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26/Sep/2017

USE OF HONEY IN HEALING VENOUS ULCERS

ALKA BHIDE (medicalstudent)

venus_ulcer2For thousands of years honey has served as a natural remedy for numerous ailments. Many believe that the therapeutic potential of uncontaminated, pure honey needs to be explored and for it to have a place in conventional medicine.

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Venous ulcers in the lower limb are one of the many complications resulting from deep vein thrombosis (DVT). Deep vein thromboses undergo organisation and recanalisation and in the process valves of the deep veins may be damaged. This leads to the valves becoming incompetent and reflux occurs resulting in chronic venous insufficiency (usually takes a period of years to develop) in the post-thrombotic limb. In the normal adult limb, the venous pressure while standing is approx. 125cmH2O and decreases while walking due to the calf pump. In the post-thrombotic limb, incompetent deep venous valves allow reflux causing the ankle pressure to remain high during calf muscle activity. This leads to incompetence of the valves in perforating veins and blood is forced into the superficial system. The result is disruption of the normal vascular dynamics of the skin and subcutaneous tissues and may cause impaired skin vitality and healing. As aforementioned venous ulceration, commonly above the medial malleolus is a characteristic sign in the post-thrombotic limb.

 

Conventional treatment of ulcers involves support and compression of the skin and superficial tissues. This can be done either by elastic bandages or correctly sized graded stockings. One must be careful of ensuring that the pressure of these stockings does not cause ischaemia or abrasions over tendons or bony prominences. The presence of infection confined to the ulcer requires excision of the dead tissue and dressing the site with saline soaks. Antiseptics are avoided as they may retard granulation tissue formation and epitheliasation. Intractable or large ulcers may require skin grafts once the ulcer base is clean.

 

However the use of honey in the treatment of venous ulcers is now under investigation. Honey has numerous properties; it has a natural anti-inflammatory effect and also is a natural antiseptic. Honey has been shown to destroy many strains of bacteria including Staphylococcus, Streptococcus, Staphaureus and Helicobacter Pylori (offering a cure for millions of peptic ulcer sufferers). Consequently many types of bacteria cannot survive in honey, reducing the risk of infection and wound healing can take place.

The mode of application of honey varies. The most commonly reported procedure is to clean the site first with saline, spread honey on the wound and cover with a dry dressing, which is changed daily. Honey is hygroscopic (able to attract moisture). It draws moisture from the wound by osmosis forming a solution of honey that does not stick to the underlying tissue. This helps the dead tissue to separate and encourages growth of new granulation tissue. Honey dressings are therefore easy to apply and remove. Application of the dressing causes no pain, or only a minor stinging sensation. The dressing is non-irritating and causes no allergic reaction and has no harmful effects on tissues. Removal of the dressing has been shown to be relatively easy and non-painful with necrotic and gangrenous tissue being lifted off easily. There is no adhesion to the underlying granulation tissue and no bleeding when removing the dressings. The high osmolarity of honey induces outflow of lymph, which assists in lifting dirt and debris from the bed of the wound. Therefore dirt is removed with the bandage when honey is used as a dressing, leaving behind a clean wound. This cleansing effect makes surgical debridement unnecessary and saves the patient pain or risks associated with anaesthesia and surgery.

Clinically it has been recorded that honey quickly reduces inflammation, swelling and pain. Studies have shown that lesions treated with honey showed less oedema and fewer polymorphonuclear and mononuclear cell infiltrations. The sloughing of necrotic and gangrenous tissue is induced. Honey has been reported to promote the formation of clean healthy granulation tissue and epithelialisation of the wound. It is thought that honey has a direct nutrient effect on regenerating tissue as it contains a wide range of amino acids, vitamins and trace elements in addition to large quantities of sugar.

Experiments carried out on burns compared honey with a sugar solution of similar composition to honey. These showed that healing was more active and advanced with honey and the time taken for complete repair was significantly less. Honey resulted in a clearly seen attenuation of inflammation and exudation and a rapid regeneration of outer epithelial tissue. From this it was concluded that it is the chemical constitution rather than the physical properties of honey that are important.

