Squamous cell carcinoma
Basal cell carcinoma
Hypertensive ulcer, Bazin’s disease, pyoderma gangrenosum, fat necrosis, necrobiosis, calciphylaxis
3.2 Venous Ulcer (Fig. 3.1)
Varicose ulcer due to saphenofemoral incompetence
Chronic venous insufficiency affects about 5 % of the adult population, and 1 % may have chronic leg ulcers in developed countries and a prevalence of 3–5 % in the population above 65 years of age [3, 4]. Ulcers of primarily venous origin can range between 54 and 57 % of chronic leg ulcers [5, 6]. Ulceration can begin before age 3.of 40 , and many patients live with one throughout their entire adult life without seeing resolution. Venous disease utilizes 1–2 % of the health budgets of European countries with annual cost estimates being around £ 400 million in the United Kingdom and $1 billion in the United States [1, 8].
Before 40, the gender incidence is equal, but above this the disease afflicts mainly the women  probably due to earlier pregnancies and hormonal factors [5, 6]. Venous disease has a multifactorial origin with prolonged standing, obesity, aging, pregnancy, and hereditary factors all playing a part .
Primary disease can be congenital when patients are born with valvular defects which herald themselves in the late teens or early twenties or familial when it affects generations and a familial factor does exist if one parent was involved and this is increased further if both parents had venous disease . Secondary valvular problems range from trauma to the surrounding tissue, motor vehicular accidents with bony fractures and crush injuries, and post-thrombotic syndrome . Deep vein thromboses (DVTs) associated with chronic leg edema, pigmentation, and ulceration were known as “postphlebitic syndrome” .
The pathology here is one of elevated venous pressure (venous hypertension) due to venous reflux through valves which are either primarily diseased or through pathological changes in the vein wall. In primary valve failure, there is degenerative change in the valve annulus and leaflets, while secondary failure is due to the diseased vein wall with secondary widening of the commissures leading to incompetence and reflux.
Venous disease is chronic, and venous ulcers tend to be more often recurrent when compared with the non-venous ulcers  and those with venous ulcers had a higher body mass index. Elevated venous pressure is the underlying cause of skin and soft tissue changes seen in chronic venous insufficiency (CVI) that ultimately lead to venous ulceration.
Increased venous pressure is transmitted to the venules and capillaries of the subcutaneous tissue causing a level with elongation of the capillary bed, increased type IV collagen in the basement membrane , and pericapillary fibrin cuff forms . These capillaries which are not normal seem to have increased permeability to larger molecules. Protein such as fibrinogen and red cells then leak into the interstitium, and this fibrinogen converts to fibrin in the pericapillary space  and the fibrin is deposited together with hemosiderin , released during red cell destruction. Fibrinolytic activity appears deficient in patients with venous ulceration deposition so there is decreased fibrin clearance and reduced lymph drainage [13, 14]. In addition, fragmentation and obliteration of cutaneous lymphatics and decreased lymphatic flow correlate with the degree of venous hypertension [15–17]. Microscopically, capillaries also demonstrate microthrombi that are occlusive and white cells sludge . Stagnation of blood flow and decreased oxygen levels occur, and the protein laden, edematous area then acts to decrease oxygen diffusion into the area leading to tissue hypoxia [19, 20]. There is good evidence that there is reduced cutaneous oxygenation . This actually improves with oxygenation which indicates that a diffusion barrier exists and not an oxygen transport problem causing low oxygen tissue content which presumably plays a major part in genesis of the ulcer. This improves if oxygen is supplied to the area [19, 20].
Venous ulcers typically occur on the lower medial leg in the so-called gaiter area, but they can be seen nearly anywhere on the lower leg or dorsum of the foot . They may be single or multiple, painful, and shallow with a red granulating floor, and usually there is a zone of stasis dermatitis and brown-to-black hemosiderin deposits  called lipodermatosclerosis. Edges may be clear-cut or irregular, and they extend onto the dorsum, up the leg, or become circumferential, and if present the ulcer will be found within this hyperpigmented area. Venous ulcers can be found on the lateral aspect of the dorsum as well especially when there is severe sapheno-popliteal reflux into the short saphenous venous system .
The skin becomes heavily pigmented and bound down to the subcutaneous tissue with extensive fibrosis which constricts the limb. This lipodermatosclerosis (LDS) usually occurs in the lower third of the leg with brawny edema above  the fibrosis and on the foot giving the typical appearance of an inverted champagne bottle with the neck being the area of lipodermatosclerosis and the edematous leg being the body of the bottle. Even though these areas of pigmentation are dark brown to black, there may be patches of depigmented macules called atrophie blanche, avascular and fibrotic in nature, that are thought to be forerunners to ulcer formation (Fig. 3.2) .
Lipodermatosclerosis with ulceration
Clinically the changes include edema, dermatitis and eczema, hyper- or hypopigmentation (called atrophie blanche), and eventually tissue hypoxia leading to ulceration which is typically non-healing or recurrent .
