[CIS PIDD] Recurrent HLH like episodes with persistent splenomegaly

[Seidel Markus]

Dear Avni,

Did EBV play a role in these episodes? Did the boy develop ENB1 Abs? How low
are the B cells, how are the B-subsets? Vaccination antibodies?

Is the T Vb repertoire skewed?

Range of iNKT cells, NK cytotoxicity, aptopostis assays?

Do you know about the CD27 expression? ITK deficiency possible? 

Has LCH, although unlikely, been excluded?

Also unlikely, but what about granulomatous disease, neutrophil function
tests (I know a boy who after recurrent massive lymphadenopathies, often
responding to antibiotics, sometimes to steroids, with chronic splenomegaly
who was identified as X-CGD at 14yrs of age; admittedly, he had had Crohn's
like disease as a toddler and [borderline] normal neutrophil tests
previously). And I am sure you measured ACE and obviously excluded
sarcoidosis (histology), yersinia pestis or other infections (would not
improve under steroids),.?

In my opinion, it appears a little too "early" to discuss BMT,

Thanks for an update,

Sincerely, Markus Seidel

 

Markus G. Seidel, M.D., Assoc.Prof.

Consultant| Dept.of Pediatric Hematology-Oncology | Univ.Clinics of
Pediatric and Adolescent Medicine | Auenbruggerpl. 34/2 | A-8036 Graz |
Austria | T. 0043 316 385 80215| F. 0043 316 385 13450

Coordinator of the Working Group for Pediatric Immunology of the Austrian
Society of Pediatrics and Adolescent Medicine

 

 

  _____  

Von: pagid-bounces at list.clinimmsoc.org
[mailto:pagid-bounces at list.clinimmsoc.org] Im Auftrag von Joshi, Avni Y.,
M.D.
Gesendet: Donnerstag, 19. Juli 2012 19:51
An: pagid at list.clinimmsoc.org
Cc: Khan, Shakila P., M.D.
Betreff: [CIS PIDD] Recurrent HLH like episodes with persistent splenomegaly

 

Dear Colleagues, 

We would appreciate input on this child who have come all the way from India
paying out of pocket for a second opinion about the possibility for BMT:

This is a 12 yr old  Asian Indian boy ( non consanguineous) who has a
history of recurrent episodes of lymphadenopathy and cytopenias.

He started off about 4 yrs. ago , with an episode of high grade fever, LAD
and splenomegaly. Infectious w/up in India was negative, yet was treated for
typhoid fever. Things were quiescent for the next two years except that his
spleen was still palpable.  Dad, being a surgeon, would examine him, but he
was symptomatically doing well. In 2008, he developed some skin lesions  was
seen by a dermatologist and were thought to be erythema nodosum and was
given prednisone for 20 mg per day.  The spleen size improved significantly
while being on prednisone, but his skin lesions did not improve.
Prednisolone was stopped after a month's time, and his skin lesions slowly
improved in the next two to three months' time. He had another recurrence of
these episodes of high-grade fever with cytopenia, splenomegaly, and
lymphadenopathy when he was seen by a hematologist , who diagnosed him to
have ALPS.  His double-negative T-cells were in the normal range.  Bone
marrow biopsy was normal and was negative for lymphoma, and his lymph node
biopsy samples were sent to Oxford which showed there were no B-cells, but
there was increased T cell numbers, mostly CD8s.Coombs testing/antiplatelet
antibody testing not done.

High dose steroids did improve his symptoms, and he did well for a year's
time until last year when he had recurrence of his splenomegaly, with his
spleen reaching into his right iliac fossa.  He was seen by an immunologist
and his double-negative T-cells were borderline high.  He was again
diagnosed with ALPS, and genetic testing for FAS, Fas-L, and Caspase-8 was
sent to Japan and was negative.  He was initially started on mycophenolate
mofetil which did not improve his symptomatology.  He was then switched to
sirolimus. His counts drop on sirolimus monotherapy but stabilize when
Prednisolone was added. He developed varicella on the combination in Dec
2011.  

More recently, in April 2012 he was diagnosed with neuropathy.  EMG is
suggestive of sensorimotor peripheral neuropathy with features that would
suggest a combination of demyelination and axonal loss.   He had recurrence
of the skin lesions which were biopsied and showed evidence of occasional
histiocytes.

His bone marrow biopsy has shown evidence of hemophagocytosis on and off
during these events. 
Only significant F/H is a maternal cousin has sensorineural hearing loss. 
He is currently on 20mg/d of prednisolone ( close to a year now)and 3mg/d of
Sirolimus. 

Labs in US: 
CBC: mild lymphopenia and thrombocytopenia, no eosinophilia. 
TBNK: T ,B and NK cell lymphopenia 
ALPS screen: Negative 
sIL-2: 1010 ( Normal: 45-1105 U/ml) 
NK subsets :Normal and robust expression of perforin and Gran A/ Gran B 
SAP and XIAP expression: Normal 
Bone/lymphnode/Skin Bx read here: essentially normal, occasion expression of
CD1a and S-100 positive Langerhans cells, relative paucity of B cells. No
granulomas.(The Bx have been on at least 20mg/d of Prednisolone)

Immunoglobulins:A,M, G and E: Normal, never been on IGIV. 
Recent Thymic Emigrant (CD4RTE): Modestly decreased. 
Vit B12: Normal 
Ferritin: Normal 

Would you consider leaky SCID, hypomorphic RAG mutation? 
Due to financial constrains, we have not performed any genetic testing yet. 
Dad is 9/10 match . 
I'd appreciate any thoughts, recommendations or insights. 
Would you recommend BMT? 

Thank you so much for your time, 
Avni 

 

Avni Y Joshi, MD, MSc
Assistant Professor of Pediatrics and Medicine
Pediatric and Adult Allergy / Immunology
Cellular and Molecular Immunology Laboratory
Pager: 507-293-5387
Secretary: 507-538-0127
Fax: 507-284-0727
E-mail: joshi.avni at mayo.edu
_______________________________
Mayo Clinic
200 First Street SW
Rochester, MN 55905
www.mayoclinic.org <file:///\\www.mayoclinic.org\>  

 

-------------- next part --------------
An HTML attachment was scrubbed...
URL: <http://seven.pairlist.net/pipermail/pagid/attachments/20120805/3e1b8aa7/attachment.html>