[CIS-PAGID] a question about a 20 mo old boy with FTT

[Dewton Vasconcelos]

Dear YaeJean

I would be aware of the use of corticosteroids as well, but he is being 
aggressively (adequately) treated for the infectious complications, and 
if the pulmonary function is worsening I would try steroids.

By the way I made a mistake, writing CD15 in my e-mail, but I was 
talking about IL15 receptor.

The presence of NKT cells suggest a classical NK cell deficiency. They 
do not present NK cell cytotoxicity even when stimulated by IL-2 or type 
1 IFNs.

Nevertheless the possibility of STAT-5 deficiency must be ruled out as well.

Obs: ZAP 70 deficient patients may present low but not absent CD8 T 
cells in mutations outside the kinase domain of ZAP70.

All the best,

Dewton


YaeJean Kim wrote:

> Dear all,

> This is a f/u.

> His thyroid fx still abnormal: endocinology people say this could be 

> secondary hypothyroidism (low free T4 and still low TSH). I think this 

> child might have abnormal HPA axis..wonder about GH def as well. I 

> read some articles about GH insensitivity and immune deficiency (hyper 

> IgM was reported, STAT 5b mutation was reported..) and growth 

> retardation (this child weighs 7 kg at 20 mo of age).

> We plan to do ACTH stimulation test and GH hormone measurement 

> tomorrow and STAT flow on monday..

> Dear Dr. Sullivan did you mean DKC (dyskeratosis congenita)? He does 

> not seem to have mucocutaenous findings and nail findings of it.

> His lung condition is getting bad (not ARDS yet) with increasing CRP, 

> more sputum, patchy pulmonary infiltration and pancytopenia : he is 

> now on meropenem, vancomycin, amphotericin, ganciclovir (antigenemia), 

> oseltamivir (still influenza positive)...

> I appreciate further comments.

> YaeJean

> ------------------------------------------------------------------------------

> Other question from  another colleague,

>

> Is there consanguinity? -> _no_

>

> Does he have liver, spleen, lymph node changes? ->_ liver is enlarged._

>

> Could this be HLH (NK=0)? -> _checked for HLH criteria...not yet 

> satisfied. _

>

> I can’t see platelets – is that the 142K? -> yes it was 142k but now 

> it is 31K

>

> Have you done ferritin, lipids? -> _will f/u the labs. Ferritin was 

> not superhigh, TG was ok. _

>

> Does DHR negative mean no activity? It doesn’t sound like CGD.-> _I 

> meant normal DHR. _

>

>

>

> On Fri, Mar 4, 2011 at 7:15 PM, Sullivan, Kathleen 

> <sullivak at mail.med.upenn.edu <mailto:sullivak at mail.med.upenn.edu>> wrote:

>

>     If he was IUGR, think about DKC.

>

>     On Mar 3, 2011, at 11:22 PM, YaeJean Kim wrote:

>

>>     Dear colleagues,

>>     Thanks for your feedback, I will talk to our lab medicine people

>>     to ask further tests.

>>     *There is a correction in my previous email: IgG level went down

>>     from 787 to 226 after about 10 days (_not 1 day_)...*

>>     His NK cells were identified by CD16+CD56-CD3- and it was 0.

>>     They also did staining for NKT and it was 3% (CD16+56+3+).

>>     If there is no bacteria from the tracheal culture...if this could

>>     be virus infection associated BOOP...should I think of steroid

>>     (at least of stress dose or steroid inhalation)? but I am very

>>     nervous about using steroid in CMV viremic baby.

>>     Anyway, this weekend will be very tough for the baby and the

>>     parents are anxious. Thanks.

>>     YaeJean

>>     PS)

>>     My previous patient with CGD (liver abscess) is doing well (now

>>     out of PICU) after multiple granulocyte infusion. I persuadeed

>>     the surgeon and we will do the surgery on this coming Monday.

>>     Thanks a lot.

>>

>>

>>     On Fri, Mar 4, 2011 at 10:56 AM, <dmvascon at usp.br

>>     <mailto:dmvascon at usp.br>> wrote:

>>

>>

>>         Hi YaeJean, good evening

>>

>>         Another very interesting case from your casuistry.

>>

>>         The clinical features look like a NK deficiency, which is

>>         very rare but must be reminded.

>>

>>         Is the family consanguineous? It is interesting to look for

>>         NK as well as NKT cells, and if possible to test for NK cell

>>         cytotoxicity (by a 51Cr release assay). It would be

>>         interesting to look for the few (if any) NK cells and their

>>         expression of CD56 (dim or high), which possess different

>>         functions.Gamma common and Jak3 deficiencies present NK cell

>>         deficiencies along with Tcell decreases as well.

>>

>>         Some years ago I saw a poster at an ESID meeting of a patient

>>         with absent expression of the alpha chain of the CD15

>>         receptor (which shares the beta and gamma chain with IL2

>>         receptor), but they didn't identify the mutation and I've

>>         never seen any other citation of this patient.

