[CIS PIDD] [cis-pidd] interesting case

Thu Jul 17 10:35:51 EDT 2014

Thanks Kim-- prf/grb staining did not get performed. Unfortunately there
are just a few precious vials of cells from the patient since he we an
infant when drawn and is now transplanted. However indeed following up on
a granule handling problem seems like a good idea-- we'd have a far easier
time if there were another person with something similar to validate the
lab and genetic findings.

Josh

On 7/16/14 7:15 PM, "Risma, Kimberly" <Kimberly.Risma at cchmc.org> wrote:

>Did he have typical CTL? ie what did prf/grB stain look like when
>measured here in Cinci for eval of HLH? Kim
>
>> On Jul 16, 2014, at 5:19 PM, "Milner, Joshua D. (NIH/NIAID) [E]"
>><jdmilner at niaid.nih.gov> wrote:
>> 
>> Hi, I am posting this along with Dr. Subhadra Siegel about a very
>>curious case we followed a few years ago. A number of you may be
>>familiar with this case. The patient has been transplanted and is doing
>>fine, but we are hoping that by describing the case it may ring a bell
>>for others, so that more could be understood about the pathophysiology,
>>and hopefully genetics, and perhaps most importantly, so that the
>>parents can be counseled properly. Will attempt to make it as concise as
>>possible:
>> 
>> A four week old boy born to unrelated parents with no family history of
>>blood or immune problems presented with a fever and left shoulder MSSA
>>abscess which was drained. Dry peeling skin was noted on exam.  A WBC
>>count of 50k was noted, with predominant lymphocytosis, T-cell counts
>>approaching 40k, elevated NK but normal B cell numbers, no eosinophilia.
>>IgA, M and E were not detectable, and IgG was 374 and likely maternal.
>>After a second clean out he defervesced and his WBC and lymphocyte
>>count almost normalized. Bone marrow biopsy was normal. After several
>>weeks of IV antibiotics he was found, on follow up, to have head to toe
>>eczematous, thick lichenified skin without substantial erythroderma.
>>Several months later, at 4 months (after failing to come to follow up
>>appts) his skin was even worse. He was in respiratory distress, not
>>tolerating feeds but no diarrhea, low grade fever, although parents did
>>not think he was sick. Repeat WBC was again elevated at 95K, . Normal
>>appearing thymus. HSM and LAD were noted, and a LN biopsy should marked
>>reactive T-cell infiltrate with no secondary B-cell follicles and almost
>>no primary B-cell follicles or plasma cells, no clonality. Eventually
>>eventually miliary lesions noted on CXR. Lung biopsy showed just
>>reactive histiocytosis and T-cell infiltrate.  AFB and gram stain
>>negative. Klebsiella bacteremia was found. EBV/CMV PCR negative.
>>Ferritin 2500 but note he was acutely ill.
>> His NY TREC screen was normal (>3000)
>> Blood was obtained at the NIH‹
>> Normal spectratype
>> CD3 43k
>> CD4 33k
>> CD8 9k
>> DNT 368
>> CD4/CD62L+/CD45RA+ 4142
>> CD4/CD62L+/CD45RA- 20157
>> CD8/CD62L+/CD45RA+ 1243
>> CD8/CD62L+/CD45RA- 5292
>> CD20 1979
>> CD20/CD5 1795
>> CD20+ IgM- absent
>> CD20/IgD+/CD27+ 322
>> CD20/IgD-/CD27+ absent
>> CD4/25/Foxp3+ 874
>> NK 506
>> NKT 414
>> 
>> LIJ labs: PWM responses were normal, ConA and PHA were low
>> Blood sent to Cincinnati- SAP staining at the low end of normal in CD8
>>(53%) and NK (55%) cells. Very poor NK cytotoxicity
>> Rag sequencing was normal, as was an HLH and XLP panel.
>> Our exome data on the trip revealed a large number of targets, so
>>looking for other cases!
>> 
>> The patient was put on IV solumedrol with some mild improvement. Over
>>the next month he received etoposide cyclosporin and dexamethasone (HLH
>>protocol) and his WBC fell closer to 15k with skin improvement and
>>LAD/HSM diminution. After stopping the the HLH chemo protocol for one
>>week for transplant conditioning his WBC and skin/LAD/HSM spiked right
>>back up. Despite all of that, he sailed through HSCT is totally healthy
>>several years out. Parents are understandably quite concerned about what
>>this could have been for future family planning.
>> 
>> Any thoughts? Does it ring any bells?
>> 
>> Thanks,
>> 
>> Josh
>> 
>> 
>> Joshua D. Milner, MD Chief, Genetics and Pathogenesis of Allergy Section
>> Laboratory of Allergic Diseases, NIAID, NIH
>> NIH Building 10-CRC Room 5-3950
>> Bethesda, MD  20892
>> Lab phone: 301 827 3662
>> Fax: 301 480 8384
>> jdmilner at niaid.nih.gov
>> 
>>http://www.niaid.nih.gov/labsandresources/labs/aboutlabs/lad/allergicinfl
>>ammation/Pages/milner.aspx
>> 
>> ---
>> The CIS-PIDD listserv is supported by the Clinical Immunology Society
>> The science & practice of human immunology
>> 
>> P: +1.414.224.8095
>> E: info at clinimmsoc.org
>> 
>> Not a member of CIS? Please visit www.clinimmsoc.org to join!
>> 
>> You are currently subscribed to cis-pidd as: kimberly.risma at cchmc.org.
>> To unsubscribe click here:
>>http://lm.clinimmsoc.org/u?id=183824732.c17c4ea3c90251f9d80d5c215e06b62d&
>>n=T&l=cis-pidd&o=45176447
>> or send a blank email to
>>leave-45176447-183824732.c17c4ea3c90251f9d80d5c215e06b62d at lists.clinimmso
>>c.org
>
>
>---
>The CIS-PIDD listserv is supported by the Clinical Immunology Society
>The science & practice of human immunology
>
>P: +1.414.224.8095
>E: info at clinimmsoc.org
>
>Not a member of CIS? Please visit www.clinimmsoc.org to join!
>
>You are currently subscribed to cis-pidd as: jdmilner at niaid.nih.gov.
>To unsubscribe click here:
>http://lm.clinimmsoc.org/u?id=183824676.04a75971ce63f292890a03511ab41354&n
>=T&l=cis-pidd&o=45176901
>or send a blank email to
>leave-45176901-183824676.04a75971ce63f292890a03511ab41354 at lists.clinimmsoc
>.org

---
The CIS-PIDD listserv is supported by the Clinical Immunology Society
The science & practice of human immunology

P: +1.414.224.8095
E: info at clinimmsoc.org

Not a member of CIS? Please visit www.clinimmsoc.org to join!

You are currently subscribed to cis-pidd as: pagid at list.clinimmsoc.org.
To unsubscribe click here: http://lm.clinimmsoc.org/u?id=183939985.3ea13d40a15475ac00ebbd9cd8a37d6d&n=T&l=cis-pidd&o=45179520
or send a blank email to leave-45179520-183939985.3ea13d40a15475ac00ebbd9cd8a37d6d at lists.clinimmsoc.org