The suspected causative drug must be immediately discontinued while nutritional and fluid replacement (crystalloid) by intravenous and nasogastric routes must be administrated upon hospital admission. Temperature maintenance is vital as well since the body's temperature regulation is impaired. Moreover, skin care and infection control entail topical silver nitrate or chlorhexidine, while silver sulfadiazine should be avoided. Dressings such as gauze with petrolatum or non-adherent nanocrystalline-containing gauze should be used. The use of adhesive tapes must be avoided. Pain relief, eye care, mouth care (mouthwashes; topical oral anesthetic), lung care (aerosols, bronchial aspiration, physiotherapy), and psychiatric support for extreme anxiety and emotional liability should also be administered.

References:

Harr T, French LE. Toxic epidermal necrolysis and Stevens-Johnson syndrome. Orphanet J Rare Dis. 2010;5:39. Published 2010 Dec 16. doi:10.1186/1750-1172-5-39

The Dermatology department in collaboration with the Child and Family Information Group. “Stevens-Johnson Syndrome.” NHS Great Ormond Street Hospital for Children, NHS, Dec. 2018,

Kumar R, Das A, Das S. Management of Stevens-Johnson Syndrome-Toxic Epidermal Necrolysis: Looking Beyond Guidelines!. Indian J Dermatol. 2018;63(2):117-124. doi:10.4103/ijd.IJD_583_17

Oakley AM, Krishnamurthy K. Stevens-Johnson Syndrome. [Updated 2023 Apr 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459323/

Yu Feng Lin & Fawziya Twam 

Stevens-Johnson syndrome (SJS) is a severe skin condition, also known as erythema multiforme major, characterized by vesicular and bullous lesions on mucous membranes like the mouth, eyes, and gastrointestinal tract. It is a rare and potentially fatal skin reaction caused primarily by medications. It is an unpredictable reaction to medications that involves drug-specific CD8+ cytotoxic lymphocytes, the Fas-Fas ligand (FasL) pathway of apoptosis, and granule-mediated exocytosis and tumor necrosis factor-alfa (TNF–alpha)/death receptor pathway. SJS is characterized by blistering and mucosal/epidermal detachment due to full-thickness epidermal necrosis without substantial dermal inflammation. SJS is diagnosed when the total body surface area of blistering and detachment is less than 10%. This condition involves sheet-like skin and mucosal loss, along with systemic symptoms.

Patients with SJS initially present with fever, malaise, upper respiratory symptoms, sore throat, conjunctivitis, and painful, dusky, target-like skin lesions. A blistering rash and erosion of the skin, mucosal surfaces, and other organs can subsequently develop. These conditions can lead to severe complications, including sepsis and organ failure. Involvement of the intestinal and upper respiratory tract, older age, and greater extent of epidermal detachment are associated with a poor prognosis. Approximately 10% of SJS and 30% of toxic epidermal necrolysis (TEN) cases result in death. 

The exact cause of SJS is not fully understood but involves the immune system's response to drugs. Medications are causative in over 80% of cases. Certain genetic factors can increase the risk, and the most common medications triggering these reactions include anticonvulsants, allopurinol, sulfonamides, antibiotics, nonsteroidal anti-inflammatory drugs, and nevirapine. Diagnosis involves skin biopsy, blood tests, and assessment using the SCORTEN scoring system to determine the severity and mortality risk.

Management and treatment for SJS is not standardized, but the best outcomes require a multidisciplinary approach and are achieved with early diagnosis, discontinuation of the suspected drug, hospitalization, meticulous supportive care in an intensive care or burn unit, fluid replacement, pain relief, and wound care. Systemic corticosteroids and other medications may be used, although their effectiveness is debated. Critical aspects of care include fluid management, atraumatic wound care, infection prevention and treatment, and ophthalmologic and respiratory support. While therapies like systemic glucocorticoids, intravenous immunoglobulin, cyclosporine, or etanercept may be used, their effectiveness lacks conclusive evidence due to limited randomized studies.

Differential diagnoses include other severe cutaneous adverse reactions and skin conditions like erythema multiforme and staphylococcal scalded skin syndrome. Prognosis depends on the extent and severity of the condition, with mortality rates ranging from 3.2% to over 90%. In the acute phase, sepsis is the most common serious risk of Stevens-Johnson syndrome/toxic epidermal necrolysis. Organ failure may occur, including pulmonary, hepatic, and renal systems. The most common long-term complications of Stevens-Johnson syndrome/toxic epidermal necrolysis are ocular (including blindness), cutaneous (pigmentary changes and scarring), and renal. Mucosal involvement with blisters and erosions can lead to strictures and scarring.

Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) are variants of the same condition and are distinct from erythema multiforme major staphylococcal scalded skin syndrome­, and other drug eruptions. SJS is a less severe form compared to TEN, with a mortality rate of 5% for SJS, while TEN has a mortality rate ranging from 25% to 50%. However, recent studies have reported a lower mortality rate of 10% for TEN. Stevens-Johnson syndrome (SJS) is characterized by skin and mucosal detachment involving less than 10% of the body surface area. Overlap Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) occurs when 10% to 30% of the body surface area is affected. Toxic epidermal necrolysis (TEN) is identified when more than 30% of the body surface area is involved. Medications are the primary cause of both SJS and TEN, with various drugs implicated in their development.

Genetic factors play a significant role in the risk of developing Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN). Specific human leukocyte antigen (HLA) allotypes have been identified as increasing the susceptibility to these conditions when individuals are exposed to certain medications like aromatic anticonvulsants and allopurinol. For individuals with a family history of SJS/TEN, it's crucial to be aware of the potential risk associated with these genetic factors and exercise caution when taking medications linked to these conditions. Notable findings include the Han Chinese, Thai, Malaysian, and South Indian populations with an increased risk of SJS/TEN if they carry HLA-B*1502 and use aromatic anticonvulsants.Han Chinese individuals carrying HLA-B*5801 and taking allopurinol are also at a heightened risk. Among Europeans, those with HLA-B5701 face an increased risk when using abacavir, while those carrying HLA-A3101 are at risk when taking carbamazepine.

The management of SJS/TEN involves an interprofessional team, including dermatologists, intensivists, ophthalmologists, and other specialists. Close medication review is essential to prevent future episodes, and patients should receive long-term follow-up care to monitor for functional deficits and complications. The outcomes for individuals with Stevens-Johnson syndrome (SJS) depend on the extent and severity of skin involvement. In mild cases, lesions typically heal within 12 to 16 weeks, with the possibility of mild scarring. However, functional loss is usually not a concern unless mucous membranes, particularly the eyes, are affected.

