SN7 SHORT NOTE 5M

Classify immunodeficiency disorders. Describe their features, investigation and management.

Microbiology · 2nd Professional — Para-Clinical

Classification

Immunodeficiency is a failure of one or more components of the immune system, resulting in increased susceptibility to infection. It is primary (congenital) or secondary (acquired), the latter being far commoner.

Component affected	Characteristic infections	Examples
B cell / antibody (about 50% of primary)	Recurrent pyogenic infection with capsulated organisms — pneumococcus, Haemophilus; sinopulmonary infection, giardiasis. Onset after 6 months, when maternal IgG has waned	BRUTON X-linked agammaglobulinaemia (no B cells, no immunoglobulins, absent tonsils); common variable immunodeficiency; selective IgA deficiency (the commonest, often asymptomatic)
T cell / cell-mediated	Viral, fungal, mycobacterial and protozoal infection; chronic candidiasis; disseminated BCG after vaccination	DiGEORGE syndrome (thymic aplasia with hypocalcaemia and cardiac anomalies, from 22q11 deletion); chronic mucocutaneous candidiasis
Combined	Severe infection of every kind from the first months of life	Severe combined immunodeficiency (SCID) — fatal without stem cell transplant; Wiskott-Aldrich syndrome (eczema, thrombocytopenia, infection); ataxia-telangiectasia
Phagocyte	Recurrent abscesses, and infection with catalase-positive organisms (Staphylococcus, Serratia, Aspergillus, Burkholderia)	Chronic granulomatous disease (failure of the NADPH oxidase respiratory burst; diagnosed by the nitroblue tetrazolium or dihydrorhodamine test); Chediak-Higashi syndrome; leucocyte adhesion deficiency (delayed cord separation)
Complement	C3 deficiency — pyogenic infection; terminal components (C5–9) — recurrent neisserial infection	C1 inhibitor deficiency causes hereditary angio-oedema rather than infection

CLINICAL PEARL

The pattern of infection tells you which arm has failed, and this is the most useful clinical reasoning in the whole subject. Recurrent pyogenic infection with capsulated organisms beginning after six months points to antibody; viral, fungal and mycobacterial infection from birth points to T cells; recurrent abscesses point to phagocytes; and recurrent neisserial infection points to terminal complement. The history narrows the investigation before any test is ordered.

Secondary Immunodeficiency

Far commoner than primary immunodeficiency, and the important causes in Indian practice are largely preventable or treatable
Infection — HIV above all; also measles, tuberculosis, malaria and chronic viral hepatitis
Malnutrition — the commonest cause of secondary immunodeficiency worldwide; protein-energy malnutrition impairs cell-mediated immunity particularly, and deficiencies of zinc, iron, vitamin A and vitamin D all contribute
Iatrogenic — corticosteroids, cytotoxic chemotherapy, immunosuppressants, biologicals, radiotherapy, splenectomy
Malignancy — lymphoma, leukaemia, myeloma (where antibody production fails despite a high total protein)
Other — diabetes mellitus, chronic kidney disease, cirrhosis, burns, protein-losing states (nephrotic syndrome, protein-losing enteropathy), extremes of age, and asplenia

Investigation

Full blood count with differential — lymphopenia, neutropenia, thrombocytopenia; and a blood film
Serum immunoglobulins and IgG subclasses; specific antibody responses to vaccines (tetanus, pneumococcus) test function rather than quantity
Lymphocyte subsets by flow cytometry — CD3, CD4, CD8, CD19, CD56
Complement — CH50 (screens the classical pathway), AH50, and individual components
Phagocyte function — nitroblue tetrazolium or dihydrorhodamine test for chronic granulomatous disease
HIV testing in every case; and genetic testing where a primary immunodeficiency is suspected
Warning signs prompting investigation — recurrent or unusually severe infection, infection with an unusual organism, failure to thrive, need for intravenous antibiotics to clear infections, deep abscesses, persistent thrush after one year, and a family history

Management and Applied Aspects

Treat and prevent infection — prompt and adequate antibiotics, and prophylaxis (co-trimoxazole for Pneumocystis, antifungals) where indicated
Immunoglobulin replacement for antibody deficiencies, given regularly and lifelong; it transforms the outlook in Bruton disease and common variable immunodeficiency
Haematopoietic stem cell transplantation is curative in SCID and some other severe defects; gene therapy has succeeded in selected conditions
Avoid live vaccines in significant T-cell or combined deficiency — BCG and oral polio vaccine have caused disseminated disease in infants with undiagnosed SCID, which is a real hazard in a programme giving BCG at birth
Give irradiated, leucodepleted and CMV-negative blood products to severely immunodeficient patients, to prevent transfusion-associated graft-versus-host disease
Address the treatable secondary causes — nutrition, diabetic control, HIV treatment; in India, correcting undernutrition and treating HIV do more for immune competence than any specific immunological intervention

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