eMedicine Specialties > Dermatology > Bullous Diseases

Pemphigus, IgA

Author: Lawrence Chan, MD, Department Head and Director of Skin Immunology Research, Professor, Departments of Dermatology and Microbiology/Immunology, University of Illinois College of Medicine
Contributor Information and Disclosures

Updated: Sep 24, 2008

Introduction

Background

Immunoglobulin A (IgA) pemphigus is a group of newly characterized immune-mediated intraepidermal blistering skin diseases. Unlike typical immunoglobulin G (IgG)–mediated pemphigus, IgA pemphigus is characterized by tissue-bound and circulating IgA autoantibodies that target the desmosomal proteins of the epidermis.

Histopathologically, epidermal acantholysis and neutrophil infiltration predominate, hence the synonyms intraepidermal neutrophilic IgA dermatosis, intraepidermal IgA pustulosis, IgA herpetiform pemphigus, and intercellular IgA vesiculopustular dermatosis have been used to describe this group of diseases. No consensus has been reached concerning the nomenclature.

IgA pemphigus has not been described in animals. Although the term IgA pemphigus has not been established in the veterinary literature, IgA deposition around epidermal cells has been detected by direct immunofluorescence in animals affected with pemphigus foliaceus.

The following eMedicine articles on other types of pemphigus may be of interest:

Pathophysiology

The exact pathomechanism of IgA pemphigus is not well defined. According to currently available data, IgA autoantibodies clearly bind to desmosomal components of the epidermis, desmogleins, or desmocollins. Since the IgA autoantibodies possess specific binding sites for the monocyte/granulocyte IgA-Fc receptor (CD89), hypothesis indicates that neutrophils accumulate intraepidermally, causing the blistering process to occur.1,2,3 The direct pathogenic effects of the IgA autoantibodies have not been established.

Frequency

United States

IgA pemphigus is a group of newly characterized diseases, and its frequency is unknown, although IgA pemphigus has been reported in the United States.

International

IgA pemphigus is a group of newly characterized diseases, and its frequency is not yet defined. IgA pemphigus has been reported in Asia (including Japan), South America, and Europe (including Scandinavian countries4 ). A 2004 article surveying patients affected by autoimmune blistering diseases in Kuwait suggested that IgA pemphigus may be extremely rare in that part of the world.5

Mortality/Morbidity

Mortality directly resulting from IgA pemphigus is not reported. In general, the clinical course of IgA pemphigus is less severe than that of IgG-mediated pemphigus, and no significant morbidity exists. In some patients with IgA pemphigus, pruritus is a significant symptom and may interfere with the patient's daily life.

Race

IgA pemphigus is a rare disease and is newly characterized; therefore, the race distribution is unknown. IgA pemphigus has been reported in American, European, South American, and Asian patients.

Sex

The sex distribution is unknown. A review of 28 cases reported from 1982-1997 revealed a male-to-female ratio of 1:1.33.

Age

IgA pemphigus has been reported to occur in persons aged 1 month6 to 85 years. A review of 28 cases reported from 1982-1997 determined the average age of onset to be 53 years.

Clinical

History

Patients affected with IgA pemphigus usually have subacute onset of disease. In more than one half of reported patients, pruritus is present.

Physical

IgA pemphigus is a vesiculopustular skin disease. In general, lesions form within erythematous plaques but also can form in skin without plaques. The initial, clear, fluid-filled blisters fill with neutrophils and transform into pustules.

  • In some patients, neutrophils settle at the lower part of the blister, forming a hypopyon pattern.
  • In most patients, the trunk and proximal extremities primarily are involved.
  • In some patients, scalp and postauricular areas are involved extensively.
  • In some patients, intertriginous areas (axillary and inframammary areas) are involved.
  • Mucous membranes, palms, and soles usually are spared.
  • Lesions usually became flaccid after an initial tense appearance. Some lesions become crusted and form a herpetiform pattern.7
  • In one patient, involvement of perianal skin and oral mucosa was observed.8

Causes

The exact pathomechanism of IgA pemphigus is not well defined at the present time. Clearly, IgA autoantibodies are initiated to target desmosomal components, although the mechanism for such initiation is unknown. At least 3 desmosomal components, including desmoglein 3 (in intraepidermal neutrophilic–type [IEN-type] IgA pemphigus), desmoglein 1, and desmocollin 1 (in subcorneal pustular dermatosis–type [SPD-type] IgA pemphigus foliaceus), have been identified as target antigens in IgA pemphigus.9,10,11,12,13,14,15 Other unidentified target antigens also may be involved.

  • Possible role of a specific cytokine: Interleukin 5, a TH 2-secreted cytokine that preferentially induces B cells to produce IgA class antibodies, may be activated preferentially in patients with IgA pemphigus.
  • Possible role of specific T-cell receptors (TCRs): Gamma/delta TCR-containing T cells, which have been found to be important in influencing mucosal IgA production, may be involved in the IgA pemphigus process.16
  • Possible role of the binding site for monocyte/granulocyte IgA-Fc receptor (CD89) in human IgA subclass 1 (IgA1): Human IgA1 antibody has a binding site for the monocyte/granulocyte IgA-Fc receptor (CD89) that is located distally to the hinge region, thus providing a stronger resistance to protease digestion. The protease-resistant property of IgA1 may provide efficient binding of neutrophils, thus allowing the intraepidermal neutrophil infiltration that may contribute to the blistering process.3
  • Postembedding immunoelectron microscopy has localized the target antigen of the SPD-type IgA pemphigus to the extracellular domain of desmocollin, whereas the target antigen of the IEN-type IgA pemphigus was found to be in an intercellular space outside the desmosomal areas. These findings suggest that the pathomechanism of IgA pemphigus involves the weakening of extracellular components of cell-to-cell adhesion molecules.
  • An association of IgA pemphigus and IgA gammopathy and lung cancer has been reported.17
  • The 2005 report of cases of pemphigus characterized by the presence of both IgA and IgG classes of autoantibodies raises the question of whether this IgA/IgG pemphigus is a subset of IgA pemphigus or a novel disease entity.18

