Sex: M
Vaccine: HPVX
Symptoms: Rheumatoid factor negative, SARS-CoV-2 test negative, Serum ferritin increased, Splenomegaly, Still's disease
Clinical narrative: adult-onset Still's disease (AOSD); worsening of his symptoms; abdominal pain; migrating polyarthritis; low-grade acalculous cholecystitis/ Sludge was also noted in the gallbladder; sore throat; salmon-pink colored rash on his chest and upper extremities; jaundice; inability to ambulate; joint effusion of the left hip; hepatosplenomegaly; small-volume ascites; diffuse mesenteric edema; moderate inflammation of portal tracts; moderate centrilobular cholestasis; leukocytosis; liver dysfunction; malaise; fevers/ recurrent fevers/ persistent fevers; headache; joint pain/severe left hip pain; dark-colored urine; vomiting; proteinuria; dehydration; splenomegaly; This serious case was reported in a literature article and described the occurrence of adult onset still's disease in a 20-year-old male patient who received HPV 16-18 (HPV vaccine) for prophylaxis. Literature Reference:   Concurrent medical conditions included acute gastroenteritis and diarrhea (self-limiting episode).   On 18-DEC-2021, the patient received the 3rd dose of HPV vaccine. In DEC-2021, less than a week after receiving HPV vaccine, the patient experienced proteinuria (Verbatim: proteinuria) (serious criteria hospitalization), dehydration (Verbatim: dehydration) (serious criteria hospitalization), splenomegaly (Verbatim: splenomegaly) (serious criteria hospitalization), condition aggravated (Verbatim: worsening of his symptoms) (serious criteria hospitalization), abdominal pain (Verbatim: abdominal pain) (serious criteria hospitalization), migratory polyarthritis (Verbatim: migrating polyarthritis) (serious criteria hospitalization, GSK medically significant), acalculous cholecystitis (Verbatim: low-grade acalculous cholecystitis/ Sludge was also noted in the gallbladder) (serious criteria hospitalization and GSK medically significant), sore throat (Verbatim: sore throat) (serious criteria hospitalization) and red rash (Verbatim: salmon-pink colored rash on his chest and upper extremities) (serious criteria hospitalization). On 19-DEC-2021, the patient experienced adult onset still's disease (Verbatim: adult-onset Still's disease (AOSD)) (serious criteria hospitalization and GSK medically significant), malaise (Verbatim: malaise) (serious criteria hospitalization), fever (Verbatim: fevers/ recurrent fevers/ persistent fevers) (serious criteria hospitalization), headache (Verbatim: headache) (serious criteria hospitalization), joint pain (Verbatim: joint pain/severe left hip pain) (serious criteria hospitalization), dark urine (Verbatim: dark-colored urine) (serious criteria hospitalization) and vomiting (Verbatim: vomiting) (serious criteria hospitalization). On an unknown date, the patient experienced jaundice (Verbatim: jaundice) (serious criteria hospitalization), unable to walk (Verbatim: inability to ambulate) (serious criteria hospitalization), joint effusion (Verbatim: joint effusion of the left hip) (serious criteria hospitalization), hepatosplenomegaly (Verbatim: hepatosplenomegaly) (serious criteria hospitalization), ascites (Verbatim: small-volume ascites) (serious criteria hospitalization and GSK medically significant), mesenteric edema (Verbatim: diffuse mesenteric edema) (serious criteria hospitalization and GSK medically significant), portal tract inflammation (Verbatim: moderate inflammation of portal tracts) (serious criteria hospitalization and GSK medically significant), cholestasis (Verbatim: moderate centrilobular cholestasis) (serious criteria hospitalization and GSK medically significant), leukocytosis (Verbatim: leukocytosis) (serious criteria hospitalization) and hepatic function disorder (Verbatim: liver dysfunction) (serious criteria hospitalization), . The patient was treated with ceftriaxone, doxycycline, ibuprofen, amoxicillin, prednisone and steroids. The outcome of the adult onset still's disease, malaise, fever, headache, joint pain, dark urine, vomiting, proteinuria, dehydration, splenomegaly, condition aggravated, abdominal pain, migratory polyarthritis, acalculous cholecystitis, jaundice, unable to walk, joint effusion, hepatosplenomegaly, ascites, mesenteric edema, portal tract inflammation, cholestasis, leukocytosis and hepatic function disorder were resolving and the outcome of the sore throat and red rash were resolved.   The reporter considered the adult onset still's disease, malaise, fever, headache, joint pain, dark urine, vomiting, proteinuria, dehydration, splenomegaly, condition aggravated, abdominal pain, migratory polyarthritis, acalculous cholecystitis, sore throat, red rash, jaundice, unable to walk, joint effusion, hepatosplenomegaly, ascites, mesenteric edema, portal tract inflammation, cholestasis, leukocytosis and hepatic function disorder to be related to HPV vaccine.     The company considered the adult onset still's disease, malaise, dark urine, proteinuria, dehydration, splenomegaly, condition aggravated, migratory polyarthritis, acalculous cholecystitis, sore throat, jaundice, unable to walk, joint effusion, hepatosplenomegaly, ascites, mesenteric edema, portal tract inflammation, cholestasis, leukocytosis and hepatic function disorder to be unrelated to HPV vaccine. The company considered the fever, headache, joint pain, vomiting, abdominal pain and red rash to be related to HPV vaccine.   