[CIS PIDD] [cis-pidd] 16 y/o F with lung and CNS lesions, lymphopenia, absent NK cells, hypocellular bone marrow and lymphohistocytic infiltrate in lung

Weimer, Eric Eric.Weimer at unchealth.unc.edu
Mon Dec 1 16:22:02 EST 2014 

Hi Tam,

What about soluble IL-2R levels? HSV-1/2 CSF PCR?

Eric

-----------------------------------

Eric T. Weimer, Ph.D., D(ABMLI)
Assistant Professor, Pathology and Laboratory Medicine
Associate Director of Flow Cytometry, HLA, and Immunology Laboratories
The University of North Carolina at Chapel Hill



-----Original Message-----
From: Rosenzweig, Sergio (NIH/CC/DLM) [E] [mailto:srosenzweig at cc.nih.gov] 
Sent: Monday, December 01, 2014 4:01 PM
To: CIS-PIDD
Subject: Re: [cis-pidd] 16 y/o F with lung and CNS lesions, lymphopenia, absent NK cells, hypocellular bone marrow and lymphohistocytic infiltrate in lung

Hi Tam, did you consider CTLA4 haploinsufficiency?
Sergio

Sergio D. Rosenzweig, MD, PhD
10 Center Dr., Bldg. 10, DLM, CC 2C-410F Bethesda, MD 20892 Phone (301) 451 8971 Fax (301) 402 1884 Cell (240) 361 7617 Pager 102 10678 srosenzweig at cc.nih.gov<mailto:srosenzweig at cc.nih.gov>

Disclaimer: The information in this e-mail and any of its attachments is confidential and may contain sensitive information. It should not be used by anyone who is not the original intended recipient. If you have received this e-mail in error please inform the sender and delete from your mailbox or any other storage devices. National Institutes of Health shall not accept liability for any statements made that are senders own and not expressly made on behalf of the NIH by one of its representatives.

From: Jonathan Tam <kiditamae at gmail.com<mailto:kiditamae at gmail.com>>
Reply-To: CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>>
Date: Monday, December 1, 2014 3:00 PM
To: CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>>
Subject: [cis-pidd] 16 y/o F with lung and CNS lesions, lymphopenia, absent NK cells, hypocellular bone marrow and lymphohistocytic infiltrate in lung


I would like any input possible on a case of a 16 y/o girl with 10 month h/o neurologic changes  with disseminated CNS lesions on MRI, then acute development of  hypoxemia and extensive nodular and ground-glass opacities throughout the lungs progressing to respiratory failure, found to have lymphopenia, absent NK cells now improved following steroids and IVIg.   She was on azathioprine from 6/2014 -10/29/14.  Her lung biopsy shows diffuse lymphohistiocytic proliferation and she has hypocellular bone marrow.



Case:

16-year-old female who initially presented to OSH 12/ 2013 with bilateral lower extremity spasticity and urinary retention.  She was initially diagnosed with ADEM by the OSH and responded well to 5 days of IV solumedrol with outpatient taper. She had symptomatic recurrence and in Feb 2014 presented her at CHLA with improvement on steroids. By June 2014, she was started on azathioprine (stopped 10/29/14) the working diagnosis of antibody-negative NMO vs. MS.  Neuro-ophthalmology evaluation July 2014 showed no ocular manifestations.



She was admitted 10/15/14-10/18/14 with worsening bilateral lower extremity spasticity and urinary retention; repeat brain/spine MRI showed "Multiple patchy scattered foci of T2 hyperintensity throughout the cervical and thoracic spinal cord, increased in number and enhancement since the prior MRI spine of 7/31/2014.



10/24/14 she presented with 3 days of dyspnea, dry cough, and fevers to Tmax 101.  CT chest/abdomen/pelvis was significant for diffuse nodular and ground-glass opacities in both lungs as well as a lesion in spleen. Her hypoxemia worsened and eventually needed intubation and transfer to PICU.  She slowly improved on high dose steroids and high dose IVIg.  During her PICU stay she developed hypercalcemia (now resolved).  Extensive work-up was performed looking for malignancy and paraneoplastic process but all negative.  Bone marrow biopsy showed hypocellular marrow.



Labs:



Absolute monocytes have ranged from 100-900 (despite monocytes in discussion with NIH for GATA2 testing)



Lymphocyte enumeration (11/10/14) -only off azathioprine 12 days



Low absolute lymphocyte count (ALC 560).

Low absolute CD4 T cell count (CD4+ H 68.2 %, 383 Cells/uL).

Low absolute CD8 T cell count (CD8+ 19.9 %, 112 Cells/uL).

CD45RA 66%

CD25+CD127dim/CD4 4%

The T cell compartment demonstrates an increase in their activation state (HLADR+ CD3+ 11%).



The absolute value of NK called is significantly decreased for age (CD16+ CD56+ 4 Cells/uL).

