What is Erythema Multiforme?
Erythema multiforme (EM) is a condition that causes sensitive skin and mouth reactions, featuring distinctive skin blisters and marks. These reactions are sparked off by different factors and can either be a one-time thing or happen multiple times. The marks and blisters can range from small raised spots, to large fluid-filled blisters, to areas of dead tissue. These reactions typically develop over a couple of days and are usually seen on the arms and legs. These spots stay in one place and usually get better on their own within one to three weeks.
Common triggers of EM include certain viruses such as the herpes simplex virus and the Epstein Barr virus and a fungus called histoplasmosis. It’s not unusual for the herpes virus to cause repeat episodes of this skin condition. While most cases of EM are quite mild, severe cases can be really serious and pose a risk to life. In 2-10% of people with EM, the mucus-producing membranes inside the body, such as the lining of the mouth or nose, are affected. In general, most cases of EM occur because of an adverse reaction to medication.
What Causes Erythema Multiforme?
Erythema multiforme (EM) is often developed as a result of infections, mainly due to a common virus known as Herpes simplex type 1 and 2, as well as a bacterium called Mycoplasma pneumoniae. This condition can also be triggered by several other types of viral, fungal, and bacterial infections. In rarer cases, some vaccines can also potentially cause EM, although this is still an ongoing subject of debate.
There are also drugs that have been linked with EM. These include antibiotics, which are medicines used to treat infections, like the penicillins, cephalosporins, macrolides, and sulfonamides, as well as drugs used for tuberculosis and fever reduction. In addition to drugs, exposure to heavy metals, herbal products, skin treatments, and even poison ivy have been known to cause EM in some cases.
Risk Factors and Frequency for Erythema Multiforme
Erythema multiforme (EM) is a condition that can occur all over the world and doesn’t favor any particular ethnic group. It can happen at any age, but it’s more commonly seen in young adults between 20 to 30 years old. Interestingly, about 20% of cases are in children. Men seem to be more often affected than women, with a ratio of 1 in 5. The exact number of people in the general population who have this condition isn’t known, but it’s estimated to be less than 1%. Also, it’s important to note that some reported cases of this illness could actually be a different condition, Stevens-Johnson Syndrome, due to unclear classifications between these two conditions.
There are certain groups of people who have a higher chance of getting EM. These include:
- People with HIV
- People taking corticosteroids
- People with a lower immune system function
- Individuals who have had a bone marrow transplant
- People diagnosed with lupus
Signs and Symptoms of Erythema Multiforme
Erythema multiforme (EM) is a skin condition that typically begins with symptoms such as fever and a general feeling of discomfort. Some people may also experience joint pain or swelling. The characteristic sign of this condition is the appearance of a specific type of skin lesion, known as a target lesion. These lesions have three concentric rings and a clearly defined border. They are less than three centimeters in diameter and commonly appear on the hands, feet, and limbs. Some people may also have them on their face and ears. However, they don’t usually appear on the trunk of the body. These lesions do not itch, but some people may experience a burning sensation.
In addition to skin lesions, some people may also develop lesions on the mucous membranes, such as the mouth, genitals, and eyes. These mucosal lesions start as blisters and quickly turn into painful sores. They may be covered by thick crusts or a white coating. Mucosal lesions often appear at the same time as skin lesions, but they can also appear a few days before or after the skin lesions develop. Unlike the skin lesions, mucosal lesions can be quite painful.
Some people with EM may also experience respiratory symptoms such as coughing and difficulty breathing, which are commonly due to an underlying infection. Moreover, extensive skin involvement may lead to dehydration, and those with mucosal lesions may lose weight because they have difficulty eating.
Testing for Erythema Multiforme
Erythema Multiforme (EM), a type of skin condition, can be diagnosed mainly through a careful review of the symptoms you are experiencing. If the doctor isn’t entirely sure or if there’s any doubt, they may perform a skin biopsy. This involves taking a small sample of the lesion’s central area, which is then examined under a microscope (this is known as histological study with immunofluorescence).
