Objective:

Hyaluronic acid (HA) is a naturally occurring polymer, present in different tissues of human cells which is a crucial component of the extracellular matrix. Its exceptional properties—including biocompatibility, non-immunogenicity, biodegradability, rheological flexibility, high hydrophilicity, ease of chemical modification, and viscoelasticity—enable a wide range of therapeutic applications. However, HA injections/ applications can lead to both early and delayed complications, ranging in severity from mild to serious. Additionally, the risk profile may evolve as therapeutic approaches and technologies continue to advance.

Materials and Methods:

In this study, a systematic literature search was achieved on PubMed on January 5, 2023 and only case reports conducted in humans in last ten years (from 2013 to 2023) were considered. Literature reviews, clinical trials, technical notes, recommendations, and instructional course were excluded. Reviewed case studies that did not match the determined criteria were removed.

Results:

109 case studies representing 154 patients with severe complications were examined. The year of publication, total number of patients, age and gender of patients, adverse effects/ symptoms, and the reason of adverse effects of each case was listed. The case studies were classified according to the reason of adverse effects after HA application as intravascular injection and vascular obstruction, hypersensitive/ allergic affect, delayed inflammatory reaction (DIR), virus infection, bacterial infections, and others. Reactions to HA were reported as frequent redness, swelling, bruising, nodules, erythema, edema, tenderness, blindness, pain, and rarely death.

Conclusion:

To conclude, adverse effects after HA application were found to be of high incidence in the population due to its widespread use. Even though adverse reactions are declared, these findings do not increase safety concerns related to the use of HA compared to the beneficial effects of it. The majority of negative situations may be avoided with improved application procedures.

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