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Table. Types of medical conditions and immunosuppressive therapy and associated levels of immunocompromise

Type of immunosuppression Example conditions (not an exhaustive list) Specific therapies that may affect level of immunocompromise Overall level of immunocompromise
Inborn errors of immunity, including primary immunodeficiency

Antibody (B-cell) immunodeficiencies: less severe

  • Selective IgA deficiency
  • IgG subclass deficiency
 No routine immunosuppressive therapies prescribed Moderate

Antibody (B-cell) immunodeficiencies: severe

  • Common variable immunodeficiency
  • X-linked agammaglobulinaemia
 Some patients may proceed to stem cell transplant, which will increase this level of immunosuppression Severe

T-cell or combined (T- and B-cell) immunodeficiencies: less severe

  • Incomplete DiGeorge syndrome
  • Ataxia telangiectasia
  • Hyper-IgE syndrome
 Some patients may proceed to stem cell transplant, which will increase this level of immunosuppression Moderate

T-cell or combined (T- and B-cell) immunodeficiencies: severe

  • Severe combined immunodeficiency 
  • Complete DiGeorge syndrome
 Some patients may proceed to stem cell transplant, which will increase this level of immunosuppression Severe

Phagocytic and neutrophil disorders

  • Congenital neutropenia
  • Cyclic neutropenia
  • Chronic granulomatous disease
 No routine immunosuppressive therapies prescribed, but antibiotic prophylaxis may be indicated Moderate

Defects of innate immunity

  • IFNAR defect
  • IFN gamma/IL-12 axis defect
  • Toll-like receptor signalling pathway defects
 No routine immunosuppressive therapies prescribed, but antibiotic prophylaxis may be indicated

Moderate

Susceptibilities to different pathogens depends on specific types of innate immune defects. See Defects of innate immunity: recommendations for vaccination

Complement deficiencies (primary)

  • C1, C2, C3, C5 or C6 deficiency
  • Properdin, factor B, D or H, and mannan-binding lectin deficiencies
 No routine immunosuppressive therapies prescribed, but antibiotic prophylaxis may be indicated

Mild

However, specific risk of infection with encapsulated bacteria (eg Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis)
Complement deficiencies (secondary) Secondary complement deficiencies due to prescribing complement inhibitors May be treated with complement inhibitors (eg eculizumab, ravulizumab)

Mild

However, specific risk of infection with encapsulated bacteria (eg Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis)
Common autoimmune and inflammatory conditions

Rheumatological

  • Rheumatoid arthritis
  • Psoriatic arthritis
  • Juvenile idiopathic arthritis
  • Ankylosing spondylitis
  • Systemic lupus erythematosus 

Dermatological

  • Severe atopic dermatitis
  • Psoriasis

Gastrointestinal

  • Crohn’s disease
  • Ulcerative colitis

  Neurological

  • Multiple sclerosis
 No active treatment and disease in remission Mild

Treated with selected or low-dose conventional immunosuppressive therapies: 

  • hydroxychloroquine
  • sulfasalazine 
  • leflunomide
  • mTOR inhibitors
  • methotrexate (≤25 mg/week)
  • azathioprine (≤3 mg/kg/day)
  • 6-mercaptopurine (≤1.5 mg/kg/day)
  1. Treated with selected biological therapies:
  • anti-CGRP antibodies
  • anti-RANK ligand antibodies
  • anti-IgE antibodies
  • IL-1, IL-5, IL-6, IL17, IL-23 inhibitors (eg anakinra, tocilizumab, mepolizumab)
  • TNF inhibitors
  • integrin inhibitors (eg natalizumab) 
  • IgE inhibitors (eg omalizumab)
 Generally mild to moderate, depending on prescribed dosage and mechanism of action. See Table. Recommended timing of live vaccine administration for people receiving immunosuppressive therapies and Table. Recommended timing of live vaccine administration for people receiving corticosteroids for more detail.

