Erythema Multiforme: Target Lesions, Causes, and Treatment

Erythema multiforme (EM) is an immune-related skin reaction best known for round, target-shaped spots that often begin on the hands and feet. It may follow an infection, especially herpes simplex virus (HSV), and less often may be linked to a medicine or another trigger. Some people develop sores on the lips or inside the mouth, eyes, or genital area. Most episodes improve over several weeks, but severe mucosal symptoms, eye involvement, or a rash after a new medicine need prompt medical assessment.

EM is a distinct condition from Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which are serious blistering and skin-detachment reactions. Because some symptoms can overlap, a new painful rash with blisters or mucosal sores should not be diagnosed at home. If the mouth, eyes, or genitals are involved, or eating, drinking, urinating, or swallowing becomes difficult, seek urgent care.

Quick takeaways: classic EM lesions have several rings of color and often favor the hands, feet, elbows, or knees; an infection is a common trigger, but sometimes no cause is found; treatment is often supportive; recurrent HSV-associated episodes may need clinician-guided prevention; and widespread painful blistering or skin peeling is an emergency.

Typical rashRound raised spots with a darker center, paler middle ring, and red outer edge.

Common locationsHands and feet first, often including palms and soles; may extend toward arms, legs, or trunk.

Common triggerAn infection, especially HSV; some medicines and other triggers are possible.

Figure 1. A brief overview of erythema multiforme. Target-shaped lesions are a clue, not a home diagnosis.

What is erythema multiforme?

Erythema multiforme is an acute immune-mediated reaction involving the skin and sometimes mucous membranes. “Erythema” refers to inflammation and color change; “multiforme” reflects the variety of shapes the rash can take. The classic lesion is a raised target or iris shape made of zones of different color. Lesions are often symmetrical and appear on the hands, feet, arms, or legs before some spread toward the trunk.

The condition can appear once, recur in episodes, or persist. A single episode is often self-limited. The target spots can be itchy, tender, swollen, or burning, though some people have few symptoms. Mouth sores may be painful and interfere with eating or drinking. Eye, genital, or urinary mucosal involvement is less common but important because it can cause complications or require hospital care.

EM is not the same as cold sores, though HSV is a frequent trigger. The immune reaction can follow an HSV episode rather than representing the virus spreading through every target lesion. A person with EM should not assume that all the spots are contagious. If there is an active cold sore or another infection, usual precautions for that infection still apply.

EM can affect people of different ages and skin tones. The rash may appear pink, red, brown, purple, or darker than surrounding skin depending on natural skin color and inflammation. Because color alone is not reliable, note the shape, raised texture, distribution, pain, blisters, and symptoms involving the mouth or eyes.

What do target lesions look like?

A classic target lesion has three zones: a central dusky or blistered area, a lighter middle ring, and a red or darker outer border. The ring pattern is usually raised, and a person may have many spots at once. Some lesions are not perfectly circular or do not show all three zones; these are called atypical targets. Early lesions may start as round red or purple bumps before the rings become clearer.

EM often favors the backs of the hands and feet, palms, soles, forearms, elbows, knees, and other outer surfaces. The rash may be fairly symmetrical. New spots can appear over several days, so different lesions may look different at the same time. In people with darker skin, the zones may look brown, gray, violet, or subtly different from one another rather than bright red.

Mucosal lesions can begin as blisters that break into painful shallow erosions. The lips and mouth are most often involved, but the eyes and genital or urinary surfaces can also be affected. Mouth or throat pain can make fluids difficult to swallow. Eye pain, light sensitivity, redness, tearing, or blurred vision needs prompt evaluation because inflammation can damage the eye.

CenterDusky, darker, or sometimes blistered area.

Middle ringPaler or swollen-looking zone around the center.

Outer borderRed, purple, or darker raised edge.

PatternSeveral round zones form a target or iris-like spot.

Figure 2. The three-zone pattern is characteristic of a classic target lesion. Not every EM spot is a perfect target.

