Identifying Nodules

Nodules..., every injector's worst nightmare! A nodule is defined as growth of abnormal tissue developed underneath the skin. They often present as a large and hard lump that is very visible on the body in areas like the lips, cheek, jaw, etc. This can occur post injection as the nodules will appear soon after. There is nothing worse when you find them on a patient after you finish a dermal injection procedure. 

Factors Leading to Nodule Formation

There are many causes that can lead to nodule formation. However, there are 3 main causes which include the properties of the hyaluronic acid tissue filler used, possible coexistent infection/colonization of pathogens, and the patient’s immune response. The plausible causes can include any of the following:

• Bolus size 
• Pathogenicity of the implanted bacteria 
• Body tolerating a normal skin commensal carriage 
• Viremia or post vaccination immune response
• Implanted bacteria 
• Age & Condition of Filler
• Activation of Toll-like receptors 
• Reactive oxygen species 
• Amount of filler per session   

Case Of Nodule Formation Due to Degradation of Hyaluronic Acid

Another big cause of nodule formation is through the degradation of hyaluronic acid in the skin. Native hyaluronic acid starts out as a high molecular weight (~5000 kDa, or anything greater 1000 kDa). Hyaluronic acid is eventually degraded by hyaluronidase 1 and 2 (Hyal-1 and Hyal-2) and reactive oxygen species into 20 kDa fragments. These fragments then undergo endocytosis and drop into the lysosomes where it is further degraded by Hyal-1. Fragments of hyaluronic acid are pro-inflammatory, which can activate an array of immune receptors leading to an inflammatory response and can serve as an early warning to nodule formation. 

Nodule Classification and Treatment 

Nodules are classified into 3 categories: Primarily Filler Related, Primarily Inflammatory, or Primarily Infective 

Nodules: Primarily Filler Related

• Signs/Symptoms: Tissue edema, displacement of filler, or Tyndall effect 
• Main Causes: Altered lymphatic drainage and/or chronic low-grade inflammation or late migration of filler
• Treatment: Removal of filler using Hyaluronidase

Nodules: Primarily Inflammatory

• Signs/Symptoms: Persistent cold inflammatory delayed nodules that arise intermittently and settle spontaneously
• Main Causes: Combined pathogenic-immunologic trigger 
• Treatment: Allow to settle if minor, anti-inflammatory treatment (prednisolone or colchicine and nonsteroidal), or antibiotics (such as tetracyclines)

Nodules: Primarily Infective 

• Signs/Symptoms: Hot delayed nodules 
• Main Causes: Pathogen through hematogenous spread or local infiltration of virulent skin pathogen 
• Treatment: Antibiotics (Doxycycline, Clarithromycin, or Cephalosporin), dissolve filler using hyaluronidase, or drainage of abscess

Keeping your patient well informed about the possibility of nodule formation is vital since early treatment is optimal. It is important for an injector to identify and classify the nodules so they can treat the nodule appropriately.