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.
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