Causes and triggers

Infections are the most common identified triggers. HSV-1, the virus that often causes cold sores, is frequently associated with EM; HSV-2 can also be involved. Other infections have been reported, including some respiratory infections. Mycoplasma pneumoniae can cause a related mucocutaneous reaction that is now often described as reactive infectious mucocutaneous eruption (RIME). If a rash occurs with a new cough, fever, or pneumonia symptoms, tell the clinician.

Some medicines have been linked to EM, including certain antibiotics, anti-seizure medicines, and nonsteroidal anti-inflammatory drugs. A medicine may be suspected if a rash began after it was started, but timing alone does not prove that it caused the reaction. The clinician will review every recent prescription, over-the-counter medicine, supplement, vaccine, and infection. Do not restart a medicine that a clinician has identified as a serious reaction trigger.

Vaccines have rarely been reported as triggers, but a temporal association does not show that a vaccine caused an individual rash. Discuss the event with a clinician before changing future vaccination plans. When a medicine or infection is suspected, a qualified professional can weigh the risks of continuing or stopping treatment and document the reaction accurately.

In many episodes no clear trigger is found. Recurrent or persistent EM may require a more detailed evaluation for HSV, another infection, or a less common underlying condition. This does not mean that most people with EM have a serious hidden illness. The extent of testing depends on the pattern, frequency, symptoms, age, and clinical findings.

InfectionsHSV is common; other viral, bacterial, or respiratory infections may be considered.

MedicinesSome antibiotics, anti-seizure medicines, or anti-inflammatory drugs are possible triggers.

No identified triggerSometimes a careful review still does not reveal what started the episode.

Figure 3. A clinician reviews timing and symptoms to assess possible triggers. Do not stop or restart a prescription without medical guidance.

Erythema multiforme minor and major

Clinicians may use the terms EM minor and EM major to describe the amount of mucosal involvement. EM minor typically involves the characteristic skin eruption with little or no mucosal disease. EM major includes more significant mucosal involvement. These labels describe a clinical pattern; they do not mean that a person can safely judge severity at home.

Even a small number of mouth sores can be serious if pain prevents drinking or leads to dehydration. Eye involvement needs prompt assessment. Genital or urinary lesions can make urination painful or difficult. A clinician may involve dermatology, ophthalmology, oral medicine, gynecology, urology, or hospital teams depending on the areas affected.

EM should be distinguished from SJS/TEN and RIME. Classic EM more often has raised, well-formed targets concentrated on the hands and feet, with limited skin detachment. SJS/TEN may begin with flu-like symptoms followed by widespread painful dusky spots, blisters, skin peeling, and mucosal involvement, often after a medicine. RIME is often linked to a respiratory infection and prominent mucositis. These descriptions can overlap, so urgent medical assessment is needed if there is widespread blistering, skin peeling, severe pain, or mucosal sores.

Feature	Erythema multiforme	Why urgent review may be needed
Skin pattern	Often raised target lesions, commonly on hands and feet	Widespread flat dusky spots, blistering, or skin peeling can suggest another serious reaction
Mucosa	May affect lips or mouth; eyes or genitals less often	Eye pain or sores that limit drinking, swallowing, or urination need urgent care
Possible trigger	Often infection; medicines can sometimes be implicated	A painful rash after a new medicine should be assessed the same day
Course	Often settles over a few weeks	Rapid progression, fever, severe pain, or feeling very unwell needs prompt assessment

Eyes or mouthEye pain, light sensitivity, blurred vision, mouth or throat sores that limit fluids.

Skin changesWidespread blistering, painful dusky patches, peeling, or rapidly spreading rash.

Medicine or illnessRash after a new medicine, high fever, severe aches, or feeling very unwell.

Figure 4. These warning signs can indicate severe EM or another urgent condition such as SJS/TEN. Seek medical care promptly.

