Introduction

Erythema multiforme (EM) is a skin condition that can be caused by infections, such as herpes simplex, or certain medications (NHS UK). ‘Erythema means redness of the skin, while ‘multiforme’ means many forms (British Association of Dermatologists). Erythema multiforme can be mild to severe. In its mild form, it can cause red spots or target-like patches on the skin that resolve without treatment. In its severe form, which is erythema multiforme major (EMM), the mucous membrane, eyes, and skin involvement.¹ Mucosal involvement is more often seen in EMM compared to the minor form.³

Mucus membranes are the soft, moist surfaces that line areas of the body such as the eyes, nose, mouth, throat and genitals. These areas are sensitive and easily irritated, hence why EMM can be painful when it affects them. EMM can affect quality of life; therefore, a need for urgent medical care, especially when the eyes are affected.⁴

It affects less than 1% of the population, and it's common in adults aged between 20-40 years and is more predominant in males (DermNet)

Causes of erythema multiforme major

Most cases of erythema multiforme major are caused by the body’s immune response. This occurs when the immune system mistakenly attacks the skin and mucus membranes as a result of triggers, thereby causing inflammation and damage.³ Common causes are:

• Infections: Herpes simplex virus (cold sore) is a major cause; however, it can also be due to Mycoplasma pneumoniae (Hopkins Medicine)
• Medications: This is less common than infections; however, antibiotics, anti-seizure medications and anti-inflammatory drugs (NSAIDs) can trigger it
• Other triggers: vaccines and some illnesses can cause EMM in rare cases

Symptoms of EMM in the mouth and other mucus membranes

Erythema multiforme major differs from erythema multiforme minor due to its involvement with the body’s mucus membranes. In erythema multiforme major, the mucus membranes of the eyes, mouth, throat, nose and genitals become inflamed and develop painful blisters.

Mouth, Nose and Throat Involvement

The mouth is the most commonly affected mucus membrane in erythema multiforme major. Symptoms include:

• Pain and irritation: the presence of painful red patches and ulcers can make eating, drinking and swallowing difficult
• Bleeding and crushing: the lips often develop cracks, thick crusts and bleeds, which can be distressing and affect confidence in social situations
• Swollen lips and gums: This makes everyday activities like brushing teeth uncomfortable
• Sore throat or hoarse voice in cases of throat involvement
• Nose involvement is less common; however, if it occurs, it can cause soreness, crusting and nosebleeds

Genital Involvement

Although this is not as frequent as mouth ulcers, it can cause genital sores, swelling, a burning sensation during urination and pain during sexual activity. This can lead to embarrassment and affect intimate relationships.

Ocular (Eye) Involvement

 In erythema multiforme major, eye involvement can range from mild irritation to severe problems that can threaten vision. This is the most important area to monitor in erythema multiforme major.

Early signs and symptoms include:

• Redness and irritation of the eyes, which can cause the whites of the eyes to appear bloodshot and sore
• Watery eyes: excessive water makes reading and working uncomfortable
• Gritty sensation: this has been described by people with EMM as if a ‘sand’ is stuck in the eye
• Sticky discharge: thick, sticky fluid may cause the eyelids to stick together, mostly in the mornings 
• Photophobia (light sensitivity) and blurred vision have been reported to cause patients with EMM to avoid well-lit places and have problems with their vision

If untreated, complications such as cornea ulcers, conjunctival scarring, uveitis and vision loss can occur. Based on these, eye involvement in EMM is an emergency. 

You should seek urgent medical help if you notice the following symptoms:

• Red and painful eyes, blurred vision or light sensitivity 
• Severe pain in the mouth and lips that makes it hard to drink
• Problem swallowing or breathing
• Fever with widespread skin rash

Diagnosis of Erythema Multiforme Major

As there is no sign or blood test to diagnose erythema multiforme major (British Association of Dermatologists), doctors diagnose EMM by looking at the patterns of symptoms on the skin and mucus membranes.

Doctors look out for “target-like” red spots on the skin and blisters or ulcers in the eyes or mouth, as these are strong clues for EMM. More importantly, the history of triggers is also noted, such as new medications, chest infections, and cold sores.

Sometimes additional tests such as blood tests, swabs and chest x-ray may be done to identify or rule out other conditions. 

If the diagnosis is uncertain, a skin biopsy can be performed (Geeky Medics).

Aim of treatment

The aim of treatment is to:

• Control pain and relieve symptoms 
• Identifying and managing triggers
• Preventing complications from eye damage
• Ensuring patients are well-hydrated and nourished by supporting the healing of the mucus membranes and skin

Treatment and Management of Erythema Multiforme Major

The management of EMM includes a combination of medical treatment and supportive care.² A multidisciplinary approach is usually required from various specialists such as ophthalmologists, dermatologists, and dentists.²

Mouth and Throat

These involve:

• Pain relief
• Nutritional support to improve swallowing and dehydration. Soft foods can be recommended to avoid irritating the mouth ulcers. IV fluid therapy may also help in severe cases
• Mouthwash: anaesthetic or antiseptic ones can help reduce the risk of infection and reduce pain

Genitals

These involve pain relief gels and strategies to help with urination

Eye

These include:

• The use of lubricating eye drops to reduce discomfort
• Topical steroids or antibiotic drops to reduce inflammation or infection risk
• Regular monitoring to prevent long-term scarring or vision loss

Skin

• The use of non-fragranced moisturisers and mild soaps can reduce irritation
• Special dressings can be used to protect the skin, thereby reducing infection risk

Medical treatment of erythema multiforme major includes steroids, antivirals, antibacterials, opioids and eye lubrication.²

Long-term management

Recurrence of erythema multiforme major is likely after recovery. To reduce the risk of this:

• Antivirals: These can be administered for long-term treatment if the herpes virus is the trigger⁵
• Self-care advice: avoid triggers, stay hydrated, and seek medical attention for new or concerning symptoms
• Routine follow-up with ophthalmology and dermatology for early detection of warning signs

Summary

Erythema multiforme major is a serious condition that affects the skin and mucus membranes. The mouth is the most commonly affected, while eye involvement is the most serious complication of EMM. Most people recover from erythema multiforme major; however, follow-up care is essential.

Recognition of early warning signs, such as red sore eyes, cracked lips, and mouth ulcers, can help patients with EMM seek medical attention immediately.

Erythema multiforme major treatment focuses on symptom relief, identifying and managing triggers and preventing complications.