[CIS PIDD] [cis-pidd] Refractory thrombocytopaenia, splenomegaly and high IgM
CIS-PIDD
cis-pidd at lists.clinimmsoc.org
Sun Feb 28 22:42:18 EST 2016
Dear all,
We are seeing a patient in Perth, Western Australia, together with our
haematology colleagues who has refractory thrombocytopaenia and
splenomegaly. She is a 10 year old girl, no significant past medical
history prior to this episode. Dad (part Japanese and born in Australia),
mum (Romanian) and a 7 year old brother are all well. No family history of
autoimmune, lymphoproliferative or immunodeficiency diseases. She has
received routine childhood vaccinations without adverse reactions.
She had a systemic illness in September 2015 lasting 5 days with high
fevers and generalised aches. About 1-2 weeks later, Mum noticed increased
bruising with blood tests confirming thrombocytopaenia (platelet count 2 x
10^9/L).
On initial review in November 2015, the patient felt well with no weight
loss, fevers or sweats. She had petechiae and ecchymoses with marked firm
splenomegaly ~10cm below costal margin.
Initial investigations
Full blood picture – normocytic anaemia (Hb 10g/dL), mild neutropaenia 1.1
x 10^9/L, lymphocytes 1.9 x 10^9, a few atypical lymphocytes on blood film
suggestive of viral infection
Ferritin 39mcg/L (normal 20-100), transferrin saturation slightly low at
10%. Normal Vitamin B12 (540pmol/L)
Normal UEC, liver function and LDH
EBV and CMV IgG and IgM negative
IgG 10.6, IgA 0.5, *IgM 16.3 g/L*, no paraprotein
C3 is slightly low at 0.69g/L, normal C4 0.29g/L
ESR 70mm/hr, CRP normal
Raised lambda > kappa serum free light chains (ratio of kappa:lambda
borderline low).
Negative ANA, dsDNA, lupus anticoagulant, rheumatoid factor.
Weak positive IgM anti-cardiolipin, moderate IgA B2GPI; negative IgG aCL
and B2GPI.
Lympohcyte immunophenotyping on 2 occasions:
CD3 (T cells) 84 82 %
(58-76) *
CD4 (CD4+ T cells) 54 53 %
(30-52) *
CD8 (CD8+ T cells) 24 23 %
(18-40)
CD4/8 Ratio 2.25 2.30
(0.70-2.60)
CD19 (B cells) 9 5 %
(11-27) *
CD16/56 (NK cells) 7 13 %
(5-19)
CD3 Absolute Count 1008 1558 x10 ^6 /L
(900-2500)
CD4 Absolute Count 648 1007 x10 ^6 /L
(500-1400)
CD8 Absolute Count 288 437 x10 ^6 /L
(400-1300) *
CD19 Absolute Count 108 95 x10 ^6 /L
(200-500) *
CD16/56 Absolute Count 72 228 x10 ^6 /L (100-500)
GATED ON CD19+ B CELLS:
Naive B (IgD+CD27-) 89.4 %
(49.0-100.0)
MZL Mem B (IgD+CD27+) 9.2 %
(2.0-28.0)
CD27+ Sw Mem B (IgD-CD27+) 1.1 %
(1.0-43.0)
CD27- Sw Mem B (IgD-CD27-) 0.3 %
(3.0-10.0)
Bone marrow was hypercellular with increased numbers of morphologically
normal megakaryocytes and normal haemopoiesis. There was no evidence of
infiltration. Cytogenetics: normal (X;X).
Treated with high dose IVIg (2g/kg) with no response.
PET scan (December 2015): diffuse moderate metabolic activity in spleen
associated with some lymphadenopathy.
Axillary lymph node excision: Reactive hyperplasia. No evidence of lymphoma
or Castleman’s disease.
No clonal B or aberrant T cell population on flow cytometry of the node.
Received IV methylprednisolone x 3 doses in January 2015 with no rise in
platelet count.
Repeat lymphocyte immunophenotyping in January and February 2016, including
TCR studies on double negative T cells
Lymphocytes 2.3 1.7 x10 ^9 /L
(1.5-7.0)
CD3 (T cells) 84 82 %
(58-76) *
CD4 (CD4+ T cells) 55 57 %
(30-52) *
CD8 (CD8+ T cells) 23 19 %
(18-40)
CD4/8 Ratio 2.39 2.95
(0.70-2.60) *
CD19 (B cells) 6 5 % (11-27)
*
CD16/56 (NK cells) 10 12 %
(5-19)
CD3 Absolute Count 1932 1394 x10 ^6 /L
(900-2500)
CD4 Absolute Count 1265 952 x10 ^6 /L
(500-1400)
CD8 Absolute Count 529 323 x10 ^6 /L
(400-1300) *
CD19 Absolute Count 138 85 x10 ^6 /L
(200-500) *
CD16/56 Absolute Count 230 204 x10 ^6 /L (100-500)
CD3+CD4-CD8- T-cells =
7.7%
TCR as a % of CD3+
cells:
CD3+CD4-CD8-TCR Alpha/Beta
=4.6%
CD3+CD4-CD8-TCR
Gamma/Delta=2.9%
TCR as a % of
Lymphocytes:
CD3+CD4-CD8-TCR Alpha/Beta =3.5%
CD3+CD4-CD8-TCR Gamma/Delta=2.2%
The patient remains well, aside from thrombocytopaenia and bruising. Her
spleen is still enlarged, IgM now 21.8 g/L, platelets remain low (3 x
10^9/L). EBV and CMV IgM and IgG were negative in both November and
February. HHV6 IgG was positive with negative IgM in November, and on
repeat in February HHV6 IgM and IgG were both positive.
We will arrange sequencing of FAS, FASL, FADD, CASP8 and CASP10 (despite
the normal vitamin B12), and were planning a trial of sirolimus in advance
of a definitive diagnosis based on the encouraging results from recent
publications in ALPS and other refractory cytopaenias.
I’d appreciate any recommendations the group may have on further
investigations or treatment options, particularly if you would suggest
considering an alternative to sirolimus?
Kind regards,
Michael
*Michael O’Sullivan *| Consultant | Immunology
*Fiona Stanley Hospital*
Level 1, Pathology, 102-118 Murdoch Drive, MURDOCH WA 6150
T: (08) 6152 8006 | F: (08) 6152 8051
*Princess Margaret Hospital*
Roberts Road, SUBIACO WA 6008
T: (08) 9340 8310 | F: (08) 9380 6246
E: michael.o’sullivan at health.wa.gov.au <first.last at health.wa.gov.au>
www.health.wa.gov.au
Delivering a *Healthy WA*
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