Logo American Journal of Case Reports

Call: 1.631.629.4328
Mon-Fri 10 am - 2 pm EST

Contact Us

Logo American Journal of Case Reports Logo American Journal of Case Reports Logo American Journal of Case Reports

20 August 2022: Articles  Australia

Unusual Case of Painful Glossitis and Xerostomia Following Vaccination with Pfizer-BioNTech SARS-CoV-2 (BNT162b2)

Unusual clinical course, Challenging differential diagnosis, Unexpected drug reaction

Elina Tan1DEF, Sam Salman123ABDEF*

DOI: 10.12659/AJCR.937212

Am J Case Rep 2022; 23:e937212

0 Comments

Abstract

BACKGROUND: Adverse events following immunization (AEFIs) remain under recognized, particularly when the symptoms experienced are uncommon and mimic natural disease. In the context of the worldwide effort to provide protection against SARS-CoV-2 using multiple doses of vaccination and with the availability of multiple vaccines, the early recognition and prompt treatment of AEFIs has increased importance, as does the ability to carefully select an alternative after an AEFI occurs.

CASE REPORT: A 60-year-old woman presented for clinical immunology review with a 9-month history of glossitis and xerostomia. Onset of symptoms occurred following her first vaccination with a COVID-19 vaccine (BNT162b2). After partial interval improvement, her symptoms progressively worsened after a second vaccination and third booster vaccination with BNT162b2. While undergoing reviews from multiple specialists for possible underlying connective tissue disease, and with other causes of her symptoms being excluded, the patient’s symptoms progressed, with worsening tongue swelling with new fissuring and xerostomia. The patient experienced an unintentional weight loss of 8 kg due to oral discomfort. It was only after this time that an AEFI was considered the cause of her presentation, after all other diagnostic considerations were considered unlikely. Targeted, symptomatic, localized treatment with topical oral corticosteroids was initiated, followed by a gradual tapering regimen, with excellent response.

CONCLUSIONS: This case highlights the need to consider AEFIs early in the differential diagnosis of unusual presentations and the importance of considering a trial of targeted symptomatic treatment for patients, even if diagnostic uncertainty remains.

Keywords: COVID-19 vaccine, BNT162 Vaccine, Glossitis, mRNA Vaccine

Background

With any vaccine there are multiple reports of associated adverse events following immunization (AEFI), which can be defined as an unfavourable or unintended sign, abnormal laboratory finding, symptom, or disease following immunization [1]. An AEFI can be coincidental, meaning that the event is caused by something other than the vaccine [1]. In other cases, a causal association can be identified when no other factors are implicated in the process and the vaccine is biologically plausibly linked to the adverse event [1]. This report describes the case of a patient with an unusual AEFI manifesting with glossitis and xerostomia.

In December 2019, an outbreak SARS-CoV-2 in Wuhan, China, rapidly led to a global pandemic [2], prompting the development of multiple vaccines [3]. The Pfizer-BioNTech COVID-19 vaccine (BNT162b2) is a modified ribonucleic acid vaccine encoding the SARS-CoV2 full-length spike protein delivered in a lipid nanoparticle, which has demonstrated significant vaccine efficacy [4]. BNT162b2 has now been incorporated into vaccination regimens worldwide. Common reported AEFIs of BNT162b2 include injection site pain, fatigue, headache, myalgias, and arthralgias [3], as well as pericarditis and myocarditis [5]. However, there are only a few reports of oral adverse effects following COVID-19 vaccination. Differentiating between causal and coincidental AEFIs is a challenge during population rollout of a new vaccine, such as in the current situation. Spontaneous occurrence of new illnesses and symptoms being coincidentally attributed to the vaccine are both likely. On the contrary, uncommon AEFIs can easily be under reported and under recognized initially, as highlighted in the present case.

We report a case of a patient who developed debilitating glossitis and xerostomia. The onset of these symptoms occurred after her first vaccination with BNT162b2 and progressively worsened after each dose, with partial interval improvement. This resulted in her seeking multiple specialist medical reviews for management of the symptoms and to explore the postulated diagnosis of Sjogren syndrome. An AEFI was considered as a differential diagnosis 9 months later, and targeted therapy was initiated for symptomatic management.

Case Report

A 60-year-old woman received her first BNT162b2 vaccination and 3 days later developed oral symptoms of glossitis with new fissuring, stomatitis, and xerostomia. There was partial resolution of the oral symptoms prior to her receiving her second BNT162b2 vaccination 3 weeks later. Over the next few months, symptoms improved gradually but not completely. After receiving her BNT162b2 booster 6 months after the second vaccination, there was significant worsening, particularly of her oral manifestations (Figure 1A, 1B), resulting in an overall 8-kg weight loss due to reduced oral intake, secondary to oral pain.

