Differentiating and Treating Hypertrophic Scars and Keloids

As hypertrophic scars and keloids both result from an exuberant healing response to skin injury some experts have questioned whether they are actually distinct entities or if keloids are exacerbations of hypertrophic scars. However, there are also fundamental differences between the 2 types of scars as the presence of invasive horizontal growth in keloids is the key distinguishing factor between these lesions.¹

“While a hypertrophic scar is a more indurated scar than one might typically expect for a particular body location or degree of skin injury, it remains confined to the initial area of injury,” Michael Cameron, MD, FAAD, assistant professor in the department of dermatology at the Icahn School of Medicine at Mount Sinai in New York, told us in a recent interview. “To the contrary, keloids can extend well beyond the original wound location.”

He further explained that hypertrophic scars typically appear within a few months following the initial skin trauma, with continued growth for up to 6 months and, in many cases, regression within 1 year. Conversely, keloids typically appear between 3 months and a few years following skin trauma and may proliferate for years after onset. “Keloids can also appear spontaneously with no identifiable preceding skin injury,” he added.

Pain and pruritus may occur with both types of scars but are more common in patients with keloids.

“Histologically, both hypertrophic scars and keloids are characterized by a thick, highly vascularized dermis containing increased amounts of inflammatory cells and collagen,” Dr Cameron stated.² “In addition, TGF-β1 appears to play a role in the pathogenesis of both keloids and hypertrophic scars.”³

Although both types of scars can affect individuals of all skin types, those of African, Asian, Hispanic, and Mediterranean descent have shown a stronger genetic predisposition for keloids.

Prevention and Treatment

In susceptible individuals, both hypertrophic scarring and keloids occur more frequently in the presence of suboptimal wound healing conditions such as excessive tension, prolonged healing, wound infection, and repetitive trauma, according to Carolyn Willis, MD, dermatologist at the Cosmetic Surgery and Skin Health Center at the University of Pittsburgh Medical Center.

Therefore, efforts to minimize these factors and thus prevent the formation of aberrant scars are recommended, including the use of wound closure materials and techniques that reduce tension and offer prolonged support during and after surgical procedures.  

Although a wide range of treatment options exist for hypertrophic scars and keloids, they are generally unsupported by high-quality evidence.⁴ “Unfortunately, there is not one treatment or treatment regimen that provides consistent and predictable outcomes,” Dr Willis noted. “Combination therapies appear to offer the highest success rates” and may include those she described below.

• Intralesional (IL) injection of corticosteroids (frequently triamcinolone), or ILTAC, is one of the most common initial treatments. It reduces active collagen synthesis and inhibits the rapid growth of fibroblasts that are involved in the abnormal wound healing. In predisposed individuals, they may be used at the time of a surgical procedure or in the post-operative period. They are used with caution because steroids can slow wound healing.
• Other medications can also be injected, including 5-fluorouracil, bleomycin, and verapamil.
• Laser treatments can be attempted with NdYAG, pulsed dye laser, intense pulsed light, or CO2 in fractional or fully ablative mode.
• Lasers are frequently combined with other treatment modalities. The CO2 laser can be used in fractional mode to assist in drug delivery. Fractional ablative CO2 treatment can be followed by topical application of steroids, fluorouracil, or other anti-proliferative products, followed by occlusion.
• Silicone gel/silicone gel sheets are useful as both a preventative and as an adjunct to other treatments. Their exact mechanism of action is unclear.
• Excision may be attempted after careful consideration due to high rates of recurrence, especially for keloids. They should be performed with appropriate tension offloading measures to reduce the risk of recurrence. Postoperative radiation therapy is sometimes performed.
• Radiation monotherapy is also an option, but efficacy data is not impressive for conventional modalities. The SRT-100 device appears to be more effective but is often cost-prohibitive.⁵
• Among emerging modalities, intralesional cryotherapy is performed using a double lumen needle to basically freeze the scar from the inside out with LN2 to ensure that the entire keloid is frozen.⁴ Good success rates and lower rates of scar recurrence have been reported. Downsides are the cost and availability of this treatment modality, and the pain and prolonged healing associated with the procedure.
• Botulinum toxin A is being used both at the time of surgery to reduce tension on the wound post-operatively, and in established keloids to reduce surrounding muscle tension.⁴ It can be used along with other treatment modalities like ILTAC.