When to seek care

Arrange medical assessment for a new target-like rash, especially if the rash is painful, keeps returning, or is accompanied by fever or a recent infection. Seek same-day urgent care if the rash involves the lips, mouth, throat, eyes, anus, or genitals; if eating, drinking, swallowing, or urinating is difficult; or if it began after starting a new medicine. Bring a list of medicines and the dates they were started.

Get emergency care for widespread painful blisters, skin peeling, rapidly spreading dusky patches, eye pain or vision changes, severe mouth or throat involvement, trouble breathing or swallowing, facial or tongue swelling, confusion, fainting, or signs of dehydration. A severe reaction can worsen quickly. Do not wait for a routine dermatology visit or rely on an online photo to rule out SJS/TEN.

During an episode, seek medical advice if pain is preventing fluids or if there are signs of dehydration such as very little urine, dizziness, or unusual sleepiness. Children and people who are pregnant, immunocompromised, or have significant chronic illness may need a lower threshold for medical review.

Medication note: If the rash started after a new medicine, contact the prescriber or urgent-care service promptly for instructions. If symptoms suggest a severe reaction, go to emergency care. Bring the medication packaging or list and do not restart a medicine that a clinician has identified as the trigger.

How erythema multiforme is diagnosed

A clinician often makes the diagnosis from the shape and distribution of the lesions, the timing, and whether mucous membranes are involved. They may ask about cold sores, cough or pneumonia symptoms, recent infections, all medicines started or changed, vaccination timing, and past episodes. The examination includes the skin as well as the mouth and, when relevant, the eyes and genital area.

A skin biopsy is not always required when the target lesions are classic. It may be useful if the appearance is unusual or the clinician needs to distinguish EM from SJS/TEN, a blistering disorder, vasculitis, fixed drug eruption, or another condition. The biopsy findings are interpreted alongside the clinical picture and do not always give a definitive answer by themselves.

Testing is guided by symptoms and likely triggers. If there are respiratory symptoms, clinicians may assess for a respiratory infection. If episodes recur, they may look more closely for HSV or other causes. Blood tests can be used when a person is significantly unwell or when another condition is suspected. There is no single blood test that confirms every case of EM.

The diagnosis may change as the rash evolves. Early lesions do not always show the classic rings, and some severe reactions begin with nonspecific fever or tenderness. If new symptoms appear after an initial assessment, especially blistering, peeling, eye symptoms, or painful mucosal sores, get reassessed promptly.

1. Describe the rashWhen it began, where it started, how it changed, and whether it hurts or itches.

2. Review triggersRecent HSV or respiratory illness, new medicines, supplements, or vaccination.

3. Examine skin and mucosaLook for target lesions, blisters, peeling, and mouth, eye, or genital symptoms.

4. Test if neededBiopsy or targeted testing helps when the diagnosis or trigger is uncertain.

Figure 5. Assessment combines lesion pattern, history, and symptoms. Tests are selected for the individual case.

Treatment and home support

Many mild episodes need little beyond symptom relief while the rash settles. The National Health Service notes that episodes usually improve within two to four weeks. Some severe episodes take longer. A clinician may recommend a moisturizer, a topical anti-inflammatory medicine, or an antihistamine for itch or discomfort. Do not apply a new medicine to blistered or open skin without asking whether it is appropriate.

For mouth soreness, a clinician may suggest gentle rinses, local pain relief, or other measures that make drinking easier. Choose cool, soft foods and avoid items that sting if oral sores are present. If pain prevents adequate fluid intake, hospital care may be needed for hydration and nutrition. Eye involvement requires prompt ophthalmology assessment; do not use leftover eye drops.

If an underlying infection is identified, it may need treatment. Treating HSV during a single EM episode does not necessarily shorten the skin reaction, but antiviral prevention may be discussed for frequent recurrent episodes that appear linked to HSV. The decision depends on the pattern, prior testing, and the possible benefits and risks of longer-term medicine.

If a medication is suspected, the prescriber will decide whether to stop, replace, or avoid it in the future. Keep a record of the suspected reaction and ask how it will be documented. Do not take someone else’s steroid, antiviral, antibiotic, or pain medicine. Systemic steroids or immune-modifying treatments are specialist decisions, particularly because severe drug reactions and infections must first be considered.