This analysis often shows an enlargement and softening of the cells that produce skin pigment and the death of skin cells, triggering a blister-like formation under the skin’s surface covered by dead skin. A cluster of immune cells (lymphohistiocytic infiltrate) usually surrounds the blood vessels in the superficial layer of the skin, but they don’t cause vascular damage. The direct immunofluorescence test, which checks for specific substances like antibodies, is typically negative in this situation.
Even though no labs can conclusively prove a diagnosis of Erythema Multiforme, running certain tests can help the doctors understand how severe the disease is. For example, a chest x-ray can be used to detect changes in the lungs (like interstitial infiltration, where the spaces between the lung’s air sacs get thickened), particularly in EM cases caused by a bacterium called Mycoplasma pneumoniae. The diagnosis can also show if there’s any damage to your kidneys, liver, or blood cells – however, doctors don’t usually look for these unless your forms are severe.
For identifying the cause of EM, the doctor’s approach is based on the symptoms. It’s not necessary to check for everything, as some aspects are more common than others:
– Herpes infection, especially due to HSV-1, is the most common cause. It often results in minor cases of EM. The herpes sores usually appear 7 to 10 days before the EM. It is important to know that not all herpes flare-ups result in EM, and some EM cases may be caused by silent (asymptomatic) herpes recurrences. The herpes virus is often not detectable at the diagnosis stage. If you’ve had recurring episodes of EM, the cause is likely to be herpes, seen in about 70% of recurring EM cases. In clinical practice, doctors would take your entire medical history (anamnesis) into consideration to identify a possible herpes origin.
– Infections in kids caused by Mycoplasma pneumoniae should be carefully checked, as they require a different treatment. EM complicates about 2% to 10% of these infections in kids and often involves the mucous membranes (mucosal involvement). This bacterial infection causes about two-thirds of EM cases with mucosal involvement. That’s why it’s recommended to get a chest x-ray and conduct a bacteria test, ideally through gene amplification (PCR). Other viral (like adenovirus, influenza, Epstein Barr, hepatitis virus, Coxsackie, parvovirus B19, HIV) and bacterial (like tuberculosis, streptococci) infections may also be responsible.
– Some pediatric vaccines have been linked with EM. However, the ties are often disputed due to the numerous vaccines available and the rarity of this association.
A blood test might show mild leucocytosis (a slight increase in white blood cells), neutropenia (low levels of a type of white blood cell called neutrophils), and mild anemia (lack of enough healthy red blood cells). Any changes in electrolyte values can indicate advanced states like dehydration or kidney failure.
Treatment Options for Erythema Multiforme
If you develop blister-like lesions due to a medical condition, it’s typically treated using antiseptic medications for the blisters, and mouthwashes for any oral symptoms. Those with eye symptoms may need to see an eye specialist (ophthalmologist). Applying vaseline on the lips and vitamin A ointment in the eyes can boost the healing process.
In severe cases, where you’re unable to eat, manage your pain, or stay hydrated, you may need to be hospitalized. In hospital, your skin lesions would need daily check-ups. While some treatments like systemic corticosteroids, or medications given through the veins, might be considered, their effectiveness is uncertain.
If a cause for your condition can be identified, specific treatments can be started. For example, an infection caused by a certain bacterium called Mycoplasma pneumoniae could be treated with a drug called azithromycin. This is usually started without waiting for lab results, particularly if you have a cough or chest-related abnormalities. It’s also suggested to use antiviral drugs aciclovir or valaciclovir if a herpes infection is suspected.
Preventing the recurrence of these skin lesions is especially important. One common cause of these skin lesions is the herpes simplex virus. If your doctor strongly suspects this, even without definitive lab results, they might suggest using long-term antivirals such as aciclovir or valaciclovir. This is typically recommended for patients who have more than 5 outbreaks per year or fewer for severe cases. If the cause of the skin lesions is unknown, other treatments like hydroxychloroquine, dapsone, or early use of corticosteroids might be recommended.
