Physical Examination

Clinical manifestations of drug-induced pemphigus depend on the pathomechanism involved.

Disease caused by thiol drugs tends to present with the clinical findings of pemphigus foliaceus. Erythematous, scaly, crusted plaques occur primarily on the trunk. Occasional superficial vesicles and bullae may be seen, but usually, they are ruptured. Oral lesions do not occur.

Nonthiol drug-induced pemphigus presents predominantly as pemphigus vulgaris. Flaccid bullae and erosions occur on normal-appearing skin and also on the oral mucosa.^[11]

Causes

Speculation exists that genetic predisposition may be important in non-thiol–triggered pemphigus. Human leukocyte antigen DR4 (HLA-DR4) is associated with idiopathic pemphigus; however, few studies have provided data concerning HLA typing in cases of drug-induced pemphigus.

Thiols implicated in drug-induced pemphigus are as follows:

Penicillamine^[12]
Bucillamine^[13]
Captopril^[9]
Lisinopril^{[14, 15]}
Pyritinol
Thiopronine
Piroxicam
Thiamazole
5-Thiopyridoxine
Gold sodium thiomalat

Antibiotics implicated in drug-induced pemphigus are as follows:

Penicillin and derivatives
Cephalosporins
Quinolones^[16]
Rifampicin

Pyrazolone derivatives implicated in drug-induced pemphigus are as follows:

Phenylbutazone
Aminopyrine
Azapropazone
Oxyphenylbutazone

Miscellaneous drugs implicated in drug-induced pemphigus are as follows:

Propranolol
Metoprolol^[17]
Levodopa
Heroin
Progesterone
Carbamazepine^[18]
Phenobarbital
Lysine acetylsalicylate
Imiquimod^[19]
Glibenclamide^[20]
Cilazapril^[20]
Imatinib^[21]