For cases where more than 20% of the body surface area is involved, mortality rates range from 1% to 27%, with concomitant bacterial infections increasing the risk of death. Several factors can negatively impact the outcome, including advanced age, leucopenia, the presence of malignancies, renal dysfunction, hyperglycemia, and involvement of more than 10% of the body surface area. Survivors of SJS may experience long-term complications such as inverted eyelids, sicca-like syndrome (dry eyes and mouth), visual loss, and the development of corneal neovascularization. However, an interprofessional approach to care can contribute to improved outcomes for these individuals.

References:

Common Skin Disorders. In: Herrier RN, Apgar DA, Boyce RW, Foster SL. eds. Patient Assessment in Pharmacy. McGraw Hill; 2015. Accessed September 25, 2023. https://accesspharmacy-mhmedical-com.jerome.stjohns.edu/content.aspx?bookid=1074&sectionid=62364288

Lewin JM, Lewin NA, Nelson LS. Dermatologic Principles. In: Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank's Toxicologic Emergencies, 11e. McGraw Hill; 2019. Accessed September 25, 2023. https://accesspharmacy-mhmedical-com.jerome.stjohns.edu/content.aspx?bookid=2569&sectionid=210268472

Micheletti RG, Rosenbach M, Wintroub BU, Shinkai K. Cutaneous Drug Reactions. In: Loscalzo J, Fauci A, Kasper D, Hauser S, Longo D, Jameson J. eds. Harrison's Principles of Internal Medicine, 21e. McGraw Hill; 2022. Accessed September 25, 2023. https://accesspharmacy-mhmedical-com.jerome.stjohns.edu/content.aspx?bookid=3095&sectionid=262791505

Oakley AM, Krishnamurthy K. Stevens-Johnson Syndrome. [Updated 2023 Apr 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459323/

SJS and TEN

        Steven-Johnsons syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are severe, life-threatening conditions that affect the skin and mucosal membranes. They are rare but dangerous. TEN has a greater hospitalization and mortality rate compared to SJS. SJS/TEN can be drug-induced. Examples of drugs that cause SJS/TEN include allopurinol, trimethoprim-sulfamethoxazole cephalosporins, quinolones, carbamazepine, phenytoin, and phenobarbital. Patients more susceptible to the condition have the genetic marker of HLA-B*1502 in the Han Chinese population. 

        Since the progression of SJS/TENS can lead to dangerous consequences, quick diagnoses are key. Therefore, one must learn the early signs of SJS/TENS to diagnose. Initially, the patient may experience a fever, stinging eyes, blistering rashes, and difficulty swallowing. These symptoms can last 1-7 days before the patient experiences the SJS/TEN condition. The skin will then experience pain, red/purple rashes, and blistering. The buccal, genital, and/or ocular mucosal membranes will have redness, erosions, and blisters. If the eyes become affected, the patient can experience dry eyes, conjunctivitis, corneal erosions, and even loss of sight. When the epidermal detachment affects less than 10% of the body, the patient has SJS. When it is 30%, the patient has TEN. If the patient experiences an epidermal detachment of 10-30%, he/she is believed to have an overlap of SJS/TEN. If the patient has 25-30% skin involvement, it is recommended to treat him/her in the burn unit. This can decrease the morbidity and mortality rate. 

        The treatment of SJS/TENs begins with withholding the medication that caused the condition. In addition, the patient must be given sufficient hydration, nutrients, and electrolytes. If needed, the patient should also receive respiratory support. Analgesics can be given for overall pain and topical anesthetics can be applied to local pain. To avoid infection, the dead skin should be removed, and the area should be cleaned with antiseptics. If a patient develops an infection, systemic antibiotics can be used. Medications used to treat SJS/TENS include systemic corticosteroids, intravenous immunoglobulins (IVIGs), cyclosporine, TNF-α antagonists (infliximab and etanercept), and plasmapheresis. There is no standard treatment due to side effects caused by medications. Systemic corticosteroids increase infection rates and may lead to higher mortality rates. IVIG mechanism is unknown and may not improve mortality rates. Cyclosporine, TNF-α antagonists, and plasmapheresis have shown benefits on SJS/TENs, however, there is not enough evidence.

         Quick diagnosis and rapid response are key in improving and treating a patient with SJS/TENs. Although there is not a set treatment plan for the condition, more research and medications continue to emerge. Morbidity and mortality rates should greatly decrease as new discoveries are made. 

Hasegawa A, Abe R. Recent advances in managing and understanding Stevens-Johnson syndrome and toxic epidermal necrolysis. F1000Res. 2020 Jun 16;9:F1000 Faculty Rev-612. doi: 10.12688/f1000research.24748.1. PMID: 32595945; PMCID: PMC7308994.

 Liotti L, Caimmi S, Bottau P, Bernardini R, Cardinale F, Saretta F, Mori F, Crisafulli G, Franceschini F, Caffarelli C. Clinical features, outcomes and treatment in children with drug induced Stevens-Johnson syndrome and toxic epidermal necrolysis. Acta Biomed. 2019 Jan 29;90(3-S):52-60. doi: 10.23750/abm.v90i3-S.8165. PMID: 30830062; PMCID: PMC6502171.

SJS/TEN

Steven-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are both rare and severe skin conditions that are often triggered by certain medications. They are characterized by a widespread detachment of skin and mucous membranes which can be life-threatening. SJS is acute compared to TEN, as it affects less than 10% of the skin. It typically begins with flu-like symptoms, such as fever, sore throat, cough, and body aches. In addition, a small red or purple rash will appear, slowly changing and spreading, which can be painful. As the rash progresses, the epidermis will start detaching from the underlying dermis layer. It can also affect mucous membranes such as, in the mouth, eyes, and genital region, leading to painful sores and blisters. On the other hand, TEN is more severe and affects more than 30% of the body. Like SJS, TEN also begins with flu-like symptoms which will progress to a widespread rash and skin detachment. 

They are commonly caused by a variety of medications including, antibiotics, anticonvulsants, nonsteroidal anti-inflammatory drugs (NSAIDs), antiviral and allopurinol. Particularly, antibiotics containing sulfa, penicillins, and cephalosporins have been linked to causing SJS/TEN. Carbamazepine, phenytoin, and lamotrigine are the anticonvulsants that can potentially cause this. In addition, antivirals that are used to treat HIV specifically such as nevirapine and abacavir, have been linked. 

The first step in treatment with SJS or TEN is to discontinue the offending agent. Next, would be supportive care. Since skin detachment and sloughing are the concerning factors, it would be treated as a burn patient where one would also experience this. Therefore, they will treat for pain management, wound care, and fluid/electrolyte replenishment. In the early stages, intravenous immunoglobulin can be used to suppress the immune system and reduce the severity of the condition. For those whose eyes are involved, eye drops can be used to lubricate the eyes. Removal of necrotic tissue and possible use of antibiotics for secondary infection prevention can also be utilized. 

