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

[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