Hyaluronic Acid-Based Products Are Strictly Contraindicated in Scleroderma-Related Skin Ulcers

Giulio Gualdi, MD; Paola Monari, MD; Daniele Cammalleri, MD; Laura Pelizzari, MD; Piergiacomo Calzavara Pinton, PhD


Wounds. 2019;31(3):81-84. 

In This Article


Of the 106 treated wounds, 56 (52.8%) ulcers achieved healing with no side effects, 40 (37.7%) ulcers developed clinical worsening (intense periwound skin erythema, pain, and increasing ulcer dimension) and discontinued therapy, and the remaining 10 (9.4%) lesions developed transient periwound skin erythema and burning but did achieve healing. For the 40 worsening ulcers, a microbiological examination of the wound bed was performed due to suspicion of a superinfection; all sample cultures were negative for bacterial growth. A patch test also was performed on these patients with the HA-based products "as-is," showing to be negative for allergic contact sensitization.

If the percentage of ulcers that achieved healing were analyzed, 3 different results emerged: patients who healed without inflammation, patients who healed with a transient erythema, and a third skin reaction in which the patients worsened until the discontinuation of HA-based product use.

Furthermore, if the data are stratified based on ulcer etiology, inflammatory ulcers versus noninflammatory ulcers, 2 groups are identified (Table 2, Figure). Group 1 is represented by patients with noninflammatory ulcers (vascular and postoperative) while group 2 is represented by only patients with scleroderma-related ulcers. In group 1, 65 patients (42 women, 23 men) with 65 ulcers were treated. The average age of the patient was 74 years (range, 40–98 years). In group 2 overall, 41 granulating skin ulcers in 14 patients with scleroderma (13 women, 1 man; lesion:patient ratio, 2.9) with a mean age of 65 years (range, 43–84 years). All 14 patients were affected with diffuse cutaneous systemic sclerosis and under continuous treatment with bosentan and periodically pulsed intravenous prostanoid.


The distinction of patients by etiology (sclerodermic vs. nonscleordermic) underlines the difference with topical treatment with hyaluronic acid-based products. Sclerodermic patients had to stop treatment due to worsening of skin lesions (92.7%) or healed with erythema (7.3%). Nonsclerodermic ulcers healed in 83.1% of wounds and healed with erythema in 15.4%.

Of the 65 ulcers treated in group 1, 54 (83.1%) achieved healing, 10 (15.4%) developed transient and nonspecific inflammatory reactions (erythema, edema, burning, redness) but ultimately healed, and 1 (1.5%) showed clinical deterioration with an increase in size and pain, in which case the treatment was interrupted.

Of the 41 ulcers treated in group 2, 38 (92.7%) developed an immediate increase in periwound skin inflammation, increased pain and burning sensations, and increased ulcer size, forcing the patient to stop treatment and anticipate medical consultation. In these patients with multiple ulcers, all wounds showed the same clinical behaviors. After the discontinuation of local therapy with HA, a steroid topical application was needed to reduce inflammation. The remaining 3 ulcers of the 41 treated (7.3%) belonged to the same patient who had an inflammatory reaction, but the ulcers finally healed.