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

[YaeJean Kim]

Dear Sergio,

Thank you for your comments and suggestions. I haven't used those
biologicals (they are not available where I practice).

I tried steroid at a dose of 2 mg/kg and gave a pulse treatment 2 days
ago since the baby's condition was getting worse. I started mmf
yesterday after hearing a suggestion from Austrailian colleagues who just
saw a very similar baby there and had a good response with mmf.

I will give you more updates later.  Many thanks!!

Regards,

YaeJean



On Wed, Sep 21, 2011 at 5:02 AM, Sergio Rosenzweig <
srosenzweig at garrahan.gov.ar> wrote:


> Hi YaeJean,

> Did you try any biologicals (Anakinra, tocilizumab)? Take a look at this

> recent paper, some of the characteristics overlaps with your patient

>

> A mutation in the immunoproteasome subunit

> PSMB8 causes autoinflammation

> and lipodystrophy in humans

> Citation for this article: J Clin Invest doi:10.1172/JCI58414.

> Sergio

>

>

> Sergio D. Rosenzweig, MD, PhD

> Chief, Infectious Diseases Susceptibility Unit

> Laboratory of Host Defenses, NIAID, NIH

> 10 Center Dr., Bldg. 10, CRC 5W-3888

> Bethesda, MD 20892-1456

> Phone (301) 451 8971

> Fax (301) 451 7901

> Cell (240) 361 7617

> Pager 102 10678

> srosenzweig at niaid.nih.gov

>

> Disclaimer: The information in this e-mail and any of its attachments is

> confidential and may contain sensitive information. It should not be used by

> anyone who is not the original intended recipient. If you have received this

> e-mail in error please inform the sender and delete from your mailbox or any

> other storage devices. National Institute of Allergy and Infectious Diseases

> shall not accept liability for any statements made that are senders own and

> not expressly made on behalf of the NIAID by one of its representatives.

>

> >>> YaeJean Kim **09/19/11 9:29 AM >>>

>

> 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:jverbs**ky at mcw.edu <jverbsky at mcw.edu>>

>>> verbskyj at yahoo.com<mailto:verb**skyj at yahoo.com <verbskyj at yahoo.com>>

>>>

>>>

>>>

>>>

>>> ______________________________**__

>>> From: pagid-bounces at list.clinimmsoc.**org<pagid-bounces at list.clinimmsoc.org>[mailto:

>>> pagid-bounces at list.**clinimmsoc.org <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:yae**jeankim at skku.edu <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

>

> **

>




-- 
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
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