[PAGID] NEMO colitis

[Jordan Orange]

Dear Stephan,

This timeframe is consistent.  In two patients, however, colitis  
appeared earlier.
In some it has been very difficult to discern histologically from GvHD  
although this does not seem to be the case with your patient.

The mechanism is most probably as you propose, as the patients with  
which I am familiar have had at least some engraftment and where  
measured some (or complete) restoration of TLR function.

Steroids seem to be uniformly useful, although clearly less than ideal  
as a long term option.
Oral vancomycin + sulfasalazine has been useful in one child and has  
he been able to wean off steroids (although this took over two years).
Infliximab has been tried in one patient with some early encouraging  
results - on the surface this would make sense mechanistically as his  
hematopoietic immunity has largely normalized.
6MP has not seemed to add much benefit.

Regarding prognosis, this is a complex issue. Of the patients which I  
am aware, I believe this intestinal issue contributed to the eventual  
demise of two.  Another seems to be doing well, and has come off of  
steroids, but has had E. Coli septicemia while being otherwise  
healthy.  Another is in thick of things presently and it is too early  
to say.
I look forward to hearing the experience of others.

As you point out, pre-existing "IBD" is not necessarily a predictor  
for the development of this post-transplant phenomenon.  In actuality  
the mechanism of the pre- and post-transplant phenomena may be  
overlapping but distinct.
Thus, the issue overall and role of transplantation warrants ongoing  
and careful consideration.

Very best,

Jordan

Jordan Orange MD/PhD
University of Pennsylvania School of Medicine
Children's Hospital of Philadelphia, Division of Immunology
3615 Civic Center Blvd,  ARC-1016H
Philadelphia, PA 19104
(Voice) 267-426-5622
(Fax) 267-426-5727
www.orangelab.org

On Jul 8, 2008, at 6:01 AM, Stephan Ehl wrote:


> Dear Colleagues,

>

> a 2 year old boy with NEMO deficiency (full EDA-ID phenotype with  

> pneumocystis, 2xinvasive staph, 2x enterococcal meningitis) was  

> transplanted 8 months ago from his HLA-identical carrier sister  

> (symptomatic with uveitis and aphtous stomatitis). He did not have  

> colitis before the SCT, the procedure went well and he is now a full  

> chimera.

>

> One months ago he started to develop steroid-responsive colitis  

> (requiring about 1 mg/kg for good control) with a histological  

> picture of severe erosive inflammation with extensive  

> intraepithelial neutrophils. No evidence of GvHD or infectious (eg.  

> atyp. MB) disease.

>

> We anticipated this complication due to the persisting epithelial  

> NEMO deficiency, but are not sure about an appropriate (steroid- 

> sparing) treatment concept. We would appreciate input concerning the  

> following questions:

> 1. steroids and antibiotics?

> 2. sulfasalazine/azathioprine?

> 3. biologicals?

> 4. prognosis?

>

> Jordan, you told me previously that you have seen colitis develop  

> after SCT in NEMO - was the time frame similar? was it also  

> independent of GvHD?

>

> Thanks for your help,

>

> Stephan

>

> Prof. Dr. Stephan Ehl

> Immunologie/Rheumatologie

>

> UNIVERSITAETSKLINIKUM FREIBURG

> Zentrum für Kinderheilkunde und Jugendmedizin

> Mathildenstrasse 1, 79106 Freiburg

>

> Tel +49 761 270-4309 (4301) / Fax -4599

> stephan.ehl at uniklinik-freiburg.de

> http://www.uniklinik-freiburg.de/kinderklinik/live/forschung/immunologie.html

>

>


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