In cases of infected wounds the use of honey has been shown to be very effective. The antimicrobial properties mentioned before prevent bacterial growth in the moist environment created. When using honey it may be necessary to warm it for easier application. However excessive heating should be avoided because the glucose oxidase enzyme in honey, which produces hydrogen peroxide, a major component of the antibacterial activity, is readily inactivated by heat. Reports show that honey is successful in cleaning up infected wounds with one study showing that wounds became sterile within one week using a honey dressing.

Honey dressings have also been shown to reduce odours from infected wounds. The high glucose levels that honey provides are used by the infected bacteria in preference to amino acids from the serum and dead cells. This gives rise to lactic acid instead of ammonia, amines and sulphur compounds that are the cause of malodour.

In the studies carried out, no adverse effects have been noted. Honey has been used topically on wounds for thousands of years without gaining a reputation for adverse effects and allergy to honey is rare. There is concern however that the high levels of glucose contained in honey may adversely elevate the blood glucose level of diabetics when applied topically on an open, large wound.

In conclusion it can be said that the use of honey should be realistically considered when treating venous ulcers. It provides a moist healing environment while preventing bacterial growth. It is effective in treating heavily infected wounds, making them sterile, without the side effects of antibiotics. It provides glucose to nourish leucocytes to drive the respiratory burst that produces hydrogen peroxide (the dominant component of the antibacterial activity of macrophages). Honey gives a fast rate of tissue regeneration and suppresses inflammation, oedema and malodour in wounds. The use of honey dressings results in better tissue organisation and consequently an improved tissue strength. All these findings suggest that honey when applied topically, is an ideal dressing for cutaneous wounds.


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26/Sep/2017

Introduction.

Swelling of the ankles and legs is common and patients usually seek advice because they want to know the cause.

 

Aetiology

The causes of a swollen leg include:

Central causes

  • Congestive cardiac failure
  • Renal diseases
  • Hepatic disease
  • Protein deficiency eg gastrointestinal disease involving malabsorption or malnutrition.
  • General allergic reactions eg to drugs.

Peripheral causes

  • Inflammation:
    • Local trauma (including a ruptured Bakers cyst)
    • Insect bites
    • Sun burn
  • Venous disease
    • Superficial incompetence (varicose veins)
    • Deep venous incompetence (absence of deep vein valves, previous DVT)
    • Venous outflow obstruction
    • Vein occlusion: eg pelvic  vein or IVCthrombosis, an aorto-caval fistula,
    • Mass (eg uterine cancer) pressing on the pelvic veins.
  •  Lymphoedema
    • Lymphoedema is the excessive accumulation of interstitial fluid as a result of defective lymphatic drainage.
    • Primary lymphoedemahas no known cause. It occurs in 1 in 33,000 people. In a third of cases there is a family history. Usually, the limb starts to swell insidiously between 10 and 25 years of age. It is 3 times more common in women than men.
    •  Secondary lymphoedema results from a pathological process disrupting the lymphatic drainage including
      • malignancies which spread to or include the lymph nodes
      • surgical block dissection of affected lymph nodes and radiotherapy
      • filariasis worm infections are a common cause world wide, but rare in the UK
      • self induced oedema from repeatedly applying a tight tourniquet to the limb or by never using it are recognised presentations of Munchausen’s syndrome.

Clinical features

Central causes

  • other suggestive symptoms have often previously been investigated
  • Both legs are  involved
  • There may be oedema elsewhere

Peripheral causes

  • Local inflammation
    • Examine for portal of entry or a haematoma
    • There may be a recent rash.
  • Venous swelling
    • Previous DVT or varicose veins are common
    • The swelling involves the ankles and legs maximally and spares the feet.
    • There may be associated haemosiderin and atrophic or ulcerated skin changes around the ankle.
  • Lymphoedema
    • It is important to determine whether this is primary or secondary
      • Note details of previous surgery and radiotherapy and recent travel abroad.
      • A family history of lymphoedema suggests a primary aetiology.
      • Examin the groins for pathological lymph nodes and a rectal and vaginal examination are indicated if a secondary cause is suspected.
    • The leg
      • Swelling is most prominent distally. Oedema is on the dorsum of the foot and the contour of the ankle is lost first. Rarely does it spread above the knee.
      • In long-standing cases the skin is hypertrophied and lichenified with cracks in the interdigital clefts.
      • Recurrent attacks of cellulitis are common, the infection entering via skin cracks.
      • Occasionally patients develop vesicles in the skin which leak clear lymph.