Differential Diagnoses

Korman NJ, Eyre RW, Zone J, Stanley JR. Drug-induced pemphigus: autoantibodies directed against the pemphigus antigen complexes are present in penicillamine and captopril-induced pemphigus. J Invest Dermatol. 1991 Feb. 96 (2):273-6. [QxMD MEDLINE Link].
Feng S, Zhou W, Zhang J, Jin P. Analysis of 6 cases of drug-induced pemphigus. Eur J Dermatol. 2011 Sep-Oct. 21(5):696-9. [QxMD MEDLINE Link].
Brenner S, Goldberg I. Drug-induced pemphigus. Clin Dermatol. 2011 Jul-Aug. 29(4):455-7. [QxMD MEDLINE Link].
Pietkiewicz P, Gornowicz-Porowska J, Bowszyc-Dmochowska M, Dmochowski M. A retrospective study of antihypertensives in pemphigus: a still unchartered odyssey particularly between thiols, amides and phenols. Arch Med Sci. 2015 Oct 12. 11 (5):1021-7. [QxMD MEDLINE Link].
Yoshimura K, Ishii N, Hamada T, Abe T, Ono F, Hashikawa K, et al. Clinical and immunological profiles in 17 Japanese patients with drug-induced pemphigus studied at Kurume University. Br J Dermatol. 2014 Sep. 171(3):544-53. [QxMD MEDLINE Link].
Khashoggi M, Machet L, Perrinaud A, Brive D, Machet MC, Maruani A, et al. [D-penicillamine-induced pemphigus: changes in anti-32-2B immunostaining patterns]. Ann Dermatol Venereol. 2013 Aug-Sep. 140(8-9):531-4. [QxMD MEDLINE Link].
Wolf R, Brenner S. An active amide group in the molecule of drugs that induce pemphigus: a casual or causal relationship?. Dermatology. 1994. 189(1):1-4. [QxMD MEDLINE Link].
Brenner S, Bialy-Golan A, Anhalt GJ. Recognition of pemphigus antigens in drug-induced pemphigus vulgaris and pemphigus foliaceus. J Am Acad Dermatol. 1997 Jun. 36(6 Pt 1):919-23. [QxMD MEDLINE Link].
Pile HD, Yarrarapu SNS, Crane JS. Drug Induced Pemphigus. 2022 Jan. [QxMD MEDLINE Link]. [Full Text].
Ramseur WL, Richards F 2nd, Duggan DB. A case of fatal pemphigus vulgaris in association with beta interferon and interleukin-2 therapy. Cancer. 1989 May 15. 63(10):2005-7. [QxMD MEDLINE Link].
Venugopal SS, Murrell DF. Diagnosis and clinical features of pemphigus vulgaris. Dermatol Clin. 2011 Jul. 29(3):373-80, vii. [QxMD MEDLINE Link].
Nagao K, Tanikawa A, Yamamoto N, Amagai M. Decline of anti-desmoglein 1 IgG ELISA scores by withdrawal of D-penicillamine in drug-induced pemphigus foliaceus. Clin Exp Dermatol. 2005 Jan. 30(1):43-5. [QxMD MEDLINE Link].
Hur JW, Lee CW, Yoo DH. Bucillamine-induced pemphigus vulgaris in a patient with rheumatoid arthritis and polymyositis overlap syndrome. J Korean Med Sci. 2006 Jun. 21(3):585-7. [QxMD MEDLINE Link]. [Full Text].
Patterson CR, Davies MG. Pemphigus foliaceus: an adverse reaction to lisinopril. J Dermatolog Treat. 2004 Jan. 15(1):60-2. [QxMD MEDLINE Link].
Ballout RA, Musharrafieh U, Khattar J. Lisinopril-associated bullous pemphigoid in an elderly woman: a case report of a rare adverse drug reaction. Br J Clin Pharmacol. 2018 Nov. 84 (11):2678-2682. [QxMD MEDLINE Link]. [Full Text].
Anadolu RY, Birol A, Bostanci S, Boyvatt A. A case of pemphigus vulgaris possibly triggered by quinolones. J Eur Acad Dermatol Venereol. 2002 Mar. 16(2):152-3. [QxMD MEDLINE Link].
Patel S, Kim S, Allen C. Metoprolol-Induced Pemphigus-Like Reaction. Clin Adv Periodontics. 2019 Mar. 9 (1):24-28. [QxMD MEDLINE Link].
Patterson CR, Davies MG. Carbamazepine-induced pemphigus. Clin Exp Dermatol. 2003 Jan. 28(1):98-9. [QxMD MEDLINE Link].
Lin R, Ladd DJ Jr, Powell DJ, Way BV. Localized pemphigus foliaceus induced by topical imiquimod treatment. Arch Dermatol. 2004 Jul. 140(7):889-90. [QxMD MEDLINE Link].
Azad Khan AK, Johnston HH, Truelove SC. Proceedings: Bacterial breakdown of sulphasalazine (salazopyrin). Gut. 1975 Oct. 16(10):832. [QxMD MEDLINE Link].
Sood A, Sinha P, Raman DK, Sinha A. Imatinib-induced IgA Pemphigus: Subcorneal Pustular Dermatosis Type. Indian Dermatol Online J. 2018 Sep-Oct. 9 (5):331-333. [QxMD MEDLINE Link]. [Full Text].
Brenner S, Goldberg I. Drug-induced pemphigus. Clin Dermatol. 2011 Jul-Aug. 29 (4):455-7. [QxMD MEDLINE Link].
Maruani A, Machet MC, Carlotti A, Giraudeau B, Vaillant L, Machet L. Immunostaining with antibodies to desmoglein provides the diagnosis of drug-induced pemphigus and allows prediction of outcome. Am J Clin Pathol. 2008 Sep. 130(3):369-74. [QxMD MEDLINE Link].
Maruani A, Machet MC, Carlotti A, Giraudeau B, Vaillant L, Machet L. Immunostaining with antibodies to desmoglein provides the diagnosis of drug-induced pemphigus and allows prediction of outcome. Am J Clin Pathol. 2008 Sep. 130 (3):369-74. [QxMD MEDLINE Link].
Landau M, Brenner S. Histopathologic findings in drug-induced pemphigus. Am J Dermatopathol. 1997 Aug. 19(4):411-4. [QxMD MEDLINE Link].
Quaresma MV, Bernardes Filho F, Hezel J, Peretti MC, Kac BK, Azulay-Abulafia L. Dapsone in the treatment of pemphigus vulgaris: adverse effects and its importance as a corticosteroid sparing agent. An Bras Dermatol. 2015 May-Jun. 90 (3 Suppl 1):51-4. [QxMD MEDLINE Link].
Ghaedi F, Etesami I, Aryanian Z, et al. Drug-induced pemphigus: A systematic review of 170 patients. Int Immunopharmacol. 2021 Mar. 92:107299. [QxMD MEDLINE Link].
Brenner S, Srebrnik A, Goldberg I. Pemphigus can be induced by topical phenol as well as by foods and drugs that contain phenols or thiols. J Cosmet Dermatol. 2003 Jul. 2 (3-4):161-5. [QxMD MEDLINE Link].

