[PAGID] Autoimmune neutropenia
Chris Seroogy
cmseroogy at pediatrics.wisc.edu
Wed Jul 16 10:36:56 EDT 2008
Stephen,
I have not excluded WAS. His platelet volume appears normal with excellent
counts. Flow does not demonstrate low CD8 (in my experience a prominent
feature) and Treg numbers robust. But, I agree remains a possibility.
Sorry I wasn't clear on the DNTCs. This was run at Cincinnati and Jack can
correct me if I misstate. For the ALPS panel, he has 2/4 criteria:
1. Absolute DNTCs 127 (reference range 6-33) of these 24.7% are B220+DNTCs
2. CD27+ B cells are low at 6% (reference range 15-52)
Interpretation, abnormal study but not clearly suggestive of ALPS.
Chris
On 7/16/08 9:22 AM, "Stephan Ehl" <stephan.ehl at uniklinik-freiburg.de> wrote:
> Chris,
>
> have you excluded WAS?
> what do you mean by ALPS panel normal but 22% DNT cells?
>
> Ashish,
>
> do you have fibroblast from your patient? We could do a VDJ
> recombination assay in these cells to investigate the significance of
> the RAG mutation in your patient.
>
> Best wishes,
>
> Stephan
>
> Ashish Kumar schrieb:
>> Chris,
>>
>> You described a typical case of autoimmune neutropenia. AIN can last
>> a long time and I don't think G-CSF is doing much other than making us
>> feel better when we temporarily fix his neutropenia. You could give
>> him all the G-CSF you want, but as soon as you stop it, his
>> neutropenia will recur. The bone marrow findings are also typical of
>> AIN. I have a hard time chalking the sepsis/osteomyelitis to AIN, and
>> it may be the other way around. MRSA osteomyelitis can occur with a
>> normal neutrophil count too.
>>
>> I have a patient who had sever AD and FTT, who had eosiniphilia, high
>> IgE, and initially also had lymphocytosis - ALC of 24k, mostly
>> T-cells. He too had normal FOXP3 expression with relatively high
>> number of CD25+/FOXP3+ cells and every other immune testing was
>> negative as well. I found him to have a heterozygous RAG-2 mutation,
>> one that hasn't been described before. No one knows if this was a red
>> herring or not, but my patient is also African-American with a strong
>> family history of atopic dermatitis. He also tested positive for all
>> food allergies. I tried several topical steroid preparations for his
>> skin, none worked and he had chronic watery diarrhea that kept him
>> from gaining weight. At 10 months, he weighed 4.5 Kg. Systemic
>> steroids made him a new kid in 1 week. When I tapered the steroids,
>> his skin and diarrhea flared again, so I have initiated a very slow
>> wean. He has finally gained some weight. I now ignore the food allergy
>> tests in these patients and rely on challenge which typically allows
>> resumption of a normal diet.
>>
>> Ashish
>>
>> Ashish Kumar, MD, PhD
>> Assistant Professor of Pediatrics
>> Division of Hematology/Oncology/Blood and Marrow Transplantation
>> University of Minnesota
>>
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>> Chris Seroogy wrote:
>>> Dear Colleagues,
>>>
>>> I would appreciate any thoughts on an enigmatic 10m/o African
>>> American boy
>>> followed at our institution for multiple medical problems. He was
>>> born term
>>> and well except for mild atopic dermatitis until Jan. of this year.
>>> At that
>>> time he presented with MRSA sepsis/osteomyelitis (hip) and
>>> neutropenia. His
>>> bone marrow showed increased myeloid precursors and trilineage
>>> hematopoiesis. Extensive immune evaluation negative. The
>>> neutropenia was
>>> felt to be secondary to his infection felt to be caused by breakdown
>>> of his
>>> integument. However, the neutropenia has persisted to the point that
>>> our ID
>>> folks started GCSF. I was consulted some months later to revisit his
>>> immune
>>> system since he had and influenza A infection and history of
>>> recurrent URTI.
>>> There is a strong family history of atopic and this child has severe
>>> AD and
>>> probable clinical food allergy with FTT thought to be secondary to poor
>>> intake. We have optimized his diet and he is making slow, but steady
>>> gains
>>> in his weight. Development is not a concern.
>>> Notable data:
>>>
>>> Repeat flow, antibody levels and titers, CH50, HIV all negative/normal.
>>> IgE 2000 with multiple food sensitivities
>>> Foxp3 detactable and high percentage in CD25+
>>> ALPS panel not indicative of ALPS, but high % B22-+DNTC (24.7%)
>>> Antineutrophil antibodies strongly positive (>3SD and run at ARUP)
>>>
>>> No enlarged liver or spleen. We held his GCSF and repeated
>>> marrow--it was
>>> difficult to interpret even 4 days off GCSF with a tremendous number of
>>> hematogones, trilinear hematopoiesis and mostly mature granulocytes
>>> in the
>>> granulocytic lineage.
>>>
>>> We tried high-dose IVIG thinking that might give a respite from GCSF and
>>> this was without success. His neutrophils have been consistently
>>> below 500
>>> while holding GCSF now. He is being admitted for fever with an ANC 180.
>>>
>>> My question is if this is a phenotype that others have seen? Any
>>> recommended additional testing or therapeutic interventions? Thank
>>> you for
>>> your opinions, Chris
>>>
>>>
>>> Chris Seroogy, M.D.
>>>
>>> University of Wisconsin
>>>
>>> Assistant Professor
>>>
>>> Dept. of Pediatrics
>>>
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>>>
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