[CIS PIDD] Recurrent HLH like episodes with persistent splenomegaly

[Joshi, Avni Y., M.D.]

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/>  

> 

> 

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