Cryosurgery for Warts

Abstract

Cryosurgery stands among the first line of treatment options for warts. Using the correct cryogen, proper delivery systems and meticulous attention to technique, over 90 % of warts can be cleared with one session with minimum discomfort to the patient and excellent cosmetic results.

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FormalPara Key Points

• Never treat a lesion with cryosurgery unless certain of the diagnosis upon clinical assessment. If unsure of the diagnosis, refer the patient to a more experienced colleague or take a biopsy.

• The easiest and most successful way to treat most warts is by using liquid nitrogen via a closed handheld cryogun and the open spray technique.

• De-bulking warts with a surgical blade under local anaesthetic will lead to a far higher cure rate and a quicker postoperative recovery and is more comfortable for the patient.

1 Introduction

Warts (verruca vulgaris) are benign epidermal skin tumours that affect almost everyone at some stage in their life. There are many types of warts (Table 9.1) and over 100 subtypes of the human papillomavirus (HPV) that can affect various parts of the body (Table 9.2). HPV is not highly contagious and most warts will not penetrate intact skin. They usually need a portal of entry such as a crack or a cut in the skin to gain access. Diagnosis is usually obvious especially in children but warts can be more difficult to diagnose in certain areas such as the feet (Table 9.3) and genital areas. Warts are less common in the elderly and can be confused with a basal cell (BCC) or squamous cell (SCC) carcinoma (Fig. 9.1). If in doubt, a biopsy should be taken or the patient referred for a second opinion.

Table 9.1 Names given to different types of warts

Table 9.2 The most common subtypes of HPV causing warts

Table 9.3 How to differentiate a plantar wart from a corn

Fig. 9.1

A “warty”-looking growth on a 56-year-old woman’s hand that was a squamous cell carcinoma in situ

Apart from anogenital warts, which are a risk factor for cervical cancer, most warts are harmless and 60 % clear spontaneously within 2 years without any treatment, especially in children and immunocompetent adults [1]. However, sometimes warts can continue to grow and spread to other parts of the body. The most common indication to treat warts is for cosmetic or comfort reasons. Warts in children are probably best left untreated unless they are particularly unsightly (i.e. warts on the face) or pain (i.e. large plantar warts). Doctors often underestimate the amount of embarrassment patients suffer with their warts, especially if they are on exposed areas (hands or face) (Fig. 9.2) and/or the patient is working with the public or is a food handler. There are many unanswered questions about the simple common wart. Why do some people appear to be immune, while other apparently healthy individuals can be plagued by persistent and recurrent warts?

Fig. 9.2

Multiple hand warts

Patients with a depressed immune system (poorly controlled diabetes, HIV, chemotherapy, lymphoma, transplant patients) are more vulnerable to warts, find it more difficult to clear them and often relapse after treatment (Fig. 9.3). In older patients, particularly if they are immunosuppressed, such as transplant patients, the wart virus may have oncogenic potential and can predispose to skin cancer such as squamous cell carcinomas.

Fig. 9.3

Warts in an immunosuppressed patient

Research into warts and their treatment are scanty and most of what is published is of poor quality and design. A recent Cochrane systemic review of 60 trials on warts showed that 46 (77 %) were classified as low quality, heterogeneity between trials was high and analysis was often inappropriate or misleading [2]. Comparison of different treatments is often difficult to assess, as the exact techniques used for treatment of the warts is not always described.

2 Nonsurgical Treatment

The decision to treat warts has to be made on a case-by-case basis according to the experience of the doctor, patient’s preference and the application of evidence-based medicine (Table 9.4). If warts have to be treated (for pain or cosmetic concerns), the first line of treatment is usually with topical treatments with salicylic acid or a traditional cure. Traditional cures probably get their reputation by the fact that most warts will regress and clear spontaneously within time. A placebo has a 27 % success rate [2]. However, one should never underestimate the power of persuasion, wishful thinking and the ability of mind to cure the body.

Table 9.4 Most common treatment modalities used for the treatment of warts

There are many over-the-counter topical agents used to treat warts in children and adults. Some of these are keratolytic such as salicylic acid which has a cure rate of up to 75 % if used daily for 12 weeks [3]. Others are verucidal such as glutaraldehyde. There is very little evidence to recommend one over the other. Success in treatment is often more dependent on the enthusiasm and persistence of the patient or parent. Most will work better if applied after paring down the keratin with an emery board or blade every night before applying the gel and continuing the treatment for at least 6–12 weeks. Most patients and parents give up long before this, unless is it clearly outlined to them how to apply the treatment and how long the treatment will take.

