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Erythema Multiforme Workup

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

Approach Considerations

No specific laboratory tests are indicated to make the diagnosis of erythema multiforme (EM), which should be arrived at clinically. The clinical picture can guide laboratory testing in severe cases.

Cultures are indicated in severe cases and should be obtained from blood, sputum, and mucosal lesions.

No specific imaging studies are necessary in most cases, although chest radiography may be useful in cases with respiratory symptoms or signs, particularly if an underlying pulmonary infection is suspected.

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CBC Count

The complete blood cell (CBC) count with differential usually reveals moderate leukocytosis with atypical lymphocytes and lymphopenia, possibly secondary to the depletion of CD4 lymphocytes (90% of patients). An eosinophil count greater than 1000/mm3 may also be seen. Neutropenia (30% of patients) may occur and indicates a poor prognosis. A severely elevated total white blood cell (WBC) counts indicate infection. Mild anemia may be present, and thrombocytopenia is found in 15% of patients.

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Chemistries and Other Laboratory Tests

Electrolytes values may be abnormal with severe skin and mucous membrane involvement due to fluid losses. These values are useful to guide volume and electrolyte replacement therapy.

Blood urea nitrogen (BUN) and creatinine tests are indicated to screen for renal involvement and dehydration in severe cases requiring hospitalization. Prerenal azotemia and elevated serum urea nitrogen levels may be found and indicate a poor prognosis.

Also in severe cases, the erythrocyte sedimentation (ESR) rate may be elevated, but this is a nonspecific finding. Mildly elevated liver transaminase levels may be found with hepatic involvement.

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Immunofluorescence and PCR

Specific herpes simplex virus (HSV) antigens have been detected within keratinocytes by immunofluorescence study. The HSV DNA has been identified primarily within the keratinocytes by polymerase chain reaction (PCR) amplification.

Direct immunofluorescence staining and examination may also identify an alternative diagnosis (eg, pemphigoid, immunoglobulin A [IgA] linear dermatosis.

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Biopsy and Histologic Features

Histopathologic examination of a cutaneous punch biopsy may be used to confirm the diagnosis of erythema multiforme (EM) and to rule out the differential diagnosis (see Differentials).A skin biopsy of the cutaneous lesions may also exclude the presence of other blistering disorders, such as in equivocal cases, particularly in absence of target lesions.

Erythema multiforme

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 (see the following image). This vacuolar change represents individual or small groups of necrotic (apoptotic) keratinocytes. In addition, a characteristic sparse-to-moderate lymphocytic infiltrate is present around the superficial vascular plexuses.

Interface dermatitis with prominent dyskeratotic c Interface dermatitis with prominent dyskeratotic cells in epidermis.

As the 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 characterized by high-density lichenoid infiltrate rich in T cells, composed of lymphocytes (CD4+ more abundant than CD8+ in the papillary dermis; in the epidermis, there is a predominance of CD8 T cells and macrophages) and macrophages, with a few neutrophils and occasional eosinophils (particularly in those cases associated with medications).

Erythema multiforme vs SJS/TEN and SSS

Histology and immunochemistry studies have shown that inflammatory infiltrates of erythema multiforme and Steven-Johnson syndrome / toxic epidermal necrolysis (SJS/TEN) are strikingly different in density and nature. Erythema multiforme has a high density of cell infiltrate rich in T-lymphocytes. By contrast, SJS/TEN is characterized by a cell-poor infiltrate of macrophages and dendrocytes with strong tumor necrosis factor (TNF)–alpha immunoreactivity. Immune complex deposition is variable and nonspecific. In severe cases, fibrinoid necrosis can occur in the stomach, spleen, trachea, and bronchi.

Histologic examination of skin biopsies in staphylococcal scalded skin syndrome (SSSS) reveals cleavage of cell layers within the epidermis.

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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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