Background: Pemphigus and pemphigoid are two distinct groups of autoimmune blistering diseases. There are many reports of the simultaneous presence of clinical and serological features of both diseases in the same patient. Objective: This study is a retrospective review of the present literature on reports of patients with features of both pemphigus and pemphigoid. We recommend that these patients be considered as having a dual diagnosis. Methods: A review of the English language, peer-reviewed literature was conducted on patients described with features of pemphigus and pemphigoid. Available data on clinical profile, histology, immunopathology, treatment, follow-up and outcome were studied in 30 patients. They were divided into three groups: (1) bullous pemphigoid and pemphigus vulgaris, (2) mucous membrane or cicatricial pemphigoid and pemphigus vulgaris and (3) bullous pemphigoid and pemphigus foliaceus. Results: In all three groups, most patients had a clinical phenotype resembling both diseases. In 17 patients with bullous pemphigoid and pemphigus vulgaris, 83% had a skin biopsy consistent with bullous pemphigoid, 70% had direct immunofluorescence studies typical of bullous pemphigoid and sera of 83% had antibodies typical of pemphigus vulgaris on indirect immunofluorescence. In 10 patients with mucous membrane or cicatricial pemphigoid and pemphigus vulgaris, a histology of mucous membrane pemphigoid was reported in 60% of the patients, direct immunofluorescence studies typical of mucous membrane pemphigoid were reported in 70% of the patients and in 80%, autoantibodies characteristic of pemphigus vulgaris were observed. In 3 patients with bullous pemphigoid and pemphigus foliaceus, the histologies were consistent with bullous pemphigoid, direct immunofluorescence was typical of pemphigus foliaceus and their sera had both autoantibodies. The majority of the 30 patients required long-term high-dose corticosteroids and immunosuppressive agents to control their disease. Three patients with bullous pemphigoid and pemphigus vulgaris (18%) died due to effects of prolonged immunosuppression. Conclusion: We characterize a group of patients who have clinical, histological and immunopathological features of bullous or mucous membrane or cicatricial pemphigoid with serological features of pemphigus. These patients did not achieve a prolonged clinical remission by conventional therapy. It is possible that early identification of these patients may improve their prognosis.

Scott JE, Ahmed AR: The blistering diseases. Med Clin North Am 1998;82:1239–1284.
Nousairi HC, Anhalt CJ: Pemphigus and bullous pemphigoid. Lancet 1999;354:667–672.
Yancey KB, Egan CA: Pemphigoid: Clinical, histologic, immunopathologic and therapeutic considerations. JAMA 2000;284:350–356.
Scully C: A review of mucocutaneous disorders affecting the mouth and lips. Ann Acad Med Singapore 1999;28:704–707.
Amagai M, Tsunoda K, Zillikens D, Nagai T, Nishikawa T: The clinical phenotype of pemphigus is defined by the anti-desmoglein autoantibody profile. J Am Acad Dermatol 1999;40:167–170.
Anhalt GJ, Labib RS, Voorhees JJ, Beals TF, Diaz LA: Induction of pemphigus in neonatal mice by passive transfer of IgG from patients with the disease. N Engl J Med 1982;306:1189–1196.
Ead RD: Pemphigus-like antibodies: A report of two cases. Br J Dermatol 1979;100:723–725.
Smolle J, Kerl H: Pitfalls in the diagnosis of pemphigus vulgaris. Am J Dermatopathol 1984;6:429–435.
Leibovici V, Ron N, Goldenhersh M, Holubar K: Coexistence of pemphigus and bullous pemphigoid. Int J Dermatol 1989;28:259–260.
Matasubara, K, Kanauchi H, Tanaka T, Imamura S: Coexistence of pemphigus and bullous pemphigoid. J Dermatol 1995;22:68–71.
Takahashi H, Wada T, Matsuo S, Iwatsuki K, Iizuka H: A case of bullous pemphigoid with antibodies against intercellular 130 kD antigen. J Dermatol 1995;22:576–581.
