Age: 11.0
Sex: M
Vaccine: UNK
Symptoms: Injection site reaction, Injection site scar, Injection site ulcer, Injection site urticaria, Product administered to patient of inappropriate age
Clinical narrative: higher dose of SARS-CoV-2 viral spike glycoprotein mRNA than recommended for his age (30ug vs. 10ug); an 11-year-old boy received Pfizer-BioNTech's COVID-19 vaccine (12-year-old dose of 30 ug/0.3 mL); Vaccine interaction; large erythematous wheal on his left arm near the COVID-19 and HPV vaccine injection sites associated with pruritus, burning and pain; rash progressed to include vesicles and bullae over several hours and eventually ulcerated; rash progressed to include vesicles and bullae over several hours and eventually ulcerated; a punch biopsy peripheral to the ulcer revealed non-specific reactive epidermal changes, dermal fibrosis and fat necrosis; a punch biopsy peripheral to the ulcer revealed non-specific reactive epidermal changes, dermal fibrosis and fat necrosis; ulceration healed with central scarring and surrounding postinflammatory pigment change; ulceration healed with central scarring and surrounding postinflammatory pigment change; This is a literature report for the following literature source(s).  An 11-year-old male patient received BNT162b2 (BNT162B2), as dose number unknown, 0.3 ml single (Batch/Lot number: unknown) at the age of 11 years, in left arm for covid-19 immunisation; hpv vaccine (HPV VACCINE), as dose number unknown, single), in left arm for human papilloma virus immunisation. The patient's relevant medical history was not reported. Concomitant medication(s) included: MENINGOCOCCAL VACCINE taken for meningococcal immunisation as dose number unknown, single; TDAP taken for diphtheria immunisation, pertussis immunisation as dose number unknown, single. The following information was reported: OVERDOSE (medically significant), outcome "unknown", described as "higher dose of SARS-CoV-2 viral spike glycoprotein mRNA than recommended for his age (30ug vs. 10ug)"; PRODUCT ADMINISTERED TO PATIENT OF INAPPROPRIATE AGE (medically significant), outcome "unknown", described as "an 11-year-old boy received Pfizer-BioNTech's COVID-19 vaccine (12-year-old dose of 30 ug/0.3 mL)"; VACCINE INTERACTION (medically significant), outcome "unknown"; VACCINATION SITE URTICARIA (medically significant), outcome "unknown", described as "large erythematous wheal on his left arm near the COVID-19 and HPV vaccine injection sites associated with pruritus, burning and pain"; DERMATITIS BULLOUS (medically significant), outcome "unknown", VACCINATION SITE ULCER (medically significant), outcome "recovered" and all described as "rash progressed to include vesicles and bullae over several hours and eventually ulcerated"; VACCINATION SITE NECROSIS (medically significant), VACCINATION SITE FIBROSIS (medically significant), outcome "unknown" and all described as "a punch biopsy peripheral to the ulcer revealed non-specific reactive epidermal changes, dermal fibrosis and fat necrosis"; VACCINATION SITE SCAR (medically significant), VACCINATION SITE DISCOLOURATION (medically significant), outcome "unknown" and all described as "ulceration healed with central scarring and surrounding postinflammatory pigment change". The patient underwent the following laboratory tests and procedures: Biopsy skin: revealed non-specific reactive, notes: Epidermal changes, dermal fibrosis and fat necrosis; Blood immunoglobulin E: normal; C-reactive protein: normal; Full blood count: normal; Image: Oedematous urticarial plaque, notes: 1 day after vaccination; Oedematous urticarial plaque, notes: with overlying vesicles and bullae 2days after vaccination; Large ulceration with crusting and surrounding, notes: post inflammatory pigmentary changes 1 week after vaccination; Large scar with areas of hypopigmentation, notes: and hyperpigmentation 10months after vaccination; Red blood cell sedimentation rate (0-15): 26, notes: Unit: mm/h, mildly elevated; Tryptase: normal.  Clinical course: Vaccines offer critical defense against severe SARS-CoV-2 infection. Here, the authors described a young boy who had a robust reaction resulting in significant cutaneous ulceration after receiving the Pfizer-BioNTech COVID-19 vaccine concomitantly with human papilloma virus (HPV), meningococcal, and tetanus, diphtheria and pertussis (Tdap) vaccines. He had no prior vaccine reactions, known allergies, or SARS-CoV-2 infection. During a paediatric wellness visit, an 11-year-old boy received Pfizer-BioNTech's COVID-19 vaccine (12-year-old dose of 30 ug/0.3 mL) and HPV vaccine in his left arm and meningococcal and Tdap vaccines in his right arm. Within minutes-to-hours after receiving the vaccines, he developed a large erythematous wheal on his left arm near the COVID-19 and HPV vaccine injection sites associated with pruritus, burning and pain. The rash progressed to include vesicles and bullae over several hours, and eventually ulcerated. Eight days after vaccination, erythema had notably subsided, but ulceration was prominent. Laboratory workup at this time revealed a mildly elevated sedimentation rate at 26 mm/h (0-15 mm/h); C-reactive protein, IgE, tryptase and complete blood counts were normal. A punch biopsy peripheral to the ulcer revealed