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.