eMedicine Specialties > Dermatology > Bullous Diseases

Pemphigus, IgA: Differential Diagnoses & Workup

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

Differential Diagnoses

Dermatitis Herpetiformis
Eosinophilic Pustular Folliculitis
Pemphigus Foliaceus
Subcorneal Pustular Dermatosis

Workup

Laboratory Studies

Other Tests

  • Perform other tests, if available, to document the diagnosis of IgA pemphigus, including immunoblotting, enzyme-linked immunosorbent assay (ELISA), and special immunofluorescence studies.
  • Immunoblotting
    • Immunoblotting documents the specific skin antigen recognized by the patient's IgA autoantibodies.
    • Immunoblotting has documented IgA autoantibodies (from 1 patient with IEN-type IgA pemphigus) that target desmosomal component desmoglein 3, which is located at the lower part of epidermis. However, other investigators were unable to detect IgA immunoreactivity to this protein in patient sera; therefore, the significance of the antigen remains unknown.
  • Enzyme-linked immunosorbent assay
    • In theory, ELISA should be a good methodology for documenting the specific desmosomal antigen(s) recognized by patient IgA autoantibodies, since it uses native protein and increases detection sensitivity.
    • In 2001, ELISA detected IgA autoantibodies recognizing desmoglein 3 and desmoglein 1 in a small percent of patients with IgA pemphigus.19
  • Special immunofluorescence tests
    • Special immunofluorescence tests using cultured cells that express recombinant desmosomal component (desmocollin 1) document the presence of circulating IgA autoantibodies that recognize desmosomal component.
    • Special immunofluorescence tests have documented IgA autoantibodies from patients with SPD-type IgA pemphigus. The tests detected desmosomal component desmocollin 1; however, this test is not generally available.

Procedures

  • Skin biopsy is performed and specimens analyzed to establish the diagnosis using histopathology and direct and indirect immunofluorescence.
    • Histopathology is performed on specimens of blistered skin.
      • Histopathology demonstrates an intraepidermal blister, which may be located subcorneally (SPD-type IgA pemphigus), suprabasally, or at mid epidermis (IEN-type IgA pemphigus).
      • Histopathology demonstrates acantholysis, but it is not characteristic as is acantholysis observed in classic pemphigus. The intraepidermal neutrophil infiltration tends to form neutrophilic microabscess, which is the hallmark of IgA pemphigus (see Media File 1).
    • Direct immunofluorescence is performed on perilesional skin sections.
      • Direct immunofluorescence documents the immune-mediated disease process.
      • Direct immunofluorescence predominantly detects IgA and sometimes, to a lesser extent, IgG and complement component C3 deposited at the cell surfaces of the epidermis.
    • Indirect immunofluorescence is performed using patient serum on monkey esophagus or other epithelial substrates.
      • Indirect immunofluorescence documents the presence of IgA circulating autoantibodies in patient serum that recognize skin epidermal cell surface components (see Media File 2).
      • Indirect immunofluorescence usually detects IgA circulating autoantibodies in serum that bind to epithelial cell surfaces in approximately 50% of patients. Titers of IgA pemphigus autoantibodies are much lower than the titers of IgG autoantibodies observed in IgG-mediated pemphigus.

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

  1. Amagai M, Klaus-Kovtun V, Stanley JR. Autoantibodies against a novel epithelial cadherin in pemphigus vulgaris, a disease of cell adhesion. Cell. Nov 29 1991;67(5):869-77. [Medline].

  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].

  6. Suzuki M, Karube S, Kobori Y, Usui K, Murata S, Kato H, et al. IgA pemphigus occurring in a 1-month-old infant. J Am Acad Dermatol. Feb 2003;48(2 Suppl):S22-4. [Medline].

  7. Chorzelski TP, Beutner EH, Kowalewski C, Olszewska M, Maciejowska E, Seferowicz E, et al. IgA pemphigus foliaceus with a clinical presentation of pemphigus herpetiformis. J Am Acad Dermatol. May 1991;24(5 Pt 2):839-44. [Medline].

  8. Erdag G, Qureshi HS, Greer KE, Patterson JW. Immunoglobulin A pemphigus involving the perianal skin and oral mucosa: an unusual presentation. Cutis. Sept/2007;80:218-220. [Medline].

