[CIS-PAGID] Challenging case:hypogammaglobulinemia and hypocomplementemia

[Berger, Melvin]

I agree about working her up for cryoglobulins and complement consumption, but I would check PFTs and look at titer against H. flu and her response to the conjugated pneumococcal disease. With low IgG and C4/C3, she is practically begging for pneumococcal pneumonia. I would keep watching very closely, and consider prophylactic antibiotics or IgG replacement if she fails to respond to conjugated pneumococcal vaccine and conjugated HiB vaccine. If her igG is actually dropping, I would certainly think about CLL. 
 
Melvin Berger, M.D., Ph.D.
Adjunct Professor of Pediatrics and Pathology
Case Western Reserve University
Cleveland, OH 44106

________________________________

From: pagid-bounces at list.clinimmsoc.org on behalf of Desa Lilic
Sent: Tue 12/13/2011 4:58 AM
To: pagid at list.clinimmsoc.org
Subject: Re: [CIS-PAGID] Challenging case:hypogammaglobulinemia and hypocomplementemia



Dear Zachary
A monoclonal gammopathy can certainly explain both the low remaining Igs and complement consumption; given that it is an IgM paraprotein (Waldenstroms disease), the low values found can be misleading as IgM is often a cryoglobulin (as Anita pointed out) and can be lost if not thought of and processed correctly. This is of crucial importance as if the above is confirmed, treatment would be chemotherapy rather than IVIG.

Desa Lilic MD MSc PhD FRCPath
Consultant and Clinical Senior lecturer in Immunology
Newcastle University
UK




>-----Original Message-----

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

>bounces at list.clinimmsoc.org] On Behalf Of Anita Gewurz

>Sent: 13 December 2011 07:49

>To: pagid at list.clinimmsoc.org

>Subject: Re: [CIS-PAGID] Challenging case: hypogammaglobulinemia and

>hypocomplementemia

>

>Dear Zachary,

>

>We agree with Mikko and would screen for a cryoglobulin that may be

>consuming complement in your patient's ex vivo serum samples, though

>apparently not in vivo, as the ESR and CRP are not elevated as would

>be likely in type III hypersensitivity.  The quantity of MGUS and the

>CH50 might be higher if ascertained ASAP on serum maintained at 37°C

>during clotting and storage; consider screening serum and urine for

>free light chain, as well.

>

>In the case of an adult with hypogammaglobulinemia whose antibody

>response to PPV (such as Pneumovax) is nonprotective, we revaccinate

>with PCV (e.g., Prevnar 13).  However, we would neither repeat the

>humoral immunity panel nor give Ig replacement therapy at this point.

>

>Good case!

>

>Anita Gewurz MD

>Section of Allergy & Immunology

>Department of Immunology/Microbiology

>Rush University Medical Center

>1725 W Harrison St - 117

>Chicago IL 60612

>CELL/PGR (847) 224-8550

>EMAIL agewurz at rush.edu

>

>

>

>

>On Dec 12, 2011, at 9:46 AM, Seppänen Mikko wrote:

>

>> Dear Zachary,

>>

>> in many hematologic clonal diseases there is a secondary hypogamma

>> as well as hypocomplementemia of classical pathway, caused

>> presumably by consumption, thus these should be excluded carefully.

>> Most described have been of B cell origin.

>>

>> In primary SLE and SLE secondary to congenital total C4 deficiency

>> both are seen, but considering the findings as well as pt age I

>> would actively search for B cell clonality at first then look at

>> more rare alternatives

>>

>> Mikko Seppänen

>> Helsinki

>>

>> ________________________________________

>> Lähettäjä: pagid-bounces at list.clinimmsoc.org [pagid-

>bounces at list.clinimmsoc.org

>> ] käyttäjän Zachary D. Jacobs, MD

>> [zjacobs.md at gmail.com] puolesta

>> Lähetetty: 12. joulukuuta 2011 17:38

>> Vastaanottaja: pagid at list.clinimmsoc.org

>> Aihe: [CIS-PAGID] Challenging case: hypogammaglobulinemia and

>> hypocomplementemia

>>

>> Hello,

>>

>> I am a (relatively) young immunologist just out of training and am

>> hoping that I could garner some helpful suggestions from this

>> incredibly adept and intelligent community for what I feel is a

>> challenging case.

