Age: 0.33
Sex: F
Vaccine: DTAPHEPBIP, HIBV, MMR, PNC13, RV1, UNK, VARCEL
Symptoms: Urine abnormality, Urine ketone body present, White blood cell count increased, White blood cells urine positive
Clinical narrative: PERIODIC APHTHOUS STOMATITIS PHARYNGITIS ADENTIS SYNDROME; This 18-month-old female subject was enrolled in a study The subject received the 4th dose of Bexsero vs Placebo (intramuscular, right thigh) on 24-JUL-2020, for prophylaxis. The subject received the 2nd dose of Hiberix (intramuscular, right thigh) on 17-JAN-2020, for prophylaxis. The subject received the 1st dose of Varivax (subcutaneous, left arm) on 24-JUL-2020, for prophylaxis. The subject received the 4th dose of Prevnar 13 (intramuscular, left thigh) on 24-JUL-2020, for prophylaxis. The subject received the 3rd dose of DTPa-HBV-IPV (intramuscular, left thigh) on 17-JAN-2020, for prophylaxis. The subject received the 2nd dose of Rotarix lyophilized formulation (oral) on 15-NOV-2019, for prophylaxis. The subject received the 1st dose of M-M-R II (subcutaneous) on 24-JUL-2020, for prophylaxis.   On 20-JAN-2021, 180 days after receiving Bexsero vs Placebo, Varivax, Prevnar 13 and M-M-R II, 369 days after receiving Hiberix and DTPa-HBV-IPV and 432 days after receiving Rotarix lyophilized formulation, the subject developed severe - grade 3 syndrome of periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (Verbatim: PERIODIC APHTHOUS STOMATITIS PHARYNGITIS ADENTIS SYNDROME). Serious criteria included clinically significant/intervention required. The outcome of syndrome of periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis was resolving.   Relevant Tests: On 19-JAN-21 and 2-FEB-21 Labs of CBC, Differential, CRP (C-Reactive Protein), Erythrocyte Sedimentation rate, IGG, IGA, IGM was done . Her labs when febrile on 19-JAN-21 no neutropenia. On 09-DEC-2024 Fluroscopy-Voiding cystourethrogram 31JUL2020 Result "Images demonstrated no evidence of bony abnormality. No calcified renal stones seen. The urinary bladder appeared normal in caliber and contour. No visible vesicoureteral reflux, the urethra is unremarkable. No significant post void residual volume".  Mile dilation of the proximal RT ureter and possible minimal distention of the central calyces only in the prone position. No significant left renal collecting system dilation.  On 12MAY2020 Urinalysis was done results was HGB QL: small; LE UA: Large; Appearance-Cloudy: Color Amber; Urine WBE greater than 182; Urine RBC 22HPF; Urine Bacteria 2+ HPF; Squamous cells 30LFF. CBC 24JUL2020 Results: PLTS= 673 k/uL. Urinalysis 01DEC202.   Diagnostic results (reference ranges are provided in parenthesis if available): Body temperature- 22-OCT-2020 up to 104 degree F: 27-NOV-2020 fevers up to 104F degree F: 15-JAN-2021 103.5F degree F and 12-SEP-2024 up to 104 degree F. C-reactive protein- 19-JAN-2021 3.6: 19-JAN-2021 3.6: 02-FEB-2021 2.0: 02-FEB-2021 2.0 and 22-MAR-2021 WNL. Culture urine- 12-MAY-2020 greater than 100,000001 Escherichia coli /ml. Red blood cell sedimentation rate- 19-JAN-2021 31: 19-JAN-2021 31: 02-FEB-2021 23: 02-FEB-2021 23 and 22-MAR-2021 WNL. Ultrasound kidney- 10-JUN-2020 Kidneys are normal in length for age. Urine analysis- 12-MAY-2020 20 mg/dL: 12-MAY-2020 Positive: 12-MAY-2020 100 mg/dL and 04-AUG-2020 20 mg/dL. White blood cell count- 19-JAN-2021 no neutropenia: 02-FEB-2021 24.6: 02-FEB-2021 24.6 and 22-MAR-2021 WNL.                                                                                                     The investigator considered that there was no reasonable possibility that the syndrome of periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis may have been caused by Bexsero vs Placebo, Hiberix, Varivax, Prevnar 13, DTPa-HBV-IPV, Rotarix lyophilized formulation and M-M-R II.   The company considered that there was no reasonable possibility that the syndrome of periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis may have been caused by Bexsero vs Placebo, Hiberix, Varivax, Prevnar 13, DTPa-HBV-IPV, Rotarix lyophilized formulation and M-M-R II.   