Working in Aesthetics? You Might See One of These Uncommon Conditions Someday

Disclaimer: This article is meant to offer some suggestions for treating two uncommon conditions in aesthetics and is not intended to be a substitute for individualized, comprehensive patient care in a similar situation.

Every day working in aesthetic practice is a gift. We provide the gift of beauty to the patient and they provide us with the gift of gratitude. Working in our busy practices, we may sometimes find ourselves faced with an unexpected patient response to treatment; one that we have read or heard about but have never personally encountered. When this happens, the only option we might have is to look in the literature for the answer. But what if there is little or no published information on the subject? What if there is little understanding of the cause of the issue, much less, a standardized treatment for it? What can we do in this situation?

Two of the unexpected responses you might see during your career in aesthetics are late onset hypersensitivity nodules or granulomas and non-response of neurotoxin treatment due to the hypothesized antibody formation.

1. GRANULOMA FORMATION

Thousands of aesthetic practices provide dermal filler treatments in the US and the potential for complications can grow over time due to increasing numbers of practitioners with varying skill levels and patients with varying medical conditions. Patients can be at risk for developing several side effects from dermal filler procedures ranging from swelling and bruising to the serious vascular occlusion. For purposes of this article, only late onset nodule formation is discussed.

Nodules are categorized as early onset or late onset. Early onset nodules can appear in minutes, hours, or days whereas late onset nodules can occur weeks, months, or years after a procedure. Nodule formation is an uncommon occurrence in dermal filler procedures when done by experienced practitioners. Typically, a nodule appears because too much product was placed into a small space and consequently, a nodule or as patients might call them, “a bump” forms. Nodules formed from hyaluronic acid (HA) dermal fillers are easily corrected and dissolved with hyaluronidase. Nodule formation from other types of dermal filler products are more challenging to treat and some may require a surgical procedure to remove them.

Nodules from HA fillers are easily identified because they usually form in one or two areas where the filler has been placed. Keep in mind, the formation of a solitary nodule may be from several origins and should be investigated. On the contrary, nodules formed by true hypersensitivity can cause granulomatous tissue occur in every area that was injected. Sometimes one area at a time becomes inflamed, firm, and raised but eventually, all areas treated form granulomas.

Granulomas from dermal fillers are a hypersensitivity response to the product. In some cases, the patient has no history of a hypersensitivity response. The formation of a granuloma is an immune response (type IV hypersensitivity reaction) where sites treated with the offending product develop a reaction, often weeks or months after the procedure. In some cases, the patient may have history of influenza prior to this delayed reaction. Histological evaluation of suspected granuloma formation is warranted and necessary to confirm diagnosis.

CASE REPORT

The following is a report on how my particular patient was treated and is by no means prescriptive: The regimen resulted in complete resolution of nodules highly suspected of being foreign body granuloma formation. We did not take biopsies of the nodules due to the location of the reactions however, the patient had an MRI to rule out malignancy, abscess, and other types of masses. The MRI was negative.

This is an example of a late-onset granulomatous hypersensitivity reaction under both eyes. Photo credit: Turkmani MG, De Boulle K, Philipp-Dormston WG (2019).

During my career, I have done tens of thousands of dermal filler injections and I believe this case to be the only (likely) granuloma formation case in my practice. The patient had a history of HA filler treatment several times over the years and had no adverse effects. She returned to the office 18 months after her most recent filler treatment with a firm, raised nodule to one of the 4 areas that had been injected with HA filler. She was promptly treated with an antibiotic in case of infection and prednisone 40mg qd X 7 days. Once the antibiotic course was finished, she was treated with 100 units of full-strength hyaluronidase every 24 hours for 3 days and then every 48 – 72 hours X 3. The nodule softened, flattened, and ultimately disappeared.

Within one week of resolution of the first nodule, a second nodule appeared in a different HA treated area. The same regimen was prescribed, and the nodule became hardly palpable. During treatment of the second area, the third and fourth treated areas also became slightly firm and raised, however, they were not visible and did not bother the patient. These last two areas were not treated with medications but were monitored for changes over the next month. The four areas treated with HA that ultimately formed nodules, completely resolved and the patient is happy. Unfortunately, in my opinion the patient is not a candidate for additional HA or other filler treatments.

