Paeds · allergy-and-immunology
Secondary immunodeficiency
Also known as Acquired immunodeficiency · Secondary immune deficiency · Secondary hypogammaglobulinaemia · Iatrogenic immunodeficiency · HIV-related immunodeficiency in children
A fellowship approach to secondary (acquired) immunodeficiency in children: recognise that it is commoner than primary inborn errors of immunity, sort it into six mechanism-based categories (infection, malignancy and its treatment, drugs and biologics, protein loss, nutritional, splenic and metabolic), link each cause to the immune arm it disables and the infection pattern that follows, then apply the five-step management ladder — treat the cause, give antimicrobial prophylaxis, replace what is missing, vaccinate safely, and surveil — reserving immunoglobulin replacement for proven infection-associated hypogammaglobulinaemia rather than a single low number.
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- Opportunistic infection — Pneumocystis, CMV, invasive fungal, atypical mycobacteria — in any child is secondary immunodeficiency until proven otherwise
- Recurrent or severe infection in a child on chemotherapy, high-dose corticosteroids, rituximab, or after transplant
- New infection in a child with nephrotic-range proteinuria, protein-losing enteropathy, or severe malnutrition
- Overwhelming sepsis with encapsulated bacteria in an asplenic or hyposplenic child
- Persistent or progressive hypogammaglobulinaemia with recurrent infection after rituximab, even months to years after the last dose
- Failure to thrive with recurrent or opportunistic infection in a child with HIV exposure or severe malnutrition
- Febrile neutropenia in a child on chemotherapy is a medical emergency requiring empirical intravenous antibiotics within the hour
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Board mappings
- General and Community Paediatrics
- Infectious Diseases, Immunology and Allergy
- Growth and Development
- Allergy and immunology - recognise, investigate and manage primary immunodeficiency and recurrent infection
- Infectious Diseases - recognise and manage immunocompromised hosts
- Respiratory - manage bronchiectasis and chronic suppurative lung disease
- Immunology and Allergy 10-12
- Clinical Applications
- Medical Sciences
- Long Cases
- Short Cases
- 9. Infection, Immunology and Allergy
- 4. Professional skills and knowledge: Patient management
- 7. Patient safety, including safe prescribing
- Foundation of Practice (FOP)
- Theory and Science (TAS)
- Applied Knowledge in Practice (AKP)
- Clinical
- History
- Communication
- Video
- General Pediatrics Content Outline - D17 Allergy and Immunology (3%)
- General Pediatrics Content Outline - D15 Infectious Diseases (8%)
- General Pediatrics Content Outline - Universal Task 4: Management and Treatment
- Patient Care 4: Clinical Reasoning
- Patient Care 5: Patient Management
- Medical Knowledge 3: Allergy and Immunology
- Systems-Based Practice 1: Patient Safety
- Medical Expert
- Pediatrics: Foundations EPA #8 - Communicating assessment findings and management plans to patients and/or families
- Pediatrics: Allergy and Clinical Immunology (0-5%)
A four-year-old girl on long-term high-dose corticosteroids for an autoimmune disease presents with a dry cough, hypoxia, and bilateral interstitial infiltrates. The same "immunocompromised" label could be written on the chart of a neutropenic oncology child with staphylococcal bacteraemia, a boy with nephrotic syndrome and pneumococcal peritonitis, and a refugee infant with severe malnutrition and Gram-negative sepsis — yet each is failing a different immune arm, will be killed by a different organism, and needs a different defence. Holding the cause-to-arm-to-organism chain in your head is what turns "immunocompromised" from a vague warning into a plan, and that chain is the whole of this topic. [1] [4]
