What Is Erythema Multiforme?

  • Dr. Prerna Yadav BDS, Kothiwal Dental College & Research Centre Moradabad, India


Erythema Multiforme (EM) is an acute immune-system response involving both skin and mucous membranes, mostly due to the Herpes simplex virus (HSV). EM lesions develop on the topmost part of the limbs, often including damage to the oral cavity, genitals, and eyes. These lesions are centralised concentric rings of different colours, which is the characteristic feature of EM.1 

EM mostly heals by itself, but it might reoccur in the future in some cases. EM is prevalent in young people between the ages of 20 to 30 years (of which 20% of them are children) with predominance in people assigned males at birth (PAMAB) as compared to people assigned females at birth (PAFAB).1  EM appears in multiple forms, which is why it is named so: multiform, from multi+formis meaning “multiple forms”. Von Hebra first reported Erythema Multiforme in 1860.


EM is broadly classified into two classes:

  • Erythema Multiforme Minor (EM minor)

Typical targetoid swollen fluid-filled bumps on the topmost part of the limbs without mucosal involvement.2

  • Erythema Multiforme Major (EM major)

Typical targetoid swollen fluid-filled bumps on the topmost part of limbs involving one or many mucosal areas; Epidermal detachment is less than 10% of total body surface area.2

Signs and symptoms

Generally, EM may resolve itself (in 3-5 days) without treatment, but in some cases, recurrent EM might keep reappearing in the future (1-2 weeks & 6 weeks in severe cases). In rare cases, the disease is persistent. Pruritis, burning sensation on the skin, oedema of hands and feet due to mucosal involvement, and inability to feed from mouth leads to longer duration of the disease. The skin lesions do not leave scars but may cause dark patches after the disease subsides. When EM affects the eyes, difficulties like keratitis, scarring, uveitis, or lifelong blindness may occur; rare critical issues like esophagitis with oesophagal restrictions and upper airway damage may further result in pneumonia.3

Preliminary symptoms

Before the emergence of EM (7 days or more), The disorder with mucosal involvement shows symptoms like restlessness, fever, and pain in muscles. When mucosa is not involved, these are uncommon. There are fewer chances these features are due to EM; these conditions may be present due to another disease.3

Skin-related features

The symptoms are different in all individuals. The disorder changes its presentation eventually and might advance.  At the earliest, the lesions appear similar to insect bites- erythematous, spherical, and fluid-filled swellings (edematous papules) with blanching present around them.3  

These papules may grow in size, leading to the typical feature of EM: the circular lesion presents as targetoid concentric rings of variable colours–the innermost ring is a blister with epidermal necrosis; its outer ring with the dark-red inflammatory area; and the outermost peripheral ring is an erythematous area.  The lesion may change into multiple polycyclic forms with time. Separate circular edematous lesions with two areas or with irregular boundaries, or these features together might also occur.3

Areas affected by EM

Mostly symmetrical lesions on the topmost portion of the limbs in comparison to the central part of the body.  Common sites are on the outer aspect of joints, and these lesions will finally propagate from the periphery towards the centre of the lesion. Palmoplantar psoriasis (psoriasis on the palms of the hand and soles of the feet) is common.  Other affected portions: seriously injured areas and sunburns.  The lesions join together around elbows & knees.  Swelling of the nail folds is also common.3

Mucous membrane involvement 

Mucosal lesions are mostly with skin lesions; 25-60% of patients are linked with mucosa.  The oral cavity is involved in 70% of cases–labial mucosa, buccal mucosa, non-attached gingiva, and vermillion lip.  Lesions include erythema and swelling, further leading to peripheral skin being worn out.  Other mucosal areas affected- eye, private parts, upper respiratory, and pharyngeal mucosa. 3


The exact aetiology is not confirmed, but some conditions are presumed to cause EM:2

  • Viral infections (Herpes simplex, Hepatitis, Influenza, etc)
  • Bacterial infections (hemolytic Streptococci, leprosy, mycoplasma pneumonia, Neisseria meningitides, Mycobacterium, Pneumococcus, Salmonella species, Staphylococcus species)
  • Fungal infections (Coccidioides immitis, Histoplasmosis, dermatophytosis etc)
  • Drug interactions: 
    • Antibiotics: sulphonamides, penicillin.
    • Anticonvulsants: phenytoin, barbiturates.
    • Corticosteroids
    • Others: NSAID, aspirin, Anti-tuberculosis drugs, modafinil, allopurinol, etc.
  • Radiotherapy, cold, sunlight.
  • Collagen vascular disorders (Rheumatoid arthritis, lupus, dermatomyositis, polyarteritis nodosa, etc)
  • Miscellaneous (Heavy metals, herbal medicines, topical treatments, poison ivy,  pregnancy, foods, hormonal reasons etc) 


Diagnosis is done based on multiple considerations. Since EM’s symptoms resemble those of other skin diseases, accurate diagnosis is important for appropriate treatment. 

