[CIS PIDD] [cis-pidd] ADA SCID with partial reconstitution and chronic leptomeningitis/encephalitis

[Christine M. Seroogy, MD]

Dear Dewton et al.

Thank you for the comments and suggestions.  Some follow up:


  1.  Toxo PCR was negative
  2.  Listeria and Brucella:  no risk factors, 16sRNA was negative from the CSF
  3.  Mycobacterium: AFB stains and culture from CSF and blood are negative
  4.  dAXP was 0.135 prior to PEG-ADA therapy and now 0.03
  5.  Pathology and imaging are not consistent with PML and CSF JC PCR was negative.
  6.  The pathology did not show evidence for vasculitis
  7.  CSF ACE level is elevated at 7.2 (0-2.5), serum ACE is normal
  8.  CSF immunofixation was negative for oligoclonal bands

Chris


From: Dewton Vasconcelos <dmvascon at usp.br<mailto:dmvascon at usp.br>>
Reply-To: CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>>
Date: Thursday, August 8, 2013 1:09 PM
To: CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>>
Subject: Re: [cis-pidd] ADA SCID with partial reconstitution and chronic leptomeningitis/encephalitis

Dear Chris

What a complex and interesting case!
In a first sight I would think about the possibility of metabolic intoxication due to dAXP (that could improve after ADA-PEG).
On the other hand I would be afraid of increasing the patients' own cells with ADA-PEG and the possibility of a graft rejection.

Another possibility should be a CNS vasculitis (sarcoid like) that occasionally occurs in PID patients (my experience with ADA def is scarce).

Is there any marker for autoimmunity? (if possible from a sample previous to Rituxan). As he presented ITP there is a possibility of anti-phospholipid Ab that could attack CNS as well.
Is there any evidence of immunologic activity in the CNS? Are there oligoclonal bands in the protein electrophoresis of CSF?
Is there any evidence of vasculitis in the brain biopsy?

You got very low levels of JC virus in blood (but not in CSF). Should it be a possibility??? - I would not think about it at the first sight, as JC usually presents as degenerative CNS disease (PML).

My colleague Thiago Bezerra suggested to start high dose IVIg trying to modulate the immune response.

Best regards,

Dewton

Dewton de Moraes Vasconcelos, MD, PhD
Primary Immunodeficiencies Outpatient Unit ADEE3003
Lab. of Medical Investigation Unit 56
University of São Paulo School of Medicine

Christine M. Seroogy, MD wrote:


Dear Colleagues,


We are caring for a 14 y/o with ADA SCID s/p non-conditioned haploidentical BMT x 2 with a 4 month history of intermittent fevers, headaches, weight loss, myalgias.  He has 100% donor T cells with adequate function and low T cell numbers, on IG therapy, and off of PEG-ADA for years but empirically restarted 2 weeks ago.  His most recent brain/spine MRI demonstrated enhancement of meninges and some parenchymal enhancement (worsening from previous studies).  His CSF has increased lymphs/monos with high protein and low glucose.He had a brain bx 10 days ago:  with no viral inclusions, fungi or bacteria visible (EM and special stains including AFB). There is granulomatous inflammation with no discrete granulomas with numerous macrophages and T cells (CD4:CD8 ratio 3:1), no B cells. One possibility is a neurosarcoid-like picture. Imaging elsewhere does not demonstrate obvious organ involvement outside the CNS.


His notable history in the past year is one episode of ITP responsive to 4 doses of rituxan and non-infectious uveitis responsive to topical steroids.


He has had an extensive infectious disease work-up and my question to the group is if there is an infectious agent we may be missing? Have any of you seen such a case?