The 3 % formalin soaks daily for 6–12 weeks can sometimes help clear mosaic plantar warts. The plantar wart should be pared down nightly with an emery board or file, and then the wart is soaked in a bowl of formalin or cotton wool soaked in formalin for 10–20 min. The surrounding healthy skin can be protected with Vaseline® if necessary.

Monochloroacetic acid crystals embedded in 50 % salicylic acid cream can be helpful in isolated plantar warts, less than 10 mm, in patients who are not suitable for cryosurgery or other topical agents. The cream and crystals are held in place over the wart using a corn plaster and tape for 3 days. It causes a sterile abscess which lifts the wart from the surrounding skin. The abscess needs to be incised and drained (which can be difficult in children), and the plantar wart can be shelled out leaving a clean ulcer which will usually heal in 2–3 weeks.

Photodynamic therapy (PDT) has been used for treating warts, but it is time consuming and expensive, and results are variable.

Pulse dye lasers can be effective when treating warts that are not too bulky. Removing the thick keratin is important before laser treatment, as the light will not penetrate thick dark keratin. Like cryosurgery, this can be painful and may require local anaesthetic. One of the advantages is that there is little or no swelling or blistering; post laser treatment, bruising can last 1 week. It is thought to work by blocking the small feeding capillaries, thus causing an ischemic necrosis.

Intralesional bleomycin or interferon can be an effective treatment for resistant warts but is again expensive, very painful and only available in some hospital dermatology departments.

Intralesional immunotherapy using various antigens such as the MMR (measles, mumps, rubella) vaccine or candida skin test antigen causes a delayed-type hypersensitivity reaction increasing the ability of the immune system to recognise and clear the HPV. This has an 85 % cure rate [4].

3 Cryosurgical Treatment

Some patients (or their parents) with unsightly or painful warts do not want to use a cumbersome, uncomfortable, time-consuming treatment with topical agents such as salicylic acid that may only have a 75 % per cent cure rate after 12 weeks [3]. They will often prefer a 10 s treatment with cryosurgery (with local anaesthetic if necessary) with an over 90 % success rate, and the wound usually heals up in 2–3 weeks without scarring (Fig. 9.4a, b).

Fig. 9.4

Hand warts (a) before, (b) 1 week and (c) 2 months post cryosurgery

3.1 Warts

Cryosurgery is a method of selectively destroying unwanted tissue using cold liquids or gasses. The aim is to cause maximum tissue destruction in the target lesion with minimal collateral damage to the surrounding healthy structures. Cryosurgery does not kill the wart virus; in fact viruses can survive and be preserved in liquid nitrogen. Cryosurgery destroys the cells that are infected with the wart virus by creating intracellular ice crystal formation that ruptures the cell, thus allowing clean, healthy, uninfected cells to take their place. Post cryosurgery, there is a lot of swelling which blocks the small feeding vessels, causing ischaemic necrosis to the frozen area, enhancing cell death. In addition, cryosurgery has the unique action of “cryoimmunostimulation”, whereby some of the wart virus is released from the frozen wart after cryosurgery, presenting the wart to the immune system. This acts like a vaccine, helping the body to fight off the HPV in the treated and sometimes even distant untreated warts. As a personal observation, occasionally patients clear their hand warts spontaneously while being treated for their plantar warts. Patients who have a suppressed immune system are less likely to benefit from “cryoimmunostimulation”. Combining imiquimod (Aldara®) with cryosurgery may enhance this response.

There is only one important rule in cryosurgery: never freeze any lesion unless one is 100 % sure of the diagnosis. If a confident named clinical diagnosis cannot be made do not freeze – take a biopsy or refer the patient for another opinion.

