A handful of medicines taken for months or years are well known for causing open sores that refuse to heal. The main culprits are hydroxyurea (leg ulcers), nicorandil (mouth and anal ulcers), low-dose methotrexate, some cancer drugs and a few blood thinners. Street drugs are a separate and growing cause, because of what they are cut with.1SurgiColl. Xylazine-induced Skin Necrosis, Emerging Public Health Crisis and the Ethical Considerations in Surgical Reconstruction: A Case Report Most of these sores heal once the responsible drug is changed, so recognizing the link is what matters most.
Signs a Sore May Be Caused by a Medicine
An ulcer is an open sore where the skin’s surface has broken down and doesn’t close on its own. Drug-caused ulcers are typically very painful.2PubMed Central. Persistent nicorandil induced oral ulceration They often fail to respond to standard wound care or steroid creams.3PubMed Central. A Hydroxyurea-induced Leg Ulcer4PubMed Central. Persistent nicorandil induced oral ulceration The risk often builds with how long you have taken the drug, not how recently you started.5DermNet®. Hydroxyurea-induced cutaneous ulcer6PubMed. Drug-induced skin ulcer: real-world pharmacovigilance analysis based on the FDA adverse event reporting system
At home, the clues are a sore that has lasted weeks without shrinking despite dressings, and pain that seems out of proportion to its size. New sores may show up in similar spots, like both ankles or the mouth. The same drug may also cause other skin changes, such as dry skin or discolored nails.
A sore that looks like a simple scrape or pressure sore can still have a medicine behind it, because appearance is not a reliable guide. A medicine you have taken since long before the sore appeared is still a suspect. Other things also cause stubborn sores, so a medicine is one possibility to raise with a clinician, not a conclusion to reach alone.
Bring a full list of every medicine and dose, including ones taken for years. Note when the sore started and how it has changed, ideally with photos, and what treatments you have already tried. If you use street drugs, say so honestly, since it changes the likely cause.
Hydroxyurea and Leg Ulcers
Hydroxyurea is a pill used long term for blood disorders where the marrow makes too many cells.7PubMed. Successful treatment of hydroxyurea-associated chronic leg ulcers associated with squamous cell carcinoma Leg ulcers appear in up to 1 in 10 people on long-term treatment.8DermNet®. Hydroxyurea-induced cutaneous ulcer The damage builds up over time, harming skin cells, small blood vessels and collagen.9DermNet®. Hydroxyurea-induced cutaneous ulcer
The ulcers are usually round, sharply edged and painful, near the inner or outer ankle bone.10DermNet®. Hydroxyurea-induced cutaneous ulcer The surrounding skin is often red, thin and scarred.11DermNet®. Hydroxyurea-induced cutaneous ulcer The drug can also cause dry skin, darkened skin and discolored nails.12PubMed Central. A Hydroxyurea-induced Leg Ulcer In one reported case, ulcers that resisted treatment healed gradually after hydroxyurea was stopped.13PubMed Central. A Hydroxyurea-induced Leg Ulcer Rarely, long-standing ulcers have developed skin cancer, so a non-healing ulcer needs checking.14PubMed. Successful treatment of hydroxyurea-associated chronic leg ulcers associated with squamous cell carcinoma
Ordinary vein ulcers around the ankle usually come with leg swelling, brownish staining and aching that eases when the leg is raised. Hydroxyurea ulcers are more often sharply defined and notably painful, and they can appear without much swelling. Because both sit near the ankle, they are easily confused, and a doctor needs to know about the hydroxyurea to think of it. The compression bandaging that helps vein ulcers may not be enough here, which is one reason the medicine itself must be reviewed.
Don’t simply stop the pill yourself. It controls a blood disorder that can cause clots if untreated. Your hematologist can lower the dose or switch to another treatment, and even then the ulcer may take weeks to heal.
Nicorandil and Mouth or Anal Ulcers
Nicorandil is used to prevent angina chest pain in some countries.15Journal of the American Academy of Dermatology. Nicorandil-induced persistent cutaneous and mucosal ulcerations It can cause very painful ulcers, most often in the mouth or around the anus.16PubMed Central. Nicorandil‐induced ulcerations: a 10‐year observational study of all cases spontaneously reported to the French pharmacovigilance network17Journal of the American Academy of Dermatology. Nicorandil-induced persistent cutaneous and mucosal ulcerations They are large, deep and long-lasting, with punched-out edges.18PubMed Central. Persistent nicorandil induced oral ulceration About 1 in 4 reported cases followed a minor injury at the spot.19PubMed Central. Nicorandil‐induced ulcerations: a 10‐year observational study of all cases spontaneously reported to the French pharmacovigilance network They rarely respond to steroid treatments and usually need the drug changed.20PubMed Central. Persistent nicorandil induced oral ulceration
In the mouth, the ulcer sits on the tongue or cheek and makes eating and speaking uncomfortable. Around the anus, it can cause pain and bleeding during bowel movements and may form a deep, punched-out sore rather than a small crack. Ulcers can also appear elsewhere in the gut or near stomas, so unexplained pain in these places while taking the drug is worth reporting. Unlike a common canker sore, it does not clear in a week or two.
