[CIS PIDD] [cis-pidd] Adult onset, multiple episodes of rapidly progressive severe sepsis, with no demonstrable immune abnormality

[Verbsky, James]

Agree with the prior comments.  Old for IRAK4/MyD88, and the LPS response argues against it but a formal TLR assay might be helpful.  You might consider a RBC pit assay for asplenia, although its hard to find people who do that.  I don't know if anyone is running a flow based HJ assay which might be more sensitive.

I always wonder about anti-cytokine antibodies (IL-6 for example) in patients who present late.  Does he mount an inflammatory response when sick (CRP, ESR, fever, neutrophilia??)

Best

James


James W. Verbsky M.D./Ph.D.
Associate Professor of Pediatrics and Microbiology
Medical College of Wisconsin
Milwaukee, WI 
414-266-6701



-----Original Message-----
From: Seppänen Mikko [mailto:Mikko.Seppanen at hus.fi] 
Sent: Wednesday, March 05, 2014 1:34 AM
To: CIS-PIDD
Subject: VS: [cis-pidd] Adult onset, multiple episodes of rapidly progressive severe sepsis, with no demonstrable immune abnormality

Dear all,
I am unaware of any MASP2 def patients with this severe a clinical picture (outside the NEJM original case report- but that person had concomitant S(P)AD). This patient does not have it. In my mind, MBL2 def and MASP2 def thus behave the same way? 

I wonder if the serotype in sepsis was the same as the one to which the patient is unresponsive? I have a similar patient with this phenomenon and clear functional asplenia, and H-Js are insensitive. 

As absurd as it sounds, is the patient responsive in mitogen stimulation test? If not, please contact me (have one mystery pt with only that finding). 

And if all other suggestions fail, TLRs do spring to mind, like Dewton suggests.

Mikko Seppänen, Helsinki Finland
________________________________________
Lähettäjä: Pere Soler Palacin [psoler at vhebron.net]
Lähetetty: 4. maaliskuuta 2014 18:36
Vastaanottaja: CIS-PIDD
Aihe: Re: [cis-pidd] Adult onset, multiple episodes of rapidly progressive severe sepsis, with no demonstrable immune abnormality

I would insist on the spleen. What about 99Tc-labelled heat-denatured red blood cell selective spleen scintigraphy?
If normal, I'd agree with Dewton that both ficolin and MASP-2 defects should be considered in addition to properdin deficiencies (XL).



P.


Pere Soler Palacín, MD, PhD.
Pediatric Infectious Diseases and Immunodeficiencies Unit. Hospital Universitari Vall d'Hebron.
Assistant Professor. Universitat Autònoma de Barcelona.
Passeig de la Vall d'Hebron 119-129.
08035 Barcelona. Spain.
Tel: 0034934893140. Fax: 0034934893039.
E-mail: psoler at vhebron.net<mailto:psoler at vhebron.net>; 34660psp at comb.cat<mailto:34660psp at comb.cat>. Web: www.upiip.com<http://www.upiip.com/>.



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----- Mensaje original -----
De: dmvascon at usp.br
Para: "CIS-PIDD" <cis-pidd at lists.clinimmsoc.org>
Enviados: Martes, 4 de Marzo 2014 16:28:04
Asunto: Re: [cis-pidd] Adult onset, multiple episodes of rapidly progressive severe sepsis, with no demonstrable immune abnormality

Dear Dr. Spriggs, good morning

Very interesting case!
What about his teeth? Are they OK, without periodontal disease?
The presence of infections due to encapsulated bacteria drives our thoughts to Ig and complement diseases too.
Despite the lack of descriptions of disease in adults due to defects of NF-kB activation (MyD88 and IRAK-4) you also thought in the possibility of defects in this pathway. Nevertheless, polymorphisms of other TLR molecules (more linked to Gram+ bacteria such as TLR1 and 2) are possible.
Moreover, defects of the lectin pathway of complement (mainly MASP2 and Ficolin3 deficiencies) are associated with severe sepsis and pneumonias due to encapsulated bacteria.
Maybe mild defects of phagocytes (such as myeloperoxidase) can account to susceptibility to infections in adult patients, when they develop any other disease that can affect immunity (such as diabetes mellitus and uremia).
Furthermore, the possibility of a secondary ID, such as those linked to neoplastic diseases such as lymphomas and leukemias can't be ruled out.

Best regards,

Dewton

Dewton de Moraes Vasconcelos, MD, PhD
University of São Paulo School of Medicine São Paulo, Brazil

________________________________
De: "Kymble Spriggs" <kymble at me.com>
Para: "CIS-PIDD" <cis-pidd at lists.clinimmsoc.org>
Enviadas: Terça-feira, 4 de Março de 2014 6:08:26
Assunto: [cis-pidd] Adult onset, multiple episodes of rapidly progressive severe sepsis, with no demonstrable immune abnormality

Thankyou for your consideration regarding the further investigation for an eitiology of this gentleman's recurrent infections:

40yo Caucasian man suffering multiple separate rapidly progressive severe episodes of sepsis.

Acute History:
-  First occurring 2 years ago - resulting in ICU admission and leg and fingertip amputation.
--  Confirmed to be pneumoccocal sepsis
-  Two further episodes of severe pneumonia treated at external hospitals
-  Last year suffering similar rapidly progressive sepsis - patient becoming unconscious within hours of feeling unwell.  Found by partner & taken to hospital.
--   Later confirmed to be Haemophilus Influenzae (non-typable, biotype IV)
-  Subsequently remaining well on prophylactic antibiotics (amoxicillin)

Past History:
- No other previous significant infection history - without significant illness until recently.
- Tonsillectomy in childhood & mild eczema and bronchiolitis.
- Possible "bruised spleen" during traumatic accident in childhood.  Anatomically present on CT scan.  No howell-jolly bodies on blood films

No significant family history or consanguinity.  Currently well offspring

Laboratory Results:
- Full blood count unremarkable
- Normal Lymphocyte Subsets (including normal CD3+, CD4+, CD8+, CD19+ and CD16+/56+)
- Normal IgG, IgA, IgM, IgE
- Excellent dynamic pneumococcal antibody responses to Pneumovax23 - high titres to 14/15 serotypes
- Good Haemophillus influenza type B antibody levels
- HIV Negative
- Normal functional complement studies (CH100, AH50)
- Normal CD62 ligand shedding (to LPS and PMA)
- Normal memory B cells/ B cell subsets

Are there any other investigations that could be performed on this gentleman, to try and clarify his underlying diagnosis?

Kind Regards,

Dr Kymble Spriggs
MBBS(Melb), MCRP(UK), DTMH(Lon), FRACP

Clinical Immunology & Allergy
Royal Melbourne Hospital












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