[CIS-PAGID] a newborn with an extensive skin lesions_a follow-up question

[Sullivan, Kathleen]

Any monocytes in the CBC?

We have two boys with similar stories and they are being worked up for GATA2 deficiency.  Clinically- they are not like those Steve Holland described but they have had low B, monocytes, and NK cells.



On Sep 18, 2011, at 5:42 AM, YaeJean Kim wrote:


> Dear All,

>  

> I asked a question about 2 months ago and this is a follow-up question. I apologize in advance that this is long.

>  

> The patient was a neonate with extensive skin lesion, increase WBC, CRP, ESR, hepatoplenomegaly, persistent fever,  depressed lymphocyte proliferation activity, and almost no B cells. 

>  

> At that time, with valuable feedbacks from you, I started to evaluate the baby but now am still without the definitive diagnosis. The initial ddx were hyper IgE, leaky SCID with maternal engraftment, Omenn's syndrome, DIRA, NOMID/CINCA, etc...

>  

> This baby got multiple blood tests including gene test, BM exam, skin biopsies...

>  

> 1. So far,  mutations in the genes for STAT 3, Rag1/2, ARTEMIS, and IL1RN were tested which were all negative. DHR was normal. Perforin expression in NK cells appears to be ok..

> 2. Bone marrow chimerism was negative. No bone lesions or joint abnormalities in the extrimities.

> 3. Bone marrow: no evidence of phagocytic lymphohistiocytosis, no malignancy

> 4. skin lesions: no evidence of histiocytosis Lnagerhans: s100, CD1a were negative. They say it looks like vasculitis but there is no C3, IgG, IgA, or IgM stained in the skin and MPO positive

> 5. autoimmune markers were negative. FANA (-) dsDNA ab.(-), Anti-SSA/Anti-SSB(-/-)

> 6. brain sono: persistently increased parenchymal echogenicity involving bilateral deep gray matter and white matter..no obvious seizure yet..but we plan to do EEG this week since I saw a very subtle but suspicious absent seizure like moment..

> 7. still no B cells as of 8/26/2011.

> 8. CBC as of 9/14/2011: 20.65(WBC)-8.8(Hb)-92K(PLT) ESR 69

>  

> At this point, we don't have a definitive dx (at least no malignancy). Until 2 weeks prior, she had been in relatively good condition with all the skin lesions appeared calming down on steroid and NSAID (so, we tapered to 1.5 mg/kg). So, Hem-Onc guy is kind of off from the scene and he is not actively talking about transplanting the baby.

>  

> But since last week, she started to have new skin lesions, mild fever, irritability... I bumped the steroid again and did the infection surveillance, gave antibiotics briefly for 3- days ..she appeared to get better but now her condition is getting really bad again and I see there is a tissue necrosis around the upper lips... we gave IVIG, started antibiotics again and will plan to do skin biopsy..just in case if this is a super infection with unusual pathogen (e.g., mold infection?). It appeared that blood flow is compromised (there is pale area first and then necrosis developed)...I just stopped NSAID(Ibuprofen) today because of worry about any relatedness to the skin necrosis...this could be her "usual just inflammation" like previous lesions and no skin infection because this necrosis got worse with other new skin lesions appeared, at the same time...but still, this time it looks different (looks like blood vessel insufficiency)...I attached the photo.

>  

> I haven't tested the gene for the NLRP3 gene(CIAS1) for NOMID/CINCA, yet. I will do the test. 

>  

> At this point, I ask your opinion on this baby. Any additional suggestions or idea what do test more? Advice for management will be also appreciated. The family is poor and have unstable family dynamics (father being hostile to the medical staff) altough with mom, we have a very good rapport...I am very concerned that this baby will eventually get deteriorated after this waxing and waning period.

>  

> Thanks a lot for your advice.

> Regards,  

> YaeJean  

>  

> 

>  

> On Mon, Jul 11, 2011 at 12:14 AM, <christian.wysocki at yale.edu> wrote:

> 

> Would this not be a great case for TREC analysis?  A rapid, PCR-based assay.  I

> would think that, based on available literature, if TRECS are absent, this

> would be extremely informative and strongly support this as Omenn/Leaky

> SCID/maternal T cell engraftment.  Would at least lead one quickly in the

> direction of immune deficiency and away from autoinflammatory

> disease/vasculitis.

> -Chris Wysocki

> A/I fellow, Yale

> 

> 

> Quoting "Verbsky, James" <jverbsky at mcw.edu>:

> 

> YaeJean

> 

> Do you have CD4 RO%..should be high with leaky scid, Omenn, maternal engraftment, etc

> 

> Does the child have bone lesions?  NOMID and IL1 receptor antagonist  deficiency presents at birth with rash (usually pustular and full of PMN).  THe rash and inflammatory markers are suggestive but the lymphocytic infiltrates on bx doesnt really fit.  Regardless, I have tried anakinra in cases like this with worsening disease without a diagnosis..its short acting and relatively safe.  If it works..it is ususally dramatic.  It there is no effect after 2-3 days..it can be stopped.

