[CIS-PAGID] Peruvian patient with EBV associated lymphoproliferation

[Notarangelo, Luigi]

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 phosphatase: 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