You have been logged out of VisualDx or your session has expired.

Please reload this page and sign into VisualDx to continue.

  VisualDx Mobile   Select Language

Get VisualDx Mobile

There are VisualDx mobile apps available for iOS and Android devices.

You will need a VisualDx account to use the mobile apps.

Already have an account? Sign In or
sign up for a free trial.

Users with VisualDx accounts earn CME credits for using VisualDx.

Already have an account? Sign In or
sign up for a free trial.

Create a Personal Account

E-mail (username)
Verify Password
First Name
Last Name

Personal Account Created

Mobile Access

You can now download VisualDx for your iOS and Android devices. Launch the VisualDx app from your device and sign in using your VisualDx personal account username and password.

CME Certification

Sign in with your personal account to earn and claim CME credits through VisualDx. Credits can be earned by building a differential or looking up a diagnosis.

Version: 7.13.1441   (build df7aed4)
Select Language

Select Region

Send us your feedback

This field is required

Oops! There was an issue during submission. Please try again. If the problem persists, email with your feedback.

Thank You!

We appreciate your feedback and you will be hearing from us soon.


Share This Page

Thank You!

We have sent an e-mail with a link to the current page.


E-mail This Patient Information Sheet

Thank You!

We have sent an e-mail with this patient information.


Image Contributors


  • Christine Ahn MD
    Carl Allen DDS, MSD
    Brandon Ayres MD
    Howard P. Baden MD
    Robert Baran MD
    Keira Barr MD
    Gregory J. Basura MD, Ph.D
    Donald Belsito MD
    Jeffrey D. Bernhard MD
    Jesse Berry MD
    Victor Blanco MD
    Benjamin R. Bohaty MD
    William Bonnez MD
    Sarah Brenner MD
    Robert A. Briggaman MD
    Robert Brodell MD
    Roman Bronfenbrener MD
    Walter Brooks MD
    William Buckley MD
    Philip Bulterys MD, PhD (candidate)
    Susan Burgin MD
    Sonya Burton MD
    Sean P. Bush MD, FACEP
    Jeffrey Callen MD
    Scott Camazine MD
    Michael Cardwell
    Shelley D. Cathcart MD
    Robert Chalmers MD, MRCP, FRCP
    Chia-Yu Chu MD, PhD
    Flavio Ciferri MD
    Maria Rosa Cordisco MD
    Noah Craft MD, PhD
    John T. Crissey MD
    Harold E. Cross MD, PhD
    Charles E. Crutchfield III MD
    Adriana Cruz MD
    Donna Culton MD, PhD
    Bart J. Currie MBBS, FRACP, DTM&H
    Chicky Dadlani MD
    Alexander Dane DO
    C. Ralph Daniel III MD
    Thomas Darling MD, PhD
    William Delaney MD
    Damian P. DiCostanzo MD
    Ncoza Dlova MD
    James Earls MD
    Libby Edwards MD
    Melissa K. Egge MD
    Charles N. Ellis MD
    Rachel Ellis MD
    David Elpern MD
    Nancy Esterly MD
    Stephen Estes MD
    E. Dale Everett MD
    Janet Fairley MD
    David Feingold MD
    Jennifer J. Findeis-Hosey MD
    Benjamin Fisher MD
    Henry Foong MBBS, FRCP
    David Foster MD, MPH
    Brian D. Foy PhD
    Michael Franzblau MD
    Vincent Fulginiti MD
    Sunir J. Garg MD, FACS
    Kevin J. Geary MD
    Lowell Goldsmith MD, MPH
    Sethuraman Gomathy MD
    Bernardo Gontijo MD, PhD
    Kenneth Greer MD
    Kenneth G. Gross MD
    Alan Gruber MD
