Ulceration is the process by which tissue erodes through a protective surface layer, creating an open sore that exposes the tissue underneath. It can happen on the stomach lining, on the skin, inside the mouth, on the surface of the eye, or along the intestinal wall. Despite appearing in wildly different parts of the body, every ulcer shares one basic feature: the body’s defenses at that site have been overwhelmed, and the tissue is breaking down faster than it can repair itself.
How Every Ulcer Starts
Your body is lined with protective surfaces. The stomach has a mucus-and-bicarbonate barrier that shields it from its own acid. The skin has multiple layers of cells, blood vessels, and connective tissue that resist mechanical and chemical damage. The cornea of the eye, the lining of the mouth, and the walls of the intestine each have their own versions of this defense system. Ulceration happens when something disrupts one of these barriers badly enough, or for long enough, that the tissue beneath is exposed and begins to break down.
The specific trigger varies by location. In the stomach, it might be a bacterium or a medication. On the skin, it could be unrelieved pressure, poor blood flow, or nerve damage. In the bowel, it might be a misdirected immune response. But the underlying pattern is the same: a protective surface fails, destructive forces gain access to deeper tissue, and the body cannot keep up with the damage.
Peptic Ulcers From Bacteria and Painkillers
Peptic ulcers form in the stomach or the first part of the small intestine (the duodenum), and the two biggest culprits are the bacterium Helicobacter pylori and nonsteroidal anti-inflammatory drugs like ibuprofen and aspirin. These work through different but related mechanisms.
H. pylori colonizes the stomach lining and triggers persistent inflammation. The bacterium can survive the stomach’s acidic environment by burrowing into the mucus layer and altering conditions around itself. Over time, the chronic inflammation it causes weakens the mucosal barrier and lets acid attack the underlying tissue. That said, most people infected with H. pylori never develop an ulcer. Research has shown that differences between bacterial strains influence how aggressively the immune system responds, which helps explain why some carriers get sick and others do not.1PubMed. Pathophysiology of Helicobacter pylori-induced gastritis and peptic ulcer disease
NSAIDs cause ulcers by a different route. These drugs work by blocking enzymes called cyclooxygenases, which produce prostaglandins. Prostaglandins do a lot of heavy lifting in stomach defense: they stimulate mucus and bicarbonate secretion, promote blood flow to the stomach lining, and help damaged cells regenerate. When NSAIDs suppress prostaglandin production, virtually every component of that defense weakens.2PubMed. Prostaglandins, NSAIDs, and gastric mucosal protection: why doesn’t the stomach digest itself? NSAIDs also cause direct chemical injury to the mucosal surface on contact, so the damage is both local and body-wide.3PubMed. Review article: cellular and molecular mechanisms of NSAID-induced peptic ulcers
The standard treatment for peptic ulcers centers on acid suppression. Proton pump inhibitors reduce the amount of acid the stomach produces, and meta-analyses have confirmed that the degree and duration of acid suppression are the main factors that determine how well an ulcer heals.4PubMed Central. Progress with proton pump inhibition When H. pylori is present, a course of antibiotics to eradicate the bacterium is added. If NSAIDs are involved, stopping or switching the medication is the first step. Proton pump inhibitors produce excellent healing of peptic ulcers in general.5PubMed Central. Pharmacology of proton pump inhibitors
Pressure Ulcers
Pressure ulcers, sometimes called bedsores or decubitus ulcers, develop when sustained mechanical force compresses the skin and underlying tissue against a hard surface, usually a mattress or wheelchair. The core problem is ischemia: the pressure squeezes blood vessels shut, cutting off oxygen and nutrients to the tissue.6PubMed Central. Pressure ulcers: Back to the basics Without blood flow, cells die, and the tissue begins to break down from the inside out.
Pressure alone is not the whole story. Shear forces, where the skin slides in one direction while deeper tissue stays anchored to bone, add an extra layer of damage. A systematic review found that while pressure reduces blood flow in a dose-dependent way (the harder the squeeze, the less blood gets through), shear on top of pressure further worsens tissue viability.7PubMed. The effect of pressure and shear on tissue viability of human skin in relation to the development of pressure ulcers: a systematic review Superficial skin damage tends to be driven more by shear, while deeper tissue destruction comes primarily from high pressure over bony prominences like the tailbone, heels, and hips.8PubMed Central. Our contemporary understanding of the aetiology of pressure ulcers/pressure injuries
People who are bedridden, wheelchair-bound, or unable to reposition themselves are at the highest risk. Moisture from incontinence or sweat makes the skin more vulnerable. Medical devices like oxygen masks and splints can also create enough localized pressure to cause ulceration if they are not repositioned regularly.
