What Is (Leukocytoclastic) Vasculitis? Symptoms and Treatment
This is the type of vasculitis most frequently encountered in daily practice. It is generally a small-vessel vasculitis involving the blood vessels of the skin.
Age: It can be seen in any age group.
Sex: There is no difference between the sexes.
Risk Factors:
In 70% of patients, leukocytoclastic vasculitis may arise in association with medication use or bacterial or viral infections, or as part of the clinical picture of cancer, connective tissue diseases or other systemic vasculitides.
Signs and Symptoms:
It may appear as urticaria-like lesions, nodules (swellings) and purpuric haemorrhages, particularly on the thighs and legs. In about half of patients, involvement of other organs such as the lungs, kidneys and gastrointestinal system may be seen.
Diagnosis
Leukocytoclastic vasculitis is diagnosed by biopsy. Once the diagnosis has been made from skin biopsy samples, underlying causes should be investigated. No underlying cause may be found.
Treatment: The treatment decision should be individualised for each patient. Simple recommendations can be made, such as protection from cold and avoiding standing for long periods. If the cause is another disease or a medicine, treating the disease or stopping the medicine is the first step of treatment. Disease limited to skin involvement rarely progresses. Steroids are often used in treatment. Non-steroidal anti-inflammatory painkillers and allergy medicines can also be used.
Course: This depends on the underlying disease and any internal organ involvement. The course is generally good.
Henoch-Schönlein Purpura
Henoch-Schönlein purpura (HSP) was first described by William Heberden in 1801. Later, in 1837, the association of arthralgia and purpura was described by Johann Schönlein, and gastrointestinal and kidney involvement by his student Henoch. Although the terms are now abandoned, it is also known as anaphylactoid purpura or allergic purpura. Henoch-Schönlein purpura is the most common vasculitis of childhood and involves the small vessels. It is a benign disease that usually appears after upper respiratory tract infections. The disease is often self-limiting and does not cause serious organ damage.
Epidemiology
Henoch-Schönlein purpura is more common in children than in adults. The annual incidence of the disease in childhood in the UK is 20.4 per 1,000,000. In children diagnosed with familial Mediterranean fever, the prevalence of HSP is 130 per 1,000. Henoch-Schönlein purpura is a seasonal disease, occurring most often in spring and winter. In 50% of cases in children, there is a history of upper respiratory tract infection before the disease develops. The disease occurs equally in girls and boys, and the average age of onset is four.
Urticarial Vasculitis
This is part of the differential diagnosis of chronic urticaria. Patients have lesions lasting longer than 24 hours, and these lesions often fade leaving a bruise or a pigmented area. A skin biopsy, preferably from a newly formed lesion, is needed to confirm the diagnosis. Once the diagnosis is confirmed, investigations are needed to exclude an underlying cause such as hepatitis B and C, systemic lupus erythematosus, paraproteinaemia and inflammatory bowel disease. Urticarial vasculitis usually does not respond to antihistamines, and corticosteroids are often needed to bring the condition under control. A second immunomodulatory medicine is often needed to reduce long-term exposure to steroids.
Livedoid Vasculitis
Although it has been described as livedo reticularis with summer ulceration, it is actually a form of livedo racemosa. Atrophie blanche is another name for the disease. There is a purple, net-like pattern on the legs due to blockage of or damage to the blood vessels. It is a condition in which very painful ulcers appear in the summer months, with involvement of the feet and ankles. The lesions heal leaving white scars known as atrophie blanche (white atrophy). The disease often accompanies systemic lupus erythematosus (LAC, lupus anticoagulant antibodies) and antiphospholipid syndrome (ACA, anticardiolipin antibodies). Anticoagulants, platelet inhibitors, pentoxifylline or immunosuppressants may be tried in treatment, but unfortunately there is no very effective treatment.
Erythema Elevatum Diutinum
Classically, it presents with painful, erythematous, yellowish-brown nodules and plaques on the extensor surfaces of the limbs, particularly the hands or elbows. There is no internal organ involvement, and it has a chronic course.
Granuloma Faciale
Granuloma faciale, whose aetiopathogenesis has not been fully explained, is a disease characterised by single or multiple facial nodules, mainly on the face, varying in colour from red and brown to purple; they are asymptomatic and firm, with prominent follicular openings. Typically the lesions do not ulcerate and grow slowly, and it is common in adults over middle age 1-4 . Granuloma faciale is resistant to treatment, and various methods have been tried. These include surgical excision, dermabrasion, laser, intralesional corticosteroids, electrocautery and cryotherapy .
