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Erythema Multiforme Treatment & Management

  • Author: Jose A Plaza, MD; Chief Editor: William D James, MD  more...
Updated: May 24, 2016

Approach Considerations

For all forms of erythema multiforme (EM), the most important treatment is usually symptomatic, including oral antihistamines, analgesics, local skin care, and soothing mouthwashes (eg, oral rinsing with warm saline or a solution of diphenhydramine, xylocaine, and kaopectate). Topical steroids may be considered. For more severe cases, meticulous wound care and use of Burrow or Domeboro solution dressings may be necessary.

The cause of the erythema multiforme should be identified, if possible. If a drug is suspected, it must be withdrawn as soon as possible. This includes all medications begun during the preceding 2 months. Discontinue all unnecessary medications. Studies have shown that prompt withdrawal of causative drugs will reduce the risk of death by about 30% per day.

Infections should be appropriately treated after cultures and/or serologic tests have been performed. The use of liquid antiseptics, such as 0.05% chlorhexidine, during bathing helps prevent superinfection. Topical treatment, including that for genital involvement, may be performed with a gauze dressing or a hydrocolloid.

Local supportive care for eye involvement is important and includes topical lubricants for dry eyes, sweeping of conjunctival fornices, and removal of fresh adhesions.

Suppression of herpes simplex virus (HSV) can prevent HSV-associated erythema multiforme, but antiviral treatment started after the eruption of erythema multiforme has no effect on the course of the erythema multiforme.


Prehospital and Emergency Department Care

In severe cases, prehospital personnel may need to treat respiratory complications and fluid imbalances aggressively, in the same manner as thermal burns.

Mild cases of erythema multiforme (EM) require only symptomatic treatment in the emergency department (ED), which may include analgesics or nonsteroidal inflammatory drugs (NSAIDs); cold compresses with saline or Burrow solution; topical steroids; and soothing oral treatments such as saline gargles, viscous lidocaine, and diphenhydramine elixir.

Aggressive monitoring and replacement of fluids and electrolytes are of paramount importance.

Provide supportive respiratory care, including suctioning and postural drainage, as needed. Use analgesics as needed to control pain, which may be severe.

Administer empiric antibiotics if clinical evidence of secondary infection exists. Most authorities advise against routine use of prophylactic antibiotics.

Avoid systemic corticosteroids in minor cases. In severe cases, their use is controversial, because these agents do not improve prognosis and may increase risk of complications.



Erythema multiforme (EM) major may require hospitalization for the treatment of complications and sequelae (eg, severe mucous membrane involvement is present or with impaired oral intake, dehydration, or secondary infection) and to manage the patient's fluid and electrolytes. The most severe cases should be managed in intensive care or burn units.

If the initial treating facility does not have facilities or experienced individuals to care for critically ill burn patients, the patient should be transferred to a regional tertiary care medical center by the most rapid means available.

Care in a surgical specialty burn unit may provide the greatest likelihood of survival. Areas of denuded skin should be managed like thermal burns, although debridement is best avoided while lesions are still progressing. Eroded areas may be bathed q1-2d with saline or Burrow's solution and dressed with nonadherent dressings.

Treat patients for herpes simplex virus (HSV) or M pneumoniae -related erythema multiforme. Intravenous (IV) antibiotics may be necessary to treat secondary infections. Implement barrier isolation to decrease risk of infection.

Immediately withdraw all potentially causative drugs. The healing process usually takes about 2 weeks, during which time proper skin care is essential. Practice aseptic handling and avoid adhesive materials. Use topical agents such as 0.5% silver nitrate solution or 0.05% chlorhexidine solution to cleanse the skin. Warm these solutions before application. Avoid silver sulfadiazine because of its causative association.

Once the patient has stabilized in the intensive care burn unit, the peak of disease progression has passed, and reepithelialization has begun, it may be appropriate to transfer the patient to a regular surgical ward. Reepithelialization usually takes 10-14 days, which is also the approximate length of hospitalization for patients without acute complications.

After the acute period of illness has passed and the patient has survived, mucous membrane sequelae may require surgical intervention.

Fluid resuscitation and nutritional support

Several issues make nutritional support critical. A liquid diet and IV fluid therapy may be necessary.

Fluid and electrolytes may be lost through the disrupted skin barrier, and widespread, painful oral erosions may make feeding difficult. In such cases, pass a soft, flexible feeding tube into the stomach or small bowel, and institute appropriate feedings. Oral antacids may be helpful for discrete oral ulcers.

Profuse diarrhea may result from gastrointestinal involvement, making oral or enteral feeding difficult. Parenteral nutrition may be appropriate.

