Hypergranulation

Figure 1: shows classical hypergranulation of varying degrees. The image in the middle below depicts a pressure sore that is clearly not clean enough. In this case, it is necessary to address the bacterial imbalance and initiate treatment with antibacterial agents. The hypergranulation often subsides as the wound becomes cleaner.

Hypergranulation, also known as "proud flesh," is simply explained as having an excess of granulation tissue to fill a wound defect. Hypergranulation is a relatively common phenomenon in wound healing and can occur throughout the healing process of both acute and chronic wounds.

To understand the concept of hypergranulation, it is necessary to have knowledge of how a normally granulating wound behaves. Granulation tissue appears as reddish or pink tissue in the wound, often with a slightly uneven surface, which is a natural phase in wound healing. Granulation tissue consists of various types of cells, such as fibroblasts (cells capable of producing various types of tissue, including capillaries, nerves, and adipose tissue), as well as immune cells (lymphocytes, macrophages, and granulocytes) (1). A wound cannot heal without healthy granulation tissue. In some cases, granulation tissue can become overstimulated, resulting in an overreaction known as hypergranulation.

A classic sign of hypergranulation is tissue that bleeds easily upon light contact. Hypergranulation is often seen as small round, raspberry-like nodules in the wound. Hypergranulation is expansive and can grow above the level of the skin. The problem with hypergranulation is that it hinders the last phase of healing- epithelialization. In many cases it stops the surrounding skin from growing over at all, sometimes it just slows down the process.

There are several causes for the occurrence of hypergranulation. The most common causes include:

Bacterial imbalance in the wound.
Irritation caused by artificial openings in the skin, such as a drain, PEG tube, or similar.
Prolonged inflammation phase in the wound due to chronic edema or other reasons.
Wounds on fingertips often exhibit hypergranulation without a specific known cause.
Malignant wounds.
Occasionally, hypergranulation can occur without any identifiable specific reason.

Generally, any process that triggers inflammation in or around the wound bed increases the likelihood of developing hypergranulation.

In burn wounds, hypergranulation is a common phenomenon, possibly because the burned tissue remains inflamed for a longer period than other types of wounds. Sometimes, infection is the cause of hypergranulation in burn wounds. Chronic colonization with Pseudomonas aeruginosa and intestinal bacteria often shows a tendency toward hypergranulation. Note that certain types of malignant skin cancer (or metastases) can present as hypergranulation. If there is no obvious explanation for the occurrence of hypergranulation, a biopsy of the tissue should be performed.

Treatment of hypergranulation:

Previously, many wound care practitioners used silver nitrate (Lapis stick) to cauterize hypergranulated tissue. This method is considered outdated today as it does not address the cause of hypergranulation, only the symptom. Cutting away hypergranulation is also extremely rarely successful; it only leads to bleeding, and the hypergranulation returns shortly after.

We often say that hypergranulation can be "our friend." This is highly vascularized tissue that can be used to our advantage. In most cases, a hypergranulated wound can be transformed into a rapidly healing wound by treating it with potent steroids.

In cases where a bacterial imbalance is not suspected to be the cause of hypergranulation, topical steroid creams/ointments (Group III/IV corticosteroids) are the first-line treatment (2-6). It is important to apply the product daily, sometimes twice a day, for best effect. Significant improvement is usually seen within 10-14 days. If daily steroid treatment has not been successful, other underlying causes should be considered. Our experience is that the petroleum jelly-based variant (i.e., the ointment) works best. However, it is a bit more challenging to apply as it does not adhere well to moist surfaces. Be patient when applying it; eventually, the ointment will adhere sufficiently. Another option is to apply the ointment to the area of the dressing that is in contact with the hypergranulation.

Very often, rapid epithelialization occurs when the hypergranulation recedes. There is no evidence suggesting that potent steroids harm the epithelialization process. On the contrary, it appears that epithelialization occurs faster when steroids are used!

Figure 2: Application of potent corticosteroid ointment is considered the standard treatment for hypergranulation where bacterial overload is not the primary cause of the problem. Class III corticosteroids can be tried, but we most commonly use class IV. We believe that the petroleum jelly-based variant (the ointment) works slightly better than the cream variant. Dermovate 0.05% is a well-known product name in this group.

Figure 3: A case with a smaller area of hypergranulation in the upper left corner of a donor site after harvesting a split-thickness skin graft. The donor site was not healing. In the middle image, granulation tissue can be seen growing above the skin level, and it is notably prone to bleeding. There is no obvious cause for the hypergranulation, and there are no signs of a bacterial problem. It is not uncommon to observe areas of hypergranulation at donor sites. We treat it with Dermovate 0.05% ointment. It is applied in a slightly thick layer so that the patient can extend the dressing change intervals, and the product is applied every other day. A polyurethane foam dressing with a silicone coating on the inner side is used as the dressing.

Some doctors inject corticosteroids directly into the hypergranulated tissue (3). For this purpose, Triamcinolone 40mg/2ml mixed with sterile saline in a 1:1 ratio can be used, and a volume equivalent to approximately 0.1 ml of this mixture is injected per square centimeter of tissue. In smaller areas of hypergranulation, a single treatment is often sufficient. In cases of more pronounced hypergranulation, repeated treatments with approximately one week intervals may be necessary. Such injections are usually painless as hypergranulation tissue contains few nerves. However, some patients may be hypersensitive in the granulation tissue, and in these cases, the tissue can be pre-anesthetized by applying Emla cream or lidocaine gel. We generally find no need for such intralesional injections, as corticosteroid ointment/cream usually suffices. An exception is hypergranulation in postoperative scars where there is concern about the development of hypertrophic scars or even keloids. In these cases, it may be advisable to inject corticosteroids directly into the granulation tissue to achieve the best possible cosmetic outcome.

