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
Diagnos...
...al Considerations...
...s critical to maintain a high index of suspic...
...nditions that can increase susceptibility to infe...
...It is important to confirm the precise focus of...
...cused family history (eg, recurrent inf...
...S 5. A stepwise approach is recommended to eva...
...ation of specific immune responses...
...S 7. PIDDs should be defined at the molecu...
...bility of an X-linked PIDD should be...
...9. Carrier status should be determi...
...re 1. General Approach for the Diagnosis...
...Characteristic Clinical Presentations...
...e 2. Laboratory Tests of Immune Function ...
...y of Laboratory Findings in the Diagn...
Treatment
Treatment
...er diagnosis of a PIDD, it is impor...
...Immunoglobulin replacement therapy is indicated...
...12. In association with low IgG levels, IgA def...
...tients receiving IgG therapy should have regular...
...14. The placement of permanent central venous...
...Aggressive and prolonged antimicrobi...
...6. Short- or long-term antimicrobial pr...
...g imaging and function should be mon...
...18. Surgical procedures undertaken with the aim...
...e recommended definitive therapy of cellu...
...rradiated, CMV-negative, lymphocyt...
...Live vaccines should not be administered...
...ctivated or subunit vaccines can be adm...
...cation for patients and families with PIDDs is...
...S 24. Patients with suspected or diagnose...
...A coordinated multidisciplinary approach to...
Table 4. Summary of Therapeutic Co...
...5. Regimens for Prophylaxis of Bac...
Combined B- and T-Cell Immunodeficiencies
...B- and T-Cell Immunodeficiencies ...
...2. Diagnosis of Combined or Syndr...
...bined immunodeficiency (SCID)Â ...
...SCID should be considered in the differen...
...s with SCID or suspected SCID should...
SS 28. Patients with SCID or suspecte...
.... Patients with SCID should receive PCP prophy...
...S 30. Early signs of infection should be pro...
...ene glycol (PEG)-conjugated ADA31. Polyethyle...
...A suspicion of SCID should be considered an...
...nts with SCID should be immunologically recons...
...Clinical and Laboratory Manifestations of Selec...
...Lymphocyte Phenotype Classification of S...
...CID syndromes ...
...nts with CID with intermediate T-cell numbers an...
...All forms of ancillary or supportive th...
...with leaky SCIDPatients with leaky SCIDPatients...
...ndrome (HIM) caused by defects of...
...iagnosis of a form of HIM should be considered in...
SS 38. CD40L expression should be evalua...
...39. CD40 expression should be measured by using...
...40. Female patients with the HIM phenotype should...
...hylaxis is indicated for all patien...
...enia in patients with CD40 or CD40L deficiency sh...
...CT should be considered for CD40L and...
...unspecified ...
...patient with abnormal serum immunoglobulin lev...
...ell-Defined Syndromes with Immunodeficie...
...diagnosis of Wiskott-Aldrich Syndrome (WAS)...
...ents suspected to have WAS should...
...48. Management of patients with WAS should i...
...49. HSCT must be seriously considered for...
...-SCID DNA repair defects...
...nd other chromosomal repair disorde...
SS 51. Immunodeficiency, centromeric...
SS 52. Postmeiotic segregation incr...
...diagnosis of radiosensitivity, immunodeficiency...
...4. Cytogenetic abnormalities, such as ch...
...Patients suspected to have AT should be screened b...
...with radiography should be used cau...
...tic prophylaxis, IgG replacement t...
...agement of malignancy in patients with A...
...9. Stem cell transplantation can be c...
...iGeorge syndrome (D...
...should be investigated in patients with thym...
SS 61. Periodic immunologic re-evaluat...
...tients suspected of having DGS should ha...
...nt of infants with complete DGS requires some f...
...athic CD4 lymphopenia (ICD4L)
...D4L should be suspected in patients...
...Management of ICD4L is supportive and dicta...
...no-osseous dysplasias...
...he immuno-osseous dysplasias should be cons...
...management of immunoosseous syndromes should in...
...CT is indicated and has been successful...
...el-Netherton synd...
...69. A diagnosis of Comel-Netherton syn...
...yper-IgE syndromes (H...
...form of HIES should be considered in patients...
...tial approach to HIES therapy should be directe...
...72. Patients with DOCK8 deficiency and poor antibo...
...3. The use of IVIG or IFN-Îł in patients...
...S 74. HSCT should be considered for both for...
...patic veno-occlusive...
SS 75. Mutations in the SP110 gene should be sough...
...atosis congenita (DKC)...
...76. DKC should be investigated in patien...
...of vitamin B12 and folate metabolism
...77. Inborn errors of folate and vitamin B12 malab...
...8. Infants with severe vitamin B12 or folate defic...
...munodeficiency with multiple intestinal at...
.... Patients born with MIA should be scre...
...80. HSCT should be considered for treatment of...
Predominantly Antibody Deficiencies
...edominantly Antibody Defi...
...mmaglobulinemiaÂ...
...ients with very low or undetectable serum...
...ammaglobulinemia should be managed aggressivel...
