Management of Over-Granulation in a Diabetic Foot Ulcer: A Clinical Experience Krishnaprasad I N1, Soumya V2, Abdulgafoor S3Abstract
Over-granulation or exuberant granulation tissue is a common problem encountered in the care of chronic wounds,especially that of diabetic foot ulcers. There are several potential options for the treatment of this challenging problem. Some have an immediate short term effect but may have a longer term unfavourable effect, for example, silver nitrateapplication and surgical excision, which may delay wound healing by reverting the wound back to the inflammatoryphase of healing. Other products, such as foams and silver dressings may offer some effect in short term, but their longterm effects are questionable. The more recent research supports Haelan cream and tape as an efficacious and costeffective treatment for over-granulation in a variety of wound types. The future of treating over-granulation may lie withsurgical lasers, since lasers can not only remove over-granulation tissue but will also cauterise small blood vessels andare very selective, leaving healing cells alone while removing excess and unhealthy tissue.
Recently Drs Lain and Carrington have demonstrated the utility of imiquimod, an immune-modulator with anti-angiogenicproperties, in the treatment exuberant granulation tissue, in a patient with long standing diabetic foot ulcer, resistant toother forms of therapy. We adapted a modified version of their protocol in the management of a similar patient in ourhospital and achieved a good result in lesser time than the former. Keywords: Over-granulation, diabetic foot ulcer, imiquimod. Introduction1-3
granulation is defined as granulation tissue which is inexcess of required amount needed to replace the tissue
Granulation tissue is composed largely of newly deficit. It often results in a raised mass above the wound.
growing capillaries. If granulation is present in the
wound, it is an indication that the wound is healing, and
It may be a difficult condition to manage as the presence
a dense network of capillaries, large number of
of such tissue will prevent or slow epithelial migration
fibroblasts, macrophages and new formed collagen fibres
across the wound, and thus delay wound healing.
will be present. However, sometimes the granulation will
Over-granulation usually presents in wounds healing by
‘over grow’ beyond the surface of the wound and this is
secondary intention. It is clinically recognised by its
called ‘hyper-granulation’ or ‘over-granulation’. Over-
friable red, often shiny and soft appearance that is abovethe level of the surrounding skin and can be healthy orunhealthy. Healthy over-granulation tissue presents as
1MD, DNB, MNAMS (PMR), Assistant Professor
moist, pinky-red tissue that may bleed easily. Unhealthy
over-granulation tissue presents as either a dark red or a
Government Medical College, Kozhikode, Kerala
pale bluish purple uneven mass rising above the level of
the surrounding skin which also bleeds very easily.
Krishnaprasad I N, Soumya V, Abdulgafoor S. Management of over-
However, whether healthy or unhealthy, the wound
granulation in a diabetic foot ulcer: A clinical experience. IJPMR March 2013; Vol 24 (1): 19-22.
generally will not heal because, epithelial tissue will find
it difficult to migrate across the surface and contraction
Dr Krishnaprasad IN, MD, DNB, MNAMS (PMR), Assistant
will be halted at the edge of the swelling. The healthy
Professor, Government Medical College, Kozhikode, KeralaEmail: [email protected]
granulation tissue has the potential to reduce naturally
Received on 08/01/2013, Accepted on 25/03/2013
and to eventually heal without intervention although thismay take longer than if it is treated.
Particular care should be taken in differential diagnosis,
smelling discharge and caused difficulty in donning a
as a fungating malignant ulcer can mimic a hypertrophic
foot wear. Also it bled whenever the patient walked
barefooted for a few distances. She had symmetricsensory peripheral neuropathy of both lower extremities. Case Report:
Peripheral pulsations were all normal in the lowerextremities. Because of the bleeding mass and ulcer, the
A 55 years old female patient, diabetic, on insulin therapy
patient was physically, socially and psychologically
for the past few years, presented with a non-healing ulcer
incapacitated. She had undergone multiple therapies,
over the past 6 months, over the inferolateral aspect of
including indigenous treatment, but none has given her
a permanent cure. She was advised surgical removal of
On examination the ulcer was about 5×5 cms, with
the excess granulation tissue by her diabetologist, but
slightly indurated and unhealthy margins. The ulcer floor
she was not willing for surgery. Then she was referred
had a dusky red fungating mass filling almost the entire
to our department for any non-surgical options in her
floor, slightly indurated, fragile and adherent to the ulcer
base. The mass was not tender but has occasional foul
We did a thorough literature search for the possiblemanagement options and came across many differentoptions, many of which she already had tried, and manywhich were not locally available. Among those methods,the utility of topical imiquimod, an immunomodulatorwith anti-angiogenic properties was demonstated by Lainand Carrington4, in a patient with a diabetic foot ulcerwith overgranulation. Their treatment protocol consistedof 4 days/week regimen of topical imiquimod at night,an enzymatic debriding agent for the remaining 3 daysand morning application of mupirocin cream. Theyreported a good ulcer healing in 7 months time.
