The Insightful Corner Hub: Unveiling the Link: Certain Drugs and Stevens-Johnson Syndrome

Article last update on 27 January, 2026

Introduction

Stevens-Johnson syndrome (SJS) is a rare, severe, and potentially life-threatening dermatologic and systemic condition characterized by widespread skin and mucous membrane involvement. While uncommon, SJS carries high morbidity and mortality, particularly if not recognized early and managed appropriately. Drug exposure remains the most significant trigger of SJS in adults, and understanding these drug-induced reactions is essential for clinicians, patients, and public health policymakers.

Globally, SJS incidence ranges from 1 to 6 cases per million persons per year, with higher prevalence noted in populations carrying certain genetic susceptibilities, such as the HLA-B*1502 allele in Southeast Asian populations, which predisposes to carbamazepine-induced SJS. Advances in pharmacovigilance, genetic screening, and dermatologic care have improved recognition and outcomes, yet many cases remain preventable through appropriate awareness and monitoring.

This article aims to comprehensively review the drug-induced mechanisms, implicated medications, risk factors, clinical features, diagnostic criteria, prevention strategies, and management approaches for SJS, with the goal of equipping healthcare providers and patients with practical knowledge to reduce incidence and mortality.

Understanding Stevens-Johnson Syndrome

Definition and Classification

Stevens-Johnson syndrome is an acute, immune-mediated hypersensitivity reaction primarily affecting the skin and mucous membranes. It is considered part of a spectrum of severe cutaneous adverse reactions (SCARs), which also includes toxic epidermal necrolysis (TEN). The distinction between SJS and TEN is based on the extent of body surface area (BSA) involvement:

SJS: <10% of BSA
SJS/TEN overlap: 10–30% of BSA
TEN: >30% of BSA

Both conditions are potentially fatal, with TEN having a mortality rate of up to 30–50%.

Pathophysiology

SJS is primarily a T-cell-mediated delayed hypersensitivity reaction. Drug metabolites can act as haptens, binding to keratinocytes and triggering cytotoxic T-cell activation. This leads to keratinocyte apoptosis, epidermal necrosis, and widespread detachment of the skin. Key mediators include:

Fas ligand (FasL) and Fas receptor interaction
Perforin and granzyme B cytotoxicity
Tumor necrosis factor-alpha (TNF-α) upregulation

Certain genetic markers increase susceptibility:

HLA-B*1502 → carbamazepine-induced SJS/TEN (especially in Han Chinese, Thai, and Malaysian populations)
HLA-B*5801 → allopurinol-induced SJS/TEN (notably in Han Chinese and Korean populations)
Other polymorphisms in drug-metabolizing enzymes may affect risk.

Drug-Induced Triggers of SJS

Drug exposure accounts for 50–80% of adult SJS cases, with onset typically occurring within 1–3 weeks of starting the medication. While many drugs have been implicated, certain classes carry higher risk:

1. Anticonvulsants

Carbamazepine: Strongly associated with SJS, particularly in individuals with HLA-B*1502.
Phenytoin, Lamotrigine, Phenobarbital: Also linked, with risk increased in slow metabolizers.
Mechanism: Reactive metabolites bind to epidermal proteins, triggering cytotoxic T-cell activation.

2. Sulfonamide Antibiotics

Sulfamethoxazole-trimethoprim (co-trimoxazole): Most commonly implicated antibiotic.
Other sulfonamides: Sulfasalazine, certain diuretics.
Mechanism: Sulfonamide metabolites may induce oxidative stress in keratinocytes, precipitating apoptosis.

3. Allopurinol

Used in gout and hyperuricemia.
Strong association with SJS/TEN in patients carrying HLA-B*5801.
Often linked to chronic renal impairment or high starting doses.

4. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

Oxicam NSAIDs (meloxicam, piroxicam) have higher SJS risk than other NSAIDs.
Mechanism involves COX inhibition and immune modulation in susceptible individuals.

