Pemphigus Erythematosus: Background, Pathophysiology, Epidemiology

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Sections Pemphigus Erythematosus
Overview
Presentation
- History
- Physical
- Causes
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DDx
Workup
Treatment
- Medical Care
- Consultations
- Diet
- Activity
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Medication
Follow-up
Media Gallery
References

Overview

Background

The various types of pemphigus include pemphigus erythematosus, pemphigoid, pemphigus vegetans, pemphigus vulgaris, and pemphigus foliaceus.

Pemphigus erythematosus, also known as Senear-Usher syndrome, is an overlap syndrome with features of lupus erythematosus (LE) and pemphigus foliaceus. Pemphigus is demonstrated by acantholysis and immunoglobulin deposits in the interkeratinocyte substance (see the image below).

Direct immunofluorescence microscopy performed on epithelial biopsy specimen obtained from a patient with pemphigus vulgaris detects immunoglobulin G deposits at the epithelial cell surfaces.

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Pérez-Pérez et al recently hypothesized that pemphigus erythematosus is a multiple autoimmune disease.^[1]

High doses of UV light are suggested to be the cause of cleavage of the desmoglein-1 ectodomain. As in cases of pemphigus foliaceus the circulating anti–desmoglein-1 antibodies precipitate this cleaved off ectodomain along with the basement membrane zone, resulting in a lupus band–like appearance.

The lupus component of pemphigus erythematosus is demonstrated by circulating antinuclear antibodies (ANA) and sometimes by immunoglobulin and complement deposits at the dermoepidermal junction

For a thorough description and introduction to the possible causes of pemphigus, see the article "Pemphigus: An Acronym for a Disease with Multiple Causes ", published by the International Pemphigus Society.^[2]

Pathophysiology

Patients with pemphigus erythematosus present with vesiculobullae or superficially eroded lesions, which may ooze and crust, particularly in sun-exposed areas, such as the face, the upper part of the chest, and the back.

Frequency

The incidence of pemphigus is 0.5-3.2 cases per 100,000 population per year. Patients with pemphigus erythematosus comprise only a small subgroup of those with pemphigus. Kumar from India, in a 2008 article, reported a high prevalence (4.4 cases per million population).^[3]

Race

Pemphigus erythematosus, like other variants of pemphigus erythematosus and LE, may be increased in patients who express specific human leukocyte antigen (HLA) haplotypes. Those identified to have pemphigus erythematosus are positive for human leukocyte antigen A10 (HLA-A10) or human leukocyte antigen A26 (HLA-A26) and human leukocyte antigen DRW6 (HLA-DRW6).

Sex

Reports generally find no difference in occurrence of pemphigus erythematosus between the 2 sexes.

Age

Pemphigus erythematosus may occur at any age, but it is unusual in children.