No other areas on the patient’s face became affected likely because there were no other areas where HA was implanted. The timeline and course of this interesting reaction supports the diagnosis of granuloma formation

2. NO RESPONSE FROM botulinumtoxin type A (BoNT/A) TREATMENT

There are occasions in aesthetic medicine where a patient does not respond as expected to botulinumtoxin type A (BoNT/A) treatments. In some cases, the simple solution is to increase the dose or re-position the injection sites. Most of the time, this is effective.

However, there are patients who initially respond to BoNT/A but then, over time, they stop responding to treatment. One theory in current literature explains that certain patients may develop resistance to the toxin. This is an interesting theory. Let me explain.

Treatment with any protein can result in antibody formation and detection is related to the sensitivity and specificity of the assay. In addition, there are several factors that may play a role in antibody detection such as the method of specimen collection, handling, timing, underlying disease, and medications. For these reasons, the detection of antibodies to BoNT/A preparations compared to antibody detection in other studies may be misleading. In three trials treating lateral canthal lines, only 14 (1.5%) out of 916 subjects developed binding antibodies and none (0%) developed neutralizing antibodies. (As a refresher, neutralizing antibodies neutralize the effect whereas binding antibodies merely flag the antigen). Although the formation of neutralizing antibodies to BoNT/A are not completely understood, some studies have demonstrated more frequent treatments or higher dosing may contribute to the formation of neutralizing antibodies. A generally accepted practice is to use the lowest effective BoNT/A dose at the longest suggested interval, usually every three to four months.

CASE REPORT

Photo: B. Haney, DNP, FNP-C, FAANP

A 40-ish male patient is fairly consistent and would come in about every 4 -6 months for Botox? or Dysport? treatment, he has been seeing me for many years. We would switch between Dysport ? and Botox ? randomly. Then I noticed over the last 3 treatments I had to slightly increase the dose to get the same response (we always use full strength medication). This did not strike me as too unusual because on occasion, people might need a little more as they age. However, after his last treatment he returned after 2 weeks with full movement. It was as if I had injected water into his forehead, glabella, and crow’s feet!

A typical suspicion could be the toxin potency or batch was somehow inferior. So I reported the lot number to the manufacturer who stated they had no other reports from that batch. I reconstituted a new vial from a different manufacturer and injected the patient again using the usual dose. Two weeks later, he returned again with no response. I was perplexed and then realized, he could be becoming unresponsive to neurotoxin. I wondered if increasing the dose would help. I also wondered if the patient should take a drug holiday. I consulted with a plastic surgeon, Dr. Christian Subbio, who suggested I double the dose “to find his breaking point”. I tried his suggestion and…it worked! Unfortunately, increasing the dosage can increase price substantially and it would be up to you to give your patient who presents in this manner a price break or not.

CONCLUSION

In conclusion, these two cases are examples of issues that can arise in aesthetic practice but in my opinion, do not get much press. I had not had experience with these two issues until 2019 and I have been practicing aesthetics since 2002. I wrote this article to help increase awareness of potential issues that can arise and to demonstrate that if you are in aesthetics long enough, you will eventually get some very interesting cases. Don’t be afraid to ask for help or ideas – it makes you a better provider.

I look forward to comments and suggestions from other experts who would add input to help others - thank you!

Happy 2020 to you all!

Descriptions for the treatment of these uncommon side effects are based on clinical experience rather than by evidence-based clinical trials; they are presented here merely as information. 

References: 

Haney, B. Aesthetic Procedures: Nurse Practitioner’s Guide to Cosmetic Dermatology. Springer Nature AG. 2020: 86-87

Beleznay K, Carruthers JD, Carruthers A, Mummert ME, Humphrey S. Delayed-onset nodules secondary to a smooth cohesive 20 mg/mL hyaluronic acid filler: cause and management. Dermatol Surg. 2015;41:929–939.

Naumann M, Boo LM, Ackerman AH, Gallagher CJ. Immunogenicity of botulinum toxins. J Neural Transm (Vienna). 2013;120(2):275-90.

Allergan. Botox? cosmetic prescribing information. Package insert2017.

Frevert J. Pharmaceutical, biological, and clinical properties of botulinum neurotoxin type A products. Drugs R D. 2015;15(1):1-9.