Primary Immunodeficiency
Key Points
Key Points
- Primary immunodeficiency diseases (PIDDs) are inherited disorders of immune system function that predispose affected subjects to an increased rate and severity of infection, immune dysregulation with autoimmune disease and aberrant inflammatory responses, and malignancy.
- Primary immunodeficiencies are distinct from secondary immunodeficiencies that occur, for example, during certain viral infections, after immunosuppression to prevent graft rejection after transplantation, during treatment of systemic autoimmune disease, and in association with cancer chemotherapy.
- Primary immunodeficiencies occur in as many as 1:2000 live births.
- The principal clinical manifestation of immunodeficiency is increased susceptibility to infection.
- Autoimmune disease and malignancy are also often seen in a variety of immunodeficiencies.
- In the course of evaluating immunodeficiency, it is critical, as much as possible, to document carefully the foci of infections, the organisms, and the response to treatment.
- This is necessary to distinguish infectious disease from other noninfectious conditions, such as allergy, or to distinguish viral infection from bacterial infection.
- Any other conditions that might predispose to infection, including anatomic defects, allergy, and metabolic disorders, should be considered where appropriate.
- However, also note that hypersensitivity to environmental allergens, food allergens, or both might be an important element of and diagnostic clue for a variety of PIDDs.
Diagnosis
...Genera...
SS 1. It is critical to maintain a high index of...
...Other conditions that can increase susceptibility...
...important to confirm the precise focus...
...A focused family history (eg, recurrent infectio...
SS 5. A stepwise approach is recomme...
...valuation of specific immune responses is essentia...
...should be defined at the molecular genet...
...The possibility of an X-linked PIDD shou...
...9. Carrier status should be determined for al...
...Figure...
...Table 1. Characte...
...Table 2. L...
...ble 3. Summary of Laboratory Findings in the Dia...
Treatment
...Treatment...
.... After diagnosis of a PIDD, it is imp...
...11. Immunoglobulin replacement therapy i...
...ation with low IgG levels, IgA deficien...
...receiving IgG therapy should have regular moni...
...e placement of permanent central ven...
...ressive and prolonged antimicrobial therapy...
...hort- or long-term antimicrobial prophylaxis sh...
...S 17. Lung imaging and function sh...
...18. Surgical procedures undertaken with the ai...
...19. The recommended definitive therapy of cel...
...20. Only irradiated, CMV-negative, lymphocyte-de...
...21. Live vaccines should not be administ...
...ivated or subunit vaccines can be admi...
SS 23. Education for patients and...
...tients with suspected or diagnosed PIDD...
...rdinated multidisciplinary approach to managem...
...Table 4. Summary...
...Table 5....
Combined B- and T-Cell Immunodeficiencies
...Figure 2. Diagno...
...Severe combin...
...hould be considered in the different...
...ents with SCID or suspected SCID shoul...
...ients with SCID or suspected SCID should be pro...
...with SCID should receive PCP prophylaxis. ( C...
...Early signs of infection should be promptly inves...
...yethylene glycol (PEG)-conjugated ADA31. Pol...
...on of SCID should be considered an urgent clin...
...tients with SCID should be immunologica...
...Table 6. Cli...
...Table 7. L...
...Other CID syndr...
.... Patients with CID with intermediate...
SS 35. All forms of ancillary or supportiv...
...Patients with leaky SCIDPatients with l...
...Hyper-IgM syndrome (...
.... The diagnosis of a form of HIM should...
...CD40L expression should be evaluated b...
...40 expression should be measured by using flo...
...Female patients with the HIM phenotype s...
...prophylaxis is indicated for all pa...
SS 42. Neutropenia in patients with C...
...should be considered for CD40L and...
...CID,...
.... Any patient with abnormal serum immunoglobul...
...6. A diagnosis of Wiskott-Aldrich Syn...
...suspected to have WAS should have...
SS 48. Management of patients with WAS sho...
...SCT must be seriously considered for patie...
...Non-SCID DNA re...
...other chromosomal repair disorders should be co...
...deficiency, centromeric instability, and facial an...
...2. Postmeiotic segregation increased 2 (PMS2) de...
...sis of radiosensitivity, immunodefici...
...tic abnormalities, such as chromosom...
...55. Patients suspected to have AT should be scr...
...ng with radiography should be used...
...iotic prophylaxis, IgG replacement therapy,...
...nagement of malignancy in patients with AT...
...S 59. Stem cell transplantation can be considered...
...DiGeorge s...
...S should be investigated in patients with thym...
SS 61. Periodic immunologic re-evaluatio...
SS 62. Patients suspected of having DGS shoul...
...atment of infants with complete DGS re...
...Idiopathic CD4...
...should be suspected in patients wit...
...ment of ICD4L is supportive and dictated by the...
...Immuno-o...
...uno-osseous dysplasias should be consider...
SS 67. Medical management of immunoos...
...8. HSCT is indicated and has been successf...
...Comel-...
...gnosis of Comel-Netherton syndrome (SPINK5 gene mu...
...Hyper...
...form of HIES should be considered in patients wit...
...The initial approach to HIES therapy should be...