Clinical Presentation

Pérez-Pérez ME, Avalos-Díaz E, Herrera-Esparza R. Autoantibodies in senear-usher syndrome: cross-reactivity or multiple autoimmunity?. Autoimmune Dis. 2012. 2012:296214. [Medline].
Brenner S, Mashiah J, Tamir E, et al. PEMPHIGUS. An Acronym for a Disease with Multiple Causes. The International Pemphigus Foundation. Available at http://www.pemphigus.org/pemphigus-an-acronym-for-a-disease-with-multiple-causes-2/. Accessed: May 29, 2005.
Kumar KA. Incidence of pemphigus in Thrissur district, south India. Indian J Dermatol Venereol Leprol. 2008 Jul-Aug. 74(4):349-51. [Medline]. [Full Text].
Oktarina DA, Poot AM, Kramer D, Diercks GF, Jonkman MF, Pas HH. The IgG "Lupus-Band" Deposition Pattern of Pemphigus Erythematosus: Association With the Desmoglein 1 Ectodomain as Revealed by 3 Cases. Arch Dermatol. 2012 Jul 16. 1-6. [Medline].
Anuradha Ch, Malathi N, Anandan S, Magesh K. Current concepts of immunofluorescence in oral mucocutaneous diseases. J Oral Maxillofac Pathol. 2011 Sep. 15(3):261-6. [Medline]. [Full Text].
Singh S. Evidence-based treatments for pemphigus vulgaris, pemphigus foliaceus, and bullous pemphigoid: a systematic review. Indian J Dermatol Venereol Leprol. 2011 Jul-Aug. 77(4):456-69. [Medline].
Griffies JD, Mendelsohn CL, Rosenkrantz WS, et al. Topical 0.1% tacrolimus for the treatment of discoid lupus erythematosus and pemphigus erythematosus in dogs. J Am Anim Hosp Assoc. 2004 Jan-Feb. 40(1):29-41. [Medline].
Basset N, Guillot B, Michel B, Meynadier J, Guilhou JJ. Dapsone as initial treatment in superficial pemphigus. Report of nine cases. Arch Dermatol. 1987 Jun. 123(6):783-5. [Medline].
Piamphongsant T. Pemphigus controlled by dapsone. Br J Dermatol. 1976 Jun. 94(6):681-6. [Medline].
Chaffins ML, Collison D, Fivenson DP. Treatment of pemphigus and linear IgA dermatosis with nicotinamide and tetracycline: a review of 13 cases. J Am Acad Dermatol. 1993 Jun. 28(6):998-1000. [Medline].
Ahmed AR, Hombal SM. Cyclophosphamide (Cytoxan). A review on relevant pharmacology and clinical uses. J Am Acad Dermatol. 1984 Dec. 11(6):1115-26. [Medline].
Pasricha JS, Sood VD, Minocha Y. Treatment of pemphigus with cyclophosphamide. Br J Dermatol. 1975 Nov. 93(5):573-6. [Medline].
Heilborn JD, Stahle-Backdahl M, Albertioni F, Vassilaki I, Peterson C, Stephansson E. Low-dose oral pulse methotrexate as monotherapy in elderly patients with bullous pemphigoid. J Am Acad Dermatol. 1999 May. 40(5 Pt 1):741-9. [Medline].
Tan-Lim R, Bystryn JC. Effect of plasmapheresis therapy on circulating levels of pemphigus antibodies. J Am Acad Dermatol. 1990 Jan. 22(1):35-40. [Medline].
Enk AH, Knop J. Mycophenolate is effective in the treatment of pemphigus vulgaris. Arch Dermatol. 1999 Jan. 135(1):54-6. [Medline].
Kaur S, Kanwar AJ. Dexamethasone-cyclophosphamide pulse therapy in pemphigus. Int J Dermatol. 1990 Jun. 29(5):371-4. [Medline].
Pasricha JS, Gupta R. Pulse therapy with dexamethasone-cyclophosphamide in pemphigus. Indian J Dermatol Venereol Leprol. 1984. 50:199-203.
Pasricha JS, Khaitan BK, Raman RS, Chandra M. Dexamethasone-cyclophosphamide pulse therapy for pemphigus. Int J Dermatol. 1995 Dec. 34(12):875-82. [Medline].
Pasricha JS, Thanzama J, Khan UK. Intermittent high-dose dexamethasone-cyclophosphamide therapy for pemphigus. Br J Dermatol. 1988 Jul. 119(1):73-7. [Medline].
Kandan S, Thappa DM. Outcome of dexamethasone-cyclophosphamide pulse therapy in pemphigus: a case series. Indian J Dermatol Venereol Leprol. 2009 Jul-Aug. 75(4):373-8. [Medline].
Pasricha JS. Current regimen of pulse therapy for pemphigus: minor modifications, improved results. Indian J Dermatol Venereol Leprol. 2008 May-Jun. 74(3):217-21. [Medline].
Ramam M. Prolonged antimicrobial and oral cyclophosphamide therapy in pemphigus: need for caution. Indian J Dermatol Venereol Leprol. 2009 Jan-Feb. 75(1):85. [Medline].
Egan CA, Meadows KP, Zone JJ. Plasmapheresis as a steroid saving procedure in bullous pemphigoid. Int J Dermatol. 2000 Mar. 39(3):230-5. [Medline].
Furue M, Iwata M, Yoon HI, et al. Epidermolysis bullosa acquisita: clinical response to plasma exchange therapy and circulating anti-basement membrane zone antibody titer. J Am Acad Dermatol. 1986 May. 14(5 Pt 2):873-8. [Medline].
Turner MS, Sutton D, Sauder DN. The use of plasmapheresis and immunosuppression in the treatment of pemphigus vulgaris. J Am Acad Dermatol. 2000 Dec. 43(6):1058-64. [Medline].
Bystryn JC. Plasmapheresis therapy of pemphigus. Arch Dermatol. 1988 Nov. 124(11):1702-4. [Medline].
