Injection site nodules

Background

The development of an injection site nodule (ISN) is a rare adverse event following immunisation (AEFI). Nodules can occur following administration of any injected vaccine.  They usually present in the days or weeks following immunisation. ISNs are most often reported following vaccines given in infancy or childhood. An ISN usually persists for weeks or months. Very rarely, a nodule may persist for years. ISNs are most often asymptomatic, but may be intermittently tender, itchy, or show overlying skin changes (e.g. flaky skin). They generally resolve spontaneously, without treatment or investigation.

Diagnosis

ISNs are defined as a firm, discrete or well-demarcated soft-tissue lump at the site of vaccination, in the absence of heat, erythema (redness) or signs of abscess (e.g. pus, pain). They are often described by parents and caregivers as a pea-size lump under the skin.

Diagnosis is generally based on a healthcare provider’s clinical assessment. Although not routinely recommended, some clinicians may request an ultrasound of the area to confirm or support the diagnosis, and to exclude alternative diagnoses.

ISNs that last for months or years, with symptoms, are referred to as ‘persisting subcutaneous nodules’ (subcutaneous meaning under the skin). Itch is generally the concerning symptom that motivates people to seek medical attention. Ongoing scratching can alter the appearance of the skin leading to excoriation (irritated skin), hair growth and pigmentation changes.

Intensified itching and an increase in size of the nodule can occur during the course of a viral illness, or following subsequent vaccinations administered at a different anatomical site.

Association and incidence

It is unclear what causes an ISN. Factors identified as possibly contributing to ISNs include administration technique, vaccine components (including adjuvants, such as aluminium), patient predisposition and normal immune-mediated responses.

There is limited data on ISN incidence rates. Some estimates are available based on small, local cohorts.

The following references provide additional context on the possible causes and incidence of ISNs:

• Silcock R, Crawford NW, Selvaraj J, McMinn A, Danchin M, Lazzaro T, et al. Subcutaneous nodules following immunization in children; in Victoria, Australia from 2007 to 2016. Vaccine. 2020 Mar 5;38:3169–3177. doi:10.1016/j.vaccine.2019.12.066 
• Silcock R, Crawford NW, Perrett KP. Subcutaneous nodules: an important adverse event following immunization. Expert Rev Vaccines. 2019 Mar 11;18(4);405-410. doi:10.1080/14760584.2019.1586540 
• Bergfors E, Lundmark K, Nyström Kronander U. A child with a long-standing, intensely itching subcutaneous nodule on a thigh: an uncommon (?) reaction to commonly used vaccines. BMJ Case Rep. 2013;2013:bcr2012007779. Published 2013 Jan 24. doi:10.1136/bcr-2012-007779 

Treatment

A conservative approach to treatment is recommended; ISNs generally resolve on their own without intervention. On some occasions, health professionals might advise topical corticosteroids to treat the itch or skin changes, and dressings to protect the area from vigorous scratching. Rarely, excision of the nodule may be considered by a specialist, based on nature and severity of symptoms.

Any AEFI should be reported to the vaccine safety service in your state. In Victoria, reports can be made to SAEFVIC.

Implications for future doses

It is recommended that people who experience ISNs continue to receive future vaccines according to the immunisation schedule. The history of, or presence of, a nodule is not a contraindication to future vaccines.

Ensure correct vaccine administration for both intramuscular (IM) and subcutaneous (SC) vaccines. For IM vaccines, consider deep IM injection to minimise the risk of potential recurrence of a nodule. Where possible, avoid vaccination at a site of an existing nodule.

Resources

• Rothstein E, Kohl KS, Ball L, Halperin SA, Halsey N, Hammer SJ, et al. Nodule at injection site as an adverse event following immunization: case definition and guidelines for data collection, analysis, and presentation. Vaccine. 2004;22;575-585. doi: 10.1016/j.vaccine.2003.09.005
• MVEC: Injection site reactions