non-specific reactive epidermal changes, dermal fibrosis and fat necrosis. Over several weeks, his ulceration healed with central scarring and surrounding post-inflammatory pigment changes. There is paucity of literature concerning COVID-19 vaccine reactions in paediatric patients. In BNT162b2 vaccine clinical trials in children 5 to 11 years old, vaccine recipients reported more local reactions than placebo recipients. These reactions were typically mild and self-limited, with average onset >7 days after vaccination and resolution in 1 to 2 days. Following rollout of COVID-19 vaccinations worldwide, including the BNT162b2 vaccine, the majority of reactions described have consisted of new onset or flares of various inflammatory dermatoses, including urticaria, psoriasis, lichen planus, pemphigus vulgaris, pityriasis rosea and others. Such reactions have also been shown to occur with COVID-19 vaccine booster injections, regardless of whether they occurred with prior injections. Our patient received a higher dose of SARS-CoV-2 viral spike glycoprotein mRNA than recommended for his age (30 ug vs. 10 ug). In Phase 1 trials, a higher percentage of participants developed local redness and swelling in the 30 ug group compared to the 10 ug group, but this was not statistically significant. There were no reports of ulcerating reactions in any trials. A review of the Vaccine Adverse Events Reporting System revealed 675 children ages 5 to 11 who received the higher 30 ug dose, with none having significant adverse events (AEs). While the number and type of vaccines our patient received concomitantly were appropriate according to CDC guidelines, it is important to consider that one or a combination of vaccines administered with the COVID-19 vaccine led to our patient's severe reaction. A systematic review evaluating safety and immunogenicity of administering the HPV vaccine alone versus co-administration of HPV, Tdap and meningococcal vaccines found no significant AE differences between these two groups. Reports of ulceration with HPV, meningococcal or Tdap vaccines were not identified. Proposed mechanisms for vaccine AEs include potential formation of an immunocompromised district in the area of vaccination which results in disruption of lymphatic circulation, altered immune cell trafficking, and peripheral nerve damage leading to defective or excessive immune responses. A review of cutaneous adverse reactions to COVID-19 vaccines suggests both IgE-dependent and IgE-independent mechanisms that result in mast cell degranulation may be involved. Thus, immunologic dysregulation triggered by the Pfizer-BioNTech COVID-19 vaccine, possibly with contributions from one or more of the other vaccines administered, may have led to robust immune cell trafficking and activation in our patient, resulting in significant tissue necrosis and ulceration. Our patient clinically presented with a robust local injection site reaction occurring within minutes-to-hours of vaccination and, to our knowledge, is the first reported that led to significant skin necrosis, ulceration and scarring at the injection site in a child. Potential hypotheses which could explain the relatively abrupt reaction onset include an excessive immune response and/or local mast cell degranulation. The severity of immune dysregulation may have been exaggerated by the number of vaccines received concomitantly and/or a higher-than-recommended COVID-19 vaccine dose for his age. Continued reporting and evaluation of AEs is needed to delineate the pathophysiology behind such reactions and for development of targeted treatment strategies when reactions do occur.  Amendment: This follow-up report is being submitted to amend previous information: Added events Vaccination site urticaria, Vesiculobullous rash, Vaccination site ulcer, Vaccination site necrosis, Vaccination site fibrosis, Vaccination site scar, Vaccination site discolouration, Vaccine interaction, and upgraded the case to serious (Medically significant). This report includes also additional follow-up information received on 18Jan2024.  Follow-up (18Jan2024): This is a literature report. This is a follow-up report based on the receipt of the publication; the case has been updated to include additional information identified in the publication. Additional information included: Updated literature information.  No follow-up attempts are possible.; Sender's Comments: Based on the current available limited information in the case provided, the causal association between the events Overdose , Product administered to patient of inappropriate age , Vaccine interaction , Vaccination site urticaria, Dermatitis bullous, Vaccination site ulcer, Vaccination site necrosis, Vaccination site fibrosis, Vaccination site scar, Vaccination site discolouration,  and the use of suspect product cannot be fully excluded. The impact of this report on the benefit/risk profile of the Pfizer product is evaluated as part of Pfizer procedures for safety evaluation, including the review and analysis of aggregate data for adverse events. Any safety concern identified as part of this review, as well as any appropriate action in response, will be promptly notified to regulatory authorities, Ethics Committees, and Investigators, as appropriate.