[CIS PIDD] [cis-pidd] Update on CVID with encephalitis

[John Ziegler]

Dewton

Have you checked for XLP?

John

From: Dewton Vasconcelos [mailto:dmvascon at usp.br]
Sent: Thursday, 26 June 2014 4:09 AM
To: CIS-PIDD
Subject: [cis-pidd] Update on CVID with encephalitis

I am posting an update on the evolution of the patient I posted previously. Below is the detailed history of the patient.

He is a 25 yo CVID patient presenting a degenerative disease with rapidly progressive dementia.
We had tested for autoantibodies and infectious diseases in CSF, all negative.

Thereafter we got a brain biopsy that showed a lymphocytic encephalitis mediated by CD8+ T cells. We are therefore thinking in trying T cell specific immunosuppression.
What is your experience on this kind of patient?

Thank you all for suggestions for therapy.

Best regards,

Dewton Vasconcelos


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Dewton de Moraes Vasconcelos, MD, PhD

Primary Immunodeficiencies Outpatient Unit ADEE3003

Lab. of Medical Investigation Unit 56

University of São Paulo School of Medicine






GPP, 24 years old male patient, born to non-consanguineous parents.
History of frequent diarrheas due to Giardia, upper respiratory infections and a few pneumonias since childhood. When he was 22 years old (in 2011) he was at the college and noted progressive loss of memory for recent events leading to dementia in two years. At the end of 2011 he was evaluated by a neurologist who diagnosed neurologic Behçet’s disease based on NMR images and increase of lymphocytes in CSF. The CSF lymphocytes at that time suggested clonality not observed later on. He was treated with pulse methylprednisolone and immunosuppression with azathioprine for one year, changed to methotrexate and high dose IVIg. There was a dosage of serum Igs showing hypogammaglobulinemia of all isotypes during this period, but the neurologic team that was treating the patient didn’t note.
When he was treated with IVIg and MTX he improved a lot from the respiratory infectious manifestations and presented some improvement of the neurologic manifestations. Nevertheless the initial neurologic improvement subsided and full-blown dementia developed, followed by progressive ataxia. At that time a new neurologist was consulted and thought about an enteroviral disease not confirmed by PCR in the CSF and sent to evaluation by immunology clinic.
The patient was sent to us a few months ago with this clinical picture.
We thought initially of an X-linked agammaglobulinemia (XLA) with enteroviral infection (there was a coincidence of his neurologic deterioration with the born of his daughter) and late-onset Adenosine Deaminase (ADA) deficiency with neurological involvement. At that time Brazilian Ministry of Health used to distribute Oral Polio Vaccine (Sabin - OPV) for administration at the 2nd, 4th and 6th month of life.
The immunological evaluation excluded XLA and was highly suggestive of Common Variable Immunodeficiency (CVID), with normal counts of T, B and NK cells, decrease of switched memory B cells, plasmablasts and low CD21+ B lymphocytes. ADA activity was normal, as well as lymphoproliferation to PHA, anti-CD3, PWM and CMV, and low to tetanus toxoid. At that time IgM, IgE, IgM below limit of detection and IgG normal (receiving IVIg anti-inflammatory dosage).
The evaluation of pathogens (fungal, mycobacterial, bacterial and mainly viral) was all negative. We tested by PCR for herpes (1-8), adenovirus, JC and BK viruses, HTLV/HIV, enteroviruses, astrovirus, flaviviruses, sapovirus, norovirus, arboviruses in CSF (all negative). Prion disease, as well as autoimmunity against brain was also performed, resulting negative.
Nuclear magnetic resonance (NMR) images showed diffuse CNS atrophy, without any area suggestive of inflammation that could drive our biopsy. Last week we performed a new NMR of the brain that presented progression of atrophy and hypersignaling mainly in frontal and right temporal areas.
We performed a brain biopsy in order to evaluate the histopathology of the lesion and to improve the sensitivity of the detection of any possible pathogen by PCR and looking at electron micrography to look for any possible viral particle.
Biopsy of brain lesion in the temporal region: - Fragment of nervous tissue with satisfactory representation of cerebral cortex and white matter. The cerebral cortex has neurons with preserved architecture and cytomorphology, absence of inclusions, neurofilament deposits or neuronialphagy, and moderate lymphocytic infiltrate, forming small clusters in the interstitium accompanied by perivascular and perineuronal distribution. The white substance presents reactive gliosis and lymphocytic infiltrate, perivascular and interstitial, forming small clusters. It has not been identified spongiosis, demyelinating disorders, necrosis, granulomas or microorganisms. Integration with immunohistochemical results characterizes an inflammatory infiltrate predominantly by CD8+ T cells and rare B lymphocytes in the perivascular region.
Based on these new findings we are thinking in T cell specific immunosuppression, trying to decrease the interference in innate immunity as low as possible.
What do you suggest to treat our patient?
Thank you very much,
Dewton







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