The prognosis for TEN is more severe and the mortality rate is around 25-30% of patients depending on the severity. However, both SJS and TEN can cause complications even after survival such as scarring, vision problems, and respiratory issues. 

References: 

1. Oakley AM, Krishnamurthy K. Stevens-Johnson Syndrome. [Updated 2023 Apr 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459323/ 

2. Labib AM, Milroy C. Toxic Epidermal Necrolysis. [Updated 2023 May 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK574530/ 

Steven-Johnson Syndrome / Toxic Epidermal Necrolysis (SJS/TEN)

Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are dermatologic emergencies characterized by widespread epidermal necrolysis and sloughing. They are considered to have the same pathophysiology and are classified based on body surface area involved. SJS/TEN are complex blistering eruptions that are immune complex or cell-mediated allergic responses to offending agents, including drugs. Medications are causative in over 80 percent of SJS/TEN cases. Usual drug culprits include sulfonamides especially sulfasalazine and sulfamethoxazole, penicillin’s, some anticonvulsants such as hydantoins, carbamazepine, barbiturates, lamotrigine, NSAIDs, and allopurinol.  

There is genetic association between some drug causes of SJS/TEN and HLA alleles. Certain HLA allotypes can lead to an increased risk of SJS/TEN when exposed to anticonvulsants and allopurinol. The HLA-B*1502 allele is shown to cause an increased risk in patients taking aromatic anticonvulsants. HLA-B*5801 allele is associated with allopurinol risk, HLA-B*5701 with abacavir, and HLA-A*3101 with carbamazepine are alleles found to date with increased SJS/TEN risk.

SJS/TEN are rare, severe, and life-threatening with an acute onset. SJS is classified as less than 10 percent of body surface area being detached skin, TEN is more than 30 percent body surface area and between 10 and 30 percent is considered an overlap between the two. Patients begin to present with nonspecific symptoms such as fever and malaise, upper respiratory tract symptoms such as cough, rhinitis, ore eyes and myalgia. Over the next three to four days, a blistering rash and erosions appear on the face, trunk, limbs, and mucosal surfaces. Patients present with erythematous, targetoid, annular, or purpuric macules, flaccid bullae, large painful erosion, and Nikolsky-positive. Early on toxic epidermal necrolysis displays widespread tender erythroderma and erosions, whereas Steven-Johnson syndrome is characterized more by a targetoid rash, with fewer areas of denudation. Mucosal ulceration and erosions can involve the lips, mouth, pharynx, esophagus and gastrointestinal tract, eyes, genitals, and upper respiratory tract.

Patients with Steven-Johnson Syndrome /Toxic epidermal necrolysis should seek immediate hospitalization in an intensive care setting. Multifaceted levels of care are required with an intensivist, dermatologist, plastic surgery or burns specialist, ophthalmologist, respiratory physician, urologist, gynecologist, physical therapist, and nutritionist. Extensive supportive care is required including, cessation of the suspected causative drug or drugs, crystalloid fluid replacement, sterile and aseptic handling, nutritional assessment as the patient may require nasogastric tube feeding. Temperature control is very important as well, the patient may require a warm environment and an emergency blanket. An important factor in treatment is pain relief, as the lesions are excruciatingly painful. Supplemental oxygen and in some cases, initiation with mechanical ventilation is required. Skincare requires daily examination of the skin and mucosal surfaces for infection, non-adherent dressings, and avoidance of trauma to the skin, The mucosal surfaces require careful cleansing and topical anesthetics. Patients require gentle removal of necrotic skin/mucosal tissue and cultures of skin lesions, axilla, and groins every two days. If secondary infection develops, antibiotics may be needed, but they should be avoided for prophylactic use. Although the benefit is unknown, systemic corticosteroids are also prescribed for the first few days after admission.

References

Oakley AM, Krishnamurthy K. Stevens-Johnson Syndrome. [Updated 2023 Apr 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459323/

Ergen EN, Hughey LC. Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis. JAMA Dermatol. 2017;153(12):1344. doi:10.1001/jamadermatol.2017.3957

Frantz, R., Huang, S., Are, A., & Motaparthi, K. (2021). Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis: A Review of Diagnosis and Management. Medicina, 57(9), 895. https://doi.org/10.3390/medicina57090895

Law R.M., & Law D.S., & Maibach H.I. (2020). Dermatologic drug reactions, contact dermatitis, and common skin conditions. DiPiro J.T., & Yee G.C., & Posey L, & Haines S.T., & Nolin T.D., & Ellingrod V(Eds.), Pharmacotherapy: A Pathophysiologic Approach, 11e. McGraw Hill. https://accesspharmacy-mhmedical-com.jerome.stjohns.edu/content.aspx?bookid=2577&sectionid=239762003

Steven-Johnson Syndrome and Toxic Epidermal Necrolysis

Steven-Johnson syndrome and toxic epidermal necrolysis are rare drug-induced adverse skin reactions that are life-threatening. They are characterized by necrosis of the epidermis with blistering. Symptoms begin with fever, malaise, sore throat, and cough. The skin reaction consists of red lesions on the trunk that progress and usually involve the mucosal surfaces. Mucositis and ulceration of the oral cavity occurs in about every case. SJS involves less than 10% of the body surface area. SJS/TEN overlap involves 10-30% of the body surface area. Lastly, TEN is the most severe involving more than 30% of the body surface area (Frantz, R. et al). Drugs are the most common cause of these conditions, followed by infection with Mycoplasma pneumonia (Frantz, R. et al.). These reactions are likely type IV hypersensitivity reactions mediated by T-cells. One proposed mechanism is that drugs can act as a hapten, bind to proteins in the serum, and be presented to T-cells as an antigen to create an immune response. Variations in the HLA genes can place individuals at increased risk. HLA phenotype testing should be done in races with known susceptibility before beginning certain medications.

When diagnosing someone with SJS/TEN, it is important to do so quickly and avoid misdiagnosis by obtaining a skin biopsy of the rash. Misdiagnosis is possible since these conditions are similar to other blistering conditions. It is important to stop the offending drug immediately. Identifying the drug can be difficult, but a reaction would typically be within 8 weeks of beginning. Most cases appear between 4 days and 4 weeks of beginning drug therapy (Frantz, R. et al). Patients need to be managed in a setting that is capable of treatment like skin departments or burn units with a diverse team. Management may consist of corticosteroids or intravenous immunoglobulin (IVIg) along with supportive care. Etanercept and cyclosporine are newer treatments that have shown potential as treatment. There is disagreement on whether there should be debridement of the blisters. It is important that the skin be taken care of with non adherent dressings and paraffin emollient (Chang, W. C. et al). All female patients should be seen by a gynecologist since there is a chance of scarring and stenosis. Supportive care includes fluid and electrolyte management, infection control, and wound care.

