[PAGID] Disseminated mycobacterium

[Sergio Rosenzweig]

Dear Chris,
  Your patient certainly looks like IFNg/IL12/IL23 signaling pathway deficient. Regarding IFNg treatment, we usually use it on patients with IL12/IL23 deficient transduction or IFNgR1 dominant negative mutations (most frequent: 818del4, usually associated with osteomyelitis, not the picture of your patient). It will take Steve 1 day to define IFNg pathway integrity (through IFNg-induced STAT1 phosphorylation) and  and a few more days to define IL12Rb1 expression and functionality (through IL12-induced STAT4 phophorylation). On the other hand, IV antimycoabcterial drugs appear central in the manegement of these kids (especially those with IL12Rb1 deficiency that almost systematically present with GI machanical and/or absortion problems). One of our IL12Rb1 def patients presented with pericarditis/cardiac insufficiency when we treated him with IFNg (it happened twice).  Based on your patient's clinical status (she almost fullfil criteria for hemophagocytic syndrome), I would
 consider adding steroids to her treatment.
  Sergio
   
  Sergio D. Rosenzweig, MD, PhD
  Servicio de Inmunologia
  Hospital Nacional de Pediatria J. P. Garrahan
  Buenos Aires, Argentina
  srosenzweig at garrahan.gov.ar

Chris Seroogy <cmseroogy at pediatrics.wisc.edu> wrote:
  Dear Colleagues:

I would like your advice on management of a 19 m/o previously healthy
caucasion girl who presented 4 days ago with thrombocyopenia and anemia.
Her bone marrow biopsy revealed numerous AFB+ organisms. Her blood grew
mycobacterium and pneumococcus and her stool is growing mycobacterium.
Further identification is pending. She has tremendous hepatospenomegaly and
high fevers. Family history is incomplete as mother is adopted and parents
are unlikely related. She is fully immunized (including live vaccines). ALC
2020, IgG and IgM elevated for age. She is being treated with a "cocktail"
of antimicrobials for mycobacterium per our ID team and vancomycin. She
remains critically ill.

It seems likely that she has a defect in IFN-g/IL-12 axis. We will be
sending blood to Steve Holland next week. In the interim, I would like
opinions about using IFN-g (or perhaps IFN-a if this is a complete IFNR1
defect.) Have any of you empirically used IFN-g in this setting? Is there
any downside? How rapid should improvement be observed if there is a
functioning IFNR? Thank you for your insights, Chris


Chris Seroogy, M.D.

University of Wisconsin

Assistant Professor

Dept. of Pediatrics

Mail:  H4/474 CSC, Mailstop 4108

Shipping:  H4/431 CSC, Mailstop 4108

600 Highland Ave.

Madison, WI  53792

phone: 608- 263-2652

fax: 608-265-0164







       
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