[PAGID] Allergy fellow seeking assistance with IRAK-4 def evaluation

[Kathleen E. Sullivan]

Is there a reason you don't think he has garden variety CVID?
Kate
Kathleen E. Sullivan MD PhD
Chief, Division of Allergy and Immunology
Professor of Pediatrics
The Children's Hospital of Philadelphia
(p) 215-590-1697
(f) 267-426-0363


On Jun 24, 2008, at 5:24 PM, Otto, Hans F Maj USAF AETC 59 MDOG/MMIA  
wrote:


> Dear Colleagues,

>

> I am a 1st year fellow at Wilford Hall Medical Center’s Allergy/ 

> Immunology training program and I would appreciate your assistance  

> with a question.  I queried the Immune deficiency foundation and  

> they recommended I post my question on this list-serve for discussion.

>

> Case:

> I have a previously healthy 7 y/o male who was admitted to our  

> hospital back in Feb08 for chest pain and fever of 104F.  He was  

> found to have a pericardial effusion which was ultimately tapped  

> and a drain placed after he developed cardiac tamponade.  His gram  

> stain and culture showed group A beta-hemolytic strep (GABHS) and  

> antibiotics were started.  As GABHS pericarditis is very rare  

> screening ID labs were checked on HD#2 on the recommendation of  

> Infectious diseases consult.  The labs showed a  

> hypogammaglobulinemia (IgG <100, IgA 18 and IgM 5) as well as  

> hypoalbuminemia and a lymphopenia which both later resolved.  We  

> were then consulted by infectious disease.  Flow cytometry was  

> normal.  Specific antibodies were drawn and tetanus and diphtheria  

> were at protective levels and several S. pneumo serotypes were  

> elevated (>1.3mcg/ml) but we still cannot find his immunization hx/ 

> documentation.  HIV was negative with negative risk factors but  

> will be re-checked again in several months.  He was given IVIG (24g  

> IV on 2 consecutive days) as an inpatient and his Ig levels  

> increased.  His Ig levels have since remained in the normal range.   

> We are continuing to follow him as an outpatient.  He has no  

> chronic medical problems, no consanguinity, no delayed cord  

> separation, no travel and normal exam including LN and was well  

> until 1 week prior.  One week prior to presentation he and his  

> brother both developed a 24 hour acute gastroenteritis-type illness  

> with vomiting x2 and some loose BM, all of which resolved after 24  

> hours without further complaints until day prior to ER visit.  He  

> has been remarkably healthy and has never had any AOM, sinus  

> infections or other significant childhood infections.  He has  

> developed normally and is a straight A student.  He did not have  

> any protein in his urine, normal chemistry other than  

> hypoalbuminemia which improved after starting TPN; stool was not  

> checked for alpha-1 antitrypsin (not considered at the time) and no  

> pleural effusions existed on presentation but did develop later in  

> the course (HD#5).  CBC was otherwise normal, CT scans are normal  

> and no sign of malignancy.

>

> DDx:

> Consideration of the differential diagnosis of  

> hypogammaglobulinemia does not support drug, genetic, chromosomal  

> nor malignancy.  Given the rarity of GABHS pericarditis (5 cases in  

> the world literature), especially in the setting of a very healthy  

> young male, we are working under the premise that he has some yet  

> unrecognized immunodeficiency (admittedly A/I bias).  Infectious  

> agents seem unlikely though we have considered a transient severe  

> protein-losing enteropathy which could cause hypogamm then open the  

> window for GABHS pericarditis but GABHS is not a common source of  

> infection in CVID nor does his acute gastroenteritis seem to have  

> been severe enough to be the source of protein-losing enteropathy 

> (mild and <24 hrs).  Constrictive pericarditis can cause  

> chylothorax which may cause hypogamm but that would be placing the  

> “cart before the horse”.  If this is the case, then he truly would  

> have a rare infection with acquired/transient hypogamm and his  

> future risk of infections would be low.  If he has a PID, then  

> recommendations would change depending on the PID.  He has been  

> well since discharge in early Mar08 with the exception of scarring  

> of his pericardial sac causing some degree of constrictive  

> pericarditis which is improving.  Our current plan is to continue  

> to monitor his quantatative Ig levels over time to see if they  

> drop, re-check HIV in Aug-Sept and try to obtain his immunizations  

> history.  He is on no prophylactic antibiotics or other treatment  

> at this time.

>

> In continuing to consider/research some primary immunodeficiency  

> that may have predisposed this patient to GABHS strep pericarditis  

> +/- hypogamm, I have come to consider IRAK-4 deficiency given the  

> pyogenic infection/pericarditis.  His presentation could be  

> consistent with this being the original PID with hypogamm being a  

> later finding secondary to the constrictive pericarditis.  I have  

> presented this case, updates and research findings to our  

> department on several occasions and we continue to find it an  

> interesting/unique case.  Surely it is possible that he had a rare  

> pyogenic infection with secondary hypogamm (chylous loss vs. sepsis  

> vs. other) vs. IRAK-4/UNG-93B w/ secondary hypogamm vs. hypogamm/ 

> CVID with no other cause whose 1st presentation was GABHS  

> pericarditis…all would be rare.  Now, however, I need help in  

> figuring how to next proceed with appropriate evaluation as we  

> believe there are still some unanswered questions.  Our department  

> discussions led to the recommendation to write to you for assistance.

>

> Question:

> I am trying to figure out how to order the test described by von  

> Bernuth H, et al. A fast procedure for the detection of defects in  

> TLR signaling. Pediatrics 2006; 118:2498-2503.  The article  

> describes a procedure for incubating fresh serum sample then  

> inducing with anti-human CD62L antibody and then analyzing by flow  

> cytometry.  IRAK-4 and UNG-93B (or MyD88) deficiency would show  

> impaired CD62L shedding on granulocytes and profoundly impaired  

> IL-6 production after activation by LPS.  I cannot figure out where  

> I could get this test done in the USA or who I would contact for  

> the logistics on their end.  I can find gene testing at http:// 

> bioinf.uta.fi/IDdiagnostics but that does not seem to be an ideal  

> 1st/screening test but maybe I am incorrect and should just order  

> the genetics.

>

> Can you please assist in guidance on how to order this test for our  

> patient?  Additionally, I am open to any other suggestions for  

> evaluation that you may have to add.

>

> Thanks for your help in advance!  Sincerely,

> Hans

> //signed//

> Hans F Otto, MC, Maj, USAF

> Allergy/Immunology Fellow

> Provider Code 012R58

> 59 MTG/SGMVDA

> Lackland AFB, Texas 78236-9908

> Comm: 210-292-5042/5723

> Fax: 210-292-5016

>

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>

>

>


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