>>

>> I recently saw a 68 year-old woman referred by rheumatology for a

>> low IgG level found incidentally.  She was seen initially by the

>> rheumatologist for evaluation of neck pain and intermittent fatigue

>> along with painful hands.  Her cervical spine showed degenerative

>> changes on X-ray.  Her diagnosis was osteoarthritis of the cervical

>> spine and hands.  In the course of her work-up for rheumatologic

>> conditions, her IgG was found to be 351 mg/dl and she was sent to me

>> for evaluation.

>>

>> As far as her infectious history, it is for all intents and purposes

>> nonexistent.  She has not had pneumonia since childhood.  She does

>> not have issues with recurrent or chronic sinusitis and does not

>> have a history of sinus surgery.  She does not have a history of

>> invasive infections, admission for infections, recurrent soft tissue

>> infections, or urinary tract infections.  She does relate that she

>> takes a little longer to get over "colds."  She does not have

>> chronic diarrhea or foamy urine.  Her exam to me was unremarkable.

>>

>> Meds:  Naprosyn prn, omeprazole, multi-vitamin, vitD

>>

>> No chronic medical illness or hospitalizations, family history is

>> negative for autoimmunity and immune deficiency.

>>

>> The following is her laboratory evaluation with some labs performed

>> twice:  Boldfaced type equals abnormal findings.

>>

>> .        CBC: Hgb 12.7, Hct 37, Plt 208 - normal

>>

>> .        WBC: 7700 (PMN 78.5%, L 16.1%, Eos 1%) - normal

>>

>> .        Liver transaminases, LDH, uric acid, serum chemistries and

>> renal function normal

>>

>> .        Urinalysis: Normal, no blood or protein, microscopy normal

>>

>> .        Anti-CCP antibody: 2 (0-30)

>>

>> .        IgG: Two occasions, 351 and 214 mg/dl (614-1286)

>>

>> .        IgA: 72 and 106 mg/dl (87-474)

>>

>> .        IgM 134 and 291 mg/dl (52-330)

>>

>> .        Serum electrophoresis: Minimal monoclonal IgM lamda at

>> approx. 0.2 g/dl, thought to be of no significance

>>

>> .        Tetanus Ab: 0.51 (nl > 0.1)

>>

>> .        Pneumococcal serotypes: All 12 tested were under <1.3 u/ml

>> (highest was 0.9, most of them undetectable at < 0.3).  Repeated 6

>> weeks post-Pneumovax and no change in any of the serotypes.

>>

>> .        CRP: 23, mildly elevated (0-10 normal)

>>

>> .        ESR: 1

>>

>> .        CH50: < 3 (repeated twice, normal 30-75)

>>

>> .        C3: 62 (83-172)

>>

>> .        C4: 6 (18-51)

>>

>> .        Flow cytometry: Normal

>>

>> o   ALC: 1300

>>

>> o   CD4: 53% (absolute 689)

>>

>> o   CD8: 27% (absolute 351)

>>

>> o   CD4:CD8: 2.0

>>

>> o   CD16/56: 20% (absolute 260)

>>

>> o   CD19: 5% (absolute 65)

>>

>> Even without a pattern of recurrent infections, my thinking is that

>> she warrants IgG replacement therapy given the low IgG and

>> completely absent specific antibody response to Pneumovax.  I have

>> failed to find anything in the literature to this point concerning

>> the concurrence of hypocomplementemia and hypogammaglobulinemia.  My

>> feeling is that they should represent the same etiology as opposed

>> to having two separate and rare etiologies.  Any thoughts on further

>> work-up, therapy, and possible diagnoses would be greatly

>> appreciated.  I have given thought towards sending complement

>> degradation products to determine production vs. consumption but

>> have never ordered this lab before.

>>

>> Thank you so much for any help provided with this case.

>>

>> Zach

>>

>> --

>> Zachary D. Jacobs, M.D.

>>

>> The Center for Allergy & Immunology

>>

>> St. Luke's Physician Partners

>>

>> Medical Plaza II

>> 4330 Wornall, Suite 40

>> Kansas City, MO 64111

>>

>> Ph: 816.531.0930<tel:816.531.0930>

>> Fax: 816.753.2671<tel:816.753.2671>

>>

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