Treated with selected or high-dose immunosuppressive therapies: 

  • azathioprine (>3 mg/kg/day)
  • 6-mercaptopurine (>1.5 mg/kg/day)
  • methotrexate (>25 mg/week)
  • mycophenolate
  • calcineurin inhibitors
  • cyclophosphamide 
  1. Treated with selected biological immunosuppressive therapies:
  • T cell inhibitors (eg abatacept, basiliximab)
  • agents targeting cellular markers (eg blinatumomab, daratumumab)
 Severe during or <3 months after therapy completion
Moderate: >3 months after therapy completion
Treated with high-dose corticosteroids: >20 mg/day (infants and children <10kg: >2 mg/kg/day) for >14 days Severe during or <4 weeks after therapy completion
Moderate: >4 weeks after therapy completion
Treated with B-cell depleting biological therapies (eg rituximab) Severe: during or <6 months after therapy completion
Moderate: >6 months after therapy completion
    Treated with small molecule targeted therapies  JAK inhibitors (eg tofacitinib)

Mild

However, specific risk of infection with certain viruses (eg herpes zoster reactivation)
Oncological diagnoses Haematological Chronic malignancies not on active treatment and in cancer remission Moderate

Treated with small molecule targeted therapies

  • BCR-ABL inhibitors (eg imatinib)
  • BTK inhibitors (eg ibrutinib)
 Moderate
Treated with immunomodulatory drugs (eg thalidomide, lenalidomide, pomalidomide) Severe: during relapsed/refractory stage or multidrug regimens
Moderate: during maintenance stage
Treated with B-cell and T-cell targeting biological therapies (eg rituximab, ofatumumab, alemtuzumab) or bispecific agents Severe: first 6 months after therapy completion 
Moderate: >6 months after therapy completion 
Treated with stem cell transplant or cellular therapies (eg HSCT, CAR-T therapy) Severe: first 24 months after therapy completion
Moderate: >24 months after therapy completion
Solid tumours Completed active therapy and in cancer remission Mild
Treated with hormonal therapy  Mild
Treated with immune checkpoint inhibitors Mild

Treated with small molecule targeted therapies 

  • ALK inhibitors (eg alectinib)
  • CDK inhibitors (eg palbociclib, ribociclib)
 Mild
Treated with radiotherapy  Generally mild, but may be moderate or severe depending on site and extent of radiotherapy.
Treated with conventional chemotherapy Severe: during or <3 months after therapy completion
Moderate: >3 months after therapy completion 
Solid organ transplant Before solid organ transplant

Multiple immunosuppressants may be prescribed to treat the underlying organ failure, for details, see: 

 Moderate
After solid organ transplant Anti-rejection agents (such as mycophenolate, mTOR inhibitors, calcineurin inhibitors, corticosteroids) may be prescribed with reduced dosing over time Severe: first 12 months after transplant
Moderate: >12 months after transplant
Asplenia or hyposplenia Anatomical or functional asplenia or hyposplenia (eg congenital asplenia, sickle cell anaemia, splenectomy) No routine immunosuppressive therapies prescribed, but antibiotic prophylaxis may be indicated Moderate, mainly due to risk of infection with specific bacterial pathogens.
HIV infection
  • Infants (<12 months): CD4+ ≥1500 cells/μL
  • Children (1–5 years): CD4+ ≥1000 cells/μL
  • Adults and children >5 years: CD4+ ≥500 cells/μL 
 No routine immunosuppressive therapies prescribed, but highly active combination antiretroviral therapy prescribed (with or without agents to prevent opportunistic infections) Mild
  • Infants (<12 months): CD4+ 750–1499 cells/μL
  • Children (1–5 years): CD4+ 500–999 cells/μL
  • Adults and children >5 years: CD4+  200–499 cells/μL
 No routine immunosuppressive therapies prescribed, but highly active combination antiretroviral therapy prescribed (with or without agents to prevent opportunistic infections) Moderate
  • Infants (<12 months): CD4+ <750 cells/μL
  • Children (1–5 years): CD4+ <500 cells/μL
  • Adults and children >5 years: CD4+ <200 cells/μL
 No routine immunosuppressive therapies prescribed, but highly active combination antiretroviral therapy prescribed (with or without agents to prevent opportunistic infections) Severe

Acronyms used: 

  • ALK = anaplastic lymphoma kinase
  • BTK = Bruton’s tyrosine kinase
  • CAR-T = chimeric antigen receptor modified T-cell
  • CDK = cyclin-dependent kinase
  • IFN = interferon 
  • IFNAR = interferon-alpha/beta receptor 
  • IL = interleukin 
  • HSCT = haematopoietic stem cell transplant 
  • JAK = Janus kinase 
  • mTOR = mammalian target of rapamycin 
  • RANK = receptor activator of nuclear factor kappa B 
  • TNF = tumour necrosis factor
Related chapters
Vaccination for people who are immunocompromised

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