It is important to note that each of the available treatment modalities carries the risk of adverse effects, such as pigmentary change and tissue atrophy with ILTAC, and the risk of under- or overtreatment with laser therapy due to variability in the thickness and density of scar tissue.

Emerging Therapies

Among the many remaining gaps in this area, there is a pressing need for novel treatment options for keloids, as current therapies are “local-acting and therefore have limited capacity to affect keloid lesions systemically as a disease process,” said Dr Cameron. In addition, these therapies often require multiple rounds of treatment and may be painful or lead to serious adverse effects.

In a recent case report co-authored by Emma Guttman-Yassky, MD, PhD, of Mount Sinai, a 53-year-old Black man with severe atopic dermatitis – an independent risk factor for keloids – demonstrated a dramatic reduction in the size of his keloids following treatment with dupilumab.⁶ As a result, Dr Guttman-Yassky is now leading a Phase 1/2 research study to investigate the efficacy of dupilumab in the treatment of keloids. [Editor’s note: To inquire about enrolling in the study, interested parties may call the clinical trials line at 212-241-3288.]

“The scientific rationale for this approach is supported by recent work in murine models showing that regulatory T cells suppress Th2-mediated profibrotic immune responses, providing an avenue by which immune dysfunction may contribute to keloid formation,” Dr Cameron explained.⁷

Other ongoing studies are investigating the safety and efficacy of STP705, an siRNA therapeutic, and AIV001, a multi-kinase inhibitor, delivered via dermal injection with the aim of preventing keloid recurrence following keloidectomy.^8,9

References

1. Limandjaja GC, Niessen FB, Scheper RJ, Gibbs S. Hypertrophic scars and keloids: Overview of the evidence and practical guide for differentiating between these abnormal scars. Exp Dermatol. 2021;30(1):146-161. doi:10.1111/exd.14121

2. Gauglitz GG, Korting HC, Pavicic T, Ruzicka T, Jeschke MG. Hypertrophic scarring and keloids: pathomechanisms and current and emerging treatment strategies. Mol Med. 2011;17(1-2):113-125. doi:10.2119/molmed.2009.00153

3. Abdou AG, Maraee AH, Al-Bara AM, Diab WM. Immunohistochemical expression of TGF-β1 in keloids and hypertrophic scars. Am J Dermatopathol. 2011;33(1):84-91. doi:10.1097/DAD.0b013e3181d0c3ad

4. Ojeh N, Bharatha A, Gaur U, Forde AL. Keloids: Current and emerging therapies. Scars Burn Heal. 2020;6:2059513120940499. doi:10.1177/2059513120940499

5. Jones ME, Ganzer CA, Bennett D, Finizio A. Surgical excision of keloids followed by in-office superficial radiation therapy: prospective study examining clinical outcomes. Plast Reconstr Surg Glob Open. 2019;7(5):e2212. doi:10.1097/GOX.0000000000002212

6. Diaz A, Tan K, He H, et al. Keloid lesions show increased IL-4/IL-13 signaling and respond to Th2-targeting dupilumab therapy. J Eur Acad Dermatol Venereol. 2020;34(4):e161-e164. doi:10.1111/jdv.16097

7. Kalekar LA, Cohen JN, Prevel N, et al. Regulatory T cells in skin are uniquely poised to suppress profibrotic immune responses. Sci Immunol. 2019;4(39):eaaw2910. doi:10.1126/sciimmunol.aaw2910

8. ClinicalTrials.gov. A Study for Safety and Efficacy Evaluation of Various Doses of STP705 in Reducing Keloid Recurrence. NCT04844840. Accessed online May 31, 2021.

9. ClinicalTrials.gov. Safety and Efficacy of AIV001 on Scar Formation and Keloid Recurrence Following Keloidectomy. NCT04827875. Accessed online May 31, 2021.