[CIS-PAGID] Advice please

[Sorensen, Ricardo]

Rohan,

You have demonstrated that your patient has recurrent respiratory
infections that improve on gammaglobulin replacement therapy. There may
be no immune defect detectable by common evaluation methods. But you
have not ruled out several possible defects:

Poor serological memory after immunization with pneumococcal vacccines,
as mentioned by Richard Wqsserman.

IgG subclass deficiencies with normal anti-penumococcal antibodies. They
are rare, but do exist beyond any doubt in my experience.

Different SAD (specific antibody deficiency phenotypes) phenotypes.
These have not been appropriately published yet, but there are several
that can not be diagnosed if you do not provide an exact immunization
history with dates, and the date of evaluation plus the specific values
and method of measuring pneumococcal antibodies. This phenotypes
include unresponsiveness to conjugate polusaccharides that may be
obscured by a subsequent normal response to the polysaccharide vaccine,
unresponsiveness to pure polysaccharides (the commonly known one, less
frequent in children that the firs one) , poor memory, and also possible
real functional deficiencies that are hard to document because trustble
opsonbpophagocytic assays are not easily available. These later
deficiencies are common in the elderly and can  be indirectly suspected
when low class switched memory B cells are present. An IgE level is also
essential and a documentation of how you diagnosed his allergies.

I will be glad to continue this discussion of you provide this
information.

Best regards,

Ricardo Sorensen

-----Original Message-----
From: pagid-bounces at list.clinimmsoc.org
[mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of Rohan Ameratunga
(ADHB)
Sent: Friday, May 18, 2012 2:23 PM
To: pagid at list.clinimmsoc.org
Subject: [CIS-PAGID] Advice please

Dear Colleagues,
I would be most grateful for your opinions on this patient.

Case history

7 year old boy. Developed asthma early infancy. Good response to asthma
prophylaxis.
Developed chronic sinus disease aged 5 including polyps.  
Multiple and continuous upper and lower respiratory infections.  
Atopic (dust mites, grasses etc) desensitised.- partial improvement.
Adenotonsillectomy- partial improvement
Placed on prophylactic antibiotics (Co-trimoxazole) - but continued to
have breakthrough bacterial infections at least 1x per month. Usually
H.influenzae in spite of vaccination and antibodies.

Investigations

CT sinuses pansinusitis/ nasal polyps
Normal Immunoglobulins 7 g/L (nr >7) and good response to HIB, dip-tet
and pneumovax vaccines
Noted to have 8% double negative T cells (CD3+CD4-CD8-) Gamma-delta
cells awaited.  No other features of ALPS.
Normal in vitro lymphocyte responses to lectins and antigens
(diphtheria, tetanus, Candida) 
Primary ciliary dyskinesia unlikely - normal ultrastructure and normal
NO.
Normal sweat test.

Management

Underwent functional endoscopic sinus surgery- rapid recurrence of upper
respiratory tract infections. Subsequently has balloon dilatation of
nasal passages.  Regular sinus lavages.
Continued to have breakthrough upper and lower respiratory tract
infections in spite of above.  
Repeat CT sinuses- worsening sinusitis
I was concerned he was at high risk of bronchiectasis.  He had a chronic
moist cough in spite of prophylactic antibiotics.  

He was given a trial of subcutaneous immunoglobulin at the beginning of
2011.  
There was a dramatic response to this.  His sinus disease settled, he no
longer needs prophylactic antibiotics and has 1-2 bacterial infections
per year while on subcut Ig.  His chest is clear.
Major improvement in QOL- was attending school/ daycare 50%- has only
missed three weeks in the last year after starting Ig.  Can participate
in soccer, watersports, gymnastics etc. Essentially normal busy life.
Previous weight gain 1.5 kg/y- has gained 4kg in 15 months since
starting Ig.
CT sinuses not repeated as he is so well.

Questions

Has anyone had a similar experience?  Presumably this is an
anti-inflammatory response rather than treating an undefined immune
defect.
Interestingly, there is support for this approach in the literature.  A
trial of IVIG seems to have shown objective markers of improvement in
similar patients.  
Any comments from any of the authors?  Not sure if Dr Ballow is on the
list serve.
The question is how long to continue the scIg given the dramatic
response.  One option is to stop in our summer (Nov) and review.  Any
comments?

Ramesh S, Brodsky L, Afshani E, Pizzuto M, Ishman M, Helm J, Ballow M.
Open trial of intravenous immune serum globulin for chronic sinusitis in
children. Ann Allergy Asthma Immunol. 1997 Aug;79(2):119-24.

Thanks in advance

Rohan Ameratunga
Adult and paediatric immunologist
Auckland 
New Zealand