  • Clinical evaluation1
    • Healthcare professionals conduct a thorough physical examination, assessing the appearance, distribution, and morphology of skin lesions and any associated mucosal involvement. The characteristic targetoid lesions are a key diagnostic clue; along with their presence on the extremities supports the diagnosis.
    • A detailed medical history is crucial, such as queries about recent infections, medications currently used, allergies, symptoms of HSV, mycoplasma pneumonia, and other infections.
    • Other details: the onset of symptoms, any triggers, and preliminary symptoms like fever, joint pain, or restlessness should also be asked.
  • Investigations1
    • Skin Biopsy: For differentiating from disorders like Stevens-Johnson syndrome (SJS) and Toxic epidermal necrolysis (TEN)
    • Histopathological tests, ESR, WBC count, and liver function tests for correct diagnosis
    • In cases of respiratory symptoms: serologic testing, chest radiograph, throat swab PCR for M. pneumoniae
    • Indirect immunofluorescence & Direct immunofluorescence: for distinguishing EM with immunoblots disease
    • Tzanck smear, PCR studies, viral culture–for doubtful skin and mucosal lesions.
    • Serum complement levels checked in in persistent EM

Management/ Treatment

The treatment of EM depends on the symptoms, triggers, and severity of the condition. EM may resolve itself, but symptomatic treatment is given if required.2

  • If a medication is the cause of EM, the medicine should be stopped.
  • Acute EM: Topical steroids, antihistamines.
  • In HSV-associated EM, anti-viral drugs are given as per the severity
  • Painful mucosal EM- topical corticosteroids, oral antiseptics, analgesics, or anaesthetic ointments are administered.
  • In long-term and serious cases where oral intake is compromised, hospitalization may be essential for providing intravenous fluids and repletion of electrolytes to compensate for dehydration; Conditions managed like burn patient if needed; Further glucocorticoids(e.g. prednisone)  with a reduction in dosage over 2-4 weeks for relief over time.
  • Mucosal disorder of the eyes: an opthalmologist is consulted and given adequate treatment
  • Recurrent EM–Cases where anti-viral drugs do not work well: Immunosuppressives, antimalarials, corticosteroids, analgesics, dapsone therapy, and other systemic treatments according to the requirement
  • If lungs are affected, respiratory therapists should also be consulted
  • In case of joint pain or related difficulties, a physical therapist is consulted
  • Required treatment and follow-ups with dermatologists, ophthalmologists, burn surgeons, respiratory therapists, physical therapists, nurses, and supportive care is essential

Risk factors

Conditions like Herpes Simplex infection, Mycoplasma pneumonia infection, some medicines, syphilis, Epstein-Barr virus, Hepatitis B vaccination, HIV infection, Lymphoma, tattoos, etc.3


  • Scars after the mucosal lesions are cured.
  • Commonly, obstruction of the urethra, vagina, oesophagus, and anus; further causes Urinary retention, phimosis, and vaginal retention of menstrual blood at puberty.
  • Uveitis, conjunctivitis, scarring, panopthalmitis, dry eyes, or permanent blindness.2


How can I prevent erythema multiforme?

We cannot avoid EM, but some measures can reduce its chances.

  • Limit antibiotics and NSAIDs in case of allergies.
  • Proper hygiene maintenance by washing hands with soap and water to stay away from fungal and bacterial infections
  • Use protection during sexual intercourse

How common is erythema multiforme?

It is common in young adults between the ages of 20 and 30 years, and 20% of children are affected. Males mostly suffer from EM, with a male-to-female ratio of 1:5. 

Is erythema multiforme contagious? 

No, EM is not contagious itself. However, infections that trigger it, such as Herpes simplex virus, bacterial infections, etc.

What can I expect if I have erythema multiforme? 

Troubling symptoms of EM may vary from one individual to another based on the severity of the lesion. Restlessness, pruritus of the skin, painful ulcers on the mucosa.

When should I see a doctor?

If you suspect you have EM or experience skin changes, especially targetoid lesions or mucosal ulcers. Proper medical attention is crucial for appropriate management.


Erythema Multiforme is a severe cell-mediated immune response resulting in skin and mucosal disorders. The clear aetiology being unknown, multiple factors are suspected to cause EM, such as HSV infection, certain medications, collagen vascular diseases, and others. The typical feature of EM is the targetoid lesion of concentric rings of multiple colours. Both clinical evaluation and histopathologic features aid in the accurate diagnosis of EM and differentiate it from other disorders with similar symptoms: Urticaria, Steven Johnson syndrome, fixed drug eruption, toxic epidermal necrolysis, bullous pemphigoid, etc. The symptoms vary in all individuals. Following an accurate diagnosis, required and symptomatic treatment should be done accordingly. Although EM may resolve itself, recurrent and persistent EM are quite severe. Serious patients are hospitalized for intravenous fluids and electrolyte repletion.


  1. Sokumbi O, Wetter DA. Clinical features, diagnosis, and treatment of erythema multiforme: a review for the practising dermatologist. Int J Dermatology [Internet]. 2012 Aug [cited 2024 Feb 29];51(8):889–902. Available from: https://onlinelibrary.wiley.com/doi/10.1111/j.1365-4632.2011.05348.x
  2. Hafsi W, Badri T. Erythema multiforme. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 [cited 2024 Feb 29]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK470259/
  3. Trayes KP, Love G, Studdiford JS. Erythema multiforme: recognition and management. afp [Internet]. 2019 Jul 15 [cited 2024 Feb 29];100(2):82–8. Available from: https://www.aafp.org/pubs/afp/issues/2019/0715/p82.html
This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Dr Prerna Yadav

Bachelor of Dental Surgery- BDS, Kothiwal Dental College & Research Centre Moradabad, India

Dr. Prerna Yadav is an accomplished Dental Surgeon with 8 years of clinical expertise. With a passion for knowledge and research, she pursued an Advanced PG Diploma in Pharmacovigilance & Clinical Research. A Certified Medical Writer as well, Prerna possesses a unique blend of dental proficiency and medical communication finesse. Her journey is a testament to dedication and an unwavering commitment to both patient care and advancing medical knowledge.

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