Leg Ulcers From Faulty Circulation
Leg ulcers fall into two broad categories depending on whether the problem is in the veins or the arteries, and the distinction matters because the mechanisms and the appearance of the ulcers are quite different.
Venous leg ulcers result from chronic venous insufficiency, a condition where the valves inside leg veins stop working properly. Healthy valves ensure blood flows upward toward the heart, but when they fail, blood pools in the lower legs and the pressure inside the veins rises. This venous hypertension triggers a cascade of problems: red blood cells leak out of swollen capillaries and break down, depositing iron in the surrounding tissue; white blood cells flood the area and release inflammatory chemicals; and over time the skin and fat layer thicken and harden, a process called lipodermatosclerosis.9PubMed Central. Chronic venous insufficiency and venous leg ulcers: Aetiology, on the pathophysiology-based treatment The chronic inflammation eventually overwhelms the skin, and an ulcer opens up, often on the inner ankle.10PubMed. Pathophysiology of venous ulceration The initial trigger can be traced to changes in the way blood flow pushes against the inner walls of veins, which sets the inflammatory process in motion.11PubMed. Molecular mechanisms in chronic venous insufficiency
Arterial ulcers develop for the opposite reason: not enough blood getting in, rather than too much staying put. Atherosclerosis (the buildup of fatty deposits inside arteries) narrows the blood vessels that supply the legs and feet. The resulting lack of oxygen and nutrients starves the tissue, which breaks down and ulcerates. Arterial ulcers tend to appear on the toes, feet, and other far-flung parts of the lower extremity. They are often extremely painful, especially at night, and the affected limb usually feels cool to the touch with weak or absent pulses.12PubMed Central. Venous and arterial leg ulcers
Compression therapy with bandages or stockings is a mainstay for venous ulcers because it counteracts the blood pooling that drives the inflammation. Arterial ulcers, by contrast, need the opposite approach: restoring blood flow through medication or surgical intervention. Applying compression to a leg with poor arterial supply can make things worse, which is why distinguishing between the two types is critical.
Diabetic Foot Ulcers
Diabetes creates a particularly nasty combination of factors that all converge on the feet. Sensory neuropathy, the loss of feeling in the feet, is the most recognized component. People with advanced diabetic neuropathy can step on a nail, develop a blister, or rub a raw spot inside a shoe without ever noticing. Without pain to signal a problem, minor injuries go unattended and develop into open ulcers.13Journal of Wound Management and Research. Investigating Diabetic Foot Pathophysiology and Amputation Prevention Strategies through Behavioral Modification – Section: Neuropathy
Motor neuropathy adds a second layer of risk. As the nerves that control foot muscles deteriorate, the muscles weaken and the foot gradually deforms. Toes may curl, the arch may flatten, and the way weight is distributed during walking shifts. These changes concentrate abnormal mechanical pressure on small areas of the sole, which accelerates tissue breakdown in those spots.
On top of the nerve damage, diabetes harms the microcirculation, the tiny blood vessels that deliver oxygen and nutrients to the skin. Research has shown that neuropathy, mechanical stress, and large-vessel disease all interact with this microcirculation, and when capillary blood flow can no longer meet the skin’s basic nutritional needs, ulceration follows.14PubMed. Aetiology of diabetic foot ulceration: a role for the microcirculation? This triple threat of no sensation, abnormal pressure, and compromised blood supply is why diabetic foot ulcers are so common and so difficult to manage.
