Stevens-Johnson Syndrome (SJS) is a rare but life-threatening hypersensitivity reaction, most commonly triggered by medications. It ranks among the most severe dermatologic emergencies, with the disease process primarily involving the skin and mucous membranes. The illness typically begins with vague flu-like symptoms and progresses rapidly. In SJS, necrosis (cell death) causes the epidermis to detach from the dermis, leading to characteristic skin peeling and extensive wounds that expose the underlying tissue.¹

SJS only affects 1–12 people per million annually, but it cannot be ignored.² In fact, without treatment, the condition can lead to infection, multi-organ damage, and even death.

Causes and Risk Factors of Stevens-Johnson Syndrome

80% of SJS cases are drug-induced, with antibiotics (e.g., sulfonamides), anticonvulsants (e.g., phenytoin), nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g., ibuprofen), and allopurinol being common triggers. The reaction usually develops within the first few weeks of starting a new drug.³
Infections can also be a trigger, especially Mycoplasma pneumoniae. Viral infections like herpes simplex or hepatitis have also been associated, though less commonly.
Occasionally, no cause is found at all. In these cases, it’s called idiopathic.

Risk Factors for SJS

In many cases, individual susceptibility plays a role. People with certain genetic markers (like HLA-B15:02 and HLA-B58:01, especially among Southeast Asian populations) are at higher risk of severe reactions to specific drugs.

Other key risk factors include:

HIV infection: Patients with human immunodeficiency virus (HIV) infection have a greater risk of SJS/TEN.⁴
Cancer, organ transplantation, or immunosuppressive therapy
Age-related vulnerability: Those aged 20 to 40 years are most likely to develop the condition. Children most commonly develop SJS secondary to infection. Older adults are at risk because of polypharmacy and comorbid conditions.

Stevens-Johnson Syndrome: Causes and Risk Factors — Causes of Stevens-Johnson Syndrome (Image generated by AI using Napkin.AI)

Stevens-Johnson Syndrome (SJS) vs Toxic Epidermal Necrolysis (TEN)

Technically, no—they are not separate diseases but rather two ends of the same spectrum of severe mucocutaneous reactions, most commonly triggered by medications. They differ only in the total body surface area affected:

SJS: less than 10% of total body surface area (TBSA)
TEN: greater than 30% of total body surface area (TBSA)
Between 10% and 30% is called SJS-TEN overlap.⁵

The pathology and mechanism are the same. TEN is more extensive and dangerous compared to SJS, and has a higher mortality (25–35%), but many clinicians consider them to be minor variations of the same disease rather than different diseases themselves.

How common is Stevens-Johnson Syndrome?

Overall, SJS and TEN are quite uncommon diseases across the world. They affect an average of 1 to 12 people per million every year. In the U.S., each year, about 5.3 out of every million children develop SJS, 0.8 develop SJS/TEN overlap, and 0.4 develop TEN.⁶

A study based on French national data (2013–2022) found that around 2.6 people per million are affected annually.⁷
However, this number differs widely by geography, genetics, and other risk factors that change between regions and populations. Some sites and groups of people have a much higher risk of developing SJS or TEN.

How does SJS happen – Pathogenesis

SJS and TEN happen when the immune system mistakenly attacks the skin, usually triggered by certain drugs. In about 15% of cases, no clear cause is found, but hidden exposures might play a role.

The reaction starts when specific drugs interact with genetic markers called HLA, activating immune cells (CD8+ T cells). These cells release toxic proteins that kill skin cells, causing blistering and peeling. The skin damage is mainly caused by toxic proteins like granulysin, leading to widespread skin cell death. Besides apoptosis (programmed cell death), other forms of cell death may also be involved.

Cytokines such as TNF-alpha and IL-15 increase inflammation and disease severity. New treatments might target immune pathways like JAK/STAT to help control the disease.

Signs & Symptoms of Stevens-Johnson Syndrome

Prodromal Symptoms

Stevens-Johnson syndrome (SJS) often begins with flu-like prodromal symptoms:

Fever
Sore throat
Fatigue
Red, watery eyes (Conjunctivitis)
Body aches⁸

These symptoms usually appear before or alongside skin and mucous membrane involvement. Within a few days, the symptoms get worse.

