Newer multi-modal approaches to treat keloids

Newer treatment approaches may soon become mainstream in the treatment and management of keloids, one expert says.

READ MORE: The problem with keloids

Keloids have always been challenging to treat with therapeutic modalities of varying efficacy, ranging from traditional surgical techniques and radiation, to relatively less invasive modalities including intralesional and topical therapies, such as corticosteroids and 5-fluorouracil, among others.

“Several of the treatment approaches that are currently used for keloids do not achieve satisfactory outcomes and are fraught with high recurrence rates as well as poor treatment responses in many cases,” says Somesh Gupta, M.D., DNB, department of dermatology and venerology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India. “This therapeutic vacuum has generated much interest in new and experimental treatment techniques that have shown to be very effective in the treatment and management of keloids.”

However, the precise etiology of keloids largely remains unknown from a therapeutic standpoint. Dr. Gupta says that many people consider keloids as a local tumor with a very high recurrence rate.

This is why chemotherapy is often used in the form of 5-fluorouracil and bleomycin. According to Dr. Gupta, keloids are also considered to be an inflammatory lesion because they are often associated with itching, inflammation and pain, as well as an increase in keloidal in ammatory markers.

This is also why the treatment with anti-inflammatory agents such as corticosteroids when administered intralesionally has seen good success in keloid therapy.

The pathology of keloids is not in the epidermis at the surface of the skin, but much deeper in the dermis. As such, any ablative, destructive, or surgical treatment performed here would be vulnerable to any of the unwanted side effects associated with damaging the epidermal layers including depigmentation and ulcerations.

READ MORE: Genetics may play role in keloid formation

“In surgery and destructive treatments, we are removing the surface epithelium as well. The damage to the keratinocytes and epidermis, in turn, will release growth factors that are fibrogenic through fibroblasts, and this is what leads to the recurrence of the lesion. Modalities that can reach the tumor and spare the epidermis would therefore have a clear therapeutic advantage,” Dr. Gupta says.

RF ABLATION
One novel targeted ablative treatment Dr. Gupta developed and regularly uses in his keloid patients is intralesional radiofrequency ablation. The goal of therapy is to treat the keloid lesion from its core using RF ablation to destroy the brous part of the tumor while sparing the surface epidermis. Using insulated probes, a few passes of RF energy is delivered directly to the center of the lesion located deep in the dermis simultaneously, while preserving the integrity of the epidermal layer and circumventing all of the brogenic fall-out of a traumatized epidermal layer. In combination, Dr. Gupta will also inject a mix of 5-fluorouracil and corticosteroids to help ensure that there is no regrowth of fibrous keloidal tissue. According to Dr. Gupta, this unique combination therapy keeps recurrence rates very low.

INTRALESIONAL CRYOSURGERY
Intralesional cryosurgery is another relatively noninvasive approach in which a needle is passed through the depth of the keloid tumor and then liquid nitrogen is released along its path. Contrary to fibroblasts, melanocytes and keratinocytes are very sensitive to cold induced by cryotherapy and, therefore, a very low temperature is required to achieve apoptosis of the targeted keloidal cell fibroblasts. As such, a deep targeted ablation using an intralesional cryosurgery technique
cannot only be effective but can also help avoid damaging the epidermis and the consequences thereof, which can include depigmentation and ulceration of the skin.

RADIOACTIVE PATCH TREATMENTS
A more noninvasive, painless treatment for keloids comes in the form of a radioactive patch containing either radioactive phorphorus-32 or rhenium-188. The patches are superficially applied to the surface of the keloid for a predetermined time (depending on thickness/size of lesion) to deliver approximately a total of 50 Gy of surface radiation dosed in 5-10 sections. According to Dr. Gupta, the depth of penetration of this treatment is only 2-3 mm, so no deeper structures are in any danger of secondary malignancies or mutations, and the risk to the patient is very low in respect to the dose of radiation therapy given.

“One caveat is that this therapy can often lead to depigmentation; however, it also leads to a near complete flattening of the keloid, even in the most challenging-to-treat lesions. Depending on the case, some patients may consider depigmentation an acceptable trade for near complete resolution of a very difficult to treat tumor,” Dr. Gupta says.

BOTULINUM TOXIN A
Botulinum toxin A (BTX) is a very promising therapy and has found its medical use in the treatment and management of keloids. In part, keloids develop and persist due to the high tension caused by the muscle groups surrounding the tumor. When injected, BTX causes temporary paralysis of the muscles surrounding the keloid, reducing the tension in and around the tumor. It is hypothesized that BTX can also interfere in the gene expression of fibroblasts and can inhibit fibroblast activity, impacting keloid development and progression; however, stronger evidence is still needed here.

In addition, BTX may also directly modulate the activity of fibroblasts by altering apoptotic and fibrotic pathways and pathologic scar formation. According to Dr. Gupta, treatments with BTX are effective, comparable or even better than intralesional injections of corticosteroids. Combination injections of BTX with intralesional corticosteroids and/or 5-fluorouracil can sometimes improve treatment outcomes.

Keloids are rarely treated with a single modality and various agents are often given in combination simultaneously intralesionally including 5-fluorouracil and corticosteroids such as triamcinolone. According to Dr. Gupta, BTX is now also being considered as another therapeutic arm that could be implemented in keloids.

“Monotherapy has no role in the management of keloids, and a multi-modality approach is usually required for optimal clinical results, whether using injectables, pressure bandages, or topical therapies. We are reasonably convinced that these new treatment modalities can be implemented in the clinical practice, some still as off-label approaches. I suspect that these innovative treatments will soon become mainstream in the treatment and management of keloids,” Dr. Gupta says.