Reaction to Synvisc and approach for other sodium hyaluronate agents
Question:
12/22/2023
I have a patient who needs an eye surgery in which a hylan/viscoelastic product will be injected and then pulled out. She had reaction after her third intra-articular Synvisc injection (approx. 2015) in which he next day her knee was red, swollen, could not put pressure on. She reportedly needed to have Synvisc removed & the swelling improved quickly. No SOB. Tolerated Euflexa 2016. Euflexa is not approved for the eye. The ophthalmologist suggests viscoat, provisc and healon (all very similar to Synviss). I am still waiting for the surgery centers package insert however I counseled do not know false positive/negative rates to the inactive ingredients. I know there is a past quetsion addressing a skin prick test concentration with a Synvisc however I do not know the false positive/negative rate. The surgeon mentioned to the patient a possible desensitization but I have not seen one published nor would understand the rationale of a desensitization for a visco-elastic agent. Do you have any insight on possible courses of action?
Answer:
There are no published positive or negative predictive values for skin testing to these agents. I will share some background about the agents and what I recommend.
The commonly used ophthalmic visco-surgical devices (OVDs) are composed of the following three building blocks: sodium hyaluronate (NaHA): a biopolymer found throughout our bodies in connective tissues; chondroitin sulfate (CS): another biopolymer, a major mucopolysaccharide in the cornea; and hydroxypropyl methycellulose (HPMC): a component of plant fibers.
Healon D is sodium hyaluronate; Viscoat is both sodium hyaluronate and chondroitin sulfate; Examples of common cohesive OVDs include Healon, Healon GV, Provisc (Alcon), and Amvisc (B&L). (1) Provisc is 1% sodium hyaluronate (2), Healon has several types ranging from 1-3% sodium hyaluronate. (1)
Note that all of these products are composed of sodium hyaluronate, and by changing the concentration different characteristics can be achieved.
SYNVISC/Synvisc-One is derived from a natural, avian source to achieve high molecular weight (6 MDa). NaHA derived from bacterial production has molecular weights of 4 MDa or less.(4)
Different side effects following injection of filler have been described in the literature, ranging from granulomas, non-granulomatous nodules, product migration, and late hypersensitivity reactions to more severe ones such as vascular occlusion and anaphylaxis. (5)
Plastic surgeons use NaHA frequently, and a survey showed ~10% of them perform skin testing before use. Skin testing involves injecting 20 units of hyaluronidase subcutaneously in the forearm and observing the results after 30 minutes. Although this survey did not explore why 90% of surgeons forego skin testing, the historically low incidence rates of an allergic reaction to hyaluronidase may be a contributing factor.(6,7)
I would see if your patient is allergic to avian, as this may be a cause of any differences in reaction to Synvisc vs the other agents. I would recommend speaking with the ophthalmologist about the concentrations of NaHA in the formulations they recommend and the risks of using those agents. The risk of reaction should be discussed with the patient, so she is aware of this beforehand. Even without known positive and negative predictive values, you could perform skin testing with each of the products to pick one that might be less likely to cause reactions.
1. https://www.reviewofophthalmology.com/article/understanding-and-using-the-full-spectrum-of-ovds, Accessed 12/29/23
2. https://www.rxlist.com/provisc-drug.htm, Accessed 12/31/23
3. https://www.jnjvisionpro.com/healon-pro, Accessed 12/31/23
4. https://www.synvisconehcp.com/science, Accessed 12/31/23
5. Kastritsi O, Kastritsi ED, Matzakanis G. Delayed hypersensitivity reaction following lip fillers, not one but four times in the same patient. JPRAS Open. 2023 Jul 17;37:130-134. doi: 10.1016/j.jpra.2023.07.003. PMID: 37534282; PMCID: PMC10393583.
6. Olaiya OR, Forbes D, Humphrey S, Beleznay K, Mosher M, Carruthers J. Hyaluronidase for Treating Complications Related to HA Fillers: A National Plastic Surgeon Survey. Plast Surg (Oakv). 2022 Aug;30(3):233-237. doi: 10.1177/22925503211019618. Epub 2021 Jun 8. PMID: 35990397; PMCID: PMC9389064.
7. Yocum RC, Kennard D, Heiner LS. Assessment and implication of the allergic sensitivity to a single dose of recombinant human hyaluronidase injection: a double-blind, placebo-controlled clinical trial. J Infus Nurs. 2007;30(5):293–299. doi:10.1097/01.NAN.0000292572.70387.
Carla M. Davis, MD, FAAAAI