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Pemphigus Foliaceus: Differential Diagnoses & Workup

Author: Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Coauthor(s): Slawomir Majewski, MD, Professor and Director, Department of Dermatology and Venereology, Warsaw School of Medicine, Poland; Sebastian S Majewski, MD, Consulting Staff, Department of Dermatology, Military Institute of Health Services, Warsaw, Poland
Contributor Information and Disclosures

Updated: May 5, 2009

Differential Diagnoses

Contact Dermatitis, Allergic
Lupus Erythematosus, Bullous
Contact Dermatitis, Irritant
Lupus Erythematosus, Drug-Induced
Drug-Induced Bullous Disorders
Lupus Erythematosus, Subacute Cutaneous
Drug-Induced Photosensitivity
Papular Urticaria
Epidermolysis Bullosa
Pemphigus Erythematosus
Epidermolysis Bullosa Acquisita
Pemphigus Herpetiformis
Erysipelas
Pemphigus Vulgaris
Erythema Multiforme
Pemphigus, Drug-Induced
Erythroderma (Generalized Exfoliative Dermatitis)
Pemphigus, IgA
Fogo Selvagem
Pemphigus, Paraneoplastic
Glucagonoma Syndrome
Pseudoporphyria
Herpes Simplex
Subcorneal Pustular Dermatosis
Impetigo
Insect Bites
Linear IgA Dermatosis

Other Problems to Be Considered

A mixed immunoblistering disorder exhibiting features of bullous pemphigoid and pemphigus foliaceus (PF), associated with the food supplement Spirulina, was described in an 82-year-old woman.24

Workup

Laboratory Studies

  • Immunofluorescence using both direct techniques and indirect techniques is the most reliable method to diagnosis pemphigus.25 Because of the rare occurrence of pemphiguslike antibodies, pemphigus cannot be diagnosed by indirect immunofluorescence (IIF) alone and must be confirmed by direct immunofluorescence (DIF). With the use of 2 appropriate substrates (ie, monkey esophagus [or human skin] and guinea pig esophagus and standardized conjugates), in IIF, PV and pemphigus foliaceus patterns are different; PV stains throughout the epidermis, and pemphigus foliaceus stains only in the upper epidermis, whereas, with DIF, the patterns are similar. With a DIF study, cell surface immune deposits are often present throughout the entire epidermis in both pemphigus foliaceus and PV.
    • Immunologic examination with DIF testing shows IgG in the intercellular space, mainly in the upper parts of the epidermis; an IIF study documents the presence of circulating pemphigus antibodies, especially with a guinea pig esophagus used as a substrate. One IIF study suggested that using both a monkey esophagus and the human skin increases the sensitivity and aids in distinguishing pemphigus foliaceus from PV.
    • In PH, IgG deposits are evident in the upper epidermis, with circulating IgG to the epidermal cell surface. The subcorneal pustular dermatosis type of IgA pemphigus foliaceus has IgA deposition on the upper epidermal cell surfaces and circulating IgA antibodies to the epidermal cell surfaces.
    • Desmogleins 1 and 3 are the major cell surface target molecules in patients with PH.
    • In the unusual instance when PV becomes pemphigus foliaceus, or vice versa, the clinical alteration is associated with a shift in the antidesmoglein autoantibody profile.
  • Other methods, such as ELISA26 and immunoblot assays,27 can be used, but they require highly purified antigens to give similar results. The sensitivity for PV and pemphigus foliaceus antibodies is more than 98% in at least the renowned laboratory of Jarzabek-Chorzelska and associates,25  with their many decades of experience. Histologic examination is useful, but it is not the preferred method for diagnosing pemphigus foliaceus because it cannot replace a highly reliable DIF method.
  • Another less experienced laboratory found ELISA to be superior to an IIF study for serodiagnosis of pemphigus foliaceus at various stages of disease activity.28
  • Pemphigus foliaceus arising during the administration of D-penicillamine was described in an elderly patient in whom withdrawal of D-penicillamine resulted in improvement of the skin lesions and ELISA scores for anti–desmoglein 1 antibodies revealed a rapid decline.29

Histologic Findings

Pemphigus foliaceus begins as acantholysis of the upper epidermis, often resulting in a subcorneal cleft. It usually enlarges and detaches without bullae formation, though a bulla may form showing acantholysis at both the roof and the floor. More established lesions may have acanthosis and mild-to-moderate papillomatosis. Hyperkeratosis and parakeratosis may also be evident, with dyskeratotic cells within the granular layer. These features may be particularly pronounced in long-standing PE. A mild dermal lymphocytic infiltrate occurs, often with the presence of eosinophils. Eosinophilic spongiosis may also be noted, especially in PH.

Histologic view shows the typical pattern of a de...

Histologic view shows the typical pattern of a detached stratum corneum without bullae formation (same patient as in Media File 4). Pigmentary incontinence is prominent in the dermis, reflecting the patient's 9-year history of recurrent superficial bullae.

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Histologic view shows the typical pattern of a de...

Histologic view shows the typical pattern of a detached stratum corneum without bullae formation (same patient as in Media File 4). Pigmentary incontinence is prominent in the dermis, reflecting the patient's 9-year history of recurrent superficial bullae.


More on Pemphigus Foliaceus

Overview: Pemphigus Foliaceus
Differential Diagnoses & Workup: Pemphigus Foliaceus
Treatment & Medication: Pemphigus Foliaceus
Follow-up: Pemphigus Foliaceus
Multimedia: Pemphigus Foliaceus
References
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Further Reading

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Keywords

superficial pemphigus, fogo selvagem, PF, pemphigus erythematosus, PE, pemphigus herpetiformis, PH, endemic PF, endemic pemphigus foliaceus, immunoglobulin A PF, IgA PF, IgA pemphigus foliaceus, immunoglobulin A pemphigus foliaceus, drug-induced PF, drug-induced pemphigus foliaceus

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Contributor Information and Disclosures

Author

Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

Coauthor(s)

Slawomir Majewski, MD, Professor and Director, Department of Dermatology and Venereology, Warsaw School of Medicine, Poland
Disclosure: Nothing to disclose.

Sebastian S Majewski, MD, Consulting Staff, Department of Dermatology, Military Institute of Health Services, Warsaw, Poland
Disclosure: Nothing to disclose.

Medical Editor

Robin Travers, MD, Assistant Professor of Medicine (Dermatology), Dartmouth University School of Medicine; Staff Dermatologist, New England Baptist Hospital; Private Practice, SkinCare Physicians
Robin Travers, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Informatics Association, Massachusetts Medical Society, Medical Dermatology Society, and Women's Dermatologic Society
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

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

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

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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