Introduction

Target lesions are the clinical hallmark sign of erythema multiforme (EM), meaning they are the most recognisable feature of the condition. 

EM is an acute condition that affects the skin and mucous membranes. It occurs when your body’s immune system overreacts, typically in response to a viral infection such as herpes simplex virus (HSV), or sometimes to certain medications.¹ EM can range in severity, from EM minor, where only the skin is affected, to EM major, where both the skin and mucous membranes are affected. EM tends to be self-limiting and usually clears up on its own without the need for treatment. 

Target lesions play a key role in helping diagnose EM and distinguishing it from other conditions that also result in a widespread rash, such as Stevens-Johnson syndrome.² 

In this article, you will learn more about target lesions in EM, including the causes, how they can appear, and the different variants in which they can present themselves. 

Causes of target lesions in erythema multiforme.

EM occurs due to an immune reaction from your body. Your immune system mistakenly attacks small blood vessels in the skin or mucous membranes, leading to target lesions. The most common cause of EM is HSV type one, although, more rarely, HSV type two can also trigger EM. Other infectious triggers might include: 

• Influenza virus
• Epstein-Barr virus
• Cytomegalovirus.

Apart from viral infections, certain medications can also trigger EM, such as:³ 

• Non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen 
• Antibiotics, such as eg, penicillin, erythromycin, and nitrofurantoin
• Anti-epileptic medicines
• Some vaccinations

Typical target lesions  

The hallmark lesion of EM is called the target lesion or the iris lesion. New lesions can form suddenly within a 24 to 48-hour time period, and may be itchy and painful. It is a round lesion composed of three different segments:⁴

• Inner zone - a darker zone, sometimes blistered
• Middle zone - a paler pink zone, which can be swollen
• Outer zone - an outer red ring, surrounding both zones

Generally, the lesion tends to be symmetrical and first affects the peripheries before spreading centrally. The lesions favour the extensor surfaces, such as the back of the hands, palms, soles, elbows, knees, and other extensor surfaces. In more severe cases, they may also appear on the face, neck, or trunk. In terms of size and shape, the target lesions tend to be round and sharply defined. They vary in size, ranging from a few millimetres to several centimetres. 

Atypical target lesions 

The classic hallmark lesion, as described previously with the three distinct zones, is considered a typical target lesion. However, they can also present atypically. Atypical target lesions share some, but not all, of the characteristics of a typical target lesion. They typically show only two zones of colour and may have less sharply defined borders. It is also possible to have a mixture of typical and atypical target lesions at the same time.⁵   

Variants of target lesions 

Target lesions can have more variants in their appearance. They can manifest as flat or raised. When lesions are raised, they are known as papular target lesions. In addition, they can affect the mucous membranes, meaning lesions can occur on areas such as the mouth, eyes, or genitals. 

Following mucosal involvement, EM becomes classed as EM major. Therefore, this distinction means that target lesions can help diagnose EM and differentiate between EM minor and EM major. Often, with mucosal lesions, you may notice early symptoms such as fever, weakness, and malaise occurring a week before the lesions appear.⁵

Complications of target lesions in erythema multiforme 

Target lesions usually clear up on their own, but they can still cause you discomfort and pain. Some complications of target lesions in EM may include:⁶

• Skin infection - open lesions may become infected with bacteria
• Scarring - whilst mucosal lesions heal completely, skin lesions may result in scars 
• Hyperpigmentation - skin inflammation may cause areas of darker pigmentation
• Painful mucosal lesions - this can make eating, drinking, or urination difficult 
• Strictures - narrowing of the urethra, oesophagus, and genitals can occur 
• Dehydration - mouth ulcers may prevent adequate fluid intake 
• Eye complications - redness, irritation, dryness, and in severe cases, scarring, infection, vision loss, or permanent blindness 
• Emotional and social impact - recurrent EM can affect self-confidence, quality of life, and be a stressful experience for people

Clinical importance of target lesions 

So, what is the clinical importance of target lesions? The diagnosis of EM is based on your medical history and examinations; therefore, the appearance of these target lesions is helpful in diagnosis. Based on medical history and clinical examination alone, most cases of EM will not need further diagnostic tests such as biopsies, blood tests, or scans. These tests are reserved for unclear presentations of EM, or to eliminate other differential diagnoses.

