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Erythema Multiforme Clinical Presentation

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

History

In addition to characterizing skin and mucous membrane lesions of erythema multiforme (EM), a complete history should document recent constitutional symptoms, previous history of or current herpes simplex (HSV) or Mycoplasma pneumoniae infection, and all use of prescription and over-the-counter (OTC) medications, with particular attention to those started in the previous 2 months. Patients may have a history of anxiety.

Symptoms

Prodromal symptoms are usually absent or mild in persons with erythema multiforme minor, consisting of a mild, nonspecific upper respiratory tract infection. The abrupt onset of a rash usually occurs within 3 days, starting on the extremities symmetrically, with centripetal spreading. Pruritus is generally absent

In erythema multiforme major, 50% of patients have prodromes similar to an influenzalike prodrome, including moderate fever, general discomfort, cough, sore throat, vomiting, chest pain, and diarrhea (secondary to gastrointestinal [GI] tract ulceration). These symptoms have a classic time course of development and are usually present for 1-14 days before the cutaneous eruption occurs. The lesions begin on the acral areas and spread similarly to the distribution of erythema multiforme minor (ie, usually symmetrical and extend from the face and torso to the trunk and proximal extremities).

Prominent mucosal involvement may also occur in erythema multiforme major. Erosions of the oral mucosa may result in difficulty in eating, drinking, or opening the mouth. Conjunctival involvement may cause lacrimation, photophobia, burning eyes, or visual impairment. Genital lesions are painful and may result in urinary retention; painful micturition due to genitourinary tract ulceration may also occur. Shortness of breath or difficulty in breathing may occur due to tracheobronchial epithelial involvement.

A localized form of erythema multiforme has been reported at the site of marrow aspiration. Half the children with erythema multiforme have a history of herpes labialis or genitalis. Although the onset usually precedes erythema multiforme by 3-14 days, it may still be present at the onset of erythema multiforme.

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Physical Examination

The hallmark of erythema multiforme (EM) is a target lesion with variable mucous membrane involvement.

Skin lesions

The initial lesion is a dull-red, purpuric macule or urticarial plaque that expands slightly to a maximum of 2 cm over 24-48 hours. In the center, a small papule, vesicle, or bulla develops, flattens, and then may clear. An intermediate ring develops and becomes raised, pale, and edematous. The periphery gradually changes to become cyanotic or violaceous and forms a typical concentric, “target” lesion. Some lesions consist of only 2 concentric rings (see the first image below). Polycyclic or arcuate lesions may occur (see second image below). Some lesions appear at areas of previous trauma (Koebner phenomenon). Postinflammatory hyperpigmentation or hypopigmentation may occur. The Nikolsky sign is negative (ie, top layers of the skin do not slip away from the lower layers when slightly rubbed).

Target lesion of erythema multiforme. Target lesion of erythema multiforme.
Raised atypical targets and arcuate lesions. Raised atypical targets and arcuate lesions.

Skin distribution

The lesions are symmetrical, predominantly on the acral extensor surfaces of the extremities, and they spread centripetally to involve the abdomen and back. Lesions may also coalesce and become generalized. The palms, neck, and face are frequently involved. Lesions of the soles and flexural aspects of the extremities are less common. A zosteriform distribution may be present. By definition, the lesions cover less than 10% of total body surface area.

The following is an image of a patient with severe skin involvement.

Note extensive sloughing of epidermis. Courtesy of Note extensive sloughing of epidermis. Courtesy of David F. Butler, MD.

Mucosal lesions

Mucosal involvement is present in as many as 70% of patients with erythema multiforme. The degree is usually mild, limited to one mucosal surface. The most common sites of mucous membrane involvement in order of frequency are the oropharynx (lips, palate, and gingiva most often affected), conjunctivae, genitalia, anus, tracheobronchial tree, esophagus, and bowel. Eye involvement (10%) is usually mild and may manifest as red conjunctivae, chemosis, and lacrimation. The genital areas may have painful, hemorrhagic bullae and erosions.

More severe erosions of at least 2 mucosal surfaces are seen in erythema multiforme major and are characterized by hemorrhagic crusting of the lips (see the image below)(25%) and ulceration of the nonkeratinized mucosa. Occasionally, painful mucosal involvement may be extensive, with few or no skin lesions.

Hemorrhagic crusts on the lips. Hemorrhagic crusts on the lips.

Mucosal lesions usually heal without sequelae. The mucosal involvement in Stevens-Johnson syndrome is more severe and more extensive than that of erythema multiforme major. Generalized lymphadenopathy often accompanies erythema multiforme major.

Other findings

Mild temperature elevation is usually noted. Hyperventilation and mild hypoxia may result from anxiety or tracheobronchial involvement.

Dehydration may range from mild to massive as a result of the following factors:

  • Evaporation through open skin lesions
  • Poor oral intake secondary to oropharyngeal mucous membrane involvement
  • Profuse diarrhea from involvement of bowel mucosa
  • Increased insensible losses secondary to elevated core body temperature
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Contributor Information and Disclosures
Author

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.

Coauthor(s)

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.

Acknowledgements

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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