Erythema multiforme is a mucocutaneous inflammatory condition that is deemed a hypersensitivity reaction (type IV). The term multiforme refers to the multiple forms that it may present (macules → papeles → vesicles).
'Multiforme' is used to describe this rash to its variable presentations that may present simultaneously or sequentially from macules to papules to vesicles.
⚠️ Pathophysiology and risk factors
It is a type IV hypersensitivity in which cytotoxic T-cells react to antigens to form complexes that attract immune cells. This then leads to an immune to keratinocytes in the dermis causing oedema, necrosis and blistering. There is no epidermal necrosis and this is the important differentiating factor between erythema multiforme and toxic epidermal necrosis and Stevens-Johnson syndrome.
Let’s look at some causes of this hypersensitivity reaction:
- Infections
- ⭐️ Herpes simplex virus - both HSV-1 and HSV-2 are implicated and account for >50% of cases.
- ⭐️ Mycoplasma pneumoniae - this is the most common cause in infants.
- Fungal infections
- Viral infections - such as VZV, CMV, HIV and Hepatitis C virus.
- Vaccinations
- Diphtheria
- Tetanus
- Hepatitis B
- Smallpox
- Influenza
- Drugs
- Barbiturates
- Aminopenicillins
- Anticonvulsants
- Antimalarials
- NSAIDs
- Sulfonamides
- Phenothiazines
- Oral contraceptive pill
- Nevirapine
🔢 Classification
Erythema multiforme can be divided into 2 forms:
- Erythema multiforme minor - cutaneous manifestation without mucosal involvement.
- Erythema multiforme major - mucocutaneous involvement.
😷 Presentation
Erythema multiforme presents with a rash that has an acute onset. It has a simultaneous or sequential presentation of the following:
- Macules
- Papules and vesicles
- Target lesions - this is the most characteristic presentation but doesn’t always present. It appears a few days after the rash develops. It has 3 zones - an inner zone that is dark red or brown followed by a pale zone and then finally a red ring on the outside. Sometimes there may be only 2 zones - the innermost brown zone and a pale pink zone surrounding it.
The rash may be completely asymptomatic, or may have some pruritus or associated pain.
- Nikolsky sign - negative. This is when the skin separates when rubbed (indicating cleavage of the dermal-epidermal junctions). It is seen in, and pathognomonic for toxic epidermal necrolysis, pemphigus, staphylococcal scalded skin syndrome.
The rash distribution is as follows:
- Symmetrical
- Most commonly on extensor surfaces and then spreads proximally. It may affect the entire body (including palms and soles).
- May involve mucous membranes (such as oral, ocular, genitals) in cases of erythema multiforme major.
🔍 Investigations
⭐️ The diagnosis is mainly a clinical diagnosis. Suspicion is encouraged if there is a recent history of infection (such as recurrent labial herpes), vaccination, or medication.
Investigations to consider:
- Serology or PCR testing - in patients with suspected HSV or pneumoniae infections
- CXR - to look for Mycoplasma pneumoniae infection.
- Skin biopsy - indicated only in doubtful cases (no target lesions, recurrent erythema multiforme).
🧰 Management
In most cases of erythema multiforme, no treatment is necessary as the condition is self-limiting.
- 🥇 Stop offending drug or treat underlying cause
- Symptomatic treatment is required for mild cases:
- Analgesics - NSAIDs
- Pruritus - antihistamines
- Emollients and saline solutions to gargle may also be used.
- Topical lubricants can be used for eye involvement
- Erythema multiforme major
Treated with prednisolone (40mg). In severe cases, it may need hospitalisation and needs to be treated as a thermal burn.
- Recurrent erythema multiforme
Treated prophylactically with oral aciclovir for 4 months. If there is no recurrence, then we can taper and stop the medication.
🚨 Complications
- Secondary bacterial infection
- Dehydration and poor nutrition - in cases where patients have oral involvement that prevents them from eating and drinking.