[CIS PIDD] [cis-pidd] Hypogammaglobulinemia and light chain deposition in kidneys

Wed Jul 2 20:41:58 EDT 2014

Dear Mikko,

Thank you so very much for your response. It was helpful. The patient does
have high serum kappa light chain. Transplant has not been a thought for
management plan in this case.

Regards,
Juthaporn

On Tue, Jul 1, 2014 at 6:06 PM, Seppänen Mikko <Mikko.Seppanen at hus.fi>
wrote:

> Dear Juthaporn,
>
> since nobody else seems to respond...
>
> LCDD is a rare disease, I have personally seen only one, thus cannot boast
> much experience in that.
> If your patient had no amyloid in staining, and has no clear clinically
> evident plasma cell dyscrasia in the normal work up, she belongs to a 25%
> minority. She has already surpassed the median survival, about a third are
> still alive more than 8 years after dg. She seems to have no extrarenal
> manifestations (heart, peripheral nerves?). Does she have LC measured from
> serum?, usually kappa would be high. My guess would be, since CH50 is
> normal (can be low in e.g. CLL, MM due to clone-related consumption) that
> her LC binds C4 and interferes with the assay?? No transplant has been
> performed, though in literature it is generally regarded as safe and can at
> least early on reverse the renal failure. She probably has not been deemed
> eligible for transplant?
>
> She also has multiple late-onset autoimmune diseases. Evans, bullous
> pemphigoid, pustular psoriasis. Some of the autoantibodies in bullous
> pemphigoid are expressed in the gut as well, and I have seen a patient with
> BP and eosinophilia, who had a similar bout of sterile diarrhea, responded
> only to steroids. I do not think this would be well recorded in the
> literature though. Fecal calprotectin and antitrypsin to exclude chronic
> loss to gut as well? Autoimmunity preceding LCDD has been reported as
> rather common occasionally in literature LCDD reviews.
>
> She has asymptomatic but severe IgG hypogammaglobulinemia. In nephrosis,
> IgA is not affected and IgM is relatively increased in follow up. Severity
> of hypogamma in nephrotic sdr usually follows serum albumin levels. So her
> IgG seems somewhat low, but other features and findings follow SID, purely
> due to nephrotic sdr?
> Anti-PnP responses to Pneumovax? If she becomes symptomatic, I would first
> attempt antibiotic prophylaxis? S
> he sounds like SID to me, (but I have for example two brothers in follow
> up, of whom the other has clear adult-onset CVID, the other symptomatic
> CVID-like hypogamma, but in  the latter first a small MGUS and then
> smoldering myeloma was diagnosed, no known gene mutation in WES). I have
> seen a couple of other MGUS patients with symptomatic hypogamma out of
> proportion compared with plasma cells being below 5% in BM and MGUS being
> truly small. Usually the monoclonal gammopathy in MM and Waldenstrom is
> quite prominent before the low IgG develops. Why occasionally this is not
> the case I do not know. Your patient's low IgG sounds like a combination of
> nephrotic sdr and loss and similarly low production of  normal IgG due to
> monoclonal LC production??
>
> Thus, in practice I would treat her as SID, would not be eager to attempt
> IgGRT as first line therapy,  especially since she is still asymptomatic.
> And I would only use IgGRT if anti-PnP are low (though evaluation might be
> uncertain due to the very low IgG). But whether there are genes or a gene
> involved as well, I can only wonder.
>
> I do not know if this was of any help?
>
> Mikko Seppänen, Helsinki, Finland
>
> ________________________________________
> Lähettäjä: Juthaporn COWAN [jtp.cowan at gmail.com]
> Lähetetty: 27. kesäkuuta 2014 21:55
> Vastaanottaja: CIS-PIDD
> Aihe: [cis-pidd] Hypogammaglobulinemia and light chain deposition in
> kidneys
>
> Hello all,
>
> Please advice what you think and what should be done for this case.
>
> A 58 yo woman with history of mild mental retardation from fetal alcohol
> syndrome. She was well up until 2009 when she was found to have
> proteinuria. Kidney bx showed light chain deposition without evidence of
> myeloma or even MGUS by bone marrow studies. She then had ITP +/- AIHA X 3
> since 2009, responded to steroids and IVIG. She was also diagnosed with
> bullous pemphigoid and pustular psoriasis in 2012 based on skin biopsy when
> she presented with rash. Early this year, she began to have profuse
> diarrhea lasted for several weeks and nothing found on work up in terms of
> infection. Colonoscopy might have been done but result was not available.
>
> We are seeing her for hypogammaglobulinemia of 1.1 g/L (Persistently low
> as of this year). Her IgG level was 5.9 in 2009 when she was diagnosed with
> light chain deposition in her kidneys and ITP. IgA and IgM are always in
> normal range. Interestingly, she also has very low C4 level <0.001 g/L with
> normal CH50. There is no feature of SLE.
>
> The question is 'could this all be PID or SID?' Is her
> hypogammaglobulinemia caused by protein loss? (serum albumin is noted to be
> 25.. not very low, proteinuria is about 1.5-2 g/day). Does she have
> hematologic malignancy that is not picked up by BM biopsy?
>
> No history of recurrent or unusual infection.
>
> I am looking forward to hearing from you. Thank you.
>
>
> Juthaporn Cowan
> Ottawa, Canada
>
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