Cryotherapy has some advantages over other treatment methods: local anaesthesia is generally not needed beforehand, the technique is quick and easy, any wounds heal quickly, and the complications are of a kind that patients can tolerate .
Sweet Syndrome
Sweet syndrome was first described in 1964 and is also called acute febrile neutrophilic dermatosis. It is a disease characterised by fever, painful red papules, nodules and plaques of acute onset, peripheral neutrophilic leucocytosis and, histologically, dense neutrophilic infiltration of the upper dermis without signs of vasculitis. It can also cause systemic symptoms such as fever and malaise. The association of Sweet syndrome with malignancy was first described by Shapiro and colleagues in a case report of a patient with testicular cancer . It was subsequently shown that Sweet syndrome can be a sign of many different neoplasms.
There are 3 main forms of the disease, linked to its aetiology: classic or idiopathic Sweet syndrome, malignancy-associated Sweet syndrome and drug-induced Sweet syndrome. In addition, a localised form of Sweet syndrome known as neutrophilic dermatosis of the hands has been described. Classic or idiopathic Sweet syndrome is seen most often in women between the ages of 30 and 60. The lesions, seen most often on the upper limbs and the head and neck region and less often on the trunk, tend to recur in 1/3 of cases.
Pyoderma Gangrenosum
Pyoderma gangrenosum (PG) is a rare, chronic, inflammatory neutrophilic dermatosis which, contrary to its name, is not infectious. PG typically starts as a painful nodule or pustule and is characterised by rapidly progressing, large skin ulcers with ill-defined, raised, violaceous edges that are tender to the touch, with mucopurulent or haemorrhagic exudate. Although its cause is not fully known, abnormal neutrophil chemotaxis is thought to be primarily responsible for its pathogenesis.
PG is more common in young and middle-aged adults, particularly between the ages of 20 and 50, and in women more than men. Its overall incidence is 3-10 per million per year. It is most often located on the trunk and limbs. The head and neck and the genital region have rarely been described as atypical sites. Powell and colleagues classified 74 cases of PG clinically into 4 main groups: ulcerative, bullous, pustular and vegetative. In each group, the clinical and histological appearance, rate of progression, associated diseases and treatment options differ. The most common, ulcerative form usually appears on the lower limbs and trunk as mucopurulent ulcers with raised, undermined edges. Healed lesions leave scars.
Subcorneal Pustular Dermatosis
Subcorneal pustular dermatosis (SPD) is a chronic, relapsing disease in which pustules predominate. It was first described by Sneddon and Wilkinson in 1956. It occurs in the middle-aged group, more often in women. The eruption is mainly located on the trunk and the flexor surfaces of the limbs; it is rarely seen on the palms and soles, and facial and mucosal lesions are almost never encountered. Although the pustules tend to heal on their own, new ones continue to appear. The pathogenesis of the disease is not fully known. Its most prominent histological feature is the formation of sterile subcorneal pustules with subcorneal neutrophil accumulation, without acantholysis or spongiosis. However, acantholysis may also be seen in late lesions. In classic SPD, direct and indirect immunofluorescence studies are negative.
Schamberg Disease
Schamberg disease is a rare, asymptomatic eruption usually seen in adolescent and young adult males, clinically characterised by orange or light-brown macules with pepper-like specks within and around them (cayenne-pepper spots). Its course is chronic and it can continue for years. The aetiology of this disease is unknown, and there is no characteristic laboratory finding. In Schamberg disease, which histopathologically produces a small-vessel necrotising vasculitis, topical and/or systemic steroids are used.
Lichen Aureus
The pigmented purpuric dermatoses are a group of diseases that resemble one another clinically and dermatologically. One of them, lichen aureus, was first described by Marten in 1958 as lichen purpuricus. Calnan named this eruption lichen aureus. Clinically it presents as orange, round macules or plaques close to a golden-copper colour, and there is no effective treatment.
Clinically, lichen aureus shows golden-copper or orange-purple round macules or plaques. These lesions can be very itchy, but are more often asymptomatic. They are most often located on one side, on the lower limbs. Linear, segmental and zosteriform variants have been described. They can also involve the forearm and trunk. The Koebner phenomenon may be positive in the lesions. Lichen aureus is particularly common in young adults, between the ages of 10 and 30.
