The management of APDS varies from patient to patient, even within affected families, and depends on the symptoms present and disease severity.1 There are no FDA approved medications for APDS.
Current treatment is symptom-based and no guidelines exist. Polypharmacy and surgical interventions are frequently necessary to treat both the immune deficiency and immune dysregulation arms of APDS.1-4
Summary: Management Landscape For APDS*
|Treatment||Effect in APDS||Proposed mechanism of action in APDS|
|Antimicrobial prophylaxis||- Reduction in respiratory tract infections 1|
- Does not address lymphoproliferation 2
|Prevention of respiratory infections1|
|Immunoglobulin replacement therapy (IRT)||- Reduction in respiratory tract infections 1|
- Does not appear to prevent herpesvirus infections or some sinopulmonary infections 2-4
- Bronchiectasis can still progress 2-4
- Does not address autoimmunity, lymphoproliferation, or lymphoma 2,3,5
|Correction of antibody deficiency1|
|Corticosteroids||- Reduction in lymphoproliferation & of autoimmune cytopenias 6-8|
- Prolonged use associated with long-term toxicity 9
- Increases susceptibility to infections9
|Inhibition of leukocyte activity and proliferation, particularly T cells9|
|Rituximab||- Some benefit in the management of autoimmune cytopenias and lymphoproliferation 6,7|
- May be complicated by sustained B cell lymphopenia 6
- Increases susceptibility to severe infection 10
|Depletion of autoreactive B cells11|
|mTOR inhibitors||- Reduction in lymphoproliferation1 & infections, 12 increase in IgG, 13 reduction in IRT or steroid use, 13,14 and prevention of end organ damage 12|
- Effects on bowel inflammation & cytopenia are mixed 14
- Difficulty dosing, adverse events, and compliance are challenges to treatment 6,13-16
|Reduction in mTOR hyperactivation1|
|Hematopoietic stem cell transplantation (HSCT)||- Reduction in respiratory & herpes infections, lymphoproliferation, & autoimmunity 1|
- Serious complications and complex conditioning regimens 17
- May not correct non-immunological manifestations such as kidney disease 17
- Paucity of long term data 17
|Replacement of leukocytes affected by PI3Kδ|
Table modified from Coulter TI, Cant AJ. Front Immunol. 2018;9:2043
* The treatments listed represent current practice as denoted in the literature. The information provided does not replace medical advice.
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- Coutler TI, Cant AJ. Front Immunol. 2018;9:2043.
- Elgizouli M, et al. Clin Exp Immunol. 2016;183(2):221-229.
- Crank MC, et al. J Clin Immunol. 2014;34(3):272-276.
- Kannan JA, et al. Ann Allergy Asthma Immunol. 2015;115(5):452-454.
- Kracker S, et al. J Allergy Clin Immunol. 2014;134(1):233-236.
- Coulter TI, et al. J Allergy Clin Immunol. 2017;139(2):597-606.
- Elkaim E, et al. J Allergy Clin Immunol. 2016;138(1):210-218.
- Jamee M, et al. Clin Rev Allergy Immunol. 2020;59(3):323-333.
- McKay LI, Cidlowski JA. In: Kufe DW, et al, eds. Holland-Frei Cancer Medicine. 6th ed. Hamilton, Ontario, Canada: BC Decker; 2003.
- Gobert D, et al. Br J Haematol. 2011;155(4):498-508.
- Rituxan [package insert]. South San Francisco, CA: Genentech Inc; 2021.
- Wang Y, et al. J Clin Immunol. 2018;38(8):854-863.
- Kang JM, et al. Yonsei Med J. 2020;61(6):542-546.
- Maccari ME, et al. Front Immunol. 2018;9:543.
- Scott JR, et al. Ther Drug Monit. 2013;35(3):332-337.
- Schubert M, et al. Am J Transplant. 2004;4(5):767-773.
- Dimitrova D, et al. [published online May 24, 2021]. J Allergy Clin Immunol.