Understanding, Avoiding, and Treating Potential Adverse Events Following the Use of Injectable Poly-L-Lactic Acid for Facial and Nonfacial Volumization

Histologically, papules and nodules consist of an overabundance of microparticles (often surrounded by skeletal muscle) surrounded by a normal foreign body reaction including foreign body giant cells.⁹ It is important to note that the presence of foreign body giant cells constitutes a histopathological diagnosis of “granuloma,” initially implicating these lesions to be inflammatory lesions. This implication led to early treatment of this problem with steroid injections. However, injection of steroids or anti-mitotics such as 5-fluorouracil (5-FU) have little clinical effect on these lesions because the majority of the lesion is product and not host reaction to product. Additionally, injection of steroids may lead to atrophy of adjacent tissue, actually accentuating the visibility of the nodule. Most nodules associated with PLLA injection will resolve on their own.²³ Many patients simply need reassurance that they are not dangerous, will not grow in size or number, and will resolve on their own. Excision is an option, but resolves a transient problem with a permanent scar.^23,24 Camouflage of these lesions with hyaluronic acid (HA) gel until they resolve may offer a more gratifying treatment (Figure 1).

Finally, the location of papules and nodules may suggest their origin. Proper dilution, reconstitution, and deep placement are critical. Superficial placement leads to visible papules. Placement in or through active muscles, particularly under the eye or near the corners of the mouth, leads to localized overcorrection and nodules (representing product trapped in muscle fibers). These may even be seen in a patient with a strong zygomaticus major muscle. Diffuse papules/nodules are likely to be an issue with reconstitution (ie, shaking the vial immediately after adding water; crystals on the sidewalls of the vial won’t hydrate), inadequate hydration time (leading to in vivo hydration), or poor suspension immediately prior to injection (leading to uneven distribution of particles). Lastly, focal papules/nodules may be an issue of placement (ie, redeposition at the apex of a “fan” when using the fanning technique).

First, it should be noted that the term “granuloma” has been used in reference to papules and nodules as well as to large inflammatory lesions in the medical literature,³ which has resulted in considerable challenges in the interpretation of granuloma incidence and, in turn, to the overall safety profile associated with the use of injectable products such as PLLA.³ In contrast to the low power histopathology of a nodule showing an overabundance of product with a “normal” foreign body reaction consisting of a few foreign body giant cells, histopathology of a true granuloma shows a smaller amount of product with an overabundance of host reaction to product and “wall-to-wall” foreign body giant cells (Figure 2).¹⁹ This is in contrast to the purposeful stimulation of a subclinical inflammation, which is, in fact, the mechanism of action of stimulatory products like PLLA, calcium hydroxyapatite, and polymethylmethacrylate. With the injection of collagen stimulators in a normal host, subclinical granulomatous inflammation is a natural and desired tissue response that follows a predictable course.¹⁹ A form of chronic inflammation, granulomatous inflammation occurs to prevent the migration of bodies that cannot be removed by phagocytosis or enzymatic breakdown; it is histologically distinctive for its accumulation of epithelioid cells, a type of modified macrophage.³ In a “normal” response, the encapsulation of the product and the subsequent fibroplasia is