Keloids are an overgrowth of fibrotic tissue outside the original boundaries of an injury and occur secondary to defective wound healing. Keloid scars commonly grow beyond the wound boundaries, while hypertrophic scars are confined to the wound’s original area. Both types of scars arise as a result of impaired fibroblastic proliferation and collagen deposition after skin injury. Keloids often have a functional, aesthetic, or psychosocial impact on patients, as highlighted by quality-of-life studies. They can greatly affect the patient’s quality of life and emotional wellbeing by causing intense pain, itching, unappealing red appearance, and inexorable spread. Interestingly, keloids and hypertrophic scars are exclusively found in humans and do not occur in animals naturally. The lack of suitable animal models that recapitulate the key processes in keloidal/hypertrophic scarring has greatly hampered our understanding and treatment of these scars.
Treatments for keloids include surgical excision, intralesional or topical corticosteroids, other intralesional therapies: 5-fluorouracil (5-FU), bleomycin, and interferon, topical imiquimod, compression, cryotherapy, radiation, silicone sheeting, and laser or light-based therapies. Recurrence is common, even with combination therapy. Laser and other light-based technology have introduced new ways to manage keloids that may improve aesthetic and symptomatic outcomes and decrease keloid recurrence. Laser and light-based therapies for keloids can be grouped into three categories: ablative lasers, non-ablative lasers, and non-coherent light sources.
Non-ablative lasers target hemoglobin or melanin. 585 or 595-nm pulsed-dye lasers (PDL) are non-ablative, and the major chromophore is oxyhemoglobin. PDL also targets melanin; therefore, care must be taken to avoid pigmentary alterations. PDL is hypothesized to treat keloids by selective damage of blood vessels that supply the scar. The 980-nm diode laser targets hemoglobin and melanin. The 1064-nm neodymium-doped: yttrium, aluminum, and garnet laser and the 532-nm neodymium-doped: vanadate laser is hypothesized to primarily treat keloids by damaging deep dermal blood vessels.
Non-laser light sources are also used to treat keloids. These techniques include intense pulsed light therapy (IPL), light-emitting diode (LED) phototherapy, also known as low-level light therapy, and photodynamic therapy (PDT). These modalities utilize light energy that may cause keloid fibroblast functional modification. IPL emits non-coherent, broadband wavelength, pulsed light, and targets pigmentation and vasculature. LED phototherapy is hypothesized to photomodulate mitochondrial cytochrome C oxidase altering intracellular signaling. PDT requires the application of a photosensitizer, commonly 5-aminolevulinic acid or methyl aminolevulinic acid, that is preferentially absorbed by highly vascularized or metabolically active tissue and converted to protoporphyrin IX. Upon exposure to light, PpIX causes reactive oxygen species free radicals that have a cytotoxic effect. PDT may also cause alterations in extracellular matrix synthesis and degradation and modulate cytokine and growth factor expression.
The mechanisms by which topical PDT improves abnormal scars are largely unknown. However, they probably involve downstream responses to the ROS produced by the photodynamic reactions: the ROS induces membrane and mitochondrial damage, which activates signaling molecules such as TNF-α and interleukins 1 6 and cell death. The cell death may be via apoptosis, necrosis, and/or autophagy. These changes may alter growth factor and cytokine expression in the lesion, thereby modulating collagen production and extracellular matrix organization.
Notably, the shallowness of PDT suggests that it may be useful as an adjunct treatment of the wound area after keloid resection. In this setting, PDT may help to prevent postoperative keloid recurrence.
