Erythema at the bacillus Calmette-Guerin scar after influenza vaccination

Chavarri-Guerra, Yanin; Soto-Perez-de-Celis, Enrique

doi:10.1590/0037-8682-0390-2019

Over 80% of children worldwide have been administered the bacillus Calmette-Guerin (BCG) vaccine for tuberculosis, with various immunological phenomena observed in relation to BCG.

A nine-year-old Mexican boy presented with pain, swelling, and redness at the BCG scar (Figure 1 A) two days after an influenza vaccination (administered 3 cm from the BCG scar). The BCG scar was erythematous, indurated, and painful, while the influenza vaccination site remained unchanged. Vital signs were normal, with no signs of lymphadenopathy. The patient had a previous history of severe local reaction after BCG vaccination at 3 months of age (ulcer formation and nonsuppurative axillary lymphadenopathy). Additionally, the patient was tested positive for a tuberculin skin test at 3 years of age and received isoniazid/rifampin treatment. Erythema and induration at the BCG scar lasted 48 h, resolving without topical or systemic treatments (Figure 1B).

FIGURE 1:
Panel A shows erythema at the site of the bacillus Calmette-Guerin (BCG) immunization scar two days after influenza vaccination. Panel B shows the same scar four months after vaccination with complete resolution of symptoms.

BCG-vaccine interacts with epidermal macrophages, neutrophils, and dendritic cells, generating an intense immune response (reactive oxygen species, cytokines, and chemokines) and leading to cutaneous complications and scarring¹1. Rezai MS, Shahmohammadi S. Erythema at BCG Inoculation Site in Kawasaki Disease Patients. Mater Sociomed. 2014;26(4):256-60.. BCG scar inflammation has been described in patients with Kawasaki disease and other immune mediated events¹1. Rezai MS, Shahmohammadi S. Erythema at BCG Inoculation Site in Kawasaki Disease Patients. Mater Sociomed. 2014;26(4):256-60.^-²2. Yokota S, Tsubaki K, Kuriyama T, Shimizu H, Ibe M, Mitusda T, et al. Presence in Kawasaki disease of antibodies to mycobacterial heat-shock protein HSP65 and autoantibodies to epitopes of human HSP65 cognate antigen. Clin Immunol Immunopathol. 1993;67(2):163-70.. This is caused by cross-reactions between mycobacterial and human homologue heat shock proteins (HSP), specifically between mycobacterium HSP65 and human HSP63³3. Lambert ND, Ovsyannikova IG, Pankratz VS, Jacobson RM, Poland GA. Understanding the immune response to seasonal influenza vaccination in older adults: a systems biology approach. Expert Rev Vaccines. 2012;11(8):985-94.. Elevated interleukin-1β (IL-1 β) and tumor necrosis factor-α (TNF- α) have been identified at the BCG scar in patients with Kawasaki disease²2. Yokota S, Tsubaki K, Kuriyama T, Shimizu H, Ibe M, Mitusda T, et al. Presence in Kawasaki disease of antibodies to mycobacterial heat-shock protein HSP65 and autoantibodies to epitopes of human HSP65 cognate antigen. Clin Immunol Immunopathol. 1993;67(2):163-70.. In this case, a mechanism involving HSP liberation after influenza vaccination could have stimulated the immune response at the BCG scar³3. Lambert ND, Ovsyannikova IG, Pankratz VS, Jacobson RM, Poland GA. Understanding the immune response to seasonal influenza vaccination in older adults: a systems biology approach. Expert Rev Vaccines. 2012;11(8):985-94..

ACKNOWLEDGEMENTS

The authors thank Jose María Saldaña-Chávarri for his help creating Figure 1.

REFERENCES

¹
Rezai MS, Shahmohammadi S. Erythema at BCG Inoculation Site in Kawasaki Disease Patients. Mater Sociomed. 2014;26(4):256-60.
²
Yokota S, Tsubaki K, Kuriyama T, Shimizu H, Ibe M, Mitusda T, et al. Presence in Kawasaki disease of antibodies to mycobacterial heat-shock protein HSP65 and autoantibodies to epitopes of human HSP65 cognate antigen. Clin Immunol Immunopathol. 1993;67(2):163-70.
³
Lambert ND, Ovsyannikova IG, Pankratz VS, Jacobson RM, Poland GA. Understanding the immune response to seasonal influenza vaccination in older adults: a systems biology approach. Expert Rev Vaccines. 2012;11(8):985-94.