Matic G, Bosch T, Ramlow W. Background and indications for protein A-based extracorporeal immunoadsorption. Ther Apher. 2001 Oct. 5(5):394-403. [Medline].
Ogata K, Yasuda K, Matsushita M, Kodama H. Successful treatment of adolescent pemphigus vulgaris by immunoadsorption method. J Dermatol. 1999 Apr. 26(4):236-9. [Medline].
Schneider KM. Plasmapheresis and immunoadsorption: different techniques and their current role in medical therapy. Kidney Int Suppl. 1998 Feb. 64:S61-5. [Medline].
Schmidt E, Klinker E, Opitz A, et al. Protein A immunoadsorption: a novel and effective adjuvant treatment of severe pemphigus. Br J Dermatol. 2003 Jun. 148(6):1222-9. [Medline].
Femiano F, Gombos F, Scully C. Pemphigus vulgaris with oral involvement: evaluation of two different systemic corticosteroid therapeutic protocols. J Eur Acad Dermatol Venereol. 2002 Jul. 16(4):353-6. [Medline].
Joly P, Roujeau JC, Benichou J, et al. A comparison of oral and topical corticosteroids in patients with bullous pemphigoid. N Engl J Med. 2002 Jan 31. 346(5):321-7. [Medline].
Hull CM, McKenna JK, Zone JJ. Topical corticosteroids and bullous pemphigoid. Arch Dermatol. 2003 Feb. 139(2):225-6. [Medline].
Cohen MA, Cohen JJ, Kerdel FA. Immunoablative high-dose cyclophosphamide without stem cell rescue in pemphigus foliaceus. Int J Dermatol. 2002 Jun. 41(6):340-4. [Medline].
Hayag MV, Cohen JA, Kerdel FA. Immunoablative high-dose cyclophosphamide without stem cell rescue in a patient with pemphigus vulgaris. J Am Acad Dermatol. 2000 Dec. 43(6):1065-9. [Medline].
Nousari HC, Brodsky RA, Jones RJ, Grever MR, Anhalt GJ. Immunoablative high-dose cyclophosphamide without stem cell rescue in paraneoplastic pemphigus: report of a case and review of this new therapy for severe autoimmune disease. J Am Acad Dermatol. 1999 May. 40(5 Pt 1):750-4. [Medline].
Glied M, Rico MJ. Treatment of autoimmune blistering diseases. Dermatol Clin. 1999 Apr. 17(2):431-40, x. [Medline].
Tan BB, Lear JT, Gawkrodger DJ, English JS. Azathioprine in dermatology: a survey of current practice in the U.K. Br J Dermatol. 1997 Mar. 136(3):351-5. [Medline].
[Guideline] Anstey AV, Wakelin S, Reynolds NJ. Guidelines for prescribing azathioprine in dermatology. Br J Dermatol. 2004 Dec. 151(6):1123-32. [Medline].
Ahmed AR, Colon JE. Comparison between intravenous immunoglobulin and conventional immunosuppressive therapy regimens in patients with severe oral pemphigoid: effects on disease progression in patients nonresponsive to dapsone therapy. Arch Dermatol. 2001 Sep. 137(9):1181-9. [Medline].
Ahmed AR. Intravenous immunoglobulin therapy for patients with bullous pemphigoid unresponsive to conventional immunosuppressive treatment. J Am Acad Dermatol. 2001 Dec. 45(6):825-35. [Medline].
Ahmed AR, Sami N. Intravenous immunoglobulin therapy for patients with pemphigus foliaceus unresponsive to conventional therapy. J Am Acad Dermatol. 2002 Jan. 46(1):42-9. [Medline].
Gourgiotou K, Exadaktylou D, Aroni K, et al. Epidermolysis bullosa acquisita: treatment with intravenous immunoglobulins. J Eur Acad Dermatol Venereol. 2002 Jan. 16(1):77-80. [Medline].
Leverkus M, Georgi M, Nie Z, Hashimoto T, Brocker EB, Zillikens D. Cicatricial pemphigoid with circulating IgA and IgG autoantibodies to the central portion of the BP180 ectodomain: beneficial effect of adjuvant therapy with high-dose intravenous immunoglobulin. J Am Acad Dermatol. 2002 Jan. 46(1):116-22. [Medline].
Sami N, Qureshi A, Ahmed AR. Steroid sparing effect of intravenous immunoglobulin therapy in patients with pemphigus foliaceus. Eur J Dermatol. 2002 Mar-Apr. 12(2):174-8. [Medline].
Ozog DM, Gogstetter DS, Scott G, Gaspari AA. Minocycline-induced hyperpigmentation in patients with pemphigus and pemphigoid. Arch Dermatol. 2000 Sep. 136(9):1133-8. [Medline].
Borradori L, Lombardi T, Samson J, Girardet C, Saurat JH, Hugli A. Anti-CD20 monoclonal antibody (rituximab) for refractory erosive stomatitis secondary to CD20(+) follicular lymphoma-associated paraneoplastic pemphigus. Arch Dermatol. 2001 Mar. 137(3):269-72. [Medline].
Goebeler M, Herzog S, Brocker EB, Zillikens D. Rapid response of treatment-resistant pemphigus foliaceus to the anti-CD20 antibody rituximab. Br J Dermatol. 2003 Oct. 149(4):899-901. [Medline].
Mrowietz U. Treatment targeted to cell surface epitopes. Clin Exp Dermatol. 2002 Oct. 27(7):591-6. [Medline].
Salopek TG, Logsetty S, Tredget EE. Anti-CD20 chimeric monoclonal antibody (rituximab) for the treatment of recalcitrant, life-threatening pemphigus vulgaris with implications in the pathogenesis of the disorder. J Am Acad Dermatol. 2002 Nov. 47(5):785-8. [Medline].