Success in cryosurgery is dependent on four main factors:

• Cryogen

• Delivery system

• Patient selection

• Technique

3.1.1 Cryogen

Maximum cell destruction is achieved by a rapid freeze, achieving temperatures of less than −40 C at the base of the lesion; a slow thaw; and carrying out at least two freeze-thaw cycles (Fig. 9.5). This can generally only be achieved by using liquid nitrogen which is the coldest (−196 °C), most versatile, cheapest cryogen available (Table 9.5). Over-the-counter cryogens such as home freezers like Wartner®, which contain a mixture of dimethyl ether and propane (DMEP), are much less effective as most only get down to −30 °C at the surface of the wart with a very slow freeze. Handheld medical devices such as the Histofreezer® or the DermaFreeze® also contain DMEP and are equally ineffective and far too expensive per unit cost to make them practical in clinical practice. Most of these devices are limited as they can only apply the cryogen via a bud applicator which is of a predefined shape and size, whereas warts come in all different shapes and sizes. Nitrous oxide gas, while not as cold as liquid nitrogen, can reach −89 °C and can give reasonably good results provided there is meticulous attention to technique.

Fig. 9.5

Maximum cell destruction achieved by a rapid freeze-thaw cycle

Table 9.5 Different cryogens and their temperatures

Liquid nitrogen is cheap, safe and easily available and is the cryogen of choice for treating warts. A 21 liter extended holding time Dewar’s flask will usually hold enough liquid nitrogen to last 10 weeks of frequent use.

3.1.2 Equipment

While the handheld cryogun is the best way to apply liquid nitrogen, cotton buds soaked in liquid nitrogen and applied to a pared-down wart are still far superior to home freezers such as the Histofreezer® or nitrous oxide gas, particularly if the wart is well pared down or debunked before treatment. When using the cotton bud technique, do not use commercially available cotton buds. Make up your own by winding a large bud of cotton wool around the end of an orange stick and tapering it near the end. This will allow you to have a reservoir of liquid nitrogen which will slowly drip down to the tip when applying it to the wart for a long enough time (usually 10–20 s) before the liquid nitrogen eventually evaporates from the cotton bud. The cotton bud can be re-dipped into the liquid nitrogen to replenish it before each freeze of the warts. Liquid nitrogen should be stored in a polystyrene cup for this technique, and everything should be safely disposed of (the cup, the liquid nitrogen and the cotton buds) to prevent cross infection between patients (Fig. 9.6).

Fig. 9.6

(a) Equipment for the cotton bud technique for treating warts with liquid nitrogen (b) Development of cryoguns over the past 50 years (Used courtesy of Brymill Corporation)

Liquid nitrogen cryosurgery via a closed, handheld cryogun is the safest, most effective, most versatile method to deliver a freeze. A cryogun is a surgical instrument just like a scalpel. Like a scalpel, a cryogun in one doctor’s hands can work wonders, while in another doctor’s hands it can cause a lot of harm.

3.1.3 Patient Selection

Patient selection is crucial in delivering effective cryosurgery. Children under the age of six do not make good candidates for cryosurgery for warts, and doctors should resist parental pressure to freeze warts in this age group. The only exception is freezing molluscum contagiosum, which usually clear up with a tiny, almost painless, three second freeze. Children between the ages of 6 and 12 years are generally poor candidates for cryosurgery unless the child (and not the parent) is highly motivated, can understand what is involved and is determined to have the treatment. As a personal opinion, I avoid treating children with cryosurgery for warts greater than 4 or 5 mm in diameter or a cluster of warts together, unless the child can tolerate a local anaesthetic injection. Other poor candidates for cryosurgery are needle phobics and patients with immunosuppression such as poorly controlled diabetics.

3.1.4 Technique

There is a limit to the depth of freeze one can achieve with cryosurgery. Hypertrophic warts are often covered with thick keratin, which acts as a thermal insulator. This has to be removed with a blade to allow the freeze to penetrate to the base of the wart. Even after removing keratin, many large warts can be 4 or 5 mm deep (Fig. 9.7). Success with cryosurgery is increased dramatically when a wart is de-bulked. Generally this can only be achieved by applying local anaesthetic and surgical paring down the wart. For hand warts, pare them down with a scalpel blade until they are flush with the surrounding skin before beginning cryosurgery. For plantar warts, pare them out leaving a crater to freeze into. In this way, probably 75–90 % of the wart is removed even before starting the freeze. Another bonus is that the local anaesthetic makes the whole procedure far more tolerable for the patients and more enjoyable for the doctor.

