Improvement of radiation-induced skin fibrosis with hyaluronic acid injections

Radiation-induced skin fibrosis (RISF) is a chronic, progressive complication of radiotherapy characterized by dermal induration, reduced elasticity, and impaired mobility, with limited effective treatment options.^1,2 Hyaluronic acid (HA)–based skin boosters have been shown to improve dermal hydration and viscoelastic properties³ and may represent a novel treatment option for RISF.

A 33-year-old woman developed progressive fibrosis and premature aging of the lateral aspect of the neck following adjuvant radiotherapy (80 Gy delivered via volumetric modulated arc therapy) for squamous cell carcinoma of the tongue. Clinical examination demonstrated poikiloderma, induration, and reduced skin mobility, with associated functional and cosmetic concerns (Fig 1, A).

Fig 1.

Clinical photographs demonstrating response to treatment with CPM-R for radiation-induced skin fibrosis: (A) baseline showing poikiloderma and fibrosis; (B) immediately after injection; (C) 3 months after treatment with improved tone and hydration; (D) 9 months after treatment with near normalization of skin appearance and improved mobility.

Treatment was initiated with intradermal microinjections of Cohesive Polydensified Matrix–Revive (CPM-R) (Anteis SA of Merz Aesthetics), a stabilized (cross-linked) HA skin booster containing 20 mg/mL HA and 17.5 mg/mL glycerol. According to the manufacturer's recommendations,⁴ injections (0.05 mL per microbolus) were administered in a grid pattern across the affected area during a treatment course comprising 3 sessions at 4-week intervals, with a total volume of 8 mL (8 1-mL syringes) delivered over the treatment course. The procedure was well tolerated without complications (Fig 1, B).

At 6-month follow-up, the patient reported marked improvement in skin texture, hydration, and mobility. Clinical examination demonstrated reduced induration and edema, improved skin tone, and increased resemblance to adjacent nonirradiated tissue (Fig 1, C). At 9 months, the treated area appeared nearly indistinguishable from surrounding skin, with sustained functional and aesthetic improvement (Fig 1, D).

The observed clinical improvements may reflect the combined hydrating and viscoelastic properties of HA and the humectant and cytoprotective effects of glycerol.^5,6 Improved dermal hydration supports skin elasticity and mechanical function and influences fibroblast behavior and extracellular matrix organization.⁷ HA has also been implicated in tissue repair processes, including angiogenesis.⁷ Recent preclinical studies of injectable CPM-R have demonstrated that the addition of glycerol promotes rapid tissue hydration through an inside-out mechanism, increases hydrated tissue volume, provides antioxidative and cytoprotective effects without inducing cellular stress responses, and improves tissue integration while reducing inflammatory responses.⁶ Clinical studies of intradermal CPM-R have similarly demonstrated improvements in skin hydration, elasticity, firmness, and overall skin quality following treatment.^6,8 In this case, these combined properties may have contributed to the improved skin pliability and texture observed in the previously irradiated tissue.

Although these findings are encouraging, limitations include the single-patient design, lack of objective quantitative measures, absence of a control comparator, and the inability to distinguish treatment effects from potential confounding factors. Future prospective studies incorporating split-area or split-neck controlled designs, where feasible, would provide a more rigorous assessment of treatment efficacy. RISF is widely regarded as a chronic, progressive fibroproliferative process characterized by persistent myofibroblast activation, extracellular matrix deposition, and impaired tissue remodeling, with limited effective treatment options.^9,10 Accordingly, meaningful spontaneous reversal of established fibrosis would generally not be expected, although it cannot be definitively excluded in a single uncontrolled case. In addition, the long-term safety of intradermal HA-based treatments in previously irradiated tissue warrants further evaluation.

In summary, this case demonstrates an observable improvement in skin texture and mobility following intradermal CPM-R treatment in RISF. Although causality cannot be established from a single case, these findings suggest that intradermal CPM-based HA injections may warrant further evaluation as a minimally invasive option for selected patients. Future prospective studies are warranted to confirm these preliminary findings.

Declaration of Generative AI and AI-Assisted Technologies in the Writing Process

During the preparation of this work the author(s) used [Microsoft Copilot] in order to assist with language editing and improving the clarity of the manuscript. After using this tool/service, the author(s) reviewed and edited the content as needed and take(s) full responsibility for the content of the publication.

Conflict of interest

Dr Borrelli is an employee of Merz Aesthetics. Drs Blessmann-Gurk and Prager have no conflicts of interest to declare.