More on Pemphigus, IgA

Overview: Pemphigus, IgA
Differential Diagnoses & Workup: Pemphigus, IgA
Treatment & Medication: Pemphigus, IgA
Follow-up: Pemphigus, IgA
Multimedia: Pemphigus, IgA
References
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References

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  2. Amagai M, Koch PJ, Nishikawa T, Stanley JR. Pemphigus vulgaris antigen (desmoglein 3) is localized in the lower epidermis, the site of blister formation in patients. J Invest Dermatol. Feb 1996;106(2):351-5. [Medline].

  3. Carayannopoulos L, Hexham JM, Capra JD. Localization of the binding site for the monocyte immunoglobulin (Ig) A- Fc receptor (CD89) to the domain boundary between Calpha2 and Calpha3 in human IgA1. J Exp Med. Apr 1 1996;183(4):1579-86. [Medline].

  4. Gniadecki R, Bygum A, Clemmensen O, Svejgaard E, Ullman S. IgA pemphigus: the first two Scandinavian cases. Acta Derm Venereol. 2002;82(6):441-5. [Medline].

  5. Nanda A, Dvorak R, Al-Saeed K, Al-Sabah H, Alsaleh QA. Spectrum of autoimmune bullous diseases in Kuwait. Int J Dermatol. Dec 2004;43(12):876-81. [Medline].

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  14. Kárpáti S, Amagai M, Liu WL, Dmochowski M, Hashimoto T, Horváth A. Identification of desmoglein 1 as autoantigen in a patient with intraepidermal neutrophilic IgA dermatosis type of IgA pemphigus. Exp Dermatol. Jun 2000;9(3):224-8. [Medline].

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  17. Petropoulou H, Politis G, Panagakis P, Hatziolou E, Aroni K, Kontochristopoulos G. Immunoglobulin A pemphigus associated with immunoglobulin A gammopathy and lung cancer. J Dermatol. June/2008;35:341-345. [Medline].

  18. Brunkner AL, Fitzpatrick JE, Hashimoto T, Weston WL, Morelli JG. Atypical IgA/IgG pemphigus involving the skin, oral mucosa, and colon in a child: a novel variant of IgA pemphigus?. Pediatr Dermatol. 2005;22:321-327. [Medline].

  19. Hashimoto T, Komai A, Futei Y, Nishikawa T, Amagai M. Detection of IgA autoantibodies to desmogleins by an enzyme-linked immunosorbent assay: the presence of new minor subtypes of IgA pemphigus. Arch Dermatol. Jun 2001;137(6):735-8. [Medline].

  20. Howell SM, Bessinger GT, Altman CE, Belnap CM. Rapid response of IgA pemphigus of the subcorneal pustular dermatosis subtype to treatment with adalimumab and mycophenolate mofetil. J Am Acad Dermatol. Sep 2005;53(3):541-3. [Medline].

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  31. Tagami H, Iwatsuki K, Iwase Y, Yamada M. Subcorneal pustular dermatosis with vesiculo-bullous eruption. Demonstration of subcorneal IgA deposits and a leukocyte chemotactic factor. Br J Dermatol. Nov 1983;109(5):581-7. [Medline].

  32. Wallach D, Janssen F, Vignon-Pennamen MD, Lemarchand-Venencie F, Cottenot F. Atypical neutrophilic dermatosis with subcorneal IgA deposits. Arch Dermatol. Jun 1987;123(6):790-5. [Medline].

  33. Weisbart RH, Kacena A, Schuh A, Golde DW. GM-CSF induces human neutrophil IgA-mediated phagocytosis by an IgA Fc receptor activation mechanism. Nature. Apr 14 1988;332(6165):647-8. [Medline].

  34. Zillikens D, Miller K, Hartmann AA, Burg G. IgA pemphigus foliaceus: a case report. Dermatologica. 1990;181(4):304-7. [Medline].

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Further Reading

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Keywords

IgA pemphigus, pemphigus IgA, pemphigus, intraepidermal neutrophilic IgA dermatosis, intercellular IgA vesiculopustular dermatosis, intercellular IgA dermatosis, intraepidermal IgA pustulosis, IgA pemphigus

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Contributor Information and Disclosures

Author

Lawrence Chan, MD, Department Head and Director of Skin Immunology Research, Professor, Departments of Dermatology and Microbiology/Immunology, University of Illinois College of Medicine
Lawrence Chan, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Association of Professors of Dermatology, Chicago Dermatological Society, Dermatology Foundation, Illinois State Medical Society, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Medical Editor

Takeji Nishikawa, MD, Emeritus Professor, Department of Dermatology, Keio University School of Medicine; Director, Samoncho Dermatology Clinic; Managing Director, The Waksman Foundation of Japan Inc
Disclosure: Nothing to disclose.

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: 3M Pharmaceutical Grant/research funds Other; Graceway Pharmaceuticals Grant/research funds Other

Managing Editor

Edward F Chan, MD, Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania School of Medicine
Edward F Chan, 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

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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