Livedo Reticularis
Livedo reticularis is a vasculopathy presenting as a bluish-red, net-like pattern on the skin, most often on the legs but also on the trunk and arms. In livedo reticularis, the basic event begins with spasm after a cold or emotional stimulus, and the tissue oxygen pressure falls. In cases of prolonged spasm, microvascular thrombosis develops.
FORMS OF LIVEDO RETICULARIS
Cutis marmorata: a physiological, reversible condition that appears in babies and in many adults in cold weather.
Congenital cutis marmorata telangiectatica: localised or widespread permanent vascular lesions of the skin seen after birth.
Primary livedo reticularis: a form seen in adults, of unknown cause, that usually has a benign course. It rarely requires treatment.
Secondary livedo reticularis: livedo that develops due to a systemic disease; there are many causes.
SECONDARY LIVEDO RETICULARIS
Form in which vascular occlusion develops due to vasculopathy:
Antiphospholipid syndrome: a reaction against phospholipids, a type of fat in the body, which leads to clots forming in the arteries and veins.
Raynaud's Phenomenon
Raynaud's phenomenon is a disturbance of blood circulation, usually in the hands and fingers and sometimes in the ears and nose.
When the circulation is cut off, the affected extremities first look white and lifeless, then turn red and burn. There is considerable pain, numbness and tingling. These symptoms are caused by intermittent interruption of blood flow resulting from constriction of the arteries in the affected area. It is triggered by touching something cold, exposure to cold or even the slightest change in temperature. Smoking and feelings of anxiety can also be triggers.
People who work with vibrating tools are prone to this condition, and it has been found to persist even after they stop working. As an industrial disease, this is known as vibration white finger. Its severity ranges from mild discomfort to the onset of ulcers or gangrene.
The disease starts at a very young age and progresses very slowly over a period of up to 30 years.
Primary Raynaud's phenomenon arises spontaneously without any particular cause. It may be hereditary and its effects are generally mild. It is nine times more common in women than in men.
Secondary Raynaud's is less common and is associated with diseases such as scleroderma, systemic lupus erythematosus, Sjögren's syndrome and rheumatoid arthritis. It is a serious disease, and early and accurate diagnosis is very important.
Purpura Fulminans
Purpura fulminans is a rapidly progressing disease that causes vascular collapse, disseminated intravascular coagulation, severe skin loss and even limb amputation. The disease usually develops in association with infections such as meningococcaemia and chickenpox and often results in amputation of the limbs.
Cholesterol Crystal Embolism Syndrome
Cholesterol crystal embolism syndrome (CES) is a syndrome whose frequency is increasing today with the widespread use of intravascular procedures and treatments such as thrombolytic agents and heparin, and which may be involved in the aetiology of more than 3% of cases of end-stage kidney failure. It is more common in male patients who are diabetic, hypertensive and smoke. The basic pathogenesis is the inflammatory and obliterative process caused in the end arteries by cholesterol crystals that are dislodged after intravascular procedures and enter the distal arterial circulation. Given that the organs frequently affected are the kidneys, skin, gastrointestinal system and limbs, worsening hypertension, purpura and ecchymoses of the skin, abdominal pain, weight loss and deterioration of kidney function tests are frequently seen clinically.
What Is Antiphospholipid Syndrome?
Antiphospholipid antibody syndrome is an autoimmune disease, seen mostly in young women, in which antiphospholipid antibodies are present in the blood together with clotting in the arteries or veins and/or miscarriage or pregnancy problems. Antiphospholipid syndrome can occur on its own or together with other diseases, most commonly lupus. In these patients' blood, antibodies that develop against some of their own tissue proteins cause clotting inside the blood vessels without signs of inflammation. These patients have pregnancy problems such as miscarriage, premature birth or fetal death in the womb. The damage to tissues and organs varies according to where the clot forms in the blood vessel. It can cause blockage of the leg veins, heart attack through blockage of the coronary vessels (which supply the heart), strokes through blockage of the blood vessels to the brain, and shortness of breath – and even death – through blockage of the main pulmonary artery to the lungs and its branches.