Cutaneous Manifestations

The skin rash typically starts on the face and upper body and then spreads symmetrically. Early signs include:

Red patches that are poorly defined (erythematous macules)
Dusky red areas with purplish spots
Atypical target-like lesions (two rings instead of three)
Blisters on the inside of the mouth, throat, or eyes, and later in the genital area, making it hard to drink, eat, or even pee. These blisters are fragile.
The skin becomes very tender, and gentle pressure can cause the outer layer to peel away—a positive Nikolsky sign, similar to severe burns.
Crusting and swelling of the lips and eyes.⁹

A collage of skin changes observed in the acute stage of SJS and post-recovery. — Epidermal detachment during the acute stage (A), followed by post-inflammatory hyperpigmentation after 3 months (B). Post-inflammatory hypopigmentation on the face (C) and trunk (D). Nail changes may include deformities in several fingers (E), progressing to nail dystrophy (F). (Image Courtesy: Yang, C., Cho, Y., Chen, K., Chen, Y., Song, H., & Chu, C. (2016). Long-term Sequelae of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis. Acta Dermato Venereologica, 96(4), 525–529. Available from Medical Journals. Licensed under CC BY 4.0.)

Collage of images showing oral mucosal lesions and blisters on the neck — SJS visual findings: (a) Oral mucosal lesions (b) Blisters on the neck (image Courtesy: Kim, J., Sohn, K., Song, W., & Kang, H. (2013). A Case of Drug Reaction with Eosinophilia and Systemic Symptoms Induced by Ethambutol with Early Features Resembling Stevens-Johnson Syndrome. Acta Dermato Venereologica, 93(6), 753–754. Available from Medical Journals. Licensed under CC BY 4.0.)

The acute phase usually lasts about one week, followed by skin healing over two to three weeks. During this time, patients are at risk for fluid loss and electrolyte imbalances.

Why is Stevens-Johnson Syndrome so dangerous?

In SJS, the outer layer of the skin dies and sloughs off, leaving bare tissue open to infection and dehydration. With a 5–10% death rate (higher in TEN), complications may include sepsis, multi-system organ failure, blindness, and scarring.¹⁰ Patients usually require an immediate hospital and burn unit admission.

Diagnosis of Stevens-Johnson Syndrome

There is no diagnostic test for SJS. As time is of the essence, doctors typically rely on a combination of their clinical judgement, history taking, and supportive tests to make the diagnosis quickly.

Clinical Evaluation:

History of recent drug intake (within the last 1–3 weeks)
Onset of symptoms: Did flu-like symptoms come first? Was there rapid skin involvement?
Visible skin lesions- extensive red or purplish skin patches, blisters, and skin peeling
The Nikolsky sign (skin slips off when lightly rubbed)
Mucosal involvement (involvement of the mouth, eyes, genitals)¹¹

It is important to differentiate Stevens-Johnson syndrome from other blistering diseases such as dystrophic epidermolysis bullosa—a genetic disorder characterized by fragile skin—and pemphigus vulgaris, an autoimmune blistering condition. These disorders have different clinical courses and require distinct management approaches.

Skin Biopsy:

When doctors want to be absolutely sure, or rule out other conditions (like bullous pemphigoid or staphylococcal scalded skin syndrome), they may do a skin biopsy. It can show:

Full-thickness epidermal necrosis (cell death)
Epidermal detachment
Minimal immune cell infiltration (helps rule out autoimmune conditions)¹²

Histopathology of skin showing full-thickness epidermal necrosis and detachment. — Histopathology of Stevens–Johnson Syndrome showing full-thickness epidermal necrosis and dermal inflammation. (Image Courtesy: 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. Available at MDPI. Licensed under CC BY 4.0.)

