eMedicine Specialties > Dermatology > Bullous Diseases

Dermatitis Herpetiformis: Differential Diagnoses & Workup

Author: Jami L Miller, MD, Assistant Professor, Division of Dermatology, Department of Internal Medicine, Vanderbilt University Medical School; Director of Phototherapy Unit, Vanderbilt University Medical Center; Consulting Attending Physician, Nashville Veterans Affairs Medical Center
Contributor Information and Disclosures

Updated: Aug 14, 2009

Differential Diagnoses

Bullous Pemphigoid
Erythema Multiforme
Linear IgA Dermatosis
Neurotic Excoriations
Scabies
Transient Acantholytic Dermatosis

Other Problems to Be Considered

Eczema25
Papular urticaria

Workup

Laboratory Studies

  • The diagnosis of dermatitis herpetiformis (DH) is made on the basis of skin biopsy results. However, other tests should be performed depending on the presence of symptoms of associated syndromes. Serum markers, such as IgA endomysial antibodies, are negative in as many as 10-37% of patients with dermatitis herpetiformis.26 Arguments have been made in favor of testing for tissue transglutaminase for diagnosis,27 but tissue transglutaminase enzyme-linked immunosorbent assay positivity can occur in many autoimmune diseases because of impurities and cross-reactivity.28

Procedures

  • The diagnosis is made after observing characteristic findings from skin biopsy specimens. The biopsy sample should be taken from the edge of a lesion for hematoxylin and eosin staining and from normal-appearing perilesional skin for direct immunofluorescence staining.
  • Results of direct immunofluorescence of lesional skin are often falsely negative. The vigorous immune response degrades the IgA antibody at the site. Therefore, biopsy specimens for the direct immunofluorescence studies should be taken from healthy-appearing skin.


Immunofluorescence showing immunoglobulin A at th...

Immunofluorescence showing immunoglobulin A at the dermoepidermal junction (direct immunofluorescence stain).

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Immunofluorescence showing immunoglobulin A at th...

Immunofluorescence showing immunoglobulin A at the dermoepidermal junction (direct immunofluorescence stain).

Histologic Findings

Biopsy specimens of lesional skin reveal neutrophils in the dermal papillae, with fibrin deposition, neutrophil fragments, and edema. Eosinophils may be present. Papillary microabscesses form and progress to subepidermal vacuolization and vesicle formation. Vesicles form in the lamina lucida, the weakest portion of the dermoepidermal junction, due to neutrophil lysosomal enzymes.29 See Media File 2.

Papillary microabscesses form and progress to sub...

Papillary microabscesses form and progress to subepidermal vacuolization and vesicle formation in the lamina lucida, the weakest portion of the dermoepidermal junction (hematoxylin and eosin stain).

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Papillary microabscesses form and progress to sub...

Papillary microabscesses form and progress to subepidermal vacuolization and vesicle formation in the lamina lucida, the weakest portion of the dermoepidermal junction (hematoxylin and eosin stain).



The histologic differential diagnosis of early skin lesions includes bullous lupus erythematosus, bullous pemphigoid, epidermolysis bullosa acquisita, and linear IgA disease.30 The histologic differential diagnosis of late skin lesions includes bullous drug eruption, bullous pemphigoid, erythema multiforme, and herpes gestationis.

Granular IgA deposits in dermal papillae of perilesional skin observed by direct immunofluorescence is the criterion standard of diagnosis. However, the presence of both granular and linear IgA deposits has been reported on direct immunofluorescence testing in a patient with dermatitis herpetiformis.31

Inflammation in lesional skin degrades the immunoreactants and is usually negative for the diagnostic granular pattern. Because deposits are found more reliably in the surrounding normal-appearing skin, the standard practice is to obtain biopsy specimens from normal-appearing perilesional skin for direct immunofluorescent staining.

More on Dermatitis Herpetiformis

Overview: Dermatitis Herpetiformis
Differential Diagnoses & Workup: Dermatitis Herpetiformis
Treatment & Medication: Dermatitis Herpetiformis
Follow-up: Dermatitis Herpetiformis
Multimedia: Dermatitis Herpetiformis
References
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Further Reading

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Keywords

dermatitis herpetiformis, Duhring's disease, Duhring disease, autoimmune blistering disorders, autoimmune blistering diseases, gluten sensitive enteropathy, gluten-sensitive enteropathy, GSE, herpetiform eruption.

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Contributor Information and Disclosures

Author

Jami L Miller, MD, Assistant Professor, Division of Dermatology, Department of Internal Medicine, Vanderbilt University Medical School; Director of Phototherapy Unit, Vanderbilt University Medical Center; Consulting Attending Physician, Nashville Veterans Affairs Medical Center
Jami L Miller, MD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, and American Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Russell Hall, MD, Chief, Professor, Department of Internal Medicine, Division of Dermatology, Duke University
Russell Hall, MD is a member of the following medical societies: American Academy of Dermatology, American Dermatological Association, American Federation for Medical Research, American Society for Clinical Investigation, and Society for Investigative Dermatology
Disclosure: Genetech Grant/research funds Principle Investigator; Centecor  Grant/research funds Principle Investigator

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

Julia R Nunley, MD, Professor, Program Director, Dermatology Residency, Department of Dermatology, Virginia Commonwealth University Medical Center
Julia R Nunley, MD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, American Society of Nephrology, International Society of Nephrology, Medical Dermatology Society, Medical Society of Virginia, National Kidney Foundation, Phi Beta Kappa, and Women's Dermatologic Society
Disclosure: Johnson and Johnson stock holder dividends; Amgen stock holder dividends; Forest Lab, Inc stock holder dividends; Galaxo Smith Klein stock holder dividends; Covidien stock holder dividends; Novartis Grant/research funds Consulting; Biolex  sub-investigator

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 Investigator; Genentech Grant/research funds investigator; Centocor Consulting fee Consulting; Abbott Grant/research funds investigator; Abbott Consulting fee Consulting; Novartis  investigator; Pfizer Grant/research funds investigator; Celgene Consulting fee DMC Chair; NIAMS and NHLBI Grant/research funds investigator

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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