ComfortUse only clinician-approved skin or pain relief; protect tender areas from friction.

Hydration and mucosaSeek help if mouth or throat pain prevents drinking or if eyes are affected.

Cause and recurrenceReview infections and medicines; discuss prevention if episodes keep recurring.

Figure 6. Care depends on severity, mucosal involvement, and the likely trigger. Recurrent disease deserves a follow-up plan.

Recurrence and outlook

Most people recover without lasting skin damage. The target spots usually fade over a few weeks, though temporary darker or lighter marks can remain for months. The rash generally heals without scars unless there has been significant blistering or skin injury. Pain and mucosal symptoms may take longer to settle than the visible skin spots.

Some people have recurrent EM, sometimes after cold sores or another infection. The time between episodes can vary. Keeping a simple record of rash dates, cold sores, respiratory symptoms, medicines, and any mouth or eye involvement can help a clinician identify a pattern. Photographs taken in consistent lighting may also help, but do not delay urgent care to take pictures.

For repeated episodes linked to HSV, a dermatologist or other clinician may discuss antiviral prevention. If the cause remains unclear or the rash persists, they may revisit the diagnosis or consider further evaluation. Long-term care is individualized; treatments used for one person's recurrent EM may not be appropriate for someone with a different trigger or a severe mucosal condition.

Ask for support if repeated outbreaks interfere with eating, sleep, school, work, or confidence. Mouth or genital involvement can be uncomfortable to discuss, but sharing these symptoms helps clinicians assess severity and prevent complications. A clear plan should identify what to do at the first sign of recurrence and which changes require urgent review.

Questions to ask your clinician

Does the rash have the classic pattern of EM, or could it be SJS/TEN, RIME, or another condition?
Do I need a biopsy or tests for an infection?
Could a medicine be involved, and what should I do before the next dose?
How should I manage mouth pain and maintain fluids?
Do eye symptoms need an ophthalmology review?
If this keeps recurring, could HSV be a trigger and would prevention be appropriate?
Which symptoms mean I should go to urgent care or emergency care?

Frequently asked questions

What does an erythema multiforme target lesion look like?

A classic target lesion has a darker or dusky center, a paler middle ring, and a red or darker outer border. Lesions often begin on the hands or feet and may be raised. Not every spot forms a perfect target.

Is erythema multiforme contagious?

EM itself is an immune reaction and is not spread by touching the rash. An infection such as HSV may have triggered it, so follow ordinary precautions for any active infection.

Is erythema multiforme the same as Stevens–Johnson syndrome?

No. They are distinct conditions, though symptoms can overlap. Widespread painful blisters, skin peeling, severe mucosal sores, or a rash after a new medicine needs urgent medical assessment.

How long does erythema multiforme last?

Many episodes improve in about two to four weeks. More severe episodes may take longer, and recurrent episodes can appear again after a trigger.

Can a cold sore cause erythema multiforme?

Yes. HSV is a common trigger, and the skin reaction may occur after a cold sore or sometimes without an obvious active sore. Recurrent episodes should be discussed with a clinician.

Can medication trigger erythema multiforme?

Some medicines have been linked to EM, but a suspected trigger needs clinical review. If the rash began after a new medicine, seek urgent advice and bring a list of medicines; do not restart a drug that a clinician identifies as a serious trigger.

When is erythema multiforme an emergency?

Get emergency care for widespread blistering or skin peeling, eye pain or vision changes, severe mouth or throat sores, trouble breathing or swallowing, facial or tongue swelling, confusion, fainting, or inability to maintain fluids.

Sources and further reading

Medical information notice: This article is for education and is not a diagnosis or substitute for individualized care. New target-like rashes, especially with mouth, eye, genital, blistering, or medication-related symptoms, need clinical assessment. Seek emergency care for severe pain, skin peeling, trouble breathing or swallowing, vision changes, confusion, fainting, or inability to drink.

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