Many studies have shown that there are biomarkers for this condition. One study demonstrated that 4 out of 5 patients with SJS/TEN had elevated levels of granulysin, but this is not specific to only SJS/TEN as other blistering disorders may show the same. Another biomarker that was studied was CCL-27 which is a cytokine involved. This molecule is also present in other conditions making it unsuitable in diagnosis of SJS/TEN. Galectin-7 is a protein that may be a biomarker that can be used in diagnosis. RIP3 is another promising biomarker that can possibly distinguish between SJS/TEN and EMM (Frantz, R. et al.).

Drugs that commonly cause SJS/TEN include antiepileptics like carbamazepine, antibiotics like Bactrim, NSAIDs, allopurinol, nevirapine and immune checkpoint inhibitors (Frants, R. et al.). Further research is required to determine the best treatment of this condition, as well as potential biomarkers that can help make correct diagnoses quickly.

Resources:

Chang, W. C., Abe, R., Anderson, P., Anderson, W., Ardern-Jones, M. R., Beachkofsky, T. M., Bellón, T., Biala, A. K., Bouchard, C., Cavalleri, G. L., Chapman, N., Chodosh, J., Choi, H. K., Cibotti, R. R., Divito, S. J., Dewar, K., Dehaeck, U., Etminan, M., Forbes, D., Fuchs, E., … Carleton, B. C. (2020). SJS/TEN 2019: From science to translation. Journal of dermatological science, 98(1), 2–12. https://doi.org/10.1016/j.jdermsci.2020.02.003

Frantz, R., Huang, S., Are, A., & Motaparthi, K. (2021). Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Review of Diagnosis and Management. Medicina (Kaunas, Lithuania), 57(9), 895. https://doi.org/10.3390/medicina57090895

SJS/TEN

Steven Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are severe immunologic skin reactions characterized by necrosis, skin detachment, and involvement of the mucous membrane of the eyes, mouth, and/or genitals. One of the first symptoms of both SJS and TEN are fever and flu-like symptoms which include body aches and cough. Following suit in 1 to 3 days is the formation of a red to purple rash, and blistering and peeling of the skin that usually begins in the face, and then spreads to other areas of the body. Other symptoms include conjunctivitis, difficulty swallowing and breathing, genital pain, and difficulty urinating. The difference between SJS and TEN is that SJS is less severe, with skin detachment involving less than 10% of the body surface; In TEN, skin detachment involves more than 30% of the body surface. Regardless of severity, both are life-threatening emergencies and are usually caused by certain medications, which include anticonvulsants, allopurinol, sulfonamides, antibiotics, NSAIDs, and contrast media. Moreover, these dermatologic reactions can also be triggered by infections like pneumonia, herpes virus, and hepatitis A. Individuals who have HIV, a compromised immune system, a family history of SJS/TEN, or variation of the HLA-B gene are at an increased risk of developing SJS/TEN.

Necrosis from SJS/TEN is caused by immune activation where induction of cytotoxic T lymphocytes, CD4+ cells, and innate immune cells lead to the secretion of granulysin and other cytokines. The drug-associated antigen or metabolite interacts and binds to the major histocompatibility complex (MHC) type 1 or cellular peptide to form an immunogenic compound. CD8+ cells present in blister fluid induces keratinocyte apoptosis. CD40 ligand cells induce the release of TNF-alpha, nitrous oxide, IL-8, and cell adhesion antibodies. TNF-alpha induces apoptosis. As a result, the secretion of these molecules puncture the cell membrane, causing widespread apoptosis. It is a Type IV cell mediated reaction. Another mechanism involved in the cause of SJS/TEN is that the drug metabolites become immunogenic and stimulate the immune system, known as the pro-hapten concept. About 5-20% of SJS/TEN are idiopathic, meaning, it is caused spontaneously with an unknown cause; however, 50-95% of cases are caused due to immune predisposition and exogenous factors, for instance, particular medications listed below:

Anticonvulsants: lamotrigine, carbamazepine, phenytoin, phenobarbitone

Allopurinol: >100 mg per day

Sulfonamides: cotrimoxazole, sulfasalazine

Antibiotics: penicillins, cephalosporins, quinolones, minocycline

Acetaminophen

Nevirapine (non-nucleoside reverse-transcriptase inhibitor)

NSAIDs: oxicam type mainly

Contrast media

Genetic factors play a role. Individuals of with the HLA-A*31:01 or HLA-B*15:02 are at risk for developing SJS/TEN upon ingestion of carbamazepine. On the other hand, those with the HLA-B*58:01 genes are more likely to develop SJS/TEN upon the ingestion of allopurinol.

SJS mortality ranges from 5 to 18% and usually lasts about 4-6 weeks. There is moderate mucocutaneous and systemic involvement that leads to blistering and atypical target lesions involving 10% of the body surface area. Clinical manifestations are epidermal detachment, hemorrhagic skin, joint pain, onset of pneumonia, and serious ocular involvement. In TEN, clinical manifestations include erythema and massive bullae formation that ruptures and peels. The mortality is 30%, often within 8 days after bullae formation. Likewise, 70% heal with potential for scarring.

In SJS/TEN, prevention is key. For instance, it is important to perform HLA-B testing in susceptible races. For instance, in Han Chinese, Thai, Malaysian, and South Indians, they have a higher likelihood of carrying the HLA-B*1502 gene. If these individuals take anticonvulsants containing aromatic compounds, they may develop SJS/TEN. Europeans that carry the HLA-B*5701 who take abacavir are also at risk, or if they carry HLA-A*3101 and take carbamazepine. Individuals with the human leukocyte antigen (HLA) allotypes are at an increased risk of SJS/TEN when exposed to aromatic anticonvulsants and allopurinol. Due to genetic factors, it is important to inform family members of the affected patient since they are at risk of developing the disease if taken particular medications as well. Managing SJS/TEN is performed in a hospital setting, and involves immediate cessation of suspected causative drug(s). Supportive care involves nutritional and fluid replacement (crystalloid) by intravenous and nasogastric routes, maintaining body temperature (since temperature regulation is impaired given dermatologic necrosis), pain relief, skin care and infection control, topical silver nitrate or chlorhexidine (avoid silver sulfadiazine), and application of dressings like gauze with petrolatum or non-adherent nanocrystalline-containing gauze. It is important to avoid using adhesive tape. Further, using mouthwashes or topical oral anesthetics may be advised if mucosal membranes are involved. Regular assessment for infection of the skin, mucous membranes, and catheter sites is necessary. According to case reports and small patient series, it has been reported that there is benefit from delivery of an active adjuvant treatment during the first 24-48 hours of illness. For instance, administration of cyclosporin 3-5 mg/kg/day, cyclophosphamide, or intravenous immunoglobulin (IVIG) 2-3 g/kg, and plasmapheresis have had variable responses.

