Varicose veins

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

The first mention of Varicose veins can be traced back to the Papyrus of Ebers. Depending on the severity, treatment ranging from compression stocking to operative procedures are available. Its treatment methods have evolved over time from procedures with very high mortality( such as stripping of veins through long incisions) to procedures that can be performed without any anesthesia such as EVLT.

Discovery

• Varicose veins probably date back to the times when we first started walking erect. Erect posture lead to increased venous pressure in lower limbs which over time lead to acute venous thrombosis, venous valvular insufficiency, and development of varicose veins.
• First known mention of Varicose Veins dates as far 1550 BCE in The Papyrus of Ebers^[1].The veins were described as “tortuous, solid with many knots as if blown up by air.” It advised avoiding any surgical procedures for treating it.
• Hippocrates, also known as the ‘Father of Medicine’ was the first to associate Varicose Veins with the ulcers^[2]. He advised the use of compression bandages and cauterisation to treat the condition. At that time, the arteries and veins were both thought to carry air.
• In 1603, Jeronimus Fabricius d’Aquapendente, a professor of Anatomy was the first to give a proper description of the venous valve in his work named ‘De Venarum Osteolis’.
• William Harvey(1578-1657), in his work De Motu Cordis showed that the flow of blood is unidirectional, which is due to the valves in the venous system^[3]. This work is the foundation of circulatory physiology as we know it today.
• Richard Wiseman (1622-1676) was the first to use the term “varicose ulcer”.

Landmark Developments in Treatment strategies

• In 1890, Friedrich Trendlenberg wrote a paper on Great Saphenous Vein ligation at the junction of the middle and lower third of the thigh. In 1896, Moore suggested some modifications to this procedure which were also backed by John Homans^[4][5]
• Babcock designed a flexible internal saphenous stripper, which could pull out the vein. It can be seen as a prototype of all modern-day strippers.^[6].
• Procedures of perforating veins were explored as a treatment option by various surgeons in the 20th century^[7][8][9].
• In 1966, Sven-Ivar Seldinger(1921-1998), a Swedish radiologist, invented the Seldinger technique which helped the expansion of Radiofrequency Ablation techniques being used in cardiology to endovenous application.
• Alongside the development of RF ablation for the endovenous procedures, Endovenous Laser Therapy(EVLT) also developed. Bone(1999) was the first to report such use^[10].
• Minimally Invasive Surgeries such as EVLT and RF ablation have become the most popular surgical procedures for Varicose veins today.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

The CEAP (Clinical, Etiological, Anatomical, and Pathophysiological) Classification has been developed to help in diagnosis, staging, and treating Varicose veins/Chronic Venous Insufficiency. The patients with Varicose veins can present with symptoms ranging from discomfort, itching, ulceration, swelling to DVT (Deep vein thrombosis) depending on the severity of the disease. This classification helps us stage the disease, while also providing useful information about the anatomy, cause, and the pathophysiology of the disease which with help in deciding the method of management. The CEAP classification has four major categories(Clinical, Etiological, Anatomical, and Pathophysiological); each of them divided into multiple subcategories^[1].

According to the CEAP classification varicose veins which is a part of chronic venous insufficiency can be staged as follows:

• C0-No visible signs of venous disease
• C1-Telengectases or reticular veins
• C2-Varicose veins
• C3- Edema without skin changes
• C4-Changes in the skin and subcutaneous tissues: A) Pigmentation or eczema, B)Lipodermatosclerosis or atrophie blanche
• C5- Healed Ulcer
• C6-Active ulcer

• Congenital(ie Klippel Trenauney Syndrome)
• Primary
• Secondary(ie Post-thrombotic syndrome,trauma)
• No venous cause identified)

• Superfiicial
• Deep
• Perforator
• No venous location identified

• Reflux
• Obstrucion or Thrombosis
• Reflux and obstruction
• No venus pathophysiology identified in advanced stages

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Varicose veins are normal veins that have become dilated beyond 3mm. They usually occur in lower limbs. The superficial and deep veins are connected by perforating veins (also have valves), which also prevent the backflow of blood from deep to superficial veins. Due to obesity, pregnancy, intra-abdominal mass, post-thrombotic destruction of the perforating veins’ valves, etc. sustained high pressures can develop in superficial veins. This causes dilation of superficial veins and the development of varicose veins over time. If unattended, they worsen over time and might be associated with pain, discomfort, localized dermatitis, discoloration, and/or ulceration. Because of slowed blood flow, they can also be associated with the formation of blood clots in the dilated veins.