If you have treated a hypergranulating wound with steroid ointment/cream for 14 days without significant improvement, you should reconsider the situation. It is uncommon for hypergranulation not to respond to such treatment, and in such cases, a biopsy is often necessary to rule out malignancy. Remember that malignancy can also develop in a chronic wound.

If there is suspicion that bacterial overload is the cause of hypergranulation, the use of antibacterial agents alone (without the use of corticosteroids) may be sufficient to calm down hypergranulation.

By antibacterial agents, we do not mean antibiotics, but rather products that reduce the presence of bacteria. It would be advisable to cleanse the wound, for example, with Polyhexanide (such as Prontosan) or Hypochlorous acid products (such as Microdacyn) at each dressing change. In addition, antibacterial products such as silver- or iodine-based products, or bacteria-binding products such as Sorbact, should be used. We have not had good experiences with the use of honey products for hypergranulation. In the initial phase, shorter dressing change intervals are recommended to quickly reduce the bacterial load.

Hypergranulation around stomas is in a class of its own and can be a significant challenge. This is most commonly seen with small bowel stomas where the bowel contents are more liquid and contain more aggressive substances than the contents of the colon. In this case, it is also appropriate to use a corticosteroid ointment initially to reduce hypergranulation. Since the ointment contains vaseline, it also has a barrier effect. However, strong corticosteroid products should not be used for several weeks as long-term use can damage the skin and worsen the situation. Around a stoma, we estimate that such products should be used for a maximum of two weeks. Significant improvement is often seen within a few days, as long as it is applied daily. Daily application is key to success here, although it can be cumbersome when the stoma plate needs to be changed every day. Remember that applying the ointment may slightly reduce the adherence of the stoma plate. Therefore, it is important to apply it only where hypergranulation is present. Once the hypergranulation has subsided, advanced barrier products such as Cavilon Advanced, which can adhere to moist surfaces, should be used. This is usually applied every three days and can prevent a recurrence of hypergranulation.

The same principle applies to hypergranulation around catheters, drains, tracheostomies, etc., essentially anywhere there is medical equipment passing through the skin and remaining in place for an extended period. Again, corticosteroid ointment can be initially used to quickly calm down the condition, followed by protecting the skin with Cavilon Advanced to prevent recurrence. By keeping the skin around such openings dry, recurrence can often be prevented. However, as long as the equipment remains in place, it will irritate the skin, and hypergranulation may reoccur. If there is suspicion of increased bacterial load around drains/catheters, silver-coated specialized dressings can be tried, which are precut to fit nicely around a tube.

Figure 4: Special products like Silverlon Lifesaver Ag are silver-coated and have a shape that makes it easy to place around tubes/drains/pins to prevent both hypergranulation and infection. Image copyright: silverlon.com.

Another specific type of hypergranulation is seen in ingrown toenails. Unfortunately, it is still common for many people to try treating this with silver nitrate (Lapis). As mentioned above, this is considered an outdated form of treatment. By cauterizing the hypergranulation, one does nothing to address the underlying cause, which is the nail being too wide and irritating the skin edge. In most cases, surgical excision of the nail edge is required. In milder cases, treatment with a nail brace that is customized by an authorized podiatrist may suffice.

Figure 5: Hypergranulation in ingrown toenails occurs due to inflammation where the nail edge irritates the skin. Treatment with silver nitrate (Lapis) is considered an outdated method. The correct treatment here is excision of the nail edge. In milder cases, a nail brace customized by an authorized podiatrist may be appropriate. Image copyright: Wikimedia Commons, Creative Commons Attribution-ShareAlike License 3.0.

Sources:

Langøen Arne, Marcus Gürgen. Sårtilhelingsprosessen, enkelt forklart. 2019 (publication in Norwegian)
Shoham Y, Tsur R, Krieger Y, Silberstein E, Bogdanov-Berezovsky A, Maor U, et al. 361 Topical Steroid Treatment for Suppression of Granulation Tissue in Burns: Results of a European Survey. J Burn Care Res. 2018;39(suppl_1).
Moio M, Mataro I, Accardo G, Canta L, Schonauer F. Treatment of hypergranulation tissue with intralesional injection of corticosteroids: Preliminary results. Vol. 67, Journal of Plastic, Reconstructive and Aesthetic Surgery. 2014.
Saikaly SK, Saikaly LE, Ramos-Caro FA. Treatment of postoperative hypergranulation tissue with topical corticosteroids: A case report and review of the literature. Vol. 34, Dermatologic Therapy. 2021.
McShane DB, Bellet JS. Treatment of hypergranulation tissue with high potency topical corticosteroids in children. Pediatr Dermatol. 2012;29(5).
Ae R, Kosami K, Yahata S. Topical corticosteroid for the treatment of hypergranulation tissue at the gastrostomy tube insertion site: A case study. Ostomy Wound Manag. 2016;62(9).