Age: 77.0
Sex: F
Vaccine: COVID19, FLUX
Symptoms: Pyrexia, Somnolence, Vomiting, Weight decreased, White blood cell count
Clinical narrative: Non-obstructive cholangitis without evidence of bacterial infection; Asymptomatic ARIA-E / ARIA-E without microhemorrhages, altered neurological exam, or seizures; Recurrence of PMR (polymyalgia rheumatica) / PMR symptoms re-appeared; Lost 2 kg, 3.5% of her baseline weight; Somnolence; Very little appetite; Flu-like symptoms; Diarrhea; Vomiting; Fever to 39°C/ daily fevers of ?39°C/ low-grade fevers; The patient's current conditions included Apolipoprotein E (APOE) e4 carrier genotype (APOE-e4 heterozygote), mild Alzheimer's disease, and polymyalgia rheumatica (PMR). The patient's concomitant medications included prednisone used for polymyalgia rheumatica, and aducanumab for mild Alzheimer's disease. The patient's historical conditions included asymptomatic amyloid-related imaging abnormalities-edema (ARIA-E), without microhemorrhages. The patient had a risk factor of a strong family history of Alzheimer's disease with apparent autosomal dominant inheritance. The patient was participating in  Safety Study and had previously participated in the placebo arm of a double-blind Phase-3 trial of aducanumab. The patient's historical vaccine included two Moderna mRNA-1273 vaccines received on an unspecified date (reported as 'seven and eight months earlier') with no notable side effects and unspecified influenza vaccine, which the patient received annually for decades, after which the patient had no reaction.  The patient had no past history of gallstones or other hepatobiliary disease. The patient had negative PCR-based test for SARS-CoV-2, obtained for international travel before the vaccination.   On an unspecified date, the patient was vaccinated with influenza vaccine (brand not specified; dose; route of administration, anatomical location, and indication: not reported). The batch number was not reported.  On the same date, the patient was vaccinated with non-company, co-suspect Pfizer BioNTech COVID-19 vaccine (reported as 'Pfizer BioNTech BNT162b2 SARS-CoV-2 vaccine booster') (tozinameran; dose, route of administration, anatomical location, and indication: not reported). The batch number was not reported.  On the same date, four hours after receiving influenza vaccine and non-company, co-suspect Pfizer BioNTech COVID-19 vaccine, the patient experienced a sudden onset of precipitous diarrhea and vomiting with fever to 39°C.   On an unspecified date, the patient recovered from the events of diarrhea and vomiting.   On an unspecified date, reported as 'followed by', the patient experienced six days of flu-like symptoms, including generalized myalgias, chills, and daily fevers of more than 39°C. Flu-like illness was a Grade-2 (moderate severity) adverse event.  On an unspecified date, after six days, the patient recovered from the event of flu-like symptoms.   On an unspecified date, following flu-like symptoms, the patient experienced eight days of somnolence with occasional low-grade fevers (38°C). Other vital signs remained stable. The patient had very little appetite, consumed mostly liquids, and lost 2 kg, 3.5% of her baseline weight.  On an unspecified, after eight days, the patient recovered from the events of somnolence and fever.   On an unspecified date, reported as 'ten days after the vaccination', the patient had laboratory bloodwork and the results were: gamma-glutamyl transferase (GGT) was 268 U/L (four times upper limit) and alkaline phosphatase was 368 U/L (three times upper limit), whereas bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), other serum chemistries, and complete blood count, including white blood cell count, were within normal limits. Brain magnetic resonance imaging (MRI) showed no evidence of ARIA-E. On the same date, aducanumab was infused. The biochemical profile indicated cholangitis rather than hepatitis. Specifically, the laboratory tests and clinical course indicated non-obstructive cholangitis without evidence of bacterial infection. The patient was managed at home with ibuprofen and oral hydration. Prednisone was continued to complete the one-year tapering course.  On an unspecified date, reported as 'during the ensuing month', the patient recovered from the event of cholangitis. It was reported that liver function tests gradually returned to normal during the ensuing month, along with her activity level and sense of well-being.   On an unspecified date, the patient experienced asymptomatic ARIA-E, bout of MRI detected ARIA-E lasting 2 months, again without microhemorrhages, altered neurological exam, or seizures.  On an unspecified date, reported as 'two months following the vaccinations and overlapping with the resolution of the second ARIA-E episode', The patient's mild PMR symptoms re-appeared (proximal upper extremity pain and weakness, without fever), less severe than the episode that started a year earlier.  On an unspecified date, the patient recovered from the event of asymptomatic ARIA-E. As it was reported as overlapping with the resolution of second ARIA-E episode.   On an unspecified date, the patient recovered from the event of PMR. It was reported that those symptoms resolved without corticosteroids over approximately six months.  