Fig. 9.7

Plantar warts are like icebergs. What you see on the surface is only a small part of the wart (Used with permission of the artist PaulGuzzo/Shutterstock.com.)

For most warts greater than 4 or 5 mm in diameter, or for a cluster of warts together, the discomfort of a prick with a 30 gauge needle with local anaesthetic is generally a lot less painful than trying to treat the wart using cryosurgery without local anaesthetic.

Emla® or Ametop® topical anaesthetic is not sufficient on its own to give good analgesia for treating ordinary warts. However, topical anaesthetics are useful in children and needle phobics, as it will allow injecting the local anaesthetic needle with little or no pain or discomfort. The biggest drawback with topical anaesthetics is that they take 30–60 min to work on the skin. Topical anaesthetics on their own work extremely well on mucous membranes (perianal, genital, lip and nostril) and usually work within 10–15 min on mucous membranes.

Local anaesthetic infiltrated with a 30 gauge needle around and under a wart is relatively painless, and it takes 2–3 min to work. Ring block anaesthesia can take 10 min to work. Use local anaesthetic with adrenaline everywhere except on the fingers, toes and the tip of the penis, as local anaesthetic with adrenaline lasts longer and reduces bleeding during and after treatment.

With local anaesthetic, de-bulking the wart is easy and the cryosurgeon can deliver an adequate length of freeze and two freeze-thaw cycles without fear of the patient becoming distressed. Using this technique, clearing of 92.5 % of plantar warts can be achieved and 90 % of these clear with one single treatment [5] (Fig. 9.8a, b). Another advantage to de-bulking is that there is less necrotic tissue to die off post cryosurgery.

Fig. 9.8

Plantar warts (a) before paring, (b) immediately post paring and (c) immediately after one session of cryosurgery

A possible disadvantage is that there can be bleeding while shaving the wart. Stop any bleeding before starting to freeze to maintain local low freezing temperatures. Use alginate dressings, aluminium chloride or cautery to control bleeding. Be careful not to contaminate the cryogun with blood. Put on a fresh glove just before picking it up for freezing.

Postoperative bleeding can usually be controlled with a pressure dressing and elevation. The warts swell up after cryosurgery, compressing the small capillaries, and the risk of bleeding is generally reduced after 24 h. Postoperative pain can usually be controlled by giving paracetamol immediately after the session of cryosurgery, before the local aesthetic has had time to wear off.

Most bulky warts require two freeze-thaw cycles (Table 9.6).

Table 9.6 Suggested freeze time and thaw cycles for some common viral skin conditions

3.1.4.1 Freeze-Thaw Cycle

• Start freezing as quickly as possible until the whole wart is frozen.

• Continue freezing until a halo of normal uninfected skin, 1 or 2 mm, around the wart is also frozen.

• Continue to freeze (at a slower rate to avoid excessive lateral spread) for 10 s.

• Let the wart thaw out completely without heating, before starting a second freeze-thaw cycle exactly the same way, if required.

Most warts are best treated with the open spray technique which is quick and does not require any equipment or probes to be autoclaved between patients. For smaller warts, less than 10 mm, use the C or E spray tip, freezing with two consecutive 10 s freeze-thaw cycles. For larger warts, one could use the B spray tip. The contact probe technique is useful when needing to protect the underlying structure such as around the eye or nose. It is also slightly less painful. Applying a small amount of ultrasound gel to the tip of the probe allows the probe to stick to the wart during the freeze so that you can elevate the wart from the surrounding structures during the freeze. Any probes that touch the skin need to be autoclaved between patients.

Freezing down the auroscope (otoscope) cone is a useful technique for plantar warts, which allows getting a deeper penetration of the freeze, without too much lateral spread. This leads to a higher success rate with lower morbidity. Use local anaesthetic for plantar warts greater that 4 or 5 mm and de-bulk the area with a blade.

The auroscope cone needs to be 1 or 2 mm larger than the plantar wart and has to be pressed firmly on the target. Spray down the auroscope cone with a C or E spray tip for 10 s only as this is a much more concentrated form of cryosurgery than using the open spray technique. Most plantar warts require two freeze-thaw cycles with the auroscope cone technique. Start the second freeze as soon as the wart is completely thawed out after the first freeze.

