Primary immunodeficiency: Difference between revisions

From IDWiki
(β†’β€: added reading)
mNo edit summary
Β 
(23 intermediate revisions by the same user not shown)
Line 1: Line 1:
  +
* See also [[immunodeficiency]] and [[acquired immunodeficiency]]
βˆ’
==Differential Diagnosis==
  
βˆ’
* '''Humoural''' (65%): B cell defects
  
βˆ’
** [[X-linked agammaglobulinemia]]
  
βˆ’
** [[Common variable immune deficiency]] (CVID)
  
βˆ’
** [[Transient hypogammaglobulinemia of infancy]]
  
βˆ’
** [[Hyper-IgM syndrome]]
  
βˆ’
** [[IgA deficiency]]
  
βˆ’
* '''Cell-mediated''' (5%): T-cell deficiencies
  
βˆ’
** [[DiGeorge syndrome]]
  
βˆ’
** [[Chronic mucocutaneous candidiasis]]
  
βˆ’
* '''Combined''' (15%): B- and T-cell deficiencies, often much more severe
  
βˆ’
** [[Severe combined immunodeficiency disease]] (SCID)
  
βˆ’
** [[Wiskott-Aldrich syndrome]]
  
βˆ’
** [[Ataxia-telangiectasia]]
  
βˆ’
** [[X-linked lymphoproliferative disease]]
  
βˆ’
** [[CD40 ligand deficiency]]
  
βˆ’
* '''Phagocytic''' (10%): neutrophil deficiencies
  
βˆ’
** Phagocyte deficiencies
  
βˆ’
** [[Chronic granulomatous disease]] (CGD)
  
βˆ’
** [[Leukocyte adhesion deficiency]]
  
βˆ’
** [[Hyper-IgE syndrome]]
  
βˆ’
* '''Complement''' (5%)
  
βˆ’
** [[C2 deficiency]]
  
βˆ’
** [[Properdin deficiency]]
  
   
  +
==Clinical Manifestations==
βˆ’
==Red Flags for Immunodeficiency==
  
  +
βˆ’
===Children===
  
  +
* See also [[Immunodeficiency#Clinical Manifestations|clinical manifestations of immunodeficiency]]
βˆ’
* β‰₯4 new ear infections in 1 year
  
  +
βˆ’
* β‰₯2 serious sinus infections in 1 year
  
  +
=== Red Flags for Immunodeficiency ===
  +
{| class="wikitable"
  +
!
  +
!Children
  +
!Adults
  +
|-
  +
|New ear infections
  +
|β‰₯4 in 1 year
  +
|β‰₯2 in 1 year
  +
|-
  +
|Serious sinus infections
  +
|β‰₯2 in 1 year
  +
|β‰₯2 in 1 year, in the absence of allergy
  +
|-
  +
|Pneumonias
  +
|β‰₯2 in 1 year
  +
|β‰₯2 in 1 year
  +
|-
  +
|Deep skin or organ abscesses
  +
|Recurrent
  +
|Recurrent
  +
|-
  +
|Oral thrush or fungal skin infections
  +
|Persistent
  +
|Persistent
  +
|-
  +
|Family history of primary immunodeficiency
  +
|Any
  +
|Any
  +
|-
  +
|Other
  +
|
 
* β‰₯2 months on antibiotics with little effect
  
* β‰₯2 months on antibiotics with little effect
βˆ’
* β‰₯2 pneumonias in 1 year
  
 
* Failure to gain weight or grow normally
  
* Failure to gain weight or grow normally
βˆ’
* Recurrent deep skin or organ abscesses
  
βˆ’
* Persistent thrush in mouth or fungal skin infection
  
 
* Need for IV antibiotics to treat infections
  
* Need for IV antibiotics to treat infections
 
* β‰₯2 deep-seated infections including bacteremia
  
* β‰₯2 deep-seated infections including bacteremia
  +
|
βˆ’
* A family history of primary immunodeficiency
  
βˆ’  
βˆ’
===Adults===
  
βˆ’
* β‰₯2 new ear infections in 1 year
  
βˆ’
* β‰₯2 new sinus infections in 1 year (in the absence of allergy)
  
