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Wound Care Today special report – overgranulation

15th October 2013

MANAGING OVERGRANULATION

Author: Jackie Stephen-Haynes, professor and consultant nurse in tissue viability, Tissue Viability Practice Development Unit, Birmingham City University and Worcestershire Health and Care NHS Trust; Stourport Health Centre, Worcestershire

Introduction

This article will consider the normal trajectory of healing as well as the challenge to clinicians presented by overgranulation in wounds. It will analyse the potential causes of overgranulation, discuss how to avoid its occurrence and provide options for treatment with reference to current literature.

An overview of granulation and overgranulation

The mechanisms involved in wound repair are complex, but our understanding of the importance of a moist wound healing environment with increased granulation, epithelialisation and improved scar quality (Winter, 1962) is well-documented, with a greater knowledge of these wound healing mechanisms developing over time (Schultz et al, 2003; Sibbald et al, 2007).

The healing process associated with an acute wound is a dynamic one, which can be divided into three phases (Dealey, 2012):

  • Inflammation
  • Proliferation
  • Maturation.

These three stages should progress in an orderly manner although they will overlap.

While acute wounds usually advance in a predictable and timely manner through the inflammation, proliferation and maturation phases of the healing process, chronic wounds diverge from this expected sequence of regeneration and repair (Krasner, 1995). As McGrath (2011) noted, an essential aspect of secondary intention wound healing is the proliferation of granulation tissue (Figure 1).

Figure 1. Granulation tissue — the surface has the appearance of granules with capillaries looping together on the surface.

Granulation tissue is an intermediary replacement for normal dermis, which matures into a scar during the re-modelling phase of wound healing (Johnson, 2007).  Granulation incorporates a dense network of blood vessels – newly growing capillaries (angiogenesis) – with an irregular upper layer created by the capillaries looping together on the wound surface. This gives granulation the appearance of red lumps (or granules) within the normal paler pink matrix, although despite this appearance, granulation does not bleed easily (Dowsett, 2002). Granulation tissue demonstrates an elevated cellular density incorporating fibroblasts and macrophages, as well as randomly organised collagen fibres (Ovington and Schultz, 2004).

The presence of granulation tissue in the wound is a sign that healing is taking place and this new tissue will protect the wound from bacterial colonisation since it is resistant to infection (Dealey, 1999; Dunsford, 1999; Collins et al, 2002).

Many factors can delay wound healing (Hampton and Collins, 2003) and a lack, or an over-proliferation, of granulation tissue may delay healing and lead to a chronic wound, thereby posing a significant challenge to the clinician.  

Any wound healing by secondary intention will need to produce granulation tissue and in some instances, such as a large cavity wound, a significant amount of granulation tissue is required. When granulation is achieved, the wound bed changes, becoming less ‘wet’ and ‘bumpy’ with a smoother wound surface (Figure 2).

Figure 2.  The granulation has smoothed out; the wound is just slightly moist and is ready for the edges to contract. This stage of healing is known as maturation.

This is the final stage of wound healing, where the epithelial cells can now grow into the centre of the wound and the wound fibres will contract the surface of the wound until it reaches closure – the quicker this takes place, the less scarring there will ultimately be (Son et al, 2005). The collagen that has been laid down during the granulation period is replaced by stronger collagen, while the tissue beneath the scar, and the scar itself, will continue to remodel for up to two years.

Overgranulation

When granulation ‘over grows’ beyond the surface of the wound, this is known as overgranulation, also referred to as hypergranulation, exuberant granulation, hyperplasia of granulation, hypertrophic granulation or ‘proud’ flesh. It is usually present in wounds healing by secondary intention and is clinically recognised by a friable red, often shiny and soft appearance, which is raised above the level of the surrounding skin (Figure 3) (Johnson, 2007). The tissue can be healthy (Figure 4) or unhealthy (Figure 5) (Harris and Rolstad, 1994).

Figure 3. Overgranulation appears as soft tissue that is ‘proud’ of the wound and does not have the granular appearance of granulation tissue.

Figure 4. Healthy granulation tissue — can be treated with pressure or steroid impregnated tape (such as HaelanTape; Typharm) steroid cream or ointment.

Figure 5. Unhealthy overgranulation. It is extremely friable and has developed as a result of clinical infection. May require oral antibiotics and pressure or steroid impregnated tape, steroid cream or ointment.

Oedema in granulation tissue may be associated with occlusive dressings that do not allow drainage of wound exudates (Vandeputte and Hoekstra, 2006). Any oedema will be increased in the presence of bacterial loading in the wound, whether that loading is associated with colonisation or with clinical infection. This oedema could possibly be seen as a ‘healthy’ overgranulation (Figure 4), which is different to ‘unhealthy’, infected and friable overgranulation.

