Inborn Errors of Immunity (IEI), formerly known as Primary Immunodeficiency Disorders (PID), encompass a spectrum of conditions characterised by recurrent infections, autoimmunity, autoinflammation, allergies, and malignancies. Contrary to the traditional belief that IEIs/PIDs primarily affect young children, recent evidence highlights their relevance in adults as well. Table 1 outlines common misconceptions related to the suspicion and diagnosis of IEIs/PIDs. In this letter, I will discuss a pattern-based diagnostic approach to specific IEIs, focusing on the characteristic infection patterns associated with each.

The classical teaching of PIDs into 4 major subgroups still holds its value today. It is divided into predominant B-cell defects, predominant T-cell defects, Granulocytic (neutrophil) defects, and Complement deficiencies. Clinical pattern recognition comprises age, the system affected, and the organisms involved. Table 2 summarises the pattern recognition steps for diagnosing PIDs [Common PIDs, though the list is not exhaustive], using age, infection patterns, and microorganisms. Although age usually aids in classifying/diagnosing certain types of PIDs, hypomorphic variants may present at any age.

With the discovery of more IEIs/PIDs, as well as an expanding understanding of innate immune defects and the role of auto-cytokine antibodies (phenocopies of PIDs), the relationship between specific pathogens and PIDs has become increasingly complex, not as simple as illustrated in Table 2. Table 3 provides an expanded overview of the most common pathogens and their associated PIDs. However, it is crucial to interpret these associations within the appropriate clinical context. Diagnosis should not rely exclusively on the identification of causative organisms; rather, a comprehensive clinical, necessary lab assessment remains vital. For example, certain opportunistic infections are frequently seen in intensive care settings, and adults with diabetes or secondary immunodeficiency are susceptible to specific infections: factors that must always be considered during evaluation.

Table 1: Common misconceptions

Table 2: Pattern recognition