Her background history included visual impairment since childhood, hypercholesterolemia, and uterine fibroids. Regular medications were stable throughout this time and included rosuvatastin and oral vitamin B12, vitamin D, and folate supplementation. She reported an allergy to Bactrim (trimethoprim/ sulfamethoxazole). No new medications were commenced prior to the onset of symptoms.

Blood tests requested by the patient’s primary physician revealed a positive anti-nuclear antibody (ANA titre ≥1: 640; homogenous pattern) and mildly elevated erythrocyte sedimentation rate of 37 mm/h (reference range: 3–20 mm/h). The B12 level was within the reference range. An oral swab was negative for human papillomavirus high-risk genotypes. She was subsequently referred to outpatient Rheumatology services for suspected Sjogren syndrome.

Further laboratory findings included normal full blood count, renal function, and liver function tests, with no proteinuria on urinalysis. The C-reactive protein level was normal. Further autoimmune serology demonstrated negative rheumatoid factor and anti-cyclic citrullinated peptide, negative anti-dsDNA, and negative anti-extractable nuclear antigen panel (anti-Ro, La, RNP/Sm, Jo-1, Scl 70). The complement C3 level was normal, while the C4 level was mildly elevated (69 mg/dL; reference range: 10–50 mg/dL).

The new-onset persistent xerostomia prompted her primary physician to appropriately consider the diagnosis of Sjogren syndrome, which most commonly presents in middle-aged females, with 95% citing sicca symptoms (dry mouth and dry eyes) at diagnosis [6]. Oral features of sore mouth and dysphagia are reported [6], and can include glossitis, angular cheilitis, and recurrent ulcerations or fissuring in severe cases [7]. Arthralgias and myalgias are reported in more than half of patients [6]. However, on a subsequent rheumatologist review, clinical findings and serology were not entirely supportive of Sjogren syndrome, nor of any other connective tissue disease, such as lupus. As outlined above, the patient’s autoimmune serology was unremarkable. Up to 25% of patients with Sjogren syndrome have an elevated erythrocyte sedimentation rate at diagnosis, and 30% have cytopenia [6]. Anti-Ro/SSA antibodies are found in two-thirds of patients, often associated with anti-La/SSB antibodies [8]. Approximately 50% have a positive rheumatoid factor [8]. Conversely, ANA positivity is seen in the absence of autoimmune disease, with increasing age and female sex being risk factors across several populations [9,10].

Oral symptoms are not a common adverse event associated with COVID-19 vaccination, and therefore an AEFI was not considered initially. A subsequent review of the timeline of history and medications, including vaccinations, identified a clear relationship between the exacerbation of oral symptoms after each BNT162b2 vaccination, raising the possibility that this represented an AEFI with causality attributable to the vaccine. The other possibility was that this was a coincidental AEFI; for example, in which the patient may have developed a new illness spontaneously or had exacerbation of a pre-existing illness that was not previously recognized. The patient did not exhibit other symptoms that might be attributable to SARS-CoV2 infection at any time and was therefore not tested for infection. While atypical presentation of infection can be a plausible differential diagnosis for a single episode, the entirety of the patient’s history did not support this.

Prior to clinical immunology review, the patient had been reviewed by a local dental clinic for the oral symptoms after her second BNT162b2 vaccination, where she was prescribed an oral topical clonazepam preparation for burning mouth syndrome, without significant improvement. Her symptoms progressed; therefore, her primary physician prescribed oral prednisolone 30 mg per day for 2 weeks, which resulted in 60% improvement in symptoms; however, this was ceased after 5 days due to significant abdominal discomfort.

Following clinical immunology review, the differential diagnosis of an AEFI was considered most likely. Management focused on addressing the oral symptoms, which were causing the most discomfort and resulting weight loss. Given the localized symptoms and her inability to tolerate systemic corticosteroids, she was commenced on a topical oral preparation of 5 mg prednisolone dissolved in 10 to 20 mL water 3 times per day, as described by the Charles Clifford Dental Hospital (National Health Service, United Kingdom) [11].

After 2 weeks, the prednisolone frequency was reduced to twice daily for 2 weeks, then once daily for 2 weeks before ceasing. The tongue fissures and stomatitis gradually resolved completely, with associated improvement in xerostomia (Figure 2). She was able to resume a normal diet, and at the last follow-up, had not had recurrence of disease.