Bernard P, Catanzano G, St Florent JDV, Fayol J, Bonnetblanc JM: Bullous pemphigoid with pemphigus-like antibodies in vivo: 2 cases. Ann Dermatol 1986;113:671–676.
Chorzelski TP, Maciejowski E, Jablonska S, DeMento FJ, Grover RW, Holubar K, Beutner EH: Coexistence of pemphigus and bullous pemphigoid. Arch Dermatol 1974;109:849–853.
Kore-eda S, Horiguchi Y, Ohtoshi E, Tanaka T, Kimio G, Okamoto H, Iokai K, Imamura S: A case of autoimmune bullous dermatosis with features of pemphigus vulgaris and bullous pemphigoid. Am J Dermatopathol 1995;17:511–516.
Ninomiya J, Nakabayahsi A, Sei Y, Takiuchi I: Bullous pemphigoid complicated with pemphigus vulgaris. Dermatology 1994;189(suppl 1):117–119.
Velthuis PJ, Hendriksen JC, Nefkens JJ: Combined features of pemphigus and pemphigoid induced by penicillamine. Br J Dermatol 1985;112:615–619.
Dobmeier LJ, Sams WM: Intercellular antibodies in a patient without clinical pemphigus. Ann NY Acad Sci 1973;177:218–223.
Ahmed AR, Workman S: Anti-intercellular substance antibodies. Arch Dermatol 1983;119:17–21.
Cram DL, Griffith MR, Fukuyama K: Pemphigus-like antibodies in cicatricial pemphigoid. Arch Dermatol 1974;109:235–238.
Kumar V, Yarbrough C, Beutner E: Complement-fixing intercellular antibodies in a case of cicatricial pemphigoid. Arch Dermatol 1980;116:812–814.
Roenigk HH, Deodhar S: Pemphigus treatment with azathioprine. Arch Dermatol 1973;107:353–357.
Buhac J, Bhol K, Padilla T, Foster SC, Ahmed AR: Coexistence of pemphigus vulgaris and ocular cicatricial pemphigoid. J Am Acad Dermatol 1996;34:884–886.
Korman NJ, Stanley JR, Woodley DT: Coexistence of pemphigus foliaceus and bullous pemphigoid. Arch Dermatol 1991;127:387–390.
Rantanen T, Niemi KM: A further case of coexisting bullous pemphigoid and pemphigus foliaceus. Br J Dermatol 1979;101:611–612.
Harrington CI, Sneddon IB: Coexistence of bullous pemphigoid and pemphigus foliaceus. Br J Dermatol 1979;100:441.
Heine KG, Kumar A, Jordan RE: Pemphigus-like antibodies in bullous pemphigoid. Arch Dermatol 1977;113:1693–1695.
Liu Z, Diaz LA, Troy JL, Taylor AF, Emery DJ, Fairley JA, Guidice GJ: A passive transfer model of the organ-specific autoimmune disease, bullous pemphigoid, using antibodies generated against the hemidesmosomal antigen, BP 180. J Clin Invest 1993;92:2480–2488.
Jeffes EWB III, Kaplan RP, Ahmed AR: Acantholysis produced in vitro with pemphigus serum: Hydrocortisone inhibits acantholysis, while dapsone and 6-mercaptopurine do not inhibit acantholysis. J Clin Immunol 1984;4:359–363.
Shirahama S, Furukawa F, Takigawa M: Recurrent pemphigus vulgaris limited to the surgical area after mastectomy. J Am Acad Dermatol 1998;39:352–355.
Floden CH, Gentele H: A case of clinically typical dermatitis herpetiformis (Duhring) presenting acantholysis. Acta Derm Venereol 1955;35:128–131.
Winkelmann RK, Roth HL: Dermatitis herpetiformis with acantholysis or pemphigus with response to sulfonamides. Arch Dermatol 1960;82:385–390.
Emmerson RW, Wilson-Jones E: Eosinophilic spongiosis in pemphigus. Arch Dermatol 1968;97:252–257.