References

Oakley, Amanda M. “Stevens-Johnson Syndrome - StatPearls - NCBI Bookshelf.” Steven-Johnson Syndrome, 10 Apr. 2023, www.ncbi.nlm.nih.gov/books/NBK459323/.

“Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis - about the Disease.” Genetic and

Rare Diseases Information Center, rarediseases.info.nih.gov/diseases/7700/stevens-johnson-syndrometoxic-epidermal-necrolysis. Accessed 8 June 2023.

Zimmerman, Danielle, and Nam Hoang Dang. “Stevens–Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN): Immunologic Reactions.” Edited by Joseph L. Nates and Kristen J. Price, Oncologic Critical Care, 9 July 2019, www.ncbi.nlm.nih.gov/pmc/articles/PMC7122590/.

Written by Aleksandra Agranovich

Steven Johnsons Syndrome (SJS)

Steven Johnson syndrome is a very rare but serious skin disease that usually occurs due to a drug-related side effect. SJS can be characterized by the detachment of the epidermis and mucous membrane. Patients who have this condition often experience flu-like symptoms, a painful rash and blisters. Toxic Epidermal Necrolysis (TEN) is also a skin disease that is very much similar to SJS. Both of these conditions, if untreated, can lead to complications of the liver, kidneys, and respiratory tract (Hasegawa, 2020). The pathogenicity of SJS/TEN can be explained by extensive epidermal cell death. In addition, this disease also tends to activate many different types of cytokines within the immune system which may lead to inflammation.

The drugs that most commonly cause this disease include carbamazepine and allopurinol. Carbamazepine is an anticonvulsant that can be used to treat seizures, epilepsy, and neuropathic pain. Allopurinol, on the other hand, is a medication that is indicated to decrease high levels of uric acid in patients who have gout. The recommended treatment for SJS/TENS most often includes supportive care. However, according to guidelines, systemic corticosteroids, intravenous immunoglobulin, cyclosporine, and TNF-α antagonists may be considered as well.

Drug Reaction with Eosinophilia and Systemic Symptoms

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a potentially life-threatening drug related reaction. DRESS occurs as a result of drug-induced hypersensitivity and can be seen with fever, lymphadenopathy, hematologic abnormalities, and organ failure (Husain, 2013).

The most common offending agents include anticonvulsants such as carbamazepine or phenytoin and sulfonamide antibiotics. Unlike SJS/TEN, DRESS syndrome usually takes 2-6 weeks to occur. The most important way to prevent and treat DRESS syndrome is to discontinue the medication that is being given.

Resources

Hasegawa A, Abe R. Recent advances in managing and understanding Stevens-Johnson syndrome and toxic epidermal necrolysis. F1000Res. 2020;9:F1000 Faculty Rev-612. Published 2020 Jun 16. doi:10.12688/f1000research.24748.1

Husain, Zain et al. “DRESS syndrome: Part I. Clinical perspectives.” Journal of the American Academy of Dermatology vol. 68,5 (2013): 693.e1-14; quiz 706-8. doi:10.1016/j.jaad.2013.01.033

Liotti, Lucia et al. “Clinical features, outcomes and treatment in children with drug induced Stevens-Johnson syndrome and toxic epidermal necrolysis.” Acta bio-medica : Atenei Parmensis vol. 90,3-S 52-60. 29 Jan. 2019, doi:10.23750/abm.v90i3-S.8165

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis

Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are rare but serious skin diseases that are characterized by widespread epidermal necrosis and sloughing of skin. These T-cell mediated, type IV hypersensitivity reactions are associated with significant morbidity and mortality. These two diseases have the same pathophysiology and symptoms with the difference in diagnosis being based on the body surface area (BSA) affected. Patients with <10% BSA affected are diagnosed with SJS while patients with >30% BSA affected receive a diagnosis of TEN. There is an overlap between the diseases between 10-30% BSA affected. Often times, SJS/TEN are caused by an adverse reaction to a medication. Symptoms usually present within 8 weeks of beginning therapy with a new medication but most cases appear between 4 days and 4 weeks. Initially, patients with SJS/TEN present with fever, malaise, sore throat, and cough. Photophobia, conjunctival itching or burning, and pain when swallowing may be early signs of mucosal involvement. After 1-3 days of this prodromal period, the skin involvement appears as erythematous macules or atypical target lesions on the trunk. These macules and lesions are painful and will start to blister and peel. When mucous membranes are involved it presents as redness, blisters and erosions on the lips and inside the mouth. Eye involvement presents as redness, irritation and pain (Ergen 2017). This acute phase lasts around 8-12 days. Re-epithelialization begins after several days and takes 2-4 weeks (Frantz 2021).

The pathophysiology behind SJS/TEN is not completely understood. There are several drugs that are known to cause these skin reactions. Those drugs include: lamotrigine, phenytoin, carbamazepine, valproic acid, phenobarbital, TMP-SMX, aminopenicillins, tetracyclines, cephalosporins, NSAIDs, allopurinol, nevirapine, nivolumab, and pembrolizumab (Frantz 2021). SJS/TEN may also be caused by infection with mycoplasma pneumonia being the most common infectious cause. There are several hypotheses for their development. The first is the hapten/pro-hapten concept that small-molecule drugs will covalently bind to proteins in serum, forming a complex that is recognized by certain HLA molecules and presented to T-cells to cause an immune response. The second is that chemically inert drugs cannot undergo covalent binding with serum proteins so they bind HLA molecules directly leading to T-cell activation. The third is that drugs bind inside HLA binding pockets in a way that alters presentation of self-proteins to T-cells, so that they are no longer recognized as self, leading to an immune response (Frantz 2021). It is still unknown which hypothesis is true but we know that the end result is T-cell activation leading to an immune response.

The first step in the management of SJS/TENs is identifying the disease and discontinuing the causative agent. After this first important step, management mostly involves supportive care. Patients should be kept in a warm environment due to their skin’s loss of thermoregulatory function. Fluids and electrolytes are needed as well as enteral nutrition due to the mucosal involvement causing difficulty with oral ingestion. Infection control and wound care are also very important parts of recovery as infection is a common complication with these diseases. There is no guideline recommended pharmacologic treatment however, corticosteroids and IV immunoglobulin are two common treatments that may be implemented (Frantz 2021).