Discussion

A variety of oral symptoms have been described in patients after COVID-19 vaccination. Case reports of oral lesions following vaccination is not a novel phenomenon and has been described following influenza [12] and hepatitis B vaccination [13], and xerostomia has been described after vaccination against human papillomavirus [14]. However, only a few cases have been reported specific to COVID-19 vaccines. Azzi et al (2021) reported on a 31-year-old woman who developed oral mucositis 3 days after her first ChAdOx1 COVID-19 vaccine, which was treated with topical corticosteroids [15]. Manfredi et al (2021) reported a case of a 34-year-old woman who presented with diffuse oral ulcerations, swelling of the lips and gingiva, and mild angular cheilitis 2 days after BNT162b2 vaccination. Following a treatment with topical antibiotics, the mucosa was completely healed by day 15 [16]. Thongprasom et al (2021) described the case of a 38-year-old woman who was diagnosed with oral pemphigus based on examination and direct immunofluorescence on mucosal biopsy, with onset of mucosal desquamation and ulceration 1 week following ChAdOx1 vaccination [17]. One week of topical steroid therapy resulted in improvement. Sayare et al (2021) reported petechial lesions developing at the injection site and palatal area in a 21-year-old man within days of the first dose of the ChAdOx1 vaccine [18]. He was found to have mild thrombocytopenia (140 000 platelets/uL blood), and the lesions self-resolved after 5 days. These cases are all reported only in the oral health literature, likely contributing to the limited widespread recognition of these AEFIs.

Riad et al (2021) reported a broad overview of oral adverse events after BNT162b2 vaccination among 877 health care workers in the Czech Republic [19], of which, 114 (13%) reported at least 1 oral adverse reaction, including blisters (36%), ulcers (14%), bleeding gingiva (11.4%), angular cheilitis (4.4%), taste disturbance (3.5%), swollen lips (3.5%), and xerostomia (2.6%). The majority (28.6%) reported onset within 1 week of vaccination. Of those with oral involvement, the tongue was involved in 13%. Despite various case reports, no definitive association between oral lesions and COVID-19 vaccines has been formally established; however, with further awareness and reporting, this may change in the future. It remains unclear if oral AEFIs are related to the mRNA vector or vaccine excipients, such as polysorbate.

Based on World Health Organization guidelines, with the available evidence in this case, we could conclude that the most likely causality classification of this AEFI was type B1 (indeterminate), whereby a temporal relationship was consistent, but there was insufficient definitive evidence for the vaccine causing the event [1]. There was no strong evidence for another cause, and there was a strong temporal relationship between onset and exacerbation of symptoms following each vaccination. There is, however, no definitively established causal relationship in the literature between any of the COVID-19 vaccines and oral adverse events.

Conclusions

This case demonstrates that oral symptoms can be associated with BNT162b2 vaccination, which is likely under recognized by practitioners outside the field of oral health. It is evident in the limited case reports encompassing oral AEFIs after COVID-19 vaccination that topical oral corticosteroids appear to be a useful treatment approach. It is important to consider medication and vaccination-induced adverse events in the differential diagnosis of any presentation, as these may rarely be implicated.

Additionally, this case highlights that in some patients a clear unifying diagnosis may not always be possible. When the diagnosis is not clear, a symptom-based approach can still be applied based on the clinical features to provide the most benefit to the patient, particularly when symptoms significantly affect quality of life. In this case, for instance, addressing our patient’s main concern of glossitis with a localized therapy aiming to reduce inflammation resulted in resolution of symptoms, and most importantly reversed her unintended weight loss and restored her quality of life.

References:

1.. : Causality assessment of an adverse event following immunization (AEFI): user manual for the revised WHO classification, 2018

2.. Zhou F, Yu T, Du R, Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study: Lancet, 2020; 395(10229); 1054-62

3.. Poland GA, Ovsyannikova IG, Kennedy RB, SARS-CoV-2 immunity: Review and applications to phase 3 vaccine candidates: Lancet, 2020; 396(10262); 1595-606

4.. Polack FP, Thomas SJ, Kitchin N, Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine: N Engl J Med, 2020; 383(27); 2603-15

5.. Hause AM, Baggs J, Marquez P, COVID-19 vaccine safety in children aged 5–11 years – United States, November 3-December 19, 2021: MMWR Morb Mortal Wkly Rep, 2021; 70(5152); 1755-60

6.. Ramos-Casals M, Brito-Zerón P, Sisó-Almirall A, Bosch X, Primary Sjogren syndrome: BMJ, 2012; 344; e3821

7.. Serrano J, Lopez-Pintor RM, Gonzalez-Serrano J, Oral lesions in Sjogren’s syndrome: A systematic review: Med Oral Patol Oral Cir Bucal, 2018; 23(4); e391-400

8.. Mariette X, Criswell LA, Primary Sjögren’s syndrome: New Engl J Med, 2018; 378(10); 931-39

9.. Satoh M, Chan EK, Ho LA, Prevalence and sociodemographic correlates of antinuclear antibodies in the United States: Arthritis Rheum, 2012; 64(7); 2319-27

10.. Guo YP, Wang CG, Liu X, The prevalence of antinuclear antibodies in the general population of china: A cross-sectional study: Curr Ther Res Clin Exp, 2014; 76; 116-19