Healthy overgranulation tissue presents as an overgrowth of moist, pink/red tissue (Figure 4) that may bleed easily (Johnson, 2007), whereas unhealthy overgranulation tissue presents as either a dark red or a pale bluish-purple uneven mass rising above the level of the surrounding skin, which also bleeds very easily (Figure 5). Healthy granulation tissue can reduce naturally and heal without intervention, although this may take longer if left untreated – particularly as the surface is moist and provides an ideal medium for bacterial colonisation and biofilm migration (McGrath, 2011).

However, whether or not the overgranulation is regarded as healthy or unhealthy, the wound generally will not heal when the tissue is 'proud' of the wound because epithelial tissue will be impeded from migrating across the wound’s surface and contraction halted at the edge of the swelling.

If clinical infection occurs, the wound may become ‘stuck’ in the first stage of wound healing, which may lead to chronic inflammation (Banerjee, 1999). Therefore, the risk of infection should always be considered in any overgranulating wound.  

Causes of overgranulation

The exact aetiology of overgranulation is unknown. The literature often links infection with overgranulation, but it is not clear which occurs first.

Vuolo (2010) suggests there are three types of overgranulation (see Table 1):

  • Type 1: inflammatory with excessive exudate due to continued minor trauma or friction from mobility
  • Type 2: occluded wound environment (possibly due to infection or chronic colonisation) (Bannerjee, 1999; Vandeputte and Hoekstra, 2006)
  • Type 3: cellular imbalance – an imbalance between collagen synthesis and degradation due to the patient’s pathology.

Table 1: A review of the literature identifies a range of potential causes of overgranulation.

Cause

Granulation tissue  type

Author

Date

Suggested causes include prolonged inflammation caused by infection or foreign body irritant

Inflammatory

Wood

Zitelli

Stone

Harris and Rolstad 

Nelsen

1976

1984

1986

1994

1999

The enhanced effect of growth factors under occlusive dressings

Occlusion

Bolton et al 

Harris and Rolstad

1991

1994

There may also be a relationship between matrix metalloproteinases (MMPs) and the development of hypergranulation

Cellular

Stephens and Thomas

2002

Occlusivity induces cytoxic effects

Occlusive

Van Luyn et al

1992

External friction in gastrostomy and suprapubic sites

Inflammatory

Hanlon and Heximer

1994

Links between the use of occlusive dressings (such as hydrocolloids) and overgranulation

Occlusive

Falanga

1998

The result of prolonged inflammation may be a stimulation of ground substance formation

Inflammatory

Dunford

1999

Clinical infection will halt the healing process and will increase fluid loss and is known to contribute to overgranulation

Cellular

Bannerjee

1999

Occlusive dressings keep the surface of the wound extremely wet, which could encourage oedema and swelling in the wound bed

Occlusion

Vandeputte, and Hoekstra

2006

An imbalance of collagen synthesis and lysis could result in the unchecked proliferation of collagen leading to overgranulation formation.

Cellular

Sussman and
Bates-Jensen

2007

Inflammation and infection

Inflammatory

Warriner and Spruce

2013

Prevention of overgranulation

Overgranulation is recognised as a clinical problem (Harris and Rolstad, 1994) and many clinicians feel the need to remove the excess tissue. However, the limited evidence regarding the development and management of overgranulation means that clinical judgement must be exercised in the management of each patient to ensure that removal of the tissue is not harmful.

Occlusion should be limited to the early stages of wound healing and once granulation is established, a less occlusive dressing could be selected (occlusion can cause an over-stimulation of granulation tissue) (Stephen-Haynes  and  Hampton, 2010).

Infection is thought to be another cause of overgranulation (Bannerjee, 1999) and in this case the best preventative measure would be to ensure the wound does not become chronically colonised or infected. A highly exuding and malodorous wound could be indicative of colonisation. Products such as honey dressings, or other antibacterial dressings, will reduce the colonisation and consequently the potential for infection. In turn, this should reduce the potential for overgranulation  (Best Practice Statement, 2011).

A significant method of prevention of overgranulation is the appropriate assessment of the wound (Stephen-Haynes et al, 2013). Continued assessment will alert the clinician to changes in the granulation status and immediate action will ensure that overgranulation does not become a clinical challenge.

Management of overgranulation

Once it has developed, overgranulation is a difficult condition to deal with. The presence of such tissue, as well as increasing the patient’s risk of infection, will also prevent or slow epithelial migration across the wound and thus delay healing (Dealey, 2012).

