Primary immunodeficiency: Difference between revisions

From IDWiki
m (Aidan moved page Primary immunodeficiencies to Primary immunodeficiency over redirect)
(turned DDx into a big table)
Line 1: Line 1:
== Clinical Manifestations ==
==Differential Diagnosis==
{| class="wikitable"
* '''Humoural''' (65%): B cell defects
!Immune Defect
** [[X-linked agammaglobulinemia]]
!Typical Infections
** [[Common variable immune deficiency]] (CVID)
!Typical Organisms
** [[Transient hypogammaglobulinemia of infancy]]
|-
** [[Hyper-IgM syndrome]]
|Humoural and complement
** [[IgA deficiency]]
|recurrent sinopulmonary infections, chronic GI infections, [[bacteremia]], and [[meningitis]]
* '''Cell-mediated''' (5%): T-cell deficiencies
|[[encapsulated bacteria]], [[Giardia]], [[Cryptosporidium]], and [[Campylobacter]]
** [[DiGeorge syndrome]]
|-
** [[Chronic mucocutaneous candidiasis]]
|Phagocytic
* '''Combined''' (15%): B- and T-cell deficiencies, often much more severe
|recurrent invasive [[Skin and soft tissue infection|skin and soft tissue infections]], especially [[Abscess|abscesses]]
** [[Severe combined immunodeficiency disease]] (SCID)
|[[Staphylococcus aureus]], [[Gram-negative bacilli]], [[Aspergillus]], and [[Nocardia]]
** [[Wiskott-Aldrich syndrome]]
|-
** [[Ataxia-telangiectasia]]
|Cell-mediated
** [[X-linked lymphoproliferative disease]]
|severe or prolonged infections with common viruses, opportunistic intracellular infections, and [[fungi]]
** [[CD40 ligand deficiency]]
|[[CMV]], [[EBV]], [[Human herpesviruses|other human herpesviruses]], [[mycobacteria]], [[Candida]], [[Cryptococcus]], and [[Pneumocystis]]
** [[Hyper-IgE syndrome]]
|}
* '''Phagocytic''' (10%): neutrophil deficiencies
** Phagocyte deficiencies
** [[Chronic granulomatous disease]] (CGD)
** [[Leukocyte adhesion deficiency]]
* '''Complement''' (5%)
** [[C2 deficiency]]
** [[Properdin deficiency]]
* Immune dysregulation
** [[Hemophagocytic lymphohistiocytosis]]
** [[Autoimmune lymphoproliferative disorder]] (ALPS)
** [[Immunodysregulation, polyendocrinopathy, enteropathy, X-linked]] (IPEX)
** [[Autoimmune polyendocrinopathy, candidiasis, and ectodermal dystrophy]] (APECED)


==Differential Diagnosis==
{| class="wikitable"
!Disease
!Defect
!Age at Diagnosis
!Notes
|-
! colspan="4" |Humoural (65%)
|-
|[[X-linked agammaglobulinemia]]
|
|
|
|-
|[[Common variable immunodeficiency]] (CVID)
|
|
|
|-
|[[Transient hypogammaglobulinemia of infancy]]
|
|
|
|-
|[[Hyper-IgM syndrome]]
|
|
|
|-
|[[IgA deficiency]]
|
|
|
|-
! 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
|
|
|-
|[[Wiskott-Aldrich syndrome]]
|
|
|
|-
|[[Ataxia-telangiectasia]]
|
|
|
|-
|[[X-linked lymphoproliferative disease]]
|
|
|
|-
|[[CD40 ligand deficiency]]
|
|
|
|-
|[[Hyper-IgE syndrome]] (Job syndrome)
|STAT3 mutation
|
|eczema, pneumatoceles, mucocutaneous candidiasis, recurrent cutaneous and respiratory infections, and elevated IgE
|-
! colspan="4" |Phagocytic (10%)
|-
|Phagocyte deficiencies
|
|
|
|-
|[[Chronic granulomatous disease]] (CGD)
|
|
|
|-
|[[Leukocyte adhesion deficiency]]
|
|
|
|-
! colspan="4" |Complement (5%)
|-
|[[C2 deficiency]]
|
|
|
|-
|[[Properdin deficiency]]
|
|
|
|-
! colspan="4" |Immune Dysregulation
|-
|[[Hemophagocytic lymphohistiocytosis]]
|
|
|
|-
|[[Autoimmune lymphoproliferative disorder]] (ALPS)
|
|
|
|-
|[[Immunodysregulation, polyendocrinopathy, enteropathy, X-linked]] (IPEX)
|
|
|
|-
|[[Autoimmune polyendocrinopathy, candidiasis, and ectodermal dystrophy]] (APECED)
|
|
|
|}
<br />
==Red Flags for Immunodeficiency==
==Red Flags for Immunodeficiency==
===Children===
===Children===