Imiquimod cream was locally available, since it is usedby dermatologists in the management of perianal andgenital warts, actinic keratosis, basal cell carcinoma,keloids etc. We discussed this treatment option with thepatient and caregivers, with explanation of the benefitsand possible side-effects and the need for a strictcompliance to the regimen. We adopted a modifiedprotocol since enzymatic debriding agents were notlocally available. We used topical imiquimod 3 days per
Fig 1- Ulcer Pre treatment
week and for the remaining 4 days, special moisture
Fig 2- 6 Weeks Follow-up Fig 3- 12 Weeks Follow-up Fig 4- 18 Weeks Follow-up Fig 5- 24 Weeks Follow-up
Management of over-granulation in a diabetic foot ulcer – Krishnaprasad I N et al
retaining dressings were given to promote autolytic
over-granulation tissue. Pressure from foam was then
debridement. Every morning a topical antiseptic
replaced by the suggestion of double application of
preparation containing nano-crystalline silver was
hydrocolloid. Controversially an occlusive dressing is
applied. Before starting treatment, malignancy and
thought to be a possible cause of over-granulation but
infection were ruled out by appropriate biopsy and
potentially the pressure of the double application may
culture methods. Correct application method was taught
with special care to protect surrounding skin and the
Morison et al7 noted that silver nitrate reduced fibroblast
patient was asked to review every 6 weeks. We also
production. However, the use of silver nitrate directly
emphasised the importance of proper foot care and
reduces fibroblast proliferation and is therefore, not
recommended for prolonged or excessive use8 and
We reviewed the patient every 6 weeks (Figs 2-5) and
should never be considered first-line therapy and
the progress was assessed. The unhealthy edge of the
should only ever be used with great care for the more
ulcer was curetted at each visit to improve the chance of
stubborn area of granulation. This is particularly
re-epithelisation. Blood sugar level was optimised and
important as chemical burns have been reported and more
nutritional anaemia was corrected. There was a dramatic
likely to occur with longer application times. When it isnecessary, a topical barrier preparation such as petroleum
reduction in the size of hypertrophied granulation tissue
jelly or white soft paraffin should be applied to protect
over a period of 12 weeks, and by 18 weeks the
the normal skin surrounding the area of over-
epithelisation was almost complete covering the entire
Another highly successful method of treatment would
The patient was extremely happy with the result and had
be a short course of a topical steroid to suppress the
very good functional improvement. She did not complain
inflammatory process10,11 and tri-adcortyl was often the
of any local or systemic adverse reaction during the
chosen steroid to be used in this case. However, it is no
therapy. She was given a proper foot wear and instructed
longer recommended for this purpose as it contains
auromycin, an antibiotic, and it is indiscriminate use ofsuch antibiotic therapy that may have initiated MRSA. Discussion:
Reducing the bacterial burden with auromycin may be
There are many treatment options for over-granulation
one of the possible reasons for the success of tri-adcortyl
with limited research to support their use or to clearly
in reducing over-granulation as reducing the bacteria load
suggest which is the most effective.
would remove the infection that stimulated the tissue toovergrow while the steroid reduces the inflammation that
A “wait and see” approach was suggested by Dunford3
but the last decade has seen some significantdevelopments in this area of tissue viability and a more
Lloyd-Jones12 reported resolution of over-granulation
pro-active approach should be taken.
tissue using a silver hydrofibre dressing, but this tooksome weeks to resolve which is much longer than other
Inflammatory response may be related to infection and
the use of an antibacterial dressing such as sliver,cadexomer iodine, honey, PHMB (polyhexamethylene
Haelan tape13 is a transparent, plastic surgical tape,
biguanide) can assist with managing local colonisation
impregnated with 4 mg/cm2 fludroxycortide, which
and reduce the potential and also reduce the over-
allows steady distribution of the steroid to the affected
site. Fludroxycortide is a fluorinated, synthetic,moderately potent corticosteroid. As with other topical
The earliest recommendation for treating over-
steroids, the therapeutic effect is primarily the result of
granulation was foam. Harris and Rolstad6 reported the
its anti-inflammatory, antimitotic and antisynthetic
findings of a prospective non-controlled correlation study
with 10 patients and 12 wounds using a polyurethanefoam dressing to reduce over-granulation tissue. The
Because granulation tissue is very delicate, it can
results demonstrated a reduction in granulation tissue.
sometimes be removed by wiping with a cotton swab.
It was concluded that the pressure of the foam on the
However, this should only be undertaken by an
granulation tissue reduced the oedema and flattened the
experienced person, as the wound could be traumatised
and healing could be further delayed. Surgical
4. Lain EL, Carrington PR. Imiquimod treatment of exuberant
debridement is also an option, but should only be
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undertaken by an experienced surgeon.
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6. Harris A, Rolstad BS. Hypergranulation tissue: a nontraumatic
genital and perianal warts, has since been approved for
method of management. Ostomy Wound Manage; 40: 20-30.
treatment of actinic keratoses and has shown activity
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against basal cell and squamous cell cancers, melanoma,other verrucae, keloids, cutaneous T-cell lymphoma,
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ligand for toll-like receptor 7 at therapeutic doses,
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