Stress Ulcers During Critical Illness
Stress ulcers are a different beast from the peptic ulcers most people think of. They develop in critically ill patients, often in the ICU, and the mechanism is tied to the body’s emergency response rather than to bacteria or medications. When someone is critically ill from trauma, burns, sepsis, or major surgery, the body diverts blood away from the gut and toward vital organs like the brain and heart. This response, called splanchnic vasoconstriction, starves the stomach lining of oxygen. The resulting ischemia weakens mucosal defenses, and the stomach’s own acid and digestive enzymes then attack the unprotected tissue.15PubMed Central. Stress ulceration: prevalence, pathology and association with adverse outcomes
Stress ulcers tend to be shallow erosions scattered across a wide area of the stomach, rather than the single deep crater typical of a peptic ulcer. Because ICU patients are already medically fragile, even modest bleeding from these erosions can be dangerous. Prophylactic acid suppression is standard in many ICU protocols for high-risk patients.
Why Some Ulcers Refuse to Heal
Under normal circumstances, the body is reasonably good at repairing wounds. An acute injury triggers an orderly sequence: inflammation clears debris and fights infection, new tissue grows in to fill the gap, and the surface re-forms. Chronic ulcers get stuck somewhere in this process, usually in the inflammatory phase, cycling through damage and partial repair without ever reaching closure.
Bacterial biofilms are one of the biggest obstacles. Bacteria in a chronic wound do not just float around individually. They organize into structured communities encased in a protective slimy matrix. This biofilm shields them from both the immune system and antibiotics, and it sustains a state of low-grade inflammation that prevents the wound from progressing to the healing stages.16PubMed Central. Microbial Biofilms as Barriers to Chronic Wound Healing: Diagnostic Challenges and Therapeutic Advances Research suggests biofilms are present in nearly all chronic wounds. Animal studies have directly demonstrated that bacterial biofilms delay the regrowth of skin over a wound.17PubMed. Staphylococcal biofilms impair wound healing by delaying reepithelialization in a murine cutaneous wound model The biofilm also impairs the formation of granulation tissue (the pink, bumpy tissue that fills in a healing wound) and reduces how well antimicrobial treatments work.18PubMed Central. Biofilm delays wound healing: A review of the evidence
At the molecular level, enzymes called matrix metalloproteinases play a crucial role. These enzymes normally help remodel tissue during healing by breaking down and reorganizing structural proteins like collagen. In chronic ulcers, certain metalloproteinases become overactive. Research on nonhealing venous ulcers found that two collagen-degrading enzymes in particular were overproduced in wounds that refused to close, suggesting that this imbalance may be a central driver of chronicity.19PubMed Central. Role of matrix metalloproteinases in non-healing venous ulcers In other words, the body’s own tissue-remodeling machinery goes into overdrive and destroys new tissue as fast as it forms.
Complications That Turn Ulcers Dangerous
Most ulcers are painful and debilitating, but certain complications elevate them from chronic nuisance to medical emergency. Peptic ulcers can erode into a blood vessel and cause internal bleeding, or they can bore completely through the stomach or intestinal wall (perforation), spilling contents into the abdominal cavity. Despite improvements in medical management over recent decades, complications still occur in roughly one in five to one in ten patients with peptic ulcer disease.20PubMed Central. Perforated and bleeding peptic ulcer: WSES guidelines Perforation requires emergency surgery, and bleeding can be life-threatening if not controlled quickly.
Chronic skin ulcers carry a different long-term risk. Wounds that persist for years can occasionally undergo malignant transformation, developing into skin cancer at the ulcer site. A population-based study spanning 25 years found that among patients with chronic leg ulcers, skin cancer in the wound occurred at a rate of about 470 per 100,000 patients, with basal cell carcinoma and squamous cell carcinoma accounting for the vast majority of cases. The risk was concentrated in elderly patients.21PubMed Central. Skin Cancer Associated With Chronic Leg Ulcers in the Population of Olmsted County, Minnesota This phenomenon, historically known as Marjolin’s ulcer when it involves squamous cell carcinoma arising in a chronic wound, is a reminder that any ulcer lasting months or years without healing deserves a thorough evaluation, including biopsy if the wound changes in appearance.
Ulceration in the Mouth, Eyes, and Bowel
Although stomach and skin ulcers get the most attention, ulceration can occur on almost any tissue surface. Oral aphthous ulcers, commonly called canker sores, are small painful craters on the inside of the cheeks, lips, or tongue. They are extremely common, and despite decades of study, their exact cause remains unclear. Various bacteria have been implicated, and immune responses against the cells lining the mouth appear to play a role, but no single definitive trigger has been established.22PubMed Central. Oral Aphthous: Pathophysiology, Clinical Aspects and Medical Treatment Stress, nutritional deficiencies, hormonal shifts, and minor mouth injuries (like biting the inside of your cheek) are all thought to contribute.