The percentage of NK cells is low (0.7 %).



Low absolute B cell count (C19+10.1 %, 57 Cells/uL).



IgD+ CD27-Cd19+/CD19 90%

IgD+ CD27+Cd19+/CD19 7%

IgD-CD27+Cd19+/CD19 2%



IgG 787 mg/dL

IgM 130 mg/dL

IgA 114 mg/dL

IgE 119 kU/L



Tetanus ab 0.69 I.U./mL

H Flu ab  1.88 mcg/mL

Pneumococcal ab 0/13 protective; <0.3 mcg/mL for all 23 serotypes



NBT (11/10): normal



-BAL path (10/28): Macrophages, lymphocytes, and bronchial epithelial cells. Gram stain negative for intracellular bacteria. GMS stain negative for fungi, including pneumocystis.

-BAL cell count (10/28): 2000 RBC, 258 WBC (86%L)



Lung Biopsy (prelim per Dr. Dishop University of Colorado):   Diffuse lymphohistiocytic proliferation, consistent with immunologic dysregulation.



The abnormal lymphohistiocytic infiltrate appears benign, and there is no evidence of lymphoma. The pattern is abnormal in that there are no reactive lymphoid follicles (germinal centers) and instead is composed of sheets of predominantly T lymphocytes and histiocytes, spanning the interstitium, perivascular regions, and peribronchiolar regions. Absence of CD 56 staining is consistent with the history of absent NK cells in the peripheral blood , and supports a form of immunodeficiency or immune dysregulation.



-Chromosomal microarray CSF (11/6): normal

-Paraneoplastic ab panel (10/17): negative



-BM bx  path (11/13): Hypocellular bone marrow (30-40%) with trilineage hematopoiesis and no morphologic or immunophenotypic evidence of a lymphoproliferative process.



-ANA (10/15): undetected

-dsDNA (10/27): negative

-Cold agglutinin (10/27): negative

-ENA-RNP (10/27): negative

-ENA-Sm Ab (10/27): negative

-Proteinase-3 ab (C-ANCA) (10/27): negative

-Myeloperoxidase ab (P-ANCA) (10/27): negative

-FVIII assay (11/17): normal

-ACE serum (10/27): normal

-ACE CSF (11/6): negative

-ESR (10/27): 7

-Ferritin (multiple): 264-308

-IL-6 (11/5): 6.82

-C3 (11/15): normal

-C4 (11/15): normal

-Total complement (10/27): 312

-Total complement send out (11/15): 292



Infectious labs:

-Bacterial gram stain and cx (CSF): negative

-Bacterial gram stain and cx (BAL): negative

-Bacterial gram stain and cx (lung bx): negative

-Bacterial gram stain and cx (bm bx): negative

-Mycoplasma PCR (BAL): negative

-ASO (10/15): negative

-Lyme EIA (10/17): negative

-Babesia microti IgG and IgM (10/31): negative



-M. tuberculosis PCR (BAL): negative

-M. avium DNA (BAL): negative

-M. intracellularae (BAL): negative

-Quantgold (10/26): negative with good mitogen response

-PPD (10/29): 0mm induration

-AFB stain sputum (10/27, 10/28): negative

-AFB stain (BAL): negative

-AFB stain (lung bx): negative



-Fungal stain and cx (CSF): negative

-Fungal stain and cx (sputum): negative

-Fungal stain and cx (BAL): negative

-Fungal stain and cx (lung bx): negative

-Fungal stain and cx (bm bx): negative

-Aspergillus ag (BAL): negative

-Galactomannan (10/29): negative

-Cryptococcal ag (BAL): negative

-Cryptococcal ag (serum) 10/29: negative

-PCP PCR (BAL): negative

-Fungitell (10/29): negative

-Cocci CF serum (10/27): negative



-RVP 1 and 2 (NP): negative

-RVP 1 and 2 (BAL): negative

-HSV 1&2 PCR NP wash (10/27): negative

-VZV PCR NP wash (10/27): negative

-CMV PCR NP wash (10/27): negative

-CMV PCR (bm bx): negative

-EBV PCR serum (11/13): negative

-EBV PCR (bm bx): negative

-EBV and EBER (lung bx): negative

-EBV IgG, IgM, EBNA (11/5): negative

-Adenovirus PCR(bm bx): negative

-HHV6 (bm bx): negative

-West nile IgG IgM (CSF): negative

-Enterovirus PCR (CSF): negative

-HIV ab (11/10): non-reactive

-HTLV I/II Western Blot (10/15): non-reactive



-Toxoplasma IgG serum (11/15): negative



-Can't find Toxocara, Brucella, Ehrlichia, Anaplasma, Chlamydia DAA

-16s and 18s/ITS sequencing (bm bx): pending

-AFB cx (bm bx, lung): pending



Antibiotics courses:

Azithromycin (10/24-10/28)

