Management
In patients with PADs, IgRT forms the mainstay of therapy for many
patients (10,11) (Figure 2). The decision to commence IgRT is clearer in
well-defined PADs with a significant infection burden and supportive
laboratory findings - hypogammaglobulinaemia with impaired response to
vaccination. The decision is more complex if these findings are not all
present such as hypogammaglobulinaemia with preserved vaccine responses
or specific antibody deficiency.
IgRT may be administered either intravenously, subcutaneously or as a
facilitated subcutaneous infusion using hyaluronidase and the decisions
regarding route and frequency of administration and site of
administration (home or hospital) are individual and are made jointly
with the patient and medical team (12). In general, IgRT is commenced
based on weight at 0.4 – 0.6g/kg/month of IgG and is the adjusted on
clinical (such as infection burden, bronchiectasis, type of PAD and
other complications) and laboratory grounds including trough IgG level
aiming for >7glL (though this may vary between centres and
countries) (13,14). In a number of circumstances antibiotic prophylaxis
may be used, such as potentially milder immunodeficiencies with a less
severe infection burden (IgG subclass deficiency or combined IgA
deficiency with IgG subclass deficiency), or in addition to IgRT in
patients with a persistently increased infection burden despite
optimally individualised IgG trough levels and in those with existing
end-organ damage such as bronchiectasis or chronic sinusitis or in those
colonised with Pseudomonas aeruginosa or Stenotrophomonas
maltophilia . Antibiotic regimens will vary according to the setting,
organism and sensitivities, but in PAD patients with frequent
respiratory tract infections on IgRT who may also have bronchiectasis
azithromycin at 250-500mg three days/wk has been shown to decrease
infective exacerbations. In patients with concomitant T cell or
neutrophil impairment (CID, SCID, HIGM), septrin (cotrimoxazole) may be
considered (10,15). PAD patients require regular follow up both to
monitor therapy and for early detection and management of complications
(4,5,16,17). Laboratory and radiological monitoring are indvidualised
but baseline testing includes full blood count, renal and liver function
and CRP 2-4 times per year (with LDH, β2 microglobulin as indicated),
lymphocyte subsets 1-2 times per year, abdomen ultrasonography, neck
ultrasonography if lymphadenopathy is investigated, chest X-ray and lung
function tests once a year, chest CT every 3-5 years or sooner if
indicated and screening endoscopies every 1-2 years in some centres
(18).
Diagnosis and management are in PAD improving with better immunologic
and molecular characterisation, more options for IgRT, personalised
pathway-specific therapies for some PADs and greater knowledge of the
role of HSCT and gene therapy/editing for the future.