[CIS-PAGID] IPEX question

[Torgerson, Troy]

Elena,


1.        I would switch from Sirolimus to IV Tacro and push the dose.  In our experience, Sirolimus works well for maintenance once inflammation has been settled down but Tacro works better as a controller.  I would give it IV since he is likely malabsorbing and push the dose to get trough levels in the 10-12 range.  Even with this, his diarrhea may not fully settle down.  If he continues to stool out and you are running into electrolyte problems because of it, it is sometimes easier to put them on bowel rest and just nitrify them with TPN and lipids as you tune them up for transplant.  With aggressive supportive care (TPN/lipids, careful monitoring for signs of diabetes & thyroid disease, carefully watching his electrolytes (by the way, his Mg++ will drop out on the Tacro), careful monitoring of his other organs, etc.) you should be able to get him tuned up and ready for transplant - it isn't uncommon for these guys to look terrible initially.

2.       As Kate indicated, IPEX kids can have lung inflammation and that could contribute to his lung disease.  These kids can develop autoantibodies to virtually anything so Myesthenia may be a possibility although it has never been described and we have never seen it in our cohort of over 60 patients with mutations.  We did however recently have a prenatally diagnosed IPEX baby die at about 36 hours of age due to severe lung hypoplasia without a clear etiology, even at autopsy - this has never been described before but in light of that, I would be suspicious whether your patient may also have a degree of hypoplasia.  If this is the case, he is small and may be able to grow more lung if you can get him through transplant with the lungs he has.

3.       As suggested, I would move toward transplant soon, working hard to tune him up in the mean time.  In a child like this who is very high risk, I would probably suggest a matched bone marrow donor with a minimal intensity conditioning regimen.  We have had success getting nice stable MUD grafts into very sick IPEX kids with a regimen consisting of pre-transplant Flu and low-dose TBI followed by post-transplant CSA/MMF for GVHD prophylaxis (Burroughs et al. JACI 126:1000-5 (2010)).  Elie's suggestion of using a cord as a way to get a rapid donor is a good one and we have had great success with cord donors in IPEX but my concern with this kid is that in order to get a stable cord graft in, you will need to use a more aggressive conditioning regimen and transplanting him while on a vent is going to be tricky even using a minimal conditioning regimen.

Best,

T

Troy R. Torgerson, MD PhD

Assistant Professor, Pediatric Immunology/Rheumatology
University of Washington, Department of Pediatrics

Director, Immunology Diagnostic Laboratory (IDL)
Center for Immunity and Immunotherapies
Seattle Children's Research Institute
1900 9th Ave., C9S-7
Seattle, WA  98101-1305

Tel:  (206) 987-7450
Fax:  (206) 987-7310

Email:  Troy.Torgerson at seattlechildrens.org<mailto:Troy.Torgerson at seattlechildrens.org>

From: pagid-bounces at list.clinimmsoc.org [mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of Perez, Elena
Sent: Tuesday, October 04, 2011 7:23 AM
To: pagid at list.clinimmsoc.org
Subject: [CIS-PAGID] IPEX question

Dear All,

We have a 3mo baby with IPEX confirmed (1156 C>T; R386C) in the hospital, with DM on insulin drip, diarrhea, dermatitis who is vent/trach dependent (able to breathe over the vent but requiring a little extra PEEP to help), unable to wean off (transferred from outside hosp w/ trach and on vent). He only weighs 3.1 kg. We have him on sirolimus (levels ~15-25) and steroids, although not yet noting improvement in stools. On TPN and minimal NG feeds.

My question(s) to group is:

1.       Any thoughts on possible reversible/treatable reasons why he could be trach/vent dependent related to IPEX? (neuro consult --considered Myasthenia testing and muscle bx pending)...

2.       Prognosis doesn't seem too good, but family meeting w/ PICU, Transplant, Immunology on Friday to discuss BMT. Any insights? hope?

Appreciate thoughts.

Thanks,

Elena Perez, MD, PhD
Division of Allergy, Immunology, Rheumatology
University of South Florida
All Children's Hospital
St. Petersburg, Florida





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