Flat warts (plain warts) are usually quite superficial and so are much easier to treat. They do not usually require paring or de-bulking because they are usually small and can often be treated without local anaesthetic. Genital and mucous membrane warts are usually soft with no keratin, and again they do not usually require paring or de-bulking before cryosurgery.

The maximum number of times to freeze any one wart is two to three times. If they are not cleared after this, there is little point in persisting with cryosurgery. It is not infrequent to find patients that have undergone a series of suboptimal painful freezes on the same wart without local anaesthetic, with no de-bulking of the lesions, over the course of many weeks or months, resulting in a very low cure rate. This should not be done.

3.2 Anogenital Warts

Anogenital warts present unique problems as they are usually sexually transmitted and may predispose to cervical cancer, especially in smokers. All patients with genital warts should have a full STI screen and contact tracing. It is usually best carried out within an STI clinic. However, the warts can be treated by a GP/dermatologist/ob-gyn who has experience in wart therapies.

Podophyllotoxin (Warticon® or Condyline®), which has antimitotic activity, was the most common way to treat genital warts. However, nowadays most genital warts are treated with 5 % imiquimod cream (Aldara®) as it will help clear the clinical and subclinical warts. Aldara® is a topical immune response modifier that stimulates the patient’s own immune response to help clear HPV. It should be applied overnight three times a week, for 6–12 weeks. Patients should be warned that the warts can become quite painful during this treatment. Recent surveys have shown that combining imiquimod with cryosurgery seems to be more effective that either treatment alone in the treatment of skin cancer (“cryoimmunostimulation”) [6]. Combination of imiquimod followed by cryosurgery is recommended when there are large and numerous genital warts. Use imiquimod for the first 2 weeks; then treat the warts with gentle cryosurgery under topical anaesthetic (10 s freeze, one freeze-thaw cycles); then continue imiquimod post cryosurgery for another 4 weeks.

Special care should be taken with anal warts in immunosuppressed patients. Numerous, large or suspicious lesions have to be biopsied before any further treatment [7] to rule out malignancies (Fig. 9.9).

Fig. 9.9

Squamous cell carcinoma on an HIV + female patient with multiple anal condilomas (Courtesy of Paola Pasquali, MD)

When treating multiple penile condilomas, care should be taken not to freeze on the same day lesions all around the foreskin as oedema can cause a paraphimosis. Treat one side first. On the second session, treat the other side.

3.3 Periungual Warts

Periungual warts usually occur as a result of damage to the cuticle, which is normally self-inflicted from biting, picking or constantly wetting the hands. Harsh soaps, shampoos and washing-up liquids can also damage the cuticles. Periungual warts can be very difficult to manage, as periungual skin is very delicate.

The first treatment should be topical agents such as salicylic acid to be applied nightly for 6–12 weeks after paring down the wart. Treat with cryosurgery the remaining lesion.

Be careful in the periungual area as too aggressive a freeze may damage the nail plate, which could cause permanent damage to the nail. Use local anaesthetic (either a ring block or local infiltration using a 30-gauge needle and local anaesthetic without adrenalin) as it is a very painful area to freeze. De-bulk as much as possible with a blade, attempting to remove 75–90 % of wart. Sometimes part of the nail will have to be cut to allow proper de-bulking and adequate cryosurgery. Treat the base with a 5–7 s freeze and only one freeze-thaw cycle. If the wart has damaged the cuticle, there may be secondary nail dystrophy in the nail distal to the site of the wart. It is important to document this before starting cryosurgery; otherwise, the patient may blame cryosurgery for the damage to the nail plate. The nail dystrophy usually resolves once the wart clears and the cuticle regenerates, but this can take months (Fig. 9.10a–c).

Fig. 9.10

Periungual warts (a) before, (b) 1 month after and (c) 2 months after cryosurgery

3.4 Complications

Patients should be warned in advance that frozen warts will swell up, may blister and will take 2–4 weeks to heal. Large mosaic plantar warts sometimes take 2 months to heal and can be very painful to walk on for at least the first few weeks. Patients should be instructed to wash the wound with an antiseptic every day and to burst any blisters with a sterile pin, leaving the roof of the blister to act as a natural dressing on the healing wart. Some cryosurgeons prefer to remove the blister completely.