Venous ulcers can be seen in patients with valvular incompetence at the superficial, deep, or perforating systems or a combination of two or even all three [25, 26], and in patients with ulcers, incompetence generally occurs at multiple locations . Indeed some researchers studied closely the patterns of reflux and agree the incidence of multiple systems being involved in lower-limb venous ulcers was 64 % . Furthermore, in 36 % patients with venous disease, one other etiological factor was a contributor to the chronic venous ulcer, and 96 % of these either had a previous history of a DVT or some condition that may have caused this pathology .
Ischemic ulcer of the heel
Ischemic heel ulcer
Arterial ulcers on the dorsum and first three toes
Peripheral arterial disease is the only etiology identified in about 10 % of patients with leg ulcers . Pure arterial ulceration is not as common as we may believe. One large study of 689 leg ulcers showed that only 15 limbs (2.2 %) were purely arterial in origin [2, 30] and another large study involving 1333 limbs with ulcers (1163 fully evaluated) indicated that 55 % were venous, 25 % were mixed, and 8.3 % were diabetic [3, 31], alluding to the fact that many clinicians do not separate leg ulcers into venous and arterial but venous, diabetic, and mixed origin. They believe that there is usually some other etiological factor present even if it is quiescent or subtle.
Arterial ulcers of the leg tend to develop distally and are seen commonly on the toes and feet. They tend to be small and multiple and may occur in the areas commonly seen in venous disease or diabetes but are notorious for lying in unusual places such as the interdigital spaces, web-space areas, lateral dorsum, or plantar surface of the foot as well as the heel. They tend to be painful and they are usually dry and crusted and devoid of granulation tissue [5, 22].
Objective parameters to diagnose arterial insufficiency were considered to be ankle-brachial index (ABI) < 0.7 and a toe systolic pressure (TP) of <50 mm Hg [4, 32]. Arterial disease is seen primarily in patients with atherosclerosis whether the cause is uncontrolled hypertension, chronic smoking, or diabetes, or in patients with dyslipidemias.
Most arterial leg ulcers may not be included in the category of chronic critical limb ischemia; however, they are unlikely to heal with conservative measures. An ankle pressure of 110 mmHg was able to determine those who should proceed to revascularization [1, 29], and generally they can be treated by conservative means using local therapy [4, 32], but wound care must be supplemented by active wound debridement, percutaneous transluminal angioplasty (PTA), or infrainguinal arterial bypass [6, 33].
The natural history of ischemic limb ulceration has not been well understood [4, 32]. Some patients with arterial ulcers can heal well in time without undergoing revascularization procedures such as angioplasty or arterial bypasses. Use of pressure relief, debridement, moist wound care, negative pressure, application of a strict antibiotic policy (with repeated wound swabs or tissue culture) for control of infections or special chemical debriding or granulation-producing agents, dipteran larvae (flies), or hyperbaric oxygen therapy (HBOT) may assist in wound healing [4, 32].
Limb salvage can be achieved in chronic non-healing ulcers that are uncomplicated, but if the ankle-brachial index (ABI) is less than 0.5, the end result can be a major amputation . Infrainguinal bypasses are likely to result in wounds healing even if the ulcer was located in the heel area [6, 33], and limb salvage rates of >85 % can be achieved once the graft remained patent but other factors are also relevant in predicting healing. These included normal renal function, a palpable pedal pulse, a patent posterior tibial artery past the ankle joint, and the number of patent tibial arteries after completion of the bypass [6, 33]. Interestingly, the ABI, the presence of infection, diabetes, nor cardiovascular risks were unable to influence outcome of these ulcers [6, 33].
Therefore, most patients with an ulcer due to arterial insufficiency that is not complicated, even if appearing to be non-healing, may do so with local therapy. The patients with a low ABI and ankle and toe systolic pressure may attain limb salvage through percutaneous angioplasty or infrainguinal bypasses .
3.4 Mixed Arterial and Venous Ulcers
The mixture of venous and arterial disease is likely to be the second most common etiological factor leading to leg ulcers . Combined arterial and venous insufficiency (CAVI)  accounted for the second largest group of patients with leg ulcers. In a study assessing 689 chronic leg ulcers, 14.5 % were of mixed origin as compared with those of a completely venous origin 72 % . Elderly patients in this category may also have some degree of venous reflux giving rise to a “mixed” arteriovenous origin of the ulcers.
Clinically these patients can be difficult to diagnose due to the mixed symptoms and clinical signs with which they present. They may have some characteristics of arterial disease that may far overwhelm the venous picture such as a cold, dry dorsum of the foot, decreased pedal pulses, small ulcers on digits or dorsum of the foot, “hammer toes,” with lipodermatosclerosis at the medial malleolar area leading an inexperienced clinician to think this may be a form of gangrene and ignore the venous component.
Alternately, a large medial malleolar ulcer typical of venous insufficiency may be accompanied by cutaneous gangrene of the covered toes or simply a dry withered foot with an absent dorsalis pedis pulse and loss of cutaneous hair on the lower leg but a good popliteal pulse. To the casual observer, this is venous disease, and the fact that the patient is diabetic or an ex-smoker of a pack a day prior to admission may be lost to an inexperienced medical officer.
