Stevens-Johnson Syndrome: Causes and Pictures

Stevens-Johnson syndrome (SJS) is a rare, potentially life-threatening skin reaction most often triggered by medications, in which the body’s immune system attacks the skin and mucous membranes, causing painful blistering, tissue death, and skin detachment. The condition sits on a severity spectrum with toxic epidermal necrolysis (TEN), its more severe counterpart: SJS involves less than 10 percent of the body’s skin surface, while TEN involves more than 30 percent. Between those thresholds, the overlap is sometimes called SJS-TEN. Despite its rarity, SJS demands urgent recognition because delayed treatment worsens outcomes dramatically, and the visual appearance of the rash evolves fast enough to catch patients and even clinicians off guard.

What Stevens-Johnson Syndrome Looks Like

SJS typically begins with symptoms that mimic a bad flu: fever, fatigue, sore throat, and burning eyes, often lasting one to three days before any visible skin changes appear. This prodrome is one reason early cases get missed. Then, a rash emerges, usually starting on the trunk and face before spreading outward. The hallmark skin lesions are dark, purplish-red spots (sometimes described as “targetoid” because of their concentric ring appearance) that are flat rather than raised and painful rather than itchy. A key clinical finding is the Nikolsky sign, where gentle lateral pressure on the skin causes the top layer to slide off, revealing raw, weeping tissue underneath.¹

As the condition progresses, the spots merge and blisters form. The blisters are filled with fluid, and when they rupture, they leave behind painful erosions that resemble a burn. The mouth is almost always involved: patients develop painful sores on the lips, gums, tongue, and inside of the cheeks, making swallowing difficult. One case report describes a 37-year-old man who first sought help at a dental clinic for mouth blisters and a burning sensation, only for a full SJS diagnosis to follow after skin lesions appeared on his forearms.² Eyes, the genital area, and the nasal passages are also frequently affected.

One important gap in medical education is that most textbook images of SJS show the condition on light skin, making recognition harder on darker skin tones. On brown or black skin, the early rash can look more violet or dark brown rather than the stereotypical bright red, and erythema (redness) may be harder to spot. A case report and educational review found significant underrepresentation of SJS in skin of color across medical training resources, raising concern that delayed recognition in darker-skinned patients may worsen outcomes.³ If you are searching for pictures of SJS to compare against your own symptoms or those of someone you know, be aware that online image databases skew heavily toward lighter skin. The pain, the mucosal involvement, and the Nikolsky sign are more reliable indicators across all skin tones than redness alone.

The Drugs Most Likely to Cause SJS

Medications are the leading cause of SJS in adults by a wide margin. Not all drugs carry the same risk. A review of patients admitted to burn units with SJS or TEN found that anticonvulsants (anti-seizure drugs) were the single most common drug class, responsible for about 30 percent of cases. The antibiotic trimethoprim-sulfamethoxazole came next at roughly 19 percent, followed by beta-lactam antibiotics at about 11 percent. NSAIDs and allopurinol (a gout medication) each accounted for around 8 percent of cases.⁴

Beyond those categories, a broader compilation of drug triggers lists antineoplastics (cancer drugs) and diuretics among the implicated classes as well.⁵ Among the individual drugs most consistently flagged as high risk are anti-infective sulfonamides, several anti-epileptic drugs (carbamazepine, phenytoin, lamotrigine), oxicam-type NSAIDs (like piroxicam), allopurinol, the HIV drug nevirapine, and chlormezanone.⁶

SJS reactions usually show up within the first one to three weeks of starting a new drug. This timing is part of what makes the diagnosis tricky: by the time the rash appears, patients may not connect it to a pill they started two weeks ago. If you have recently begun a new medication and develop an unexplained fever followed by a spreading painful rash or mouth sores, that timeline matters and should be communicated to your doctor immediately.

When Infections Are the Trigger

While drugs dominate the cause list in adults, infections are a significant trigger, especially in children and young adults. The single most commonly identified infectious cause is Mycoplasma pneumoniae, the bacterium responsible for “walking pneumonia.”⁷ SJS occurs in an estimated 1 to 5 percent of Mycoplasma infections and has been mainly reported in children, though adult cases exist too.⁸

Mycoplasma-associated SJS sometimes looks a bit different from drug-triggered cases. It tends to affect the mucous membranes more prominently, and some clinicians refer to cases with mucosal involvement but minimal skin detachment as “incomplete SJS” or “Mycoplasma-induced rash and mucositis.”⁹ This matters because a child with a cough and sudden painful mouth sores might not be immediately considered for SJS if clinicians are only thinking about drug reactions. Other infections linked to SJS include herpes simplex virus, hepatitis viruses, and HIV, though Mycoplasma remains the infectious culprit seen most frequently.

