Petechial rash after mRNA COVID-19 vaccine
Question:
6/24/2021
34 year-old female with no significant past medical history who presented for the evaluation of petechiae rash from Pfizer COVID-19 vaccine. 24 hours after the first Pfizer COVID-19 vaccine, the patient developed petechiae on the left lower leg. Also had fever, tmax 102.0, and myalgias. Petechiae worsened over the next several days and she developed left lower leg swelling, paresthesia in left lower leg, and dizziness, and the patient went to ER. Bilateral doppler of lower extremity negative for clot. CBC showed normal white blood cell count, normal hemoglobin/hematocrit, normal platelet count. Negative d-Dimer. Normal basic metabolic panel, normal hepatic function panel. COVID-19 nasal PCR negative. Did not endorse cough, hives, lip swelling, tongue swelling, throat closing, shortness of breath, wheeze, vomiting or abdominal pain. Reporting mother has autoimmune disorder, but unknown what kind. Petechiae, fevers and myalgias lasted for one week. Reporting since the vaccine, has bilateral knee pain. No joint swelling. No rash. Patient is asking if it is okay to receive the second vaccine. IgG anti-spike COVID-19 assay was ordered and pending. Should there be any further workup for petechiae? Is it okay to receive the second Pfizer vaccine?
Answer:
There are reports of ‘blue toes” or “COVID toes” following mRNA vaccination (1), and these events are not associated with thrombocytopenia. To my knowledge the mechanism is not known. The manifestations appear to be vasospasm but are associated with petechiae. However, the location is the toes and not the legs, so I do not think the description you provided is consistent with this phenomenon.
The development of a petechial rash 24 hours following a mRNA immunization might suggest preexisting immunity to the SARS-CoV-2 virus. Petechia without thrombocytopenia would be consistent with serum sickness like response, although it is inexplicable to me why this would occur in the left leg more than the right. You did not mention complement studies as there may have been an associated consumption of complement. I do not think the PEG2000 and cholesterol and lipids had any role in the response due to the small amount in the vaccine and prolonged petechial response.
It is also possible the events described were not related to the vaccine or was another problem triggered by the vaccine. An unrelated viral illness would be one consideration. Vaccinations can be associated with flares of autoimmunity although this is controversial as well. Autoantibody testing was not mentioned but is a consideration in light of the duration of symptoms.
There are 233 reports in the Vaccine Adverse Event Reporting System (VAERS) of petechiae with the Pfizer vaccine, but all that I could review were associated with thrombocytopenia (The Vaccine Adverse Event Reporting System (VAERS) Results Form (cdc.gov). [2]
Causal role of adverse events associated with vaccines is challenging and depends upon number of reports, plausible mechanisms and timing of events. Petechiae, fever, myalgias developing within 24 hours of vaccination and persistent joint pain strongly suggest a relationship with vaccination, but a plausible mechanism is difficult for me to formulate. I would be concerned that repeat vaccination could result in an accelerated and more severe reaction. If the adverse events were linked to a specific viral immune response, I would not be confident that other COVID-19 vaccines would not result in a similar problem. However, if the patient did not have prior COVID-19 with pre-existent immunity, the timing is not consistent with an anti-viral immune response as longer time would have been required. Prelimianry data show mixing vaccine platforms results in a robust immune response (3,4).
The risk of SARS-CoV-2 infection is also a concern. A discussion with the patient would need to include these unknowns prior to a decision about subsequent vaccination versus depending on the efficacy of a single dose (5). It is important to note that a single dose of the mRNA vaccines may be insufficient to prevent against the delta variant of SARS-CoV-2.
In summary, I would obtain a CH50, C4, C3, ESR, CRP, urine analysis and ANA and continue to monitor the patient. I personally would not favor repeat vaccination with the Pfizer or other COVID19 vaccines, but I think there could be a discussion and repeat vaccination, with the Pfizer or an alternative vaccine.
1. Davido, Benjamin, et al. "‘Blue toes’ following vaccination with the BNT162b2 mRNA COVID-19 vaccine." Journal of Travel Medicine 28.4 (2021): taab024.
2. United States Department of Health and Human Services (DHHS), Public Health Service (PHS), Centers for Disease Control (CDC) / Food and Drug Administration (FDA), Vaccine Adverse Event Reporting System (VAERS) 1990 - 06/18/2021, CDC WONDER On-line Database. Accessed at http://wonder.cdc.gov/vaers.html on Jun 29, 2021 9:01:58 AM
3. Borobia AM, Carcas AJ et al. Reactogenicity and immunogenicity of BNT162b2 in subjects having received a first does of ChAdOx1s: Initial results of a randomized, adaptive phase 2 trial (CombiVacS). Lancet 2021; (https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3854768)
4. Shaw RH, Stuart A, Greenland M et al. Heterologous prime-boost COVID-19 vaccination: initial reactogenicity data. Lancet 2021;397:2043-6 (https://doi.org/10.1016/S0140-6736(21)01115-6).
5. Hunter, Paul R., and Julii Suzanne Brainard. "Estimating the effectiveness of the Pfizer COVID-19 BNT162b2 vaccine after a single dose. A reanalysis of a study of real-world vaccination outcomes from Israel." Medrxiv (2021).
I hope this information is of help to you and your practice.
All my best.
Dennis K. Ledford, MD, FAAAAI