Blood Tests:

Blood tests can assess the severity, monitor complications, and rule out similar conditions:

Complete Blood Count (CBC): Signs of infection, anemia, or low platelet count
Liver Function Tests (LFTs): Elevated enzymes like ALT/AST may suggest liver involvement
Renal Function Tests: Increased creatinine and BUN can show decreased kidney filtration, important in cases of dehydration, sepsis
Electrolytes: Skin loss and poor intake can lead to sodium or potassium imbalances
Inflammatory Markers (CRP, ESR): Elevated in severe systemic inflammation
Blood Cultures: Ordered if there’s fever, to rule out sepsis (a life-threatening complication)

Treatment of Stevens-Johnson Syndrome

Treating SJS is a medical emergency. The goal is to stop the damage, manage symptoms, and prevent complications.¹³

Step 1: Stop the Trigger Drug (Immediately):

This is priority number one. If a medication is suspected (and it usually is), it must be stopped immediately. One extra dose can make things worse.

Step 2: Hospitalization in a Specialized Unit:

Patients with SJS are usually admitted to an ICU or burn unit because:

Their skin is compromised like a burn injury
Fluid loss, electrolyte imbalance, and infections are serious risks
They need expert wound care

Step 3: Supportive Care (The Backbone of Treatment):

Supportive care includes:

Replacement for fluid and electrolyte loss
Nutritional support (often through a feeding)
Pain management (IV opioids or other pain meds)
Wound care (non-adhesive dressings, gentle cleaning)

Mucosal Care:

Special attention is given to eyes, mouth, and genitals:

Ophthalmology consults early to prevent long-term vision issues
Topical treatments for oral and genital lesions to reduce pain and scarring

Medications: Still Controversial:

Several medications are used in some cases, but their effectiveness is debated. These include:

Corticosteroids (to reduce inflammation) — helpful in early stages, but risky if there’s an infection
IVIG (Intravenous Immunoglobulin): Can halt disease progression by blocking Fas-mediated cell death
Cyclosporine or TNF-alpha inhibitors: Occasionally used in severe, unresponsive cases

Treatment decisions vary depending on the patient’s condition and hospital protocols.

Infographic displaying the management timeline of SJS — Timeline of the management of Stevens-Johnson Syndrome (Image generated by AI using Napkin.AI)

What are the Complications?

SJS has systemic complications and can be life-threatening:

Sepsis: Open skin = infection risk = potentially fatal
Dehydration & Electrolyte Imbalance
Acute respiratory distress syndrome (ARDS): Especially if lung tissue is involved
Chronic eye issues: Dry eyes, scarring, even blindness
Skin changes: Scarring, pigmentation changes, and sensitivity
Psychological impact: Especially in children and young adults—trauma, anxiety, PTSD¹⁴

Recovery from Stevens-Johnson Syndrome

Recovery from SJS is slow and depends upon severity, age, and overall health. The skin often heals over weeks, but complications, such as scarring, chronic eye issues, and mucosal damage, can last much longer. Emotional recovery is also a real part of the journey.
The prognosis varies: for SJS, the mortality is said to be around 5–10%, however, TEN has a higher mortality, often greater than 30%, although it can vary widely.¹⁵

The SCORTEN system can help clinicians evaluate the severity of the disease. The SCORTEN score is used to predict the likelihood of all-cause mortality in patients with SJS or TEN based on the following parameters: age, presence of cancer, heart rate, and serum lab values.¹⁶

Parameter	Weight
Age ≥ 40 years	1
Malignancy—Yes	1
BSA detached > 10%	1
Serum bicarbonate < 20 mmol/L	1
Serum urea nitrogen > 28 mg/dL	1
Serum glucose > 252 mg/dL	1
Tachycardia ≥ 120 bpm	1

A higher SCORTEN score is associated with a higher likelihood of death and can be helpful for clinicians to make decisions about how aggressively to manage these patients.

SCORTEN Score	Estimated Mortality (%)
0-1	3.2
2	12.1
3	35.3
4	58.3
>5	90

Early diagnosis, immediate withdrawal of the offending drug, and intensive supportive care significantly improve outcomes. Survivors usually require long-term follow-up and must avoid the trigger medication for life.