βˆ’
* β‰₯2 new pneumonias in 2 years
  
 
* Chronic diarrhea with weight loss
  
* Chronic diarrhea with weight loss
βˆ’
* Recurrent viral infections, such as colds, herpes, warts, or condylomata
  
 
* Recurrent need for IV antibiotics to treat infections
  
* Recurrent need for IV antibiotics to treat infections
βˆ’
* Recurrent, deep abscesses of skin or internal organs
 +
* Recurrent viral infections, such as colds, [[herpes]], warts, or condylomata
  +
* Infection with [[non-tuberculous mycobacteria]]
βˆ’
* Persistent thrush or fungal infections
  
  +
|}
βˆ’
* Infection with non-tuberculous mycobacteria
  
  +
βˆ’
* A family history of primary immunodeficiency
  
  +
==Differential Diagnosis==
  +
  +
===Children===
  +
{| class="wikitable"
  +
!Disease
  +
!Defect
  +
!Age at Diagnosis
  +
!Notes
  +
|-
  +
! colspan="4" |Humoural (65%)
  +
|-
  +
|[[X-linked agammaglobulinemia]]
  +
|BTK mutation
  +
|
  +
|X-linked, very low antibody levels
  +
|-
  +
|[[Common variable immunodeficiency]] (CVID)
  +
|multiple
  +
|20-40 years
  +
|low IgG with poor antibody response
  +
|-
  +
|[[Transient hypogammaglobulinemia of infancy]]
  +
|
  +
|
  +
|
  +
|-
  +
|[[Hyper-IgM syndrome]]
  +
|multiple
  +
|
  +
|X-linked or autosomal recessive, high IgM with poor T-cell function
  +
|-
  +
|[[IgA deficiency]]
  +
|decreased IgA
  +
|
  +
|low IgA, often associated with other immunodeficiencies
  +
|-
  +
! colspan="4" |Cell-Mediated (5%)
  +
|-
  +
|[[DiGeorge syndrome]]
  +
|thymus aplasia
  +
|
  +
|
  +
|-
  +
|[[Chronic mucocutaneous candidiasis]]
  +
|
  +
|
  +
|
  +
|-
  +
! colspan="4" |Combined (15%)
  +
|-
  +
|[[Severe combined immunodeficiency disease]] (SCID)
  +
|near-absolute T cell deficiency
  +
|
  +
|lymphopenia with hypogammaglobulinemia
  +
|-
  +
|[[Wiskott-Aldrich syndrome]]
  +
|WASP mutation
  +
|
  +
|X-linked, [[eczema]], [[thrombocytopenia]], low IgM with high IgA
  +
|-
  +
|[[Ataxia-telangiectasia]]
  +
|ATM mutation
  +
|
  +
|autosomal recessive, with low IgA, CD3, and CD4, and malignancies
  +
|-
  +
|[[X-linked lymphoproliferative disease]]
  +
|SAP mutation
  +
|
  +
|X-linked, low EBNA antibodies
  +
|-
  +
|[[CD40 ligand deficiency]]
  +
|
  +
|
  +
|
  +
|-
  +
|[[Hyper-IgE syndrome]] (Job syndrome)
  +
|STAT3 mutation
  +
|
  +
|[[eczema]], [[Pneumatocele|pneumatoceles]], [[mucocutaneous candidiasis]], recurrent cutaneous and respiratory infections, and elevated IgE
  +
|-
  +
! colspan="4" |Phagocytic (10%)
  +
|-
  +
|[[Chronic granulomatous disease]] (CGD)
  +
|NADPH oxidase
  +
|
  +
|GI and GU granulomas, infections with [[Staphylococcus aureus]], [[Burkholderia cepacia]], [[Serratia marcescens]], [[Nocardia]], and [[Aspergillus]]
  +
|-
  +
|[[Leukocyte adhesion deficiency]]
  +
|multiple types
  +
|
  +
|autosomal recessive
  +
|-
  +
|TLR3 deficiency
  +
|
  +
|
  +
|recurrent [[Herpes simplex encephalitis|HSV encephalitis]]
  +
|-
  +
! colspan="4" |Complement (5%)
  +
|-
  +
|[[C2 deficiency]] and other classical complement deficiencies
  +
|classical complement pathway
  +
|
  +
|low CH<sub>50</sub>, autoimmune disease in C1-C4, bacteremia and meningitis
  +
|-
  +
|[[Properdin deficiency]]
  +
|alternative complement pathway
  +
|
  +
|more severe than classical complement deficiencies
  +
|-
  +
! colspan="4" |Immune Dysregulation
  +
|-
  +
