Eosinophils, Autoimmune hepatitis and influenza

Today's case involved a 55-year-old woman with autoimmune hepatitis, admitted with dyspnea.  She had come to hospital on more than one occasion with dyspnea and was treated with clarithromycin and prednisone (for presumed reactive airways disease).  She had transient resolution of the dyspnea but it recurred prompting investigation.  Ultimately, she was diagnosed with influenza infection which may explain some of the symptoms.

Learning points:

·      We discussed patients with autoimmune hepatitis.  There are two types of autoimmune hepatitis.  Type 1 refers to the classic type with Antinuclear antibodies and anti-smooth muscle antibodies.  Type 2 refers to autoimmune hepatitis with anti-liver/kidney microsome (Anti-LKM-1) or anti-liver cytosol antigen (ALC-1) antibodies.  The clinical presentation is heterogeneous and not necessarily different between the two subtypes.  The clinical range can encompass small elevations in transaminases, all the way to transaminases in the 1000’s with fulminant liver failure requiring transplantation.  Typically, treatment is with immunosuppressive medications like prednisone.

·      All patients with cirrhosis are at risk for several things:

o   Portal hypertensive shunting – the most common manifestation is esophageal varices, but gastric varices, caput medusa and hemorrhoids can also occur.  Varices can bleed and are typically banded by hepatologists when they have bled or exceed a certain size.  Nadolol is a non-specific beta blocker that reduces the severity of variceal bleeding.  It should be stopped in patients with SBP as it increases mortality in these settings.

o   Spontaneous bacterial peritonitis – this occurs as a result of transient monomicrobial bacteremia seeding the ascetic fluid.  Diagnosis is made by determining the number of PMNs in the ascetic fluid (>250) and treatment is typically with ceftriaxone 2g Q24H.  Direct bacterial translocation from bowel to ascites is no longer thought to be the causative mechanism.  Patients with ascites and no portal hypertension (e.g. cancer patients) do not get SBP.  Patients with an elevated serum creatinine (> 88umol/L), a urea level > 10.7, or a very high bilirubin (>68) should receive prophylaxis against hepatorenal syndrome with albumin when diagnosed with SBP.

·      We discussed drug reactions with macrolides.  There are three generally available macrolides.  Erythromycin is the oldest and its predominant use now is in gastric motility.  Clarithromycin is of a newer generation, but both of these medications inhibit CYP3A4 leading to multiple drug interactions.  Azithromycin is the newest and most commonly used, and does not inhibit CYP3A4 but does inhibit P-glycoprotein.  This is a gut-based molecular transporter that, when turned off by macrolides (and other drugs) leads to higher drug levels of certain medications like digoxin, rivaroxaban, etc.

·      We discussed the differential diagnoses for eosinophilia which can be summarized with NAACP:

o   Neoplasm – eosinophilic leukemias and primary clonal eosinophil overproduction

o   Allergy or DRESS (Drug Reaction with Eosinophilia and systemic symptoms)

o   Adrenal insufficiency

o   Collagen Vascular disease such as SLE, EGPA (formerly Churg-Strauss)

o   Parasitic infections – Strongyloides and Ascaris are classical but others are possible

·      Eosinophila responds readily to prednisone for the most part, but this can be quite dangerous if the patient has Strongyloides as it can lead to the nearly-fatal hyperinfection syndrome.

·      In general, there are FOUR major things to consider when putting someone on immunosuppression or high-dose steroids:

o   Strongyloides – send serology and then treat if indeterminate or positive to prevent hyperinfection syndrome

o   Tuberculosis – you can do a TB skin test or IGRA within 2 weeks of starting steroids, and may need to treat latent TB if positive

o   Hepatitis B virus – This can be screened for using surface antibody, antigen, and core total antibody (HBcAb IgM and IGG) to catch the “window period”

o   Pneumocystis – This isn’t something that reactivates like the other 3, but people who are on long-term steroids (>20mg/day for >2 months) should probably be considered for prophylaxis (which may take the form of cotrimoxazole, dapsone, pentamidine, or atovaquone).

Further Reading:

Rothenberg, M. E. (1998). Eosinophilia. New England Journal of Medicine, 338(22), 1592-1600.

Shafran, D. M., Bunce, P. E., & Gold, W. L. (2014). Reducing the risk of infection in a 74-year-old man who is to receive prednisone. Canadian Medical Association Journal, 186(16), 1239-1240.

Krawitt, E. L. (2006). Autoimmune hepatitis. New England Journal of Medicine, 354(1), 54-66.