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Investigations

Investigations are undertaken to identify the cause of the leg swelling.

Central causes suspected

  • Serum urea and electrolyte levels
  • Liver function tests (including albumen and total protein)
  • Full blood count
  • ESR, CRP

Venous causes suspected

  • Duplex ultrasound scans of leg veins will demonstrate:
    • superficial venous incompetence and identify the sites of communication between deep and superficial venous systems.
    • patency of the deep venous system to exclude a deep vein thrombosis and determine if there is reflux
  • Pelvic and abdominal ultrasound to identify masses which may be compressing the pelvic veins or occluding the pelvic lymphatics. CT or MRIscan may be required to confirm
  • Photoplethysmography will confirm the findings of the duplex scan and provide information about the patency of the pelvic veins. If this suggests there is a venous outflow problem then a venogram should be performed.

Lymphoedema suspected

  • Pelvic and abdominal ultrasound to exclude a secondary cause
  • Radionuclear lymphscintogram is a simple test in which a small volume of a high-energy-emitting colloid-bound radionucleotide is injected into a webspace in both feet. Scintogram scans are then taken at regular intervals over the next few hours. This not only makes the diagnosis but also identifies the site of obstruction to lymphatic flow in the leg or the abdomen/thorax. This test is safe, uses a low dose of radiation, is easy to perform and is not painful
  • Lymphography is no longer used.

 

Management

  • Treatment depends on the aetiology and severity
  • Although cosmetically embarrassing, swollen legs are often only of nuisance value
  • In many cases aggressive treatment is not needed and only advice and reassurance need be given

 

Venous leg oedema management

  • If oedema is minor, a conservative approach is best as outlined below under “limiting oedema progression”.
  • If oedema is a major problem or there are concomitant venous leg problems then surgical intervention may be required. If appropriate this involves removing the superficial veins.

Primary Lymphoedema Management

  • Conservative (the vast majority)
    • Counselling explains that the disorder does not involve any major pathology and although it may progress it very rarely requires surgery. It is a life-long condition
    • Limiting oedema progression can be achieved by:web-soa-stockings
      • the continuous use of graduated compression stockings throughout the day (www.pebbleuk.com  to provide symptomatic relief from aching and to reduce the likelihood of progression. Compliance is a problem especially in hot weather and young female patients. Often the stocking is old or does not compress sufficiently to reduce the swelling as is the case here.
      • raising the foot of the bed at night and elevating the leg whenever possible
      • use of pneumatic compression pumps and leggings. The flowtron-boot sequential segmental machines such as the lymphopress are probably more effective than the single chamber boots, but are usually more expensive.
      • The patient and their partner can be taught leg and foot massage which provides both psychological and physical relief. Long term, regular massage prevents subcutaneous fibrous thickening.
      • Weight reduction is often beneficial
      • Drug treatment is of little proven value and diuretics and anticoagulation should be avoided.
    • web-soa-oilsSkin care:   As the lymphoedema progresses the skin of the foot, ankle and eventually the leg becomes hardened and irregular. To prevent this the patient needs to oil the skin at least once a day with a low allergenic oil; often olive oil is best. This is seen in this photo.
    • Treatment of infections
      • Lymphoedematous limbs do not respond normally to minor trauma or insect bites. Infection is more likely, causing increased swelling and cellulitis which can spread rapidly.
      • Antibiotics should be given promptly and hospital admission will be required if there is no rapid response.
      • Prevention requires careful foot hygieneweb-soa-infection, including the use of antifungal powder or cream to prevent athlete’s foot.

 

  • Surgical intervention
    • Should only be undertaken when the heaviness of the leg is severely hampering the patient’s quality of life.
    • It is possible to remove the mass of oedematous fatty tissue under the skin, superficial to the muscular fascia; only half the leg is treated at a time.
    • Post-operatively bed rest is required for several weeks. The leg is treated with a lymphopress; wound healing is often a severe problem.
    • The result is not always cosmetically pleasing.
    • This is only a temporary measure and the lymphoedema will redevelop.
    • However, if patients are selected carefully a very high patient satisfaction rate is achieved.

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26/Sep/2017

Laval or Maggot therapy is used to remove the thick sloughy material that collects on a venous ulcer.

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Saline is added to the pot of maggots and placed on a straining cloth

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The maggots are placed on the wound supported by a surrounding bridge.

