These ulcers are difficult to heal by basic wound care and require advanced therapy, such as hyperbaric oxygen therapy or bioengineered skin substitutes. If not taken care of in time, there are very high chances that these may become infected and eventually may have to be amputated. Individuals with history of previous ulcerations are 36 times more likely to develop another ulcer.

Compression stockings appear to prevent the formation of new ulcers in people with a history of venous ulcers.

The ulcers are caused by lack of blood flow to the capillary beds of the lower extremities. Most often endothelial dysfunction is causative factor in diabetic microangiopathy and macroangiopathy. In microangiopathy, neuropathy and autoregulation of capillaries leads to poor perfusion of tissues, especially wound base. When pressure is placed on the skin, the skin is damaged and is unable to be repaired due to the lack of blood perfusing the tissue. The wound has a characteristic deep, punched out look, often extending down to the tendons. The wounds are very painful.

Stem cell therapy may represent a treatment for promoting healing of diabetic foot ulcers. Diabetic foot ulcers develop their own, distinctive microbiota. Investigations into characterizing and identifying the phyla, genera and species of nonpathogenic bacteria or other microorganisms populating these ulcers may help identify one group of microbiota that promotes healing.

Approximately 15 percent of people with diabetes experience foot ulcers. And approximately 84 percent of lower limb amputations have a history of ulceration with only approximately half of amputees surviving for more than 2 years. 56 percent of individuals with foot ulcers who do not have an amputations survive for 5 years. Foot ulcers and amputations significantly reduce the quality of life. Approximately 8.8 percent of hospital admissions of diabetic patients are for foot related problems, and such hospital admissions are about 13 days longer than for diabetics without foot related admissions. Approximately 35 to 40 percent of ulcers recur within 3 years and up to 70 percent recur within 5 years. Diabetic foot disease is the leading cause of non-traumatic lower limb amputations.

The current ‘best’ practice in the UK is to treat the underlying venous reflux once an ulcer has healed. It is questionable as to whether endovenous treatment should be offered before ulcer healing, as current evidence would not support this approach as standard care. EVRA (Early Venous Reflux Ablation) ulcer trial - A UK NIHR HTA funded randomised clinical trial to compare early versus delayed endovenous treatment of superficial venous reflux in patients with chronic venous ulceration opened for recruitment in October 2013. The study hopes to show an increase in healing rates from 60% to 75% at 24 weeks.

Research from the University of Surrey and funded by the Leg Ulcer Charity is currently looking at the psychological impact of having a leg ulcer, on the relatives and friends of the affected person, and the influence of treatment.

There are over 100 risk factors for pressure ulcers. Factors that may place a patient at risk include immobility, diabetes mellitus, peripheral vascular disease, malnutrition, cerebral vascular accident and hypotension. Other factors are age of 70 years and older, current smoking history, dry skin, low body mass index, urinary and fecal incontinence, physical restraints, malignancy, and history of pressure ulcers.

PTS can affect 23-60% of patients in the two years following DVT of the leg. Of those, 10% may go on to develop severe PTS, involving venous ulcers.

In addition, adequate intake of protein and calories is important. vitamin C has been shown to reduce the risk of pressure ulcers. People with higher intakes of vitamin C have a lower frequency of bed sores in those who are bedridden than those with lower intakes. Maintaining proper nutrition in newborns is also important in preventing pressure ulcers. If unable to maintain proper nutrition through protein and calorie intake, it is advised to use supplements to support the proper nutrition levels. Skin care is also important because damaged skin does not tolerate pressure. However, skin that is damaged by exposure to urine or stool is not considered a pressure ulcer. These skin wounds should be classified as Incontinence Associated Dermatitis.

Patients with upper-extremity DVT may develop upper-extremity PTS, but the incidence is lower than that for lower-extremity PTS (15-25%). No treatment or prevention methods are established, but patients with upper-extremity PTS may wear a compression sleeve for persistent symptoms.