De Mento FJ, Grover RW: Acantholytic herpetiform dermatitis. Arch Dermatol 1973;107:883–887.
Honeyman JF, Honeyman A, Lobitz WC, Storrs FJ: The enigma of bullous pemphigoid and dermatitis herpetiformis. Arch Dermatol 1972;106:21–25.
Watanabe K, Hashimoto T, Ishiko A, Shimizu H, Hangaku H, Kimura S, Nishikawa T: A case of bullous pemphigoid with antidesmoplakin autoantibodies. Dermatology 1994;189:126–128.
Hashimoto T, Amagai M, Murakami H, Higashiyama M, Hashimoto K, Nishikawa T: Specific detection of anti-cell surface antibodies in herpes gestationis sera. Exp Dermatol 1996;5:96–101.
Chan H: Pemphigus vulgaris associated with systemic lupus erythematosus. Int J Dermatol 1999;38:948.
Kuchabal DS, Kuchabal SD, Pandit AM, Nashi HK: Pemphigus vulgaris associated with systemic lupus erythematosus. Int J Dermatol 1998;37:636–638.
Patten SF, Valenzuela R, Dijkstra JW, Bergfeld WF, Slaughter S: Unmasking the presence of circulating pemphigus antibodies in a patient with coexistent pemphigus, SLE, multiple autoantibodies, and gastric carcinoma. Int J Dermatol 1993;32:890–892.
Fong PH, Chan HL: Systemic lupus erythematosus with pemphigus vulgaris. Arch Dermatol 1995;121:26–27.
Russell JG: Pemphigus, Sjögren’s syndrome and mucosal pigmentation. Acta Stomatol Int 1987;8:25–29.
Meiner Z, Zlotogorski A, Brautbar C: Pemphigus associated with multiple sclerosis. Clin Exp Dermatol 1992;17:217.
Friedel J, Jeandel C, Abensour M, Heid E: Multiple sclerosis and autoimmune skin bullae: A case of pemphigus. Dermatologica 1987;175:159–160.
Hamlet KR, Stevens SR, Gushurst C, Karabin G, Cooper KD: Juvenile pemphigus vulgaris associated with Grave’s disease. J Am Acad Dermatol 1995;33:132–134.
Shabbir SG, Hassan M, Kazmi SA, Suhail S: Myasthenia gravis and pemphigus vulgaris. J Pak Med Assoc 1984;34:349–351.
Noguchi S, Nishitani H: Case of myasthenia gravis associated with pemphigus vulgaris thymectomy: Immunological studies and a review of the literature. Rinsho Shinkeigaku 1976;16:625–632.
Shapiro M, Jimenez S, Werth VP: Pemphigus vulgaris induced by D-penicillamine therapy in a patient with systemic sclerosis. J Am Acad Dermatol 2000;42:297–299.
Katz AL, Nashel DJ, Goard CP, Bauer H: Pemphigus vulgaris and lymphoma in a patient with scleroderma. South Med J 1979;72:1463–1466.
Huang CY, Chen TC: Bullous pemphigoid associated with systemic lupus erythematosus: The discrimination of antibasement membrane zone antibody. Int J Dermatol 1997;36:40–42.
Stoll DM, King LE Jr: Association of bullous pemphigoid with systemic lupus erythematosus. Arch Dermatol 1984;120:362–366.
Clayton CA, Burnham TK: Systemic lupus erythematosus and coexisting bullous pemphigoid immunofluorescent investigations. J Am Acad Dermatol 1982;7:236–245.
Sant SM, O’Loughlin S, Murphy GM: Bullous pemphigoid and rheumatoid arthritis: Is there disease association? Ir J Med Sci 1997;166:106–107.
Hsu VM, Krey PR, Schwartz RA: Bullous pemphigoid and rheumatoid arthritis. Cutis 1989;43:30–32.
Giannini JM, Callen JP, Gruber GG: Bullous pemphigoid and rheumatoid arthritis. J Am Acad Dermatol 1981;4:695–697.
