DILD Case

D.J. is a 70 y. o. female presenting at the ER with jaundice, upper abdominal pain, nausea, vomiting.  Pain had a sudden onset and has lasted for a couple of days.  She also mentioned itching in her palms and legs.  Upon abdominal examination, MD noticed that liver was enlarged (via palpation and percussion). 

The following lab results were obtained (normal ranges in parentheses):
PT 13.2 sec (10-12 sec)
Total bilirubin 20 mg/dL (0.1-1.0 mg/dL)
ALT 105 IU/L (5-35 IU/L)
Alk phos. 355.6 IU/L (30-120 IU/L)
GGT 150 IU/L (0-30 IU/L)
AST 65 IU/L (5-40 IU/L)
WBC 5200/mm3 (4500-10000/mm3)
          Eosinophils at 10 % (0-3%)
Hgb 11.5 g/dL (10-12 g/dL)

Current medication list:
Acetaminophen 500mg TID for Osteoarthritis, started 5 years ago
Hydrochlorothiazide 25 mg q am for Hypertension, started 2 years ago
Atorvastatin 10 mg qd for Hyperlipidemia, started 3 years ago
Erythromycin 400 mg q 6h X 14 days for upper respiratory tract infection, started 10 days ago
No use of OTC or herbal medications
DJ. is allergic to Pen VK (rash), she does not consume alcohol.

Questions:

What type of hepatic injury does D. J. have?  What is the evidence?

Cholestasis Bilirubin, Alk Phos, GGT are increased significantly.  Some increase in AST and ALT indicates the presence of some degree of cellular destruction as well.          

What is Cholestasis?

Cholestasis is an impairment of the hepatocellular secretion of bile.  Alk Phos. and GGT are synthesized at an increased rate and released by bile duct epithelium when bile duct obstruction occurs. AST and ALT are released by damaged hepatocytes, and their increase is indicative of cellular destruction and tissue necrosis rather than bile duct obstruction. 

Will increased bilirubin confirm the diagnosis of cholestasis?

Bilirubin is a substance cleared by the liver.  In the liver, it is conjugated with glucuronide before being secreted in the bile. Increase in bilirubin could be indicative of necrosis, cholestasis, or hemolysis.  Increase in conjugated (direct) bilirubin would be more helpful to confirm the presence of bile duct obstruction.  However, a normal hemoglobin in the presence of such a high bilirubin effectively rules out hemolysis.  The minimal elev. in AST/ALT rules out necrosis.

Which medication is the most likely cause of DJ’s “acute hepatitis”?

Although acetaminophen and atorvastatin can both affect liver function, in this case they are unlikely causes of the problem.  DJ has been taking these medications for several years, and providing that she has not increased the doses recently, or has escalated her alcohol use, these drugs are unlikely to have caused this acute onset of symptoms. 

Erythromycin was added to her regimen ten days ago.  This drug is known to cause DILD.  Increased eosinophil count suggests an idiosyncratic, immunologic reaction (itching not consistent with this unless there is a rash as the same time).  Macrolide antibiotics are well-known to cause cholestatic liver injury.

What would be an appropriate TX for D. J.?

            D/C Erythromycin.  Follow LFTs to monitor reaction.

Would you suggest using this medication in the future?

No.  Other antimicrobials are available and therefore there is no need to rechallenge D. J. with Erythromycin.  Beware all macrolides in the future.