The management of keloids can be a simple or complex process depending on their size and location. Dermatologists need to be aware of the differences between patients prone to keloids compared with those who are not in order to better understand current and new treatment options.
In an interview with The Dermatologist, Maritza Perez, MD, discussed the pathology and various approaches to treating keloids, including topical and surgical interventions. Dr Perez is a clinical professor of dermatology at Mount Sinai Icahn School of Medicine and visiting professor at Uconn Health in CT. She presented on this topic at the Skin of Color Update in New York City, NY, held from September 7 through September 8.1
The Dermatologist: What are some of the challenges for managing keloids?
Dr Perez: One of the major challenges for managing keloids is understanding the pathogenesis, specifically the differences between patients prone to keloids vs those who are not prone to them.
Basically, the mechanisms responsible for wound healing in a patient prone to keloids is wrong at every stage of the process. The inflammatory response, which begins immediately following an injury, starts with the recruitment of white blood cells, platelets, lymphocytes, and numerous mediators. After this phase, the proliferative response begins with the degranulation of the platelets. In patients prone to keloids, platelets produce more of the profibrotic transforming growth factor beta- (TGFβ) 1 and 2, and lower levels of the anti-fibrotic TGFβ-3. TGFβ-1 induce profibrotic proteins such as fibronectin, integrins- (IFN) α2-β1 and cyclooxygenase- (COX) 1. There are many mast cells in the keloid-prone dermis that release profibrotic mediators as well. Even the metalloproteases (MMP), which are proteins that degrade collagen, are profibrotic in the patient prone to keloids. These patients have higher levels of the profibrotic MMP-13. In addition, tumor necrosis factor-α is produced, which in turn produces profibrotic COX-2.
The next phase is the apoptotic response, which downregulates the proliferative response. In patients prone to keloids, this response is delayed, and there is resistance to apoptosis. Additionally, it has been demonstrated that patients prone to keloids have a defect in the apoptotic response, with increased levels of p53 tumor suppressor gene and bell lymphoma protein 2.
In addition, patients prone to keloids also have altered immune response, which occurs during the inflammatory phase. They predominantly produce T helper cell 2, which produces profibrotic IL-4, IL-5, IL-8, and IL-13.
In other words, the first cells in the whole system are profibrotic and produce mediators that are profibrotic. Then, to top it off, they cannot stop the process.
The Dermatologist: What treatment options are available for patients with keloids?
Dr Perez: You can treat keloids with topicals, injectables, or more aggressive interventions.
Topical options include compression therapy, which does not destroy the keloid but improves its appearance. Imiquimod can be applied topically as well to induce cells to produce gamma interferon. A well-known option is the use of silicone sheathing; however, it will only help improve the appearance of keloids not get rid of it. Also, flavonoids, such as Mederma, can provide some improvement, but this option has limited usage.
Intralesional corticosteroids are considered standard of care for keloids. They decrease the inflammatory component and collagen production. Other intralesional options include bleomycin and intralesional 5‑fluorouracil. Clinical trials investigating the potential of TGFβ-3 and IFNα-2-β-1 are underway.
Another option is cryotherapy. When performing cryotherapy, a probe needs to be inserted into the keloid. First, the keloid is numbed, the probe is inserted, and the entire lesion is frozen from the inside because freezing the keloid on the outside can cause hypopigmentation.
Small keloids, such as keloids on the earlobe, can be effectively treated with excision followed by intralesional corticosteroid administered on a monthly basis to prevent regrowth.
Larger keloids are more difficult to treat. They can be removed and healed by secondary intention, which takes about 6 weeks, and most of them will not recur. While they are healing, intralesional corticosteroids can be used to help in the healing process and prevent regrowth.
For both large keloids and keloids that are recalcitrant, patients can undergo excision and radiation at major centers, such as the Langone Center in Manhattan. These centers have very tenuous protocols, which starts with 3 treatments of traditional corticosteroids prior to excision, intralesional steroids through excision and after stitches are removed, followed by radiation. It is a very laborious process.
Additionally, lasers can be used for keloids. In 2013, I co-author a paper with Rossi et al2 that demonstrated the effectiveness of 300 microsecond 1064nm Nd;YAG laser for improving the clinical appearance of keloids. We induced remissions in some patients for up to 5 years with this combination of laser and intralesional injections.
The Dermatologist: How should dermatologists determine which option to use?
Dr Perez: The treatment method depends on the size and duration of the keloid. For example, most keloids on the earlobe can be excised and healed by secondary intention or with intralesional corticosteroids because they are small and most likely will not recur. The same process can be done for keloids on the nape of the next.
For more resistant keloids, intralesional 5-FU or bleomycin can be used, but dermatologists should discuss potential complications with the patient.
Surgical removal of large keloids should be the last resort because they have an almost 90% recurrence rate following excision. Surgery should be performed at a tertiary center or in an office that has a well-defined protocol, such as the one implemented at the Langone Center.
Lastly, laser therapy, such as the one we studied2, can be offered as well and should be performed by expert laser surgeons.
1. Perez M. Surgical approaches for keloids. Presented at: The Skin of Color Update; September 7-8, 2019: New York, NY.
2. Rossi A, Lu R, Frey MK, Kubota T, Smith LA, Perez M. The use of the 300 microsecond 1064nm Nd:YAG laser in the treatment of keloids. JDD. 2013;12(11):1256-1262.