Antiphospholipid-related clot formation can occur anywhere in the bloodstream and can affect any organ in the body. Blood clotting in the vessels is most often seen in the legs. Blood clots in the leg veins can break off and travel to the lungs, causing a very serious condition called pulmonary embolism. In pulmonary embolism, blood flow to the lungs is blocked and the amount of oxygen in the blood falls.
Sometimes recurrent thrombotic events can progress rapidly and become an acute, life-threatening condition causing progressive damage in various organs. This is called catastrophic antiphospholipid syndrome.
During pregnancy, antiphospholipid syndrome can cause early and late miscarriages and pre-eclampsia in women.
Patients with antiphospholipid syndrome have a low platelet count. A mottled purplish appearance of the skin (livedo reticularis), Raynaud's phenomenon in the hands and feet, and skin ulceration (sores) may be seen.
What Causes Antiphospholipid Syndrome?
It is not fully understood why these autoantibodies form in some people and cause disease. It is thought that a person's genetic make-up, together with certain environmental factors (such as infections), may predispose to the production of these autoantibodies.
Even if antiphospholipid antibodies are present in the blood for a long time, no thrombotic event may develop. Antiphospholipids increase the risk of blood clotting; however, other risk factors such as prolonged immobility (for example, being bedridden), surgery or pregnancy also increase clotting. Additional risk factors for thrombosis include high blood pressure, obesity, smoking, atherosclerosis (hardening of the arteries) and the use of oestrogens (such as contraceptive pills, hormone replacement therapy, and medicines acting on oestrogen receptors used for breast cancer or osteoporosis).
Who Develops Antiphospholipid Syndrome?
Antiphospholipid syndrome is five times more common in women than in men. It is usually diagnosed between the ages of 30 and 40. Although up to 40% of patients with lupus have antiphospholipid antibodies, only half of them develop thrombosis and/or miscarriage.
As with other autoimmune diseases, there is a genetic predisposition in antiphospholipid syndrome. However, it is not passed on directly; relatives are only slightly more predisposed than the general population.
How Is Antiphospholipid Syndrome Diagnosed?
Antiphospholipid syndrome is diagnosed when thrombosis and/or recurrent miscarriage occur together with antiphospholipid antibodies (anticardiolipin antibodies, anti-beta-2 glycoprotein 1 antibodies, lupus anticoagulant, anti-phosphatidylserine antibodies) demonstrated in a blood test. The test is expected to be positive again when repeated three months later. A positive test on its own, without thrombosis or miscarriage, does not establish a diagnosis of antiphospholipid syndrome. There are also healthy people who carry these antibodies in their blood throughout their lives without ever developing thrombosis.
How Is Antiphospholipid Syndrome Treated?
The main aim of antiphospholipid treatment is to prevent recurrent miscarriages and thrombosis.
Vascular events: In the presence of acute thrombosis, treatment starts with intravenous heparin and continues with the oral anticoagulant (blood thinner) warfarin (Coumadin). The warfarin dose is adjusted by monitoring the INR. In severe vascular occlusion, low-dose aspirin is also added to treatment. Where warfarin cannot be used, low-molecular-weight heparins given under the skin are used. In patients with antiphospholipid syndrome, oral anticoagulants are used for many years to prevent vascular occlusion due to possible thrombi. In arterial events, medicines that prevent platelet aggregation, such as aspirin and clopidogrel, are added to warfarin.
Pregnancy events: Low-molecular-weight heparin injections under the skin and low-dose aspirin are the standard treatments used to prevent miscarriage. Treatment starts at the beginning of pregnancy and continues until after delivery. The mother should be given sufficient calcium and vitamin D supplements to protect against osteoporosis. Where this treatment is insufficient, alternative treatments such as corticosteroids and intravenous immunoglobulin infusion may be given.
A pregnant woman with antiphospholipid syndrome who has had vascular events is managed with heparin and low-dose aspirin during and after pregnancy.
Treatment with heparin and aspirin has been shown to be safe for mother and baby.
Advice for Patients with Antiphospholipid Syndrome:
- The dose of the warfarin you take to prevent thrombosis is very important. Your doctor will adjust the dose by monitoring your INR. Warfarin levels vary greatly with certain foods and medicines; ask your doctor about this. The INR should be monitored regularly.
- Correcting risk factors that predispose to thrombosis (clotting inside the blood vessels) – such as diabetes, high blood pressure, high cholesterol, obesity, smoking and certain medicines – is essential in patients with antiphospholipid syndrome. Oestrogen treatment for contraception or menopausal symptoms (oral contraceptives – birth control pills) should be avoided.
