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

[Sergio Rosenzweig]

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
 
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>>> 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.edujverbsky@mcw.edu>
verbskyj at yahoo.comverbskyj@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.eduyaejeankim@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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