Digital ulcers are painful, open wounds that develop on the fingertips and hands of people with scleroderma. They result from damaged blood vessels that cannot deliver enough oxygen and nutrients to the skin, leading to tissue breakdown. While these ulcers can be challenging to manage, both standard treatments and emerging therapies are helping patients heal existing wounds and prevent new ones from forming.

Managing Wounds in Scleroderma: Goals and Approaches

When digital ulcers develop in people with scleroderma, the main goals of treatment focus on healing existing wounds, reducing pain, preventing infections, and stopping new ulcers from appearing. Treatment decisions depend on how severe the ulcers are, how many a person has, and whether they keep coming back. Some patients may have just one or two small ulcers that heal with basic care, while others experience multiple deep wounds that require more intensive approaches.^[2]

The approach to treating these ulcers typically combines several strategies. Doctors work to improve blood flow to the affected areas, protect the wounds from infection, manage pain, and help patients avoid triggers that can make things worse. There is currently no medication approved specifically for digital ulcers by the US Food and Drug Administration, though several treatments have shown promise in clinical trials and are used based on evidence from research studies.^[2]

Treatment usually requires a team approach involving rheumatologists, wound care specialists, and sometimes vascular surgeons. The severity of ulcers can be classified based on the number present: mild cases involve one to five ulcers, moderate cases have six to ten, and severe cases involve more than ten digital ulcers at one time.^[2]

Understanding How Digital Ulcers Develop

To understand why certain treatments are chosen, it helps to know how these ulcers form. In scleroderma, the blood vessels that supply the fingers undergo both structural and functional damage. The structural problem involves a process called intimal proliferation, where the inner lining of blood vessels thickens and becomes scarred, narrowing the space through which blood can flow. This damaged vessel lining also produces more chemicals that cause blood vessels to constrict while producing fewer chemicals that help them relax and widen.^[2]

The functional problem involves frequent episodes of vasospasm—sudden, excessive narrowing of blood vessels—which further reduces blood flow. This repeated constriction leads to progressive tissue damage from lack of oxygen and the formation of harmful molecules called oxygen-free radicals. The combination of structurally damaged vessels and frequent spasms creates an environment where the skin simply cannot receive enough blood to stay healthy. Eventually, the tissue begins to break down, forming an ulcer.^[2]

Digital ulcers are defined as areas of visible depth where both the outer layer of skin (epidermis) and the deeper layer (dermis) have been lost. They appear as open wounds with well-defined borders. The wounds typically occur in two locations: on the fingertips, where they result directly from inadequate blood supply, or over bony areas like knuckles, where repeated minor trauma to tight skin causes breakdown.^[2]

These ulcers are closely linked to Raynaud’s phenomenon, a condition where fingers change color in response to cold or stress. In scleroderma, Raynaud’s is “secondary,” meaning the blood vessels have permanent structural damage rather than just temporary overreaction to cold. Unlike primary Raynaud’s, where vessels return to normal between episodes, in scleroderma the vessels become progressively smaller and may even disappear entirely over time.^[6]

Standard Treatment Approaches

Non-Drug Measures: The Foundation of Care

Before starting any medication, doctors emphasize protective measures that all patients should follow. These lifestyle modifications form the foundation of ulcer prevention and management. Keeping the hands warm is critical, as cold triggers blood vessel constriction. Patients are advised to dress in layers, wear hats in cold weather (since heat loss from the head can trigger Raynaud’s throughout the body), and use insulated gloves or mittens. Even brief cold exposure in grocery stores or air-conditioned spaces can trigger attacks, so being prepared is essential.^[4]

Stress management is equally important, as emotional stress can trigger the same blood vessel constriction as cold exposure. Avoiding tobacco and caffeine is essential because these substances constrict blood vessels, directly working against treatment goals. For patients with existing ulcers, proper wound care is critical. Keeping ulcers clean and dry helps them heal faster, though this can be challenging since moisture tends to increase pain and discharge. Some patients find success using waterproof coverings during showers.^[2][4]

Basic wound care includes gentle cleaning and appropriate dressings. Some patients and doctors have found that medical-grade honey, particularly mānuka honey, has antibacterial properties that may help ulcers form protective scabs and heal more quickly. Band-aids or specialized wound dressings can protect ulcers from further trauma and contamination.^[6][17]