  9. Ebihara T, Hashimoto T, Iwatsuki K, Takigawa M, Ando M, Ohkawara A, et al. Autoantigens for IgA anti-intercellular antibodies of intercellular IgA vesiculopustular dermatosis. J Invest Dermatol. Oct 1991;97(4):742-5. [Medline].

  10. Hashimoto T, Ebihara T, Nishikawa T. Studies of autoantigens recognized by IgA anti-keratinocyte cell surface antibodies. J Dermatol Sci. Apr 1996;12(1):10-7. [Medline].

  11. Hashimoto T, Inamoto N, Nakamura K, Nishikawa T. Intercellular IgA dermatosis with clinical features of subcorneal pustular dermatosis. Arch Dermatol. Aug 1987;123(8):1062-5. [Medline].

  12. Hashimoto T, Kiyokawa C, Mori O, Miyasato M, Chidgey MA, Garrod DR, et al. Human desmocollin 1 (Dsc1) is an autoantigen for the subcorneal pustular dermatosis type of IgA pemphigus. J Invest Dermatol. Aug 1997;109(2):127-31. [Medline].

  13. Ishii N, Ishida-Yamamoto A, Hashimoto T. Immunolocalization of target autoantigens in IgA pemphigus. Clin Exp Dermatol. Jan 2004;29(1):62-6. [Medline].

  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].

  15. Wang J, Kwon J, Ding X, Fairley JA, Woodley DT, Chan LS. Nonsecretory IgA1 autoantibodies targeting desmosomal component desmoglein 3 in intraepidermal neutrophilic IgA dermatosis. Am J Pathol. Jun 1997;150(6):1901-7. [Medline].

  16. Fujihashi K, McGhee JR, Kweon MN, Cooper MD, Tonegawa S, Takahashi I, et al. gamma/delta T cell-deficient mice have impaired mucosal immunoglobulin A responses. J Exp Med. Apr 1 1996;183(4):1929-35. [Medline].

  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].

  21. Gruss C, Zillikens D, Hashimoto T, Amagai M, Kroiss M, Vogt T, et al. Rapid response of IgA pemphigus of subcorneal pustular dermatosis type to treatment with isotretinoin. J Am Acad Dermatol. Nov 2000;43(5 Pt 2):923-6. [Medline].

  22. Ruiz-Genao DP, Hernández-Núñez A, Hashimoto T, Amagai M, Fernández-Herrera J, García-Díez A. A case of IgA pemphigus successfully treated with acitretin. Br J Dermatol. Nov 2002;147(5):1040-2. [Medline].

  23. Amagai M, Tsunoda K, Suzuki H, Nishifuji K, Koyasu S, Nishikawa T. Use of autoantigen-knockout mice in developing an active autoimmune disease model for pemphigus. J Clin Invest. Mar 2000;105(5):625-31. [Medline].

  24. Beutner EH, Chorzelski TP, Wilson RM, Kumar V, Michel B, Helm F, et al. IgA pemphigus foliaceus. Report of two cases and a review of the literature. J Am Acad Dermatol. Jan 1989;20(1):89-97. [Medline].

  25. Coffman RL, Shrader B, Carty J, Mosmann TR, Bond MW. A mouse T cell product that preferentially enhances IgA production. I. Biologic characterization. J Immunol. Dec 1 1987;139(11):3685-90. [Medline].

  26. de Oliveira JP, Gabbi TV, Hashimoto T, Aoki V, Santi CG, Maruta CW, et al. Two Brazilian cases of IgA pemphigus. J Dermatol. Dec 2003;30(12):886-91. [Medline].

  27. Hall RP, Lawley TJ. Characterization of circulating and cutaneous IgA immune complexes in patients with dermatitis herpetiformis. J Immunol. Sep 1985;135(3):1760-5. [Medline].

  28. Hodak E, David M, Ingber A, Rotem A, Hazaz B, Shamai-Lubovitz O, et al. The clinical and histopathological spectrum of IgA-pemphigus--report of two cases. Clin Exp Dermatol. Nov 1990;15(6):433-7. [Medline].

  29. Huff JC, Golitz LE, Kunke KS. Intraepidermal neutrophilic IgA dermatosis. N Engl J Med. Dec 26 1985;313(26):1643-5. [Medline].

  30. Robinson ND, Hashimoto T, Amagai M, Chan LS. The new pemphigus variants. J Am Acad Dermatol. May 1999;40(5 Pt 1):649-71; quiz 672-3. [Medline].

  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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