[CIS PIDD] 8mo old boy hypereosinophilia

[Reichenbach Janine]

Dear colleagues,

We would like to ask for your advice concerning a 7 months old boy, first child of non-consanguineous Swiss-Italian and Italian-South American parents, born at term with normal weight (3040g) and length (48cm).

The neonatal period was absolutely unremarkable, and then from 8 weeks onward severe, ongoing eczema with secondary total alopecia, and failure to thrive (no diarrhoea) was noted. At 5 months of age he developed fever and symptoms of upper respiratory tract infection with positive test for Picornavirus in nasal fluid (only 3 days of fever and no complications under symptomatic therapy). He had clinical and laboratory features of HLH without evidence for hemophagocytosis in bone marrow or blood, which resolved under low dose steroid treatment. Shortly after this episode a blood count showed excessive leukocytosis so that he was referred to our Division of Immunology/BMT for further investigation.

We noted massive eosinophilia and lymphocytosis, as well as elevated IgA and IgM in presence of normal IgG, the bone marrow-biopsy revealed no signs of malignancy, HLH or mastocytosis. The skin biopsy and LEKTI analysis excluded Netherton Syndrome, but evidenced massive T cell infiltrates in the skin. Histopathologists described the lesions as "juvenile xanthogranuloma". He had splenomegaly > hepatomegaly. Besides he is described to have recurrent urticarial skin lesions and recurrent swelling of the face.

Recently he has developed a central paresis of the facial nerve and multiple small cerebral infarctions (new ones and old ones) as well as a general cerebral atrophy, and lesions which could be suggestive of bleeding or vasculitis were noted on the MRI. The repeated bone marrow done for anaemia and thrombocytopenia showed progressive myelofibrosis. Oncologists have then treated him with high dose corticosteroid and Imatinib, resulting in reduction of the eosinophilia from 30G/l to 5G/l.

The lymphocyte phenotyping showed a marked lymphocytosis with elevation of all lymphocyte subsets and NK cells, normal CD4+25+/127- , perforin, CD40 and HLA class I and II expression. NK cell cytotoxicity test is pending.
PBMC show normal proliferation to stimulation with mitogens (PHA, Staph. Enterotoxin, Anti-CD3), but absent proliferation to stimulation with antigens (Candidin, Tetanus, CMV, PPD). Vaccination antibody titres for Tetanus and Pneumococcus are negative 2 weeks after the second immunization.
The T cell receptor rearrangement was normal and there is no evidence for maternal T cells in the peripheral blood.

The total IgE was 412 kU/l and TH17 cells were low, the analysis of STAT3 Hotspots and DOCK8 is ongoing.

Although local dermatologists do not think the alopecia is linked to EDA (he began to loose his hair, eyebrows and eyelashes by the age of 8 weeks, is able to sweat and his mother does not have signs of Incontinentia pigmenti), in the presence of unspecific eosinophil dermatitis, we are considering to study NEMO/IKBA, if DOCK8 and STAT3 are normal.

Any input concerning this puzzling patient would be greatly appreciated.
Thank you very much in advance for your help and advice.

Please contact Dr. Miriam Hoernes (Miriam.hoernes at kispi.uzh.ch<mailto:Miriam.hoernes at kispi.uzh.ch>) who is not yet on the CIS-PIDD listservs for further information.

Best regards,
Janine Reichenbach


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PD Dr. med. Janine Reichenbach
Oberärztin Abteilung Immunologie/Hämatologie/KMT
Jeffrey Modell Diagnostic and Research
Center for Primary Immunodeficiencies

Universitäts-Kinderspital Zürich
Steinwiesstrasse 75
CH-8032 Zürich
Tel.: +41 (0)44-266-7341
Fax: +41 (0)44-266-7914
e-mail: janine.reichenbach at kispi.uzh.ch<BLOCKED::mailto:janine.reichenbach at kispi.uzh.ch>
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