The wounds from which ulcers arise can be caused by a wide variety of factors, but the main cause is impaired blood circulation. Especially, chronic wounds and ulcers are caused by poor circulation, either through cardiovascular issues or external pressure from a bed or a wheelchair. A very common and dangerous type of skin ulcers are caused by what are called pressure-sensitive sores, more commonly called bed sores and which are frequent in people who are bedridden or who use wheelchairs for long periods. Other causes producing skin ulcers include bacterial or viral infections, fungal infections and cancers. Blood disorders and chronic wounds can result in skin ulcers as well.

Venous leg ulcers due to impaired circulation or a blood flow disorder are more common in the elderly.

The cracks and poor skin-condition of this disorder predisposes for the entry of bacterial infection causing spreading cellulitis infection in the leg. If the skin condition deteriorates further and breaks down, a venous ulcer (also known as a stasis ulcer) may form.

Among those in the intensive care unit, ulceration resulting in bleeding is very rare.

This condition results from denervation of areas exposed to day-to-day friction of bony prominences. The denervation may be result of any of the following diseases:

- Spinal injuries

- Leprosy

- Peripheral nerve injury

- Diabetic neuropathy

- Tabes dorsalis

- Transverse myelitis

- Meningomyelocele

Risk factors contributing to PAD are the same as those for atherosclerosis:

- Smoking – tobacco use in any form is the single most important modifiable cause of PAD internationally. Smokers have up to a tenfold increase in relative risk for PAD in a dose-response relationship. Exposure to second-hand smoke from environmental exposure has also been shown to promote changes in blood vessel lining (endothelium) which is a precursor to atherosclerosis. Smokers are 2 to 3 times more likely to have lower extremity peripheral arterial disease than coronary artery disease. More than 80%-90% of patients with lower extremity peripheral arterial disease are current or former smokers. The risk of PAD increases with the number of cigarettes smoked per day and the number of years smoked.

- Diabetes mellitus – causes between two and four times increased risk of PAD by causing endothelial and smooth muscle cell dysfunction in peripheral arteries. The risk of developing lower extremity peripheral arterial disease is proportional to the severity and duration of diabetes.

- Dyslipidemia – a high level of low-density lipoprotein (LDL cholesterol) and a low level of high-density lipoprotein (HDL cholesterol) in the blood) - elevation of total cholesterol, LDL cholesterol, and triglyceride levels each have been correlated with accelerated PAD. Correction of dyslipidemia by diet and/or medication is associated with a major improvement in rates of heart attack and stroke.

- Hypertension – elevated blood pressure is correlated with an increase in the risk of developing PAD, as well as in associated coronary and cerebrovascular events (heart attack and stroke). Hypertension increased the risk of intermittent claudication 2.5- to 4-fold in men and women, respectively.

- Risk of PAD also increases in individuals who are over the age of 50, male, obese, heart attack, or stroke or with a family history of vascular disease.

- Other risk factors which are being studied include levels of various inflammatory mediators such as C-reactive protein, fibrinogen, hyperviscosity, hypercoagulable state.

Treatment may consist of topical applications of steroid based creams and the use of compression stockings to help force the underlying buildup of fluids back out of the lower leg or intermittent pneumatic compression pumps.

Risk factors for stress ulcer formation that have been identified are numerous and varied. However, two landmark studies and one position paper exist that addresses the topic of risk factors for stress ulcer formation:

- Non-critically ill medical patients with 2 or more of the following: respiratory failure, sepsis, heart failure, hepatic encephalopathy, jaundice, kidney failure, stroke, hypertension, previous gastrointestinal disease and treatment with corticosteroids, NSAIDS, heparin, or warfarin.

- In surgical critically ill patients, only those patients who are on a mechanical ventilator for more than 48 hours and/or those with a coagulopathy.

- The American Society of Health-System Pharmacists guideline recommends against the practice of stress ulcer prophylaxis in non-critically ill patients.

The prevalence of peripheral artery disease in the general population is 12–14%, affecting up to 20% of those over 70; 70%–80% of affected individuals are asymptomatic; only a minority ever require revascularisation or amputation. Peripheral artery disease affects 1 in 3 diabetics over the age of 50.