Varicose veins originate from sustained raised blood pressure in the superficial veins. Veins are normally gated by a one-way bicuspid valve system that prevents the backward flow of blood. The venous system of limbs is divided by fascia into two sub-systems- Superficial veins and Deep veins. These two venous systems are connected intermittently by perforating veins that travel across fascia. The deep veins are a high-pressure system supported by muscle and deep fascia, which prevent abnormal dilatation of these veins. Additionally, the muscles surrounding the deep veins help in pumping blood towards the heart. The one-way valves and the negative pressure generated by the emptying of deep veins help the blood in superficial veins flow into the deep veins via the perforant/perforating collateral veins^[1]. The superficial veins are not supported by fascia. The valves in perforating collateral veins allow blood to flow from superficial to deep veins only. They inhibit backward blood flow from deep to superficial veins. Even though the pressure inside them is low, they are prone to dilation when exposed to high pressure.

The pathogenesis of varicose veins is multifactorial. Most of the risk factors for varicose veins either cause the weakening/destruction of valves of perforating veins or cause raise the overall pressure in the veins. There are several risk factors for varicose veins^[2]:

• Age: With advancing age, the valves of the veins are exposed to wear and tear. This can lead to the development of the incompetence of the one-way valves^[3] that regulate the venous blood flow. This leads to backward leaking of pressure from deep veins to the superficial veins. This leads to increased prevalence of varicose veins in the elderly.

• Sex: It has been found that females are more prone to develop varicose veins. It has been hypothesized that estrogen plays are role in this. Estrogen caused increased relaxation of veins, limiting proper closure of the valves^[4]. Varicose portions of veins often have higher density of estrogen receptors when compared with non-varicose portions of the veins^[5]. Oral contraceptive pills may increase the chances of varicose veins.

• Pregnancy: During pregnancy, several physiologic changes occur. These changes help make sure that the fetus gets proper nutrition and increase the chances of its survival. The expansion of intravascular blood volume is one of these changes. Previous pregnancies have been found to be an independent risk factor for varicose veins in women^[6]. Hormonal changes of pregnancy also play a role in this predispostion.

• Family history: Positive family history is present in a lot of cases varicose veins. The association seems to be more with prevalence rather than incidence^[7]. In 2019, a genetic makeup study for varicose veins’ patients revealed that most patients shared a host of abnormal genes that are responsible for angiogenesis^[8]. This might help in development of new therapies targeting these genes.

• Obesity: Obese patients have been to be associated with significantly higher CEAP clinical stages as compared to non-obese patients even in people with similar anatomical patterns of venous incompetence^[9]. The obese patients were observed to have significantly more saphenofemoral reflux^[10].
• Prolonged standing: People in prolonged hours of standing tend to develop Varicose veins. Prolonged standing can raise the venous pressure in the legs.

Varicose Veins have a tortuous, beady appearance on gross examination.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]

Varicose veins are more common in women than in men, and are linked with heredity.^[1] Other related factors are pregnancy, obesity, menopause, aging, prolonged standing, leg injury and abdominal straining. Varicose veins are bulging veins that are larger than spider veins, typically 3 mm or more in diameter.^[2] Varicose veins are distinguished from reticular veins (blue veins) and telangiectasias (spider veins) which also involve valvular insufficiency,^[3] by the size and location of the veins.

The causes of varicose veins are not clearly understood. In some cases, it is caused by weak or damaged valves that are usually present in veins. These valves help ensure that blood in veins down not flow in the backward direction. However, when these valves are weak or damaged, blood tends to flow backward^[4]. This increases the pressure inside the veins, causing them to become ballooned and tortuous over time. In some other cases, walls of veins are already weak and they might form outpouchings from the pooling and pressure of blood ^[5].

There are no clearly established causes of varicose veins. However, there are a few established risk factors such as Pregnancy, obesity, age, sex, family history etc. To review the risk factor please refer to the relevant section.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: M. Khurram Afzal, MD [2]

Varicose veins maybe differentiated from other diseases that cause swelling in the lower limb, such as femoral hernia, inguinal hernia, femoral artery aneurysm, lymphadenopathy and lipoma.

Varicose veins maybe differentiated from other diseases that cause swelling in the lower limb. The differentials include the following:^{[1][2][3][4][5][6][7][8][9][10][11][12][13]}

†In cases of incarceration or strangulation, tenderness can be present.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Varicose veins are a common disease. Its reported prevalence all over the world varies between 10% to 30%^[1][2]. The majority of the cases are reported in developed and industrialised countries. The prevalence of varicose veins in the USA is estimated to be 23% of the adult population. It is more common in women than in men. The prevalence increases with age. Heredity seems to play a major role in development of Varicose veins. 50% of the patients have a family history of the disease. The children with two affected parents are at almost 90% risk^[3].

Prevalence: Worldwide the prevalence varies between 10-30% of the population. In the USA, the prevalence is around 4500/100,000 ^[4]. It affects around 22 million women and 11 million men^[5].

Region: Varicose Veins are more common in western and industrialized countries compared to the developing countries^[6]. The paper noted that the prevalence rates between Egypt and England was upwards of five-fold after standardization for age.

Case fatality: Varicose veins is not a fatal disease.

Age: The prevalence increases with age. The most affected age group is 40-80 years old.

