Pantoprazole: An Unusual Suspect in a Patient with Fever
A 42-year-old woman with a previous history of well-controlled asthma, alcoholism, and breast cancer was admitted to the emergency department due to malaise and anorexia with 1 week of evolution. On admission, she was febrile (38.3°C), her blood pressure was 103/76 mmHg, heart rate was 110 bpm, and she presented with mild icterus and painful hepatomegaly. Blood analysis showed acute hepatitis with hyperbilirubinemia with normal coagulation tests and slightly elevated C-reactive protein. Viral serologies were negative and abdominal ultrasonography only showed mild hepatomegaly with no additional pathological findings. She denied the use of recreational drugs or intentional drug poisoning.

The patient was admitted to the general ward. On day 1, she showed signs of grade 1 encephalopathy and her blood results showed a marked rise in transaminases with increased hyperbilirubinemia. Acute liver failure was diagnosed and the patient was transferred to an intensive care unit. Pantoprazole for stress ulcer prophylaxis and N-acetylcysteine (NAC) (initial loading dose of 150 mg/kg/hour of NAC over 1 hour, followed by 12.5 mg/kg/hour for 4 hours, then continuous infusions of 6.25 mg/kg for the remaining 67 hours) for putative toxic hepatitis, were started. Abdominal Doppler ultrasonography excluded portal vein or inferior vena cava thrombosis, and a larger panel of viral serologies was negative. Acetaminophen was undetectable in plasma, and no substances of abuse were found in urine. A liver autoimmune panel was negative. Alpha-1 antitrypsin was normal. Urinary copper and ceruloplasmin were both normal. Ferritin was elevated, but serum iron and transferrin were both normal.

By the following day, hepatic function had dramatically improved: coagulation tests were normal, there were significant drops in serum transaminases and total bilirubin, and the patient presented no signs of encephalopathy. Despite the clinical and analytical improvement, a liver biopsy was taken, which showed mild iron overload with no additional clues to a specific etiology.

However, the patient developed nicotine withdrawal symptoms which precluded transfer to the general ward. She had one episode of low-grade fever, which was interpreted as part of the withdrawal syndrome. She was transferred to the general ward after 6 days in the ICU. Liver function was normal and serum transaminases continued to decline. Despite the absence of any symptoms or signs of infection, the patient presented low-grade fever during the following days. Since she had no new symptoms and physical examination was unremarkable, antibiotics were withheld. Blood and urine cultures were negative. Renal function and urinalysis were normal. Chest and abdominopelvic CT scans were normal and a transthoracic echocardiogram showed no signs of infective endocarditis. C-reactive protein and the erythrocyte sedimentation rate were low. Several drugs were suspended but the fever persisted. Anti-nuclear antibodies, ANCA, and anti-dsDNA were negative and a Doppler ultrasound of temporal arteries was normal. A PET-CT scan was normal. Eventually, pantoprazole was suspended and the febrile episodes resolved. A diagnosis of drug fever associated with pantoprazole was made and the patient was discharged. She remained well, without any new febrile episodes, during 1 year of follow-up.

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