Laval therapy and Wound Management

By Frances Dear (Medical Student)

Chronic wounds represent a serious challenge for today’s NHS. Larval therapy involves the use of fly larvae (maggots) to heal wounds and combat infection. This practice may, at first, sound unlikely but it is effective and its use been known of for centuries.

The term “biosurgery” describes the use of living maggots on wounds to remove devitalised tissue, decrease infection and improve wound healing (Wollina et al2000), whilst leaving the healthy surrounding tissue alone. This is principally used to debride wounds such as leg ulcers, pressure sores and other lesions which contain large amounts of necrotic or infected tissue, including those with methicillin resistant Staphylococcus aureus (MRSA). Larval therapy has also been used to successfully treat burns, osteomyelitis, mastoiditis and the management of squamous cell carcinomas.

History

Many cultures around the world, such as the Mayan Indians and the Australian aborigines, have used the deliberate introduction of maggots into gangrenous and infected wounds. Prior to the introduction of penicillin and sulphonamides, larval therapy was used to debride wounds and improve patient prognosis.

The first medical studies of the use of maggots were documented by Dr William Baer, a US surgeon who had observed first hand the effects of maggot infestation on soldiers’ wounds in France during World War I. During the 1920’s and 1930’s, Baer successfully treated osteomyelitis and leg ulcers with maggots and reported that the therapy debrided necrotic wounds and promoted the formation of granulation tissue. Many doctors of the time used maggots to treat chronically infected and necrotic wounds. However, larval therapy fell out of favour with the introduction of antibiotics and new surgical techniques. Nevertheless, the emergence of antibiotic resistance has, once again, given birth to the renaissance of maggot therapy.

As an interesting side note, maggot infestation also plays an occasional role in solving crimes, particularly that of homicide. In a branch of science known as forensic entomology, pathologists in the US use the age of maggots found within a victim’s body to help determine the time of death.

 

Cost Effectiveness of Larval Therapy

The treatment of necrotic ulcers involves considerable time and expense, particularly since the current standard treatment involves the application of hydrogels. In studies, Wayman et al (2000) compared larval debridement therapy with conventional hydrogel dressings in the treatment of necrotic venous ulcers. Twelve patients were randomised to receive either larval therapy or conventional therapy. All six patients treated with larval therapy had their ulcers successfully debrided with a single three-day application. On the other hand, two of the six conventionally-treated patients still needed dressings after a month has passed. The median cost of treatment of the larval group was £78 compared with £136 for that of the conventional group.

The advantages of larval therapy therefore include decreased cost, reduced hospitalisation time, rapid debridement of necrotic tissue and infection control.

Despite this, large-scale trials of maggot therapy have yet to be carried out and are hampered by a lack of funding.

Application of Larval Dressings

Larval therapy is often used when conventional therapy has failed. Maggot infestation in vertebrates is termed ‘myiasis’. Naturally occurring myiasis can be either beneficial or harmful, depending upon the species of maggot involved. It is important to note that only certain species of maggot are suitable for medical use as some species will also attack viable tissue. The larvae of the common greenbottle fly Lucilia (Phaenicia) sericata is often used because it will only feed on necrotic tissue. In the UK, sterile maggots are bred at the Biosurgical Research Unit, Princess of Wales Hospital at Bridgend in Glamorgan, by allowing flies to lay eggs on strips of liver, after which the eggs are sterilised.

A hole is cut out of a dressing the same size and shape as the wound. Next, this dressing is applied to the wound, providing a base for the outer dressing and protecting the surrounding skin from the proteolytic enzymes of the larvae. Approximately 10 larvae per square centimetre of lesion are then applied. The wound and larvae are covered by a fine net, which is attached with adhesive tape. An absorbent pad is placed on top of the netting. The larvae should be extracted from the wound after three days, by removing the netting and rinsing the lesion with sterile saline.

No significant risks or severe adverse events have been reported from maggot debridement. There is the possibility that an allergy may develop to the foreign protein material of the larvae, though this has not been reported. The larvae must leave the wound in order to pupate or they will die, and consequently, there is no danger of them remaining in the wound and multiplying. Some patients report a tickling/moving sensation when the dressing is in place.