Walker MJ: Bullous pemphigoid and rheumatoid arthritis with herpes simplex vesicular fluid. Cutis 1997;19:93–94.
Yamamoti T, Yokoyama A, Mamada A, Miyazaki Y, Nishioka K: Familial occurrence of coexistence of bullous pemphigoid and Sjögren’s syndrome. Int J Dermatol 1998;37:475–476.
James WD: Bullous pemphigoid, myasthenia gravis, and thymoma. Arch Dermatol 1984;120:397.
Kirtschig G, Walkden VM, Venning VA, Wojnarowska F: Bullous pemphigoid and multiple sclerosis: A report of three cases in the literature. Clin Exp Dermatol 1995;20:449–453.
Masouyé I, Schmied E, Didierjean L, Abba Z, Saurat JH: Bullous pemphigoid and multiple sclerosis: More than coincidence? Report of three cases. J Am Acad Dermatol 1989;21:63–68.
Coopers A, Wells JV: Pemphigus foliaceus, myasthenia gravis, and thymoma in pattern serological evidence of SLE. Aust NZ J Med 1981;11:277–280.
Allen BR, Reeves WG: Pemphigus foliaceus associated with SLE. Br J Dermatol 1978;99:33–34.
Wilkinson SM, Smith AG, Davis MJ, Hollowood K, Dawes PT: Rheumatoid arthritis: An association with pemphigus foliaceus. Acta Derm Venerol 1992;72:289–291.
Falk ES: Pemphigus foliaceus in a patient with rheumatoid arthritis and Sjögren’s syndrome: A case report. Dermatologica 1979;158:348–354.
Kim HT, Kim SH, Kim JH, Kim MH, Lee CW: Coexistence of myasthenia gravis and pemphigus foliaceus. J Korean Med Sci 1995;10:298–302.
Barbosa ER, Alchorne AO, De Assis JL, Medawar J: Myasthenia gravis and pemphigus foliaceus. Med Cutan Ibero Lat Am 1982;10:283–288.
Imamura S, Takigawa M, Ikai K, Yoshinaga H, Yamada M: Pemphigus foliaceus, myasthenia gravis, thymoma and red cell aplasia: A case report and indirect immunofluorescence study on 38 patients with myasthenia gravis. Clin Exp Dermatol 1978;3:385–391.
Levine L, Bernstein JE, Soltani K, Medenica MM, Yung CW: Coexisting childhood pemphigus foliaceus and Graves’ disease. Arch Dermatol 1982;118:602–604.
Redman RS, Thorne EG: Cicatricial pemphigoid in a patient with systemic lupus erythematosus. Arch Dermatol 1981;117:109–110.
Spigel GT, Winkelmann RK: Cicatricial pemphigoid and rheumatoid arthritis. Arch Dermatol 1978;114:415–417.
Olsen KE, Holland EJ: The association between ocular cicatricial pemphigoid and rheumatoid arthritis. Cornea 1998;17:504–507.
Peyri J, Sevrvitje O, Ribera M, Henkes J, Ferrandiz C: Cicatricial pemphigoid in a patient with rheumatoid arthritis with penicillamine. J Am Acad Dermatol 1986;14:681.
Shuttleworth D, Graham-Brown RA, Hutchinson PE, Jollife DS: Cicatricial pemphigoid in D- penicillamine treated patients with arthritis – A report of three cases. Clin Exp Dermatol 1985;10:392–397.
Spigel GT: Association of cicatricial pemphigoid and rheumatoid arthritis. Arch Dermatol 1979;115:108–109.
Callen JP: Internal disorders associated with bullous disease of the skin. A critical review. J Am Acad Dermatol 1980;3:107–119.
Reunala T, Collin P: Diseases associated with dermatitis herpetiformis. Br J Dermatol 1997;136:315–318.
