[CIS PIDD] patient with susceptibility to herpetic infections

[Laia Alsina Manrique de Lara]

Thank you Joao,
We haven't tried valgancyclovir prophylaxis. Indeed the patient has currently no CMV, VVZ, HSV, EBV replication. His immunological problem seems to interfere with the control of the primary infection, because thereafter he doesn't seem to have a reactivation of the infection (at least in the following 4 years of the infection).
I will check for GATA2 study.

Thanks

Laia Alsina
Allergy and clinical immunology department
Hospital Sant Joan de Deu
Barcelona



El 11/09/2012, a las 19:27, "João" <jpfn13 at gmail.com<mailto:jpfn13 at gmail.com>> escribió:


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Dear Laia,

I wouldn't rule out monomac.

Have you tried valgancyclovir prophylaxis?

IGIV/IGSC have been used with sucess  in  AT patients with recurrent HSV infections, namely ocular, despite normal Ig levels...

João

João Farela Neves
Primary Immunodeficiencies Unit
Hospital dona Estefania
Lisbon
Portugal

Enviado do meu iPad

No dia 10/09/2012, às 09:32, Ales Janda <ales.janda at uniklinik-freiburg.de<mailto:ales.janda at uniklinik-freiburg.de>> escreveu:


Dear Alsina,
regarding the monocytes one should be careful as the values received from routine heamatology lab are usually based on FCC and SCC and can be falsely positive. So, to be sure that those cells are really monocytes one should consider immunophenotyping.
We also had one patient with GATA-2 deficiency with low B cells, recurrent viral infections, warts and progression to MDS who had monocytes though in a lower normal range. I guess that the phenotype of GATA-2 defect is rather broad and presence of some monocytes do not exclude this diagnosis.
best,
Ales

Dr. Ales Janda


UNIVERSITÄTSKLINIKUM FREIBURG
CCI - Centrum für Chronische Immundefizienz

Ales Janda, M.D., M.Sc., Ph.D.
Hospitant

Engesser Straße 4 - 2. OG, 79108 Freiburg
Tel:+49(0)761-270-77755
Fax:+49(0)761-270-62070
ales.janda at uniklinik-freiburg.de<mailto:ales.janda at uniklinik-freiburg.de>

www.uniklinik-freiburg.de<http://www.uniklinik-freiburg.de>




Am 10.09.2012 09:10, schrieb Laia Alsina Manrique de Lara:


Thank you Pere and Joao,

This patient has always had normal values of monocytes ( above 500/mmcc). This rules out the possibility of a GATA2 deficiency, right?
I cannot perform specific proliferation to HSV.

As for the management of this patient, my main concern, any other suggestion?
Also, what do you think about NK us populations?


Thank you ,

Laia Alsina
Allergy and Clinical Immunology Department
Hospital Sant Joan de Deu,  Barcelona


El 07/09/2012, a las 13:03, "João Farela Neves" <jpfn13 at gmail.com<mailto:jpfn13 at gmail.com>> escribió:


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Hi Laia.

Agree with Pere.
GATA2 should be excluded, specially regarding the relative B lymphocytopenia.

What about T cell proliferation to HSV and CMV? If absent, don't overlook RAG...

Although controversial, Have you gave a thought about valgancyclovir prophylaxis?

Yours,

João
João Farela Neves
Primary Immunodeficiencies Unit
Hospital dona Estefania
Lisbon
Portugal



Enviado do meu iPhone

No dia 07/09/2012, às 10:22, Pere Soler Palacin <psoler at vhebron.net<mailto:psoler at vhebron.net>> escreveu:



Dear Laia, we have a similar patient in whom MonoMac was diagnosed. Nevertheless, I see that monocyte count is normal in this blood test. Is there monocytopenia in previous exams?



Yours,



Pere.


Pere Soler Palacín, MD, PhD.
Pediatric Infectious Diseases and Immunodeficiencies Unit. Hospital Universitari Vall d'Hebron.
Assistant Professor. Universitat Autònoma de Barcelona.
Passeig de la Vall d'Hebron 119-129.
08035 Barcelona. Spain.
Tel: 0034934893140. Fax: 0034934893039.
E-mail: psoler at vhebron.net<mailto:psoler at vhebron.net>; 34660psp at comb.cat<mailto:34660psp at comb.cat>. Web: www.upiip.com<http://www.upiip.com/>.



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----- Mensaje original -----
De: "Laia Alsina Manrique de Lara" <lalsina at hsjdbcn.org<mailto:lalsina at hsjdbcn.org>>
Para: pagid at list.clinimmsoc.org<mailto:pagid at list.clinimmsoc.org>
Enviados: Viernes, 7 de Septiembre 2012 10:42:16
Asunto: [CIS PIDD]  patient with susceptibility to herpetic infections




Dear all,

I follow in the Clinic a 5 yo male patient who displays a very narrow infectious phenotype (viral infections, herpetic in particular).

Here is the summary of the clinical history:

Date of Birth: 29/07/2007
Visit Date: 06/09/2012

Family history:
-No family history of consanguinity. Parents are from the Philippines. Patient was born in Spain. No family history of recurrent infections.

