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Chronic Spontaneous Urticaria (CSU) Following COVID-19 Vaccine: Preliminary Observations and Self-Tracking Data

Chronic Spontaneous Urticaria (CSU) Following COVID-19 Vaccine:
Preliminary Observations and Self-Tracking Data
Isaac Gerg,
Information Processing & Algorithms Laboratory (iPAL)
Dept. of Electrical Engineering & Computer Science (EECS)
Pennsylvania State University (PSU)
April 2022
1Preliminary Observations
VAERS Database
Shift from Urticaria to CSU?
2Next Steps
Preliminary ObservationsIy 0/16Iy
I developed urticaria (CSU) after getting COVID-19 vaccine booster (2 doses + booster).
Others are developing this condition under similar circumstances.
Anecdote: My dermatologist reported seeing a lot of urticaria in January 2022.
Online Facebook group “Chronic Spontaneous Urticaria After COVID-19 Vaccine Support Group, ” 6k members.
Literature reports this phenomenon: [1], [2], [3], [4], [5], [6], [7], [8].
[1].A. R. Wolfson et al. “Urticaria 12 Days After COVID-19 mRNA Booster Vaccination”. In: JAMA (Apr. 2022). issn: 0098-7484. doi:10.1001/jama.2022.5247. eprint:\_wolfson\_2022\_cg\_220004\_1649878889.00732.pdf.
[2].Chronic urticaria for 4 months after the first dose of Pfizer mRNA COVID-19 vaccine. Expert/Answers/2021/chronicurticaria.
Accessed: 2022-03-01.
[3].M. Smee et al. “COVID-19 Vaccine Induced Flares of Chronic Spontaneous Urticaria: A Case Series”. In: Journal of Allergy and Clinical Immunology 149.2 (2022), AB180.
[4].J. Thomas et al. “Chronic Spontaneous Urticaria After COVID-19 Vaccine”. In: Cureus 13.9 (2021).
[5].C. Alflen et al. “Two cases of well controlled chronic spontaneous urticaria triggered by the moderna COVID-19 vaccine”. In: Allergy & Rhinology 12 (2021), p. 21526567211026271.
[6].C. A. e. a. Thomas J Thomas G. Chronic Spontaneous Urticaria After COVID-19 Vaccine. spontaneous-urticaria- after-covid- 19-vaccine. Accessed: 2022-04-14.
[7].M. S. Johnston et al. “Delayed localized hypersensitivity reactions to the Moderna COVID-19 vaccine: a case series”. In: JAMA dermatology 157.6 (2021), pp. 716–720.
[8].S. G. Brooks et al. “Chronic Spontaneous Urticaria Triggered by the AstraZeneca/Oxford COVID-19 Vaccine with Achieved Remission: A Case Rep ort”. In: Allergy & Rhinology 13 (2022),
p. 21526567211068458.
Preliminary ObservationsIy 1/16Iy
Is Urticaria from COVID-19 Vaccine Reported in the VAERS Database?
If urticaria patients don’t show a “signal” in the reporting system, we can’t get our problem addressed.
YES, we see urticaria post-COVID19-vaccine in VAERS database.
Overview of Vaccine Adverse Event Reporting System (VAERS)
Maintained by US Department Health and Human Services (HHS)
Established in 1990
Co-managed by Centers for Disease Control and Prevention (CDC) and the U.S. Food and Drug Administration
Anyone can report. However, “Healthcare professionals are required to report certain adverse events and vaccine
manufacturers are required to report all adverse events” -
We considered VAERS records from 2021-2022
Start with 873,253 records.
Filter for COVID19 vaccine: 810,687 (93%)
Filter by symptom type “urticaria”, “wheals”, “hives”: 25,486 (3%)
VAERS DatabaseIy 2/16Iy
Onset of Symptoms by Vaccination Date
Figure 1: (Left) 2D Histogram of pertinent cases by date of vaccine and number of days until symptom onset. We
categorize this data into three cohorts: early (2021-01 thru 2021-05), late (2021-11 thru 2022-01), and overall (everyone).
