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
Diagnosis
...l Considerations...
...1. It is critical to maintain a h...
...nditions that can increase susceptibility t...
...ortant to confirm the precise focus of infect...
SS 4. A focused family history (eg, re...
...se approach is recommended to evaluate suspecte...
...on of specific immune responses is essential...
...IDDs should be defined at the molecular geneti...
.... The possibility of an X-linked PIDD...
...status should be determined for all...
...eneral Approach for the Diagnosis of...
...le 1. Characteristic Clinical Presentations...
...e 2. Laboratory Tests of Immune Function ...
...ble 3. Summary of Laboratory Findings in the...
Treatment
...reatment
...After diagnosis of a PIDD, it is important to proc...
...munoglobulin replacement therapy is indi...
...association with low IgG levels, Ig...
...13. Patients receiving IgG therapy should have...
...placement of permanent central ven...
...ve and prolonged antimicrobial therapy should be...
...ort- or long-term antimicrobial proph...
.... Lung imaging and function should be monitored...
...Surgical procedures undertaken with the aim of...
.... The recommended definitive therapy of cel...
...Only irradiated, CMV-negative, lympho...
...cines should not be administered to patients wi...
...tivated or subunit vaccines can be administered t...
SS 23. Education for patients and families...
...s with suspected or diagnosed PIDDs a...
...5. A coordinated multidisciplinary approach to...
...mmary of Therapeutic Considerations for Pr...
...ns for Prophylaxis of Bacterial Respiratory...
Combined B- and T-Cell Immunodeficiencies
...ined B- and T-Cell Immunodefic...
...Diagnosis of Combined or Syndromic Immunode...
...ere combined immunodeficiency (SCID)Â ...
...D should be considered in the differe...
...with SCID or suspected SCID should re...
...atients with SCID or suspected SCID shou...
...29. Patients with SCID should receive PCP prop...
...ly signs of infection should be pr...
...ethylene glycol (PEG)-conjugated AD...
...32. A suspicion of SCID should be co...
...3. Patients with SCID should be imm...
...linical and Laboratory Manifestations of S...
...e 7. Lymphocyte Phenotype Classification of SCIDÂ...
Other CID syndromesÂ
...s with CID with intermediate T-cel...
...ms of ancillary or supportive therapy a...
...with leaky SCIDPatients with leaky SCIDPa...
...per-IgM syndrome (HIM) caused by def...
...gnosis of a form of HIM should be considere...
...8. CD40L expression should be evalu...
...expression should be measured by using f...
...atients with the HIM phenotype should be stu...
...41. PCP prophylaxis is indicated for all patients...
...Neutropenia in patients with CD40 or CD4...
...ld be considered for CD40L and CD40 de...
...unspecifiedÂ...
...patient with abnormal serum immunoglobul...
...yndromes with Immunodeficiency...
...iagnosis of Wiskott-Aldrich Syndrome (WAS) should...
...47. Patients suspected to have WAS should...
...48. Management of patients with WAS sho...
...CT must be seriously considered for patien...
...DNA repair defects...
...other chromosomal repair disorders sh...
...51. Immunodeficiency, centromeric in...
...stmeiotic segregation increased 2 (PMS2)...
...diagnosis of radiosensitivity, immunodeficie...
...Cytogenetic abnormalities, such as chromosomal...
...ients suspected to have AT should be sc...
...with radiography should be used cautiously...
...tibiotic prophylaxis, IgG replacement therapy,...
...anagement of malignancy in patients w...
...59. Stem cell transplantation can b...
DiGeorge syndrome (DGS)
...d be investigated in patients with thymic hypopl...
...immunologic re-evaluation is recommended for patie...
...nts suspected of having DGS should have molec...
...ment of infants with complete DGS requires some f...
...iopathic CD4 lymphopenia (ICD4L)
...ICD4L should be suspected in patients...
...anagement of ICD4L is supportive an...
Immuno-osseous dysplas...
...he immuno-osseous dysplasias should be conside...
...edical management of immunoosseous syndromes shoul...
...indicated and has been successful for...
Comel-Netherton synd...
...agnosis of Comel-Netherton syndrome (SPINK5 gene...
...er-IgE syndromes (HIES)...
...form of HIES should be considered in patient...
...The initial approach to HIES therapy shoul...
...s with DOCK8 deficiency and poor antibody prod...
...S 73. The use of IVIG or IFN-Îł in...
...HSCT should be considered for both forms o...
...ic veno-occlusive disease...
...ations in the SP110 gene should be...
...ratosis congenita (D...
...6. DKC should be investigated in patients with...
...of vitamin B12 and folate metabolism
...errors of folate and vitamin B12 malabsorpti...
...with severe vitamin B12 or folate de...
...ency with multiple intestinal atresia (M...
...nts born with MIA should be screened for CID...
...uld be considered for treatment of MIA-SCID. ( C...
Predominantly Antibody Deficiencies
...inantly Antibody Deficiencie...
...globulinemia ...
...Patients with very low or undetectable serum...
...globulinemia should be managed aggressively...
