[CIS-PAGID] Help for refractory CVID associated enteropathy

[John Ziegler]

Dear Chris

Have you considered or do you have any information about TNF antagonists in this setting?

John


A/Prof. John B. Ziegler
School of Women's & Children's Health, University of NSW
C/o Department of Immunology & Infectious Diseases
Sydney Children's Hospital
High St., Randwick NSW 2031
Australia
T: (02) 93821515
F: + 61 + 2 93821580
E: j.ziegler at unsw.edu.au


-----Original Message-----
From: pagid-bounces at list.clinimmsoc.org [mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of christian.wysocki at yale.edu
Sent: Thursday, 23 February 2012 9:49 AM
To: PAGID
Subject: [CIS-PAGID] Help for refractory CVID associated enteropathy

...sorry, no subject heading on my last post...

We have a really sick young lady, 24 years old with CVID, enteropathy and other
autoimmune sequelae.  Her enteropathy has been severe for many years and
refractory to numerous immunomodulatory therapies as detailed below.  She has
required TPN since september 2011.  We are hoping to get opinions as to any
therapies for severe, refractory CVID associated enteropathy, that people have
had success with...we are particularly interested in Rituximab, and wondered
what peoples experience with it were, but are open to any and all suggestions.
Please see a more detailed clinical description below.

Severe chronic diarrhea since age 3.  Biopsies in the past showed a celiac-like
process with villous blunting in the small bowel and lymphocytic infiltrates
(primarily CD3+....don't know CD4 or 8) in small and large bowel.  She failed a
gluten-free diet, and was somewhat improved on prednisone and Imuran.

In adolescence, she developed a bad pneumonia, and recurrent sinusitis, and was
referred to us when total IgG, A and M were found to be undetectable (total IgG
had been 1500, IgA <7 when tested at age 3).  In the meantime, she had
developed type 1 diabetes and JRA.  She has been on Ig replacement since...made
more difficult by GI protein loss causing difficulty maintaining troughs.  She
is now on Hizentra and doing better from that perspective. We have done
numerous flow analyses over the years....initially B total B cells were quite
low (27/ul), but those have come up to normal more recently.  We did a detailed
analysis 2 years ago, which showed almost no class switched memory B cells,
normal CD21.

The GI process still rages out of control, such that she has been on TPN since
September.  The GI docs have tried numerous immunomodulatory agents over the
years which seem to provide only transient, if any, benefit, including oral
steroids (which she is now on chronically), Imuran, cyclosporin, Remicade,
Humira and most recently, Cimzia.  A 6 month trial of Cimzia has failed.

Thanks for any help or advice you can provide,
- Chris Wysocki, Yale Allergy and Immunology fellow