[CIS-PAGID] Challenging case: hypogammaglobulinemia and hypocomplementemia

[Anita Gewurz]

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

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> Kansas City, MO 64111

>

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