Gender: Females are twice as likely to be affected by varicose veins as compared to males. Although, males are nearly twice as likely to have visible disease^[6].

Race: The San Diego Population Study, a first of its kind multi-ethnic study of Chronic venous disease noted that the prevalence of visible varicose veins was significantly higher in Hispanics; while it was lowest in Asians^[6].

Developed countries: The prevalence in developed countries tends to be more in developed countries when compared to developing countries.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Varicose veins are associated with multiple risk factors. The most important one is a family history of varicose veins. Other risk factors include increasing age, female sex, prolonged periods of standing, Pregnancy, Obesity. These risk factors can lead to the incompetence of venous valves.

There are several risk factors for varicose veins^[1]:

• Age: With advancing age, the valves of the veins are exposed to wear and tear. This can lead to the development of the incompetence of the one-way valves^[2] that regulate the venous blood flow. This leads to backward leaking of pressure from deep veins to the superficial veins. This leads to increased prevalence of varicose veins in the elderly.

• Sex: It has been found that females are more prone to develop varicose veins. It has been hypothesized that estrogen plays are role in this. Estrogen caused increased relaxation of veins, limiting proper closure of the valves^[3]. Varicose portions of veins often have higher density of estrogen receptors when compared with non-varicose portions of the veins^[4]. Oral contraceptive pills may increase the chances of varicose veins.

• Pregnancy: During pregnancy, several physiologic changes occur. These changes help make sure that the fetus gets proper nutrition and increase the chances of its survival. The expansion of intravascular blood volume is one of these changes. Previous pregnancies have been found to be an independent risk factor for varicose veins in women^[5]. Hormonal changes of pregnancy also play a role in this predispostion.

• Family history: Positive family history is present in a lot of cases varicose veins. The association seems to be more with prevalence rather than incidence^[6]. In 2019, a genetic makeup study for varicose veins’ patients revealed that most patients shared a host of abnormal genes that are responsible for angiogenesis^[7]. This might help in development of new therapies targeting these genes.

• Obesity: Obese patients have been to be associated with significantly higher CEAP clinical stages as compared to non-obese patients even in people with similar anatomical patterns of venous incompetence^[8]. The obese patients were observed to have significantly more saphenofemoral reflux^[9].
• Prolonged standing: People in prolonged hours of standing tend to develop Varicose veins. Prolonged standing can raise the venous pressure in the legs.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Duplex ultrasonography is a cheap and easily accessible technology that can be used to screen for and diagnose varicose veins. Routine testing is not done to screen for varicose veins.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

The progression of chronic venous insufficiency over time is not well understood. The progression follows quite a variable path. Some patients might initially have varicose veins but not have any clinical symptoms; others might develop clinical symptoms(such as heaviness,eczema, etc.) without any clinically visible disease. Without treatment most patients will show worsening of the condition over time^[1].

Serious complications are rare but severe varicosities can lead to major complications, due to the poor circulation through the affected limb.

The natural history of varicose veins is not well understood. This has been a roadblock in prioritizing patients on the basis of stage of clinical disease. For different patients, the disease progresses in different manners. The progression of the varicose veins is driven by a cycle of venous hypertension, inflammation, capillary damage, and edema ^[2]. In a study by Lee et al^[3], it was found that almost half(57%) the patients who develop some level of chronic venous disease initially would show a progression of the disease when followed over time. 98% of the patients who had both varicose veins and chronic venous insufficiency at baseline showed deterioration with time. While the progression was affected by a family history of varicose veins, age, history of DVT, being overweight; gender did not seem to play a role in determining the rate of progression. On duplex ultrasonography scanning, venous reflux especially, superficial combined with deep vein reflux was found to be associated with higher rates of disease progression.

Most varicose veins are relatively benign, but severe varicosities can lead to major complications, due to the poor circulation through the affected limb ^[4].

• Pain, heaviness, inability to walk or stand for long hours thus hindering work
• Skin conditions / dermatitis often occurs with chronic stasis of venous blood
• Bleeding: although uncommon, a life-threatening bleed can happen from injury to the varicose vein
• Ulcer: non-healing varicose ulcer could threaten limb amputation.
• Development of carcinoma or sarcoma in long-standing venous ulcers. There have been over 100 reported cases of malignant transformation and the rate is reported as 0.4% to 1%.^[5]
• Coagulation of blood in varicose veins cause superficial venous thrombosis, deep vein thrombosis (DVT), pulmonary embolism (PE) & could precipitate stroke in the rare case of predisposed individuals (that is, patients with patent foramen ovale).

Even though Varicose veins are a chronic condition, the prognosis is often benign. Most of the mortality associated with varicose veins is due to venous thromboembolism. The possibility of DVT should always be considered in patients with varicose veins. In a 14 year study conducted in Taiwan during the year 2018, the incidence of DVT was found to be 5 times higher in subjects with varicose veins as compared to without^[6]. This can be prevented with timely intervention.

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