Increased energy expenditure, such as from increased core body temperature, must be recognized and treated appropriately. Nitrogen balance and other nutritional parameters are useful to estimate nutritional needs and to evaluate the efficacy of nutritional therapy.

Fluid and electrolyte resuscitation are approximately 66-75% of that required for a similarly sized burn wound. Administer warmed fluids through a peripheral intravenous angiocatheter at a site removed from the skin eruptions.

Avoid central venous access if at all possible in order to decrease the risk of line infection. Change all catheters, peripheral or central, at regular intervals.

Monitor the adequacy of fluid resuscitation with the use of a urinary bladder catheter. Minimum urine output for adults is 0.5 mL/kg/h; for children, it is 1 mL/kg/h.

Pulmonary support

Patients with tracheobronchial involvement may present with hyperventilation and mild hypoxemia. Careful monitoring and aggressive pulmonary support may lead to early detection and treatment of diffuse interstitial pneumonitis and thus prevent the development of acute respiratory distress syndrome (ARDS).

Other supportive care

Maintain thermoregulation by keeping the environmental temperature at 30-32°C, administering only warmed fluids, and using heating lamps or warming blankets.

The use of a pressure support surface, an air or gel mattress, or a specialty bed is recommended to prevent pressure sores. Use antacids, proton pump inhibitors, or histamine 2 blockers to prevent stress ulceration.

Administer subcutaneous heparin to prevent the development of deep venous thrombosis (DVT).



Most patients with erythema multiforme (EM) have an uncomplicated course, with the exception of hosts who are immunocompromised and those with secondary bacterial infections of the skin or the mucosa. Healing of the mucosal areas is usually complete.

Scars and strictures of the esophageal, urethral, vaginal, and anal mucosa rarely occur. However, severe oral involvement may be accompanied by difficulty in consuming food and fluid and can result in dehydration, and vaginal and urethral erosions may cause urinary retention and phimosis. Hematocolpos is the result of genital lesions in teenage females. Severe scarring of the genitourinary tract may cause vaginal and urethral stenosis.

Severe eye complications (20%), such as purulent conjunctivitis, anterior uveitis, panophthalmitis, scarring of the conjunctivae, symblepharon, may result in permanent blindness. Other ocular sequelae may include the following:

  • Epiphora secondary to obstruction of the lacrimal ducts
  • Sjögren-like sicca syndrome of dry eyes, punctate keratitis, corneal pannus, and mucin deficiency in tears
  • In-turned eyelashes, corneal scarring, corneal and conjunctival neovascularization, epithelial proliferation with squamous metaplasia, photophobia, burning eyes, visual impairment

Other complications include the following:

  • Patchwork appearance of the skin, with hypopigmented regions and potential hypertrophic scarring
  • Pneumonia / acute respiratory distress syndrome (ARDS)
  • Dehydration and electrolyte disturbances
  • Possible gastrointestinal (GI) hemorrhage, nephritis, and renal failure


Consultation with the following specialists may be necessary:

  • Dermatologist: For diagnosis and management and for performance of skin biopsies, if indicated
  • Internal medicine specialist or a pediatric specialist: For evaluation of the underlying causes of disorders and systemic sequelae
  • Ophthalmologist: For early consultation in the evaluation and management of ocular involvement; daily examinations for signs of ocular involvement; if necessary, disruption of synechiae can be accomplished by administration of wetting or antibiotic eyedrops
  • Burn or trauma surgeon: For familiarity with caring for critically ill patients with burn wounds who have open wounds
  • Infectious disease specialists: For evaluation of intercurrent infections and treatment recommendations
  • Respiratory therapist: For tracheobronchial involvement
  • Physical or occupational therapists
  • Psychologists, psychiatrists, or social workers may be helpful.

Monitoring and Prevention

The medical professional(s) who treated the patient during hospitalization should see the patient regularly and provide symptomatic relief, as needed. Such practitioners may include burn or trauma surgeons, ophthalmologists, nephrologists, infectious disease specialists, and gastroenterologists.

The affected skin should be protected from any pressure or shear forces. Otherwise, early institution of physical and occupational therapies is appropriate. To reduce the likelihood of developing hyperpigmentation, recommend the use of sunscreens for 1 year after the incident has resolved.

Topical corticosteroids are useful for outpatient treatment of patients with limited disease.