11.. , Dental Services STH, Pharmacy and Medicines Management: Prednisolone soluble 5 mg tablets as mouth wash, 2021 (May 2021)

12.. Sawires L, Effects of the influenza vaccine on the oral cavity [Honors Undergraduate Thesis], 2018, University of Central Florida

13.. Rebora A, Rongioletti F, Drago F, Parodi A, Lichen planus as a side effect of HBV vaccination: Dermatology, 1999; 198(1); 1-2

14.. Palmieri B, Poddighe D, Vadalà M, Severe somatoform and dysautonomic syndromes after HPV vaccination: Case series and review of literature: Immunol Res, 2017; 65(1); 106-16

15.. Azzi L, Toia M, Stevanello N, Maggi F, Forlani G, An episode of oral mucositis after the first administration of the ChAdOx1 COVID-19 vaccine: Oral Dis, 2021 [Online ahead of print]

16.. Manfredi M, Ghidini G, Ridolo E, Pizzi S, Oral lesions postinjection of the first administration of Pfizer-BioNTech SARS-CoV-2 (BNT162b2) vaccine: Oral Dis, 2021 [Online ahead of print]

17.. Thongprasom K, Pengpis N, Phattarataratip E, Samaranayake L, Oral pemphigus after COVID-19 vaccination: Oral Dis, 2021 [Online ahead of print]

18.. Sayare B, Bhardwaj VK, Sharma D, Palatal petechiae: An uncommon oral adverse effect of COVID-19 vaccine: The Egyptian Journal of Otolaryngology, 2021; 37(1); 1-4

19.. Riad A, Pokorná A, Attia S, Prevalence of COVID-19 vaccine side effects among healthcare workers in the Czech Republic: J Clin Med, 2021; 10(7); 1428

SARS-CoV-2/COVID-19

22 September 2022 : Case report  USA

Rare Case of Persistently Depressed T Lymphocyte Subsets After SARS-CoV-2 Infection

Am J Case Rep In Press; DOI: 10.12659/AJCR.937760  

22 September 2022 : Case report  Poland

Central Retinal Vein Occlusion After Discontinuation of Rivaroxaban Therapy in a Young Patient with COVID-1...

Am J Case Rep In Press; DOI: 10.12659/AJCR.937739  

19 September 2022 : Case report  Spain

Inhaled Nitric Oxide in Acute Severe Pulmonary Hypertension and Severe Acute Respiratory Distress Syndrome ...

Am J Case Rep In Press; DOI: 10.12659/AJCR.937147  

14 September 2022 : Case report  Japan

Case Report: A 29-Year-Old Pregnant Woman at 24 Weeks of Gestation Presenting with Laryngotracheitis and CO...

Am J Case Rep In Press; DOI: 10.12659/AJCR.937834  

In Press

26 Sep 2022 : Case report  Saudi Arabia

An Infant Presenting with Interstitial Lung Disease Diagnosed Later as Hunter Syndrome: A Case Report

Am J Case Rep In Press; DOI: 10.12659/AJCR.937527  

26 Sep 2022 : Case report  Thailand

Acute Intermittent Porphyria: Complete Phenotype in a Patient with p.Arg173Trp Variant in Thailand

Am J Case Rep In Press; DOI: 10.12659/AJCR.937695  

26 Sep 2022 : Case report  USA

Injury to the Posterior Horn of the Lateral Meniscus from a Misplaced Tibial Tunnel for Anterior Cruciate L...

Am J Case Rep In Press; DOI: 10.12659/AJCR.937581  

26 Sep 2022 : Case report  USA

Recurrent Gastrointestinal Bleed Due to Small Bowel Vascular Malformation in a Patient with Turner Syndrome...

Am J Case Rep In Press; DOI: 10.12659/AJCR.937259  

Most Viewed Current Articles

13 Jul 2022 : Case report  USA

Whistling Scrotum: An Unusual Presentation of Pneumomediastinum in the Setting of an Open Scrotal Wound

DOI :10.12659/AJCR.936441

Am J Case Rep 2022; 23:e936441

23 Feb 2022 : Case report  USA

Penile Necrosis Associated with Local Intravenous Injection of Cocaine

DOI :10.12659/AJCR.935250

Am J Case Rep 2022; 23:e935250

06 Dec 2021 : Case report  Brazil

Lipedema Can Be Treated Non-Surgically: A Report of 5 Cases

DOI :10.12659/AJCR.934406

Am J Case Rep 2021; 22:e934406

17 Feb 2022 : Case report  Oman

Myocarditis, Pulmonary Hemorrhage, and Extensive Myositis with Rhabdomyolysis 12 Days After First Dose of P...

DOI :10.12659/AJCR.934399

Am J Case Rep 2022; 23:e934399

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

American Journal of Case Reports eISSN: 1941-5923
American Journal of Case Reports eISSN: 1941-5923