Media Gallery

Direct immunofluorescence microscopy performed on epithelial biopsy specimen obtained from a patient with pemphigus vulgaris detects immunoglobulin G deposits at the epithelial cell surfaces.
Biopsy shows moderate epithelial hyperplasia with a suprabasal cleft that shows suprabasal acantholysis. The rest of the epithelium shows spongiosis with neutrophils. The submucosa has a moderately dense mixed perivascular infiltrate of lymphocytes and neutrophils. At places, the epithelium is missing, and the surface is covered by fibrin and necrotic inflammatory cells. Photo courtesy of Dr. Uday Khopkar.
Biopsy shows upper epidermal acantholytic blistering dermatitis involving the granular and upper spinous layer. The blister contains plasma, RBCs, and few acute inflammatory cells. The epidermis at the periphery of the blister shows mild spongiosis with neutrophils. In the roof of the blister, a few elongated acantholytic cells can be seen. Underlying dermis shows superficial and mid perivascular mixed infiltrate of neutrophils and lymphocytes. Photo courtesy of Dr. Uday Khopkar.
Biopsy shows upper epidermal acantholytic blistering dermatitis involving the granular and upper spinous layer with absence of roof of blister. The epidermis shows mild spongiosis with neutrophils. Underlying dermis shows superficial and mid perivascular mixed infiltrate of neutrophils and lymphocytes. Photo courtesy of Dr. Uday Khopkar.
Biopsy shows sparse superficial and deep perivascular infiltrate of lymphocytes. The papillary dermis is edematous and there is extravasation of RBCs. Basal layer shows vacuolization and interface infiltration by lymphocytes. Reticular dermis shows small amount of mucin. Photo courtesy of Dr. Uday Khopkar.

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Author

Rakesh Bharti, MD, MBBS Consultant Dermatologist and HIV Specialist, BDC Research Centre, India

Rakesh Bharti, MD, MBBS is a member of the following medical societies: International AIDS Society

Disclosure: Nothing to disclose.

Specialty Editor Board

David F Butler, MD Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: American Medical Association, Alpha Omega Alpha, Association of Military Dermatologists, American Academy of Dermatology, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Phi Beta Kappa

Disclosure: Nothing to disclose.

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, Women's Dermatologic Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: American Board of Dermatology<br/>Co-Editor for the text Dermatological Manifestations of Kidney Disease .

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: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Naked Biome<br/>Received income in an amount equal to or greater than $250 from: Elsevier; WebMD<br/>StatPearls; Editor.

Additional Contributors

Ponciano D Cruz, Jr, MD Professor and Vice-Chair, Paul R Bergstresser Chair, Department of Dermatology, University of Texas Southwestern Medical Center

Ponciano D Cruz, Jr, MD is a member of the following medical societies: Texas Medical Association

Disclosure: Received consulting fee from RCTS for independent contractor; Received honoraria from Mary Kay Cosmetics for consulting; Received grant/research funds from Galderma for principal investigator.

Acknowledgements

The author acknowledges the patience of his wife Prabha Bharti while carrying out work on this article and the constant pushing of his learned sons Aseem and Anshul.

Sections Pemphigus Erythematosus
Overview
Presentation
- History
- Physical
- Causes
- Show All
DDx
Workup
Treatment
- Medical Care
- Consultations
- Diet
- Activity
- Show All
Medication
Follow-up
Media Gallery
References

Pemphigus Erythematosus

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