If your condition is severe, you might need hospitalization to manage complications, dehydration, or infections. In some cases, you might need to be treated similarly to patients with serious burns, and admitted to an intensive care unit (ICU). The lesions should be gently cleaned with specific solutions and covered with non-stick dressings. Any medications suspected to have caused the condition should be stopped. Some treatments can speed up skin regeneration, which can take anywhere from 7 to 21 days. Nutritional support is crucial, and in some cases, you may need nutrition delivered through your veins (TPN) especially if you are experiencing severe diarrhea. Regular practices to prevent infections should be followed. In some situations, if you are feeling cold, measures like warming blankets, warmed IV solutions, or heat lamps may be needed. It is also important to prevent potential complications, such as blood clots and ulcers caused by stress during this period.
What else can Erythema Multiforme be?
Stevens-Johnson Syndrome (SJS) is a serious medical condition that impacts up to 10% of the skin area on a person’s body. This is a larger range than a condition called erythema multiforme (EM). Both conditions affect the mucous membranes in similar ways.
In SJS, the skin conditions differ from EM due to the absence of typical target-like marks and a more central location spreading across the body. The marks that do appear are irregular and composed of two circular areas with a purplish discoloration. This condition often arises due to reactions to certain medications.
What makes SJS more dangerous is its potential to escalate into a severe condition known as Lyell syndrome, something that does not occur with EM. Additionally, another condition, Behçet’s disease, can cause skin lesions that resemble those seen in erythema multiforme.
What to expect with Erythema Multiforme
The healing and outcomes from a skin condition largely depend on how much of the skin is affected. Healing usually happens naturally; minor conditions can clear up in about 2 to 3 weeks, while more serious ones can take 4 to 6 weeks. When the condition affects the mucous membranes (the soft, wet parts of the body such as the inside of the mouth), it always takes longer to heal.
When the skin and mucous membranes do heal, they usually do so without leaving scars, but often there is a change in skin color. It’s good to note that these conditions might reoccur in fewer than 5% of patients, mostly when it’s due to a herpes infection.
The main concern with long-term effects is when the mucous membranes are affected. At this point, they can form connections or bands (known as synechiae) that aren’t supposed to be there. This could be a serious issue when it involves the eyes, potentially leading to blindness. If it affects the genital area, it can cause functional problems.
To avoid these long-term effects, it’s very important to be vigilant during the early stages of the condition. The good news is that with proper care, it’s a rarity for these conditions to become life-threatening. However, there are two situations that need special attention: severe involvement of the mucous membranes and bacterial infections on top of the original skin condition.
Factors that could make the conditions worse are damage to the kidneys, having had a bone marrow transplant, involvement of the internal organs, and being elderly.
In some unfortunate cases, patients might experience a continuous condition that doesn’t respond to treatment. This might happen with conditions linked to herpes simplex virus (HSV) infection, a condition where the Epstein-Barr virus (that causes glandular fever) flares up again, inflammatory bowel disease, and a hidden type of kidney cell cancer.
Possible Complications When Diagnosed with Erythema Multiforme
The healing process for mucosal lesions typically leaves no trace; however, skin lesions tend to leave scars. It’s also pretty common to find narrow, constricted areas in the urethra, esophagus, vagina, and anus. Some people experience being unable to urinate, foreskin of the penis becoming too tight, or blood accumulation within the vagina as a result of these constrictions.
Furthermore, up to 20% of patients might develop eye complications such as inflammation within the eye (uveitis), an inflammation of the eye’s outermost layer (conjunctivitis), scarring, a severe infection that spreads throughout the eye (panophthalmitis), and in the most extreme cases, permanent blindness. If the tear duct becomes narrowed, it might result in excessive tearing (epiphora). There are also instances where patients develop a condition known as ‘dry eye syndrome’ as well as scarring on the cornea.
Key Things to Note:
- Complete healing for internal body surface (mucosal) lesions, but skin lesions may leave scars.
- Common narrow, constricted regions in the urethra, esophagus, vagina, and anus.
- Possible urinary issues, foreskin tightness or blood accumulation in the vagina due to these constrictions.
- Eye complications in up to 20% of cases that could escalate to permanent blindness.
- Potential narrowing of the tear duct leading to excessive tearing.
- Possibility of developing ‘dry eye syndrome’ and corneal scarring.
