[CIS PIDD] [cis-pidd] Renal transplantation in CVID

Tue Jun 9 01:35:23 EDT 2015

Dear Stan, Dear Jack, 

I agree with Jack clinically it sounds like NRH the unusual findings however are the granulomatous lesions and the increasing liver enzymes, although this can happen. Jack, we don't usually apply immunosuppressive treatment to NRH since the evidence is rather low that this is helpful. Like Mel asked which drug du you usually apply? IN this concrete case however with the presence of granulomatous disease and elevated enzymes Stan you might consider. IN case of portal hypertension, splenomegaly and hypersplenism we have successfully applied TIPS (usually however after the first bleeding event or advanced state of varicosis) which not only reduced the portal vein pressure but also improved the hypersplenism. We have seen NRH more often in the context of inflammatory GI disease, are there any signs for this? I would also recommend to exclude an infectious origin of the liver disease if not already done including atypical mycobacterial disease (we have currently one patient which looked like NRH and had granulomatous disease T cell infiltration of the liver due to atypical mycobacteria). if these are excluded I would try treating the patient with systemic steroids also for the renal disease, since we have one patient with interstitial nephritis who stabilized nicely on steroids despite advanced renal insufficiency. I would not wait for the transplant. 
In regard to the risk of immunosuppressive therapy yes you run the risk of increased infection, even opportunistic infection which you obviously need to control for. we add PjP prophylaxis in patients with high immunosuppression especially when the CD4 count drops under 200/µbut with the renal failure you have to probably go for pentamidine inhalation. 
these are my thoughts
Jack, I would be very interested in your experience with immunosuppression in NRH
best regards

klaus

Prof. Dr. med. Klaus Warnatz

MEDICAL CENTER – UNIVERSITY OF FREIBURG
Center for Chronic Immunodeficiency – CCI
Department of Rheumatology and Clinical Immunology

Breisacher Str. 117, 79106 Freiburg, Germany
Tel. +49 761 270 77640 / FAX -71000 / Pager 12-7100
klaus.warnatz at uniklinik-freiburg.de

www.uniklinik-freiburg.de/cci

________________________________________
Von: Stan Ress <stan.ress at uct.ac.za>
Gesendet: Dienstag, 9. Juni 2015 00:09
An: CIS-PIDD
Betreff: RE: [cis-pidd] Renal transplantation in CVID

Thanks so much to Bodo Grimbacher, Mary Hogan, & John Routes for your very helpful replies.

I think Jack's correct about the liver. I certainly assumed it was nodular regenerative hyperplasia based on my reading of this liver complication in CVID (Ward et al Clin & Exp Immunology: 2008, 153, 331-7, Fuss et al J. Clin Immunol 2013, 33(4) 748-58). The actual liver histology report described granulomatous inflammation with granulomas in the portal tract accompanied by an infiltrate of lymphocytes, histiocytes and eosinophils. There were necro-inflammatory foci in the lobule, also with inflammatory infiltrates. Reticulin stain showed foci of "focal nodular hyperplasia" with nodules of hyperplastic hepatocytes with liver cell plates two cells thick. Bile Sirius Red stain shows extensive pericellular fibrosis in zone 3. The inflamed portal tracts show fibrous expansion.

So this fits NRH rather than FNH? And needs more aggressive immunosuppressive therapy?

Thanks so much again.

Stan
-------------------------------------------------------------------------------------
Stanley Ress
Emeritus Associate Professor of Medicine, UCT
Specialist physician & Clinical Immunologist
UCT Private Academic hospital,
Anzio Road, Observatory,
Cape Town, 7925
South Africa
TEL:INTERN. + 2721-4421966 or 4421816
FAX:   "    + 2721-(0)865173095
Cell: 0833115482
email: stan.ress at uct.ac.za

-----Original Message-----
From: Routes, John [mailto:jroutes at mcw.edu]
Sent: 08 June 2015 10:06 PM
To: CIS-PIDD
Subject: Re: [cis-pidd] Renal transplantation in CVID

