[PAGID] Autoimmune neutropenia

[Stephan Ehl]

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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>>

>>   


-- 
Prof. Dr. Stephan Ehl
Immunologie/Rheumatologie

UNIVERSITAETSKLINIKUM FREIBURG
Zentrum für Kinderheilkunde und Jugendmedizin
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79106 Freiburg

Tel +49 761 270-4309 (4301) / Fax -4599
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