Ulcers may develop anywhere on the foot or calf in mixed disease , and patients need the eye of an experienced clinician to properly assess and manage the patient. Patients with a previous history of a previous deep vein thrombosis (DVT) of the calf or thigh vessels complicate not only the diagnosis but subsequent treatment since these mixed ulcers are unlikely to heal .
In a large study of 689 limbs with chronic venous ulcers, 100 (14.5 %) were of mixed origin  and 56 had arterial revascularization via bypass procedures, 36 had venous surgery, 23 had local therapy (compression bandaging) whilst of 15 with pure arterial origin 13 had angioplasty (PTA) and the remaining 2 patients had dressings to the area . This shows the multifactorial nature of the disease, the array of treatment options available, and therefore the treatment modalities adopted. Investigations always center on a careful clinical examination including bedside ankle-brachial index (ABI), handheld Doppler investigation, color flow duplex scan, and either MR, CT, or conventional arteriography. Ankle pressures are crucial in determination of the pathway management should follow and are required even with respect to the venous component since it allows estimation for the degree of compression allowed in the patient.
The value of ankle pressure of below 110 mmHg identified those patients for revascularization , but an ankle pressure (AP) of > or = 80 mmHg predicts favorable outcome as well as a toe pressure of 30 mmHg . In any case a practical bedside test such as the ankle-brachial index (ABI) of < 0.5 should alert clinicians to seek revascularization for these slowly healing ulcers .
Neuropathic ulcer with underlying sesamoid bone
Traumatic neuropathic ulcer from foreign body embedded in slipper
Neuropathic ulcer opposite to the 5th metatarsal head with underlying bony destruction
Ulcers on the dorsum of hammer toes
Ulcers from neuropathic foot on hot surface
Diabetes mellitus patients may have a whole host of pathologies, some of which have the greatest effect on the foot. Ulceration of the foot is the commonest major end point in diabetic complications. Diabetic neuropathy and peripheral arterial disease are the main players in foot ulceration alone or in tandem or with other factors such as mechanical issues (poor footwear, deformities with points of increased pressure), limited joint mobility, microvascular disease, and infections.
One study found foot ulceration in 7 % of diabetic patients over the age of 60 years; another study showed a 3 % history of ulceration in insulin-dependent diabetes patients (IDDM); patients aged 15–50 years are 45–60 % purely neuropathic, 10 % are purely ischemic, and 25–45 % are mixed.
Neuropathic ulcers are usually at the site of repeated trauma as in the area at the metatarsal heads where a high pressure exists or dorsal surface of the “hammer toes” or the distal-most portion of these hammer toes where there is flexion at the interphalangeal joint (IPJ) of these “clawed” toes. The foot is warm, well perfused, and pulse bounding. A foreign body may get lodged in the footwear, or a sharp object like a nail can penetrate the shoe or slipper. The presence of callus continues to impede ulcer healing since wounds heal from margins or edge, and epidermal cells from this area are prevented from so doing by position of the callus.
The pure ischemic ulcer is rare and most are neuroischemic occurring at the medial aspect of the first metatarsal head, the heel, and the digits. There is no callus present but there is a ring of hyperemia, with or without a necrotic center. Again ulcer formation is preceded by mild trauma and the tight or poorly fitting usually “under”-sized shoe in women and the hard boot in the industrial areas. Diabetic neuropathy affects approximately 30–50 % of patients. Diabetics then suffer from another source of ulceration, namely, those of a neuropathic origin which tends to be typically small, shallow, and painful and lies in relation to the digits and the plantar surface of the hallux at the metatarsal-phalangeal joint (MPJ). The ulcers in diabetics could be ischemic, neuropathic, or mixed neuroischemic. These account for the majority of ulcers seen in the practice of clinical surgery at the emergency room, clinic, or long-stay “sepsis ward.” However, they are not by any means the only (etiology of) ulcers encountered in practice of surgery, and indeed there are more striking, chronic, and lethal forms of ulcers encountered on the legs and feet of patients.
3.6 Hematological Ulcers
Patients with hematological diseases such as sickle-cell anemia as well as β-thalassemia (genetic disorders of hemoglobin synthesis frequently present with leg ulcers, which tend to be painful and slow to heal [1–3, 36–38]. The incidence varies from 8 to 10 % of sickle-cell patients (with the homozygote SS disease) between ages of 10 to 50 years . Leg ulcers did not occur in sickle beta plus thalassemia and sickle hemoglobin C disease. Low steady-state hemoglobin patients had a higher incidence of ulcer formation, and fetal hemoglobin seemed to have a protective effect on sickle-cell patients . The pathophysiology of the ulcers is unclear, but there may be a relation to vaso-occlusive complications where decreased oxygen-carrying capacity of the abnormal hemoglobin has been suggested . There were no ulcers in patients below age 10, and males were much more affected than female patients for reasons unknown to clinicians .