The reporter did not provide causality assessment. The patient had never received the Pfizer BioNTech BNT162b2 vaccine and had no prior history of reactions to influenza vaccination. Hence, the SARS-CoV-2 mRNA vaccine seems likely to have been the immediate trigger and involvement of the influenza vaccine seems less likely, although it may have contributed to additional immune stimulation.  The events of cholangitis, asymptomatic ARIA-E, and polymyalgia rheumatica were considered to be medically significant by a Physician within Department.  In conclusion, in the current case of acute cholangitis, it seems plausible that there was an interaction among (i) aducanumab toxicity (inflammation leading to ARIA-E); (ii) COVID-19 mRNA vaccine toxicity, perhaps exacerbated by the influenza vaccine; and (iii) PMR-associated autoantibodies and/or TLRs, resulting in biliary duct inflammation. Given that mRNA vaccines against SARS-CoV-2 continue to be recommended and given the Food and Drug Administration's conditional approval of aducanumab and full approval of lecanemab, with other anti-amyloid monoclonals in the pipeline, analysis of clinical trials data should be alert to acute cholangitis after vaccination, especially in patients with a history of ARIA-E or PMR. It is hoped that this unusual clinical scenario will spur investigation of interactions among immune-mediated disease (e.g., PMR), immunotherapy with anti-amyloid antibodies, and acute cholangitis following SARS-CoV-2 mRNA vaccination.     Company comment: A 77-year-old female patient was vaccinated with influenza vaccine and with non-company, co-suspect Pfizer BioNTech COVID-19 vaccine, on the same day. Reportedly, 4 hours following vaccination, patient experienced diarrhoea, pyrexia, and vomiting. These symptoms were followed by influenza like illness, and somnolence. The patient had decreased appetite, and decreased weight. As reported, 10 days following vaccination, gamma-glutamyl transferase was four times upper limit and alkaline phosphatase was three times upper limit, which indicated non-obstructive cholangitis without evidence of bacterial infection. The patient had no past history of gallstones or other hepatobiliary disease, nevertheless biochemical profile indicated cholangitis rather than hepatitis. The patient was prescribed ibuprofen and oral hydration. Brain magnetic resonance imaging (MRI) was performed and showed no evidence of asymptomatic amyloid-related imaging abnormalities-edema (ARIA-E). However, on an unknown day and unknown amount of time following vaccination, patient experienced ARIA-E. Two months after being vaccinated, the patient's mild polymyalgia rheumatica (PMR) symptoms re-appeared and were overlapping with the resolution of the second ARIA-E episode. The patient's current conditions included PMR, and the patient's historical conditions included ARIA-E, without microhaemorrhages. Considering information provided, current and historical conditions, causality for PMR and ARIA-E is assessed as not related. Despite confounding by co-suspect vaccine, causal role of the suspect product cannot be excluded. Therefore, causality for diarrhoea, pyrexia, vomiting, influenza like illness, somnolence, decreased appetite, decreased weight, and cholangitis is assessed as possibly related, due to plausible temporal relationship.; Reporter's Comments: The patient had never received the Pfizer BioNTech BNT162b2 vaccine and had no prior history of reactions to influenza vaccination. Hence, the SARS-CoV-2 mRNA vaccine seems likely to have been the immediate trigger and involvement of the influenza vaccine seems less likely, although it may have contributed to additional immune stimulation.; Sender's Comments: A 77-year-old female patient was vaccinated with influenza vaccine and with non-company, co-suspect Pfizer BioNTech COVID-19 vaccine, on the same day. Reportedly, 4 hours following vaccination, patient experienced diarrhoea, pyrexia, and vomiting. These symptoms were followed by influenza like illness, and somnolence. The patient had decreased appetite, and decreased weight. As reported, 10 days following vaccination, gamma-glutamyl transferase was four times upper limit and alkaline phosphatase was three times upper limit, which indicated non-obstructive cholangitis without evidence of bacterial infection. The patient had no past history of gallstones or other hepatobiliary disease, nevertheless biochemical profile indicated cholangitis rather than hepatitis. The patient was prescribed ibuprofen and oral hydration. Brain magnetic resonance imaging (MRI) was performed and showed no evidence of asymptomatic amyloid-related imaging abnormalities-edema (ARIA-E). However, on an unknown day and unknown amount of time following vaccination, patient experienced ARIA-E. Two months after being vaccinated, the patient's mild polymyalgia rheumatica (PMR) symptoms re-appeared and were overlapping with the resolution of the second ARIA-E episode. The patient's current conditions included PMR, and the patient's historical conditions included ARIA-E, without microhaemorrhages. Considering information provided, current and historical conditions, causality for PMR and ARIA-E is assessed as not related. Despite confounding by co-suspect vaccine, causal role of the suspect product cannot be excluded. Therefore, causality for diarrhoea, pyrexia, vomiting, influenza like illness, somnolence, decreased appetite, decreased weight, and cholangitis is assessed as possibly related, due to plausible temporal relationship.