Resources:

Ergen EN, Hughey LC. Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis. JAMA Dermatol. 2017;153(12):1344. doi:10.1001/jamadermatol.2017.3957

Frantz R, Huang S, Are A, Motaparthi K. Stevens–Johnson Syndrome and toxic epidermal necrolysis: A review of diagnosis and management. Medicina. 2021;57(9):895. doi:10.3390/medicina57090895

Stevens-Johnson Syndrome, also known as SJS, is a rare albeit a very serious and unpredictable disorder that affects the skin, mucous membrane, genitals and eyes. It is denoted as an adverse reaction primarily to certain medications and can occasionally be caused by an infection. Key examples of medication that are causative agents include allopurinol, nevirapine, the “oxicam” class of non-steroidal anti-inflammatory drugs (NSAIDs) such as meloxicam, sulfa antibiotics including sulfamethoxazole (commonly available as the combination antibiotic Bactrim; sulfamethoxazole-trimethoprim), lamotrigine, sertraline, and sulfasalazine, and several different antipsychotics including carbamazepine, phenobarbital, and phenytoin. What I found to be one of the scariest parts of this syndrome is that SJS can occur up to two weeks after a person has discontinued the use of a medication. This is why certain of these causative agents like lamotrigine are required to have very careful tapering up or tapering off. There are also certain risk factors that predisposes a patient to SJS which include an HIV infection, cancer, and a weakened immune system such as an organ transplant and other autoimmune diseases.

The most common symptoms of SJS is skin pain in conjunction with flu-like symptoms which may include but are not limited to a general feeling of malaise, a high temperature of equal to or greater than 100.4 degrees Fahrenheit, a headache, and a cough. These symptoms are all presented in the initial stages of the clinical presentation of SJS and a couple of days later are subsequently followed by a rash that resembles the appearance of a target as they resemble spots that are lighter around the border and darker towards the center. Albeit the rash isn’t itchy, it typically spreads over a number of days or even hours. This is followed by large blisters on the skin that burst and result in painful sores. Other distinctive symptoms are facial and lip swelling in addition to blistered and ulcerated mucous membranes inside a person’s mouth, throat, eyes, and genital tract.

Treating Stevens-Johnson Syndrome requires immediate medical attention. The first step in treating SJS is complete cessation of any medications that may be the causative agents of SJS; since this may be difficult to determine, complete cessation of all non-essential medications is strongly recommended. Treatment for relief of SJS symptoms while under hospitalization include strong painkillers in order to alleviate the pain of affected areas of the skin, moist and cool compressions held against affected areas of the skin, replacement fluids to supply fluids and nutrition that’s inserted into the human body through a nasogastric tube (a tube that is placed through the nose and into the stomach), and a short course of oral steroids in order to better control inflammation of the skin. In addition to this, antibiotics can be administered in case sepsis (which is extremely dangerous) is detected in the blood and eye drops/eye ointments for particular eye-related SJS symptoms. Severe cases of SJS may be needed to treat in either the burn unit or the intensive care unit (ICU).

References-

Stevens-Johnson Syndrome. National Health Service (NHS) UK. https://www.nhs.uk/conditions/stevens-johnson-syndrome/

Stevens-Johnson Syndrome. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/stevens-johnson-syndrome/symptoms-causes/syc-20355936

Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) are rare and severe mucocutaneous blistering diseases associated with high mortality. SJS and TEN are not separate conditions, rather are part of a disease spectrum with SJS as less severe and TEN as more severe. SJS is when skin detachment includes less than 10% of the body's surface and TEN is when skin detachment includes more than 30% of the body’s surface. Patients with 10-30% skin detachment may experience SJS/TEN overlap. But whether the patient experiences SJS, TEN or both SJS/TEN all these forms are life threatening medical emergencies that require immediate treatment.

SJS/TEN is usually caused by idiosyncratic drug reactions due to certain medications, infections, pre-existing health conditions, and family history. High-risk drugs that trigger SJS/TEN include allopurinol and antibiotics such as penicillins, cephalosporins, sulfonamides and quinolones. Other high risk drugs include antiepileptics such as lamotrigine, carbamazepine, and phenobarbital. Non-steroidal anti inflammatory drugs such as abacavir, nevirapine and oxicam derivatives are also known triggers of SJS/TEN. Symptoms of SJS/TEN that result from adverse drug reactions are often observed within a month to two months, and may even last up to two weeks after discontinuing the offending agent. Infections that trigger SJS/TEN involve both bacterial and viral infections such as herpes, pneumonia, hepatitis A, tuberculosis, influenza, measles and mumps. Health conditions that increase a person’s risk for SJS/TEN include patients who are HIV positive, HLA-B gene mutations, weakened immune system (ex. cancer), and family history of SJS/TEN.

The earlier the diagnosis and management of SJS/TEN, the better the recovery for the patient affected. Symptoms of SJS/TEN may appear within a one to four day influenza-like stage that includes fever, chills, headache and sore throat. Before any cutaneous lesions appear, signs of mucosal irritation (conjunctivitis, dysphagia, and dysuria) will occur. The skin blisters and peels leading to detachment of the skin which leaves the patient in immense pain. The areas of the body affected by SJS/TEN may typically start on the face and chest and eventually spread over the rest of the body. Skin rashes start as macules/patches that blister and erode. Skin lesions are irregular in shape, purpuric with necrotic centers. Individual skin lesions may coalesce to form large painful erythematous patches on the body. These skin lesions may display a positive Nikolsky sign in which the skin peels upon pressure applied.

Involvement of mucous membrane in multiple areas is a hallmark of SJS/TEN, and can range from a mild to severe form. The affected mucous membrane areas are located in oral (mouth), nasopharyngeal (throat), digestive tract, respiratory, genitourinary (genitals), and rectal routes.

Early signs of mucous membrane involvement are itching/burning on the eyes, light sensitivity, and painful swallowing. The greater the total body surface area involvement (TBSA) the more severe the disease. Patients who are taking high-risk drugs and develop SJS/TEN could develop red plaques or papules, blisters, erosions, and mucosal involvement which will persist for 2 months during usage.

In treating SJS/TEN is crucial to immediately discontinue the offending agent and all other unnecessary medications. The patient must be admitted into the hospital in an intensive care unit, burn unit or specialized dermatology unit to seek appropriate care, improving chances of recovery. Patients need to be stabilized hemodynamically through intensive skin/eye/mucous membrane treatment such as wound care & pain control, temperature management, infection prophylaxis, fluids and electrolytes and calorie replacement. Affected eyes must be treated immediately to prevent permanent eye damage and vision loss. Eye treatment includes saline rinses, lubrication through eye ointments and eye drops, topical corticosteroids, antibiotics and amniotic membrane transplantation (AMT). Aside from supportive care, various treatments have been tried by doctors that include intravenous immune globulin (IVIG), systemic corticosteroids, cyclosporine and anti-tumor necrosis factor (TNF) monoclonal antibodies however no agent other than cyclosporine have shown conclusive benefits.

