Post-vaccination delayed hypersensitivity reaction to aluminum salts can result in injection site adverse reactions like erythema, subcutaneous nodules, and sterile abscess formation.7,8 The formation of granulomas in patients with local vaccine reactions has been reported and supports a delayed-type hypersensitivity reaction.4,5,9 Previous articles have also shown an association between positive aluminum patch tests and post-vaccination subcutaneous nodules.9,10 Lehman et al describes an infant with recurrent sterile abscesses at vaccination sites who also had a positive aluminum patch test.11 Further studies are needed to confirm the association between aluminum allergy, delayed hypersensitivity reaction, and formation of persistent nodules following vaccination. Though our patient had frank necrosis rather than an itchy subcutaneous nodule, a delayed type hypersensitivity reaction should be a consideration in the etiology of her ulcer.Correct vaccine placement and proper needle length and size can minimize vaccine reactions to aluminum salts and improve patient outcomes. Placement of vaccines into subcutaneous tissue rather than deep into muscle can cause irritation and decreases efficacy of the vaccine.3,12 Frederiksen et al describes a child with an itching granuloma at vaccine injection site on the second shot in a series; however, no granuloma formed when the third shot was carefully placed intramuscularly.13 A longer needle and larger gauge may facilitate deep intramuscular injection and greater vaccine dispersion, respectively.3 The blood supply to muscle is larger than subcutaneous tissue, facilitating faster absorption of the vaccine into the circulation. Thus, deep intramuscular injection may reduce local reaction to aluminum salts and improve integration of vaccine components into the blood. Ipp et al demonstrated that a longer needle reduced local redness and swelling in children given the diphtheria, tetanus, pertussis-polio vaccine.14 A wider bore injects the vaccine over a larger surface area and prevents concentration of vaccine contents in one localized area. Muscles also have fewer pain fibers than the skin and subcutaneous tissue, indicating that intramuscular injection using a longer needle may actually reduce pain at the injection site.3 To prevent local adverse reactions to aluminum adjuvants, healthcare providers should evaluate each patient prior to vaccination and select an appropriate needle size and gauge to accomplish deep intramuscular injection.The previous report of necrotizing granulomatous reaction to subcutaneous aluminum salts warrants evaluation for this same condition in our patient.1 Her current biopsy shows no evidence of granulomatous inflammation, only nonspecific necrosis of the epidermis and dermal appendages. The absence of granulomas in our patient is extremely unique, although it is possible that granulomas were present but missed due to sampling error from the biopsy.Improper placement and subsequent inflammatory reaction to aluminum salts is the likely cause of our patient’s current condition; however, allergic reaction to aluminum or other vaccine components should be considered. The Pneumovax vaccine contains the preservative phenol, a potential allergen. Neomycin is a known contact allergen, and application at the ulcer site may have elicited a delayed-hypersensitivity; however, neomycin-induced granulomatous reaction has not previously been reported. It is also possible that this represented a hypersensitivity reaction to aluminum. However, even in aluminum-allergic patients, proper intramuscular injection reduces local adverse reactions and allows these patients to safely receive aluminum-adjuvant vaccines.15 Infection was thought to be unlikely given our patient’s negative cultures, afebrile state, and normal leukocyte count. It is imperative that healthcare professionals recognize the importance of proper vaccine placement, needle size, and needle length in the placement of vaccines. Proper placement not only reduces adverse local reactions but also improves vaccine efficacy and patients’ trust in their healthcare providers.
Local necrosis at the site of vaccination is a rare adverse event, with only one case reported to date. Aluminum salt toxicity was thought to be the likely culprit in this case, especially if injected subcutaneously rather than intramuscularly. Proper intramuscular placement and appropriate needle size and length may prevent this severe vaccine reaction and improve patient outcomes.
Drs. Canavan, Pavlidakey, Cantrell, and Ms. Donaldson have no conflicts of interest to disclose. Dr. Elewski receives support from the following companies for clinical research at UAB: Amgen, Abbvie, Boehringer Ingelheim, Celgene, Incyte, Lilly, Merck, Novartis, Pfizer, Viamet, and Valeant. She has also received honorarium from the following companies: Anacor, Celgene, Lilly, Novartis, Pfizer, and Valeant. There was no funding source for this case report.Statement of Ethics:Informed consent was obtained from the patient.
- Alsuwaidi AR, Albawardi A, Khan NH, Souid A-K. A 4-month-old baby presenting with dermal necrotizing granulomatous giant cell reaction at the injection site of 13-valent pneumococcal conjugate vaccine: a case report. J Med Case Reports. 2014;8(1).
- Batista-Duharte A, Lindblad EB, Oviedo-Orta E. Progress in understanding adjuvant immunotoxicity mechanisms. Toxicol Lett. 2011;203(2):97-105.
- Zuckerman JN. The importance of injecting vaccines into muscle. Different patients need different needle sizes. BMJ. 2000;321(7271):1237-1238.
- Lam M, Patel AN, Leach IH. Nodule on the upper arm. Clin Exp Dermatol. 2014;39(7):844-846.
- Bergfors E, Hermansson G, Nyström Kronander U, et al. How common are long-lasting, intensely itching vaccination granulomas and contact allergy to aluminium induced by currently used pediatric vaccines? A prospective cohort study. Eur J Pediatr. 2014;173(10):1297-1307.
- Chong H, Brady K, Metze D, Calonje E. Persistent nodules at injection sites (aluminium granuloma) -- clinicopathological study of 14 cases with a diverse range of histological reaction patterns. Histopathology. 2006;48(2):182-188.
- Fritsche PJ, Helbling A, Ballmer-Weber BK. Vaccine hypersensitivity--update and overview. Swiss Med Wkly. 2010;140(17-18):238-246.
- Lauren CT, Belsito DV, Morel KD, LaRussa P. Case Report of Subcutaneous Nodules and Sterile Abscesses Due to Delayed Type Hypersensitivity to Aluminum-Containing Vaccines. Pediatrics. 2016;138(4).
- Bergfors E, Trollfors B. Sixty-four children with persistent itching nodules and contact allergy to aluminium after vaccination with aluminium-adsorbed vaccines-prognosis and outcome after booster vaccination. Eur J Pediatr. 2013;172(2):171-177.
- Salik E, Løvik I, Andersen KE, Bygum A. Persistent Skin Reactions and Aluminium Hypersensitivity Induced by Childhood Vaccines. Acta Derm Venereol. 2016;96(7):967-971.
- Lehman HK, Faden HS, Fang YV, Ballow M. A case of recurrent sterile abscesses following vaccination: delayed hypersensitivity to aluminum. J Pediatr. 2008;152(1):133-135.
- Shaw FE, Guess HA, Roets JM, et al. Effect of anatomic injection site, age and smoking on the immune response to hepatitis B vaccination. Vaccine. 1989;7(5):425-430.
- Frederiksen MS, Tofte H. Immunisation with aluminium-containing vaccine of a child with itching nodule following previous vaccination. Vaccine. 2004;23(1):1-2.
- Ipp MM, Gold R, Goldbach M, et al. Adverse reactions to diphtheria, tetanus, pertussis-polio vaccination at 18 months of age: effect of injection site and needle length. Pediatrics. 1989;83(5):679-682.
- Beveridge MG, Polcari IC, Burns JL, et al. Local Vaccine Site Reactions and Contact Allergy to Aluminum: Local Vaccine Site Reactions. Pediatr Dermatol. 2012;29(1):68-72
Stephanie Donaldson BS firstname.lastname@example.org