    Nathan D. Gundacker MD
    Akshya Gupta MD
    Vidal Haddad MSC, PhD, MD
    Edward Halperin MD, MA
    Ronald Hansen MD
    John Harvey
    Rizwan Hassan MD
    Michael Hawke MD
    Jason E. Hawkes MD
    Peter W. Heald MD
    David G. Hicks MD
    Sarah Hocker DO
    Ryan J. Hoefen MD, PhD
    Li-Yang Hsu MD
    William Huang MD
    Sanjana Iyengar MD
    Alvin H. Jacobs MD
    Saagar Jadeja MD
    Shahbaz A. Janjua MD
    Joshua J. Jarvis MD
    Kit Johnson
    Zachary John Jones MD
    Robert Kalb MD
    A. Paul Kelly MD
    Henry Kempe MD
    Loren Ketai MD
    Sidney Klaus MD
    Ashwin Kosambia MD
    Jessica A. Kozel MD
    Carl Krucke
    Mario E. Lacouture MD
    Joseph Lam MD
    Alfred T. Lane MD
    Edith Lederman MD
    Nahyoung Grace Lee MD
    Pedro Legua MD, PhD
    Robert Levin MD
    Bethany Lewis MD
    Sue Lewis-Jones FRCP, FRCPCH
    Taisheng Li MD
    Christine Liang MD
    Shari Lipner MD, PhD
    Adam Lipworth MD
    Jason Maguire MD
    Mark Malek MD, MPH
    Jere Mammino DO
    Ricardo Mandojana MD
    Lynne Margesson MD
    Thomas J. Marrie MD
    Maydel Martinez MD
    Ralph Massey MD
    Patrick McCleskey MD
    Karen McKoy MD
    Thomas McMeekin MD
    Josette McMichael MD
    Somchai Meesiri MD
    Joseph F. Merola MD
    Mary Gail Mercurio MD
    Anis Miladi MD
    Larry E. Millikan MD
    Dan Milner Jr. MD
    Zaw Min MD
    Stephanie Montero
    Alastair Moore MD
    Keith Morley MD
    Dean Morrell MD
    Samuel Moschella MD
    Rehan Naseemuddin MD
    Taimor Nawaz MD
    Vic Newcomer MD
    John Nguyen MD
    Matilda Nicholas MD
    Thomas P. Nigra MD
    Steven Oberlender MD, PhD
    Maria Teresa Ochoa MD
    Art Papier MD
    Lawrence Parish MD
    Tanner Parrent MD
    Mukesh Patel MD
    Lauren Patty-Daskivich MD
    David Peng MD, MPH
    Robert Penne MD
    Nitipong Permpalung MD
    Miriam Pomeranz MD
    Doug Powell MD
    Harold S. Rabinovitz MD
    Christopher J. Rapuano MD
    Sireesha Reddy MD
    Angela Restrepo MD, PhD
    Bertrand Richert MD, PhD
    J. Martin Rodriguez, MD, FACP
    Theodore Rosen MD
    Misha Rosenbach MD
    Scott Schiffman MD
    Robert H. Schosser MD
    Glynis A. Scott MD
    Carlos Seas MD, MSc
    Deniz Seçkin MD
    Daniel Sexton MD
    Paul K. Shitabata MD
    Tor Shwayder MD, FAAP, FAAD
    Elaine Siegfried MD
    Gene Sienkiewicz MD
    Christye Sisson
    Philip I. Song MD
    Mary J. Spencer MD, FAAP
    Lawrence B. Stack MD
    Sarah Stein MD
    William Van Stoecker MD
    Frances J. Storrs MD
    Erik J. Stratman MD
    Lindsay C. Strowd MD
    Erika Summers MD
    Belinda Tan MD, PhD
    Robert Tomsick MD
    Hensin Tsao MD, PhD
    Richard P. Usatine MD
    Jenny Valverde MD
    Vishalakshi Viswanath MD
    Susan Voci MD
    Lisa Wallin ANP, FCCWS
    Douglas Walsh MD
    Ryan R. Walsh MD
    George Watt MD
    Clayton E. Wheeler MD
    Sally-Ann Whelan MS, NP, CWOCN
    Jan Willems MD, PhD
    James Henry Willig MD, MPH
    Karen Wiss MD
    Vivian Wong MD, PhD
    Sook-Bin Woo MS, DMD, MMSc
    Jamie Woodcock MD
    Stephen J. Xenias MD
    Nathaniel Yohannes
    Lisa Zaba MD
    Vijay Zawar MD
    Bonnnie Zhang MD
    Carolyn Ziemer MD
    Jeffrey P. Zwerner MD, PhD