There are many treatment options for overgranulation, although research to support their use or to clearly suggest which is the most effective is limited. The treatments reported in the literature (see Table 2) attempt to eliminate the causative factor and focus on reducing any bacteria present, applying compression, reducing the occlusiveness of the dressings used, removing any overgranulation tissue and the use of steroid therapy.  

Table 2: Treatment for overgranulation

Treatment option

Objective of treatment

Evidence base

Application of foam dressing

To flatten and absorb moisture

Harris and Rolstad, 1994; Williams, 1996; Rollins, 2000; Carter, 2003

Change from an occlusive to a non-occlusive dressing

To reduce moisture

Carter, 2003

Use of antimicrobials

To reduce bacteria

Leak, 2002; Lloyd Jones, 2006

Use of a fixative device

To reduce movement and stimulation of new granulation tissue

Best, 2004; Edwards-Jones and Leahy-Gilmartin, 2013

Haelan Tape (Typharm)

To reduce the production of new granulation cells

Johnson, 2007; Oldfield, 2009

Haelan Cream (Typharm)

To reduce the production of new granulation cells (although not licensed for use in overgranulation)

Johnson, 2007; Oldfield, 2009

Topical corticosteroid

Reduces the cell division and production of granulation tissue

Carter, 2003; Cooper 2007

Silver nitrate pencil

Only if all else has been ineffective

Borkowski, 2005

Foam and silver

Has antimicrobial effect as well as providing compression due to the foam

Lloyd Jones, 2006

Surgical excision

Undertaken in theatre as very last resort


Harris and Rolstad (1994) reported the findings of a prospective non-controlled correlational study in 10 patients (12 wounds) using a non-adherent polyurethane foam dressing to reduce overgranulation tissue. The results demonstrated a reduction in granulation, thought to be due to the pressure of the foam impeding the oedema and flattening the overgranulation tissue. Despite the low numbers in the research, its p-value (p < 0.01) led to its adoption in clinical practice. Indeed, several clinicians advocated the application of two pieces of foam dressing to increase the pressure on the tissue (Williams, 1996; Rollins, 2000; Carter, 2003). In this study (Harris and Rolstad,1994), the pressure of the foam dressing was subsequently replaced by a double application of hydrocolloid. Controversially, occlusive dressings are thought to be a possible cause of overgranulation, but the pressure of the double foam application potentially reduced the excess tissue (Harris and Rolstad,1994).

One of the most successful treatments for overgranulation is topical administration of silver nitrate and this has produced good results in practice (Borkowski, 2005). However, the use of silver nitrate directly reduces fibroblast proliferation and is, therefore, not recommended for prolonged or excessive use (Dealey, 1999). For the same reason it should never be considered first-line therapy and should only ever be used with great care in more stubborn areas of granulation (Griffiths et al, 2001). This is particularly important as chemical burns have also been reported with the use of silver nitrate and are more likely to occur with prolonged application. Where necessary, a topical barrier preparation such as petroleum jelly or white soft paraffin, should be applied to protect the normal skin surrounding the area of overgranulation (Griffiths et al, 2001).

Another treatment method is a short course of topical steroid, which is used to suppress the inflammatory process leading to overgranulation (Carter, 2003; Cooper, 2007). Tri-adcortyl cream or ointment (Bristol-Myers Squibb – now discontinued in the UK) was often the chosen steroid in this case, however, as it contains the antibiotic aureomycin it is no longer used due to issues with the over-use of antibiotics. However, aureomycin’s action in reducing the bacterial burden may be one of the possible reasons for the success of Tri-adcortyl, as it removed the infection that stimulated the tissue to overgrow in the first place – similarly, the steroid component of Tri-adcortyl reduced the inflammation, which also stimulates overgrowth.

As overgranulation can be associated with infection, use of an antibacterial dressing such as silver, cadexomer iodine or honey can assist with managing local colonisation and reduce the potential for overgranulation, as well as removing overgranulated tissue itself (Leak, 2002).

Lloyd-Jones (2006) reported the resolution of overgranulating tissue using a silver Hydrofiber dressing (Aquacel Ag; ConvaTec), but this took some weeks to work, much longer than other treatments. The author does, however, pose the question as to whether the most appropriate silver dressing product was used in this study and if the use of silver products on overgranulating tissue is even appropriate. Bearing in mind the length of time the overgranulation tissue took to resolve, it could be argued that the same result would have been achieved without any intervention – similarly it may have been the pressure from the outer dressing that resolved the overgranulation.