...ents with DOCK8 deficiency and poor antibody pro...
...73. The use of IVIG or IFN-γ in patients with...
...hould be considered for both forms of...
...Hepatic veno...
...5. Mutations in the SP110 gene shou...
Dyskera...
SS 76. DKC should be investigated...
...Defects o...
...7. Inborn errors of folate and vitamin...
...Infants with severe vitamin B12 or folate defici...
...Immunodeficiency...
...S 79. Patients born with MIA should be scr...
.... HSCT should be considered for treatment...
Predominantly Antibody Deficiencies
...Predominantly...
...Agammaglobulinem...
...tients with very low or undetectable seru...
...82. Agammaglobulinemia should be managed ag...
...3. Enteroviral meningoencephalitis in pati...
...transplantation should be considered...
...Commo...
...nosis of CVID should be considered...
...6. Grouping of patients with CVID based on...
SS 87. Selected diseases, molecular defect...
.... CVID should be managed aggressively with anti...
...89. Gastrointestinal status should be m...
...0. Vigilance for possible autoimmune di...
...igilance for nonmalignant and maligna...
...toimmune, lymphoproliferative, or ma...
...93. Stem cell transplantation can be considered...
...tients having hypogammaglobulinemia...
...atients with Good syndrome, thymomas should be e...
...Sele...
.... Subjects older than 4 years with a serum Ig...
.... Patients with serum IgA levels of less th...
...nts with SIGAD should be monitored over time f...
...99. Medication use should be investigated in patie...
...sive antimicrobial therapy, prophylaxis, or both...
...ic disease should be treated aggressively in p...
...are patients with SIGAD might benefit fro...
...IgG subcla...
...diagnosis of IGGSD should be considere...
...104. The principles of management of IGGSD sho...
...Specific antibo...
...nosis of SAD should be given to patients o...
...106. Patients with SAD might benefit from add...
...ssing Serotype-Specific Responses to...
...Transient hypo...
.... Infants and young children with frequent vir...
...08. The principles of management of THI sh...
...Immunoglobulin cla...
...s with immunoglobulin class-switch defects s...
SS 110. The principles of management of immu...
...une, lymphoproliferative, or malignant d...
...Unspecified...
...Any patient with primary hypogamm...
...gement of unspecified hypogammaglobulin...
...Diseases of Immune...
...gnosis of Diseases of Immune Dysregulation...
...Chediak-Higash...
...114. CHS should be suspected in patie...
...tion of a peripheral blood smear should be the...
...eatment of HLH in patients with CH...
...Griscelli sy...
...GS type 2 should be suspected in pa...
...Hermansky-Pud...
...type 2 should be suspected in patient...
...Familial hemophagocytic ly...
...uld be suspected in patients with fever...
...aboratory screening for FHL should be perf...
...should be treated with high-dose glu...
...Lymphoproliferative sy...
...S 122. X-linked lymphoproliferative dis...
...123. Patients with suspected XLP should...
...IG should be given to patients with XLP and h...
...with XLP and HLH should be treated with che...
...Autoimmune lympho...
...ALPS-related disorder should be suspecte...
...127. Measurement of T cells expressing the α/β...
...reatment of ALPS should be tailored to addre...
...Autoimmu...
SS 129. APECED should be suspected in patients...
...130. Patients with clinical features consisten...
...nosuppressive therapy should be considered in pat...
...ther specific genetic lesions should be so...
IPEX syndr...
...IPEX syndrome should be suspected in patients with...
...nosis of IPEX syndrome should be s...
...treatment of IPEX syndrome should in...
...hould be considered early in the c...
.... Other specific genetic lesions should...
...lement deficiency should be conside...
...Phagocytic Cell...
...e 4. Diagnosis of Phagocyte D...
...Defects of neutrophil diffe...
...Severe congeni...
...ents with recurrent bacterial respi...
...ts with neutropenia should receive G-CSF (...
...S 141. HSCT should be considered for pati...
...Defects of neutro...
...Leukocyt...
...should be suspected in patients with ce...
.... A blood cell count should be the first scr...
...4. LAD-I/II should be diagnosed by using f...
...for LAD-I/II should be supportive...
...supplementation can ameliorate the course...
...S 147. HSCT is curative for LAD-I and LAD-III and...
...Specific granule defi...
...8. SGD should be considered in patient...
...Management of SGD should be supportive, but...
...Other...
...itional genetic lesions should be inve...
Defects of the respiratory burst
...Defects of the r...
...Chronic gran...
...151. CGD should be suspected in patients with d...
...rement of phagocyte oxidase activity...
...Patients with CGD should be given p...
.... Granulocyte transfusions should be considered a...
...ents with CGD, aggressive surgical...
...6. HSCT should be considered early in the course o...
Mendelian susceptibility to mycobacterial disease (MSMD)
Mendel...
...with severe tuberculous or atypical mycobacteri...
...ts suspected of having MSMD should have measureme...
.... Management of MSMD should includ...
...ts with partial IFNGR1/2 mutations and...
...HLA-identical sibling HSCT can be...
Pulmonary alveolar proteinosis (PAP)
...Pulmonary alveola...
...2. Patients with PAP should be tested fo...