[CIS PIDD] [cis-pidd] CVID, hyper-eosinophilia, lymphadenopathy

[Bleesing, Jacob]

Zach:

Thanks for sharing this interesting case. It reads like a textbook case of a CVID patient that does NOT (and will never) belong in the San Remo green piece of the pie-chart  (26% - Infections Only group) in  the paper by Helen Chapel and Charlotte from 2009.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2718064/figure/F2/


For as long as I can remember, cases like this have been shared through the CIS list server, and it seems to me that we (as the Experts) continue to struggle with managing these patients. From an anticipatory (healthcare) standpoint, we seem to be diagnosing these complications like we are announcing a hurricane when we and everything around us is already flying through the air (reacting to issues/complications rather than anticipating and preventing them).

There has to be a better way. If not us, then who? The assorted Subspecialists (Pulmonologists, Hematologists, Oncologists, Gastroenterologists, to name a few) that get involved to take care of the complications?


Thus - -

I would propose that we establish a CVID Treatment Consortium [CVIDTC).

The main goal would be to develop and /or use diagnostic guides, consensus/ treatment protocols, etc., for example, as it relates to these interrelated topics:

CVID - classification (integrating genotyping with immunophenotyping, etc.). It seems to me that sufficient data and tools are now available such that the future Troublemakers can be identified early on (like Zach's patient). This ties into:

CIVD - treatment strategies (beyond IVIG [been there; done that] and including who/when/how to transplant). With regard to BMT, we could consider interfacing the consortium with established entities such as PIDTC, EBMT, the Westhafen Intercontinential Group (http://www.ncbi.nlm.nih.gov/pubmed/23883618), as it relates to defining the parameters and contexts of HCT in the treatment of CVID, etc., etc. Zach's patient is perfect example of potentially missed opportunities.

CVID - the "4th dimension" (the dimension of time, as coined by Warnatz et al)

CVID -  the "5th dimension" (patient-relevant research - genomic, immunologic and beyond  -what tools [not influenced by IVIG for example] are relevant and how to get them into the clinical testing arena - apples compared to apples).


These are just some initial thoughts!


J


From: Zachary D. Jacobs, MD [mailto:zjacobs.md at gmail.com]
Sent: Wednesday, December 11, 2013 11:29 AM
To: CIS-PIDD
Subject: [cis-pidd] CVID, hyper-eosinophilia, lymphadenopathy

Hello all,

I am hoping for some help in a case.  He is a man with CVID who I have been following for the last couple of years.  Here is the rundown:

*         Currently he is a 39 year-old man with CVID, diagnosed at the age of 15.  He was  having recurrent sinopulmonary infections at the time and responded well to IVIG when started.  Currently receives he 55 grams IV every four weeks with troughs in the 800 - 900 mg/dl range.  He has undetectable IgA with normal IgM in the 100-150 mg/dl range.
*         Age 26, developed AIHA.  Treated with splenectomy and corticosteroids.  Was also noted to have persistent lymphadenopathy at that time.  Biopsy of LN showed polymorphous lymphoid aggregrates as well as atypical follicular hyperplasia.  There was no concern for a malignant process based upon flow cytometry and immunohistochemistry
*         Age 32, developed ITP which was treated successfully with corticosteroids.
*         Age 34, developed progressive dyspnea and respiratory complaints with pulmonary lesions.  He underwent a lung biopsy via VATS at that time and a biopsy of a nodule showed bronchiolitis with organizing pneumonia. Biopsy of a pulmonary lymph node showed a polymorphous population of lymphocytes, mostly T-cells mature T-cells with a normal ratio.  The histological architecture was normal and the final diagnosis was a reactive lymphoid hyperplasia without features of a lymphoproliferative disorder.
*         His PFTs have remained within normal limits and until recently q 6 months CT scans were stable.
*         Nearly concurrent with his diagnosis of follicular bronchiolitis he developed hypereosinophilia.   His absolute eosinophil count since then has waxed waned since then but it is never less than a 1,000 cells per microliter and upon review of his record since then it has gone as high as 4000 cells per microliter on one occasion.  His average AEC is about 2500.
o   Hypereosinophilia is moderately steroid sensitive when they are used short term (takes AEC down to about 800).  Hydroxycholoroquine has no effect and he has been resistant to undergo treatment with other agents such as azathioprine.
o   Echo obtained ~ 6 months ago was normal.
o   Bone marrow biopsy obtained about six months ago showed no molecular defects associated with hyper-eosinophilia syndrome.
*         Limited CT scan of sinuses show near complete opacification of sinuses with nasal polyposis.
*         B-cell subset analysis shows low switched memory-B cell counts and low CD21 expression.  CD4, CD8 and NK cell numbers were normal with normal relative frequencies.
*         Bronchoscopy with BAL in August 2012 as well as last month showed negative cytology, no eos, and negative cultures.
*         About six weeks ago he had increased shortness of air and fatigue.  He went to the ER where an echo showed hyperdynamic left ventricle function and right ventricular dilatation with moderately reduced systolic function.  He was found to have severe pulmonary hypertension with PA pressure 90/54.  Remodulin was started.
*         CT scans showed interval development of multiple discreet large pulmonary nodules bilaterally predominately in the lower lobes.  He also had interval development of mediastinal hilar lymphadenopathy.  Abdominal scan showed stable retroperitoneal and peritoneal adenopathy.
*         PET scan showed extensive mediastinal axillary, peritoneal and inguinal hypermetablic lymphadenopathy.  He had a dominant right lower lob infiltrate with increased uptake.  Multifocal pulmonary nodules also had increased FDG intake.  Nuclear med bone marrow scan showed no evidence of extramedullary hematopoiesis.  SPECT imaging showed no evidence of abnormal accumulation in any of the pulmonary modules.
*         Flow cytometry of peripheral blood and axillary lymph nodes showed no evidence of monoclonality or increased blasts.
*         The biggest problem right now is an open lung biopsy cannot be performed because of his pulmonary hypertension.  He is scheduled for another bronchoscopy next week, at which point a transbronchial biopsy can be obtained.