In the USA peripheral arterial disease affects 12–20 percent of Americans age 65 and older. Approximately 10 million Americans have PAD. Despite its prevalence and cardiovascular risk implications, only 25 percent of PAD patients are undergoing treatment.

The incidence of symptomatic PAD increases with age, from about 0.3% per year for men aged 40–55 years to about 1% per year for men aged over 75 years. The prevalence of PAD varies considerably depending on how PAD is defined, and the age of the population being studied. Diagnosis is critical, as people with PAD have a four to five times higher risk of heart attack or stroke.

The Diabetes Control and Complications Trial, and the U.K. Prospective Diabetes Study trials, in people with type 1 and type 2 diabetes, respectively, demonstrated that glycemic control is more strongly associated with microvascular disease than macrovascular disease. It may be that pathologic changes occurring in small vessels are more sensitive to chronically elevated glucose levels than is atherosclerosis occurring in larger arteries.

The pathogenesis of this disease is unclear. Arteriosclerosis obliterans has been postulated as the cause, along with errors of the clotting and fibrinolytic pathways such as antiphospholipid syndrome.

These ulcers have punched-out edge and slough in floor, resembling gummatous ulcer. Surrounding area might have loss of sensation.

Different types of discharges from ulcer are:

- Serous, usually seen in healing ulcer

- Purulent, seen in infected ulcer. Yellow creamy discharge is observed in staphylococcal infection; bloody opalescent discharge in streptococcal infection, while greenish discharge is seen in pseudomonas ulcer

- Bloody (sanguineous), usually seen in malignant ulcers and in healing ulcers with healthy granulation tissue

- Seropurulent

- Serosanguinous

- Serous with sulphur granules, seen in actinomycosis

- Yellowish, as seen in tuberculous ulcer

The most common cause of chronic venous insufficiency is reflux of the venous valves of superficial veins. This may in turn be caused by several conditions:

- Deep vein thrombosis (DVT), that is, blood clots in the deep veins. Chronic venous insufficiency caused by DVT may be described as postthrombotic syndrome.

- Superficial vein thrombosis.

- Phlebitis

- May–Thurner syndrome. This is a rare condition in which blood clots occur in the iliofemoral vein due to compression of the blood vessels in the leg. The specific problem is compression of the left common iliac vein by the overlying right common iliac artery. Many May-Thurner compressions are overlooked when there is no blood clot. More and more of them get nowadays diagnosed and treated (by stenting) due to advanced imaging techniques.

Deep and superficial vein thrombosis may in turn be caused by thrombophilia, which is an increased propensity of forming blood clots.

Arteriovenous fistula (an abnormal connection or passageway between an artery and a vein) may cause chronic venous insufficiency even with working vein valves.

This condition is most common after age 50.

It is more prevalent in females.

There is a hereditary role.

It has been seen in smokers, those who have chronic constipation and in people with occupations which necessitate long periods of standing such as lecturers, nurses, conductors (musical and bus), stage actors, umpires (cricket, javelin, etc.), the Queen's guard, lectern orators, security guards, etc.

While emergency surgery was once the only treatment, combination therapies including enteral feeding with powerful antacids such as H-receptor antagonists or, more recently, proton pump inhibitors such as omeprazole have made Curling's ulcer a rare complication.

A large number of conditions may cause symptoms and signs similar to diabetic myonecrosis and include: deep vein thrombosis, thrombophlebitis, cellulitis, fasciitis, abscess, haematoma, myositis, pseudothrombophlebitis (ruptured synovial cyst), pyomyositis, parasitic myositis, osteomyelitis, calcific myonecrosis, myositis ossificans, diabetic myotrophy, muscle strain or rupture, bursitis, vasculitis, arterial occlusion, haemangioma, lymphoedema, sarcoidosis, tuberculosis, cat-scratch disease, amyloidosis, as well as tumours of lipoma, chondroma, fibroma, leiomyoma and sarcoma.