[PAGID] 22q11 deletion and granulomas

[Chinen, Javier]

These 'sterile' granulomas are always a challenge.
I would first establish degree of T cell deficiency found within the 22q11.2 spectrum by measuring naïve CD4 T cells, and also look at memory B cells to help assessing humoral immunity. Secondary immunodeficiencies may need be in consideration: immunosuppresion for Evans syndreom, HIV infection in adolescents.

Besides clinical history, it may be helpful to look at specific antigens, and Fungitell (though not good for Crypto and Blastomyces) and Aspergillus galactomannan looking for negatives that would help decision on steroids. We also send tissue for mycobacteria PCR (though no high yield if AFB not seen)
Donors for IgG products are supposed to be healthy, though we and others have found antibodies for infectious diseases at diagnostic titers in scid patients receiving IVIG before immunoreconstituion.

Javier
________________________________
From: pagid-bounces at list.clinimmsoc.org [mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of MacGinnitie, Andrew
Sent: Tuesday, July 06, 2010 7:57 AM
To: pagid at list.clinimmsoc.org
Subject: [PAGID] 22q11 deletion and granulomas

I'd appreciate any input on the following patient, who I met for the first time last week

15 year old girl with 22q11.2 diagnosed by FISH at age 9 secondary to hypocalcemia, heart defects (VSD and PDA) and Evans syndrome (autoimmune thrombocytopenia and anemia).

She has also had severe lichen planus primarily on the legs that has not responded to topical steroids.  She had one lesion that became superinfected and needed 6 months of therapy by a wound clinic

Over the last few years she has had several CXR diagnosed pneumonias which have typically responded to antibiotics as well as some sinus infections.  Another immunologist started her on subcutaneous IgG replacement 9 mos ago based on the history of pneumonias and low normal IgG (564) with normal IgA and IgM.  She had an adequate response to Tetanus but responded to 1/14 pneumococcal serotypes (no  vaccination).  Interestingly, she feels the SCIG has improved her lichen planus.

Last fall she had cough, shortness of breath and chest pain that she attributed to another pneumonia.  A course of azithromycin didn't help and a repeat CXR showed a nodular pattern, that on reexamination was present on the first CXR.

She got CT, brochoscipy  with BAL and then transthoracic biopsy that revealed granulomas but no organisms were visualized or grew in culture.  The pathologists initially thought these were likely infectious but on reexamination don't feel they can rule out sarcoidosis although they don't think the lesions are typical.
A PPD was negative

The lesions are being followed by CT and seem to be slowly getting worse although clinically she is well.  ID felt that serologies for possible fungal causes like Cryptococcus, blastomycosis and histoplasmosis would be uninterpretable due to IgG replacement

A literature search turned up an abstract at the AAAAI several years ago of 3 patients with 22q11 and sarcoid but not much else

I wonder if anyone has seen a similar case or has other ideas.
I also wonder if anyone knows if there are significant antifungal titers in IgG products.

Given the diagnostic uncertainty and possible infectious etiology  we are hesitant to treat with steroids unless we have too.

Thanks

Andy


Andrew J. MacGinnitie MD PhD
Assistant Professor of Pediatrics
Division of Pulmonary Medicine, Allergy and Immunology
Children's Hospital of Pittsburgh
45th Street and Penn Ave 15201
andrew.macginnitie at chp.edu
412/692-8903 (office) 412/692-8499 (fax)


------------------------------------------------------------
CONFIDENTIALITY NOTICE:
 The information in this e-mail may be confidential and/or
 privileged.  If you are not the intended recipient or an
 authorized representative of the intended recipient, you
 are hereby notified that any review, dissemination, or
 copying of this e-mail and its attachments, if any, or
 the information contained herein is prohibited.  If you
 have received this e-mail in error, please immediately
 notify the sender by return e-mail and delete this e-mail
 from your computer system.  Thank you.
============================================================
-------------- next part --------------
An HTML attachment was scrubbed...
URL: <http://seven.pairlist.net/mailman/private/pagid/attachments/20100706/9d814b6b/attachment-0001.htm>