[CIS PIDD] [cis-pidd] interesting case

Wed Jul 16 17:17:09 EDT 2014

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/allergicinflammation/Pages/milner.aspx

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