>>

>>         I would try to test for STAT-5 phosphorylation after

>>         stimulation by IL-2 and IL-15.

>>

>>         On the clinical side I would treat aggressively for CMV (and

>>         other possible herpesvirus) and think about the possibility

>>         of a virus induced BOOP instead of several bacterial pneumonitis.

>>

>>         Good luck for your patient.

>>

>>         Best regards,

>>

>>         Dewton

>>

>>         Dewton de Moraes-Vasconcelos

>>         University of São Paulo School of Medicine

>>

>>         Citando YaeJean Kim <yaejeankim at skku.edu

>>         <mailto:yaejeankim at skku.edu>>:

>>

>>

>>             Dear all,

>>

>>             I have another 20 mo old boy to ask your opinions. Sorry

>>             but this is long.

>>

>>             20 mo old boy presented with chronic sino-pulmonary

>>             infections.

>>             already has 4 hospitalization d/t pneumonia to other

>>             hospital in 2010

>>

>>             This time, first presented to other hospital d/t

>>             influenza and pneumococcal

>>             bacteremia for which he received ICU care (IVIG was given)

>>             He continued to have desaturation and pulmonary sx ->

>>             transferred to our

>>             PICU.

>>

>>             FHX: his sister died at age 3 y d/t aspiration pneumonia

>>             per mom. She

>>             had develpmental delay, FTT and serious infection [r/o

>>             pulmonary TB (AFB

>>             trace one time-> medication done, candida septisemia

>>             (nosocomial?)], seizure

>>             disorder. [immune w/o of sister showed normal DHR, lympho

>>             subset shoed

>>             decreased NK (less than 1%), C4 (5.2)] no further w/o.

>>

>>             Back to this patient:

>>             His condition has been up and down (pulmonary sx

>>             aggravated with eating, we

>>             were concerned about gastroesophageal reflux and plan to

>>             pH monitoring but

>>             missed the chance to do the study..esophagogram was done

>>             to check for H type

>>             TE fistula which was negative.

>>

>>             His lab on arrival at our hospital:

>>             CBC (2/19)  4.77-42.1-142K (diff count: S75, L21, M3.6),

>>             NAC 3.5, ALC 1.0

>>

>>             DHR negative, IgG 787 mg/dL, IgA 73 mg/dL, IgM 452 mg/dL,

>>             IgE 0 U/mL,  CH50

>>             44 U/mL

>>              -> before we got the lympho subset..based on incrased

>>             IgM, we did CD40/CDL

>>             flow which was OK.

>>

>>             Lympho subet

>>             CD 19:  0.18 x10^9/L [median 0.8 (nl range 0.2-2.1)]

>>             CD3:     0.74             [2.3 (nl 0.9-4.5)]

>>             CD4      0.67             [1.3 nl 0.5-2.4)]

>>             CD8      0.69             [0.8 (nl 0.3-1.6)]

>>             NK        0                 [0.4 (nl 0.1-1.0)]

>>

>>             CD19   19%   [24 (14-44)]

>>             CD3     77%   [64 (43-760)]

>>             CD4     70%   [37 (23-48)]

>>             CD8     9%     [24 (14-33)]

>>             NK       0%     [10  (4-23)]

>>

>>             He has now CMV antigenemia over 100/slide for which he is

>>             on ganciclovir, I

>>             started bactrim (no PCP identified though), and he also

>>             has on amp/sulbactam

>>             (sinusitis and pneumonia, d/t prabable aspiration..)

>>             His chest CT (1/26 outside hospital): multifocal

>>             consolidation and

>>             peribronchild infilraion wih multiple mediastinal LN

>>             enlargement (this was

>>             after influenza, pneumococcal bacteremia)

>>             a f/u chest CT (2/19 on arrival to our hospital): internal

>>             improvement...with periportal edema..

>>

>>             NOW, his condition really deteriorated after (waxing and

>>             waning over the 10

>>             d), He is in PICU again. lympho proliferation is

>>             pending..other gene studies

>>             pending..

>>             with ganciclovir, he has significant

>>             cytopenia..1.35-30.8-31K: we are giving

>>             GCSF..

>>             He has thyroid function abnormality, persistent

>>             hyponatremia...

>>

>>             I thougth first he might have hyper IgM..then I thought

>>             SCID. But the

>>             initial lympho subset could have been just low d/t recent

>>             significnat

>>             infection and the percent does not really match..He has

>>             0% of NK cell (his

>>             sister had also low countss)..

>>             His IgG went down from 787 to 226 after about 1 days...I

>>             gave further IVIG.

>>

>>             At this point, I'd like to ask your opinion about which

>>             direction I should

>>             go to narrow down the ddx.

>>             Thanks a lot.

>>

>>             YaeJean

>>

>>

>>

>>

>>

>

>     Kate Sullivan, MD PhD

>     Professor of Pediatrics

>     ARC 1216 Immunology CHOP

>     3615 Civic Center Blvd.

>     Philadelphia, PA 19104

>     (p) 215-590-1697

>     (f) 267-426-0363

>

>

>