* ≥4 new ear infections in 1 year
* ≥2 serious sinus infections in 1 year
*≥4 new ear infections in 1 year
* ≥2 months on antibiotics with little effect
*≥2 serious sinus infections in 1 year
*≥2 months on antibiotics with little effect
* ≥2 pneumonias in 1 year
*≥2 pneumonias in 1 year
* Failure to gain weight or grow normally
*Failure to gain weight or grow normally
* Recurrent deep skin or organ abscesses
*Recurrent deep skin or organ abscesses
* Persistent thrush in mouth or fungal skin infection
*Persistent thrush in mouth or fungal skin infection
* Need for IV antibiotics to treat infections
*Need for IV antibiotics to treat infections
* ≥2 deep-seated infections including bacteremia
*≥2 deep-seated infections including bacteremia
* A family history of primary immunodeficiency
*A family history of primary immunodeficiency


===Adults===
===Adults===

* ≥2 new ear infections in 1 year
* ≥2 new sinus infections in 1 year (in the absence of allergy)
*≥2 new ear infections in 1 year
* ≥2 new pneumonias in 2 years
*≥2 new sinus infections in 1 year (in the absence of allergy)
*≥2 new pneumonias in 2 years
* Chronic diarrhea with weight loss
*Chronic diarrhea with weight loss
* Recurrent viral infections, such as colds, herpes, warts, or condylomata
* Recurrent need for IV antibiotics to treat infections
*Recurrent viral infections, such as colds, herpes, warts, or condylomata
* Recurrent, deep abscesses of skin or internal organs
*Recurrent need for IV antibiotics to treat infections
*Recurrent, deep abscesses of skin or internal organs
* Persistent thrush or fungal infections
*Persistent thrush or fungal infections
* Infection with non-tuberculous mycobacteria
*Infection with non-tuberculous mycobacteria
* A family history of primary immunodeficiency
*A family history of primary immunodeficiency


==Investigations==
==Investigations==

* CBC and peripheral blood film, for lymphopenia, abnormal or unusual lymphocytes or phagocytes, and any other notable abnormalities
*CBC and peripheral blood film, for lymphopenia, abnormal or unusual lymphocytes or phagocytes, and any other notable abnormalities
** Lymphopenia may suggest T-cell immunodeficiency
**Lymphopenia may suggest T-cell immunodeficiency
* For suspected defect in '''humoural immunity'''
*For suspected defect in '''humoural immunity'''
** Serum immunoglobulin levels (IgG, IgM, IgA, and IgE)
**Serum immunoglobulin levels (IgG, IgM, IgA, and IgE)
** Specific antibody titres
** Pre- and post-vaccination IgG titres
**Specific antibody titres
**Pre- and post-vaccination IgG titres
** Flow cytometry to count B cells
**Flow cytometry to count B cells
* For suspected defect in '''cellular immunity'''
*For suspected defect in '''cellular immunity'''
** TREC newborn screen
**TREC newborn screen
** Flow cytometry to count CD4 and CD8 T-cells and NK cells
*** Flow cytometry is almost always abnormal in [[SCID]]
**Flow cytometry to count CD4 and CD8 T-cells and NK cells
***Flow cytometry is almost always abnormal in [[SCID]]
** Cutaneous delayed hypersensitivity
**Cutaneous delayed hypersensitivity
** Spontaneous NK cytotoxicity
**Spontaneous NK cytotoxicity
* For suspected deficiencies in '''phagocytes'''
*For suspected deficiencies in '''phagocytes'''
** CBC and differential
**CBC and differential
** Neutrophil staining for morphology on a peripheral blood film
**Neutrophil staining for morphology on a peripheral blood film
** Dihydrorhodamine 1,2,3 response (DHR) for neutrophil function
**Dihydrorhodamine 1,2,3 response (DHR) for neutrophil function
** Flow cytometry for adhesion molecules
**Flow cytometry for adhesion molecules
* For suspected '''complement deficiencies'''
** CH50 assay (for total complement activity)
*For suspected '''complement deficiencies'''
** AH50 assay (for alternative pathway activity)
**CH50 assay (for total complement activity)
** Lectin pathway function
**AH50 assay (for alternative pathway activity)
**Lectin pathway function
** Level and/or function of specific complement factors
**Level and/or function of specific complement factors


