Primary and secondary immunodeficiency

Immunodeficiency means inadequate defence against infection or immune dysregulation caused by an intrinsic immune disorder or an acquired process. “Primary” now encompasses many inborn errors of immunity and need not present in childhood. “Secondary” includes loss, suppression or consumption of otherwise intact components. The distinction matters for genetics, prognosis and family counselling, but the first clinical task is the same: recognise dangerous infection and stabilise it without waiting for a complete classification.

Patterns can localise function. Antibody defects often cause recurrent sinopulmonary infection with encapsulated bacteria and may emerge after maternal antibody wanes or in adulthood. T-cell or combined defects predispose to viral, fungal and opportunistic disease, chronic diarrhoea and failure to thrive. Phagocyte number or function defects can cause deep bacterial or fungal infection and poor wound healing. Terminal complement defects associate with invasive Neisseria, while early complement defects can combine infection with immune-complex disease. These are clues rather than one-to-one rules.

Immune dysregulation broadens the phenotype. Autoimmune cytopenia, enteropathy, eczema, granulomatous inflammation, persistent lymphadenopathy, splenomegaly and unusual malignancy can accompany an inborn disorder. Family history may show recurrent infection, early infant deaths, consanguinity or affected males, but de novo and recessive disorders can lack a clear pedigree. An unexpectedly weak inflammatory response does not reassure: certain signalling defects can produce severe bacterial infection with little fever or acute-phase response.

Secondary causes must be actively sought. Corticosteroids, cytotoxic therapy, B-cell depletion, transplantation and targeted immunomodulators create mechanism-specific and time-dependent risk. HIV affects cellular immunity; haematological malignancy can impair quantity and quality of lymphocytes and antibodies. Nephrotic or gastrointestinal protein loss lowers immunoglobulin; splenectomy weakens clearance of encapsulated organisms; malnutrition and critical illness disrupt several defences. Structural lung or urinary disease may mimic immune failure by causing recurrent infection at one site.

Investigation is layered. Document organisms, sites, severity, response, cultures, antimicrobial exposure and imaging rather than relying on the word “recurrent.” Initial tests commonly include full blood count with differential and film, quantitative IgG, IgA and IgM, renal and liver profiles, albumin and HIV testing. Further lymphocyte subsets, vaccine antibody responses, complement pathways, neutrophil function, bone marrow or genomic testing are selected with immunology input because timing, age, infection and treatment alter results.

Management matches mechanism and patient outcome. Prompt infection treatment, vaccination planning, antimicrobial prophylaxis, immunoglobulin replacement, haematopoietic transplantation or gene-based therapy may be appropriate in different disorders. Immunoglobulin replacement is specialist treatment based on diagnosis, functional antibody failure and infection burden rather than a single low value, and dosing is individualised to clinical outcomes. Protect organs through pulmonary review, microbiology, physiotherapy and surveillance while supporting genetic counselling and emergency plans.