[CIS PIDD] [MARKETING][cis-pidd] CVID and profuse diarrhea

Thu Jan 21 03:31:53 EST 2016

I agree with Mikko: there are (too) many problems in a child with "CVID" 
and I would evaluate for the possibility of an underlying CID (have you 
followed naive T-cells over time? Is there an expansion of g/d T cells 
or do you see increased senescence (e.g. by CD57 expression)?  How is 
the T-cell function? B-cell subsets (CD21?)
Depending on the results you may consider a leaky SCID or one of the 
more recently described defects (e.g. PI3Kd, CTLA4, LRBA, STAT3, ...): 
with some of these maybe having some additional (somewhat specific) 
treatment options (sirolimus, PI3Kd inhinitors in the future, abatacept, 
a-IL6, ...). Mikko also pointed towards SCT: certainly risky with the 
described infection pattern, but probably also important to evaluate (in 
case the patient stabilizes in the near future). With the back-up of 
antimicrobial treatment/prophylaxis a clinically well observed treatmend 
with steroids (e.g. 1mg/kg of prednisone for 2 weeks and then taper) 
might be helpful with the observed immune dysregulation (before playing 
with other immunosuppressive drugs). Regarding the norovirus infection 
the oral ribavirin you started sounds like a good idea and I would wait 
for the effect over the next weeks (and rather try additional systemic 
steroids for the moment). Good luck, BW Carsten

-- 
PD Dr. Carsten Speckmann
Pediatrician
Group Leader: Benign lymphoproliferative disorders
Pediatric Hematology and Oncology
and Center for Chronic Immunodeficiency
University of Freiburg
Germany
phone: +49 (0)761 270 43010
fax: +49 (0)761 270 45990
www.uniklinik-freiburg.de/cci/studien/alps.html