Stan
Are you sure the liver pathology wasn't nodular regenerative hyperplasia-certainly has the clinical features of this? If so, then immunosuppressives would be needed as this is increasingly recognized as a potentially fatal complication of CVID 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: Office 414-266-6840
Fax: 414-955-6487 (Clinical)
Fax: 414-955-6323 (Laboratory)
Email: jroutes at mcw.edu<mailto:jroutes at mcw.edu>

From: Bodo Grimbacher <bodo.grimbacher at uniklinik-freiburg.de<mailto:bodo.grimbacher at uniklinik-freiburg.de>>
Reply-To: CIS-PIDD <cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>>
Date: Monday, June 8, 2015 at 2:59 PM
To: CIS-PIDD <cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>>
Subject: Re: [cis-pidd] Renal transplantation in CVID

Dear Stan,
We have many patients with CVID and autoimmune features on immunosupressive treatment.
If you take care of good trough levels and give antibiotics early and long enough, the bronchiectatic lung disease may not progress at all.
Immunosupression may actually help the granulomatous complications seen in your patient.
So it is a clear option for your patient.
We do prefer steroids and MMF over the other immunosupressants though. Best, Bodo
****************************************
Univ.-Prof. Dr. med. B. Grimbacher

Scientific-Director
CCI-Center for Chronic Immunodeficiency
UNIVERSITÄTSKLINIKUM FREIBURG
Tel.: 0761 270-77731  Fax: -77744
Engesserstraße 4, 79108 Freiburg
bodo.grimbacher at uniklinik-freiburg.de<mailto:bodo.grimbacher at uniklinik-freiburg.de>
www.uniklinik-freiburg.de/cci

Von: Stan Ress <stan.ress at uct.ac.za<mailto:stan.ress at uct.ac.za>>
Antworten an: CIS-PIDD <cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>>
Datum: Monday 8 June 2015 21:42
An: CIS-PIDD <cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>>
Betreff: [cis-pidd] Renal transplantation in CVID

Dear Colleagues,

I would be grateful for advice regarding further management in a complicated case of CVID.

A 35 year-old lady was diagnosed with CVID in 2008 and commenced on IVIG. She has had a complicated course. In 2010  a chest CT scan showed bilateral bronchiectasis as a result of recurrent RTI's. She then developed hepatomegaly and progressive splenomegaly. Bone marrow trephines done at another centre in 2008 & 2010 showed normal T-and B-cell gene rearrangements, but she developed severe bicytopenia due to hypersplenism, and eventually required splenectomy in April 2014 when splenic size was 24 cm, platelet count < 80, WCC  < 1.5. US and MRI of liver indicated increased porta-venous shunting of blood with portal hypertension, liver biopsy reported features compatible with focal nodular hyperplasia (FNH) with T-cell infiltration but no B-cells present. Liver enzymes then progressively increased post-splenectomy (alkaline phosphatase & gamma GT especially), this has improved on low dose prednisone. However, her renal function had also deteriorated and simultaneous renal biopsy (at the time of splenectomy)  was reported as showing interstitial nephritis.

She is managed on SC Immunoglobulin replacement, her current renal function has been stable with serum urea of 22 mmol/L  (2.8-7.2), creatinine of 371 umol/L (estimated GFR of 12 ml/min). Her nephrologist is exploring the possibility of a live related renal transplant and asks about the experience in this regard. While the QOL on haemodialysis would be less good than following a renal transplant, my concern is for the effect of immune suppression on an already immunocompromised patient who also has bronchiectasis.

We would appreciate any advice and would also be grateful to hear of any other experience with regard to transplantation in CVID patients.

Many thanks.

Stan
-------------------
Stanley Ress
Emeritus Associate Professor of Medicine, UCT Specialist physician & Clinical Immunologist UCT Private Academic hospital, Anzio Road, Observatory, Cape Town, 7925 South Africa TEL:INTERN<tel:INTERN>. + 2721-4421966 or 4421816
FAX:   "    + 2721-(0)865173095
Cell: 0833115482
email: stan.ress at uct.ac.za<mailto:stan.ress at uct.ac.za>

________________________________
UNIVERSITY OF CAPE TOWN

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