The American Academy of Allergy, Asthma & Immunology (AAAAI) and the American College of Allergy, Asthma and Immunology (ACAAI) recently released a 2025 update to their 2015 guideline on the diagnosis and care of patients with primary immunodeficiencies.
Today, we are comparing the 2025 ACAAI/AAAAI clinical practice guideline to its 2015 version, Diagnosis and Management of Primary Immunodeficiency. Particularly focusing on three topics: immunoglobulin replacement, infection prevention, and immunizations. Refer to the full-text versions of each guideline, which are linked below, for the most thorough look at the complete recommendations and their related rationale.
Guidelines Referenced:
Diagnosis and Management of Primary Immunodeficiency vs. Inborn Errors of Immunity (2015-2026)
The following table reflects the latest recommendations included in the 2025 update compared to ones from the 2015 iteration. To view the complete lists of recommendations, along with the accompanying rationale themselves, view the full-text versions using the links featured above.
| Topic | 2015 | 2025 |
|---|---|---|
| Immunoglobulin Replacement | Immunoglobulin replacement therapy is indicated for all disorders with significantly impaired antibody production. In association with low IgG levels, IgA deficiency is not a contraindication to IgG therapy. Patients receiving IgG therapy should have regular monitoring of IgG trough levels, blood cell counts, and serum chemistry Patients with NEMO syndrome should receive IgG replacement. | We recommend immunoglobulin replacement therapy (IgRT) for patients with IEI with IgG antibody deficiency. We recommend that initial dosing of immunoglobulin for replacement therapy be at 400 mg/kg to 600 mg/kg per month, followed by dose adjustment, if necessary. We recommend the monitoring of serum IgG levels, complete blood cell counts with differential, and serum chemistry panel for patients on immunoglobulin replacement therapy. We recommend maintaining serum IgG levels at more than 800 mg/dL to improve outcomes. We recommend that immunoglobulin replacement therapy is indicated as a continuous therapy for IEI. We recommend that a low or absent IgA level, in the setting of low IgG levels, is not a contraindication for immunoglobulin replacement therapy. We suggest that the route of immunoglobulin replacement therapy be determined based on patient tolerance or preference. |
| Infection Prevention in Inborn Errors of Immunity | Aggressive and prolonged antimicrobial therapy should be considered for immunodeficient patients. Short- or long-term antimicrobial prophylaxis should be considered for patients with immunodeficiency. | We recommend targeted antimicrobial prophylaxis for patients with IEI and increased susceptibility to infections. We recommend using only irradiated, CMV-negative, lymphocyte depleted blood products for administration to patients with combined immunodeficiencies or athymia. We recommend educating patients regarding environmental exposures that may increase the risk of infections for patients with IEI. We suggest prompt diagnostic testing in patients with IEI with acute infection symptoms and the use of antimicrobial regimens with duration longer than recommended for immunocompetent patients. |
| Immunizations | Inactivated or subunit vaccines can be administered to immunocompromised patients. Live vaccines should not be administered to patients with severely impaired specific immunity. | We recommend the use of vaccine recommendations from public agencies (eg, World Health Organization [WHO] and Centers for Disease Control and Prevention [CDC]) and professional medical organizations (eg, the American Academy of Allergy, Asthma and Immunology [AAAAI], the American College of Allergy, Asthma and Immunology [ACAAI], and CIS) for patients with IEI. |
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