Manifestations of Primary Immunodeficiencies Beyond Infections

Research encourages health care professionals to look beyond only infection-centered warning signs in identifying primary immunodeficiencies since these immunodeficiencies may manifest in patients in several other forms, according to a recent study published in the Journal of Allergy and Clinical Immunology.

“An exclusive focus on infection-centered warning signs would have missed around 25% of patients with inborn errors of immunity who initially present with other manifestations,” the investigators cautioned.

Primary immunodeficiencies, also known as inborn errors of immunity, present a rare challenge because little is known about the frequency of other presenting manifestations. Better knowledge of their initial presenting manifestations would help improve awareness among patients and also avoid diagnostic delay.

To analyze the initial presenting manifestations of IEI among different disease cohorts, the researchers studied data on 16,486 patients from the European Society for Immunodeficiencies Registry. The research did not include patients with autoinflammatory diseases.

Majority of the patients (68%) initially presented with infections only. However, 9% of the patients presented with immune dysregulation only, 9% with a combination of both infections and immune dysregulation, 12% with syndromic features, 4% had laboratory abnormalities, 1.5% were diagnosed because of family history, and 0.8% presented with malignancy. Focusing solely on infections would most likely overlook the other patients who initially presented other non-infection related manifestations, the researchers emphasized.

Additionally, they found that immune dysregulation was the most frequent initial manifestation between the age 6 and 25 years, with “male predominance until age 10 years, shifting to female predominance after age 40 years.” For patients after age 30, infections became the most prevalent first manifestation of primary immunodeficiency.

—Priyam Vora

Reference:
Thalhammer J, Kindle G, Nieters A et al. Initial presenting manifestations in 16,486 patients with inborn errors of immunity include infections and noninfectious manifestations. The Journal of Allergy and Clinical Immunology. Published online: April 22, 2021. DOI: https://doi.org/10.1016/j.jaci.2021.04.015