GLASGOW, Scotland — Orofacial fibrosis in systemic sclerosis (SSc) can be substantially eased by giving affected patients facial injections of their own fat, according to research presented at the British Society for Rheumatology (BSR) 2026 Annual Meeting.

Results of the Sys-Stem study showed that stem cell-enriched autologous lipotransfer was associated with significantly greater improvement in the Mouth Handicap in Systemic Sclerosis scale (MHISS) than routine care at both 3 and 6 months.

The lipotransfer technique used was also associated with significant improvements in the Brief Fear of Negative Evaluation Scale (BFNE), the Derriford Appearance Scale (DAS24), and the Hospital Anxiety and Depression Scale (HADS). There was also significant improvement in mouth opening as measured by the inter-incisor distance, and in stimulated salivary flow at 6 months.

‘Should Be Routine Care’

“We would suggest [this surgical intervention] should be a routine care in these patients,” said c onsultant plastic and reconstructive surgeon Peter Butler, MD, of the Royal Free London NHS Foundation Trust and University College London, who has been perfecting the technique alongside rheumatology colleagues, including co-author and consultant rheumatologist Christopher Denton, MD, PhD, University College London in London, England.

“These patients are living longer with an increasing nonlethal burden,” Butler said. Orofacial scleroderma can result in microstomia, xerostomia, increasing problems with dental hygiene, periodontal and dental disease, and in some patients, can affect oral competence resulting in eating and speech difficulties. These were issues that patients found more concerning than complications affecting other organs, he said.

Consultant rheumatologist Francesco Del Galdo, MD, PhD, who works for The Leeds Teaching Hospitals NHS Trust, Leeds, England, told Medscape Medical News that the work was “pioneering,” although it’s been ongoing for many years.

“I think it would be important to know what the patient perspective is; would many patients do it again?” said Del Galdo, who was not involved in the work and has a specialist interest in scleroderma and connective tissue disease. He is also an associate professor of rheumatology and professor of experimental medicine at the University of Leeds, Leeds, England.

He added, “It’s good to see that there is [increased] mouth opening, but I want to ask you, as a patient, do you feel that? Do you think it was worth it or not?”

There is a psychological element to increasing orofacial fibrosis and watching your face change, Del Galdo said. The pros of the technique were potentially not just aesthetic but also functional. “But I would like to see all the data to judge that,” he said.

Serendipitous Discovery in Scleroderma

Butler has treated patients with orofacial fibrosis due to SSc for years using various surgical techniques to help alleviate microstomia, such as soft tissue release, skin grafts, mucosal grafts, and skin flaps. The realization that lipotransfer may have more than a postsurgical face-plumping effect came by chance.

“A sequence of about five or six patients came back to me 6 months following their intervention to say that their dentist has noticed improved dental access to teeth they hadn’t been able to” reach previously, he said. “This had never been written in the literature at that time. So we had a ‘eureka’ moment where we realized there was an antifibrotic effect of this intervention.”

Upon investigation, lipotransfer was found to not only restore orofacial volume but also reverse the effects of orofacial fibrosis, and these effects could potentially last for several years. Although multiple studies followed, there has been no prospective randomized control trial. Hence, the Sys-Stem study was undertaken.

The Sys-Stem Study

Designed as an open-label feasibility study, the Sys-Stem study involved 49 adult patients with disease that had been stable for 3 or more years. A total of 41 patients completed 6-month follow-up, including 20 who had been randomly allocated to the lipotransfer arm and 21 in the “treatment as usual” control arm. The median age was 47.5 years and 54.5 years in each group, respectively. The average time to diagnosis was 7.5 and 7.0 years, respectively; 11 (46%) and 13 (52%) had diffuse cutaneous SSc, respectively; and 15 (60%) and 17 (71%) were taking immunosuppressants, respectively.

Butler told Medscape Medical News that the intervention involved taking a fat graft from the abdomen of the patient, fractionating it to extract adipose-derived stem cells (ADSCs), and then including the cells in a preparation that was then injected back into the same patient via intra- and extra-oral routes.

While the procedure was relatively simple and could potentially be performed in other centers, Butler stressed that there is a very particular way in which the ADSCs need to be harvested, right down to the cannula size. The procedure also required patients to undergo general anesthesia because using local anesthesia would be detrimental to the stem cell preparation.

The main side effects included bruising and swelling at the site of abdominal fat removal and at the injection sites into the orofacial area.

Study Results

All outcome measures were assessed at baseline, 6 weeks, 3 months, and 6 months from the time of intervention in the treatment arm or from baseline in the control arm.

The primary outcome was the change in MHISS from baseline to 6 months. This measure specifically assesses disability involving the mouth in patients with SSc and is scored from 0 to 48 in which higher numbers indicate worse mouth functioning. Baseline scores were a respective 33.6 and 37.1 points in the lipotransfer and control arms, falling to 30.7 and rising to 38.8 points, respectively. The estimated treatment effect was -5.04, significantly in favor of the intervention.

Significant improvement favoring lipotransfer was also observed for MHISS at 3 months (-5.97 estimated treatment effect), as well as for the BFNE at 3 and 6 months, the DAS24 at 6 months, and the HADS at 3 and 6 months.

Mouth opening measured using a plastic cone increased from 3.84 cm at baseline to 3.89 cm at 6 months in the lipotransfer arm and declined from 3.87 cm at baseline to 3.66 cm in the control arm. The inter-incisor distance rose from 3.20 cm at baseline to 3.72 cm in the lipotransfer arm and decreased from 3.68 cm at baseline to 3.56 cm at 6 months in the control arm.

The researchers saw significant improvement in stimulated but not unstimulated salivary flow at 6 months in the lipotransfer arm, with stimulated salivary flow increasing from 0.94 mL/min at baseline to 1.25 mL/min at 6 months compared to a decrease from a baseline of 0.86 mL/min to 0.77 mL/min in the control arm.

“We do need further studies to assess optimal delivery outcomes and biological mechanisms,” Butler said.

How lipotransfer exerts it’s “putative” antifibrotic effect is currently unknown, Butler said, but “we think that it’s a regenerative effect driven by the adipocyte-derived stem cell.” He noted that the procedure also has been used successfully to treat radiation-induced fibrosis and lichen sclerosis.

The study was funded by the National Institute for Health and Care Research. Butler reported having no relevant financial relationships. Del Galdo was not involved in the study and had no conflicts of interest.

Sara Freeman is a medical journalist based in London, England.