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
...agnosis...
...neral Considerations...
...It is critical to maintain a high index of suspi...
...Other conditions that can increase susce...
...ortant to confirm the precise focus of infec...
...ocused family history (eg, recurrent...
.... A stepwise approach is recommended to evaluate...
...of specific immune responses is essential for dia...
...ould be defined at the molecular genetic lev...
...he possibility of an X-linked PIDD...
.... Carrier status should be determined...
.... General Approach for the Diagnos...
...teristic Clinical Presentations of Some...
...atory Tests of Immune Function ...
...3. Summary of Laboratory Findings in the Diagnosi...
Treatment
Treatme...
...gnosis of a PIDD, it is important to proceed qui...
...lobulin replacement therapy is indica...
...12. In association with low IgG levels, IgA de...
...13. Patients receiving IgG therapy...
...he placement of permanent central ve...
...5. Aggressive and prolonged antimicro...
...Short- or long-term antimicrobial prophyl...
...ing and function should be monitore...
...18. Surgical procedures undertaken with the...
...commended definitive therapy of cellular...
.... Only irradiated, CMV-negative, lymph...
.... Live vaccines should not be adminis...
...Inactivated or subunit vaccines can be ad...
...23. Education for patients and families with...
...ts with suspected or diagnosed PIDDs ar...
...A coordinated multidisciplinary appr...
...y of Therapeutic Considerations for Pri...
...mens for Prophylaxis of Bacterial Respiratory...
Combined B- and T-Cell Immunodeficiencies
...nd T-Cell Immunodeficiencies ...
...2. Diagnosis of Combined or Syndromi...
Severe combined immunodeficiency (S...
...uld be considered in the differential...
SS 27. Patients with SCID or suspected SCID s...
...28. Patients with SCID or suspected SCID sho...
...nts with SCID should receive PCP prophylaxis....
...y signs of infection should be promptly investig...
...31. Polyethylene glycol (PEG)-conjugated ADA3...
...icion of SCID should be considered...
...3. Patients with SCID should be immunolo...
...al and Laboratory Manifestations of S...
...Lymphocyte Phenotype Classification of SCIDÂ ...
...CID syndromes...
...s with CID with intermediate T-cel...
...All forms of ancillary or supportive therapy admin...
SS 36. Patients with leaky SCIDPatient...
...IgM syndrome (HIM) caused by defects of CD40L...
...e diagnosis of a form of HIM should be c...
...38. CD40L expression should be eval...
...expression should be measured by using...
...S 40. Female patients with the HIM phen...
...1. PCP prophylaxis is indicated for...
...2. Neutropenia in patients with CD40 or CD40L d...
.... HSCT should be considered for CD...
CID, unspecifie...
...5. Any patient with abnormal serum immunoglob...
...Syndromes with Immunodeficiency...
...S 46. A diagnosis of Wiskott-Aldrich Syndrome (WAS...
...Patients suspected to have WAS sho...
...ement of patients with WAS should incl...
...HSCT must be seriously considered for...
...DNA repair defects...
...her chromosomal repair disorders should be...
...eficiency, centromeric instability, and facial...
.... Postmeiotic segregation increased 2...
...is of radiosensitivity, immunodeficiency, dys...
...genetic abnormalities, such as chromosom...
...Patients suspected to have AT should be screene...
...g with radiography should be used cautious...
...Antibiotic prophylaxis, IgG replaceme...
...58. Management of malignancy in patients with...
...transplantation can be considered i...
...rge syndrome (DGS)...
...hould be investigated in patients wit...
...eriodic immunologic re-evaluation is...
...Patients suspected of having DGS shoul...
.... Treatment of infants with complete DGS re...
...CD4 lymphopenia (ICD4L)...
...should be suspected in patients with o...
...anagement of ICD4L is supportive and dicta...
...sseous dysplasias...
SS 66. The immuno-osseous dysplasias should be co...
...S 67. Medical management of immunoos...
...T is indicated and has been successful...
...Netherton syndrom...
SS 69. A diagnosis of Comel-Netherton s...
...E syndromes (HIES)...
...70. A form of HIES should be cons...
...ial approach to HIES therapy should be...
...s with DOCK8 deficiency and poor anti...
...73. The use of IVIG or IFN-Îł in patients with...
...hould be considered for both forms of HI...
...patic veno-occlusive di...
...s in the SP110 gene should be sought in pati...
...tosis congenita (DK...
...76. DKC should be investigated in patie...
...fects of vitamin B12 and folate metabo...
SS 77. Inborn errors of folate and vi...
SS 78. Infants with severe vitamin B12 or...
...mmunodeficiency with multiple intestinal atr...
...79. Patients born with MIA should be screened fo...
...ld be considered for treatment of MIA-SCID. (...
Predominantly Antibody Deficiencies
...tly Antibody DeficienciesÂ
...globulinemia ...
...81. Patients with very low or undetectabl...
...bulinemia should be managed aggressively...
...Enteroviral meningoencephalitis in patients wit...