...iral meningoencephalitis in patien...
...ransplantation should be considere...
Common variable immunodeficiency (CV...
...S 85. The diagnosis of CVID should...
...uping of patients with CVID based on analysis of B...
...d diseases, molecular defects, or both shou...
...VID should be managed aggressively with ant...
...S 89. Gastrointestinal status should...
...Vigilance for possible autoimmune diseases sh...
...1. Vigilance for nonmalignant and malignant...
SS 92. Autoimmune, lymphoproliferat...
...93. Stem cell transplantation can be considered...
.... Patients having hypogammaglobuli...
...patients with Good syndrome, thymomas shoul...
...lective IgA deficiency (S...
...ubjects older than 4 years with a se...
...s with serum IgA levels of less than the normal ra...
...ents with SIGAD should be monitored over time...
...S 99. Medication use should be investigated in p...
...sive antimicrobial therapy, prophylax...
...Atopic disease should be treated aggr...
...e patients with SIGAD might benefit from IVIG rep...
...s deficiency (IGGSD)Â ...
SS 103. A diagnosis of IGGSD should be c...
SS 104. The principles of management o...
...fic antibody deficiency (SAD)Â ...
...nosis of SAD should be given to pat...
...106. Patients with SAD might benefit from additi...
...le 8. Assessing Serotype-Specific Responses t...
...nsient hypogammaglobulinemia of infancy...
...and young children with frequent viral...
...8. The principles of management of THI sh...
...lin class-switch defects...
...nts with immunoglobulin class-swit...
...nciples of management of immunoglobulin class...
...1. Autoimmune, lymphoproliferative,...
...cified hypogammaglobulinemia...
...12. Any patient with primary hypogammaglo...
...gement of unspecified hypogammaglobulinemia shoul...
...eases of Immune Dysregulat...
.... Diagnosis of Diseases of Immune...
...gashi syndrome (CHS)...
.... CHS should be suspected in patients with partial...
...Examination of a peripheral blood smear should...
...16. The treatment of HLH in patients with CHS...
...iscelli syndrome (GS) type...
...2 should be suspected in patients with pigmentary...
...rmansky-Pudlak syndrome (HP...
...118. HPS type 2 should be suspecte...
...amilial hemophagocytic lymphohistiocytosis (FHL...
...S 119. FHL should be suspected in patients with fe...
...120. Laboratory screening for FHL should b...
...21. HLH should be treated with high-dos...
...phoproliferative syndromes...
...S 122. X-linked lymphoproliferative disease (X...
...Patients with suspected XLP should b...
.... IVIG should be given to patients wi...
...nts with XLP and HLH should be treated with chem...
Syndromes with aut...
...oproliferative syndrome (ALPS) and ALPSâ...
...PS or an ALPS-related disorder should be suspec...
SS 127. Measurement of T cells expr...
...8. Treatment of ALPS should be tailored to add...
...toimmune polyendocrinopathy–candidiasis–ectod...
...9. APECED should be suspected in patients with im...
...ients with clinical features consistent with aut...
...ppressive therapy should be considere...
SS 132. Other specific genetic lesions...
...EX syndrom...
...syndrome should be suspected in pa...
...agnosis of IPEX syndrome should be sou...
...itial treatment of IPEX syndrome should include...
...uld be considered early in the course of IP...
...137. Other specific genetic lesions should be...
...nt deficiency should be considered in the evalua...
...ytic Cell Defects
...Diagnosis of Phagocyte Defects...
...f neutrophil differentiation...
...ere congenital neutropenia...
SS 139. Patients with recurrent bacterial re...
...S 140. Patients with neutropenia should receive G-...
...HSCT should be considered for pati...
...f neutrophil motility...
...on deficiency (LAD) types I, II, and III...
...ld be suspected in patients with cellu...
.... A blood cell count should be the first screeni...
...144. LAD-I/II should be diagnosed by using...
...for LAD-I/II should be supportive and dictated...
SS 146. Fucose supplementation can...
...147. HSCT is curative for LAD-I and LAD-III a...
...fic granule deficiency (S...
...should be considered in patients with r...
...ement of SGD should be supportive, but HSCT migh...
Other syndromes of defective neutrophi...
...ional genetic lesions should be inv...
Defects of the respiratory burst
...cts of the respiratory burst...
...c granulomatous disease (CGD)...
...151. CGD should be suspected in patients with d...
...ent of phagocyte oxidase activity should be the...
SS 153. Patients with CGD should be giv...
...yte transfusions should be considered as a last-r...
...In patients with CGD, aggressive surgica...
SS 156. HSCT should be considered early in the co...
Mendelian susceptibility to mycobacterial disease (MSMD)
...elian susceptibility to mycobacterial dis...
...57. Patients with severe tuberculous or atypical...
...ients suspected of having MSMD shou...
...Management of MSMD should include vigilance for...
...ts with partial IFNGR1/2 mutations an...
...identical sibling HSCT can be considered for thera...
Pulmonary alveolar proteinosis (PAP)
...monary alveolar proteinosis...
...2. Patients with PAP should be tested for mu...