Corticosteroids and chemo (neutropenia, T-cell and macrophage suppression) · Asplenia (encapsulated-bacterial sepsis) · Urinary or gut protein loss (IgG waste — nephrotic syndrome, enteropathy) · Severe malnutrition (thymic atrophy, barrier and cellular failure) · Exogenous biologics (rituximab depletes B cells; anti-TNF impairs granulomas) · Systemic infection (HIV depletes CD4 cells). Six categories, six arms, six organism patterns — match the cause to the prophylaxis. [1] [2]
Overview & Definition
A secondary immunodeficiency is a state in which an otherwise normal immune system is disabled by an acquired external factor, leaving the child vulnerable to infection. The defect is not inherited; it is imposed by an infection, a malignancy and its treatment, a drug, the loss of immune proteins, malnutrition, or the loss of a lymphoid organ. Because the cause is external, much of the damage is reversible if the cause is treated — and that reversibility is the feature that most distinguishes secondary from primary immunodeficiency in practice. [1] [2]
The reason secondary immunodeficiency dominates clinical paediatrics is simple arithmetic. The conditions that produce it — oncology treatment, transplant immunosuppression, biologics, nephrotic syndrome, severe malnutrition, and HIV — are each individually far commoner than even the most frequent primary antibody defect. A general paediatrician will meet secondary immune failure many times a year and a primary inborn error perhaps a few times in a career. Defaulting to the question "what is disabling this child's immunity?" before reaching for a primary-disease work-up is the discipline of the topic. [2] [4]
The framework that organises every secondary cause is mechanism-based: sort by which arm of the immune system the cause disables. A cause that depletes CD4 T cells (HIV) produces opportunistic infection; one that wastes IgG (nephrotic syndrome) produces encapsulated-bacterial infection; one that causes neutropenia (chemotherapy) produces Gram-negative and staphylococcal bacteraemia. The mechanism predicts the organism, and the organism predicts both the empiric treatment and the prophylaxis you put in place afterwards. [1] [10]
References10ShowHide
- [1]Chinen J, Shearer WT. Secondary immunodeficiencies, including HIV infection. J Allergy Clin Immunol, 2010.PMID 20042227
- [2]Tuano KS, Seth N, Chinen J. Secondary immunodeficiencies: An overview. Ann Allergy Asthma Immunol, 2021.PMID 34481993
- [3]Otani IM, Lehman HK, Jongco AM, Tsao LR, Azar AE, Tarrant TK. Practical guidance for the diagnosis and management of secondary hypogammaglobulinemia: A Work Group Report of the AAAAI Primary Immunodeficiency and Altered Immune Response Committees. J Allergy Clin Immunol, 2022.PMID 35176351
- [4]Ballow M, Sánchez-Ramón S, Walter JE. Secondary Immune Deficiency and Primary Immune Deficiency Crossovers: Hematological Malignancies and Autoimmune Diseases. Front Immunol, 2022.PMID 35924244
- [5]Rytter MJ, Kolte L, Briend A, Friis H, Christensen VB. The immune system in children with malnutrition--a systematic review. PLoS One, 2014.PMID 25153531
- [6]Maertens J, Cesaro S, Maschmeyer G, Einsele H, Donnelly JP, Alanio A. ECIL guidelines for preventing Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients. J Antimicrob Chemother, 2016.PMID 27550992
- [7]Stern A, Green H, Paul M, Vidal L, Leibovici L. Prophylaxis for Pneumocystis pneumonia (PCP) in non-HIV immunocompromised patients. Cochrane Database Syst Rev, 2014.PMID 25269391
- [8]Chan EY, Yap DY, Colucci M, Ma AL, Parekh RS, Tullus K. Use of Rituximab in Childhood Idiopathic Nephrotic Syndrome. Clin J Am Soc Nephrol, 2023.PMID 36456193
- [9]Lee GM. Preventing infections in children and adults with asplenia. Hematology Am Soc Hematol Educ Program, 2020.PMID 33275684
- [10]Youssef J, Novosad SA, Winthrop KL. Infection Risk and Safety of Corticosteroid Use. Rheum Dis Clin North Am, 2016.PMID 26611557