For patients with multiple lesions in both feet and/or hands, a sound advice could be to treat one hand or one foot at a time and only do five to ten small warts per session. If patients have multiple warts, it may take three or four sessions to treat them all. Treat the large, unsightly or uncomfortable warts, and you may leave the other smaller warts for topical treatment, especially in children.

With more aggressive cryosurgery, swelling, blistering and pain is more likely. Provide verbal and written instructions on how to manage the wound post cryosurgery. Melanocytes are very sensitive to cold, and pigmented changes (hypopigmentation or hyperpigmentation) can sometimes occur particularly in dark-skinned patients. Pigment usually comes back after a few months, particularly when the freeze time is not more than 10 s with no more than two freeze-thaw cycles. Alopecia is a risk but this does not usually occur with the type of freeze-thaw cycles used for warts (10 s, two freeze-thaw style cycles). The myelin sheet of the nerve is relatively insensitive to cold. However when freezing over a nerve, for example, the digital nerve on the side of the finger, temporary numbness may occur but usually resolves after a few months. This has the added advantage of reducing postoperative pain after cryosurgery. Collagen and fibroblasts are the least sensitive to the cold, and this is why the skin usually heals without scarring when treating warts with cryosurgery.

The wart virus can display the Köbner phenomenon. The wart seeds in to a scratch or scar. This is sometimes helpful in diagnosing warts, such as a line of plain warts in a scar. The Köbner phenomenon can also cause warts to recur in the scar of previous surgery such as cautery, excision or cryosurgery, if the initial treatment is suboptimal and does not clear all the warts (Fig. 9.11a–c). This is another good reason to treat warts aggressively from the onset and attempt to kill all the wart-infected cells in one single session by combining surgical de-bulking followed by cryosurgery under local aesthetic.

Fig. 9.11

(a) Wart recurring in the scar of a previous suboptimal freeze. (b) De-bulking of wart under local anaesthetic. (c) Shown 6 weeks post cryosurgery

Essential Titbits

• Keratin is a bad conducting material. De-bulking lesions prior to freezing will allow better penetration of the freezing front, reducing freezing time.

• Previously wet keratin (using a wet gauze applied for 1 min) will increase permeability and allow a better freezing procedure.

• Combination treatment with imiquimod enhances the response.

4 What’s Next in the Approach to Cryosurgery for Warts?

Combining imiquimod (Aldara®) with gentle cryosurgery has been shown to enhance the results of treatment for some skin cancers (immunocryosurgery, Chap. 20). This combination may also help in the treatment of recalcitrant viral warts (Fig. 9.12a, b).

Fig. 9.12

Recalcitrant warts (a) before and (b) after two sessions of cryosurgery combined with imiquimod 5 % (Aldara®)

Additional clinical studies aimed to establish differences between treatment wart modalities and recurrence rates are warranted.

Alopecia :

Hair loss

Cryogen :

Liquids or gasses used to lower temperature in tissues

Cryosurgery :

The controlled application of ultralow temperatures to tissues in order to achieve selective tissue necrosis

Cryoimmunostimulation :

Stimulation of the immune system by the release of tumour-specific antigens resulting in the production of anti-tumour antibodies after cryosurgery

De-bulked :

Surgical removal of part of a tumour so as to enhance the effectiveness of other treatments such as cryosurgery

DMEP :

Dimethyl ether and propane

HPV :

Human papillomavirus

Hypertrophic warts :

Warts with a lot of overlying thick hard keratin

Immunocryosurgery :

The combination of immuno-modulators and cryosurgery to enhance the cryoimmunostimulation response

Isotherms :

Lines linking areas of similar temperature

Keratin :

The hard outer layer of the skin

Molluscum contagiosum :

A viral infection for the skin caused by the poxvirus

Mosaic plantar warts :

A cluster of warts that coalesce to form one single large lesion

Mucus membranes :

Membranes lining body cavities and canals that lead to the outside of the body such as the respiratory, digestive and urogenital tracts

Nail dystrophy :

Misshaped, damaged, infected or discoloured nails

Necrotic :

Death of cells of tissues through injury or disease

Numbness :

When you cannot feel anything in part of your body or skin

Periungual warts :

Warts around the proximal end of the nail

Recalcitrant warts :

Warts resistant to standard therapies

Suboptimal :

Being below an optimal level or standard

Warts :

Benign epithelial tumours caused by infection by the human papillomavirus