...nsplantation should be considered for pa...
...n variable immunodeficiency (CVID)Â...
...iagnosis of CVID should be consider...
...86. Grouping of patients with CVID based on analy...
SS 87. Selected diseases, molecular defects...
...S 88. CVID should be managed aggressively with...
...ointestinal status should be monit...
...90. Vigilance for possible autoimmune...
...igilance for nonmalignant and malignant lym...
...Autoimmune, lymphoproliferative, or malignan...
...m cell transplantation can be considere...
...having hypogammaglobulinemia and thymoma shou...
...nts with Good syndrome, thymomas should be exc...
...lective IgA deficiency (SIGAD)Â ...
...jects older than 4 years with a serum IgA...
...ents with serum IgA levels of less than the...
...Patients with SIGAD should be monitored over time...
...on use should be investigated in patient...
...Aggressive antimicrobial therapy, prophylaxis, or...
...pic disease should be treated aggress...
...02. Rare patients with SIGAD might benefit...
...subclass deficiency (IGGSD)Â...
SS 103. A diagnosis of IGGSD should be...
SS 104. The principles of management of IGGSD...
...pecific antibody deficie...
...diagnosis of SAD should be given to patients o...
...ents with SAD might benefit from additional immuni...
...ble 8. Assessing Serotype-Specific Responses to...
...ansient hypogammaglobulinemia of...
...s and young children with frequent viral and bac...
SS 108. The principles of management of THI...
...oglobulin class-switch defects...
...nts with immunoglobulin class-switch defec...
...The principles of management of imm...
...mune, lymphoproliferative, or mali...
...specified hypogammaglobul...
...atient with primary hypogammaglobulinemi...
...anagement of unspecified hypogammaglobulinemia sho...
...iseases of Immune Dysregul...
...sis of Diseases of Immune Dysregulation...
...gashi syndrome (CHS)...
...S 114. CHS should be suspected in patients wit...
...115. Examination of a peripheral bloo...
...tment of HLH in patients with CHS is identic...
...li syndrome (GS) type 2
SS 117. GS type 2 should be suspected in patie...
...Pudlak syndrome (HPS)...
...type 2 should be suspected in patients with hy...
...hagocytic lymphohistiocytosis (FHL...
SS 119. FHL should be suspected in patients with...
...ry screening for FHL should be per...
...uld be treated with high-dose glucocorticosteroid...
...hoproliferative syndrome...
...122. X-linked lymphoproliferative disease (XLP) s...
...123. Patients with suspected XLP should be scree...
...ould be given to patients with XLP and hypogamm...
...tients with XLP and HLH should be treated w...
...omes with autoimmunity...
...lymphoproliferative syndrome (ALPS) and AL...
...ALPS-related disorder should be su...
...urement of T cells expressing the Î...
...Treatment of ALPS should be tailored to add...
...mune polyendocrinopathy–candidias...
...129. APECED should be suspected in patients wi...
...ients with clinical features consis...
...S 131. Immunosuppressive therapy should...
...32. Other specific genetic lesions s...
...X syndrome...
...X syndrome should be suspected in patients with...
...diagnosis of IPEX syndrome should be...
...l treatment of IPEX syndrome should in...
...uld be considered early in the course of IPEX synd...
...r specific genetic lesions should b...
...omplement deficiency should be considered in t...
...tic Cell Defects...
...agnosis of Phagocyte Defects...
...cts of neutrophil differentiati...
...evere congenital neutropenia...
...Patients with recurrent bacterial respiratory t...
...ents with neutropenia should receive...
...41. HSCT should be considered for patients wi...
Defects of neutrophil motil...
...yte adhesion deficiency (LAD) types I...
...42. LAD should be suspected in pat...
...blood cell count should be the first sc...
...S 144. LAD-I/II should be diagnosed by usi...
...y for LAD-I/II should be supportive a...
...e supplementation can ameliorate t...
.... HSCT is curative for LAD-I and LAD-I...
...ranule deficiency (SGD)...
...148. SGD should be considered in patients...
...nagement of SGD should be supportive, b...
...r syndromes of defective neutrophil motil...
...ional genetic lesions should be inve...
Defects of the respiratory burst
...ts of the respiratory burst...
Chronic granulomatous diseas...
SS 151. CGD should be suspected in patients with d...
.... Measurement of phagocyte oxidase activity shou...
...s with CGD should be given prophylaxis with anti...
...154. Granulocyte transfusions should be consi...
...S 155. In patients with CGD, aggressive...
...S 156. HSCT should be considered early in th...
Mendelian susceptibility to mycobacterial disease (MSMD)
...ceptibility to mycobacterial disease (MSM...
...57. Patients with severe tuberculous or atypical m...
...Patients suspected of having MSMD sho...
...ement of MSMD should include vigilance for inf...
...Patients with partial IFNGR1/2 mutations...
...61. HLA-identical sibling HSCT can be conside...
Pulmonary alveolar proteinosis (PAP)
...alveolar proteinosis (PAP)...
...162. Patients with PAP should be t...