These ulcers are often missed. Mouth ulcers get blamed on dentures or biting, and anal ulcers can be mistaken for fissures or hemorrhoid problems. People may also have taken nicorandil for years before ulcers appear. Ask your cardiologist about alternatives rather than stopping on your own.
Methotrexate and Cancer Treatments
Surprisingly, most methotrexate ulcers occur at the low weekly doses of 7.5 to 25 mg used for psoriasis and arthritis.21PubMed Central. Low-dose methotrexate-induced ulcerated psoriatic plaques: A rare case Sores may form inside psoriasis patches or on normal skin.22Cosmoderma. Cutaneous ulceration as a manifestation of systemic methotrexate toxicity Sores on normal skin or in the mouth can signal the drug is affecting the whole body, but sores inside psoriasis patches matter too.23PubMed Central. Acute methotrexate-induced cutaneous ulceration in generalized pustular psoriasis: A case report and review of the literature New sores on methotrexate warrant a prompt call to your doctor.
The call matters because mouth sores or new skin sores can mean the drug is building up or affecting blood counts and the lining of the body. Your doctor may check blood tests, pause a dose or look for dosing errors. The drug is taken weekly, and taking it daily by mistake is a known danger. Keep taking folic acid if it was prescribed.
Some targeted cancer drugs, called EGFR inhibitors, often cause an acne-like rash and very dry skin.24PubMed. Clinical signs, pathophysiology and management of skin toxicity during therapy with epidermal growth factor receptor inhibitors About 1 in 4 people develop painful, slow-healing cracks on fingertips, heels and around nails.25PubMed Central. The incidence and management of cutaneous adverse events of the epidermal growth factor receptor inhibitors These cracks can become infected.26PubMed Central. The incidence and management of cutaneous adverse events of the epidermal growth factor receptor inhibitors Some chemotherapy drugs that leak out of the vein can destroy the tissue around the drip site.27PubMed Central. Chemotherapy Extravasation Causing Soft-Tissue Necrosis Mimicking Infection: A Longitudinal Case Study This damage can appear right away or days later, even away from the drip site.28Journal of the American Academy of Dermatology. Mitomycin extravasation injury: A case series
During treatment, moisturize hands and feet often with thick creams and wear gloves for wet chores. Tell your oncology team about red, oozing cracks, and report pain or blistering near an IV site at once.
Blood Thinners and Skin Death
Skin death happens when skin loses its blood supply. Warfarin can rarely cause this, particularly in people with low levels of protein C, a natural anti-clotting protein.29PubMed Central. Anticoagulation therapy for thromboembolism prevention: a case of warfarin-induced skin necrosis in the setting of protein C deficiency Other blood thinners can be used instead in those people.30PubMed Central. Anticoagulation therapy for thromboembolism prevention: a case of warfarin-induced skin necrosis in the setting of protein C deficiency Heparin can cause skin death through immune reactions in the blood vessels.31Journal of Obstetrics, Gynecology and Cancer Research. A Rare Case of Mortality Following Heparin-induced Necrotizing Skin Lesions as Thromboprophylaxis After Total Abdominal Hysterectomy Most red patches at heparin injection sites, though, are allergy-type reactions rather than the dangerous clotting form.32PubMed. Heparin-induced non-necrotizing skin lesions: rarely associated with heparin-induced thrombocytopenia
Warfarin skin death usually starts days after beginning the drug. A painful red area turns dark or purple, often on fatty areas like the thighs, breasts or belly. This is urgent and needs same-day care.
It is rare and is linked to a brief imbalance when the drug first lowers natural anti-clotting proteins faster than the clotting factors it targets. People with low protein C are at higher risk, and women and people with obesity are described more often. Because it happens near the start of treatment, someone who has taken warfarin steadily for years is unlikely to develop it for the first time. Your doctor may use other blood thinners if you have a known deficiency or past reaction.
Immune Reactions From Other Medicines
Vasculitis means inflamed blood vessels, which can produce raised purple spots, lumps and ulcers.33Reumatología Clínica (English Edition). Skin Lesions and Treatment With Tumor Necrosis Factor Alpha Antagonists Anti-TNF drugs for arthritis and bowel disease have been linked to it.34Reumatología Clínica (English Edition). Skin Lesions and Treatment With Tumor Necrosis Factor Alpha Antagonists35PubMed Central. Adalimumab‐induced leukocytoclastic vasculitis in a patient with ankylosing spondylitis: A case report Pyoderma gangrenosum, a rapidly growing painful ulcer, can be triggered by isotretinoin, propylthiouracil and sunitinib.36DermNet. Pyoderma Gangrenosum: Symptoms, Causes, and Treatment Sirolimus, a transplant drug, slows wound healing.37PubMed Central. Impaired Lower Extremity Wound Healing Secondary to Sirolimus After Kidney Transplantation38PubMed Central. Defects in skin γδ T cell function contribute to delayed wound repair in rapamycin-treated mice Excess iodide or bromide can rarely cause ulcerating skin eruptions.39Journal of the European Academy of Dermatology and Venereology. Halogenoderma: A Case Report and Review of the Literature
Anti-TNF vasculitis often appears as purple spots you can feel when you run a finger over them, most often on the legs. Some people also have ulcers, painful lumps, numbness or tingling, or fever and tiredness. It can start months or even years into treatment. A skin biopsy helps confirm it, and the usual approach is to reassess whether to continue or switch the drug.
