Imagine developing flu-like symptoms fever, sore throat, and fatigue and then noticing a painful red rash begin to spread across your body. Within hours or days, this rash progresses to widespread blistering, and the top layer of your skin begins to peel away, leaving raw, painful sores. This devastating scenario is the reality of Stevens-Johnson Syndrome (SJS), a rare but severe and life-threatening disorder of the skin and mucous membranes. It is crucial to understand that SJS is not an infection, but rather a severe, unpredictable adverse reaction, most often to a medication. The onset of a rapidly progressing, painful, blistering rash, especially if it involves the mouth, eyes, or genitals, is a true medical emergency that requires immediate withdrawal of the offending drug and urgent hospitalization, often in a specialized burn unit.

Stevens-Johnson syndrome is a type of severe cutaneous adverse reaction (SCAR). It is characterized by the widespread death of the top layer of the skin (the epidermis) and the mucous membranes.

The SJS/TEN Spectrum It is essential to know that SJS and another condition, Toxic Epidermal Necrolysis (TEN), are now considered to be the same disease process, existing on a spectrum of severity. The distinction is based on the percentage of body surface area affected by skin detachment:

• SJS: Involves less than 10% of the body surface area.
• SJS/TEN Overlap: Involves between 10% and 30% of the body surface area.
• TEN: Involves more than 30% of the body surface area and is the most severe form with the highest mortality rate.

The core problem in SJS/TEN is a hypersensitivity reaction that triggers widespread apoptosis, or programmed cell death, of the keratinocytes, which are the main cells that make up the epidermis.

• A helpful analogy is to think of the epidermis as a lush, green lawn of grass that is tightly rooted to the soil (the dermis) beneath it.
• A simple scab is like a temporary patch of dried grass placed over a scraped area.
• In SJS/TEN, a trigger, usually a medication, causes a catastrophic overreaction from the body’s immune system. It is as if the immune system suddenly identifies the grass itself as a foreign enemy and carpet-bombs the entire lawn.
• This causes the grass to die and separate from the soil in massive sheets. This widespread death and detachment of the skin is what happens in SJS/TEN, leaving the raw, vulnerable “soil” underneath exposed to massive fluid loss and severe risk of infection, similar to a major burn.

In my experience, patients often present with what seems like a bad drug reaction but once mucosal involvement is seen, the urgency of potential SJS becomes clear.

The direct cause of SJS/TEN is a severe, delayed-type hypersensitivity reaction driven by the body’s own immune system. It is a complex process where the immune system, particularly a type of white blood cell called the cytotoxic T-cell, recognizes a drug or its metabolite as a foreign threat. This triggers a massive, uncontrolled inflammatory cascade that releases chemicals which signal the skin cells to undergo apoptosis and die.

The underlying question of why this severe reaction occurs in some rare individuals and not others is a combination of the specific trigger and the person’s unique genetic makeup.

Clinically, I’ve seen the most common triggers as medications like sulfa drugs, antiepileptics, and allopurinol, viral infections and malignancies can also contribute.

A person develops SJS/TEN as an unpredictable, idiosyncratic reaction to a specific trigger. It is not contagious.

Medications: The Number One Cause

In adults, the vast majority of SJS/TEN cases are triggered by medication. The reaction does not occur immediately upon starting the drug, but typically begins 1 to 4 weeks after the initial exposure.

While hundreds of drugs have been implicated, several classes are considered high-risk. These include:

• Allopurinol: A common medication used to treat gout.
• Anti-seizure Medications (Anticonvulsants): Especially lamotrigine, carbamazepine, phenobarbital, and phenytoin.
• Sulfa Antibiotics: Particularly trimethoprim-sulfamethoxazole.
• Certain NSAIDs (Nonsteroidal Anti-inflammatory Drugs): Specifically, the oxicam type.
• Nevirapine: A medication used to treat HIV.

Infections (A Less Common Cause)

In some cases, particularly in children, SJS can be triggered by an infection.

• Mycoplasma pneumoniae is the most well-known infectious trigger, causing a respiratory infection often referred to as “walking pneumonia.”

Genetic Predisposition

Researchers have discovered that individuals with certain genetic markers are at a vastly increased risk of developing SJS/TEN in response to specific drugs. These genes, known as human leukocyte antigens (HLA), are part of the immune system. For example:

• There is a very strong association between the gene HLA-B*1502 and the risk of developing SJS from carbamazepine in people of Asian descent.
• Another gene, HLA-B*5801, is strongly linked to the risk of SJS from allopurinol.

In my experience, even over-the-counter drugs or recent antibiotic use can set off this reaction, especially in genetically predisposed individuals.

Symptoms of SJS/TEN progress rapidly and require immediate recognition.

The Prodromal Phase

The illness often begins with a 1 to 3 day period of non-specific, flu-like symptoms before any rash appears. These include:

• Fever
• A general feeling of being unwell (malaise)
• Sore throat and cough
• Body aches
• Burning or stinging of the eyes

The Eruptive Phase

Following the prodrome, the characteristic and painful skin and mucous membrane lesions appear and evolve quickly.