5. Others

Antiretroviral therapy: Nevirapine (commonly associated with SJS in HIV patients)
Allergic reactions to chemotherapy agents: E.g., methotrexate, vemurafenib.
Vaccines and biologics: Rare reports; immune activation may play a role.

Clinical Features of SJS

SJS typically evolves in three phases:

1. Prodromal Phase

Duration: 1–7 days
Symptoms: Fever, malaise, myalgia, sore throat, cough
Importance: Often misdiagnosed as viral infection, delaying recognition.

2. Acute Skin and Mucosal Phase

Rapid onset of painful erythematous macules, targetoid lesions, and blisters.
Mucosal involvement occurs in >90% of cases: oral cavity, eyes, genitalia.
Nikolsky sign: Gentle lateral pressure causes epidermal detachment.

3. Recovery or Complications

Healing occurs over 2–6 weeks, sometimes with post-inflammatory hyperpigmentation or scarring.
Complications: Sepsis, ocular damage (corneal scarring), multi-organ failure.

Diagnosis of Drug-Induced SJS

Diagnosis relies on clinical presentation and history of drug exposure. Key diagnostic criteria include:

Recent exposure (usually 1–3 weeks) to high-risk drugs.
Acute onset of mucocutaneous lesions.
BSA involvement <10% (for SJS).
Histopathology (optional): Epidermal necrosis, keratinocyte apoptosis.

Differential diagnoses: Bullous pemphigoid, erythema multiforme major, toxic shock syndrome, staphylococcal scalded skin syndrome.

Management and Treatment

SJS is a medical emergency. Early drug discontinuation and supportive care are crucial.

1. Immediate Measures

Stop the suspected drug.
Admit to intensive care or burn unit for severe cases.

2. Supportive Care

Fluid and electrolyte management
Wound care to prevent secondary infection
Pain management
Nutritional support

3. Pharmacologic Interventions

Corticosteroids: Controversial; may reduce inflammation in early SJS.
Intravenous immunoglobulin (IVIG): May block Fas-FasL-mediated apoptosis.
Cyclosporine: Immunosuppressive agent with promising outcomes.
Antibiotics: Only if secondary infection is confirmed.

4. Ophthalmologic Care

Early consultation is essential due to risk of blindness and ocular scarring.
Lubricating eye drops, topical antibiotics, or corticosteroids may be indicated.

Prevention and Risk Reduction

1. Pharmacogenetic Screening

HLA-B*1502 testing prior to carbamazepine initiation in Asian populations.
HLA-B*5801 testing for allopurinol susceptibility.

2. Patient Education

Inform patients about early signs: fever, rash, mucosal ulcers.
Encourage immediate reporting of symptoms.

3. Rational Prescribing

Avoid high-risk drugs in patients with known allergies or genetic predispositions.
Use alternative medications where feasible.

Global Public Health Significance

SJS poses a challenge beyond individual patients:

High healthcare costs due to ICU care and prolonged hospitalization.
Risk of long-term sequelae (ocular, cutaneous, and mucosal complications).
Necessitates pharmacovigilance, reporting systems, and educational campaigns for both healthcare providers and patients.

Case Studies and Epidemiology

1. Carbamazepine-Induced SJS in Asia

Han Chinese population: incidence 10–15 times higher in HLA-B*1502 carriers.
Implementation of genetic screening has dramatically reduced cases.

2. Allopurinol-Induced SJS

Common in gout patients with renal impairment.
Early recognition and HLA-B*5801 screening can prevent fatal reactions.

3. Antibiotic-Associated SJS

Sulfonamide antibiotics account for up to 30% of SJS cases in some adult cohorts.
Often presents in the context of upper respiratory tract infection treatment.