GSK Receipt date was: 20-JUL-2021 24 month old female who had had a fever monthly since May 2020. In May 2020, had urinary tract infection, pyelonephritis and mild grade 1 hydronephrosis. In August 2020, another episode of fever with no other diagnosis. In the beginning of September 2020, another episode of fever with no diagnosis, In mid September 2020 another episode of fever. In January 2021, fever with no other diagnosis. Subject was referred to a rheumatologist in January 20, 2021 for possible periodic fever syndrome. Per Rheumatologist, her symptoms may indicate an emerging periodic fever syndrome. She suspects this was most like PFAPA (Periodic Fever Apthous-Stomatitis Pharyngitis Adenitis Syndrome). Typically the first step was a trial abortive prednisone, which subject never used.  Subject was to repeat lab when afebrile, ideally 2 weeks from last episode of fever, but was not able to until 22-MAR-21. ESR, CPR and WBC all WNL. Since 31-MAR-20 subject had been on Poly Vi Sol Multivitamins, 1ml everyday of 400 IU, and since 22-MAR-21 added D Vi Sol Vitamin D, 1ml everyday of 400 IU for a total of 800 IU Vitamin D. She has been fever free since last episode on March 10, 2021. This subject had no family history of PFAPA syndrome. Mother had kept a log of the child's fever that she started in September 2020. On 12-SEP-2020 the child had fevers up to 104F lasting for 3 days, decreasing only with antipyretic medication and finally ended 15-SEP-2020. Then on 22-OCT-2020 the child had fevers of up to 104F, lasting until 20-OCT-2020, decreasing only with antipyretics. Again on 27-NOV-2020 had fevers up to 104F that ended on 01-DEC-2020 and then on 15-JAN-2021 the child had fevers of 103.5F and ended on 21-JAN-2021. During the episodes of fevers antipyretics were given to release the fevers. Antibiotics were prescribed the first 2 episodes. It was in January 2021 that the PCP first suspected Periodic Fever Syndrome and was referred to a rheumatologist, suggested trying abortive prednisone as treatment for the next episode of fevers. The mother of this child decided to start Vitamin D drops, since then the child had had no fevers since the January 2021 episode. At this time no alternative etiology had been determined and the child had not met exclusion criteria, it was not until July 9 2021 was an actual diagnosis of PFAPA (Periodic Fever Aphthous Stomatitis Adenitis Syndrome) was determined by the rheumatologist. Periodic Fever Aphthous Stomatitis Pharyngitis Adenitis Syndrome is a chronic condition. Correction to previous narrative comment from initial report. Subject had been on Poly Vi Sol multivitamin since 22MAR2021.  The subject received D Vi SOL VITAMIN D on 22-MAR-2021 1 ml 4D through oral route for periodic fever syndrome. The subject received POLY Vi SOL MULTIVITAMIN on 22-MAR-2021 1 ml 4D through oral route for periodic fever syndrome.  This case contains an event assessed by the investigator as a serious possible immune mediated disorder (pIMD).  Follow up information received on 20-MAY-2022.  This follow up was considered significant.  Summary of changes: The rotarix device coding were updated.  Follow up information received on 20-SEP-2022.  This follow up was considered non-significant.  Summary of changes: The treatment drug details were updated  Follow up information received on: 09-DEC-2024 Summary of changes: Lad data and relevant tests was added.; Sender's Comments: A case of PFAPA syndrome, 180 days after receiving 4th dose of Bexsero vs Placebo, 1st dose of Varivax, 4th dose of Prevnar 13 and 1st dose of and M-M-R II, 369 days after receiving 2nd dose of Hiberix and 3rd dose of DTPa-HBV-IPV and 432 days after receiving 2nd dose of Rotarix lyophilized formulation in a 18-month-old female subject. Report is inconsistent with causal relation to the vaccine product, considering implausible time to onset and absence of biological plausibility.