- Treatment is very effective in preventing pregnancy events (such as miscarriage or stillbirth). With treatment, most women with antiphospholipid syndrome give birth to healthy children.
Cryoglobulinaemic Vasculitis (Inflammation of the Blood Vessels)
A small-vessel vasculitis characterised by the presence in the serum of proteins called cryoglobulins, i.e. cryoglobulinaemia.
Age: Patients are usually between 40 and 50 years old.
Sex: It is 2-3 times more common in women.
Risk Factors: Cryoglobulins can form in association with certain blood diseases or connective tissue diseases, or as a result of viral (mostly hepatitis C virus) and bacterial infections. More than 90% of patients with cryoglobulinaemia are HCV positive.
Signs and Symptoms: Cryoglobulins are a type of protein that can be found in the blood in some diseases; they can solidify reversibly in the cold, block small blood vessels and damage the tissue supplied by that vessel. If no underlying disease that could lead to cryoglobulin formation is found, it is called essential cryoglobulinaemia; if cryoglobulins form as a result of a disease, it is called secondary cryoglobulinaemia.
Cryoglobulinaemic vasculitis is a systemic disease characterised by purpuric skin rashes (pinpoint or larger bleeding under the skin), skin ulcers, joint pain, peripheral nervous system involvement and nephritis. Raynaud's phenomenon is common. Kidney involvement is the most important consequence of the disease and affects about 1/3 of patients.
Diagnosis: For a diagnosis of essential cryoglobulinaemia, other diseases that can produce cryoglobulins must be excluded. Various blood and urine tests and tissue biopsies may be needed for diagnosis. Kidney, nervous system and lung involvement is less common in patients with cryoglobulinaemic vasculitis.
Treatment: In the treatment of cryoglobulinaemia, treating the underlying disease (such as treatment of chronic hepatitis) is important. In cases with serious organ involvement, partial exchange of the blood (plasmapheresis) and medicines that suppress the immune system may be used.
Course: Half of patients have a good course. Male sex, kidney involvement and age over 60 at diagnosis indicate a poor course.
Cryoglobulinaemia
Cryoglobulinaemia and cryofibrinogenaemia cause purpura, livedoid lesions, ulcers and necrosis, particularly in the acral regions. Cryoglobulins and cryofibrinogens are serum immunoglobulins that precipitate in the cold.
Cryofibrinogenaemia is associated with systemic diseases (malignancy, diabetes), pregnancy and oral contraceptive use. Diagnosis is made by raised serum cryoglobulin/cryofibrinogen. Non-steroidal anti-inflammatory drugs (NSAIDs) and systemic steroids can be used in the treatment of cryoglobulinaemia, whereas in cryofibrinogenaemia the underlying cause must be removed.
Purpura (Petechiae and Ecchymoses)
Petechiae and ecchymoses, a type of bleeding localised within the skin tissue, are collectively called "purpura". They usually occur after trauma. Petechiae are the size of a pinhead and are easily distinguished from other skin rashes because they do not fade when pressed. Ecchymoses are very easily recognised, even by lay people, as "bruises".
If a patient with a low platelet count has purpura, ITP should be considered first. If the platelet count is normal, platelet function disorders should be considered.
Skin and mucosal bleeding other than purpura should also be carefully assessed.
These include frequently recurring or hard-to-stop nosebleeds (epistaxis), bleeding from the lining of the mouth, bleeding gums, bleeding after tooth extraction, gastrointestinal bleeding, uterine bleeding (menorrhagia) and bleeding from the urinary tract.
Acroangiodermatitis
Acroangiodermatitis (AAD) is a self-limiting angioproliferative disease that can arise from congenital, acquired or iatrogenic causes. Because AAD can be confused clinically and histologically with Kaposi sarcoma, it is also called pseudo-Kaposi sarcoma. Pseudo-Kaposi sarcoma, whose aetiology is unknown, has two types: Stewart-Bluefarb syndrome, associated with congenital arteriovenous (AV) malformations, and Mali-type acroangiodermatitis, resulting from chronic venous insufficiency. Iatrogenically, it can also develop in patients with AV fistulas for haemodialysis, in those with paralysis of a limb, and in the stump area after limb amputation. The congenital type can be seen from birth, while the acquired types become more common with age.