 

Mechanism of Action

The ways in which maggots clean a wound are not fully understood but there are thought to be at least four possible mechanisms:

1.      Larvae secretion of proteolytic enzymes which liquefy necrotic tissue

2.      Actual ingestion of the tissue by the larvae

3.      Secretions from the larvae change the wound pH

4.      Bacteria are destroyed in the larval alimentary tract due to antimicrobial substances. In vitro, maggots kill or inhibit the growth of S. aureus and group A and B streptococci. Additionally, they show some activity against Pseudomonas spp.

It is suggested that larvae also stimulate the production of granulation tissue.

In vitro studies show that larval alimentary secretions have a significant effect on human fibroblasts when used in conjunction with Epidermal Growth Factor (EGF) or the cytokine Interleukin 6 (IL-6) (Prete 1997).

Conclusion

Maggots can quickly and efficiently debride necrotic wound tissue and promote healing. The exact mechanism of action has yet to be fully elucidated but studies suggest that larval secretions significantly amplify the effects of EGF and IL-6. Over the centuries, the benefits of larval therapy have been documented and it is becoming a re-emerging treatment option.

References

Bonn, D  Maggot Therapy: an alternative for wound infection  The Lancet 356: 1174  Sept 30 2000

Jones, M & Thomas, S  Larval Therapy  Nursing Standard 14(20): 47-51 Feb 2000

Prete P E, Growth effects of Phaenicia sericata larval extracts on fibroblasts: Mechanism for wound healing by maggot therapy  Life Sci  60(8): 505-10  Feb 1997

Thomas S, Jones M, Shulter S, Jones S  Using larvae in modern wound management  Journal of Wound Care  5(2): 60-9  1996

Wayman J, Nirojogi V, Walker A, Sowinski A, Walker M A,  The cost effectiveness of larval therapy in venous ulcers  Journal of Tissue Viability  10(3): 91-4  Jul 2000

Wollina U, Karte K, Herold C, Looks A,  Biosurgery in wound healing – the renaissance of maggot therapy  Journal Eur Dermatol Venereol  14(4): 285-9  Jul 2000


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26/Sep/2017

Varicose veins

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Definition

Varicose veins are abnormal tortuous dilated superficial veins seen mostly on the legs. Reticular veins are prominent normal superficial veins, which do not usually vary in thickness. Thread or spider veins are fine thin cutaneous veins of a millimetre or so diameter.

Epidemiology

Incidence:     50% of those over 50 years of age have signs of venous disease on                      their legs50% of these have true varicose veins

Age range:  increases with increasing age

Sex ratio:      Distribution is equal, but more women than men present (5:1)

Race:             Caucasians have a higher incidence than other races

Associations:   Family history, obesity, pregnancy, oral contraceptive pill, possibly                                      HRT; occupations which result in standing for long periods may worsen varicose vein symptoms

 

Varicose veins and their complications account for 500,000 general practitioner consultationsper year. 10% of these will receive hospital treatment.

 

Aetiology

  • Primary varicose veins (95%) are caused by an increase in venous pressure in the superficial leg veins. This is due to damage to the venous valves between the deep and superficial venous systems. This may be at the saphenofemoral junction between the long saphenous vein and the common femoral vein in the groin; at the sapheno-popliteal junction between the short saphenous vein and the popliteal vein in the popliteal fossa; or at other sites when they are known as perforators.
  • Secondary varicose veins (5%) occur when the increased venous pressure in the superficial venous system is due to a disturbance in venous blood flow elsewhere, for example in pelvic and extensive leg vein thrombosis, and arterioveonus malformations (either congenital or acquired as a result of a fracture)

 

Clinical features

  • The clinical features of varicose veins fall into two groups.
  • Group I symptoms

These are associated with a low morbidity, but can affect the patient’s quality of life. Treatment is therefore dependent on the patient’s perception of disruption caused.

  • Aching – dull heaviness or fullness in the leg, relieved by leg elevation
  • Cosmetically unsightly
  • Itching  and throbbing
  • Swelling of ankles or leg
  • Group II complications

These symptoms can be associated with significant morbidity and therefore intervention is indicated.