Here is the infectious work up to date:


Studies:

Bacterial--

4/29/13 Culture, CSF negative

4/29/13 Lyme PCR (CSF) negative

4/29/13 Bartonella PCR (CSF) negative

4/29/13 AFB smear/culture (CSF) negative

7/11/13 blood, peripheral: negative

7/12/13 blood, peripheral: negative

7/14/13 CSF culture, negative

7/14/13 AFB smear & culture, CSF Negative

7/14/13 16s ribosomal PCR, CSF negative

7/26/13 CSF culture negative

Viral--

4/8/13 EBV PCR negative

4/8/13 CMV PCR negative

4/8/13 Flu A/B, RSV PCR negative

4/9/13 Enterovirus PCR negative

4/23/13 Respiratory viral panel (WI state lab): negative

4/29/13 West Nile PCR (CSF) negative

4/29/13 adenovirus PCR (CSF) negative

4/29/13 CMV PCR (CSF) negative

4/29/13 Arbovirus Ig panel (CSF) Negative

4/29/13 HHV-6 PCR (CSF) Negative

4/29/13 HHV-8 PCR (CSF) negative

4/29/13 HSV PCR (CSF) negative

4/29/13 Enteroviral PCR (CSF) negative

4/29/13 VZV PCR (CSF) negative

4/29/13 EBV PCR (CSF) negative

5/1/13 Enterovirus RNA PCR, stool negative

7/8/13 Resp viral panel (Viracor): positive for rhinovirus

7/8/13 Enterovirus PCR negative

7/11/13 BK virus qPCR: negative

7/12/13 JC virus PCR (blood): positive (very low levels: initially postive at 42 cycles, repeat positive at 36 cycles)

7/12/13 adenovirus PCR: negative

7/12/13 enterovirus PCR: negative

7/14/13 CMV PCR (CSF) negative

7/14/13 JC virus PCR (CSF): negative

7/14/13 BK virus PCR (CSF) negative

7/14/13 Enterovirus PCR (CSF) negative

7/14/13 Adenovirus PCR (CSF) negative

7/14/13 EBV PCR (CSF) negative

7/14/13 LCM IgG/M (CSF) pending

7/14/13 Herpes simplex PCR (CSF) negative

7/16/13 respiratory viral panel (Viracor) positive for rhinovirus

7/16/13 Herpes simplex PCR (blood) negative

7/18/13 blood JC virus qPCR <500/mL

7/23/13 Blood HTLV PCR Negative

7/23/13 Blood HIV RNA, qPCR Not detected

7/26/13 VZV PCR from brain biopsy negative

7/26/13 EBV PCR from brain biopsy negative

7/26/13 CMV PCR from brain biopsy negative

7/26/13 adenovirus PCR from brain biopsy negative

7/26/13 adenovirus PCR from CSF negative

7/26/13 enterovirus PCR from brain biopsy negative

7/26/13 coxsackie/echovirus PCR from rectal swab negative

7/26/13 coxsackie/echovirus PCR, throat swab negative

7/26/13 EBV RTPCR, CSF negative

7/26/13 VZV RTPCR, CSF negative

7/26/13 CMV RTPCR, CSF negative

7/26/13 enterovirus RTPCR, CSF negative

7/26/13 enterovirus culture from CSF, brain, and dura negative at 10 days

8/2/13 respiratory virus panel (in-house) negative

Fungal--

4/29/13 Fungal culture, CSF negative

4/29/13 Histoplasma Ag (CSF) negative

4/29/13 Blastomyces Ag (CSF) negative

4/29/13 Cryptococcal AG, CSF negative

7/14/13 Blastomyces antigen, urine negative

7/14/13 Histoplasma antigen, urine negative

7/14/13 CSF fungal culture NGTD

7/14/13 Cryptococcus antigen, CSF negative

7/26/13 Fungal culture, CSF NGTD

Other--

4/29/13 Mycoplasma PCR CSF negative

7/14/13 Mycoplasma PCR CSF negative

7/14/13 Toxoplasma PCR CSF negative


Thank you

Chris


Christine M. Seroogy MD,  FAAAAI
Associate Professor
University of Wisconsin
Department of Pediatrics
Division of Allergy, Immunology & Rheumatology
1111 Highland Avenue
4139 WIMR
Madison, WI  53705-2275
phone: 608-263-2652
fax: 608-265-9721





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