(Right) Histogram of early (blue) and late (orange) cohorts.
The late cohort has a mode at 10-11 days where as the early cohort has one at 7-8 days.
Early and late cohorts have different symptom profile which could indicate booster-related effect.
In the late cohort, we see urticaria-like symptoms start 10 days post vaccine (similar to what is reported in
online FB group as I will show).
VAERS DatabaseIy 3/16Iy
VAERS Reports by Vaccine Manufacturer
(a) Overall (b) Early (c) Late
Figure 2: Vaccine manufacturer distribution by cohort.
Why Moderna vaccine increase in late cohort? Trying to find overall numbers of each vaccine administered
as prior.
VAERS DatabaseIy 4/16Iy
Onset of Symptoms by Vaccination Date - Non-COVID19 Vaccines
Figure 3: (Left) Scatterplot of pertinent cases by date of vaccine and number of days until symptom onset. We use the
same three cohorts previously defined: early (2021-01 thru 2021-05), late (2021-11 thru 2022-01), and overall (everyone).
(Right) Histogram of early (blue) and late (orange) cohorts. Difficult to tell if any correlation with COVID-19 vaccine.
Further statistical testing warranted but sample size is very small.
We see a similar pattern in the late cohort as the COVID-19 vaccination results.
Too few data points to check for significance. Could be reporting error (truly COVID-19 vaccine
administered but incorrect vaccine selected when reporting)? Time of year effect?
VAERS DatabaseIy 5/16Iy
Shift from Acute Urticaria to Chronic Spontaneous Urticaria?
Majority of literature reports focus on immediate onset and quick resolution of symptoms, but this becomes
a chronic problem for some.
Are these the 10 day post-vaccine urticaria patients we saw in VAERS which now have progressed to CSU?
Facebook group “Chronic Spontaneous Urticaria After COVID-19 Vaccine Support Group”
Started around December 15, 2021
As of April 2022 6k+ members
Informal surveys of members show median onset of symptoms 11 days after second shot or booster,
predominantly Moderna.
As of March 2022, GP and Allergists treating primarily with 2nd generation anti-histamine but with double and
quadruple doses, augmenting with H2antagonists.
Performed several “polls” in the Facebook group to collect data on cohort in late April 2022.
Following slides show results.
Shift from Urticaria to CSU?Iy 6/16Iy
FB Group - Members
Shift from Urticaria to CSU?Iy 7/16Iy
FB Group - Country of Origin
Likely biased since USA likely uses FB more than other countries and group language is English (there is a
German language forum also!).
Shift from Urticaria to CSU?Iy 8/16Iy
FB Group - Gender & Age
Shift from Urticaria to CSU?Iy 9/16Iy
FB Group - Vaccine Manufacturer & Symptom Onset after Vaccine
Similar to VAERS
Trying to located overall numbers of each vaccine administered.
Shift from Urticaria to CSU?Iy 10/16Iy
FB Group - Patient Blood Type
p = 0.02 of being USA blood type distribution (unknown how many participants are from USA due to FB
poll limitations)
Shift from Urticaria to CSU?Iy 11/16Iy
FB Group - Pharmaceutical Treatments
Most patients use multiple pharmaceutical treatments.
Difficult to obtain Ndue to FB poll limitations.
Shift from Urticaria to CSU?Iy 12/16Iy
FB Group - Symptom Change from Exercise
Most report that exercise results in no change of symptoms.
Shift from Urticaria to CSU?Iy 13/16Iy
My Self-Tracking Results
Majority of bloodwork normal, C-reactive protein (CRP) [9], [10].
SARS Cov2 Ab above reporting threshold. Wife is 100.0; same vaccination schedule as myself. Several FB
members noted outside of detection limits (i.e. high levels) also. Suggestive of a diagnostic test?
