Phys · general-medicine
Primary Immunodeficiency in Adults
Also known as inborn errors of immunity · CVID · common variable immunodeficiency · selective IgA deficiency · specific antibody deficiency · terminal complement deficiency · hereditary angioedema · C1 inhibitor deficiency · chronic granulomatous disease · recurrent infection workup · Jeffrey Modell warning signs · humoral immunodeficiency · immunoglobulin replacement therapy
Consultant-physician guide to when to suspect primary immunodeficiency in adults (Jeffrey Modell Foundation warning signs), the four-arm classification (humoral, cellular, complement, phagocyte), the adult-presentation disorders in each arm (CVID as the most common symptomatic PID in adults; selective IgA deficiency; specific antibody deficiency; terminal complement and properdin deficiency with recurrent Neisseria; hereditary angioedema from C1 inhibitor deficiency; chronic granulomatous disease), and the structured investigation pathway (immunoglobulins, vaccine response, lymphocyte subsets, CH50 and AH50, and the mandatory HIV test to exclude secondary causes). Treatment principles for immunoglobulin replacement therapy, complement-deficiency prevention, and HAE-specific acute and prophylactic therapy are covered at consultant viva depth.
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Red flags
- Any adult with two or more pneumonias in one year, four or more new ear infections, chronic sinusitis or bronchitis for over 12 weeks, or two or more deep-seated infections (sepsis, cellulitis, osteomyelitis) in one year meets the Jeffrey Modell Foundation warning signs and warrants serum immunoglobulins — primary immunodeficiency is more common than believed (prevalence about 1 in 1,200) and the diagnosis is delayed by a median of 4 to 7 years
- Any adult with two or more episodes of invasive meningococcal disease must have a CH50 measured — terminal complement deficiency (C5 to C9) is the cause in a significant proportion, and the diagnosis changes the preventive plan (vaccination, standby antibiotics, family screening)
- Recurrent non-urticarial, non-pruritic angioedema (no hives, no itch, no response to adrenaline) with a family history is hereditary angioedema (C1 inhibitor deficiency) until proven otherwise — acute attacks do NOT respond to adrenaline, antihistamines, or corticosteroids; give C1 inhibitor concentrate or icatibant, because laryngeal oedema is the leading cause of death
- A normal immunoglobulin panel does NOT exclude primary immunodeficiency — specific antibody deficiency (normal immunoglobulins, poor polysaccharide response) and complement deficiency (normal immunoglobulins) are missed if you stop at the immunoglobulin screen; measure pneumococcal vaccine response and CH50 when the pattern warrants
- Immunoglobulin replacement is NOT indicated for isolated IgA deficiency (it contains minimal IgA and does not correct the mucosal defect) — it is indicated for CVID and significant combined antibody deficiency where IgG is low and the functional defect is documented
- In any adult being evaluated for immunodeficiency, secondary causes (especially HIV, but also CLL, myeloma, immunosuppressive drugs, protein-losing states) are far more common than primary defects — an HIV test is mandatory before attributing hypogammaglobulinaemia or recurrent infection to CVID
- About 25 per cent of CVID patients have autoimmune disease, and the lymphoma risk is markedly increased (non-Hodgkin lymphoma 30 to 200-fold) — any new lymphadenopathy, B-symptoms, or unexplained cytopenia in CVID warrants urgent investigation for lymphoma
- Selective IgA deficiency with anti-IgA antibodies can cause anaphylaxis to blood products — in an emergency do not delay transfusion, but for elective transfusion in a patient with a known reaction use washed or IgA-deficient products
Primary Immunodeficiency in Adults
Meet the patient
A 32-year-old woman presents to the respiratory clinic with her fourth pneumonia in two years, chronic diarrhoea she blames on irritable bowel syndrome, and an autoimmune thrombocytopenia diagnosed six months ago. Her immunoglobulins have never been measured. A chest CT shows early bronchiectasis.[1]
The question that should have been asked three years ago is the one that decides her next hour: is recurrent sinopulmonary infection plus autoimmunity plus chronic diarrhoea the signature of a humoral defect? The answer is yes — and the immunoglobulin panel nobody ordered would have made the diagnosis years ago. Everyone reaches for the antibiotic. That is how you get bronchiectasis.[2]
References9ShowHide
- [1]Boyle JM, Buckley RH Population prevalence of diagnosed primary immunodeficiency diseases in the United States J Clin Immunol, 2007.PMID 17577648
- [2]Bonilla FA Common variable immunodeficiency Pediatr Res, 2009.PMID 19190529
- [3]Bonilla FA, Barlan I, Chapel H, et al. International Consensus Document (ICON): Common Variable Immunodeficiency Disorders J Allergy Clin Immunol Pract, 2016.PMID 26563668
- [4]Yel L Selective IgA deficiency J Clin Immunol, 2010.PMID 20101521
- [5]Figueroa JE, Densen P. Infectious diseases associated with complement deficiencies Clin Microbiol Rev, 1991.PMID 1889047
- [6]Grumach AS, Kirschfink M. Are complement deficiencies really rare? Overview on prevalence, clinical importance and modern diagnostic approach Mol Immunol, 2014.PMID 25037634
- [7]Craig T, Aygören-Pürsün E, Bork K, et al. WAO Guideline for the Management of Hereditary Angioedema World Allergy Organ J, 2012.PMID 23282420
- [8]Busse PJ, Christiansen SC. Hereditary Angioedema N Engl J Med, 2020.PMID 32187470
- [9]Patel SY, Carbone J, Jolles S. The Expanding Field of Secondary Antibody Deficiency: Causes, Diagnosis, and Management Front Immunol, 2019.PMID 30800120