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BMJ Case Rep. 2009; 2009: bcr09.2008.0951.
Published online 2009 March 17. doi:  10.1136/bcr.09.2008.0951
PMCID: PMC3029045
Findings that shed new light on the possible pathogenesis of a disease or an adverse effect

Recurrent sterile abscesses following aluminium adjuvant-containing vaccines

Nicola P Klein,1 Kathryn M Edwards,3 Robert C Sparks,3 Cornelia L Dekker,2 and on behalf of the Clinical Immunization Safety Assessment (CISA) Network

Abstract

Abscess formation following immunisation is a previously reported complication, generally associated with microbial contamination of the vaccine. Less commonly, such abscesses have been sterile. Here we describe two children evaluated in the Center for Disease Control and Prevention (CDC)-funded Clinical Immunization Safety Assessment (CISA) network who developed recurrent sterile abscesses after administration of vaccines containing aluminium adjuvant, either individually or in combination. Although the abscesses healed without sequelae, these occurrences support an association between receipt of aluminium adjuvant and sterile abscesses in susceptible patients. For patients with similar symptoms, clinicians may wish to choose a vaccine formulation containing the least amount of aluminium adjuvant.

BACKGROUND

Although abscess formation following immunisation is a previously recognised complication,1,2 it generally results from microbial contamination of the vaccine. However, sterile abscess formation following immunisation with diphtheria and tetanus toxoids and whole cell pertussis vaccines (DTwP) has also been reported3 and recurrent sterile abscesses following administration of other vaccines have been described.4,5

Recently the Centers for Disease Control and Prevention (CDC)-funded Clinical Immunization Safety Assessment (CISA) network evaluated two reports of children with recurrent sterile abscesses following vaccination. Detailed descriptions of administered vaccines are given in table 1.

Table 1
Vaccine administration site, manufacturer, aluminium content and clinical outcome for the cases presented

CASE PRESENTATION

Case 1

A 2-month-old girl received initial immunisations consisting of inactivated poliovirus (IPV), diphtheria and tetanus toxoids and acellular pertussis (DTaP), Haemophilus influenzae type B conjugate–hepatitis B virus (Hib–HBV) and pneumococcal conjugate vaccines (PCV7) without incident. At 4 months, she again received IPV and DTaP vaccines in the left thigh and Hib–HBV and PCV7 vaccines in the right thigh (table 1). Three weeks later, induration without tenderness, warmth or erythema was noted at the injection sites in both thighs, the site became increasingly discoloured over the next 3 days, until the right thigh spontaneously drained 15 ml of purulent fluid. Her physician cultured a small amount of draining fluid from the right thigh the next day and the patient was given oral cefalexin. Six days later, purulent fluid from the left thigh mass was cultured. Cultures from both the right abscess (before antibiotics) and the left abscess (after antibiotics) were sterile. Both thigh lesions healed completely over the next month. Investigators in the CISA network discussed the case and recommended that subsequent vaccines be administered individually and that an evaluation of the patient’s immune status be completed. The findings included a normal complete blood count, slightly elevated total IgG 1360 mg/dl (normal range, 208–868 mg/dl) and IgM 162 mg/dl (normal range, 32–120 mg/dl), normal IgA and a normal CH50 level.

At 7 months, she received her 3rd PCV7 dose without incident. At 9 months, she received her 3rd doses of IPV (left thigh) and DTaP (right thigh) (table 1). Approximately 3 weeks later, induration without swelling was noted in the right thigh, increasing until it measured 6×5 cm by 11 days after vaccination. No antibiotics were prescribed and surgical drainage yielded material negative for bacterial growth. Additional immunologic evaluations revealed normal IgE level and neutrophil oxidase activity. Antibody titers against tetanus toxoid, diphtheria, pertussis toxins and pneumococcal serotypes were consistent with normal vaccine responses. Lymphocyte proliferation studies following stimulation with mitogens, tetanus toxoid and pneumococcal antigen also revealed an adequate, but not excessive, proliferative response. The patient subsequently received the measles–mumps–rubella (MMR) vaccine at 23 months of age without incident.

During the ensuing months, the patient had a diagnosis of trimethylaminuria (TMAU), a congenital disorder in which the enzyme needed to breakdown the chemical trimethylamine is lacking. At 38 months, she received her 4th dose of DTaP (table 1). Two weeks later, increased induration and swelling without erythema or warmth were noted at the injection site. Bacterial cultures yielded meticillin-resistant Staphylococcus aureus (MRSA) only in the thioglycolate broth and not on the solid media. Despite oral clindamycin, the abscess did not resolve over the next 2 weeks. Additional bacterial cultures of the abscess fluid were negative. Subsequent evaluation by local paediatric infectious disease specialists concluded that the MRSA probably resulted from skin contamination and diagnosed this episode as recurrent sterile abscess at the DTaP vaccination site.

Case 2

A healthy 2-month-old boy received immunisations with DTaP, Hib–HBV and IPV (table 1). At 4 months, he again received these three vaccines in the right thigh (table 1). An immediate swelling developed at the injection sites in the right thigh, and this progressed to a painless, indurated mass without erythema. Over the next week, the lesion developed a “purplish” discolouration. Two months later, because of a persistent 3×3 cm indurated right thigh mass, he received DTaP vaccine in the left thigh (table 1) and injection site swelling appeared within hours, evolving into a furuncle.

Approximately 3 weeks later, a bilateral thigh ultrasound revealed two echogenic subcutaneous masses measuring 3×1×3 cm (right) and 3×1×2 cm (left). Neither fever nor tenderness was noted. Both lesions spontaneously drained purulent material 8 days later (1 month after the 6-month immunisations on the right and 3 months after the 4-month immunisations on the left) but the fluid was not cultured. Both thighs healed with minimal scarring.

