[CIS-PAGID] Peruvian patient with EBV associated lymphoproliferation

[Jack Bleesing]

We (in Cincinnati) have gone back through our freezer to look at ITK
mutations in patients with EBV-associated issues (mainly HLH). We have
no found any patients with bi-allelic ITK mutations as far as I can
tell. 
 
Now, if there is consanguinity in the family, this may chance the odds.
In that setting, it would still be more likely that a primary HLH gene
(PRF1, MUNCH13-4, STXBP2, STX11) is involved.
 
Regards,
 
JB
 
---------------------------------------------------------------------------
Jack J.H. Bleesing, M.D., Ph.D.
Associate Professor of Pediatrics
Cincinnati Children's Hospital Medical Center
Division of Bone Marrow Transplantation & Immune Deficiency
3333 Burnet Avenue, MLC 7015
Cincinnati, OH 45229
513-636-4266 (phone)
513-636-3549 (fax)
Jack.Bleesing at CCHMC.org 
http://www.cincinnatichildrens.org/immunodeficiencies/ 


>>> "Notarangelo, Luigi" <Luigi.Notarangelo at childrens.harvard.edu>

12/1/2011 11:37 AM >>>
Dear Juan:

Please, add sCD25 which you can also send to Cincinnati (and also NK
cell functional studies). I would also suggest that you ask them to
stain slieds of the marrow for CD163, another very good marker of HLH.

Gigi


On 12/1/11 11:35 AM, "Juan Carlos Aldave Becerra"
<jucapul_84 at hotmail.com> wrote:

Dear Dr. Notarangelo,

Thank you very much for your response, I have contacted with Cincinnati
lab for help with the flow citometry studies that we dońt have
available in Peru.

For the biochemical and functional screening for HLH, apart from
ferritin and triglicerydes, what else should I request?

Juan


> From: Luigi.Notarangelo at childrens.harvard.edu 

> To: pagid at list.clinimmsoc.org 

> Date: Thu, 1 Dec 2011 16:30:51 +0000

> Subject: Re: [CIS-PAGID] Peruvian patient with EBV associated

lymphoproliferation

>

> Dear Juan Carlos:

>

> I suggest to consider HLH in the differential diagnosis. This is way

more common than ITK deficiency.

> Biochemical and functional screening for HLH should be done first,

and I would also look at perforin and CD107 expression to get insights
into possible gene defects.

>

>

> Luigi D. Notarangelo

> Professor of Pediatrics and Pathology, Harvard Medical School

> Jeffrey Modell Chair of Pediatric Immunology Research

> Division of Immunology, Children’s Hospital Boston

> Karp Research Building, Room 9210

> 1 Blackfan Circle

> Boston, MA 02115

>

> teL: +1-(617)-919-2276

> FAX: +1-(617)-730-0709

>

>

>

>

> On 12/1/11 11:26 AM, "Juan Carlos Aldave Becerra"

<jucapul_84 at hotmail.com> wrote:

>

> Good morning dear Doctors, I was presented this case from Peru:

>

> Female patient

> 4 years old

>

> Parents are not blood relatives.

> No previous medical history before 4 years of age.

> Normal psychomotor development

>

> May 2011: First hospitalization for Probable Infection by Epstein

Barr Virus (fever; cervical, mesenteric and mediastinal lymphadenopathy
(4 mm); hepatosplenomegaly; hypergammaglobulinemia).

>

> Bone marrow smear:

> •         Lymphocytic marrow infiltration versus reactive

lymphoproliferative syndrome (June 2011)

>

> Bone marrow biopsy

> •        90% cellularity, presence of all three series, 40% CD8

cytotoxic T lymphocytes of mature appearance (June 2011)

> Liver biopsy:

>

> •        Extramedullary hematopoiesis (June 2011)

>

> Lymph node biopsy:

> •        Paracortical hyperplasia with no evidence of malignancy 

(June 2011)

>

>

>

> September 2011: Second hospitalization: sudden onset of fever, cough

and respiratory distress, managed in ICU for septic shock with
respiratory focus, needing oxygen and inotropic support; oliguria,
anemia (received transfusion), hepatosplenomegaly.

>

> Laboratory: mild anemia, lymphocytosis, elevated liver enzymes, and

hypergammaglobulinemia

> Leukocytes: 11.400 cells/mm3

> Lymphocytes: 8.430 cells/mm3

> Neutrophils: 1999 cells/mm3

> Hemoglobin: 10.1 g / L

> Platelets: 343 000 cel/mm3

> C reactive protein: 5.3

> Creatinine: 0.21 mg / dl

> ALT: 142 IU; AST: 127

> Alkaline ph

osphatase: 470 (normal up to 300)

> Albumin: 3.32 g / dl

> Total Protein: 9.14 g / dl

> Urinalysis: normal

> Haptoglobin: normal

> IgA: 217 mg / dl

> IgM: 369 mg / dl

> IgG: 2401 mg / dl

> IgE: 41.9 mg / dl

> EBV EBNA IgG: positive

> EBV EBNA IgM negative

> EBV VCA IgG positive

> Direct Coombs positive (1+)

> Fibrinogen: normal

> LDH 967 (high)

> Electrophoretic proteinogram: hyperproteinemia, polyclonal increase

of gamma fraction

> Epstein Barr Virus Viral load (PCR): 1070 copies / ml

> Cytomegalovirus viral load <600 copies

> Bronchoscopy: thick secretions and fluffy whitish plaques

> TCR clonality study: negative

> Negative blood cultures

> Autoantibodies (ANA, ANCA, ASMA, Anti KLM1, antithyroid): negative

> Negative PPD

> Negative viral markers for hepatitis

>

>

> The patient has received IV acyclovir for 21 days; fluconazole for 10

days. Good evolution from the respiratory standpoint. No fever.
Persistent hepatosplenomegaly (7 cm below the costal margin) and
cervical microadenopathies.

>

> I have read about the PID that predispose to EBV infections and,

because of the gender of the patient, I suspect of Itk deficiency.
Please feel free to make me the suggestions that you have.

> Thank you very much,

>

> Juan Carlos Aldave

> Allergy and Clinical Immunology

> Lima-Peru

>

>

>

>



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