  • Am. Journal of Trop. Med & Hygiene
  • Armed Forces Pest Management Board
  • Blackwell Publishing
  • Bugwood Network
  • Centers For Disease Control and Prevention
  • Centro Internacional de Entrenamiento e Investigaciones Mèdicas (CIDEIM)
  • Dermatology Online Journal
  • East Carolina University (ECU), Division of Dermatology
  • International Atomic Energy Agency
  • Massachusetts Medical Society
  • Oxford University Press
  • Radiological Society of North America
  • Washington Hospital Center
  • Wikipedia
  • World Health Organization
ContentsSynopsisCodesLook ForDiagnostic PearlsDifferential Diagnosis & PitfallsBest TestsManagement PearlsTherapyDrug Reaction DataReferencesView all Images (3)
Drug-induced skin ulcers
Other Resources UpToDate PubMed

Drug-induced skin ulcers

Print Images (3)
Contributors: John Barbieri, Misha A. Rosenbach MD, Noah Craft MD, PhD
Other Resources UpToDate PubMed


Drug-induced cutaneous ulcers are a rare reaction associated with a few medications. This article focuses on commonly cited etiologies of these ulcers, but it does not address cutaneous ulcers secondary to drug-induced vasculitis or necrosis.


Hydroxyurea is used in the treatment of myeloproliferative disorders and to prevent painful attacks in sickle-cell disease. Painful leg ulcers occur in approximately 9% of patients taking long-term high-dose hydroxyurea (greater than 1 g/day for at least 1 year) for myeloproliferative diseases. The etiology of the leg ulcers is thought to be related to reduced skin cell viability due to inhibition of DNA synthesis. Some reports have described these ulcerations occurring when hydroxyurea therapy is stopped.

All-trans-Retinoic Acid
All-trans-retinoic acid (ATRA) is a generally well-tolerated induction chemotherapeutic agent used for acute promyelocytic leukemia. In rare cases, patients may develop multiple small, painless ulcers limited to the scrotum. The etiology of the scrotal ulcers is poorly understood, but they may be due to ATRA-induced release of cytokines and interleukins resulting in leukocyte activation and tissue damage.

Systemic Retinoids
Systemic retinoids, such as isotretinoin, are used in the treatment of a variety of skin conditions, including acne. There are rare reports of patients on isotretinoin subsequently developing ulcerative lesions consistent with pyoderma gangrenosum. The etiology is unknown but may be related to increased skin fragility, vascular proliferation, or alteration of neutrophil adhesion requirements.


Methotrexate is used for a variety of conditions, including psoriasis. Rarely, patients taking methotrexate for psoriasis have developed burning ulcerations at the sites of former psoriatic lesions, most commonly within days to weeks after starting therapy. Increases in the dose of methotrexate and concurrent use of NSAIDs are risk factors. Although the underlying mechanism is unknown, these ulcers are thought to be due to reduced keratinocyte viability as a result of DNA synthesis inhibition. Methotrexate can also induce oral ulcerations, which may be a sign of leukopenia.

Interferon-β is a therapy used in the treatment of multiple sclerosis. There are rare reports of patients developing ulcers at inoculation sites. The ulcer etiology is poorly understood but may be related to cytokine-mediated inflammatory reactions in the dermis due to interferon-β.

Antiviral Medications

There are rare case reports in the literature of patients developing genital ulcerations while receiving foscarnet or lamivudine antiviral therapies. This is most commonly reported in human immunodeficiency virus (HIV)-infected patients receiving foscarnet for resistant herpetic infections. The etiology of these ulcerations is not understood, but some have proposed that the excreted drug in the urine causes an irritant contact dermatitis after being trapped under the foreskin of the penis in uncircumcised male patients.

Kinase Inhibitors

Kinase inhibitors are used in the treatment of certain cancers. There are rare case reports in the literature of patients developing painful leg ulcers (sunitinib) and painful oral ulcers (imatinib). The etiologies of these reactions are unknown; however, in the case of sunitinib, it is thought that ischemia due to inhibition of vascular endothelial growth factor (VEGF) may play a role, with pre-existing diabetes being a risk factor.