Media Gallery

Early small blister filled with clear fluid arises on healthy skin.
Flaccid blister filled with clear fluid arises on healthy skin.
An erosion.

of 3

Author

Chris G Adigun, MD, FAAD Director and Physician, Dermatology and Laser Center of Chapel Hill; Senior Medical Advisor, Klara

Chris G Adigun, MD, FAAD is a member of the following medical societies: American Academy of Dermatology, American Society for Dermatologic Surgery, Council for Nail Disorders, North Carolina Dermatology Association, North Carolina Medical Society

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Amgen; Sciton; OrthoDermatologics; Lumenis; DermTech; PhotonMD; Galderma<br/>Received income in an amount equal to or greater than $250 from: Amgen; Lumenis; DermTech; Galderma.

Coauthor(s)

Omobola Onikoyi, DO, MSc American Osteopathic Association (AOA) Internship, Manchester Memorial Hospital, Eastern Connecticut Health Network

Omobola Onikoyi, DO, MSc is a member of the following medical societies: American Osteopathic College of Dermatology, American Vitiligo Research Foundation, Council for Nail Disorders, Medical Dermatology Society, National Psoriasis Foundation, North American Hair Research Society, Wound Healing Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Michael J Wells, MD, FAAD Dermatologic/Mohs Surgeon, The Surgery Center at Plano Dermatology

Michael J Wells, MD, FAAD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Texas Medical Association

Disclosure: Nothing to disclose.

Jeffrey J Miller, MD Associate Professor of Dermatology, Pennsylvania State University College of Medicine; Staff Dermatologist, Pennsylvania State Milton S Hershey Medical Center

Jeffrey J Miller, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Society for Investigative Dermatology, Association of Professors of Dermatology, North American Hair Research Society

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Diane M Scott, MD Dermatologist, Arch Health Partners

Diane M Scott, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

David Timothy Woodley, MD Professor and Chair, Department of Dermatology, Keck School of Medicine of the University of Southern California

David Timothy Woodley, MD is a member of the following medical societies: American Academy of Dermatology, American Association for the Advancement of Science, American College of Emergency Physicians, American College of Physicians, American Federation for Medical Research, American Society for Clinical Investigation, New York Academy of Medicine, Society for Investigative Dermatology, Southern Medical Association

Disclosure: Received consulting fee from Shire Pharmaceuticals for consulting.

Daniel Davis, MD Associate Professor, Departments of Dermatology, Otolaryngology, and Pathology, University of Arkansas for Medical Science

Disclosure: Nothing to disclose.

Acknowledgements

Kimberly I Soderberg, MD Consulting Staff, Oyster Point Dermatology

Kimberly I Soderberg, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Arkansas Medical Society, and Women's Dermatologic Society

Disclosure: Nothing to disclose.