Elevated IgE (cutoff 87 kU/L), IL-10 (cutoff 2.8 pg/mL)
[9].H. M. Akca et al. “Correlation of urticaria activity score in chronic spontaneous urticaria with serum C-reactive protein level and neutrophil/lymphocyte ratio”. In: Dermatologic Therapy 33.6
(2020), e14532.
[10].I. Puxeddu et al. “Biomarkers in chronic spontaneous urticaria: current targets and clinical implications”. In: Journal of asthma and allergy 12 (2019), p. 285.
Self-TrackingIy 14/16Iy
1Preliminary Observations
VAERS Database
Shift from Urticaria to CSU?
2Next Steps
Next StepsIy 14/16Iy
Next Steps...
Looking for Collaborators
Consider donating to Dr. Blumenthal’s Vaccine Allergy Research
Join the Citizen Scientists for the Understanding of CSU Following COVID19 Vaccination (CSU2FCV) as
a CSU sufferer or control.
Next StepsIy 15/16Iy
Open Humans Community: Dr. Bastian Greshake Tzovaras, Dr. Mad Price Ball, Richard Sprague
Members of Chronic Spontaneous Urticaria After COVID-19 Vaccine Support Group
( and Chronic Spontaneous Urticaria After
COVID-19 Vaccine Science Group (
Stryx Biotech - Dr. Rick Roy
AcknowledgementsIy 16/16Iy
BackupIy 17/16Iy
BackupIy 18/16Iy
Additional Self-Tracking Resources
Serimmune - “Our goal is to understand differences in personal immune response to infection by the
COVID-19 virus, SARS-CoV-2.” (
COVID-19 Vaccine Allergy Case Registry (
FB CSU Support Group Surveys
Age -
Exercise -
Pharmaceutical Treatments -
Gender -
Manufacturer -
Blood Type -
Country -
BackupIy 19/16Iy
How can patients self-track their condition?
Serum tests
Good overview of serum tests [9]
Many US states don’t require MD order to get serum tests
Anti-FcϵRI or Anti-IgE autoantibodies and IgE =more severe
symptoms [10]
C-reactive protein level and neutrophil/lymphocyte ratio [11]
Total IgE [12]
CRP , D-dimer in H1non-responders [13]
Urticaria Activity Score (UAS7) [14] 1.pdf
urticaria-score- sheet.pdf From Puxeddu, et al. (2019)
[11].Puxeddu et al., “Biomarkers in chronic spontaneous urticaria: current targets and clinical implications”.
[12].R. Sabroe et al. “Chronic idiopathic urticaria: comparison of the clinical features of patients with and without anti-FcϵRI or anti-IgE autoantibodies”. In: Journal of the American Academy of
Dermatology 40.3 (1999), pp. 443–450.
[13].Akca et al., “Correlation of urticaria activity score in chronic spontaneous urticaria with serum C-reactive protein level and neutrophil/lymphocyte ratio”.
[14].S. Altrichter et al. “Total IgE as a marker for chronic spontaneous urticaria”. In: Allergy, Asthma & Immunology Research 13.2 (2021), p. 206.
[15].L. de Montjoye et al. “Correlations between disease activity, autoimmunity and biological parameters in patients with chronic spontaneous urticaria”. In: Eur Ann Allergy Clin Immunol 53.2
(2020), pp. 55–66.
[16].T. Hawro et al. “The Urticaria Activity Score—validity, reliability, and responsiveness”. In: The Journal of Allergy and Clinical Immunology: In Practice 6.4 (2018), pp. 1185–1190.
BackupIy 20/16Iy
Treatment Evidence
Vitamin D [17], [18]
[17].I. Oguz Topal et al. “Does replacement of vitamin D reduce the symptom scores and improve quality of life in patients with chronic urticaria?” In: Journal of Dermatological Treatment 27.2
(2016), pp. 163–166.