Chronic Venous Insufficiency
Chronic venous insufficiency (CVI) is an advanced stage of leg vein disease in which the leg veins become incompetent, resulting in pooling of blood in the feet and legs. It occurs when there is a blockage in the leg veins or damage to the one-way valves in the veins. Under normal conditions these valves allow blood to flow only back towards the heart. Incompetent valves allow blood travelling from the legs to the heart to flow back under the effect of gravity and pool lower down.
Causes of chronic venous insufficiency
- Blood clots (venous thrombosis), inflammation (phlebitis) or damaged valves blocking blood flow in the veins
- Leg injury or surgery
- Obesity, which increases pressure in the leg veins in a way that damages the valves
- Standing still for long periods
- Congenital genetic defects
If it is not carefully treated, CVI can progress to leg ulcers; in the long term this happens in 25 per cent of patients with CVI.
Leg ulcers are a serious complication accompanying CVI. Leg ulcers accompanying CVI may be on the outer side, but they are usually located on the inner side of the ankle. They do not form on the front of the foot or above the knee.
Signs and symptoms of CVI
CVI often arises as a result of deep vein thrombosis.
Symptoms and predisposing factors include:
- Swelling (oedema) of the legs or ankles
- Long-standing itching or pain in the legs
- A feeling of fullness in the legs that is aggravated by standing for long periods
- Hardening of the layers under the skin (induration)
- Brown discolouration of the skin, especially around the ankles
- Inflammation of the skin (dermatitis)
- Varicose veins
- Painful ulceration at the ankles or higher (leg ulcers, stasis ulcers)
Arterial Ulceration
Arterial ulceration is the result of insufficient blood flow to the legs, due to problems with the blood vessels themselves or to another underlying disease affecting blood flow. Occlusive arterial disease is a disease in which plaques form in the vessel wall, narrowing the vessels and making them lose their elasticity, so that blood flow is reduced. It is closely associated with high blood pressure and smoking.
Symptoms:
- The skin of the leg is cold, pale, dry and shiny.
- Thickening of the nails
- Pedal pulses are reduced or absent.
- Leg pain that increases when walking
- In later stages, unbearable pain that does not go away and steadily worsens
- Wounds that do not heal
Migratory Thrombophlebitis
The finding of migratory thrombophlebitis on the limbs or trunk in internal malignancies – especially pancreatic cancer, but also stomach, lung, prostate, colon, ovarian and gallbladder cancer – is called Trousseau's sign. These are multiple, tender, erythematous nodules a few cm long, palpable as cords, most often located on the lower limbs and sometimes on the upper limbs and trunk. The superficial veins of the lower limbs are mostly affected, and the lesions are numerous. The mechanism is thought to be low-grade intravascular hypercoagulation, and the response to anticoagulant treatment is poor.
Lymphoedema
A clinical condition resulting from the accumulation of protein-rich fluid in the tissues due to a disorder of the lymphatic circulation. Swelling, heaviness, a feeling of tightness, pain and susceptibility to infection appear in the affected area. It has a negative effect on the patient's quality of life and social life. In later stages it causes cosmetic deformities and limits the function of the arms and legs. Although at a low rate, malignant change (development of lymphangiosarcoma) in the soft tissues of this area is possible.
What are the symptoms of lymphoedema?
Diagnosis is difficult in the early stages of the disease. At this stage, symptoms such as swelling, tightness and a feeling of heaviness are observed in the affected area. Many patients do not take the symptoms seriously at first, or do not receive a satisfactory diagnosis from the medical specialties they consult. If lymphoedema is not diagnosed and preventive measures are not taken, the symptoms increase over time and become irreversible. Symptoms such as thickening of the skin, hardening of the arms and legs, lymph leakage and severe swelling to the point of making movement difficult then appear.
How is lymphoedema diagnosed?
In the early stage, swelling and increased circumference of the affected area are the most noticeable signs. Jewellery, accessories, clothes and shoes start to feel tight. When the arm or leg is compared with the other side, a difference in circumference and a change in tissue consistency are found. Symptoms increase after excessive exercise and fatigue. Symptoms that initially appear in the evening become permanent during the day as the disease progresses. Blood tests, assessment of the veins (venous Doppler ultrasound), lymphoscintigraphy and lymphatic MRI are useful in the diagnosis and differential diagnosis of lymphoedema.