An ulcer that grows fast and gets worse after minor injury may be pyoderma gangrenosum and needs prompt review. Purple spots that you can feel need prompt review. And tell surgeons you take sirolimus before any procedure.
Mouth and Skin Sores That Are Emergencies
Stevens-Johnson syndrome (SJS) is a drug reaction that kills and peels away the skin’s top layer.40PubMed Central. A Compilation of Drug Etiologies of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis It usually affects at least two moist surfaces, causing sore eyes, crusted lips, mouth ulcers or genital sores.41DermNet. Stevens Johnson Syndrome / Toxic Epidermal Necrolysis. SJS/TEN Painful sores plus a spreading rash after a new medicine means going to an emergency department.
It often begins with flu-like fever and sore eyes, usually within weeks of starting a new drug. The skin may become painful before it blisters. Bring the medicine’s name to the hospital.
A common drug rash is usually itchy, flat or bumpy and does not cause painful sores on the lips, mouth or eyes. Pain bigger than the rash looks is a warning feature. If you cannot tell the difference, treat it as the emergency.
Street Drugs That Cause Wounds
Xylazine, an animal sedative added to street opioids, causes distinctive ulcers, mainly on arms and legs.42SurgiColl. Xylazine-induced Skin Necrosis, Emerging Public Health Crisis and the Ethical Considerations in Surgical Reconstruction: A Case Report These worsen with continued use and can spread to deep infection and bone.43SurgiColl. Xylazine-induced Skin Necrosis, Emerging Public Health Crisis and the Ethical Considerations in Surgical Reconstruction: A Case Report Cocaine cut with levamisole, a deworming drug, can cause purple net-like patches and dying skin, classically on the ears.44Journal of the American Academy of Dermatology. Two cases of retiform purpura and cutaneous necrosis induced by levamisole contaminated cocaine It can also affect the legs.45PubMed Central. Retiform Purpura of the Lower Limbs Associated with Levamisole-Adulterated Cocaine Cocaine itself is a trigger of pyoderma gangrenosum.46PubMed. Drug-Induced Pyoderma Gangrenosum: A Review
Xylazine wounds often start as blisters or scabbed patches and become deep ulcers covered by dark, dry dead tissue. They can appear away from any injection site, including in people who smoke or snort. They heal poorly while use continues and can be very painful. Because xylazine is not an opioid, naloxone does not reverse its sedation, but it should still be used in a suspected opioid overdose.
People who inject black tar heroin are far more likely to get abscesses.47PubMed. Injection-site vein loss and soft tissue abscesses associated with black tar heroin injection: A cross-sectional study of two distinct populations in USA Injecting under the skin rather than into a vein raises that risk further.48PubMed. Injection-site vein loss and soft tissue abscesses associated with black tar heroin injection: A cross-sectional study of two distinct populations in USA Injecting black tar heroin under the skin has also been linked to wound botulism.49PubMed. Black Tar Heroin Skin Popping as a Cause of Wound Botulism
Watch for spreading redness, fever, black tissue, weakness or trouble swallowing, and get care promptly. Harm reduction services can offer test strips that identify xylazine, and wound clinics treat without judgment.
What to Do and What Else It Could Be
Only about 15 of 50 drugs most often reported with ulcers mention them in their leaflets.50PubMed. Drug-induced skin ulcer: real-world pharmacovigilance analysis based on the FDA adverse event reporting system A missing warning on your label doesn’t rule your medicine out. Skin sores are underreported as side effects, so labels often lag behind what clinicians see. The better test is timing: did the sore appear or worsen after starting or raising a dose, and has it improved when the dose changed? Ask your pharmacist or prescriber to check current reports, not just your leaflet, and report a suspected reaction through your country’s medicine safety reporting system. Never stop a heart, blood, transplant or cancer drug yourself; ask for a dose change or alternative.
Plenty of sores have nothing to do with drugs. Poor vein circulation causes ankle ulcers, often with swelling, while diabetes and artery disease cause foot ulcers. Infections and pressure sores are other common causes. Some mouth sores come from chemical burns, such as aspirin held against the gum.51PubMed Central. Oral chemical burns caused by topical application of policresulen: a case report Mouth ulcers from viruses or injury usually heal in about two weeks.