1. Smith C. Erythema Multiforme, Stevens–Johnson Syndrome, Toxic Epidermal Necrolysis, Staphylococcal Scalded Skin Syndrome. In: Soutor C, Hordinsky MK. eds. Clinical Dermatology. McGraw-Hill; Accessed June 15, 2021. https://accessmedicine-mhmedical-com.jerome.stjohns.edu/content.aspx?bookid=2184&sectionid=165460970

2. Stevens-Johnson Syndrome/ Toxic Epidermal Necrolysis. U.S. Department of Health & Human Services; National Institutes of Health. https://rarediseases.info.nih.gov/diseases/7700/stevens-johnson-syndrometoxic-epidermal-necrolysis. Accessed 2021 June 15.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are two of the most life-threatening dermatologic skin reactions, typically caused by medications. These two adverse cutaneous reactions appear as erythematous or violaceous patches of skin with various types of skin lesions, such as bullae, blisters, and ulcers, and epidermal detachment. SJS is classified as less than 10% of the body surface area with epidermal detachment while TEN is classified as over 30% and there is SJS/TEN overlap in between (10-30%). The SJS/TEN overlap typically involves the oral mucosa and other mucocutaneous areas. Other non-specific symptoms may include pain, fever, stinging eyes, malaise, sore throat, etc. SJS and TEN are commonly associated with drugs such as allopurinol, carbamazepine, phenytoin, lamotrigine, oxcarbazepine, phenobarbital, sulfonamide antibiotics, etc. Some of these drugs require patients to undergo pharmacogenomic testing before initiation of the drug to screen for certain genetic factors that may put the patient at high risk for SJS/TEN. For example, carbamazepine typically requires screening for the HLA-B*1502 allele prior to treatment initiation and patients who test positive for the allele should avoid using carbamazepine unless there are no other drug options and the benefits outweigh the risks. Even after being approved to use the drug, patients must be counseled to monitor for any skin reactions or other adverse reactions, especially during the first two months after drug initiation since a negative allele detection does not completely rule out the possibility of SJS/TEN. Management of SJS/TEN involves immediate discontinuation of the offending drug and supportive care. Supportive care usually consists of fluid and electrolyte replenishment and careful wound care. Treatment of SJS/TEN should be tailored to the individual patient because there is no drug to cure these conditions. Even after initial resolution, patients tend to live with long-term consequences such as scarring, irregular pigmentation, and other chronic skin conditions.

References:

1. Schneider JA, Cohen PR. Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Concise Review with a Comprehensive Summary of Therapeutic Interventions Emphasizing Supportive Measures. Adv Ther. 2017;34(6):1235-1244. doi:10.1007/s12325-017-0530-y

2. Harr T, French LE. Toxic epidermal necrolysis and Stevens-Johnson syndrome. Orphanet J Rare Dis. 2010;5:39. Published 2010 Dec 16. doi:10.1186/1750-1172-5-39

Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are often confused since they are so clinically similar. They are a delayed-type hypersensitivity reaction and differ in their distribution on the body. SJS affects <10% of body surface area while TEN affects 30% or more. The range of 10 to 30% of body distribution is known as the SJS/TEN overlap. Notably, both disorders affect 1 to 5 people in a million, making it extremely rare. Source 1 notes that severity and incidence may be increased in the case of bone marrow transplant recipients. The most common drugs that put patients in risk of SJS or TEN includes sulfa drugs, antibiotics like aminopenicillins, fluoroquinolones, and cephalosporins, antiseizures like phenytoin, carbamazepine, phenobarbital, valproate, NSAIDs, and antiretroviral drugs. If not drug related, other causes include infection, vaccination, or graft vs host disease. Merck notes that it is rare that a cause cannot be identified and this is valuable in that the more documentation of causes collected, the more efficiently future cases can be diagnosed due to statistics. Current perspective on Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis from Lerch, Marianne, et.al states “the acute management of SJS/TEN requires a multidisciplinary approach. Immediate withdrawal of potentially causative drugs is mandatory. Prompt referral to an appropriate medical center for specific supportive treatment is of utmost importance. The most frequently used treatments for SJS/TEN are systemic corticosteroids, immunoglobulins, and cyclosporine A.”

1. https://www.merckmanuals.com/professional/dermatologic-disorders/hypersensitivity-and-inflammatory-skin-disorders/stevens-johnson-syndrome-sjs-and-toxic-epidermal-necrolysis-ten

2. https://pubmed.ncbi.nlm.nih.gov/29188475/

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe and life-threatening skin reactions that have various causes such as viral or bacterial infections, drugs, or genetics (HLA-B*15:02 with carbamazepine in Asian population). With mortality rate being high, it is important for patients to receive immediate medical attention. Both skin conditions are commonly referred to as erythematous rashes that can be bullae or atypical lesions that will develop on the face and trunk of the body. These lesions will eventually spread out to other regions on the body with the epidermal layer separating from the dermis which is described as extremely painful. SJS/TEN is thought to be brought on by the activation of T-cells. The T-cells will be stimulated by drugs binding to the T-cell receptor through the antigen-presenting cells. The stimulation further transverses into the destruction of the epidermis caused by cytotoxic CD8+ T-cell apoptosis. SJS covers about 10% of the total body surface area while TEN is a more extreme case that covers more than 30% of the total body surface area. A patient suffering from SJS/TEN will first appear with systemic symptoms such as a fever and upper respiratory tract conditions followed by the painful rash. Other areas that can be affected could be the mucous membranes of the eyes, genitalia, and the mouth leading to dryness and erosion. There have been reports of SJS/TEN affecting major organ systems involving the liver, kidneys, and the lungs which is the reason why healthcare professionals must leap into action to provide specialized care for patients to reduce mortality risk. SJS/TEN has a large association with drugs. The most common type of drugs to cause SJS/TEN are antibiotics, allopurinol, NSAIDs, and anticonvulsants. Along with drug assessment, physicians may incorporate genetic testing for certain patients if they possess risk factors that put them at a higher risk of developing SJS/TEN.

One of the ways to initially manage the condition is to discontinue the offending agent as soon as possible. This step is crucial to prevent worsening of the disease. After discontinuing the agent, patients are then given supportive care to improve drying effects with fluid and electrolyte replacement (0.7ml/kg/% affected area), nutritional supplementation (albumin solution), pain relief, and supplemental oxygen if it is needed. It is also important that patients receive proper skin care treatment to the epidermis to promote wound healing due the destroyed keratinocytes. If a patient is suspected to have bacterial or viral infection, they are given an antibiotic to help decrease the risk of sepsis. Patients may also be treated with adjunctive therapy. Although there is still lack of evidence on the efficacy of adjunctive treatment such as systemic steroids, TNF-a blockers, and IV immunoglobulins, they may play a role in the treatment of SJS/TEN. Some studies have shown that high-dose systemic corticosteroids used short-term may reduce the risk of mortality and improved wound healing. Reports on the use of IV immunoglobulins is still controversial due to the conflicting data. Furthermore, there is still a lack of evidence with TNF-a blockers. Also, different countries follow different treatment guidelines with some providing supportive care as first-line while others providing systemic adjunctive therapy as first-line. Nonetheless, all the guidelines agree to stop the offending agent immediately and use supportive care to increase survival rate.