|[[Hemophagocytic lymphohistiocytosis]]
  +
|
  +
|
  +
|
  +
|-
  +
|[[Autoimmune lymphoproliferative disorder]] (ALPS)
  +
|
  +
|
  +
|
  +
|-
  +
|[[Immunodysregulation, polyendocrinopathy, enteropathy, X-linked]] (IPEX)
  +
|
  +
|
  +
|
  +
|-
  +
|[[Autoimmune polyendocrinopathy, candidiasis, and ectodermal dystrophy]] (APECED)
  +
|
  +
|
  +
|
  +
|}
  +
  +
===Adults===
  +
{| class="wikitable"
  +
!Disease
  +
!Arm of Immune System
  +
!Notes
  +
|-
  +
! colspan="3" |Adult-Onset Common
  +
|-
  +
|[[IgA deficiency]]
  +
|Humoural
  +
|
  +
|-
  +
|[[Common variable immunodeficiency]]
  +
|Humoural
  +
|
  +
|-
  +
|[[IgG subclass deficiency]]
  +
|Humoural
  +
|
  +
|-
  +
|[[Complement deficiencies]]
  +
|Complement
  +
|
  +
|-
  +
|[[Good syndrome]]
  +
|Combined humoural and cell-mediated
  +
|Very rare. Associated with thymoma and autoimmune diseases
  +
|-
  +
! colspan="3" |Delayed Presentation Possible
  +
|-
  +
|[[Adenosine deaminase deficiency]]
  +
|Combined
  +
|
  +
|-
  +
|[[Wiskott-Aldrich syndrome]]
  +
|Combined
  +
|
  +
|-
  +
|[[X-linked agammaglobulinemia]]
  +
|Humoural
  +
|
  +
|-
  +
|[[Chronic granulomatous disease]]
  +
|Phagocytic
  +
|
  +
|-
  +
! colspan="3" |Childhood Onset with Survival to Adulthood
  +
|-
  +
|[[Common variable immunodeficiency]]
  +
|Humoural
  +
|
  +
|-
  +
|[[IgA deficiency]]
  +
|Humoural
  +
|
  +
|-
  +
|[[IgG subclass deficiency]]
  +
|Humoural
  +
|
  +
|-
  +
|[[Complement deficiencies]]
  +
|Complement
  +
|
  +
|-
  +
|[[X-linked agammaglobulinemia]]
  +
|Humoural
  +
|
  +
|-
  +
|[[X-linked hyper-IgM syndrome]]
  +
|Humoural
  +
|
  +
|-
  +
|[[Chronic granulomatous disease]]
  +
|Phagocytic
  +
|
  +
|-
  +
|[[Severe combined immunodeficiency]]
  +
|Combined
  +
|
  +
|-
  +
|[[Wiskott-Aldrich syndrome]]
  +
|Combined
  +
|
  +
|-
  +
|[[Ataxia-telangiectasia]]
  +
|Combined
  +
|
  +
|-
  +
|[[Leukocyte adhesion deficiency]]
  +
|Phagocytic
  +
|
  +
|}
  +
  +
==Investigations==
  +
  +
*CBC and peripheral blood film, for lymphopenia, abnormal or unusual lymphocytes or phagocytes, and any other notable abnormalities
  +
**Lymphopenia may suggest T-cell immunodeficiency
  +
*Other general screening tests for immunodeficiency: immunoglobulin levels (IgG, IgM, IgA), lymphocyte subpopulations, vaccine titres, and complement assessment (e.g. CH50, AH50)
  +
*For suspected defect in '''humoural immunity'''
  +
**Serum immunoglobulin levels (IgG, IgM, IgA, and IgE)
  +
**Specific antibody titres
  +
**Pre- and post-vaccination IgG titres
  +
**Flow cytometry to count B cells
  +
*For suspected defect in '''cellular immunity'''
  +
**TREC newborn screen
  +
**Flow cytometry to count CD4 and CD8 T-cells and NK cells
  +
***Flow cytometry is almost always abnormal in [[SCID]]
  +
**Cutaneous delayed hypersensitivity
  +
**Spontaneous NK cytotoxicity
  +
*For suspected deficiencies in '''phagocytes'''
  +
**CBC and differential
  +
**Neutrophil staining for morphology on a peripheral blood film
  +
**Dihydrorhodamine 1,2,3 response (DHR) for neutrophil function
  +
**Flow cytometry for adhesion molecules
  +
*For suspected '''complement deficiencies'''
  +
**CH50 assay (for total complement activity)
  +
**AH50 assay (for alternative pathway activity)
  +
**Lectin pathway function
  +
**Level and/or function of specific complement factors
   