The cornea, the clear front surface of the eye, can ulcerate when infection takes hold. Bacterial, viral, fungal, and parasitic infections can all trigger it, and the destruction is driven in part by the same metalloproteinase enzymes that cause trouble in chronic skin ulcers. During corneal infection, these enzymes chew through the collagen that gives the cornea its structure, and the damage can persist even after the infection itself is controlled. If unchecked, the result can be permanent scarring, thinning of the cornea, or even perforation.23PubMed Central. The role of matrix metalloproteinases in infectious corneal ulcers
Inflammatory bowel disease produces some of the most dramatic examples of internal ulceration. Crohn’s disease and ulcerative colitis are both driven by an overactive immune response against the intestinal lining, but the pattern of damage differs. Crohn’s disease can affect any part of the digestive tract, producing patchy, discontinuous ulcers that may penetrate the full thickness of the bowel wall and sometimes form granulomas. Ulcerative colitis, by contrast, involves continuous inflammation of the colon’s inner lining, nearly always starting at the rectum and extending upward. The two diseases are channeled by different arms of the immune system, but both ultimately result in the immune system attacking its own gut tissue.24Journal of Clinical Investigation. The fundamental basis of inflammatory bowel disease
Toxin-Driven Ulceration and Buruli Ulcer
Most ulcers are caused by mechanical, vascular, or inflammatory processes. A less familiar mechanism involves a bacterium that produces a tissue-destroying toxin. Buruli ulcer is caused by Mycobacterium ulcerans, a relative of the bacteria that cause tuberculosis and leprosy. What makes this pathogen unusual is that it secretes a family of toxins called mycolactones, which directly kill tissue cells.25PubMed Central. Buruli Ulcer: Review of a Neglected Skin Mycobacterial Disease The necrosis can be extensive, eating away large areas of skin and soft tissue before the patient seeks treatment.
Buruli ulcer occurs in scattered foci around the world, with the heaviest concentration of cases in West Africa. It is classified as a neglected tropical disease, meaning it affects populations with limited access to healthcare and receives comparatively little research funding. The exact route of transmission is still debated, though contact with contaminated water environments is suspected. Early antibiotic treatment can prevent the worst outcomes, but delays in diagnosis, common in rural settings, allow the toxin to cause extensive destruction that may require surgery and prolonged wound care.26JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH. Metagenomics Comparison of Buruli and Non Buruli Ulcer Skin Wound
Wound Therapies That Help Ulcers Close
Treatment depends entirely on the type of ulcer, but a few principles cut across categories. For ulcers caused by acid, suppressing acid production is the key. For ulcers driven by poor blood flow, restoring circulation takes priority. For ulcers sustained by infection or biofilm, antimicrobial strategies are essential. And for all chronic wounds, keeping the wound bed clean, moist, and protected from further mechanical injury creates the environment most favorable for healing.
Negative pressure wound therapy (sometimes called wound vac therapy) has become a widely used tool for difficult chronic wounds. The technique applies controlled suction to the wound bed through a sealed dressing. This removes excess fluid, reduces swelling, and promotes the growth of new tissue. It has shown advantages across a range of clinical situations, including acute and chronic wounds, injuries where bone or tendons are exposed, and infections associated with orthopedic implants.27PubMed Central. The mechanism by which negative pressure wound therapy promotes wound healing
For venous leg ulcers specifically, compression bandaging remains the cornerstone. By squeezing the leg and supporting the faulty veins, compression reduces the venous hypertension that drives the inflammation. Arterial ulcers, on the other hand, often require vascular procedures to reopen or bypass blocked arteries before the wound can heal. Diabetic foot ulcers demand a combined approach: offloading pressure from the affected area (often with specialized footwear or casts), managing blood sugar, treating infection, and addressing circulation. The recurring theme across all ulcer types is that simply dressing the wound is rarely enough. Unless the underlying cause is addressed, the tissue will keep breaking down.