eMedicine Specialties > Dermatology > Reactive & Inflammatory Dermatoses

Erythema Multiforme: Differential Diagnoses & Workup

Author: Jose Antonio Plaza, MD, Director of Dermatopathology, Department of Pathology, Froedtert Hospital; Assistant Professor, Department of Pathology, Section of Dermatopathology, Medical College of Wisconsin
Coauthor(s): Victor G Prieto, MD, PhD, Director of Dermatopathology, Professor, Departments of Pathology and Dermatology, University of Texas MD Anderson Cancer Center
Contributor Information and Disclosures

Updated: May 29, 2009

Differential Diagnoses

Acute Febrile Neutrophilic Dermatosis
Pemphigus, Paraneoplastic
Acute Hemorrhagic Edema of Infancy
Staphylococcal Scalded Skin Syndrome
Behcet Disease
Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
Bullous Pemphigoid
Urticarial Vasculitis
Contact Dermatitis, Allergic
Contact Dermatitis, Irritant
Drug Eruptions

Other Problems to Be Considered

Disseminated lesions of contact dermatitis
Figurate erythema
Fixed drug eruption 
Herpes gestationis
Lupus erythematosus27
Urticaria
Primary herpetic gingivostomatitis
Major oral aphthae

Workup

Laboratory Studies

Complete blood cell count; electrolyte levels; BUN determination; erythrocyte sedimentation rate (ESR); liver function tests; and cultures from blood, sputum, and erosive areas are indicated in severe cases of erythema multiforme (EM) major. In severe cases, elevated ESR, moderate leukocytosis, and mildly elevated liver transaminase levels may be found.

Specific HSV antigens have been detected within keratinocytes by immunofluorescence study. The HSV DNA has been identified primarily within the keratinocytes by polymerase chain reaction amplification.

Procedures

Histopathologic examination of a cutaneous punch biopsy may be used to confirm the diagnosis and to rule out the differential diagnoses.

Histologic Findings

Histologically, erythema multiforme is the prototypical vacuolar interface dermatitis showing a lymphocytic infiltrate along the dermoepidermal junction associated with hydropic changes and dyskeratosis of basal keratinocytes. In addition, a characteristic sparse-to-moderate lymphocytic infiltrate is present around the superficial vascular plexuses. As lesions progress, partial-to-full-thickness epidermal necrosis, intraepidermal vesiculation, or subepidermal blisters may appear, owing to spongiosis and to the cellular damage of the basal layer of the epidermis. Occasionally, severe papillary edema is present. The dermal inflammatory infiltrate is composed of macrophages and lymphocytes (CD4+ more abundant than CD8+), with a few neutrophils and occasional eosinophils (particularly in those cases associated with medications) (see Medial File 4).


Interface dermatitis with prominent dyskeratotic ...

Interface dermatitis with prominent dyskeratotic cells in epidermis.

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Interface dermatitis with prominent dyskeratotic ...

Interface dermatitis with prominent dyskeratotic cells in epidermis.

More on Erythema Multiforme

Overview: Erythema Multiforme
Differential Diagnoses & Workup: Erythema Multiforme
Treatment & Medication: Erythema Multiforme
Follow-up: Erythema Multiforme
Multimedia: Erythema Multiforme
References
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References

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Further Reading

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Keywords

erythema multiforme, EM, Stevens-Johnson syndrome, SJS, erythema multiforme major, EM major, erythema multiforme minor, EM minor, herpes-induced EM major, HAEM, herpes-associated erythema multiforme, herpes-associated EM, drug-induced SJS, drug-induced Stevens-Johnson syndrome

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Contributor Information and Disclosures

Author

Jose Antonio Plaza, MD, Director of Dermatopathology, Department of Pathology, Froedtert Hospital; Assistant Professor, Department of Pathology, Section of Dermatopathology, Medical College of Wisconsin
Jose Antonio Plaza, MD is a member of the following medical societies: American Medical Association and 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 Association for the Advancement of Science, American Medical Association, American Society for Clinical Pathology, American Society of Dermatopathology, College of American Pathologists, European Society of Pathology, International Society of Dermatopathology, Society for Investigative Dermatology, and United States and Canadian Academy of Pathology
Disclosure: Nothing to disclose.

Medical Editor

Evan R Farmer, MD, Professor of Dermatology, Johns Hopkins University School of Medicine, Clinical Professor of Pathology, Virginia Commonwealth University School of Medicine; Consulting Staff, Department of Dermatology, Johns Hopkins Hospital, VCU Health Services
Evan R Farmer, MD is a member of the following medical societies: American Academy of Dermatology, American Dermatological Association, American Medical Association, American Society of Dermatopathology, and International Society of Dermatology
Disclosure: Nothing to disclose.

Pharmacy Editor

Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center
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.

Managing Editor

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

CME Editor

Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania
Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology
Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds None; Genentech Consulting fee Consulting; Centocor Consulting fee Consulting; Centocor Grant/research funds None; Covance Consulting fee Consulting; Shire  Consulting

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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