  • Bleeding
  • Superficial thrombophlebitis (see other chapter)
  • Venus skin changes – venous hypertension causes an increase in capillary pressure and eventually leads to skin and subcutaneous tissue changes usually at the ankle. The main skin changes are:
    • induration (lipodermatosclerosis) – diffuse fibrosis of subcutaneous tissues accentuated by fat necrosis and chronic inflammatory changes leads to areas of hard tissue in which veins form large hollow grooves
    • pigmentation – deposits of haemosiderin in the skin from degraded extravasated erythrocytes
    • ulceration – caused by chronic venous hypertension. As areas attempt to heal the surrounding areas show a white scarring –  “atrophie blanche”.
    • eczema – often occurs without frank ulceration.

 

Investigations

Investigations should be undertaken only if treatment is indicated. Investigations aim to answer three questions:

  • What is the site of incompetence between the deep and superficial venous systems? This can usually be identified using the hand held Doppler or a Duplex ultrasound
  • Is the deep venous system patent? Removal of the superficial venous system when the deep system is not patent will markedly worsen venous hypertension. Identify with Duplex ultrasound
  • Are the pelvic and abdominal veins (the venous outflow) patent? This is confirmed using MRIor venography.

 

Management

  • Treatment options.
    •  No intervention
    • Graduated compression stockings
    • Surgery
  • Treatment depends on the patient and their symptoms
    • Group I symptoms,
      • The decision to operate depends very much on the impact of symptoms on quality of life
      • All symptoms (apart from cosmetic improvement) can be managed by wearing graduated compression stockings
      • Varicose vein surgery will not remove thread or reticular veins. Other forms of treatment are needed (see below).
      • Surgery is only indicated for symptoms the patient has now and not as prophylaxis against development or progression of symptoms.
      • Surgery often requires a general anaesthetic and has a risk of complications.
  • Group II complications
    • serious consideration to surgery should be given.
    •  This group of patients, however are usually of an older age group and  often have co-morbidity which increases their anaesthetic risk. In these patients graduated compression stockings may be an alternative.
    • For those patients with varicose veins, which arise from unusual causes such as arteriovenous malformations, surgery is usually best avoided.

 

  • The Surgery
    • There are methods of removing varicose veins.
    •                Saphenous vein stripping
    •                Endovenous ablation
    •                Foam sclerotherapy.
  • Potential complications of surgery
    • Bleeding
      • A little blood may ooze from the wounds during the first 12 hours. This usually stops spontaneously, especially if the wound is pressed for ten minutes.
      • Bruising is variable, but common and will cleared within 3 weeks
      • Large wound haematomas are rare.
    • Healing fibrosis can produce firmness under the operation scars or in the line of the treated veins. If there is associated swelling, redness and tenderness, a wound infection needs  to be excluded.
    • Wound infections
    • Neuropraxia – some numbness over phlebectomy sites is common and temporary. True permanent neuropraxia may occur over the skin supplied by the saphenous nerve, which is damaged while stripping the long saphenous vein or during a phlebectomy. Sural nerve damaged during a short saphenous vein ligation in the popliteal fossa also produces neuropraxia.
    • Recurrence – there is a one in five chance of developing further varicose veins within five years.
  • Post-op care includes:
    • graduated compression stockings or bandages are warn day and night for seven to ten days and thereafter only during the day for a month
    • simple oral analgesics
    • sitting with the feet elevated so that heels are higher than hips to aid drainage of excess fluid from the tissues and assist healing.
    • Patients are advised to take a short walk of a few hundred yards three times a day
    • return to work and driving within 2 weeks of surgery; swimming and cycling are allowed after the dressings have been removed.

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26/Sep/2017

“Does horse chestnut have any effect on treating varicose veins?”

By Lucy Bell, . Medical Student,  Royal Free Hospital

 

Introduction

Current Varicose vein treatments include compression therapy; lifestyle measures such as weight loss and regular walking; injection sclerotherapy; laser coagulation; and surgical treatments to remove the veins, which is accepted as the most effective treatment in terms of long term prognosis (Paraskeva, 2010). However, as rates of recurrence and ineffectuality of treatments remain a problem – as well as the advantages that a completely non-invasive treatment would offer – finding a pharmaceutical treatment for CVI and varicose veins is an attractive prospect. A suggested source for such an agent is the extract of the nuts of the horse chestnut tree (aesculus hippocastanum), a dedicuous tree found widely throughout the temperate world (Alt. Med. Rev., 2009), which was first suggested in British Medical Journal as a treatment for venous conditions in 1928 in a letter, claiming the extract as an effective treatment for phlebitis (Patterson & Cyriax, 1928). Horse chestnut seed extract (HCSE) is currently used in Germany and, increasingly, in the USA in the treatment of CVI, as well as other conditions such as haemorrhoids and post-operative oedema. However, the mode of action by which the agent acts is a matter of discussion, as is the evidence for their efficacy in treating highly progressed CVI including varicose veins.