Personal history:
-Born preterm at 32 weeks, weight 1000 g (-2.6 SD), height 37 cm (-3DS). IUGR. Oligohydramnios. As neonatal complications, wet lung treated with CPAP during the first 30 hours of life.
- November 2007 (4 months of age): respiratory infection by influenza B virus (RSV-) and acute otitis media, requiring admission 1 week with oxygen.
- December 2007 (5 months of age): readmission for bronchiolitis. Condensation in right upper lobe and retrocardium. RSV-, flu -. After 2 weeks of admission he presents clinical worsening and was transferred to our hospital PICU for ventilatory support. BAL culture negative. Requires mechanical ventilation for 6 days with maximum FiO2 50%, followed by NIV for 4 days.
- January 2008 (6 months of age): two exacerbations of respiratory symptoms, with same radiological findings, which are managed as outpatient.  Associates diarrhoea with negative culture and ponderal stagnation.
- March 2008 (7 months): persistence of respiratory symptoms. Admitted to hospital. A viral load for CMV is detected in blood (2,058,000 copies / ml). Congenital CMV infection is ruled out: negative PCR in Guthrie card and negative PCR in mother's urine. No CMV VL can me determied in respiratory samples. Completed 14 days of ganciclovir. VL to CMV is well controlled --> diagnosed of acquired CMV infection with pneumonitis.
- July 2009 (2 years): severe varicella (generalized skin lesions that end up scarring as a major burn injury) with severe pneumonitis requiring mechanical ventilation for 9 days, complicated with ARDS. Source for VVZ: big brother at home. During intubation, lesions consistent with Candida in larynx and esophagus are observed. During this episode, the CV is reactivated CMV in blood and BAL.
- For the last 2 years, he has been suffering from recurrent upper respiratory tract infections and bronchitis. No other severe infections except fro a pneumonia in May 2011.
- July 2012: starts growth hormone treatment (no catch up in height at 4 yo, and past history of intrauterine growth retardation.
-Surgery for hypospadias.
-Correct vaccinations, including MMR (last dose in July 2012), no vaccine reaction.

Physical examination:
Weight 15 kg (3rd percentile)
Height 93 cm (3rd percentile)
Physical exam: No dysmorphic. Chickenpox scar lesions in skin.

Supplementary examinations (21/08/2012):
CBC: Hemoglobin 11.1 g / dl, Hematocrit 38.8%, Platelets 411 thousand / mmcc (150-500), Leukocytes 13.5 Mil / mmcc (5.0 to 13.0), absolute lymphocytes 5400/mm3. Monocytes: 0,6 Mil/mmcc (0,1-0,7).

B lymphocytes 12%  (21 to 28). Absolute 648 /mmcc (390-1400).
T lymphocytes 71% (62-69)
T4 lymphocytes 25% (30 to 40). Absolute 1350/mmcc (1000-1800).
T8 lymphocytes 45% (25-32)
T4/T8 Index 0.68  (1.00 to 1.60)
Natural Killer 8% (8 to 15) NKT cells present (see attached subphenotype of NK cells).
 --> Expansion of CD8 + and inversion of CD4/CD8 ratio.
 --> PCR to CMV, VVZ, EBV, herpes simplex are negative.

Immunoglobulins
Immunoglobulin G 19640 mg / L (4540-12000)
Immunoglobulin A 1415 mg / L 244-1510
Immunoglobulin M 1868 mg / L 436-1890
Immunoglobulin E <1 KIU / L 0-59
IgG subclasses
Immunoglobulin G1 15763 mg / L 3200-9000
Immunoglobulin G2 1727 mg / L 520 to 2800
Immunoglobulin G3 2766 mg / L 140-1200
Immunoglobulin G4 19 mg / L 10-1060

 --> Expansion of IgG1 and IgG3.

Other studies
-Study NK cytotoxicity and degranulation:
--16/01/2012 Cytotoxicity reduced but not absent, with increased expression of perforin in CD8 + with respect to control (indicates hyper-activation of CTLs).
--19/03/2012: Normal, both cytotoxicity and degranulation.

-Test of lymphocyte proliferation to mitogens (PHA and PWD): normal
-T lymphocyte phenotyping: normal (alphabeta populations: 91%, gammadelta 7.5%, RO+: 24%; RA+: 65%).
-CD18 expression: normal
-MHC class 1 expression: normal

-Isohemagglutinins and protein and polysaccharide vaccine responses: normal

-Ab VVZ IgG positive
-Ab CMV IgG positive

High resolution lung CT (16/01/2012): no bronchiectasis. Mild diffuse air trapping. There are some small bilateral subpleural dense linear image, probably related to discrete changes of pulmonary dysplasia secondary to prematurity.



Diagnosis:

-increased susceptibility to viral infections, herpetic in particular.

-a combined immunodeficiency is ruled out.

-might be a functional NK cell deficiency?



My questions regarding this patient are:
1- Do you suspect a paticular PIDD? What other immunological tests would you perform?
2- What management do you suggest? (early treatment of infections, IVIG?).



Thank you very much for your help,


Dra. Laia Alsina
Sección de Alergia e Inmunología Clínica
Hospital Sant Joan de Déu
Passeig Sant Joan de Déu nº2
08950 Esplugues de Llobregat, Barcelona
+34932804000 ext 3330
________________________________________

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The CIS-PIDD listserv is supported by:
Clinical Immunology Society - The science & practice of human immunology

P: +1.414.224.8095
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The CIS-PIDD listserv is supported by:
Clinical Immunology Society - The science & practice of human immunology

P: +1.414.224.8095
E: info at clinimmsoc.org<mailto:info at clinimmsoc.org>

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