Stevens-Johnson syndrome (SJS) is a rare, serious reaction in which the skin and mucous membranes blister and peel away from the body. It is most often triggered by medications, though infections can also cause it. SJS affects less than 10% of the body’s skin surface. When more skin is involved, it is classified as a more severe condition called toxic epidermal necrolysis (TEN).
How SJS Relates to TEN
SJS and TEN are not separate diseases. They exist on a spectrum, classified by how much skin detaches from the body. When less than 10% of the body’s skin surface peels off, it is called SJS. Between 10% and 30% is considered SJS/TEN overlap. Above 30% is classified as TEN, the most dangerous form. Think of it as the same underlying process at different levels of severity, with mortality rising as more skin is lost.
What Causes It
Medications are the most common trigger. The highest-risk drugs include allopurinol (used for gout), anticonvulsants like carbamazepine and lamotrigine, sulfonamide antibiotics, the HIV drug nevirapine, and certain pain relievers including acetaminophen, ibuprofen, and naproxen. The reaction does not happen because of an overdose or misuse. It is an immune system response that can occur at normal doses.
In children and adolescents, infections are a notable trigger. Mycoplasma pneumoniae, a common cause of “walking pneumonia,” has been linked to outbreaks of SJS in pediatric hospitals. Other infections, including herpes simplex virus, can also set it off. In some cases, no clear cause is ever identified.
What Happens Inside the Body
SJS is driven by the immune system turning against the skin. When the body reacts to a medication or infection, certain immune cells release a protein called granulysin in extremely high concentrations. In people with SJS or TEN, granulysin levels in blister fluid can reach some of the highest ever recorded in humans. This protein normally helps fight bacteria, and it is roughly a thousand times less effective at damaging human cells than microbial ones. But at the massive concentrations found in SJS, it overwhelms that safety margin and directly kills skin cells called keratinocytes. The severity of the disease, including the risk of death, correlates with how much granulysin is released into the skin.
Symptoms and How They Progress
SJS typically begins one to three weeks after starting a new medication, though the timeline can vary. The first signs feel like a bad flu: fever, sore throat, fatigue, burning eyes, and body aches. These symptoms are easy to mistake for a viral illness, which is part of what makes early diagnosis difficult.
Within days, flat reddish or purplish spots appear, often starting on the face, neck, and upper chest before spreading. These spots frequently have a darker center resembling a target. They then merge and develop into fluid-filled blisters that are fragile and break easily. Over a period of one to three days, the skin begins to slough off in sheets. Pressing on the skin near a blister can cause it to slide away, a clinical sign known as the Nikolsky sign.
The damage is not limited to the outer skin. Painful sores and crusting develop inside the mouth, making eating and drinking extremely difficult. The eyes become red, swollen, and sensitive. The lining of the genitals, urinary tract, and airways can also be affected. Most people with SJS have involvement in at least two of these mucous membrane areas alongside the skin.
Genetic Risk Factors
Certain genetic markers significantly increase the risk of SJS from specific drugs. People who carry a gene variant called HLA-B*15:02, which is more common in people of Southeast Asian, South Asian, and East Asian descent, face a much higher risk of developing SJS when taking carbamazepine or oxcarbazepine. The FDA recommends genetic screening for this variant before prescribing these medications to patients with Asian ancestry. A second variant, HLA-A*31:01, is associated with carbamazepine-related skin reactions across all ethnic backgrounds, though mandatory screening is not yet standard for it.
These genetic tests are a blood draw, and they only need to be done once. If you are prescribed carbamazepine or a related seizure medication, particularly if you have Asian ancestry, ask whether genetic testing has been considered.
How It Is Diagnosed
Doctors can usually recognize SJS by its appearance: the combination of target-like skin lesions progressing to blisters, mucous membrane involvement (eyes, mouth, genitals), and skin that peels away in sheets is distinctive. When the picture is less clear, a skin biopsy confirms the diagnosis. Under a microscope, the hallmark finding is widespread death of the skin’s outer layer. This distinguishes SJS from other blistering conditions that can look similar on the surface.
Hospital Treatment
SJS is a medical emergency treated in a hospital, often in a burn unit or intensive care unit. The priorities are the same ones that apply to severe burns: replacing lost fluids, preventing infection, managing pain, and supporting the body while the skin heals.
Fluid replacement starts immediately, though people with SJS generally need less fluid than burn patients with the same amount of skin loss. Within the first couple of days, nutrition through a feeding tube typically begins because mouth sores make eating impossible. Protein loss through the damaged skin is substantial, so aggressive nutritional support is critical for healing. Blood sugar levels can become unstable, sometimes requiring insulin even in people without diabetes.
Wound care is delicate and specialized. In some cases, dead skin is carefully removed and covered with biological dressings, which can include donor skin, porcine grafts, or collagen-based substitutes. Other approaches leave blistered skin that has not yet peeled in place as a natural barrier. These dressings reduce pain, prevent fluid loss, help regulate body temperature, and lower infection risk. Room temperature is kept between 86 and 90°F, with heat lamps and shields used to reduce the calories the body burns trying to stay warm. Sterile handling protocols are essential because exposed skin is extremely vulnerable to hospital-acquired infections.
Predicting Severity
Doctors use a scoring system called SCORTEN to estimate how dangerous a case is likely to be. It assigns one point each for seven risk factors: age over 40, presence of cancer, heart rate above 120, initial skin detachment above 10% of body surface, and three blood chemistry values indicating metabolic stress. Each point roughly triples the odds of death. Someone with a score of zero or one has a very different outlook than someone with four or five points, and the score helps guide how aggressively to treat.
Long-Term Complications
Surviving SJS does not mean the problems are over. The eyes are the most commonly affected area in the long term. Roughly half of all SJS survivors develop serious eye complications. These include severe chronic dry eye, scarring that fuses the eyelid to the surface of the eye (symblepharon), inward-turning eyelashes that scratch the cornea (trichiasis), and growth of blood vessels and tissue over the clear surface of the eye. Without ongoing eye care, these complications can lead to significant vision loss.
Skin changes after SJS can include uneven pigmentation, scarring, and sensitivity. Scarring in the genital and urinary tract can cause narrowing or adhesions. Some people develop chronic lung problems. The psychological impact is also significant. Many survivors experience anxiety, depression, and post-traumatic stress related to the experience and ongoing physical changes.
Equally important is the lifelong need to avoid the drug that triggered the reaction. A second exposure to the same medication, or sometimes a chemically related one, can cause a recurrence that is often more severe than the first episode. Wearing a medical alert bracelet and ensuring every healthcare provider knows about the drug allergy is essential for prevention.