> 

> Best

> 

> 

> James W. Verbsky M.D./Ph.D.

> Assistant Professor of Pediatrics and Microbiology and Molecular Genetics

> Medical College of Wisconsin

> Children's Corporate Center

> Pediatric Rheumatology, Suite C465

> 9000 W. Wisconsin Ave., PO Box 1997

> Milwaukee, WI 53201-1997

> (work) 414-266-6585

> (pager) 414-907-3134

> (fax) 414-266-6695

> jverbsky at mcw.edu<mailto:jverbsky at mcw.edu>

> verbskyj at yahoo.com<mailto:verbskyj at yahoo.com>

> 

> 

> 

> 

> ________________________________

> From: pagid-bounces at list.clinimmsoc.org [mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of YaeJean Kim

> Sent: Thursday, July 07, 2011 7:56 AM

> To: pagid

> Subject: [CIS-PAGID] a newborn with an extensive skin lesions

> 

> Dear All,

> 

> I have a question about a neonate with severe skin lesions.

> 

> 40 days old female full-term baby who presented with whole body rash since day 3 after birth.

> She has been treated multiple rounds of antibiotics for r/o sepsis (leukocytosis and high CRP, no pathogen, skin lesion) and was transferred to our NICU.

> 

> No significant birth hx (full-term, 2.8 kg, vaginal delivery), or family hx of PID.

> 

> On arrivail, extensive skin lesions and striking leukocytosis continued

> 6/14/2011 WBC 39.4 (Myelocyte 10, metamyelo 8, band 4, seg53, lymph 18, mono 6, atypical lymph 1, eos 0), Hb 10, plt 99

> 7/2/2011   WBC 56.5 (myelo 9, metamyelo 9, ban 7, seg 59, eos 1, lympho 12, mono 11),  Hb 8.9, Plt 55K

> HIV-, VDRL-

> 

> -> recently fever continued, developed mild hepatosplenomegaly

> 

> DHR normal

> 

> IgG 1090 mg/dL (<- IVIG was given at other place)

> IgA 5 mg/dL

> IgM 8 mg/dL

> IgE 161.5 IU/mL

> CH50 85 U/mL

> 

> lymphocyte subset

> =========================

> Parameter             Test value            reference   for her age

>  (MoAb)              %  Count(/ul)                            %                     count

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

> T  (CD3)                 88   5,974                  72% (60-85%) ,   4,600 (2,300-7,000)

> T4 (CD4)                72   4,867                  55% (41-68%),    3,500 (1,700-5,300)

> T8 (CD8)                14     959                    16% (9-23%),    1,000    (400-1,700)

> T4/T8 ratio           5.08

> B  (CD19)                  1      74                     15% (4-26%)      1,000 (600-1,000)

> NK (CD16+56+3-)  10     664                   8% (3-23%)        500 (200-1,400)

> NKT(CD16+56+3+)  1      74

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

> 

> Bone marrow, non-diagnostic, RF (-)

> 

> skin bx showed lymphocyte infiltraion in vascular wall and dermis -> vasculitis, no organisms (fungus -, bacteria -, mycobacteria -, HSV -, adenovirus -, CMV -, EBV -)

> 

> At first, I thought of hyper IgE then I was suspecting SCID. B cell is very low but T cells are within normal. I was also thinking the possibility of maternal engraftment, but there is no eosinophilia although she has IgE already 161. Should check for chimerism?

> 

> Her condition is waxing and waning and deteriorating gradually.  Skin lesions are now quite nodular.. we are quite concerned about this baby and I hope to get some help from you for further work-up.

> I would appreciate any suggestion.

> 

> YaeJean

> 

> 

> 

> 

> 

> --

> Yae-Jean Kim, MD

> Assistant Professor

> Division of Infectious Diseases

> Department of Pediatrics

> Sungkyunkwan University School of Medicine

> Samsung Medical Center

> 50 Irwon-dong Gangnam-gu

> Seoul, Korea

> Tel)  +82-2-3410-0987  Fax) +82-2-3410-0043

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

> 

> 

> 

> 

> 

> 

> 

> -- 

> Yae-Jean Kim, MD

> Assistant Professor

> Division of Infectious Diseases

> Department of Pediatrics

> Sungkyunkwan University School of Medicine

> Samsung Medical Center

> 50 Irwon-dong Gangnam-gu

> Seoul, Korea

> Tel)  +82-2-3410-0987  Fax) +82-2-3410-0043

> yaejeankim at skku.edu

> 

> <09.18.2011.bmp>


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


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