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Curriculum standards

Knowledge guides

LG14: Immunodeficiency

Key presentations and conditions

Advanced Trainees will have a comprehensive depth of knowledge of these presentations and conditions.

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Less common or more complex presentations and conditions

Advanced Trainees will understand these presentations and conditions.

Advanced Trainees will understand the resources that should be used to help manage patients with these presentations and conditions.

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Epidemiology, pathophysiology, and clinical sciences

Advanced Trainees will have a comprehensive depth of knowledge of the principles of the foundational sciences.

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Investigations, procedures, and clinical assessment tools

Advanced Trainees will know the scientific foundation of each investigation and procedure, including relevant anatomy and physiology. They will be able to interpret the reported results of each investigation or procedure.

Advanced Trainees will know how to explain the investigation or procedure to patients, families, and carers, and be able to explain procedural risk and obtain informed consent where applicable.

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Important specific issues

Advanced Trainees will identify important specialty-specific issues and the impact of these on diagnosis and management and integrate these into care.

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Presentations
  • Complex or multisystem with associated:
    • allergy
    • autoimmunity
    • bone marrow failure and/or malignancies
    • infection
  • Inadequate or non-response to vaccinations
  • Infections:
    • associated developmental or syndromic features due to inborn errors of immunity (IEIs)
    • recurrent, with low virulence or opportunistic organisms, difficult to treat, or atypical infection
  • Macrophage activation and related conditions
Conditions
  • Acquired / Secondary immunodeficiency:
    • human immunodeficiency virus (HIV)
    • hyposplenism or splenectomy
    • immunosuppressive therapies
    • malignancy and related therapies
    • nutrition and metabolic disorders, such as type 2 diabetes
    • phenocopies, including:
      • anticytokine antibodies
      • somatic mutations
    • post-solid organ or stem cell transplantation
    • protein-losing conditions
    • thymoma (Good syndrome)
  • IEIs / Primary immunodeficiency diseases (PIDs):
    • complement disorders:
      • C1 esterase inhibitor deficiency
    • immune deficiencies of cellular and humoral immunity:
      • combined immunodeficiency (CID)
      • T-B- severe combined immune deficiency (SCID)
      • T-B+ SCID
    • immune dysregulation diseases:
      • haemophagocytic lymphohistiocytosis (HLH)
      • immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome
    • phagocyte number or function defects:
      • defects of respiratory burst, such as chronic granulomatous disease
    • predominantly humoral deficiencies:
      • common variable immunodeficiency (CVID)
      • isotype / light chain and functional (specific) antibody deficiencies
      • low IgG / IgA with normal / high immunoglobulin M and normal B cells, including selective immunoglobulin A deficiency
      • x-linked agammaglobulinanemia (XLA)

AIM

  • Secondary causes:
    • phenocopies, including:
      • anticytokine antibodies
      • somatic mutations

PCH

  • Diseases of immune dysregulation
  • Familial haemophagocytic lymphohistiocytosis syndromes

For each presentation and condition, Advanced Trainees will know how to:

Synthesise
  • recognise the clinical presentation
  • identify relevant epidemiology, prevalence, pathophysiology, and clinical science
  • take a comprehensive clinical history
  • conduct an appropriate examination
  • establish a differential diagnosis
  • plan and arrange appropriate investigations
  • consider the impact of illness and disease on patients and their quality of life when developing a management plan
Manage
  • provide evidence-based management
  • prescribe therapies tailored to patients’ needs and conditions
  • recognise potential complications of disease and its management, and initiate preventative strategies
  • involve multidisciplinary teams
Consider other factors
  • identify individual and social factors and the impact of these on diagnosis and management
IEIs / PIDs
  • IEIs / PIDs including, but not limited to:
    • complement deficiencies
    • epidermodysplasia verruciformis (human papillomavirus infection)
    • herpes simplex encephalitis, such as toll-like receptors 3 (TLR) defect
    • immune dysregulation diseases:
      • autoimmune lymphoproliferative syndrome (ALPS)
      • autoimmunity with or without lymphoproliferation
      • immune dysregulation with colitis
      • regulatory T cell defects
      • susceptibility to Epstein–Barr virus and lymphoproliferative conditions
    • intrinsic and innate immunity defects
    • Mendelian susceptibility to mycobacterial disease (MSMD)
    • other IEI due to non-haemopoietic tissues or leucocytes
    • phagocyte number or function defects:
      • congential neutropenias
      • defects of motility
      • other non-lymphoid defects
    • phenotypes:
      • moderate, such as:
        • activator of transcription 1 (STAT1) loss-of-function (LOF)
        • signal transducer
      • severe, such as:
        • interferon gamma receptor 1 (IFNGR1) deficiency
    • predisposition to mucocutaneous candidiasis, such as STAT1 gain-offunction (GOF)
    • predisposition to severe viral infection, such as STAT1 deficiency
    • toll-like receptor signalling pathway deficiencies with bacterial susceptibility, such as:
      • interleukin-1 receptor-associated kinase 4 (IRAK4)
      • myeloid differentiation primary response protein (MyD88) deficiency