Red Man Syndrome vs. Stevens-Johnson Syndrome (SJS)

	Red Man Syndrome (now Vancomycin Infusion Reaction)¹⁷	Stevens-Johnson Syndrome (SJS)
Cause	Infusion reaction (not allergy), usually vancomycin	Severe hypersensitivity reaction to medications or infections
Onset	Minutes after starting IV infusion	Days to weeks after drug exposure
Common Triggers	Rapid vancomycin infusion	Antibiotics, anti-epileptics, NSAIDs, infections
Symptoms	Flushing, redness (face/neck), itching, ± low BP	Fever, sore throat, painful rash, blisters, skin peeling
Mucosal Involvement	No	Yes – mouth, eyes, genitals
Skin Detachment	No	Yes, extensive in severe cases
Severity	Mild to moderate (self-limiting)	Severe, life-threatening
Treatment	Slow infusion, antihistamines, supportive care	Immediate drug withdrawal, ICU care, wound management
Prognosis	Excellent with proper management	Variable; mortality rate 10–30% depending on severity

Conclusion

Stevens-Johnson Syndrome is rare but relentless — a reminder of how fragile and fierce the human body can be in the face of hypersensitivity. Whether you’re a patient navigating recovery or a clinician racing to intervene, early recognition and the right response can make all the difference. Education, vigilance, and empathy remain our best defense because in conditions like SJS, timing is everything.

Refrences

1
Shah, H., Parisi, R., Mukherjee, E., Phillips, E. J., & Dodiuk-Gad, R. P. (2024). Update on Stevens–Johnson Syndrome and toxic epidermal necrolysis: Diagnosis and management. American Journal of Clinical Dermatology, 25(6), 891–908. https://doi.org/10.1007/s40257-024-00889-6
2
Saeed, H. N., Micheletti, R., & Phillips, E. J. (2024). Editorial: Stevens Johnson syndrome: Past, present, and future directions. Frontiers in Medicine, 11, 1383891. https://doi.org/10.3389/fmed.2024.1383891
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Saeed, H. N., Micheletti, R., & Phillips, E. J. (2024). Editorial: Stevens Johnson syndrome: Past, present, and future directions. Frontiers in Medicine, 11, 1383891. https://doi.org/10.3389/fmed.2024.1383891
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Sekula P, Dunant A, Mockenhaupt M, Naldi L, Bouwes Bavinck JN, Halevy S, Kardaun S, Sidoroff A, Liss Y, Schumacher M, Roujeau JC; RegiSCAR study group. Comprehensive survival analysis of a cohort of patients with Stevens-Johnson syndrome and toxic epidermal necrolysis. J Invest Dermatol. 2013 May;133(5):1197-204. doi: 10.1038/jid.2012.510. Epub 2013 Feb 7. PMID: 23389396.
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Zimmerman, D., & Dang, N. H. (2020). Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). In J. Nates & K. Price (Eds.), Oncologic critical care (pp. 267–280). Springer. https://doi.org/10.1007/978-3-319-74588-6_195
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Hsu DY, Brieva J, Silverberg NB, Paller AS, Silverberg JI. Pediatric Stevens-Johnson syndrome and toxic epidermal necrolysis in the United States. J Am Acad Dermatol. 2017 May;76(5):811-817.e4. doi: 10.1016/j.jaad.2016.12.024. Epub 2017 Mar 9. PMID: 28285784; PMCID: PMC5502094.
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Bettuzzi T, Lebrun-Vignes B, Ingen-Housz-Oro S, Sbidian E. Incidence, In-Hospital and Long-Term Mortality, and Sequelae of Epidermal Necrolysis in Adults. JAMA Dermatol. 2024 Dec 1;160(12):1288-1296. doi: 10.1001/jamadermatol.2024.3575. PMID: 39356525; PMCID: PMC11447629.
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Noe, M. H., & Micheletti, R. G. (2020). Diagnosis and management of Stevens-Johnson syndrome/toxic epidermal necrolysis. Clinics in Dermatology, 38(6), 607-612. https://doi.org/10.1016/j.clindermatol.2020.06.016
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Wasuwanich, P., So, J. M., Chakrala, T. S., Chen, J., & Motaparthi, K. (2023). Epidemiology of Stevens-Johnson syndrome and toxic epidermal necrolysis in the United States and factors predictive of outcome. JAAD International, 13, 17. https://doi.org/10.1016/j.jdin.2023.06.014
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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
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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
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Stevens-Johnson Syndrome: A Deadly Drug Reaction

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