Nicorandil is an anti-anginal medication that is not currently available in the United States but commonly used in Europe. In rare cases, it may be associated with painful ulcerations developing within several weeks to months after starting treatment. Oral ulcers are most common, but perianal ulcers and cutaneous ulcers are also seen. The etiology of the ulcers is unknown, but some have suggested that susceptibility to ulceration may be due to nicotinic acid accumulation or poor perfusion as a result of dilation of capacitance vessels.

Nicolau Syndrome
While not a cutaneous ulceration due to a particular medication, this syndrome describes a cutaneous phenotype associated with multiple different medications. Nicolau syndrome describes cutaneous ulceration due to intradermal or intravascular injection of a medication that leads to subsequent tissue necrosis. This has been described with a variety of drugs but may occur particularly with medications that exist in a crystallized form which are then not dissolved completely prior to injection. Some medications are stored refrigerated and intended to be brought to room temperature prior to injection; if the medications are injected while cold and crystals remain, it can lead to intravascular injury and tissue damage, and secondary cutaneous ulceration due to physical factors unrelated to the particular medication.

Illicit Drug Abuse

While beyond the scope of this section, it is possible for patients to develop cutaneous ulcerations at sites of intradermal injections of recreational drugs. "Skin popping," eg, self-injection of pentazocine, is an important example. Cocaine can also cause cutaneous ulcerations due to vasculitis and/or vasculopathy, particularly if the cocaine is diluted or adulterated with levamisole (see cocaine levamisole toxicity).


L27.1 – Localized skin eruption due to drugs and medicaments taken internally

403642000 – Cutaneous ulceration due to cytotoxic therapy

Look For

Subscription Required

Diagnostic Pearls

Subscription Required

Differential Diagnosis & Pitfalls

  • Herpes simplex virus – Vesicles and ulcers are usually grouped and painful. There is often a past history of similar lesions.
  • Ulceration may be seen in severe cases of varicella-zoster infection (shingles).
  • Vasculitis – Often painful cutaneous nodules (polyarteritis nodosa, livedo reticularis, other medium-vessel vasculitides) or palpable purpura (leukocytoclastic vasculitis) is present.
  • Pyoderma gangrenosum – Ulcers are painful, typically involve the lower extremities or hands, and may exhibit pathergy, which is the term used to describe the development of lesions of a particular disorder as a response to trauma.
  • Ecthyma – Superficial ulcerations with overlying gray-yellow to purple crust. Gram stain and cultures will reveal gram-positive cocci. Most commonly found on shins, legs, or buttocks.
  • Candidiasis – Patients typically report pruritus and burning. Potassium hydroxide (KOH) preparation will show pseudohyphae and budding yeasts.
  • Behçet syndrome – Oral aphthous-like ulcers are always present. Genital ulcers are fewer in number and may be associated with epididymitis. Pathergy occurs.
  • Ecthyma gangrenosum – Acute-onset disseminated painful hemorrhagic vesicles and bullae; associated with Pseudomonas aeruginosa infections in immunocompromised patients.
  • Secondary syphilis – Skin manifestations are variable, but most commonly include a diffuse, generalized papulosquamous eruption on the palms and soles.
  • Pemphigus vulgaris – Lesions are common on mucosal surfaces. Look for Nikolsky sign (superficial layer of skin slips freely over deeper layers with lateral pressure).
  • Bullous pemphigoid – Tense bullae present on the abdomen, thighs, and forearms. Significant pruritus is often present.
Also consider:
Anything that can cause cutaneous ulceration is in the differential.

Best Tests

Subscription Required

Management Pearls

Subscription Required


Subscription Required

Drug Reaction Data

Below is a list of drugs with literature evidence indicating an adverse association with this diagnosis. The list is continually updated through ongoing research and new medication approvals. Click on Citations to sort by number of citations or click on Medication to sort the medications alphabetically.

Subscription Required


Subscription Required

Last Updated: 02/19/2018
Copyright © 2018 VisualDx®. All rights reserved.
Drug-induced skin ulcers
Print 3 Images
View all Images (3)
(with subscription)
Drug-induced skin ulcers : Lower leg, Painful skin lesions, Scrotum, Skin erosion, Skin ulcer, Legs
Clinical image of Drug-induced skin ulcers
Copyright © 2018 VisualDx®. All rights reserved.