For each presentation and condition, Advanced Trainees will know how to:

Synthesise
  • recognise the clinical presentation
  • identify relevant epidemiology, prevalence, pathophysiology, and clinical science
  • take a comprehensive clinical history
  • conduct an appropriate examination
  • establish a differential diagnosis
  • plan and arrange appropriate investigations
  • consider the impact of illness and disease on patients and their quality of life when developing a management plan
Manage
  • provide evidence-based management
  • prescribe therapies tailored to patients’ needs and conditions
  • recognise potential complications of disease and its management, and initiate preventative strategies
  • involve multidisciplinary teams
Consider other factors
  • identify individual and social factors and the impact of these on diagnosis and management
  • Intravenous and subcutaneous immunoglobulin preparations available, and their:
    • composition
    • pharmacokinetics
    • safety considerations
  • Pathogenesis of immunodeficiency in other acquired immunodeficiencies
  • Pathogenic mechanisms underlying immunodeficiency disease states, such as:
    • factors influencing genotype-phenotype correlations in PID
    • pathogenesis of immunodeficiency in HIV infection:
      • role of clusters of differentiation 4 (CD4) T cell as a correlate of immunodeficiency and role in monitoring
      • spectrum of opportunistic pathogens and malignancies in untreated HIV infection
Investigations
  • Albumin, full blood count, globulins, and serum protein
  • Complement assays:
    • antibody, C1 / C3 / C4 esterase inhibitor, and C1q levels
    • functional C1 inhibitor
    • mannose-binding lectin (MBL)
    • normal total haemolytic complement (CH50) absent complement alternative pathway (AH50)
  • Cytokine release assays, such as interferon gamma release assay (IGRA)
  • Cytotoxicity assays
  • IgG subclasses
  • Immune pathway function assessment, such as:
    • activator of transcription (STAT5)
    • signal transducer
  • Immunisation with polysaccharide and protein vaccines to assess T cell independent and dependant antigen-specific responses
  • Lymphocyte and neutrophil function assays
  • Lymphocyte B and T subset enumeration, and memory B cell immunophenotyping
  • Molecular diagnostics:
    • assessment of likely pathogenicity of genetic variance
    • clinical utility of different methods of genetic analysis, such as candidate gene sequencing versus whole exome or whole genome sequencing, on patient care and consent process
    • understand the clinical impact and definition of variants of uncertain significance (VOUS)
  • Recall antigen- or vaccine-specific serology
  • Serum immunoglobulins – IgG A / E / M
  • Understanding the role and indications for genetic testing
  • Age- and ethnicity-related differences in reference ranges in relevant biomarkers, such as serum immunoglobulins
  • PIDs:
    • age-related differences in infection susceptibility, including the impact of transplacental immunoglobulin transfer and the effect of ageing on the immune system
    • appropriate and inappropriate vaccines according to PID advice, regarding benefits and risks, and prescribe reconstructive therapy as indicated
    • appropriate patient education, governance, and stewardship prior to and during treatment with immunoglobulin replacement therapy, including differences between subcutaneous and intravenous administration
    • discussion with patients regarding the role of genetic diagnosis and informed consent, particularly regarding other potentially affected family members
    • early detection of infections and neoplasia
    • maintain knowledge on newly described conditions
    • provide support and enhanced communication with transfer clinical teams in cases of transition from paediatric to adult immunology
    • support organisations available for patients with PID
    • use of prophylactic antibiotics and replacement immunoglobulin

PCH

  • Transient hypogammaglobulinemia of infancy, and primary immunodeficiency of childhood