Removal of overgranulating tissue 

Because granulation tissue is very delicate, can bleed easily and frequently returns after being removed, this should only be undertaken by a skilled surgeon or dermatologist following holistic assessment. Particular caution should be taken to ensure an accurate differential diagnosis as the removal of malignant tissue may cause harm and should be avoided

Increased pressure

The application of extra pressure using compression bandaging or firm fixation tape may help. However, this should be monitored closely and if changes are not seen within a week, another solutions should be considered (see Table 2). However, there is a lack of literature to back up many of treatment claims and advice is often based on anecdotal and expert opinion. Also, with time, healthy overgranulation may resolve itself without intervention and the tissue only needs to be removed if epithelialisation is impaired and healing is impeded, as the skin’s surface will be restored during the remodelling or maturation stage (Dealey, 2012).

It is clear that there is a lack of overall consensus for treatment, however, broad principles of care should be considered following holistic patient/wound assessment, clinical examination, investigations – including wound swab and tissue biopsy – and referral for dermatological opinion.

Steroid-impregnated tapes

Importantly, most corticosteroids, while fast acting, are not licensed for use on overgranulation. However, the only available steroid-impregnated tape (Haelan Tape; Typharm), contains fludroxycortide, a moderately potent steroid, and is the only product licensed for overgranulation.

Haelan Tape is a transparent, plastic surgical tape, impregnated with 4mg/cm2 fludroxycortide (flurandrenolone), which allows a steady distribution of the steroid at the affected area. Fludroxycortide is a fluorinated, synthetic, moderately potent corticosteroid. As with other topical steroids, the therapeutic effect is primarily the result of its anti-inflammatory, anti-mitotic and anti-synthetic activities. One advantage of the steroid being produced in tape form is that it can be cut to fit around tubes, e.g. percutaneous endoscopic gastrostomy (PEG) tubes and suprapubic catheters.

Layton (2004) reviewed the use of Haelan Tape in dermatology practice, concluding that it is effective in the management of overgranulation. Additionally, the pressure exerted by the tape while in situ may have a positive effect on the reduction of overgranulation tissue.

Importantly, resolution of overgranulation using Haelan Tape was noted within seven days or less by Johnson (2007), who reported successful outcomes in seven patients, including the following conditions/factors:

  • Post-surgery
  • Lymphocele
  • Dehisced abdominal wounds
  • Venous leg ulceration
  • PEG and supra-pubic catheter sites.

Similarly, Oldfield (2009) reports successful treatment of individual cases with Haelan Tape, including an overgranulated surgical wound, a tracheostomy site, a diabetic foot ulcer, a PEG insertion site and a stoma site. 

Overgranulation in diabetes

Soft tissue coverage of chronic diabetic ulcers can be particularly troublesome because of the lack of adequate blood supply available to the wound, which can result in the inadequate formation of granulation tissue (Younes et al, 2006). Also, a person with diabetes will be very prone to clinical infection in wounds due to the inadequate delivery of oxygen and nutrients to the wound bed, which increases the potential for abnormal tissue development such as overgranulation. 

Overgranulation and podiatry

In a 41-patient study of wound healing and infection in nail matrix phenolisation wounds, Dovison and Keenan (2001) report an increase in overgranulation when the wounds were dressed with an amorphous hydrogel.

Cahill et al (2009) advise caution with the differential diagnosis of overgranulation and malignant melanoma in the nail sulcus of the hallux, which on initial presentation was mistaken for overgranulation tissue due to an in-growing toenail.

Silver nitrate, in the form of a stick or a 0.25% compress, has been used in the treatment of overgranulation tissue on the feet, most commonly following nail evulsion. However, Morison (1992) described the treatment as caustic and identified its potential for initiating methaemoglobinaemia, argyria and metabolic disturbances. Similarly, Dealey (1994) stated that prolonged use causes hyponatraemia, hypokalaemia and hypocalcaemia, and does not recommend its use. Therefore, its use should be restricted and alternatives sought.

Overgranulation in PEG sites

Edwards-Jones and Leahy-Gilmartin (2013) note the increase in enteral feeding via PEG tubes due to the ability to insert them via endoscopy. As these tubes are made of polyurethane or silicone it is important that they are held in place with a fixing device to reduce excessive movement. This should be positioned approximately 2mm away from the skin and rotated at least once a week, unless there is a suture in place (Best, 2004).

Infection can be a significant clinical challenge at the PEG site, the most common organisms being Staphylococcus aureus, Candida species and Pseudomonas aeruginosa  (Rolston et al, 2011). Repeated infection may precede the development of overgranulation tissue (Edwards-Jones and Leahy-Gilmartin, 2013) and appropriate care will be required to prevent this, as the moist tissue around the site provides an ideal environment for bacterial colonisation and further biofilm formation (McGrath, 2011). Indeed, Crosby and Duerkson (2007) identified overgranulation as the most common reason for patients with a peri-stomal gastrostomy to seek expert advice.  

