PURPOSE:

To review presentation, diagnosis, and workup for rare but known sulfonamide-associated DILI in a patient with multiple risk factors

INTRODUCTION:

Drug-induced liver injury (DILI) is a rare though known adverse drug reaction that can progress to hepatic failure. Though the mechanism of liver injury remains unclear, several classes of medications have been clearly associated with DILI and continue to inform FDA regulatory actions on these agents. Sulfonamide drugs, a potent class of drugs with diverse applications, comprise one such class of drugs associated with DILI. It is believed that sulfonamides cause hepatotoxicity in < 1% of treated patients. A diagnosis of exclusion, DILI thus requires thorough workup to rule out possible etiologies for acute and fulminant liver failure. Here, we present a case of acute liver injury in a 32-year-old ulcerative colitis patient with multiple risk factors including recent travel and frequent alcohol use.

SUMMARY:

A 32-year-old male with ulcerative colitis presented with acute hepatitis of unknown etiology. Patient’s liver enzymes, which were within normal limits 4 weeks prior, were elevated to 1000s u/L with associated symptoms such as scleral icterus, jaundice, and hepatomegaly. Other symptoms on presentation included fever, fatigue, nausea, vomiting, loss of appetite, and dark urine.

Patient has history of ulcerative colitis but no other significant history such as viral hepatitis or HIV. His medications included a recently completed prednisone taper and a change from balasazide to sulfasalazine 4 weeks prior due to drug rash. Patient had prior history of urticaria on mesalamine. He recently traveled to Colorado where he ate sushi and had been to Bolivia prior to that. Patient drank 2-3 beers every other day but denied other drug use.

Despite immediately discontinuing sulfasalazine upon admission, liver enzymes continued to increase at a rate of approximately 1000 u/L every other day. Index of suspicion for primary sclerosing cholangitis was high in the setting of patient’s ulcerative colitis, however ultrasound imaging failed to show biliary dilation/strictures. Abdominal ultrasound was also negative for hepatic vein or artery thrombosis, as one would observe in Budd-Chiari syndrome. Abdominal CT also largely unremarkable, demonstrating mild splenomegaly and fatty infiltration of the liver with gallbladder wall thickening. Other possible etiologies such as Autoimmune Hepatitis, Celiac disease, Alpha 1 Antitrypsin deficiency, Wilson’s disease, Hemochromatosis, malignancy, and HLH were ruled out. Workup was negative including for HAV, HBV, HCV, HDV. Ethanol and acetaminophen levels were undetectable.  

Patient also revealed recent exposure to fleas/ticks during home renovation and possible exposure during travel to Colorado. Zosyn was empirically started, however workup for zoonoses was negative. Transfer of care for liver transplant was initiated. With sufficient time, the patient’s liver inflammation markers downtrended. His symptoms improved with minimal supportive care and discharged home with close follow-up.

CONCLUSION

DILI is a rare but known adverse effect of sulfasalazine use. Though a delayed hypersensitivity  reaction is the purported mechanism of action, the process remains largely unclear. Nonetheless, the acute liver injury observed can progress to fulminant hepatic failure if untreated. A diagnosis of exclusion, DILI thus requires in-depth review of a patient’s history and workup especially in instances of possible zoonotic exposures and alcohol use history as with our patient.