Ceftriaxone (10/24-10/25), then Unasyn (10/26-10/30), then Cefepime (10/30-11/3)

Fluconazole (10/29- 11/4)

Clarithromycin (10/29-11/5) for non-tuberculous mycobacteria

RIPE: (10/29-11/4)

Vancomycin (11/8-11/12)

Cefepime (11/9 - 11/25)

Doxy (11/13 - ) Plan for a 14 day course, last day 11/26

Ambisome ( 11/14 - 11/25)



Imaging:



-CT chest/abd/pel (10/30): 1. Diffuse nodular and groundglass opacities throughout the lungs, most significant and consolidative within the lower lobes suggestive of diffuse fungal, typical, and/or atypical pneumonia. 2. Splenomegaly with large hypodense lesion arising from the superior anterior portion. Question of adjacent gastroesophageal involvement. Multiple other scattered hypodensities throughout the splenic parenchyma. Differential considerations include lymphoma versus disseminated fungal or granulomatous (TB, sarcoid) disease. 3. Hilar lymphadenopathy. 4. Enlarged gastroepiploic/perisplenic lymph nodes. Multiple perisplenic subcentimeter lymph nodes. 5. Hepatomegaly.



-MRI Brain w/ and w/o contrast (10/17): Interval marked increase in size and number of now innumerable T2 hyperintense, enhancing, punctate foci throughout the brain parenchyma, brainstem, and throughout the cerebellum, with some of these lesions likely leptomeningeal in location. Some of these lesions also demonstrate mild diffusion restriction. Differential considerations again include lymphoma, infectious and noninfectious granulomatous disease, as well as metastatic disease from an unknown primary malignancy. Demyelinating processes such as multiple sclerosis are less likely given the distribution of these enhancing foci.



-MRI spec (10/17): MRS is not specific considering the large partial volume of surrounding tissue. The nevertheless elevated Cho and Lac may indicate significant abnormal Cho and Lac levels within lesions when extrapolated.



-MRI cervical and thoracic spine (10/17): Multiple patchy scattered foci of T2 hyperintensity throughout the cervical and thoracic spinal cord, increased in number and enhancement since the prior MRI spine of 7/31/2014. Additionally, there is more pronounced leptomeningeal enhancement compared to prior exam, particularly involving the lower thoracic spinal cord. Given the concurrent findings within the brain, differential considerations again include lymphoma, leptomeningeal spread of tumor, or granulomatous disease. A demyelinating process is considered less likely. Recommend CSF sampling.



-LP (11/6): RBC 2, WBC 2(99%L)

-LP (10/15): RBC 1, WBC 2 (100%L)

-MS panel (CSF) (10/15): normal other than oligoclonal bandfs

-Oligoclonal bands (10/15): The patient's CSF contains multiple restriction bands that are also present in the patient's corresponding serum sample. We are unable to define whether these gammaglobulins are of systemic or intracerebral origin



-NMO/AQP-IgG4 (10/17): negative

-Fundoscopic and anterior chamber exam by ophto (10/29): normal



-ECHO (11/14): nl


--------------------------------
Jonathan Tam, MD
Assistant Professor of Pediatrics
Division of Clinical Immunology & Allergy Children's Hospital Los Angeles
4650 Sunset Blvd, MS#75
Los Angeles, CA 90027
jstam at chla.usc.edu<mailto:jstam at chla.usc.edu>
Phone: 323.361.2501
Fax: 323.361.1191

---

The CIS-PIDD listserv is supported by:

[http://www.clinimmsoc.org/UserFiles/image/cis-pidd-list-logo_v1.jpg]
The science & practice of human immunology

P: +1.414.224.8095
E: info at clinimmsoc.org<mailto:info at clinimmsoc.org>

Not a member of CIS? Please visit www.clinimmsoc.org<https://cis.execinc.com/edibo/Signup> to join!

You are currently subscribed to cis-pidd as: srosenzweig at cc.nih.gov<mailto:srosenzweig at cc.nih.gov>.
To unsubscribe click here: http://lm.clinimmsoc.org/u?id=207736502.dbed1e35a2a023491d9cd5e9046c558b&n=T&l=cis-pidd&o=45797030

---
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: eric.weimer at unchealth.unc.edu.
To unsubscribe click here: http://lm.clinimmsoc.org/u?id=208263932.f079bb1f561f45b3e40f3e53b72d03fd&n=T&l=cis-pidd&o=45797313
or send a blank email to leave-45797313-208263932.f079bb1f561f45b3e40f3e53b72d03fd at lists.clinimmsoc.org
----- Confidentiality Notice -----
The information contained in (or attached to) this electronic message may be legally privileged and/or confidential information. If you have received this communication in error, please notify the sender immediately and delete the message.


---
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=45797409
or send a blank email to leave-45797409-183939985.3ea13d40a15475ac00ebbd9cd8a37d6d at lists.clinimmsoc.org

More information about the PAGID mailing list