A poorly secured tube can exacerbate overgranulation around a PEG site, leading to infection, bleeding, an increase in exudate and odour (Johnson, 2007). It is important to determine the underlying cause and to use appropriate management, for instance, Edwards-Jones and Leahy-Gilmartin (2013) propose that overgranulation can be managed effectively with topical antiseptics and pressure.

In a study of 58 adult patients who were seen by a home enteral nursing service over a six-month period, Warriner and Spruce (2013) used a polyurethane foam dressing with polyhexamethylene biguanide (PHMB) (Kendall AMD Antimicrobial Foam Dressing; Covidien). Of the patients, 45% (n=22) experienced overgranulation but following two weeks of treatment this had resolved in eight of the patients. At four weeks, overgranulation had resolved in a further three patients; with three more resolving at six weeks, resulting in a total of 16 patients with resolved overgranulation at this stage.

Importantly, this was not a comparative study and it is unknown whether an alternative treatment would have been more effective. However, the results do indicate that there is a need to manage infection and, if overgranulation persists, to move onto other options, such as removing or fixing devices and then steroids.

Malignancy

A malignancy can be mistaken for overgranulation, therefore, if there is any suspicion the patient should be referred for a biopsy. Indications of malignancy include:

  • The presence of overgranulation over many months
  • A  ‘cauliflower’-like appearance
  • The area being hard to the touch
  • Where the tissue grows beyond the wound margins
  • When there is no response to any of the above treatments.

Accurate assessment is important as the removal of malignant tissue could lead to significant blood loss and would have a negative rather than a positive impact on the wound and the patient.

The quality agenda

All NHS organisations across England and Wales have been encouraged to work towards improving essential skin care with the introduction of High Impact Actions, such as ‘Your skin matters’ (Department of Health [DH], 2010a) and the Quality, Innovation, Productivity and Prevention agenda (QIPP) (DH, 2010b). The increased emphasis is on patient safety and quality care (NPSA, 2010a; 2010b) and involves clinicians delivering high quality care with a focus upon clinical and financial outcomes. Any treatment used should be based upon evidence and with a shorter time to resolution and reduced intervention from health care staff.

In practice

The author has extensive clinical experience of advising clinicians and providing care for patients in relation to overgranulation and has designed an algorithm for its management (Figure 6), which includes excluding malignancy, using non-adherent dressings with a high moisture/vapour transmission rate and the use of use of topical steroids (i.e. Healan Tape). Haelan Tape was introduced onto the author’s local wound management formulary five years ago and has been a valuable addition to the management of overgranulation in clinical practice.  

Haelan Tape has also been found to be a cost-effective measure for the management of overgranulation, due to the reduced time to healing compared to other measures (Johnson, 2013).

Conclusion

Overgranulation tissue is a common problem encountered in wound care.  There are several potential options for treatment, with some, e.g. silver nitrate and surgical excision, having an immediate short term effect – although this can be negated with long-term use. Long-term use of these treatment options may delay wound healing by moving the wound back to the inflammatory phase of healing.

Other products such as foams and silver dressings may be effective but are often used as long-term treatments without clinical benefit. The more recent research supporting steroid-impregnated tapes indicates that these can be an efficient and cost-effective treatment for overgranulation in a variety of wound types.

Further research is required to establish exactly why overgranulation develops, as the cause will indicate the most appropriate prevention and treatment.

There is a great difference between chronic wound healing and acute wound healing. An acute wound will progress in an orderly fashion unless the underlying pathology is not supportive of healing or the wound becomes clinically infected. Any wound that does not heal in a ‘normal’ way will become chronic and will then require a skilled clinician to provide appropriate care.

The ability of the clinician to assess and differentiate between healthy and unhealthy granulation is essential in making informed clinical decisions on effective treatment.  In conclusion, the clinician should not be overly concerned about overgranulation as a number of treatment options exist.

Figure 6: Algorithm for management of overgranulation 

Key points

  • A number of options are available to treat overgranulation tissue, but clinical effectiveness, patient safety and comfort should be a consideration
  • A strategic approach for preventing and treating overgranulation tissue ensures that patients receive the most effective and safe care
  • For those presenting with an overgranulating wound it is essential to undertake a differential diagnosis, to exclude malignancy, to assess and manage infection, to remove or secure any devices and then consider the application of Haelan Tape.

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To cite this document: Stephen-Haynes. Managing overgranulation. Wound Care Today, 2013

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