Regional grafting of autologous adipose tissue is effective in inducing prompt healing of indolent digital ulcers in patients with systemic sclerosis: results of a monocentric randomized controlled study

Abstract

Background: A randomized controlled trial (RCT) was performed to confirm preliminary uncontrolled data indicating that regional adipose tissue (AT) grafting (G) is effective in inducing ischemic digital ulcer (IDU) healing in patients with systemic sclerosis (SSc).

Patients and methods: SSc patients with IDUs were randomized to be blindly treated with AT-G or a sham procedure (SP). AT-G consisted of injection, at the base of the finger with the IDU, of 0.5-1 ml AT after centrifugation of fat aspirate. The SP consisted of false liposuction and local injection of saline solution. The primary endpoint was to compare the cumulative prevalence of healed IDUs in the two groups within the following 8 weeks.

Results: AT-G and the SP were carried out in 25 and 13 patients, respectively. The two groups were comparable for age, gender, disease duration, and SSc subtypes. IDU healing was observed in 23/25 and 1/13 patients treated with AT-G and the SP, respectively (p < 0.0001). The 12 patients who received the unsuccessful SP underwent a rescue AT-G. In all of them, IDU healing was observed after 8 weeks of observation. It was noticeable that in the AT-G-treated patients a significant reduction of pain intensity (measured by visual analogue scale) was recorded after 4 and 8 weeks (p < 0.0001 in all cases). Similarly, a significant increase of capillary numbers in the affected finger was recorded by nailfold videocapillaroscopy after 4 and 8 weeks (p < 0.0001 in both cases).

Conclusion: This RCT strongly confirms that AT-G is effective in inducing IDU healing in SSc patients.

Trial registration: ClinicalTrials.gov, NCT03406988 . Registered retrospectively on 25 January 2018.

Keywords: Adipose tissue stem cells; Autologous fat grafting; Digital ulcers; Systemic sclerosis.

Conflict of interest statement

Ethics approval and consent to participate

All participants provided written informed consent prior to data collection. This study was conducted according to the Helsinki declaration and was approved by the local Ethical Committee (Comitato Etico Milano Area 2, Session 04.07.2017, Reference Number 138).

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1

Flowchart for consecutive steps of the study. For more details, see Patients and methods. AT-G adipose tissue grafting, DU digital ulcer, SP sham procedure

Fig. 2

Percentages of healed IDUs in patients treated with AT-G and in those who underwent SP. During 8 weeks of RCT follow-up, number of AT-G-treated patients who achieved IDU healing was significantly higher than number of patients who underwent SP (log-rank p < 0.0001), with hazard ratio of 22.2 (95% CI 9.97–49.42). At 10 weeks, all 12 patients of control group whose IDU did not heal received a rescue AT-G. In following 8 weeks, DU healing was observed in all of these patients. AT-G adipose tissue grafting, RCT randomized controlled trial, SP sham procedure

Fig. 3

Digital ulcer progressive healing of patient 2 (a) and patient 8 (b) after autologous AT-G

Fig. 4

Variations of pain intensity measured by VAS in patients treated with AT-G as active therapy (a) and in those who underwent SP as placebo treatment (b). VAS for pain measured every week in all study patients. (a) Comparisons between baseline VAS values and those recorded at 4 and 8 weeks of follow-up, and between values at 4 and 8 weeks, in patients treated with AT-G are all highly significant. (b) VAS values remained unchanged in patients who underwent SP. VAS visual analog scale, w weeks

Fig. 5

Variations in number of capillaries assessed by NVC in fingers of patients with cardinal IDU treated with AT-G as active therapy (a) and who underwent SP as placebo treatment (b). (a) Comparisons between baseline counts with those recorded at 4 and 8 weeks, and between counts recorded at 4 and 8 weeks, of follow-up in AT-G-treated patients are all highly significant. (b) Capillary counts remained unchanged in patients who underwent SP. w weeks