[18].R. Rasool et al. “Chronic urticaria merits serum vitamin D evaluation and supplementation; a randomized case control study”. In: World Allergy Organization Journal 8.1 (2015), pp. 1–10.
BackupIy 21/16Iy
Vaccine Approval Dates
Pfizer-BioNTech COVID-19
EUA, ages 12-15, Aug 23, 2021. ages 16+ Dec 11, 2020
Moderna COVID-19 Vaccine
EUA. Dec 18, 2020, ages 18+ . Approved Ages 18+ Jan 31, 2022
BackupIy 22/16Iy
Pending Results...
BackupIy 23/16Iy
ResearchGate has not been able to resolve any citations for this publication.
Full-text available
Objective Immunoglobulin E (IgE) and its receptor, FcɛRI, importantly contribute to the pathophysiology of chronic spontaneous urticaria (CSU). Recent findings point to a possible role of total IgE as a marker of CSU disease activity, endotypes, and responses to treatment. The evidence in support of total IgE included in the diagnostic workup of patients with CSU has not yet been reviewed. Methods Publications were searched via PubMed. The search terms used were “chronic urticaria” and “total IgE.” Studies were screened by titles and abstracts, and 141 were used in the review. Results CSU patients frequently had elevated total IgE serum levels (up to 50%), but normal or very low total IgE levels also occurred. High total IgE may represent high disease activity, longer disease duration, high chance of responding to omalizumab treatment, quick relapse after stopping omalizumab, and lower chance of responding to cyclosporine. Low IgE, in contrast, may suggest Type IIb autoimmune CSU, poor response to treatment with omalizumab and a better chance to benefits from cyclosporine treatment. Furthermore, IgE in different CSU cohorts may have different physicochemical properties that could explain differences in treatment responses to IgE-directed therapies. Conclusion The results of our review suggest that total IgE is a valuable marker for CSU, and we recommend its assessment in the routine diagnostic workup of CSU patients. Keywords:Urticaria; chronic spontaneous urticaria; immunoglobulin E; biomarkers; omalizumab; cyclosporine; therapeutics; diagnosis; receptor
Full-text available
Ilaria Puxeddu, Fiorella Petrelli, Francesca Angelotti, Cristina Croia, Paola Migliorini Clinical Immunology Unit, Department of Clinical and Experimental Medicine, Pisa University, Pisa, ItalyCorrespondence: Ilaria PuxedduClinical Immunology Unit, Department of Clinical and Experimental Medicine, Pisa University, Via Roma 67, Pisa 56126, ItalyTel +39-50-558628Fax +39-50-558630Email ilaria.puxeddu@unipi.itAbstract: Chronic urticaria (CU) is a mast cell-driven disease characterized by the development of wheals, angioedema, or both for more than 6 weeks. The two major sub-types are chronic spontaneous urticaria (CSU) and inducible urticaria. In the last decade different pathophysiological mechanisms, potentially responsible for the development of the disease, have been described. It is likely that the activation of mast cells and basophils in CSU can be the results of immune system dysregulation, activation of the inflammatory cascade, and of the extrinsic coagulation pathway. Some of the mediators involved in the pathophysiological mechanisms of CSU have recently been identified as potential biomarkers useful for the diagnosis, follow-up, and management of the disease, even if they are not yet available in clinical practice. Thus, in this review we discuss new insights in the mediators involved in the pathogenesis of CSU, highlighting their potential role as biomarkers in the activity and progression of the disease and response to therapies.Keywords: chronic urticaria, inflammation, biomarkers, angiogenesis