References

Schneider, J. A., & Cohen, P. R. (2017). Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Concise Review with a Comprehensive Summary of Therapeutic Interventions Emphasizing Supportive Measures. Advances in therapy, 34(6), 1235–1244. https://doi.org/10.1007/s12325-017-0530-y

Hasegawa, A., & Abe, R. (2020). Recent advances in managing and understanding Stevens-Johnson syndrome and toxic epidermal necrolysis. F1000Research, 9, F1000 Faculty Rev-612. https://doi.org/10.12688/f1000research.24748.1

Stevens-Johnson Syndrome, or SJS, is a mucocutaneous reaction usually caused by medications, characterized by extensive necrosis and detachment of the skin. Mucous membranes like the eyes, mouth and genitals are often affected in SJS. This disease is classified as SJS when less than 10% of the body’s skin falls off, whereas with TENS, or toxic epidermal necrolysis, more than 30% of the skin falls off. TENS is much more severe and fatal, and SJS can progress into it (known as SJS/TENS overlap). The incidence of this serious condition is more prominent in immunocompromised populations, like those living with HIV/AIDS or cancer. It is also more common in women than in men, and it can present a fatality range ranging from 10-40% depending on the patient, severity and duration of the symptoms.

SJS/TENS is caused by drugs in the majority of cases in both adults and children. The typical onset of symptoms is 4 days to 4 weeks of that specific drug treatment, so drugs that are used for a long period of time (> 8 weeks) are unlikely to be the cause of SJS/TENS. In a large case control study on UpToDate, it was found that the main causative agents included Allopurinol, aromatic antiepileptic drugs and lamotrigine, antibacterial sulfonamides (including sulfasalazine), Nevirapine, and oxicam nonsteroidal anti-inflammatory drugs (NSAIDs). Anticancer therapies have also been found to cause SJS or SJS-like presentations. Infections (for example, Mycoplasma pneumoniae) are also known to cause SJS/TENS.

While the pathology is not completely understood, it is suggested that a cell-mediated cytotoxic reaction occurs against keratinocytes leading to massive apoptosis. Drugs also target specific mediators in the skin that cause toxic reactions. SJS/TENs will usually occur rapidly and this acute phase will last about 8 to 12 days. It will present in the patient as fever, severe mucous membrane involvement, and epidermal sloughing that may be generalized and result in large, raw, painful areas of denuded skin. this sloughing of the skin will occur a few days after vesicles and bullae form. This can progress to more life-threatening complications like fluid loss, electrolyte imbalance, hypovolemic shock, bacteremia and multiple organ failure.

Prompt withdrawal and discontinuation of the suspected causative agent is the first step in treating and managing SJS/TENS. Any ocular involvement requires immediate attention. Then begins supportive care, similar for a burn victim, like wound care, fluid and electrolyte management, nutritional support, temperature management, pain control, and monitoring or treatment of superinfections. These patients will be in an immense amount of pain and will likely require therapy (ex: opioids) and close attention regarding pain control. The use of any drug therapies to specifically treat SJS/TENS is controversial. For example, the use of systemic corticosteroids has been studied but not fully evaluated.

1. Whitney A High, MD. Stevens-Johnson syndrome and toxic epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis. UpToDate. Mar 2019.

2. Whitney A High, MD. Stevens-Johnson syndrome and toxic epidermal necrolysis: Management, prognosis, and long-term sequelae. UpToDate. Jan 2021.

Stevens Johnson Syndrome is a rare and acute form of toxic epidermal necrolysis. This rare form of TEN often comes as a reaction to drug-associated CD8+ lymphocytes and the process involves an apoptosis pathway as well as granule-mediated exocytosis. The TNF alpha death pathway is also implicated in the development of SJS. There are numerous medication agents that are known to be culprits behind SJS include: lamotrigine, carbamazepine, phenytoin, phenobarbitone, Allopurinol, sulfonamides such as cotrimoxazole, sulfasalazine, penicillins, cephalosporins, quinolones, minocycline, Paracetamol/acetaminophen, Nevirapine (non-nucleoside reverse-transcriptase inhibitor), Nonsteroidal anti-inflammatory drugs (NSAIDs), and contrast media. For some patients, there may be a genetic predisposition to developing SJS. Unique human leukocyte antigen (HLA) allotypes within patients can cause them to become severely sensitive to medications such as abacavir and allopurinol.

While the exact mechanism of SJS is speculated, it is theorized that the irritant (such as the medication) binds with the antigen or metabolite with the major histocompatibility complex (MHC) type 1 to form an immunogenic compound. The necrolysis process is T-cell mediated, leading to the recruitment of CD8+ cells, CD40 cells, TNF alpha, and interleukins. This reaction then ultimately leads to the breakdown of keratinocytes as well as epidermal necrosis. When a patient presents with SJS, the initial symptoms are nonspecific. This includes fever and malaise, which may not be easily identified as onset of SJS. Other nonspecific symptoms include myalgia, rhinitis, and sore eyes. However, by days three and fore, a rash may begin to form. As the rash progresses into a blistering rash, erosions appear on the face, trunk, limbs, and mucosal surfaces. Mucosal ulcerations that affect the lips, mouth and inner gastrointestinal tracts may also become present as SJS worsens.

If a patient is undergoing SJS then the first thing that is necessary is hospitalization. Patients are more than likely admitted to the intensive care unit or even the burn victim units due to the level of the epidermis that is involved. Once admitted to the hospital, one of the first measures that must be taken includes the discontinuation of current medications in order to eliminate the agent that is responsible for the manifestation of SJS. Due to the nature of the condition, fluid replacement and replenishment is a necessary step. This is something that is commonly done in burn victims, as well, due to the loss of much of the integumentary system. Wound care is another important aspect of treating SJS. Cool compresses to soothe blisters and regular cleaning of open wounds are necessary to ensure that the patient’s skin barrier remains infection-free. In addition, eye care may be required if SJS has progressed to the point where the mucosal barriers present are affected. Some medications may be initiated as well, including pain killers for symptomatic relief and antibiotics to prevent an infection.

https://www.mayoclinic.org/diseases-conditions/stevens-johnson-syndrome/diagnosis-treatment/drc-20355942

https://www.ncbi.nlm.nih.gov/books/NBK459323/