The Research

 

HCSE is a mixture of substances including bioflavinoids such as quercetin and kaempferol, proanthocyanidin A2 (an anti-oxidant), coumarins such as fraxin and aesculin, and the constituent which is proposed as the primary active agent in treatment of venous disease – aescin, a mixture of αand βtriterpine saponins, the latter of which is suggested to have anti-oedematous, anti-inflammatory and vasoprotective properties (Alt. Med. Rev., 2009). The chemical structure of aescin is shown in Figure 1.

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Figure 1: chemical structure of aescin. (Sirtori, 2001).

The vast majority of the research into the action of aescin was carried out in Germanyin the 1960s and 1970s. Recent translations of research postulate it acts by selectively increasing the calcium sensitivity of smooth muscle in the walls of veins, and thus increases venous tone (Sirtori, 2001), as well as inhibiting hypoxia in the vessel walls and thus inhibiting the release of vasoactive substances and hence reducing vascular permeability. This is additionally combined with suggested actions reducing the adherence or activation of leukocytes in veins. All of these mechanisms could potentially reduce dilation of vessels and oedema, and preserve venous function (Guillame et al, 1994). An alternative or concomitant foundation of the action of aescin is suggested to involve inhibition of enzymes such as elastase and hyaluronidase which are involved in proteoglycan degradation, leading to a shift in balance of proteoglycan metabolism towards net synthesis rather than net breakdown, which could potentially  “firm” vessel walls and prevent leakage and dilation (Pittler & Ernst, 1998).

The experiments used to elucidate these actions include studies of animal models in which aescin has been shown to prevent oedema from veins in its initial exudative stages, as well as significantly increasing venous contraction in experiments in which dog veins were exposed to aescin in vitro (Sirtori, 2001). However, one study which tested the constriction/relaxation function in vitro of non-varicose and varicose segments of human saphenous vein showed that while vasoactive contraction-stimulating drugs tested – aescin and phenylephrine – could stimulate contraction in the non-varicose veins but not in the varicose specimens (Brunner et al, 2000). The authors of this study suggest that venotonic drugs cannot be expected to work in veins which have walls which are severely diseased and insufficient, and thus that agents such as HCSE may only be effective in treatment of CVI in early stages and not when it has progressed to varicose veins due to inherent features of their pathophysiology. These conclusions are somewhat ramified by the clinical studies which have examined the efficacy of HCSE in the treatment of venous disease.

The Clinical Efficacy

An assortment of clinical trials have been performed which examine the use of HCSE in the treatment of CVI and/or varicose veins, including double-blind randomised control trials (RCTs) comparing HCSE to placebo controls or to reference medication controls. HCSE was typically trialled as an orally dosed capsule containing 100-150mg of aescin, taken twice daily; use of a topical gel was also examined, although not in any RCTs. Eight placebo controlled RCTs reviewed by Pittler & Ernst, 1998 suggested that HCSE can cause significant decreases in CVI clinical indicators such as lower leg volume and leg circumference at the calf and ankle. Patients also reported significant reduction of symptoms such as leg pain, fatigue and tenseness.  Five reference medication controlled RCTs reviewed by the same authors reported similar findings, with HCSE showing similar efficacy to reference medications such as 0-rutosides. In all studies, patients generally reported tolerance to HCSE as a treatment option.  Adverse drug reactions such as nausea, headache, dizziness and pruritis occurred in a minority of patients (0.9-3.0%), with no major oral toxicity, mutagenic/teratogenic effects or anaphylaxis reported. It must be noted that half of these trials involved small sample sizes (<100 patients) and that is likely that any trials producing negative results may have remained unpublished, due to some bias present in alternative medicine journals in which they are reported; before any definitive conclusions about efficacy of HCSE for widespread acceptable clinical use can be drawn, larger RCTs will be necessary.