Am 21.01.2016 06:42, schrieb CIS-PIDD:
> Hi Yae-Jean,
>
> Your listing of all her troubles left me with a lot of questions and 
> just as worried as you?
>
> In my opinion she needs urgent re-evaluation of her diagnosis, her 
> disease is unlikely CVID, rather some CID despite normal looking CD4 
> and CD8 subsets. Quite a number of candidates spring to mind, so many 
> indeed that urgent exomes would be truly nice. Immunomodulatory agents 
> could then be considered in unblinded fashion.
>
> To pinpoint fewer candidates the exact biopsy findings might help?
>
> SCTx would be risky with 3 active infections. Have you already 
> attempted salmonella eradication w antibiotics? Which ones?
>
> Noro th attempt with p.o./ nasojejunal IgG + Alinia + IFN? All at the 
> same time?
>
> At the moment her lungs seem to be in bad shape, what is her diffusion 
> capacity? Aspergillus: means of dg- restricted to lungs in imaging and 
> blood tests or systemic? Biopsy?
>
> Fecal antitrypsin? protein losing enteropathy seems likely with that 
> history and hypoalbuminemia, extent of intestinal lymphangiectasia 
> seems limited if no CD4&8 lymphopenia? Has PN been started to improve 
> nutritional status?
>
> The cause of tubulopathy, biopsy findings? Lymphadenopathy, the same? 
> Liver biopsy?
>
> Yours,
>
> Mikko
>
> Oyl Mikko Seppänen
> Harvinaissairauksien yksikkö (HAKE)
>
> Head, Rare Disease Center,
> Helsinki University Hospital (HUH)
> FINLAND
>
> phone +358 947180201
> GSM +358 50 4279606
> fax +358 9 47174703
>
> CIS-PIDD <cis-pidd at lists.clinimmsoc.org 
> <mailto:cis-pidd at lists.clinimmsoc.org>> kirjoitti 21.1.2016 kello 5.52:
>
>> Dear all,
>>
>> I have a difficult case of CVID patient whom I recently started to 
>> see and would like to ask your opinions
>>
>> - 18 year old female diagnose as CVID at the age of 3 years in 2002
>> - currently, bronchiectasia with probable invasive aspergilosis, 
>> liver cirrhosis, renal tubulopathy, and _significant diarrhea with 
>> PCR only positive salmonella and norovirus_
>>
>> <2002>
>> - was diagnosed as CVID with a hx of frequent pneumonia
>> - managed to grow along growth curve until age 10-11
>> - failure to grow since age 12
>> - performed ok school life on IVIG without hospitalization until 2010-11
>>
>> <20010-11>
>> - hospitalization for work-up on poor weight gain and GI pathology
>> - 2010: pathology reported, esophageal varix grade I,  duodenal bx 
>> showed atrophy of villi, apoptotic bodies with increased 
>> intraepithelial lymphocytes, abdomen CT showed multiple LN 
>> enlargement and enterocolitis, hepatosplenomegaly
>> - 2011: bx of terminal ileum showed also above findings and 
>> intestinal lymphangiectaisa
>>
>> <2015>
>> - In August, she developed really really serious profuse diarrhea.
>> - significant weight loss and now the body weight is  25-30 kg, 
>> seriously cachexia condition since then
>> - extensive parasite, bacterial, viral, fungal infection as for 
>> enteric pathogen revealed positive PCR for salmonella spp. and 
>> norovirus in the stool and no other cultured organisms
>> - colon bx showed lots of damaged mucosa and massive neutrophil 
>> infiltration, crypt abscesses, increased lymphocyte infiltration than 
>> before.
>> - I reviewed the slides with the pathologist and he says her 
>> pathology looks somewhat different from inflammatory bowel diseases 
>> (UC or Crohn's disease)
>>
>> <2016>
>> - Early this month, she presented to ER with hemopysis -> w/u showed 
>> possible invasive  pulmonary aspergillois, for this she is on 
>> _*ambisome*_
>> - She still has serious diarrhea 15 times per day. Her output is 
>> almost over 3000 cc and she is 26 kg today.
>> - Salmonella and norovirus PCR is still positive as of Jan 2016 >) 
>> oral *rifaximin and ribavirin* were started 5 days ago.
>> - It seems like whatever she eats or we infuse, she cannot hold 
>> nutrients, electrolytes in her body.
>>
>> <labs>
>> _- Initial labs in July 2002 was _
>> lympho subset: CD3 2870, CD4 1790, CD8 1080, B cells 160 (5%), NK cell 5
>> Ig G 33, IgA 6, IgM 4 mg/dL
>> - As I reviewed her past labs, her IgG level has been in 200-400 
>> mg/dL on IVIG tx and IgA and IgM levels has been also less than 5 
>> mg/dL..
>>
>> _- Labs in December 2015 was_
>> CD3 2072 cells /uL, CD4 833, CD8 1175, _B cells 0_, NK 43 cells/uL
>> hypoalbuminemia, electrolyte imbalance, etc..
>>
>> At this point, I would like to ask your opinion on management option. 
>> Is there anything that I can do further for her?
>> - I plan to f/u PCR for salmonella and norovirus after two wks of tx 
>> and also perform terminal ileum and colon bx to see the pathology 
>> change. But I am not sure whether pathogens would be easily cleared 
>> and the pathology would be improved..
>> - I am thinking she might need some immunomoluatory agents or 
>> steroid..but I am concerned with her lung (aspergillosis) and gut 
>> pathogens (salmonella and noro) at this point..Maybe can I try at 
>> least oral budesonide?
>>
>> I would appreciate your thoughts and suggestion.
>>
>> Regards,
>>
>> YaeJean
>>
>>
>> Yae-Jean Kim, MD, PhD
>>
>> Associate Professor
>> Division of Infectious Diseases and Immunodeficiency
>> Department of Pediatrics,
>> Samsung Medical Center,
>> Sungkyunkwan University School of Medicine,
>> 81 Irwon-ro, Gangnam-gu, Seoul, South Korea
>>
>>
>>
>>
>>
>>
>>
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>>
>>
>>
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