Background.Biomarkers of disease activity/severity and criteria of autoimmune chronic spontaneous urticaria (CSU) are still a matter of debate. Objective. To investigate possible correlations between clinical and biological markers and their associations with: (i) disease activity; (ii) resistance to H1-antihistamines; (iii) autoimmunity; and (iiii) autologous serum skin test (ASST) in patients with CSU. To also analyze biological parameter modifications in patients with CSU treated with omalizumab. Materials and methods. Disease activity, H1-antihistamines response and presence of concomitant autoimmune disease were prospectively recorded in 95 patients with CSU. For 60 of them, ASST was performed. Broad biological analysis were performed. Results. C-reactive protein (CRP) serum levels were higher in H1-antihistamines unresponders (p minor 0.0001) and in more active diseases (p=0.033). D-dimer plasma levels were higher in H1-antihistamines unresponders (p=0.008) and in patients with autoimmune status (concomitant autoimmune disease and/or with autoantibodies) (p=0.016). Total immunoglobuline E (IgE) serum level was lower in patients with positive ASST. Blood basophil counts were lower in patients with CSU and especially in H1-antihistamines unresponders (p=0.023), in patients with more active disease (p=0.023), with positive ASST (p=0.001), and with autoimmune status (p=0.057). Conversely, under omalizumab, a decrease of CRP (p=0.0038) and D-dimer serum/plasma levels (p=0.0002) and an increase of blood basophil counts (p=0.0023) and total IgE serum levels (p=0.0007) were observed. Conclusions. This study brings additional evidences of interest to investigate IgE, D-dimer serum/plasma levels and basophil blood counts in patients with CSU as they could be correlated to disease activity, response to treatment and/or autoimmunity.
Background: Chronic spontaneous urticaria is characterized by fluctuating symptoms. Its activity is assessed with the urticaria activity score (UAS). Two versions of the urticaria activity score used for 7 consecutive days (UAS7) are available: (1) The guideline-recommended UAS7, with once-daily documentation, and (2) the UAS7TD, with twice-daily documentation. Objective: To better characterize both UAS7 versions with regard to their validity, reliability, sensitivity to change, minimal important difference (MID), and smallest detectable change (SDC). Methods: One hundred thirty adult patients with chronic spontaneous urticaria completed both UAS7 versions, the Patients Global Assessment (PatGA) of disease activity, the Urticaria Control Test (UCT), the Chronic Urticaria Quality of Life Questionnaire, and the Dermatology Life Quality Index before and after the initiation of omalizumab therapy. Physicians completed a Physician Global Assessment of disease activity. Results: The UAS7 and the UAS7TD showed high correlation with the activity anchor PatGA (r = 0.568, P < .001 and r = 0.605, P < .001) and the UCT (r = -0.580, P < .001 and r = -0.585, P < .001). The wheal and pruritus scores of the UAS7 and the UAS7TD exhibited respectable internal consistency and, in each UAS7 version, correlated well with each other (Cronbach α = 0.78, r = 0.640, P < .001, and Cronbach α = 0.77, r = 0.626, P < .001). Changes in the UAS7 and UAS7TD correlated well with PatGA changes (r = 639, P < .001, and r = .763, P < .001) and with UCT changes (r = -0.642, P < .001, and r = -0.703, P < .001). The MID was 11 for the UAS7 (SDC = 12) and 12 for the UAS7TD (SDC = 11). Conclusions: The UAS7 and UAS7TD show good and comparable clinimetric properties, including good sensitivity to change, and similar MIDs.
Previous studies defining the clinical features of patients with chronic idiopathic urticaria (CIU) were performed before the identification of functional autoantibodies against FcepsilonRI and/or IgE, now known to be present in approximately 30% of patients with CIU. Our purpose was to determine whether there are differences between patients with and those without autoantibodies in the clinical features or severity of CIU. The clinical features of 107 patients with CIU were evaluated prospectively. Patients were identified as having functional autoantibodies on the basis of the serum-evoked histamine release in vitro from the basophils of 2 healthy donors. Patients with autoantibodies (31%) had more wheals (P = .005), a wider distribution of wheals (P = .009), higher itch scores for the most severe episodes of itching (P = .002), more systemic symptoms (P = .03), and lower serum IgE levels (P < .0005) than patients without autoantibodies. The presence of autoantibodies indicates a subset of patients with more severe CIU.