An additional factor which must also be examined when considering HCSE as a clinical option is whether it has increased or comparable efficacy compared to other treatments for varicose veins and CVI. Two clinical studies have been undertaken which compare oral HCSE vs. placebo to compression therapy vs. placebo in the treatment of CVI; one in patients with early stage CVI without varicose veins and one in patients in later stage CVI when varicose veins are present (Ottillinger & Greeske, 2001). The former study found HCSE and compression therapy to be significantly and equally better than placebo in reducing leg volume (again used as a clinical indicator), but the latter found only compression therapy to demonstrate a significant effect with HCSE falling in efficacy as CVI severity increased. The results of this study are shown in Figure 2.

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Figure 2: reduction of leg volume in CVI patients using HCSE vs. placebo and compression therapy vs. placebo. Grade I is defined as early CVI, Grade II and IIIa are defined as advanced CVI, by the Widmer/Marshall classification. (Ottillinger & Greeske, 2001).

This corroborates the basic science findings that aescin exhibits vasocontractive effects on non-varicose veins and not on varicose veins, as it may be that in early CVI, venous walls are not yet permanently damaged and so HCSE may have use in limiting or slowing the disease process, or at least in reducing symptoms, whereas later in disease progression, i.e. at the point of varicose veins, it is not an effective treatment option – thus compression therapy or surgery is likely to offer a better option at this point.

Conclusions

Chronic venous insufficiency (CVI), with the possibility of varicose veins as a consequence of disease progression, affects 25% of the population of Western Europe (Ottillinger & Greeske, 2001), and due to the severe morbidity that insufficient treatment may lead to, effective treatment options are clinically essential. Horse chestnut seed extract (HCSE), and in particular one constituent of the extract, aescin, has been suggested as a potential source of a pharmaceutical agent which may be effective in the treatment of these diseases. Examination of the scientific and clinical evidence investigating this claim suggests that aescin may indeed have some vasoactive effects which may be useful in the treatment of early stage CVI due to vaso-protective actions which can slow disease progression and prevent symptoms while veins are still capable of responding to vasoactive agents. However, in later stage disease, including when varicose veins are present, the pathophysiology of the disease state means that aescin may no longer be an effective treatment option; the fact that varicose veins are insufficient and do not respond to vascular control can be considered one of their cardinal clinical features and treatment must recognise this. Taken as a whole, these findings indicate that HCSE may have a use in early stage CVI in the prevention of varicose veins and other complications of venous insufficiency, but in treating varicose veins themselves, it is unlikely that HCSE will be of any significant benefit. However, before any widespread clinical use for any condition is ratified, there is still a requirement for larger and more thorough RCTs comparing HCSE to placebo and to alternative treatments including surgery, in order to fully verify it as a safe and effective treatment option.

References

Aesculus hippocastanum (horse chestnut) – monograph. Alternative Medicine Review 2009; 14: 3, 272-283.

Brunner, F. et al. Responsiveness of human varicose saphenous veins to vasoactive agents. British Journal of Clinical Pharmacology 2001; 51: 219-224.

Guillame et al. Arzneimittelforschung (Drug Research) 1994; 44: 25-35.

Lim, C.S. and Davies, A.H. Pathogenesis of primary varicose veins. British Journal of Surgery 2009; 96: 1231-1242.

Ottillinger, B & Greeske, K. Rational therapy of chronic venous insufficiency – chances and limits of the therapeutic use of horse-chestnut seeds extract. BMCCardiovascular Disorders 2001; 1: 5.

Paraskeva, 2010. Oxford Handbook of Clinical Medicine, Surgery, Chapter 31. 8th ed 2010. Pg 660-661.

Patterson, G. & Cyriax, E. The British Medical Journal 1928; 2: 3545, 1111-1112

Pittler, M & Ernst, E. Horse-Chestnut Seed Extract for Chronic Venous Insufficiency. Arch. Dermatol. 1998; 134: 1356-1359

Sirtori, C. Aescin: pharmacology, pharmacokinetics and therapeutic profile. Pharmaceutical research 2001; 44: 3


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Daryll Baker is a Consultant Vascular Surgeon at the Royal Free Hospital London and Clinical Lead for North Central Region Vascular Services.

He read Medicine at Oxford University and trained in Vascular Surgery in Nottingham, London and Edinburgh. He obtained his research PhD from the University of Wales.

Contact

Wellington Hospital
34 Circus Road
London
NW8 9SG

020 7722 7370

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