Calcium Channel Blockers: First-Line Medication

The first medication typically prescribed for Raynaud’s phenomenon and to prevent digital ulcers is a calcium channel blocker. These drugs work by relaxing blood vessels, allowing them to widen and increasing blood flow to the fingers. The most commonly used calcium channel blockers are nifedipine extended-release and amlodipine.^[4]

Doctors usually start with a low dose and gradually increase it until symptoms improve or the highest tolerable dose is reached. The medication needs to be taken regularly, not just when symptoms occur, because it works by maintaining steady blood vessel relaxation over time. Treatment duration is typically long-term or even lifelong, as the underlying blood vessel damage in scleroderma does not resolve on its own.^[4]

Side effects of calcium channel blockers can include dizziness, headaches, and swelling of the feet or ankles. These effects happen because the medication relaxes blood vessels throughout the body, not just in the fingers. If one calcium channel blocker causes intolerable side effects or doesn’t work well enough, doctors may try switching to a different one. Some patients cannot tolerate these medications at all and need alternative approaches.^[4]

Endothelin Receptor Antagonists: Targeting a Key Pathway

Endothelin is a powerful substance produced by blood vessel walls that causes vessels to constrict. In scleroderma, levels of endothelin are often elevated, contributing to poor blood flow. Drugs called endothelin receptor antagonists block the action of endothelin, helping blood vessels stay more relaxed and open.^[9]

The most studied endothelin receptor antagonist for digital ulcers is bosentan. Clinical trials have shown that bosentan can reduce the formation of new digital ulcers, though its effect on healing existing ulcers has been less consistent. The medication is taken as a pill, typically twice daily. Because bosentan can affect liver function, patients taking this medication need regular blood tests to monitor their liver enzymes.^[9]

Treatment with bosentan is usually considered when calcium channel blockers alone are not sufficient, particularly for patients who develop multiple or recurrent ulcers. The medication is used for long-term prevention rather than as a quick fix for active ulcers. Other side effects can include fluid retention, headache, and anemia. Due to potential risks to developing fetuses, the medication requires special precautions in women of childbearing age.^[9]

Prostacyclin Analogues: Potent Vasodilators

Prostacyclin is a naturally occurring substance in the body that relaxes blood vessels and prevents blood from clotting too easily. In scleroderma, prostacyclin levels may be reduced. Medications that mimic prostacyclin’s effects can significantly improve blood flow to the fingers.^[9]

The most commonly used prostacyclin analogue is iloprost. Unlike pills that are taken at home, iloprost is typically given intravenously (through an IV) over several hours. Treatment usually involves daily infusions for three to five consecutive days, and courses may be repeated periodically—for example, every few months or as needed when symptoms worsen or new ulcers appear. This intensive treatment requires hospital or clinic visits but can provide substantial relief.^[9]

During iloprost infusions, patients may experience side effects including headache, flushing, nausea, and jaw pain. These effects are related to the widespread blood vessel dilation the drug causes and usually resolve shortly after the infusion is complete. Despite these temporary discomforts, many patients find that the improvement in their digital ulcers makes the treatment worthwhile.^[9]

Clinical trials have shown that iloprost and other prostacyclin analogues can help both heal existing digital ulcers and prevent new ones from forming. The treatment appears to work better when given early, before ulcers become severe or chronic.^[9]

Phosphodiesterase-5 Inhibitors: Enhancing Blood Flow

Phosphodiesterase-5 (PDE-5) inhibitors are medications originally developed for other conditions but found to be helpful for improving blood flow in scleroderma. These drugs work by helping blood vessels relax and stay open. Examples include sildenafil and tadalafil.^[9]

These medications are taken as pills, making them more convenient than IV treatments. They are often used when calcium channel blockers alone are insufficient or when patients cannot tolerate other medications. Research has shown that PDE-5 inhibitors can reduce the frequency and severity of Raynaud’s attacks and may help with ulcer healing and prevention.^[9]

Side effects can include headache, flushing, indigestion, and nasal congestion—all related to the medication’s effect of widening blood vessels throughout the body. These medications require careful use in patients taking certain other drugs, particularly nitrates for heart conditions, due to the risk of dangerous blood pressure drops.^[9]

