[PAGID] Possible Autoimmune enteropathy

[sullivak at mail.med.upenn.edu]

Was the baby small at birth?  Is she microcephalic?
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-----Original Message-----
From: "Ciaccio, Christina, E" <ceciaccio at cmh.edu>
Sender: pagid-bounces at list.clinimmsoc.org
Date: Tue, 29 Jun 2010 14:33:39 
To: <pagid at list.clinimmsoc.org>
Reply-To: pagid at list.clinimmsoc.org
Subject: [PAGID] Possible Autoimmune enteropathy

Sorry for the lengthy email.  I have I case I wanted to run by everyone
(and tried to present as concisely as possible).

I am seeing a 10 month old girl who has been hospitalized since 2 months
of age with chronic bloody diarrhea.  Her biopsy on presentation showed
severe chronic inflammation of the stomach, duodenum and colon.
("apoptosis within the crypts of the gastric mucosa, segmental goblet
cells depletion within the duodenal mucosa, and active ulcerative
process within the colonic mucosa").  The pathologist suggested
diagnoses of autoimmune enteropathy vs. inflammatory bowel disease.
Considering her age of presentation, we were consulted to rule out
immunodeficiency.

Her IBD panel was negative and anti-enterocyte and anti-goblet cell
antibodies were not found.  At 2 months, her B, T, and NK cells were
normal.  Mitogen stimulation was normal.  IRAK-4, AIRE, TLR signaling
was all normal.  HIV negative. Adhesion molecules were normal.
Oxidative burst was normal.  She had detectable IgA, IgE and IgM.  Her
IgG has been low but not replaced as she has protein losing enteropathy
and has had only 1 infection requiring antibiotics to date.  Off
treatment, she has peripheral eosinophilia as high as 2000. 

Her treatment course is below:
-Mycophenolate with no normal levels
-Cyclosporin- developed good levels but not a good clinical response,
also had bad hirsutism and gingival hyperplasia
-Tacrolimus- developed better clinical response with goal troughs of
12-16 but could get no further clinical improvement
-Remicade- no detectable levels though treated with doses of 7mg/kg x2
and 10mg/kg x1, developed + antibodies after 3 doses
-Entocort- amazing clinical response with stable albumin and hemoglobin,
tolerance now to feeds and lack of vomiting
  
A 1st degree cousin was well known to our service. She had a similar
presentation at the same age, but her immune evaluation revealed low
CD3+ (low CD4+ and CD8+) cells and low IgG with normal B and NK cell
numbers.  Her mother (sister of our current patient's mother) has
autoimmune disease.  She was started on IVIG and later had no response
to bacteriophage.  She never developed other autoimmune disease.  After
much debate across several institutions, she was diagnosed with SCID and
went to transplant.  She passed as a result of very aggressive graft vs.
host. 

Any opinion about where to go for diagnosis from here?  We have talked
about NOD2, FoxP3, TGF-beta (IL-10 is pending), Artemis, RAG...

Thanks so much

Christina Ciaccio, M.D.
Faculty, Allergy, Asthma and Immunology
Children's Mercy Hospitals and Clinics
2401 Gillham Road
Kansas City, Missouri  64108
816-234-3097 (phone)
816-346-1301 (fax)