Any thoughts on these findings, especially in the context of his longstanding hyper-eosinophilia, would be much appreciated.  Further approaches to his diagnosis and treatment would also be great.  Sarcoid-like disease associated with CVID would otherwise be high on my differential because it can theoretically be associated with eosinophilia, but prior biopsies have failed to show any granulomatous inflammation.  ACE level, for what it's worth, was very mildly elevated at 69 (reference range 12 - 68 U/L).

Thanks, as always, for the help.

Zach

--
Zachary D. Jacobs, M.D.

The Center for Allergy & Immunology

Saint Luke's Physician Partners
Medical Plaza II
4330 Wornall, Suite 40
Kansas City, MO 64111

Ph: 816.531.0930
Fax: 816.753.2671

CONFIDENTIALITY NOTICE. This e-mail and attachments (if any) may contain information that is confidential, proprietary, privileged or otherwise prohibited by law from disclosure or re-disclosure. This information is intended solely for the individual(s) or entity(ies) to whom this e-mail or attachments are addressed. If you have received this e-mail in error, you are prohibited from using, copying, saving or disclosing this information to anyone else. Please destroy the message and any attachments immediately and notify the sender by return e-mail. Thank you.

P Please consider the environment before printing this message.


---

The CIS-PIDD listserv is supported by:

[http://www.clinimmsoc.org/UserFiles/image/cis-pidd-list-logo_v1.jpg]
The science & practice of human immunology

P: +1.414.224.8095
E: info at clinimmsoc.org<mailto:info at clinimmsoc.org>

Not a member of CIS? Please visit www.clinimmsoc.org<https://cis.execinc.com/edibo/Signup> to join!

You are currently subscribed to cis-pidd as: jack.bleesing at cchmc.org<mailto:jack.bleesing at cchmc.org>.
To unsubscribe click here: http://lm.clinimmsoc.org/u?id=183824396.60ab2025d9ab67496282f5c977f33e12&n=T&l=cis-pidd&o=44230585

---
The CIS-PIDD listserv is supported by the Clinical Immunology Society
The science & practice of human immunology

P: +1.414.224.8095
E: info at clinimmsoc.org

Not a member of CIS? Please visit www.clinimmsoc.org to join!

You are currently subscribed to cis-pidd as: pagid at list.clinimmsoc.org.
To unsubscribe click here: http://lm.clinimmsoc.org/u?id=183939985.3ea13d40a15475ac00ebbd9cd8a37d6d&n=T&l=cis-pidd&o=44234888
or send a blank email to leave-44234888-183939985.3ea13d40a15475ac00ebbd9cd8a37d6d at lists.clinimmsoc.org
-------------- next part --------------
An HTML attachment was scrubbed...
URL: <http://seven.pairlist.net/pipermail/pagid/attachments/20131212/40e62e9d/attachment.html>