Additional Information: GSK Receipt Date: 10-JUL-2024 The patient was a 20-year-old male with no significant medical history presented to the emergency department for 2 days of fever, malaise, headaches, dark-colored urine, joint pain and vomiting. Of note, the patient received his third dose of the HPV vaccine the day prior to the onset of symptoms and had an episode of self-limiting diarrhea approximately 2 weeks prior. Initial labs were significant for WBC 22.7 K/µL, AST 107 IU/L, ALT 145 IU/L, Alk Phos193 IU/L, total bilirubin 7.9 mg/dL, CRP 17 mg/dL, ESR106 mm/h, haptoglobin 341.9 mg/dL, ferritin 885 ng/mL, and aldolase 18.7 U/L. His urinalysis also demonstrated significant proteinuria and large amounts of bilirubin, which in combination with dehydration, explained the dark-colored urine. Initial imaging via abdominal ultra-sound was significant for splenomegaly but otherwise unremarkable. Ancillary testing including HIV, EBV,CMV, Lyme, hepatitis serology, parvovirus, syphilis, and toxoplasmosis was negative. While in the hospital, the patient was treated with 1 day of ceftriaxone, then transitioned to empiric doxycycline. He was discharged after2 days in the hospital with a 7-day course of doxycycline with a diagnosis of fever of unknown origin, likely secondary to infectious cause. He then returned to the hospital 2 days later due to worsening liver function tests (LFTs) at his outpatient follow-up appointment and worsening of his symptoms, including recurrent fevers, abdominal pain, and migrating polyarthritis. The gastroenterology, infectious disease, endocrinology, and hematology teams were consulted. The patient's workup at this time was largely unremarkable including a negative infectious workup including blood cultures, COVID, EBV PCR, influenza, hepatitis, syphilis, treponema, leptospira and ehrlichia, and a negative autoimmune panel including ANA, thy-roid antibodies and autoimmune hepatitis. A CT scan of the abdomen and pelvis was also performed to rule out any hepatobiliary process and was negative. An abdominal ultrasound was repeated and showed prominence of the gallbladder wall with trace pericholecystic fluid noted. Sludge was also noted in the gallbladder with the findings being equivocal for low-grade acalculous cholecystitis. Throughout the course of his stay, the patient continued to have intermittent, recurrent fevers and he developed a sore throat and salmon-pink colored rash on his chest and upper extremities. He was started on ibuprofen 800 mg. On the second day the patient's condition began to improve and his LFTs also showed mild improvement. The patient was discharged with a 5-daycourse of amoxicillin. The patient presented to the ED again 3 days later with persistent fevers, jaundice, and severe left hip pain causing an inability to ambulate. On arrival, the patient was found to have a small joint effusion of the left hip through point of care ultrasound. Despite intermit-tent fevers, the patient's infectious disease workup was negative and antibiotics were discontinued based on recommendations from the infectious disease team. During this visit, the hepatology and rheumatology teams were further consulted. The patient had a magnetic resonance cholangiopancreatography done which showed hepato-splenomegaly, but no significant liver parenchymal abnormalities. However, there was some small-volume ascites and diffuse mesenteric edema. The patient also had a liver biopsy done which revealed moderate inflammation of the portal tracts and moderate centrilobular cholestasis. Other than an IL-6 of 293.3 pg/mL, serological work-up(i.e; ANA, RF, ACPA, extractable nuclear antigens, complements, antineutrophil cytoplasmic antibodies, creatinephosphokinase, autoimmune hepatitis panel, and urine protein and creatinine) was negative. The patient was diagnosed with Adult-onset Still's disease (AOSD) based on the Yamaguchi Criteria: he fulfilled all four major criteria consisting of having a fever, arthralgias, typical rash, and leukocytosis along with four of the five minor criteria with a sore throat, hepato-splenomegaly, liver dysfunction, and absence of ANA andRF.12 The patient was started on Prednisone 40 mg and his symptoms improved significantly in a matter of days including resolution of his rash, decreased joint pains, and resolution of his sore throat within 1 day. He was dis-charged on day 3 of starting steroids (day 9 of his hospital stay) with recommendations for outpatient follow-up with a rheumatologist in 2 weeks. At his first outpatient follow-up, the rheumatologist decreased the prednisone dosage to 30 mg and recommended a gradual reduction of 10 mg every 3 weeks. The patient maintained regular follow-ups with the rheumatologist, initially on a monthly basis, and then at intervals of 3-4 months, showing remarkable improvement in response to the steroid treatment. Notably, his LFTs also showed excellent response, with AST and ALT levels returning to normal by June. Although there was consideration of starting the patient on anakinra, it was decided to avoid its use unless another episode of AOSD flare occurred. This article is not available for regulatory reporting purpose due to copyright restriction.; Sender's Comments: A case of 20-year-old male patient  with multiple events for HPV vaccine. There is insufficient evidence to establish a conclusive causal relationship. The case is confounded by comorbidities.