 
==Further Reading==
  
==Further Reading==
  +
βˆ’
* Primary immunodeficiency. ''Allergy Asthma Clin Immunol''. 2018;14(Suppl 2):61. doi: [https://doi.org/10.1186/s13223-018-0290-5 10.1186/s13223-018-0290-5]
  
βˆ’
* Attending to Warning Signs of Primary Immunodeficiency Diseases Across the Range of Clinical Practice. ''J Clin Immunol''. 2014;34(1):10-22. doi: [https://doi.org/10.1007/s10875-013-9954-6 10.1007/s10875-013-9954-6]
 +
*Primary immunodeficiency. ''Allergy Asthma Clin Immunol''. 2018;14(Suppl 2):61. doi: [https://doi.org/10.1186/s13223-018-0290-5 10.1186/s13223-018-0290-5]
  +
*Attending to Warning Signs of Primary Immunodeficiency Diseases Across the Range of Clinical Practice. ''J Clin Immunol''. 2014;34(1):10-22. doi: [https://doi.org/10.1007/s10875-013-9954-6 10.1007/s10875-013-9954-6]
  +
*Primary Immunodeficiency Diseases: an Update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015. ''J Clin Immunol''. 2015;35(8):696-726. doi: [https://doi.org/10.1007/s10875-015-0201-1 10.1007/s10875-015-0201-1]
   
 
[[Category:Immunocompromised hostsβ€β€Ž]]
  
[[Category:Immunocompromised hostsβ€β€Ž]]

Latest revision as of 11:21, 25 October 2023

Clinical Manifestations

Red Flags for Immunodeficiency

Children Adults
New ear infections β‰₯4 in 1 year β‰₯2 in 1 year
Serious sinus infections β‰₯2 in 1 year β‰₯2 in 1 year, in the absence of allergy
Pneumonias β‰₯2 in 1 year β‰₯2 in 1 year
Deep skin or organ abscesses Recurrent Recurrent
Oral thrush or fungal skin infections Persistent Persistent
Family history of primary immunodeficiency Any Any
Other
  • β‰₯2 months on antibiotics with little effect
  • Failure to gain weight or grow normally
  • Need for IV antibiotics to treat infections
  • β‰₯2 deep-seated infections including bacteremia
  • Chronic diarrhea with weight loss
  • Recurrent need for IV antibiotics to treat infections
  • Recurrent viral infections, such as colds, herpes, warts, or condylomata
  • Infection with non-tuberculous mycobacteria