• The Rash: It often starts as poorly defined red or purplish macules (flat spots), frequently on the face and trunk, which then spread. The rash is typically painful to the touch.
• Mucous Membrane Involvement: This is a hallmark of SJS and is present in over 90% of cases. It is often the most distressing feature. It involves the development of painful crusts, blisters, and erosions on at least two mucosal surfaces:
  • Oral: Severe crusting of the lips, and painful ulcers inside the mouth and on the tongue, making it difficult to eat or drink.
  • Ocular: Severe conjunctivitis (red eyes), pain, and erosions on the surface of the eye.
  • Genital: Painful sores on the genitals and urinary tract.
• Blistering and Skin Detachment: The red patches on the skin progress to form flaccid (limp) blisters. The top layer of the skin then begins to detach and slough off in sheets with even gentle pressure or rubbing. A doctor can often elicit this by gently rubbing the skin, which is known as a positive Nikolsky sign.

Clinically, I recognize early SJS by painful erythematous skin that sloughs off with minimal pressure (positive Nikolsky sign) prompt identification is critical.

A diagnosis of SJS/TEN is a medical emergency requiring immediate hospitalization. The diagnosis is usually made by a dermatologist or an emergency physician based on the characteristic clinical presentation.

The key diagnostic features are:

1. A history of a recent exposure to a new, high-risk medication, typically within the last one to four weeks.
2. The presence of a rapidly progressing, painful, atypical targetoid rash.
3. Severe involvement of at least two mucosal surfaces (e.g., mouth and eyes).

Skin Biopsy

A skin biopsy is almost always performed to confirm the diagnosis. A small sample of skin is taken from a blistered area and sent to a pathologist. The microscopic examination will show the characteristic full-thickness death (necrosis) of the epidermis, causing it to separate from the dermis below. This finding confirms the diagnosis and differentiates it from other conditions.

In my experience, SJS must be differentiated from other blistering disorders, timely biopsy and ophthalmology consultation are often essential.

The treatment for SJS/TEN requires a highly specialized, multidisciplinary approach and must take place in a hospital, almost always in a burn unit or an intensive care unit (ICU). The principles of care are very similar to those for a patient with a major thermal burn.

1. Immediate Withdrawal of the Offending Drug

The absolute first and most critical step is to identify and immediately discontinue any potential causative medications.

2. Supportive Care: The Cornerstone of Management

There is no single “cure” for SJS/TEN. Treatment is entirely supportive, aimed at keeping the patient alive while their skin heals and regrows. This involves:

• Fluid and Electrolyte Management: Patients lose massive amounts of fluid through their denuded skin. Aggressive intravenous (IV) fluid and electrolyte replacement is essential to prevent dehydration and shock.
• Nutritional Support: Because the mouth is so painful, patients cannot eat. Nutrition is provided through a nasogastric or other type of feeding tube.
• Wound Care: The skin is treated like a severe burn. This involves gentle cleansing and the application of special non-adherent dressings to protect the raw, exposed dermis and promote healing.
• Pain Management: The condition is extremely painful, and adequate pain control with IV medications is a priority.
• Temperature Regulation: Patients have difficulty regulating their body temperature and are often cared for in a warm environment.
• Meticulous Eye Care: This is absolutely critical to prevent permanent vision loss. An ophthalmologist must be involved daily. Treatment includes frequent lubricating drops, clearing away discharge, and breaking up any adhesions that may form, to prevent the cornea from scarring and drying out.

3. Immunomodulatory Therapies

The use of specific medications to modulate the immune response is still debated, and no single therapy has been proven superior in large clinical trials. However, depending on the center and the specific case, therapies that may be considered include intravenous immunoglobulin (IVIG), corticosteroids, or other immunosuppressive agents.

Clinically, I’ve seen IVIG, corticosteroids, and cyclosporine used in some cases, but evidence is mixed, early withdrawal of the causative agent remains the most critical step.

Stevens-Johnson Syndrome and its more severe form, Toxic Epidermal Necrolysis, represent one of the most devastating and life-threatening adverse drug reactions known to medicine. This rare hypersensitivity reaction leads to a catastrophic, widespread death of the skin and mucous membranes, creating a condition that is managed like a major burn. While the experience is harrowing for patients and their families, it is important to focus on the key to survival: early recognition and immediate action. Any person who develops a fever and a new, rapidly spreading, painful, or blistering rash especially if it involves the mouth or eyes after starting a new medication must stop the drug and seek immediate emergency medical care. Clinically, I’ve learned that patient education about high-risk medications and genetic screening (when appropriate) can prevent recurrence and even first-time development in vulnerable groups.

1. The National Organization for Rare Disorders (NORD). (2022). Stevens Johnson Syndrome and Toxic Epidermal Necrolysis. Retrieved from https://rarediseases.org/rare-diseases/stevens-johnson-syndrome-and-toxic-epidermal-necrolysis/
2. The Mayo Clinic. (2022). Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Retrieved from https://www.mayoclinic.org/diseases-conditions/stevens-johnson-syndrome/symptoms-causes/syc-20355936
3. The American Academy of Dermatology (AAD). (n.d.). Stevens-Johnson syndrome and toxic epidermal necrolysis. Retrieved from https://www.aad.org/public/diseases/a-z/stevens-johnson-syndrome