Topical Treatments: Targeting the Wound Directly

In addition to medications that improve blood flow throughout the body, some treatments are applied directly to the ulcer. Beyond basic wound dressings, medical-grade honey and other topical agents with antibacterial properties may be used. Topical nitroglycerin patches or creams, which release a substance that dilates blood vessels locally, have been tried with variable success.^[3]

Some clinicians use vitamin E topical gel, which may have antioxidant properties that help protect damaged tissue. However, evidence for many topical treatments remains limited, and they are generally used as supplementary measures rather than primary therapy.^[3]

Managing Complications: Infections and Severe Ischemia

When digital ulcers become infected, prompt treatment with antibiotics is necessary. Infections may involve just the skin (cellulitis) or, in more serious cases, can extend to the underlying bone (osteitis or osteomyelitis). Superficial infections may be treated with oral antibiotics at home, but deeper infections often require hospitalization for intravenous antibiotics and close monitoring.^[4]

In cases where blood flow is severely compromised and tissue death (necrosis) occurs, surgical options may be considered. Sometimes removing dead tissue (debridement) is necessary. In extreme cases, when tissue cannot be saved, amputation of part or all of a finger may be required to prevent further complications, though this is relatively rare.^[6]

Treatment in Clinical Trials: New Hope on the Horizon

Researchers are actively investigating new approaches to treating digital ulcers in scleroderma. These investigational treatments target different aspects of the disease process and offer hope for patients who don’t respond adequately to current standard therapies.

Advanced Prostacyclin Therapies and Delivery Methods

While intravenous iloprost is already used in standard care, researchers are exploring new prostacyclin analogues and alternative delivery methods. Some studies are investigating longer-acting formulations that might require less frequent administration, reducing the burden of repeated hospital visits. Other research focuses on oral prostacyclin analogues that could provide similar benefits without the need for intravenous access.^[9]

These newer prostacyclin-based therapies are being tested in Phase II and Phase III clinical trials. Phase II trials evaluate whether the treatment works and what doses are most effective, while Phase III trials compare the new treatment directly to existing standard treatments to determine if it offers meaningful advantages. Early results suggest these approaches may offer similar or improved benefits with better tolerability or convenience.^[9]

Botulinum Toxin Injections: A Novel Approach

In some specialized centers, doctors are studying the use of botulinum toxin (commonly known by brand names like Botox) injected around digital ulcers. This may sound surprising, since botulinum toxin is known for its use in cosmetic procedures, but the mechanism of action is quite different when used for ulcers.^[9]

The theory behind this approach is that botulinum toxin may help relax blood vessels and reduce pain signals. When injected into specific areas around the affected fingers, it might improve blood flow and reduce the severe pain associated with digital ulcers. This treatment is still considered experimental and is not widely available. It requires specialized training to perform correctly and is typically reserved for cases where other treatments have failed.^[9]

Small clinical studies have shown promising results, with some patients experiencing significant pain relief and improved ulcer healing. However, larger, controlled trials are needed to confirm these findings and establish the best techniques and dosing. The effects of botulinum toxin are temporary, lasting several months, so repeat treatments would likely be necessary.^[9]

Autologous Fat Grafting: Regenerative Medicine

Autologous fat grafting involves taking a patient’s own fat cells from one part of the body (usually the abdomen or thighs) and injecting them into the hands and fingers affected by scleroderma. This approach is based on the understanding that fat tissue contains stem cells and growth factors that may help regenerate blood vessels and improve tissue health.^[9]

The procedure requires a minor surgical operation to harvest the fat, process it, and then carefully inject it into the affected areas. Studies have reported that patients receiving this treatment may experience reduced frequency of Raynaud’s attacks, fewer new ulcers, and improved hand function. The injected fat may provide both mechanical cushioning to protect the fingers and biological factors that promote healing.^[9]

This treatment is not yet widely available and remains in the investigational stage. It requires specialized surgical expertise and is typically offered only at major medical centers with experience in scleroderma care. Clinical trials are ongoing to better understand which patients might benefit most from this approach and to standardize the technique.^[9]

Other Investigational Medications

Several other drugs are being studied in clinical trials for digital ulcers. Cilostazol, a medication that prevents blood from clotting too easily and also dilates blood vessels, has shown some promise in small studies. Statins, typically used to lower cholesterol, are being investigated because they may have additional effects on blood vessel function and inflammation.^[3]