Differential Diagnosis

Children

Disease Defect Age at Diagnosis Notes
Humoural (65%)
X-linked agammaglobulinemia BTK mutation X-linked, very low antibody levels
Common variable immunodeficiency (CVID) multiple 20-40 years low IgG with poor antibody response
Transient hypogammaglobulinemia of infancy
Hyper-IgM syndrome multiple X-linked or autosomal recessive, high IgM with poor T-cell function
IgA deficiency decreased IgA low IgA, often associated with other immunodeficiencies
Cell-Mediated (5%)
DiGeorge syndrome thymus aplasia
Chronic mucocutaneous candidiasis
Combined (15%)
Severe combined immunodeficiency disease (SCID) near-absolute T cell deficiency lymphopenia with hypogammaglobulinemia
Wiskott-Aldrich syndrome WASP mutation X-linked, eczema, thrombocytopenia, low IgM with high IgA
Ataxia-telangiectasia ATM mutation autosomal recessive, with low IgA, CD3, and CD4, and malignancies
X-linked lymphoproliferative disease SAP mutation X-linked, low EBNA antibodies
CD40 ligand deficiency
Hyper-IgE syndrome (Job syndrome) STAT3 mutation eczema, pneumatoceles, mucocutaneous candidiasis, recurrent cutaneous and respiratory infections, and elevated IgE
Phagocytic (10%)
Chronic granulomatous disease (CGD) NADPH oxidase GI and GU granulomas, infections with Staphylococcus aureus, Burkholderia cepacia, Serratia marcescens, Nocardia, and Aspergillus
Leukocyte adhesion deficiency multiple types autosomal recessive
TLR3 deficiency recurrent HSV encephalitis
Complement (5%)
C2 deficiency and other classical complement deficiencies classical complement pathway low CH50, autoimmune disease in C1-C4, bacteremia and meningitis
Properdin deficiency alternative complement pathway more severe than classical complement deficiencies
Immune Dysregulation
Hemophagocytic lymphohistiocytosis
Autoimmune lymphoproliferative disorder (ALPS)
Immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX)
Autoimmune polyendocrinopathy, candidiasis, and ectodermal dystrophy (APECED)

Adults

Disease Arm of Immune System Notes
Adult-Onset Common
IgA deficiency Humoural
Common variable immunodeficiency Humoural
IgG subclass deficiency Humoural
Complement deficiencies Complement
Good syndrome Combined humoural and cell-mediated Very rare. Associated with thymoma and autoimmune diseases
Delayed Presentation Possible
Adenosine deaminase deficiency Combined
Wiskott-Aldrich syndrome Combined
X-linked agammaglobulinemia Humoural
Chronic granulomatous disease Phagocytic
Childhood Onset with Survival to Adulthood
Common variable immunodeficiency Humoural
IgA deficiency Humoural
IgG subclass deficiency Humoural
Complement deficiencies Complement
X-linked agammaglobulinemia Humoural
X-linked hyper-IgM syndrome Humoural
Chronic granulomatous disease Phagocytic
Severe combined immunodeficiency Combined
Wiskott-Aldrich syndrome Combined
Ataxia-telangiectasia Combined
Leukocyte adhesion deficiency Phagocytic

Investigations

  • CBC and peripheral blood film, for lymphopenia, abnormal or unusual lymphocytes or phagocytes, and any other notable abnormalities
    • Lymphopenia may suggest T-cell immunodeficiency
  • Other general screening tests for immunodeficiency: immunoglobulin levels (IgG, IgM, IgA), lymphocyte subpopulations, vaccine titres, and complement assessment (e.g. CH50, AH50)
  • For suspected defect in humoural immunity
    • Serum immunoglobulin levels (IgG, IgM, IgA, and IgE)
    • Specific antibody titres
    • Pre- and post-vaccination IgG titres
    • Flow cytometry to count B cells
  • For suspected defect in cellular immunity
    • TREC newborn screen
    • Flow cytometry to count CD4 and CD8 T-cells and NK cells
      • Flow cytometry is almost always abnormal in SCID
    • Cutaneous delayed hypersensitivity
    • Spontaneous NK cytotoxicity
  • For suspected deficiencies in phagocytes
    • CBC and differential
    • Neutrophil staining for morphology on a peripheral blood film
    • Dihydrorhodamine 1,2,3 response (DHR) for neutrophil function
    • Flow cytometry for adhesion molecules
  • For suspected complement deficiencies
    • CH50 assay (for total complement activity)
    • AH50 assay (for alternative pathway activity)
    • Lectin pathway function
    • Level and/or function of specific complement factors

Further Reading

  • Primary immunodeficiency. Allergy Asthma Clin Immunol. 2018;14(Suppl 2):61. doi: 10.1186/s13223-018-0290-5
  • Attending to Warning Signs of Primary Immunodeficiency Diseases Across the Range of Clinical Practice. J Clin Immunol. 2014;34(1):10-22. doi: 10.1007/s10875-013-9954-6
  • Primary Immunodeficiency Diseases: an Update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015. J Clin Immunol. 2015;35(8):696-726. doi: 10.1007/s10875-015-0201-1
Retrieved from "https://idwiki.org/index.php?title=Primary_immunodeficiency&oldid=10247"
Powered by MediaWiki
Powered by Semantic MediaWiki