At 13 months of age, the patient received varicella vaccine without incident, and at 18 months, he received Hib–HBV (left thigh) and PCV7 and MMR (right thigh) (table 1). Swelling was noted immediately at the injection sites of both thighs. Over the next four days, an erythematous, tender 3×3 cm mass developed on the left at the site of the Hib–HBV injection. Brownish serosanguinous material spontaneously drained over the next week; this was not cultured. The lesion resolved without scarring. He subsequently received MMR at 26 months and DTaP at 28 months without incident.

INVESTIGATIONS

A search of the Vaccine Adverse Event Reporting System (VAERS) for abscess after vaccination from 2003 to 2007 yielded 116 reports, two of which described recurrent abscesses following vaccination. In the first report, the abscesses were sterile on both occasions, while in the second report, the initial abscess was sterile but the subsequent abscess grew mixed bacteria.

OUTCOME AND FOLLOW-UP

After the last abscess in the patient in case 1, the baby’s parents decided not to continue with the remainder of her recommended vaccine.

DISCUSSION

The patients in this report developed bilateral, recurrent sterile abscesses following receipt of different vaccines in different sites, resulting in delayed or incomplete immunisation for these children. Hypersensitivity to a vaccine component is one potential explanation for vaccine-associated sterile abscesses, as has been postulated for DTwP.4 However, in our two cases, no single antigen was associated with each abscess; nevertheless, we cannot rule out the possibility that hypersensitivity to multiple antigens may have played a role.

Most vaccines contain aluminium adjuvant to enhance the immune responses (table 2). Both patients described here developed abscesses after receiving vaccines containing aluminium adjuvant. No abscesses developed following vaccines containing 0.17 mg or less of aluminium adjuvant or after MMR or varicella vaccines, neither containing aluminium adjuvant (table 1). A recent similar case report described recurrent sterile abscesses after aluminium adjuvant-containing vaccines.5 Whether the individuals in the current report have a particular sensitivity, or whether other vaccine components may also be implicated in the development of recurrent abscesses is not known.

Table 2
Aluminium adjuvant content in vaccines currently licensed in the USA

One complicating factor in case 1 was the diagnosis of TMAU. No reports describing a relationship of TMAU with recurrent abscesses have been published and neither the patient’s history nor her immune studies suggests an immunodeficiency. Together with her appropriate vaccine immune responses, it is unlikely that the recurrent abscesses resulted from TMAU.

In summary, this report describes two patients who developed recurrent abscesses following immunisation with vaccines containing aluminium adjuvants, beginning at 4 months of age. No long-lasting effects were observed and the lesions healed without sequelae. Although the vast majority of children do not develop abscesses after immunisation, for patients with such symptoms, we recommend that, in addition to obtaining cultures, the clinician should choose vaccines containing the minimum amount of aluminium adjuvant available for further immuunisations (see table 2).

LEARNING POINTS

  • No long-lasting effects of recurrent sterile abscesses after immunisations were observed and the lesions healed without sequelae.
  • The vast majority of children do not develop abscesses after immunisation.
  • For patients who do develop recurrent abscesses following vaccination, in addition to obtaining cultures, further immunisations should be completed choosing vaccines containing the minimum amount of aluminium adjuvant available (see table 2).

Acknowledgments

We are indebted to Melvin Berger, MD, PhD, and Stephen Dreskin, MD, for their clinical guidance and their critical review of the manuscript. We are also grateful to the CISA Hypersensitivity Working Group for insightful discussions regarding these cases, to Barbara Pahud, MD, and Candice Smith, MD, for case 1 clinical follow-up and to Roger Baxter, MD, for his careful manuscript review. We would also like to acknowledge the CDC VAERS team for allowing CISA access to VAERS data. The findings and conclusions in this presentation are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention. This work was support by CISA contract number 200-2002-00732 with America’s Health Insurance Plans, funded by the Centers for Disease Control and Prevention.

Footnotes

Competing interests: NP Klein reports receiving research support from CDC, GlaxoSmithKline, Sanofi Pasteur, Novartis, Merck & Co and MedImmune. KM Edwards reports receiving research support from NIH, CDC, Wyeth, Sanofi Pasteur and Novartis. CL Dekker receives research support from NIH and CDC.

Patient consent: Patient/guardian consent was obtained for publication

REFERENCES

1. Stetler HC, Garbe PL, Dwyer DM, et al. Outbreaks of group A streptococcal abscesses following diphtheria-tetanus toxoid-pertussis vaccination. Pediatrics 1985; 75: 299–303 [PubMed]
2. Simon PA, Chen RT, Elliott JA, et al. Outbreak of pyogenic abscesses after diphtheria and tetanus toxoids and pertussis vaccination. Pediatr Infect Dis J 1993; 12: 368–71 [PubMed]
3. Bernier RH, Frank JA, Jr, Nolan TF., Jr Abscesses complicating DTP vaccination. Am J Dis Child 1981; 135: 826–8 [PubMed]
4. Church JA, Richards W. Recurrent abscess formation following DTP immunizations: association with hypersensitivity to tetanus toxoid. Pediatrics 1985; 75: 899–900 [PubMed]
5. Lehman HK, Faden HS, Fang YV, et al. A case of recurrent sterile abscesses following vaccination: delayed hypersensitivity to aluminum. J Pediatr 2008; 152: 133–5 [PubMed]

Articles from BMJ Case Reports are provided here courtesy of BMJ Publishing Group