Genetic Susceptibility and Pharmacogenomic Screening

Not everyone who takes carbamazepine or allopurinol develops SJS. The difference often comes down to genetics, specifically certain variations in the HLA (human leukocyte antigen) genes that help the immune system distinguish the body’s own tissues from foreign threats. The most well-established link is between HLA-B*15:02 and carbamazepine-induced SJS/TEN, particularly in people of Southeast Asian descent. An umbrella review confirmed a strong association between HLA-B*15:02 and SJS/TEN caused by carbamazepine and oxcarbazepine, with a milder association for lamotrigine and phenytoin.¹⁰

For allopurinol, the relevant marker is HLA-B*58:01. A meta-analysis found an extremely strong association between this allele and allopurinol-induced SJS/TEN, with odds ratios near 80 to 97 depending on the study design.¹¹ That is an enormous effect size, and it has driven guidelines in several countries to recommend HLA-B*58:01 testing before prescribing allopurinol, particularly in populations where the allele is more common (Southeast Asian, African American, and Korean populations, among others).

The screening picture is not perfectly clean, though. In a study of Southern Han Chinese patients with carbamazepine-induced SJS, about 28 percent were negative for HLA-B*15:02, meaning the test would have missed them. The researchers also identified HLA-A*24:02 as a potential additional risk marker present in over half the cases.¹² And a real-world study of a screening policy in practice found a mixed result: after HLA-B*15:02 testing was introduced, carbamazepine-induced SJS dropped to zero in the tested group, but phenytoin-induced SJS trended upward, and overall SJS rates from anti-epileptic drugs remained statistically unchanged. Compliance with the screening policy was also low, with only about a quarter of relevant patients actually being tested before starting medication.¹³ Genetic screening is a valuable tool but not a guarantee, and it works best when embedded in systems where physicians consistently follow the guidelines.

How the Immune System Destroys the Skin

The underlying mechanism of SJS is an immune system overreaction that targets keratinocytes, the cells making up most of the skin’s outer layer. The trigger (usually a drug or its metabolite) appears to alter proteins on the surface of keratinocytes in a way that the immune system reads as foreign. Cytotoxic T cells and natural killer cells then launch an attack, killing skin cells through several pathways including the release of molecules like Fas ligand, granzymes, perforin, and granulysin.¹⁴

Granulysin deserves particular mention because research has shown it can kill cells without needing direct cell-to-cell contact, and it is found at elevated levels in SJS/TEN blister fluid.¹⁵ This helps explain why the skin destruction in SJS can spread so rapidly and extensively: once the immune cascade begins, soluble molecules circulating through the skin amplify the damage far beyond the initial site. The result is widespread cell death in the epidermis, blistering, and eventually detachment of sheets of skin, clinically resembling a burn.

Distinguishing SJS From Look-Alikes

Several other conditions produce rashes that overlap visually with SJS, and sorting them out can be difficult even for experienced clinicians. The most common source of confusion is erythema multiforme major (EMM), which also causes widespread rash and mucous membrane involvement. The distinguishing features are subtle: EMM usually presents with raised, well-defined target lesions concentrated on the extremities, while SJS features flat, widespread spots and blisters that favor the trunk and face. SJS also tends to involve two or more mucosal surfaces and is preceded by systemic symptoms like fever, whereas EMM may not produce the same degree of malaise beforehand.¹⁶

Skin biopsy helps confirm the diagnosis. In one series from Mayo Clinic, biopsies showed epidermal necrosis, changes at the base of the epidermis, and blistering beneath the epidermis in a substantial proportion of cases.¹⁷ Other conditions on the differential include autoimmune blistering diseases (like pemphigus), staphylococcal scalded skin syndrome (which looks similar but is caused by bacterial toxins and is more common in young children), and severe drug rash with eosinophilia and systemic symptoms (DRESS syndrome), which involves internal organs more than skin detachment. If you are in an emergency department and a clinician is trying to figure out what is happening, expect questions about every medication started in the past month, recent infections, and a thorough exam of the mouth, eyes, and genital area.

Acute Treatment and Why Speed Matters

The single most important step in treating SJS is stopping the offending drug as quickly as possible. A study adjusting for multiple confounding factors found that each additional day before the causative drug was withdrawn worsened the odds of death.¹⁸ This makes identification of the triggering medication an urgent priority, not an academic exercise. When multiple medications have been started recently, clinicians often stop all plausible culprits at once rather than waiting to pinpoint the one responsible.