==Further Reading==
==Further Reading==

* 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. ''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]
* 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]
*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 hosts‏‎]]
[[Category:Immunocompromised hosts‏‎]]

Revision as of 17:31, 16 August 2020

Clinical Manifestations

Immune Defect Typical Infections Typical Organisms
Humoural and complement recurrent sinopulmonary infections, chronic GI infections, bacteremia, and meningitis encapsulated bacteria, Giardia, Cryptosporidium, and Campylobacter
Phagocytic recurrent invasive skin and soft tissue infections, especially abscesses Staphylococcus aureus, Gram-negative bacilli, Aspergillus, and Nocardia
Cell-mediated severe or prolonged infections with common viruses, opportunistic intracellular infections, and fungi CMV, EBV, other human herpesviruses, mycobacteria, Candida, Cryptococcus, and Pneumocystis

Differential Diagnosis

Disease Defect Age at Diagnosis Notes
Humoural (65%)
X-linked agammaglobulinemia
Common variable immunodeficiency (CVID)
Transient hypogammaglobulinemia of infancy
Hyper-IgM syndrome
IgA deficiency
Cell-Mediated (5%)
DiGeorge syndrome thymus aplasia
Chronic mucocutaneous candidiasis
Combined (15%)
Severe combined immunodeficiency disease (SCID) near-absolute T cell deficiency
Wiskott-Aldrich syndrome
Ataxia-telangiectasia
X-linked lymphoproliferative disease
CD40 ligand deficiency
Hyper-IgE syndrome (Job syndrome) STAT3 mutation eczema, pneumatoceles, mucocutaneous candidiasis, recurrent cutaneous and respiratory infections, and elevated IgE
Phagocytic (10%)
Phagocyte deficiencies
Chronic granulomatous disease (CGD)
Leukocyte adhesion deficiency
Complement (5%)
C2 deficiency
Properdin deficiency
Immune Dysregulation
Hemophagocytic lymphohistiocytosis
Autoimmune lymphoproliferative disorder (ALPS)
Immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX)
Autoimmune polyendocrinopathy, candidiasis, and ectodermal dystrophy (APECED)


Red Flags for Immunodeficiency

Children

  • ≥4 new ear infections in 1 year
  • ≥2 serious sinus infections in 1 year
  • ≥2 months on antibiotics with little effect
  • ≥2 pneumonias in 1 year
  • Failure to gain weight or grow normally
  • Recurrent deep skin or organ abscesses
  • Persistent thrush in mouth or fungal skin infection
  • Need for IV antibiotics to treat infections
  • ≥2 deep-seated infections including bacteremia
  • A family history of primary immunodeficiency

Adults

  • ≥2 new ear infections in 1 year
  • ≥2 new sinus infections in 1 year (in the absence of allergy)
  • ≥2 new pneumonias in 2 years
  • Chronic diarrhea with weight loss
  • Recurrent viral infections, such as colds, herpes, warts, or condylomata
  • Recurrent need for IV antibiotics to treat infections
  • Recurrent, deep abscesses of skin or internal organs
  • Persistent thrush or fungal infections
  • Infection with non-tuberculous mycobacteria
  • A family history of primary immunodeficiency

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
  • 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=6052"
Powered by MediaWiki
Powered by Semantic MediaWiki