...ral meningoencephalitis in patients...
...nsplantation should be considered for patients wit...
...variable immunodeficiency (CVID)Â ...
...nosis of CVID should be considered in ma...
...Grouping of patients with CVID based on anal...
...diseases, molecular defects, or both sho...
...uld be managed aggressively with antimicrob...
...testinal status should be monitored regularly in p...
...e for possible autoimmune diseases should be main...
...91. Vigilance for nonmalignant and malign...
...oimmune, lymphoproliferative, or malign...
...m cell transplantation can be consi...
...94. Patients having hypogammaglobulinemia an...
...patients with Good syndrome, thym...
...tive IgA deficiency (SIGA...
...ects older than 4 years with a serum IgA level...
...ients with serum IgA levels of less than the...
...with SIGAD should be monitored over tim...
...tion use should be investigated in patients w...
...00. Aggressive antimicrobial therapy, prophy...
...ic disease should be treated aggress...
...tients with SIGAD might benefit fro...
...G subclass deficiency (IGGSD)Â ...
...diagnosis of IGGSD should be considered for a...
...4. The principles of management of IGGSD should...
...c antibody deficiency (SA...
...5. The diagnosis of SAD should be given to patient...
...atients with SAD might benefit from addi...
...able 8. Assessing Serotype-Specific R...
...ammaglobulinemia of infancy (THI)...
...07. Infants and young children wit...
...rinciples of management of THI shou...
...munoglobulin class-switch defects
...atients with immunoglobulin class-switch d...
...rinciples of management of immunoglobulin c...
...mune, lymphoproliferative, or mali...
...hypogammaglobulinemia...
.... Any patient with primary hypogammaglobulinemia...
...Management of unspecified hypogamma...
...s of Immune Dysregulation...
...igure 3. Diagnosis of Diseases of Immune...
...Higashi syndrome (CHS)...
...S 114. CHS should be suspected in pa...
...amination of a peripheral blood smear should...
...reatment of HLH in patients with CHS i...
...lli syndrome (GS) type 2...
...2 should be suspected in patients...
...mansky-Pudlak syndrome (HPS...
...S 118. HPS type 2 should be suspected in patient...
...ophagocytic lymphohistiocytosis (FHL) syndrome...
...HL should be suspected in patients with fe...
...tory screening for FHL should be performed...
...121. HLH should be treated with high-dose g...
...hoproliferative syndromes...
...inked lymphoproliferative disease (XLP)...
...ients with suspected XLP should be screened by...
...IG should be given to patients with XLP and hypoga...
...with XLP and HLH should be treated...
...ndromes with autoimm...
...une lymphoproliferative syndrome (ALPS) and ALPSâ...
126. ALPS or an ALPS-related disorder sh...
...127. Measurement of T cells expressing the α/β...
...Treatment of ALPS should be tailored to addre...
...ndocrinopathy–candidiasis–ectoderma...
...should be suspected in patients with...
...130. Patients with clinical features...
...S 131. Immunosuppressive therapy should be...
...specific genetic lesions should be sough...
...X syndrome...
SS 133. IPEX syndrome should be suspected...
SS 134. A diagnosis of IPEX syndrome should be s...
...Initial treatment of IPEX syndrome shou...
...136. HSCT should be considered early in the cour...
...37. Other specific genetic lesions should be sou...
...Complement deficiency should be considered in...
Phagocytic Cell Def...
...iagnosis of Phagocyte Defects...
...of neutrophil differentiation...
...congenital neutropenia
...Patients with recurrent bacterial respiratory...
...0. Patients with neutropenia should recei...
...CT should be considered for patients with sever...
...of neutrophil motility...
...eukocyte adhesion deficiency (LAD) types I,...
...D should be suspected in patients with cellul...
SS 143. A blood cell count should be the firs...
.../II should be diagnosed by using flow cytom...
...apy for LAD-I/II should be supportive and dictate...
...ose supplementation can ameliorate the course of...
...7. HSCT is curative for LAD-I and LAD-III a...
...ranule deficiency (SGD)...
.... SGD should be considered in patients with...
...ent of SGD should be supportive, but HSCT might ha...
...syndromes of defective neutrophil motility...
...itional genetic lesions should be inves...
Defects of the respiratory burst
...of the respiratory burst...
...ranulomatous disease (CGD)
...151. CGD should be suspected in patients with d...
...easurement of phagocyte oxidase activity s...
...ents with CGD should be given prophylaxis with a...
...cyte transfusions should be considered as a las...
...5. In patients with CGD, aggressive...
...HSCT should be considered early in...
Mendelian susceptibility to mycobacterial disease (MSMD)
...susceptibility to mycobacterial disease (MSMD...
...ents with severe tuberculous or atypical myco...
...Patients suspected of having MSMD should have...
...159. Management of MSMD should include vigi...
...Patients with partial IFNGR1/2 mutation...
SS 161. HLA-identical sibling HSCT can be consider...
Pulmonary alveolar proteinosis (PAP)
...alveolar proteinosis (PAP)...
...nts with PAP should be tested for mut...