Additionally, target lesions help classify EM as minor or major. EM major is the more severe form and can lead to hospitalisation and may even be life-threatening. 

Most importantly, they help differentiate EM from other similar presenting conditions, such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN), which are life-threatening conditions that require immediate hospital treatment. Some other similar presenting conditions include:

• Urticaria (Hives)
• Fixed drug reaction 
• Pityriasis rosea
• Bullous pemphigoid
• Mycoplasma Pneumonia
• HSV infection

FAQS

Why are they called target lesions?

This is due to the lesions having three concentric zones that look like a shooting target. Sometimes it can also be referred to as “bull’s-eye’’ or “iris’’. 

How long will my target lesions last? 

As mentioned previously, EM is self-limiting. However, each lesion can take up to a couple of weeks to clear. During this time, new lesions could appear while older lesions start to heal and fade, therefore prolonging the process. In EM minor, most cases subside within two to three weeks, whereas in EM major, it can take from four to six weeks to resolve. Persistent EM is a rare chronic subtype of EM, which can last for years. The cause for persistent EM is less clear and has been associated with conditions such as Epstein-Barr Virus, cytomegalovirus, hepatitis C, influenza, inflammatory bowel disease, and malignancies.⁵

Can the target lesions come back? 

Yes, EM can come back. HSV is the most common cause of recurrent EM. This can be due to the virus becoming reactivated, which can present without obvious symptoms, suggesting an active HSV outbreak. 

Can children get target lesions? 

Yes, children can also get target lesions, as EM can affect people of all ages. 

How are target lesions treated?

The treatment will depend on the symptoms and severity of the rash. Usually, your doctor will look for known triggers for the skin conditions. For example, if it was due to a particular medication, you could stop taking that medicine. If it is due to an infection like HSV and treatment exists specifically for that infection, it could be prescribed. For the target lesions themselves:⁵

• Mild rashes will usually clear up on their own. Moisturisers and topical corticosteroids can help speed the process 
• Severe rashes can be dangerous and may require hospital treatment
• Recurrent EM may occur. If it is due to HSV, a drug designed to suppress HSV may be given.

Are target lesions contagious?

Target lesions are not contagious, so they cannot be spread from person to person. However, the causes for EM, like HSV, can be contagious and lead to target lesions forming on another person. 

Can lifestyle factors cause target lesions?

Lifestyle factors do not directly cause EM. EM is usually triggered by infections like HSV. Certain lifestyle factors, like stress, fatigue, or sun UV exposure, can reactivate HSV, which could then trigger EM and thus lead to target lesions. Good infection prevention, sleep hygiene, and stress management can help reduce recurrent EM.

Summary

Target lesions are the hallmark sign of erythema multiforme (EM), which gives the condition its distinctive and recognisable appearance. Their unique bull’s eye-like appearance, with a dark centre, pale ring, and red outer rim, makes them the most recognisable feature of this skin and mucosal condition. The lesions form due to an immune reaction, usually caused by triggers such as viral infections or medications. 

Understanding the variants of target lesions, from flat to blistering forms, and recognising when mucous membranes are involved, allows doctors to distinguish EM from other serious conditions such as Stevens-Johnson syndrome and toxic epidermal necrosis. Additionally, distinguishing different variants of target lesions helps in differentiating between EM minor and EM major. This is important as target lesions in EM major signify a cause for hospital treatment, whilst target lesions in EM minor are usually mild and clear up without serious problems.

Recognising a target lesion remains one of the most valuable tools in the clinical diagnosis of erythema multiforme.