Serotonin receptor antagonists and serotonin reuptake inhibitors are being explored based on the theory that serotonin may play a role in blood vessel constriction in scleroderma. N-acetylcysteine, an antioxidant medication, is being studied for its potential to reduce the harmful oxygen-free radicals that contribute to tissue damage.^[3]

These medications are in various stages of clinical development, from early Phase I trials (which primarily assess safety in small numbers of patients) to more advanced Phase II trials evaluating effectiveness. Results have been mixed, and more research is needed to determine which patients might benefit from these approaches.^[9]

Combination Therapy Approaches

An important area of investigation involves using multiple medications together. Since digital ulcers result from several different problems—blood vessel damage, constriction, inflammation, and impaired healing—combining treatments that target different mechanisms might be more effective than using any single drug alone.^[9]

Clinical trials are examining combinations such as endothelin receptor antagonists plus PDE-5 inhibitors, or calcium channel blockers plus prostacyclin analogues. Early results suggest that combination approaches may offer improved ulcer prevention and healing compared to single-drug therapy, though they also increase the risk of side effects and drug interactions. Careful monitoring is essential when using multiple medications.^[9]

Advanced Surgical Techniques

For patients with severe, recurrent digital ulcers who don’t respond to medications, surgical options are being refined. Digital sympathectomy is a procedure where surgeons remove scar tissue from the arteries and veins supplying the hand, potentially improving blood flow. This involves delicate microsurgery and is only performed at specialized centers.^[17]

Another experimental approach involves using hyperbaric oxygen chambers, where patients breathe pure oxygen in a pressurized room. This dramatically increases the amount of oxygen delivered to tissues throughout the body, potentially helping severe ulcers heal. While not suitable for everyone, some patients with very difficult-to-heal ulcers have seen improvement with this approach.^[17]

Participation in Clinical Trials

Clinical trials for digital ulcers in scleroderma are being conducted at major medical centers in the United States, Europe, and other regions. Patients interested in participating typically need to meet specific eligibility criteria, such as having active digital ulcers or a history of recurrent ulcers. Participation in a trial may provide access to promising new treatments before they become widely available, along with close medical monitoring.^[2]

Patients should discuss with their rheumatologist whether participation in a clinical trial might be appropriate for their situation. Factors to consider include the trial’s location, time commitment required, potential risks and benefits of the investigational treatment, and whether they would receive active treatment or possibly a placebo (though many trials now ensure all participants receive at least standard-of-care treatment).^[2]

Most common treatment methods

• Calcium channel blockers
  • First-line medications such as nifedipine extended-release and amlodipine that relax blood vessels and improve blood flow to the fingers
  • Taken as daily oral medication with gradual dose increases as tolerated
  • Side effects may include dizziness, headaches, and ankle swelling
• Endothelin receptor antagonists
  • Bosentan blocks endothelin, a substance that causes blood vessel constriction
  • Used primarily for preventing new digital ulcers rather than healing existing ones
  • Requires regular monitoring of liver function through blood tests
• Prostacyclin analogues
  • Iloprost is given intravenously over several hours for multiple consecutive days
  • Powerful vasodilators that help both heal existing ulcers and prevent new ones
  • Temporary side effects include headache, flushing, and nausea during infusions
• Phosphodiesterase-5 inhibitors
  • Sildenafil and tadalafil taken as oral medications
  • Help blood vessels relax and improve circulation
  • May reduce Raynaud’s attacks and assist with ulcer healing
• Wound care and topical treatments
  • Basic wound cleaning and appropriate dressings
  • Medical-grade honey for antibacterial protection
  • Keeping ulcers dry to promote scab formation and healing
• Lifestyle modifications
  • Avoiding cold exposure through layered clothing and protective gloves
  • Eliminating tobacco and caffeine which constrict blood vessels
  • Stress management to reduce Raynaud’s triggers
• Experimental treatments in clinical trials
  • Botulinum toxin injections for pain relief and improved blood flow
  • Autologous fat grafting to regenerate blood vessels and tissue
  • Advanced prostacyclin formulations and combination therapies
  • Digital sympathectomy surgery for severe, refractory cases
  • Hyperbaric oxygen therapy for difficult-to-heal ulcers