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
