[CIS PIDD] [cis-pidd] Fw: HLH in SCid with CMV?

Thu Nov 2 16:03:54 EDT 2017

Thanks James -

I was reading about cases of presumed secondary HLH in SCID/CID (especially common gamma chain): "Haemophagocytic lymphohistiocytosis in X-linked severe combined immunodeficiency (Grunebaum, Roifman, 2000)";

"The syndrome of hemophagocytic lymphohistiocytosis in primary immunodeficiencies: implications for differential diagnosis and pathogenesis  (Bode et al 2014)."
These are so interesting because they are occurring primarily in X-SCID where there are no/extremely low T and NK cells..But I agree, it would seem unlikely to be primary HLH at this point...

He has 4% NK cells (52 cells/mcl).

He does not have specific features of DiGEorge (no hypocalcemia/no cleft palate/normal echo/no dysmorphic features). Parents are 3/4 Mennonite, but he does not have the usual T/B/NK profile of ZAP70, ADA or CD3 deficiency that we often see in this population.

Tamar

________________________________
From: cis-pidd at lyris.dundee.net <cis-pidd at lyris.dundee.net> on behalf of CIS-PIDD <cis-pidd at lists.clinimmsoc.org>
Sent: Thursday, November 2, 2017 2:51:58 PM
To: CIS-PIDD
Subject: RE: [cis-pidd] Fw: HLH in SCid with CMV?

Tamar

I agree with IVIG and maybe steroids.  I would be cautious of etoposide.  Not sure this is HLH.  No fever.  No splenomegaly.  No hemophagocytosis (not very sensitive I know).  All can be explained by bad CMV in the setting of SCID.  CD25 is likely unreliable if you don’t have T cells…and if you don’t have T cells then how can you have primary HLH.

Regardless I think treating as you have planned +/- steroids and see if the T cell counts come back.  What was the NK count?  I know NK cells like to disappear when sick, but trying to fit this with IL7R deficiency.  Any signs of DiGeorge or CHARGE??

Best

James

James W. Verbsky M.D./Ph.D.

Associate Professor of Pediatrics and Microbiology

Medical Director, Clinical Immunology Research Laboratory

Medical Director, Clinical and Translational Research

Medical College of Wisconsin

Milwaukee, WI

From: cis-pidd at lyris.dundee.net [mailto:cis-pidd at lyris.dundee.net] On Behalf Of CIS-PIDD
Sent: Thursday, November 02, 2017 2:12 PM
To: CIS-PIDD <cis-pidd at lyris.dundee.net>
Subject: Re: [cis-pidd] Fw: HLH in SCid with CMV?

Thank you so much for the advice. I gave 1 gram/kg of the IVIG (5 grams) - rather than 0.5 g/kg, which seemed to result in significant improvement in his CBC. I will consider giving a second dose as well. I briefly had him on 2 g/kg/day of prednisone (more so as an addition for empiric PJP treatment ), but was worried in the context of his significant CMV viremia (once those results returned), so stopped it. We are awaiting the HLA typing results and trying to control the infection, but will certainly not delay definitive treatment while awaiting the genetic panel.

Thank you again,

Tamar

________________________________

From: cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net> <cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>> on behalf of CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>>
Sent: Thursday, November 2, 2017 12:59:43 PM
To: CIS-PIDD
Subject: Re: [cis-pidd] Fw: HLH in SCid with CMV?

Dear Tamar,

Partial or full-blown presentations of (2') HLH can occur in (S)CID patients, typically infection associated.

In addition to CMV directed therapy high dose (2g) IVIG may help you to dampen the immune activation. I would also not hesitate to use steroids. If things threaten to get out of control, conditioning for haplo rather than etoposide would be my last resort.

Do not wait for genetics for your clinical decisions!

Best wishes, Stephan

Von meinem iPhone gesendet

Am 02.11.2017 um 17:35 schrieb CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>>:

Hello all - my apologies if this is being sent a second time, but I am not sure if the first email went through.

I would greatly appreciate your expert management advice on a 3 month old boy with suspected SCID and disseminated CMV infection, with some HLH-like features.

My main question is regarding treatment for immune activation versus simply trying to treat infection (and of course any other suggestions for managing the severe infection). On a secondary note- what is the role of holding breastfeeding  in the context of established CMV infection?

Here is the story:

3 month old boy with some HLH features but not meeting criteria: Ferritin >3500, pancytopenia with hemoglobin 70 g/L, platelets 20 x 10^9/L, WBC 2-5 x 10^9/L, hypofibrinogenemia, hypertriglyceridemia, massive hepatomegaly, normocellular bone marrow in keeping with inflammatory/reactive process without hemophagocytosis; no fever and no splenomegaly at any point, normal soluble IL2R levels). Not enough T cells or NK for Cd107a, Perforin/granzyme expression. He has prominent neurologic symptoms (seizures, irritability) with increased protein and cell count in CSF (evenly lymphocytes, neutrophils and monos/macro), but no infections identified there (CMV PCR pending). He has rising liver enzymes (AST, GGT both in hundreds). MRI/CT brain normal. Worsening bilateral infiltrates and ground glass opacities on CXR and CT chest, small effusion. He is on low flow oxygen.

His immune workup showed almost no T or NK cells (36 cells/mcl T cells) on two occasions, but normal B cells in peripheral blood (similar distribution in the marrow). He has low IgG 1.5 g/L, absent IgA, and normal IgM (0.27 g/L). No thymus seen on CT/CXR (acknowledging he is sick/stressed), no secondary lymphoid tissue on exam. Diarrhea since receiving rotavirus 1 month ago (however no rotavirus in stool- repeat pending).

Pending investigations: SAP, XIAP, CD132 by flow; mitogen proliferations, TRECs (retrospectively since we don’t screen in this province yet), CD45Ra/Ro/recent thymic emigrants, bronchoscopy infectious results, Genetic panel for SCID.

Current management includes:

-IVIG replacement recently given

-Septra PJP treatment dose

-Gancyclovir

-Ceftriaxone

Thank you so much!

Sincerely,

Tamar Rubin

Tamar Rubin, MD, FRCPC

Pediatric Clinical Immunology and Allergy

University of Manitoba

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