Zaitz C, Guimaraes Proenca N, Duarte I, Muller H, Pinto Paes R: Dermatitis herpetiformis and systemic lupus erythematosus. Med Cutan Ibero Lat Am 1984;12:311–317.
Fraser NG, Rennie AG, Donald D: Dermatitis herpetiformis and Sjögren’s syndrome. Br J Dermatol 1979;100:213–215.
White SW, Tesar JT: Dermatomyositis and dermatitis herpetiformis. Arch Dermatol 1982;118:599–601.
Rothwell RS, Percy JS, Davis P: Dermatitis herpetiformis and rheumatoid arthritis. Arch Rheum Dis 1979;38:399.
Fischman AS, Abeles M, Zanetti M, Weinstein A, Rothfield NF: The coexistence of rheumatoid arthritis and systemic lupus erythematosus. J Rheumatol 1981;8:405–415.
Venegoni C, Chevallard M, Mele G, Banafi G, Carrabba M: The coexistence of rheumatoid arthritis and systemic lupus erythematosus. Clin Rheumatol 1987;6:439–445.
Brzezinska B, Graff-Wroblewska T: Case of coexistence of rheumatoid arthritis and systemic lupus erythematosus. Pol Tyg Lek 1973;28:1981–1983.
Venegoni C, Chevallard M, Mele G, Banfi G, Carrabba M: The coexistence of rheumatoid arthritis and systemic lupus erythematosus. Clin Rheumatol 1987;6:439–445.
Yamane K, Shome GP, Akama T, Suzuki H, Matsui H, Matsui Y, Kashiwagi H: Clinical features of patients with mild systemic lupus erythematosus. Scand J Rheumatol 1991;20:397–405.
Steinberg AD, Talal N: The coexistence of Sjögren’s syndrome and systemic lupus erythematosus. Ann Intern Med 1971;74:55–61.
Kameda H, Kuwana M, Hama N, Kaburaki J, Homma M: Coexistence of serum anti-DNA topoisomerase I and anti-Sm antibodies: Report of 3 cases. J Rheumatol 1997;24:400–403.
Lee CW, Kwon CW, Yoo DH, Kim SY: Linear scleroderma occurring in a patient with systemic lupus erythematosus – Short report. J Korean Med Sci 1994;9:197–199.
Shelkovitz-Shiloh I, Ehrenfeld M, Schewach-Millet M, Feinstein A: Coexistence of familial systemic lupus erythematosus and local scleroderma. Int J Dermatol 1992;31:819–820.
Chorzelski T, Jablonska S: Coexistence of lupus erythematosus and scleroderma in light of immunopathological investigations. Acta Derm Venereol 1970;50:81–85.
Chen HM, Tsai CP, Lin KP, Wang SJ, Wu ZA, Kao KP: Myasthenia gravis with hyperthyroidism, thymoma and serological evidence of systemic lupus erythematosus: A case report. Chung Hua I Hsueh Tsa Chih (Taipei) 1996;58:62–65.
Killian PJ, Hoffman GS: Coexistence of systemic lupus erythematosus and myasthenia gravis. South Med J 1980;73:244–246.
Sanchez de Rivera JM, Barbado Hernandez FJ, Vasquez Rodriguez JJ, Augado A, Garcia Puig J, Viguer Garcia-Moreno JM: Scleroderma with traces of disseminated lupus erythematosus associated with Hashimoto’s thyroiditis and papillary carcincoma of the thyroid gland. Med Clin (Barc) 1979;73:342–346.
Horiki T, Moriuchi J, Takaya M, Uchiyama M, Hoshina Y, Inada K, Inoko H Tsuji K, Ichikawa Y: The coexistence of systemic sclerosis and rheumatoid arthritis in five patients: Clinical and immunogenetic features suggest a distinct entity. Arthritis Rheum 1996;39:152–156.
Hrycaj P, Mackiewick S: The coexistence of mutilating rheumatoid arthritis, progressive sclerosis and polycythemia vera – A case report. J Rheumatol 1992;51:249–252.