Future Directions

Precision medicine: Pharmacogenetic-guided prescribing is becoming standard in high-risk populations.
Novel therapies: Biologic agents targeting inflammatory pathways (e.g., TNF-α inhibitors) are under investigation.
Global reporting systems: Improved data collection allows identification of emerging drug risks and safety measures.

FAQs: Certain Drugs and Stevens-Johnson Syndrome

1. What is Stevens-Johnson Syndrome (SJS)?
SJS is a rare, severe skin reaction that affects the skin and mucous membranes, often triggered by medications or infections. It can lead to blistering, skin peeling, and in severe cases, organ involvement.

2. Which drugs are most commonly linked to SJS?
Medications associated with increased SJS risk include:

Carbamazepine (anticonvulsant)
Lamotrigine (anticonvulsant)
Sulfamethoxazole-trimethoprim (antibiotic)
Allopurinol (for gout)
Ibuprofen (NSAID)

3. How does SJS develop after taking these drugs?
SJS is an immune-mediated reaction. Certain drugs can trigger an abnormal immune response, attacking skin and mucous membranes, leading to inflammation, blistering, and tissue damage.

4. What are the early signs and symptoms of SJS?
Early symptoms may include:

Fever and fatigue
Sore throat or cough
Painful skin rash, red or purplish spots
Blisters on the skin or mucous membranes (eyes, mouth, genitals)

5. How quickly does SJS appear after starting a drug?
Symptoms typically appear within 1–3 weeks after starting the offending medication, but timing may vary depending on the drug and individual sensitivity.

6. Can SJS be life-threatening?
Yes. Severe SJS can cause widespread skin detachment, infections, organ damage, and may require intensive care or hospitalization. Prompt recognition and drug discontinuation are crucial.

7. How is SJS treated?
Treatment focuses on:

Immediate discontinuation of the suspected drug
Hospitalization in severe cases (burn unit or ICU)
Supportive care: fluids, wound care, pain management, and prevention of infection
Sometimes systemic corticosteroids or immunoglobulins are used under specialist guidance

8. How can SJS be prevented?
Prevention strategies include:

Careful prescription of high-risk drugs
Monitoring patients when starting new medications
Educating patients on early warning signs
Reporting any adverse drug reactions promptly

9. Who is at higher risk for developing SJS?
Individuals with certain genetic predispositions, previous drug reactions, or concurrent infections may have a higher risk. Genetic testing (e.g., HLA-B*1502 for carbamazepine in some Asian populations) can guide safer prescribing.

10. Should patients stop taking medication on their own if concerned about SJS?
No. Patients should contact a healthcare provider immediately. Stopping some medications abruptly without guidance may be harmful. Early medical evaluation is essential.

Conclusion

Stevens-Johnson syndrome is a rare but life-threatening adverse drug reaction that demands urgent attention. Awareness of high-risk medications, early recognition of prodromal and skin manifestations, and prompt discontinuation of the offending drug are key to reducing morbidity and mortality. Advances in genetic screening, patient education, and clinical management have improved outcomes, yet vigilance remains essential. Healthcare professionals must prioritize prevention, early intervention, and multidisciplinary care to safeguard patients from this severe condition.

References

Mockenhaupt M. Epidemiology of cutaneous adverse drug reactions. Chem Immunol Allergy. 2012;97:1–17.
Roujeau JC, Stern RS. Severe adverse cutaneous reactions to drugs. N Engl J Med. 1994;331(19):1272–1285.
Yang CY, et al. HLA-B*1502 and carbamazepine-induced Stevens-Johnson syndrome in Han Chinese. N Engl J Med. 2004;351:1966–1973.
Chung WH, et al. Medical genetics and the prevention of severe cutaneous adverse reactions. Nat Rev Genet. 2016;17:331–343.
Halevy S, et al. Clinical aspects of Stevens-Johnson syndrome and toxic epidermal necrolysis. J Am Acad Dermatol. 2008;58:181–191.

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Unveiling the Link: Certain Drugs and Stevens-Johnson Syndrome