[CIS-PAGID] Rituximab and Chronic ITP

[Routes, John]

Rapheal
The IgG level is not low enough to be certain of CVID. Did you order an IgA
or IgM? If one or both were low would help in the diagnosis although I would
not call a definitive diagnosis this close to rituximab therapy. I would
likely keep on IVIG until the late spring, stop and determine the ability to
make specific Ab after 3-4 months off IVIG. At that point, the rituximab
effect would likely be gone (check flow) and he would be going into the
summer months with a lower risk of infection. Autoimmunity  affecting 2 or
more hematopoietic lineages is a risk factor to develop CVID, so the patient
should be monitored regardless of the immune assessment in the summer. Would
not make much of the flow at this point as ongoing immune dysregulation and
viral infection will increase CD4RO+ cells (would also predict that the CD8
population would be expanded and/or activated as well). Repeat flow studies
in the summer, when clinically stable  and include B cell subsets.
Jack


John M. Routes, MD
Chief, Section of Allergy and Clinical Immunology
Professor of Pediatrics, Medicine, Microbiology and Molecular Genetics
Department of Pediatrics
Children's Hospital of Wisconsin
Medical College of Wisconsin
9000 W. Wisconsin Ave.
Milwaukee, WI  53226-4874
 
Phone: 414-456-4802; 414-266-6997
Fax: 414-456-6487 (Clinical)
Fax: 414-456-6323 (Laboratory)
Email: jroutes at mcw.edu
 




> From: Seppänen Mikko <Mikko.Seppanen at hus.fi>

> Reply-To: "pagid at list.clinimmsoc.org" <pagid at list.clinimmsoc.org>

> Date: Wed, 7 Dec 2011 00:17:21 -0600

> To: "pagid at list.clinimmsoc.org" <pagid at list.clinimmsoc.org>

> Subject: Re: [CIS-PAGID] Rituximab and Chronic ITP

> 

> Dear Raphael,

> 

> testing vaccine responses at this phase would also be problematic, since he

> has recently gotten rituximab. Though IgM-levels correct within 6 months,

> vaccine responses can be secondarily low for at least 18 months, though

> studies to assess this are few.

> 

> Low NK- and CD4-levels are common in CVIDs, at least in Finland (even when

> B-cells normal), reduced thymic output seen as well (though B-cells normal, I

> would however ask to exclude thymoma, when I would check his HRCT anyway, to

> rule out bronchiectasis as a part of early clinical evaluation, especially if

> mitogen responses are low, and ask to assess the size of spleen at the same

> time). Evans' syndrome, low IgG (which partly may be caused by rituximab

> anyway) and the findings make one think of developing CVID, though other

> immunodeficiencies should be excluded along the way (listed in the

> below-mentioned article and additional PIDDs for example in Rezaei N et al.'s

> book/Springer. 

> 

> There is an excellent recent, country-wide, study from France on Evans and

> associated diseases (non-PIDD and PIDD, a.o. J-L Casanova is author), worth

> reading!

> 

> I would go on with therapy, then test vaccine responses >18 months after

> rituximab, and after at least 5 months since therapy has been stopped. Thus

> the break in therapy should be during "non-flu season". If he is recovering

> from encephalitis, I would however also be wary of enteroviral infection (when

> IgG trough probably should be kept >10-12 g/l), if it actually is enteroviral

> encephalitis and he recovers, I would ponder whether I am ready to have a

> break in therapy for testing...

> 

> Yours

> mikko

> __________________________________________________

> Mikko Seppänen, MD, PhD

> Specialist in Internal Medicine and Infectious Diseases

> Senior Consultant, Physician in charge (PIDD)

> Immunodeficiency Unit

> Division of Infectious Diseases

> Department of Medicine

> Helsinki University Central Hospital

> Hospital District of Helsinki and Uusimaa

> Aurora Hospital, Ward 4-2 and Outpatient Clinic

> P.O.Box 348

> FI-00029 HUS, Helsinki

> FINLAND

> phone +358 9 47175923, fax +358 9 47175945

> EM(E)A Expert, PIDDs and Intravenous Immunoglobulin Therapy

> 

> _________________________________________

> 

> -----Alkuperäinen viesti-----

> Lähettäjä: pagid-bounces at list.clinimmsoc.org

> [mailto:pagid-bounces at list.clinimmsoc.org] Puolesta John Ziegler

> Lähetetty: 7. joulukuuta 2011 1:43

> Vastaanottaja: pagid at list.clinimmsoc.org

> Aihe: Re: [CIS-PAGID] Rituximab and Chronic ITP

> 

> Was CSF cultured for enteroviruses?

> 

> -----Original Message-----

> From: pagid-bounces at list.clinimmsoc.org

> [mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of Rafael Firszt

> Sent: Wednesday, 7 December 2011 7:26 AM

> To: pagid at list.clinimmsoc.org

> Subject: [CIS-PAGID] Rituximab and Chronic ITP

> 

> I am seeing a 14 yo boy with a history of chronic ITP and neutropenia who got

> Rituximab in March of this year.  He was just admitted to hospital with

> encephalitis of unknown cause. Before Rituximab was given he had an IgG of

> 478.  Since being admitted he got a dose of IVIG but no functional studies

> have ever been done on him.  He has no history of other infections.

> 

> His Enumeration drawn last week shows:

> CD4:CD8 Ratio:   ratio  * 1.05

> % CD19:  %  * 12 

> % Natural Killer Cells:    * 3 L

> % CD3:  * 84  

> % CD2:  %   86  

> Absolute CD4   * 373 L

> CD4+CD45RO+ cells   * 249

> Absolute CD45RA   * 112 L

> Absolute CD8   * 356

> Absolute CD19   * 105

> Absolute Natural Killer Cells   * 30 L

> Absolute CD3  * 747

> 

> Therefore he has low NK cells, low CD4 and low CD45RA.  It is interesting that

> his B cell count is normal.

> 

> He has ongoing work-up for his encephalitis but ID feels it is most likely

> virally-induced. 

> 

> I can't test him for function because of recent IVIG.

> 

> With history of ITP, neutropenia, initial low IgG and now encephalitis he

> likely has a form of CVID (I think).

> Based on this history I several questions:

> 

> 1) Any other investigations?  (I have mitogen studies pending)

> 2) Would you continue IVIG monthly assuming he has CVID or would you stop and

> re-evaluate his function after several months to confirm the possible CVID

> 3) In CVID or after rituximab, have any of you seen low NK cells and low CD4

> and low CD45RA in either of these situations?

> 

> Thanks for any help

> 

> Rafael Firszt

> University of Utah