[CIS-PAGID] Rituximab and Chronic ITP

[Seppänen Mikko]

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