[CIS PIDD] [cis-pidd] ?SCID with severe neutropenia

Sun Dec 10 13:38:13 EST 2017

The B cells numbers are low and this seems a little leaky.  Did you get skin fibroblast culture when you did skin biopsy?  You should consider doing radiation sensitivity testing which is something we could do for you if you had fibroblasts.  Mayo (Roshini Abraham) has a new assay using peripheral blood and if it’s positive it would be informative; if negative then would do fibroblasts which is the “gold” standard.

We see neutropenia not infrequently with SCID and not with any particular SCID genotype.  A single dose of GCSF may not be sufficient so would try giving for several days before giving up.  They usually will respond.

Mort

Morton J. Cowan, M.D.
Allergy, Immunology, and Blood and Marrow Transplant Division
UCSF Department of Pediatrics, Box 0434
550 16thSt., Floor 4
San Francisco, CA 94143-0434
Cowan office:
Smith Building, CVRI MC:3118
555 Mission Bay Blvd South, Room 252J
PO Box 589001
San Francisco, CA 94158-9001
Cowan Lab
CVRI-MC:3118
555 Mission Bay Blvd South, Room 282
PO Box 589001
San Francisco, CA 94158-9001

Phone: 415-476-2188  Office phone: 415-476-2659
FAX: 415-502-4867 (clinical) 415 476-5356 (academic)

**Confidentiality Notice** This email communication and any attachments may contain confidential and privileged information for the use of the designated recipients named above. Distribution, reproduction or any other use of this transmission by any party other than the intended recipient is prohibited.

From: <cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>> on behalf of Immunology Listserve <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>>
Reply-To: CIS-PIDD <cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>>
Date: Friday, December 8, 2017 at 2:28 PM
To: CIS-PIDD <cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>>
Subject: [cis-pidd] ?SCID with severe neutropenia

I wanted to reach out about a patient who came to us because of positive newborn screen and an original TREC level of 3.  She is now  1 month old with presumed SCID.

Flow showed (repeated and confirmed results):

CD3-80

CD4-29

CD8-19

CD19-75

CD16/56-460

CD45/4/RA-4 (15%)

CD45/4/R0-22 (77%)

CD45/8/RA-11 (57%)

CD45/8/R0-6 (31%)

56% of CD4+ cells and 9% of CD8+ are positive for HLA-DR.

ALC has remained low (500-700 depending on day) and absolute neutrophil count is zero, she has not responded to G-CSF (2 different occasions).  She also has a very faint erythema and scaling (honestly not that bad at all and nothing like omenn I have seen, but also definitely not normal skin).  IgE is <2 and eosinophils have been normal.  No lymphadenopathy and no hepatosplenomegaly.  She had spectratyping that came and showed oligoclonal/non-Gaussian distribution, polyclonal expression in 3 families of TCR V beta repertoires.   Proliferation was normal to PHA for % of CD45-53.5% (normal>49.9) and CD3-83.1 (normal>58.5), not enough cells for PWM.

Genetic testing showed a heterozygous variant of unknown significance in PRKDC c.5446C>T (p.R1816C).  Not present in ExAC and predicted to be deleterious, but heterozygous.  Also tested and no pathogenic variants in ADA, AK2, ATM, CD3D, CD3E, CD3Z, CORO1A, DCLRE1C, DOCK8, FOXN1, IL2RG, IL7R, JAK3, LIG4, NHEJ1, ORAI1, PNP, PTPRC, PRKDC, RAC2, RAG1, RAG2, RMRP, STIM1, TBX1, ZAP70.

Skin biopsy

Examination of the biopsy reveals orthokeratosis and a relatively unremarkable epidermis overlying a mildly dense superficial and mid dermal periadnexal and interstitial infiltrate composed of lymphocytes, histiocytes, scattered neutrophils and rare eosinophils. To better evaluate the infiltrate, immunohistochemical stains were performed. The infiltrate is composed predominantly of CD20 positive B cells. Very rare scattered CD3 positive T-cells are present, with retention of CD5 and CD7 expression. The CD4 to CD8 ratio is within normal limits; however, very few T-cells are present. C25 and CD30 are negative. The Ki-67 proliferative index is approximately 30% within the infiltrate. Neither fungal microorganisms nor basement membrane changes are seen with interpretation of a PAS histochemical stain.

Overall, the findings are relatively mild and not entirely specific. Given the composition of the infiltrate, we considered the possibility of a dermal hypersensitivity reaction, such as urticaria, a drug eruption, or an arthropod bite eruption; however, this does not seem to fit the clinical impression. We also considered the possibility of a viral exanthem. The findings present in the current biopsy do not show an increased population of activated T-cells, as can be seen in Omenn syndrome. These findings are best interpreted in correlation with physical findings, clinical history, and the results of additional studies, as clinically indicated

We just got the results on genetic testing back today and are attempting to figure out the significance (if any) of the PRKDC variant.  Obviously only 1 potentially deleterious variant was identified in an AR condition.

Thank you everyone for any help/assistance with this difficult case.  Have a great weekend
Nick

--

Nicholas Hartog, MD

Allergy/Immunology

Assistant Professor

Michigan State University College of Human Medicine

C: 608-347-1856

---

You are currently subscribed to cis-pidd as: mort.cowan at ucsf.edu<mailto:mort.cowan at ucsf.edu>.

To unsubscribe click here: http://cts.dundee.net/u?id=96396801.2afa8185762a47b637a79867019631bd&n=T&l=cis-pidd&o=4694502

(It may be necessary to cut and paste the above URL if the line is broken)

or send a blank email to leave-4694502-96396801.2afa8185762a47b637a79867019631bd at lyris.dundee.net<mailto:leave-4694502-96396801.2afa8185762a47b637a79867019631bd at lyris.dundee.net>

---
You are currently subscribed to cis-pidd as: pagid at list.clinimmsoc.org.
To unsubscribe click here: http://cts.dundee.net/u?id=96396833.5a9591ccd1e327fe6bc4d1543298c482&n=T&l=cis-pidd&o=4695658
or send a blank email to leave-4695658-96396833.5a9591ccd1e327fe6bc4d1543298c482 at lyris.dundee.net
-------------- next part --------------
An HTML attachment was scrubbed...
URL: <https://pairlist7.pair.net/pipermail/pagid/attachments/20171210/7191c366/attachment-0001.html>