Baron M, Srolovitz H, Lander P, Kapusta M: The coexistence of rheumatoid arthritis and scleroderma: A case report and review of the literature. J Rheumatol 1982;9:947–950.
Bhettay EM, Kalla AA: Coexistence of myasthenia gravis and seropositive juvenile chronic arthritis. Clin Exp Rheumatol 1992;10:499–501.
LeRiche NG, Bell DA: Hashimoto’s thyroiditis and polyarthritis: A possible subset of seronegative polyarthritis. Ann Rheum Dis 1984;43:594–598.
Reiner M, Goldhirsch A, Kaplan E, Luscieti P, Pedrini E, Noseda G: Unusual autoimmune and neoplastic associated diseases in Sjögren’s syndrome. Schweiz Med Wochenschr 1979;109:1741–1742.
Fryze W, Obiedzinski, R, Klos M: Coexistence of multiple sclerosis and myasthenia gravis. Neurol Neurochir Pol 1991;25:259–262.
Yasuda M, Nobunaga M: The association of myasthenia gravis and connective tissue diseases – The role of Sjögren’s syndrome. Fukuoka Igaku Zasshi 1994;85:38–51.
Widjaja A, Rademaker J, Golkel C, Holstein A, Leifke E, Wat N: Graves ophthalmopathy and ocular myasthenia. Ophthalmologe 2000;97:38–40.
Roitt IM, Hutchings PR, Dawe KI, Sumar N, Bodman KB, Cooke A: The forces driving autoimmune disease. J Autoimmun 1992;5:11–26.
Coutinho A: The network theory: 21 years later. Scand J Immunol 1995;42:3–8.
De Carli, D’Elios MM, Zancuoghi G, Romagnani S, Del Prete G: Human Th1 and Th2: Functional properties, regulation of development and role in autoimmunity. Autoimmunity 1994;18:301–308.
Nicholson LB, Kuchroo K: Manipulation of the Th1/Th2 balance in autoimmune disease. Curr Opin Immunol 1996;8:837–842.
Lo D, Reilly C, Marconi LA, Ogata L, Wei O, Prud’homme G, Kono D, Burkly L:. Regulation of CD4 T cell reactivity to self and non-self. Int Rev Immunol 1995;13:147–160.
Van der Meide PH, Schellekens H: Cytokines and the immune response. Biotherapy 1996;8:243–249.
Cavallo MG, Pozzilli P, Thorpe R: Cytokines and autoimmunity. Clin Exp Immunol 1994;96:1–7.
Van Parijs L, Perez VL, Abbas AK: Mechanisms of peripheral T cell tolerance. Novartis Found Symp 1998;215:5–14, discussion 14–20, 33–40.
Ahmed AR, Yunis EJ, Khatri K, Wagner R, Notani G, Awdeh Z, Alper CA: Major histocompatibility complex haplotype studies in Ashkenazi Jewish patients with pemphigus vulgaris. Proc Natl Acad Sci USA1990;87:7568–7662.
Ahmed AR, Wagner R, Khatri K, Notani G, Awdeh Z, Alper CA, Yunis EJ: Major histocompatibility complex haplotype and class II genes in non-Jewish patients with pemphigus vulgaris. Proc Natl Acad Sci USA 1991;88:5056–5060.
Wucherpennig KW, Yu B, Bhol K, Monos DS, Argyris E, Karr RW, Ahmed AR, Strominger JL: Structural basis of major histocompatibility complex (MHC) linked susceptibility to autoimmunity: Charged residues of a single MHC binding pocket confer selective presentation of self peptides in pemphigus vulgaris. Proc Natl Acad Sci USA 1995;92:11935–11939.
Delgado JC, Turbay D, Yunis EJ, Yunis JJ, Morton ED, Bhol K, Norman R, Alper CA, Good RA, Ahmed AR: A common MHC class II allele HLA-DQB1*0301 is present in clinical variants of pemphigoid. Proc Natl Acad Sci USA 1996;93:8569–8571.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.