History

Most patients develop the eruption a few weeks after starting therapy with the offending agent. In penicillamine use, the eruption may not develop until 6 months after the onset of therapy. Some patients may give a history of a nonspecific eruption prior to the development of pemphigus type lesions.

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.^[17]

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^[10]
Bucillamine^[11]
Captopril
Lisinopril^[12]
Pyritinol
Thiopronine
Piroxicam
Thiamazole
5-Thiopyridoxine
Gold sodium thiomalat

Antibiotics implicated in drug-induced pemphigus are as follows:

Penicillin and derivatives
Cephalosporins
Quinolones^[13]
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
Levodopa
Heroin
Progesterone
Carbamazepine^[14]
Phenobarbital
Lysine acetylsalicylate
Imiquimod^[15]
Glibenclamide^[16]
Cilazapril^[16]

Complications

Secondary infections may occur in drug-induced pemphigus because of the disruption of the skin barrier. Extensive erosions may promote entrance of bacteria, resulting in cutaneous infections, bacteremia, or sepsis.

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. [Medline].
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. [Medline].
Brenner S, Goldberg I. Drug-induced pemphigus. Clin Dermatol. 2011 Jul-Aug. 29(4):455-7. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
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. [Medline]. [Full Text].
Patterson CR, Davies MG. Pemphigus foliaceus: an adverse reaction to lisinopril. J Dermatolog Treat. 2004 Jan. 15(1):60-2. [Medline].
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. [Medline].
Patterson CR, Davies MG. Carbamazepine-induced pemphigus. Clin Exp Dermatol. 2003 Jan. 28(1):98-9. [Medline].
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. [Medline].
Azad Khan AK, Johnston HH, Truelove SC. Proceedings: Bacterial breakdown of sulphasalazine (salazopyrin). Gut. 1975 Oct. 16(10):832. [Medline].
Venugopal SS, Murrell DF. Diagnosis and clinical features of pemphigus vulgaris. Dermatol Clin. 2011 Jul. 29(3):373-80, vii. [Medline].
Brenner S, Goldberg I. Drug-induced pemphigus. Clin Dermatol. 2011 Jul-Aug. 29 (4):455-7. [Medline].
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. [Medline].
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. [Medline].
Landau M, Brenner S. Histopathologic findings in drug-induced pemphigus. Am J Dermatopathol. 1997 Aug. 19(4):411-4. [Medline].
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. [Medline].
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. [Medline].

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.