[CIS-PAGID] Common Variable Immunodeficiency patient with CNS lesion

[Klaus Warnatz]

Sorry for the delayed response to your request.
I would just like to add to Carsten Speckmanns commentary which I find 
very important, that the patient we had seen and who died due to 
compound heterozygous MUNC 13 mutation initially had presented with one 
episode of seizure (aged 32) and one episode of hepatitis (aged 34) very 
similar to the patient you describe.
Ferritin and sIL2 R were helpful in the diagnosis, (sIl2R less so since 
we find also elevated levels in CVID with lymphoproliferation),
any cytopenia?? (in our patient tricytopenia), in case of elevated 
ferritin / cytopenia urgent further work up for HLH indicated
peripheral blood EBV copy number? in our patient pos. (would be helpful 
also in making decision regarding use of RTX)
brain histology EBER pos?
Spinal fluid analysis in our case was however pathologic: increased cell 
number and protein
How was Spinal fluid screened for viruses? including Enteroviruses?

Any signs for radiosensitivity (B cell numbers are very low)?

therapeutically we were able to control the activity to some extent by 
CSA + fortecortin but obviousl yinfection should be ruled out as much as 
possible. Depending on the clarification of the diagnosis and the course 
furhter escalation according to the HLH protocol needs to be considered 
early even so I felt that we may have to still define the protocols for 
adults.
our patient perforated his bowel twice was operated, back on ICU when he 
died due to respiratory infection.

greetings to Regis (remember the great time in Bahia!)

klaus



Am 07.08.2011 23:36, schrieb dmvascon at usp.br:

> I am writing to discuss about a patient my colleague Regis Campos is 

> following in Bahia, Brazil.

>

> A 37-year-old female with diagnosis of Common Variable 

> Immunodeficiency was made in October 2010 after a pneumonia and 

> seizure without further neurologic symptoms. Her serum immunoglobulin 

> were low (IgG : 46mg/dl; IgM: 46 mg/dl; IgA: 12 mg/dl) and had a long 

> history of recurrent respiratory infections in the last four years, 

> mainly sinusitis and six episodes of pneumonia.

>

> Ten years ago she had a diagnosis of hemolytic anemia which was 

> treated with Prednisone but was under control without use of 

> medication in the last year.

>

> She performed a MRI of the brain in September 2010 which showed a left 

> periventricular lesion with involvement mostly of the Thalamus and 

> scattered subcortical lesions. The cerebrospinal fluid analysis was 

> normal. It was not found CMV, Mycobacterium, EBV or herpes infection. 

> She received an empirical treatment to cerebral toxoplasmosis but had 

> an allergic reaction to the treatment and there is no change in the 

> MRI lesion. She was released taking Dapsone and diphenylhidantoine.

>

> Immunophenotypic analysis of peripheral blood lymphocytes demonstrated 

> 1% B cells (CD19) with normal percentages of CD3+, CD3CD4+ and CD3CD8+ 

> T cells but with a slight reduction on absolute counts of CD4 T cells 

> (487 mm3) and CD3 cells (898 mm3; reference values: 1000 ? 3900).

>

> She started IVIG treatment in November 2010. She improved and stopped 

> having recurrent respiratory infections.

>

> In December 2010, she had an allergic skin reaction which was 

> suspected to be due to diphenylhidantoine or Dapsone and both 

> treatment were suspended. She received a short course of one week of 

> Prednisone with improvement of the skin reaction and started taking 

> Topiramate for seizures prevention.

>

> She was doing well, when in March 2011, she developed a left ptosis 

> and another CNS MRI showed an extension of the lesion to the 

> mesencephalon and also a spleen and liver enlargement.  She went a 

> hematology consultation looking for lymphoma. It was not found any 

> evidence of hematologic involvement. A liver biopsy was not 

> conclusive, without granulomatous lesions or lymphoma infiltration.

>

> The neurologic status got worse and the patient was admitted to the 

> hospital in June 12th 2011. She developed right hemiparesis and 

> worsened the palpebral ptosis with some periods of disorientation. 

> There were no signs of laboratory infection and the CSF was normal. A 

> new CNS MRI showed an extension of the lesion close to the thalamus 

> and also a lesion in the cervical spinal cord. The patient had also a 

> gait involvement.

>

> She started on Dexamethasone and took 1,0 g of methylprednisolone for 

> five days with a transient improvement in June 2011. She performed a 

> brain biopsy with did not show lymphoma and only signals of T and B 

> cells, however the neurosurgeon did reach only the periphery of the 

> lesion.

>

> She worsened the neurologic picture and two weeks after the 

> methylprednisolone pulse, she took Cyclophosphamide.  Without 

> improvement, another brain biopsy was performed in July 25th 2011 

> which showed unspecific encephalitis plenty of plasma cells, CD19 B 

> cells and CD3 T cells into the vessels with a diagnosis of vasculitis.

>

> In July 29th, she took a new pulse of methylprednisolone for three 

> days.  In the last week, she did not improve also showing fever and 

> mental confusion.

>

> What do you think we should do to improve her clinical features? Do 

> you think that rituximab could be a good option?

>

> Thank you very much for your opinions.

>

> Dewton de Moraes Vasconcelos

> Regis de Albuquerque Campos

>


-- 
Prof. Dr. Klaus Warnatz

UNIVERSITÄTSKLINIKUM FREIBURG
University Freiburg-Medical Center
Centrum für Chronische Immundefizienz (CCI)
Abteilung für Rheumatologie und Klinische Immunologie


Tel +49-761-270-77640 / Fax -71000 / Pager: 12-7100

Breisacher Str. 117, 79106 Freiburg, Germany
klaus.warnatz at uniklinik-freiburg.de
http://www.uniklinik-freiburg.de