Nodule Formation Following Treatment With Hyaluronic Acid Fillers: A Report of Two Challenging Cases

May 2018 | Volume 17 | Issue 5 | Case Reports | 580 | Copyright © May 2018

Meredith L. Orseth MD,a Nicole Lee MD,b Omer Ibrahim MD,c Kenneth A. Arndt MD,d and Michael Kaminer MDd

aUniversity of Texas Southwestern Medical Center, Dallas, TX bWesson Dermatology, Great Neck, NY cChicago Cosmetic Surgery and Dermatology, Chicago, IL dSkinCare Physicians, Chestnut Hill, MA

Nodule formation can be a potentially disfiguring adverse event of soft tissue fillers. Limited treatment consensus exists regarding the optimal approach for addressing recurrent and persistent nodules. Here we describe two challenging cases of nodules that developed following injection with Restylane and Juvéderm Voluma. We review suspected pathophysiology and discuss our treatment approach. J Drugs Dermatol. 2018;17(5):580-581.


Recurrent and persistent nodule formation following soft tissue filler injection presents a therapeutic challenge as there is limited agreement about the optimal approach for treatment. Here we report two cases of nodule formation after treatment with two different hyaluronic acid (HA) fillers and review potential etiologies and therapeutic options.


Case 1In 2011, a 65-year-old woman presented with volume loss of the central and lower face. Past treatments had included Restylane to the central face and jawline without complications. After consultation, 1 ml of Restylane-L was injected into the marionette lines and oral commissures. Two weeks later, she developed a tender nodule on the left jawline without erythema or fluctuance. Hyaluronidase mixed 1:1 with normal saline for a total of 0.4 mL (30 units) was injected into the nodule and she was given doxycycline 100 mg twice daily. Although there was initial diminution of the nodule, it persisted and clindamycin 150 mg twice daily was added to her regimen. Despite several months of antibiotic therapy, she continued to develop additional nodules involving her mandible and chin.Histopathology of the nodule of the left jaw lesion revealed septal fibrosis, chronic inflammation, occasional giant cells and residual HA in the subcutaneous tissue. Stains and cultures demonstrated rare surface bacteria and were negative for fungus and atypical mycobacterium. Treatment continued with alternating injections of hyaluronidase mixed 1:1 with either triamcinolone 5-10 mg/ml and clindamycin 150 mg/ml, in addition to oral doxycycline and clindamycin. After several months, the nodules resolved and therapy was discontinued. Following resolution of symptoms, she continued to receive ongoing treatment with Restylane without adverse effect.In 2016, 2 ml of Restylane Silk were injected into the upper cutaneous lip and nasolabial folds. The following month she underwent a root canal procedure and shortly thereafter developed nodules in the left marionette area. Despite use of oral antibiotics and intralesional hyaluronidase, she continued to develop additional nodules. One nodule was drained and the culture showed rare growth of Staphylococcus Epidermidis. The nodules resolved following treatment with a combination of intralesional triamcinolone 40 mg/kg, hyaluronidase 150 USP/mL, and 5-fluoruracil 50 mg/mL in a 1:1:1 ratio, 0.3 mL total.Case 2In 2016, a 69-year-old woman presented with malar atrophy and was treated with 1 ml of Juvéderm Voluma to the bilateral cheeks. She returned one month later with an erythematous, tender nodule on the left cheek, which was treated with 2.3 mL of undiluted hyaluronidase and clarithromycin 500 mg twice daily. Over the ensuing months, she developed additional nodules that required the same treatment resulting in resolution of each episode of nodules. She remained on clarithromycin for 30 days after her last nodule injection, with complete resolution of symptoms to date.


HA is a biodegradable glycosaminoglycan polysaccharide present in nearly all species and is regarded as having low immunologic potential.1,2 Restylane is a non-animal HA filler that was approved for use in the United States for soft tissue augmentation in 2003.3 In 2013, Juvéderm Voluma, a viscoelastic gel with crosslinked HA, obtained FDA approval for correction of mid-face volume loss.4