Beyond drug withdrawal, treatment is largely supportive and resembles burn care: wound management, fluid replacement, pain control, nutritional support, and prevention of infection. Many patients are treated in burn units or intensive care settings. Clinicians use a scoring system called SCORTEN, which factors in age, heart rate, cancer history, percentage of skin detachment, blood urea nitrogen, blood glucose, and bicarbonate levels, to estimate mortality risk. High SCORTEN scores accurately predict death, while most patients with low scores survive.¹⁹

For targeted drug therapy, cyclosporine has the strongest evidence base. A meta-analysis of nine studies found a significant reduction in mortality risk with cyclosporine treatment, and it was generally well tolerated even in critically ill patients.²⁰ Biologic therapies, particularly the anti-TNF-alpha drug etanercept, have also shown promising results in systematic reviews.²¹ Intravenous immunoglobulin (IVIG) is used at many centers but remains more controversial; the evidence for mortality benefit is less consistent. A multidisciplinary team that includes dermatologists, ophthalmologists, gynecologists (for genital involvement), and burn specialists yields the best care, as each affected tissue needs attention to prevent long-term scarring.²²

Eye Complications Deserve Their Own Attention

Eye involvement is reported in up to 75 percent of SJS/TEN patients during the acute phase, making it one of the most common and consequential features of the disease. Initial symptoms include red, irritated eyes, pseudomembrane formation on the inner eyelids, and corneal erosions.²³ Without aggressive early treatment by an ophthalmologist, the inflammation can scar the conjunctiva (the membrane lining the eyelids and the white of the eye), destroy the goblet cells that produce the mucus layer of tears, and damage the lacrimal gland ducts. The downstream result is severe chronic dry eye, one of the most common lasting complications of the disease.²⁴

More advanced scarring can fuse the eyelid to the eyeball (symblepharon), restrict eye movement, and cause the eyelids to turn inward so that lashes scratch the cornea. Some patients eventually develop limbal stem cell deficiency, where the cells that regenerate the cornea’s surface are depleted, leading to clouding and potential vision loss. These complications are treatable but often require long-term management: artificial tears, anti-inflammatory drops, scleral contact lenses to protect the corneal surface, and sometimes surgical reconstruction. Eye involvement during SJS should always prompt immediate ophthalmologic consultation, not a wait-and-see approach.

Life After SJS

Surviving the acute phase does not mean the condition is over. Long-term physical sequelae are the norm rather than the exception. In one study of SJS/TEN survivors, roughly 84 percent reported lasting skin problems (scarring, pigmentation changes, nail abnormalities), about 60 percent had ongoing eye issues, and around 51 percent had chronic oral mucosal problems.²⁵ Genital scarring, vaginal stenosis, and urethral complications are also documented, particularly in women, and are frequently underaddressed in follow-up care.²⁶

The psychological toll is substantial and often overlooked. In the same survey, over half of respondents scored positive for depression, about 43 percent showed signs of anxiety, and roughly one in five had results consistent with post-traumatic stress disorder.²⁵ A separate review estimated psychological complications at about 60 percent and emphasized that these are treatable but underrecognized, recommending psychological support during hospitalization, before discharge, and throughout follow-up for all SJS/TEN patients.²⁷

Quality of life scores among survivors reflect this burden. Physical and mental health component scores fall below population averages, often substantially so, even years after the acute event. People who have survived SJS frequently describe ongoing fear of taking any medication at all, social withdrawal related to visible scarring, and frustration with a medical system that often has limited familiarity with the condition. Online patient communities and organizations like the SJS Foundation can help connect survivors with specialists who understand the full scope of follow-up care these patients need.

Medication Safety After a Prior Episode

If you have had SJS once, avoiding the culprit drug and all structurally related medications is critical for the rest of your life. Cross-reactivity between drugs in the same family is a real concern: a person who had SJS from carbamazepine should generally avoid oxcarbazepine, and possibly other aromatic anticonvulsants, depending on the clinical and genetic workup. Wearing a medical alert bracelet or carrying documentation of your reaction, including the specific drug and diagnosis, is practical advice that could prevent a dangerous re-exposure during an emergency when you might not be able to communicate.

If genetic testing was not done during the initial episode, it can still be worthwhile afterward. Knowing your HLA type helps inform which entire classes of drugs to avoid in the future and can be useful information for blood relatives as well, since the same HLA alleles run in families. For instance, if you carry HLA-B*58:01, your siblings have a reasonable chance of carrying it too, and they should know this before being prescribed allopurinol. The U.S. FDA currently recommends HLA-B*15:02 testing before starting carbamazepine in patients of Southeast Asian ancestry, and clinical pharmacogenomics guidelines from organizations like CPIC provide broader recommendations. These tests are typically a simple blood draw and are increasingly covered by insurance when there is a clinical indication.