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Pemphigus Herpetiformis

  • Author: Neil Sandhu, MD; Chief Editor: William D James, MD  more...
 
Updated: Oct 07, 2014
 

Background

Pemphigus herpetiformis is a clinical variant of pemphigus that combines the clinical features of dermatitis herpetiformis with the immunopathologic features of pemphigus. Previously, pemphigus was described using various terms, including herpetiform pemphigus, acantholytic herpetiform dermatitis, pemphigus controlled by sulfapyridine, and mixed bullous disease. Because pemphigus herpetiformis is a clinical variant of pemphigus, it may be more appropriately described with a term that begins with the general group term (pemphigus), followed by a term for the variant subset (herpetiformis), similar to the terms for other pemphigus variants, such as pemphigus vulgaris, pemphigus foliaceus, pemphigus erythematosus, and pemphigus vegetans.[1]

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Pathophysiology

Pemphigus herpetiformis appears to be mediated by the immunoglobulin G (IgG) class of autoantibodies that target the skin epidermis desmoglein components. Most patients demonstrate autoantibodies to desmoglein 1, a desmosomal component predominantly located in the upper epidermis, while a minority of patients demonstrates autoantibodies to desmoglein 3, which is predominantly located in the lower epidermis, and, most recently, desmocollin.[2, 3] The ability of desmoglein 3 to induce an experimental model of pemphigus after transfer of splenocytes from desmoglein 3-immunized desmoglein 3-knockout mice to Rag-2 immunodeficient mice further supports the role of desmogleins as autoantigens. Histologically demonstrated eosinophil and/or neutrophil infiltration into the epidermis may be relevant pathogenically in the disease process of pemphigus herpetiformis.[4]

In the neutrophil-dominant subset, epidermal cells secrete a neutrophil chemokine interleukin 8 (IL-8), which apparently is induced by IgG autoantibodies to desmoglein and may be responsible for the recruitment of neutrophils to the epidermis, resulting in the subsequent blistering process.

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Epidemiology

Frequency

United States

Pemphigus herpetiformis is a rare clinical variant of pemphigus. Frequency of occurrence remains undetermined.

International

Although frequency of occurrence of pemphigus herpetiformis is not determined, pemphigus herpetiformis has been reported in Europe, Japan, and the United States. In a large study conducted in Eastern Europe, 15 patients (7.3%) with pemphigus herpetiformis were found among 205 patients with pemphigus. In a smaller study conducted in Italy, 5 patients with pemphigus herpetiformis were found among 84 patients with pemphigus. Therefore, pemphigus herpetiformis accounts for approximately 6-7% of pemphigus in European populations.

Mortality/Morbidity

Pemphigus herpetiformis is not associated with significant mortality; however, pemphigus herpetiformis is associated with significant pruritus. Treatment regimens for pemphigus herpetiformis may cause significant adverse effects that must be monitored closely by the patient's physicians. Severe pruritus is noted in approximately one half of patients affected with pemphigus herpetiformis. At least 2 cases of pemphigus herpetiformis have been reported to occur in association with lung cancer. Whether this association was coincidental is not clear.[5, 6] In addition, pemphigus herpetiformis has been associated with prostate cancer development in one case.[7]

Race

Because pemphigus herpetiformis is rare, ethnic distribution is not determined yet. Because pemphigus herpetiformis occurs in the United States, Europe, and Asia, it does not appear to have a specific ethnic predominance.

Sex

Because pemphigus herpetiformis is rare, sex distribution has yet to be defined clearly. Studies in the literature do not appear to support a sex predilection.

Age

The age of onset for pemphigus herpetiformis ranges from 30-80 years, with a mean age of onset of 60 years. Moutran describes an unusual case of onset at age 6 years successfully treated with dapsone.[8]

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Contributor Information and Disclosures
Author

Neil Sandhu, MD Dermatologist (Medical/Cosmetics) and Mohs Surgeon, Gulf Coast Dermatology

Neil Sandhu, MD is a member of the following medical societies: American Academy of Dermatology, American Society for Dermatologic Surgery, American Society for MOHS Surgery

Disclosure: Nothing to disclose.

Specialty Editor Board

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

Jeffrey Meffert, MD Associate Clinical Professor of Dermatology, University of Texas School of Medicine at San Antonio

Jeffrey Meffert, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Association of Military Dermatologists, Texas Dermatological Society

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

Lawrence S Chan, MD Dr Orville J Stone Professor of Dermatology, Head, Department of Dermatology, University of Illinois College of Medicine

Lawrence S Chan, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Dermatological Association, American Medical Association, Association of Professors of Dermatology, Chicago Dermatological Society, Dermatology Foundation, Illinois State Medical Society, Microcirculatory Society, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Smeena Khan, MD Private Practice, Adult and Pediatric Dermatology Associates

Smeena Khan, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology

Disclosure: Nothing to disclose.

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Histopathologic examination of a blister lesion obtained from a patient with pemphigus herpetiformis shows a subcorneal blistering process, acantholysis, and neutrophilic infiltrate.
Direct immunofluorescence microscopy performed on a skin biopsy specimen obtained from a patient with pemphigus herpetiformis detects immunoglobulin G deposits on the epithelial cell surfaces but sparing the basal layers.
 
 
 
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