Prophylaxis for recurrence of herpes-associated erythema multiforme (HAEM) should be considered in patients with more than 5 attacks per year; oral acyclovir may be helpful in reducing recurrence (see Medications). Prophylaxis may be required for 6-12 months or longer. If the patient's condition is unresponsive, continuous therapy with valacyclovir has been reported to be effective.[31]

Tamoxifen may prevent premenstrual erythema multiforme.

Prophylactic antibiotics are not recommended because of the increased likelihood of selecting out resistant strains. However, evidence of infection should lead to prompt culturing and the selection of appropriate antimicrobial therapy based on culture and sensitivity results. Some authors recommend routine alternate-day skin biopsy for culture to distinguish simple skin colonization from true infectious invasion and to guide antimicrobial therapy.

Once erythema multiforme (EM) due to a drug has been diagnosed, the patient should never be rechallenged with the same drug or any other drug of the same class or similar chemical structure. Chemically related compounds often share a common metabolic pathway that may be abnormal in the affected individual. Sulfonamide-containing ointments should also be avoided.

First-degree relatives of an affected patient have an increased risk of reactions to similar drugs.

Contributor Information and Disclosures

Jose A Plaza, MD Director of Dermatopathology, Department of Pathology, Froedtert Hospital; Assistant Professor, Department of Pathology, Section of Dermatopathology, Medical College of Wisconsin

Jose A Plaza, MD is a member of the following medical societies: American Medical Association, American Society for Clinical Pathology

Disclosure: Nothing to disclose.


Victor G Prieto, MD, PhD Director of Dermatopathology, Professor, Departments of Pathology and Dermatology, University of Texas MD Anderson Cancer Center

Victor G Prieto, MD, PhD is a member of the following medical societies: American Society of Dermatopathology, College of American Pathologists, American Association for the Advancement of Science, International Society of Dermatopathology, European Society of Pathology, American Medical Association, American Society for Clinical Pathology, Society for Investigative Dermatology, United States and Canadian Academy of Pathology

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.


Burke A Cunha, MD Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Steven C Dronen, MD, FAAEM Chair, Department of Emergency Medicine, LeConte Medical Center

Steven C Dronen, MD, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

James Foster, MD, MS Consulting Staff, Department of Emergency Medicine, Palomar Pomerado Health

James Foster, MD, MS is a member of the following medical societies: Alpha Omega Alpha, American College of Emergency Physicians, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Warren R Heymann, MD Head, Division of Dermatology, Professor, Department of Internal Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Warren R Heymann, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Jeffrey Lee Kishiyama, MD Assistant Clinical Professor of Medicine, University of California, San Francisco, School of Medicine; Consulting Staff, Allergy and Asthma Associates of Santa Clara Valley Research Center

Disclosure: Nothing to disclose.

Olufunmilayo Ogundele, MD Clinical Assistant Instructor, Staff Physician, Departments of Emergency and Internal Medicine, State University of New York Downstate, Kings County Hospital Center

Olufunmilayo Ogundele, MD is a member of the following medical societies: American Medical Association and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Chulabhorn Pruksachatkunakorn, MD Chief, Division of Dermatology, Professor, Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Thailand

Chulabhorn Pruksachatkunakorn is a member of the following medical societies: American Academy of Dermatology, International Society of Pediatric Dermatology, and Society for Pediatric Dermatology

Disclosure: Nothing to disclose.

Don R Revis Jr, MD Consulting Staff, Department of Surgery, Division of Plastic and Reconstructive Surgery, University of Florida College of Medicine

Don R Revis Jr, MD is a member of the following medical societies: American College of Surgeons, American Medical Association, American Society for Aesthetic Plastic Surgery, and American Society of Plastic Surgeons

Disclosure: Nothing to disclose.

Mark A Silverberg, MD, MMB, FACEP Assistant Professor, Associate Residency Director, Department of Emergency Medicine, State University of New York Downstate College of Medicine; Consulting Staff, Department of Emergency Medicine, Staten Island University Hospital, Kings County Hospital, University Hospital, State University of New York Downstate Medical Center

Mark A Silverberg, MD, MMB, FACEP is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, Council of Emergency Medicine Residency Directors, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Debra Slapper, MD Consulting Staff, Department of Emergency Medicine, St Anthony's Hospital

Debra Slapper, MD is a member of the following medical societies: American Academy of Emergency Medicine

Disclosure: Nothing to disclose.

Michael J Wells, MD Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association

Disclosure: Nothing to disclose.

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Target lesion of erythema multiforme.
Raised atypical targets and arcuate lesions.
Hemorrhagic crusts on the lips.
Interface dermatitis with prominent dyskeratotic cells in epidermis.
Note extensive sloughing of epidermis. Courtesy of David F. Butler, MD.
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