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
...iagnos...
...Considerations...
.... It is critical to maintain a high index of susp...
...Other conditions that can increase suscept...
...important to confirm the precise focus...
SS 4. A focused family history (eg, r...
.... A stepwise approach is recommended to eva...
...luation of specific immune responses is ess...
...hould be defined at the molecular genetic lev...
...ossibility of an X-linked PIDD should be...
...Carrier status should be determined for all...
...ure 1. General Approach for the Dia...
...haracteristic Clinical Presentations of Some Im...
...2. Laboratory Tests of Immune Func...
...ummary of Laboratory Findings in th...
Treatment
...atment...
...S 10. After diagnosis of a PIDD, it is important...
...1. Immunoglobulin replacement thera...
...In association with low IgG levels, IgA...
...tients receiving IgG therapy should...
...ment of permanent central venous access sol...
...essive and prolonged antimicrobial therapy shou...
...Short- or long-term antimicrobial p...
...g imaging and function should be mon...
...8. Surgical procedures undertaken with the...
...mmended definitive therapy of cellular...
...irradiated, CMV-negative, lymphocyte-deplete...
...Live vaccines should not be administered to patien...
...Inactivated or subunit vaccines can be administe...
...ucation for patients and families with...
...ients with suspected or diagnosed PIDDs ar...
...A coordinated multidisciplinary appr...
...ble 4. Summary of Therapeutic Consideration...
...Regimens for Prophylaxis of Bacterial Respirator...
Combined B- and T-Cell Immunodeficiencies
...mbined B- and T-Cell Immunodefi...
...e 2. Diagnosis of Combined or Syndromi...
Severe combined immunodefici...
...26. SCID should be considered in the d...
.... Patients with SCID or suspected SCI...
...28. Patients with SCID or suspected SCID should...
.... Patients with SCID should receive PCP p...
...ly signs of infection should be pro...
...yethylene glycol (PEG)-conjugated ADA31. Polyeth...
...suspicion of SCID should be considered an urgent c...
...s with SCID should be immunologically recons...
...ble 6. Clinical and Laboratory Manifestati...
...ble 7. Lymphocyte Phenotype Classif...
...CID syndromesÂ...
...Patients with CID with intermediat...
...of ancillary or supportive therapy admin...
.... Patients with leaky SCIDPatients with leaky SC...
...-IgM syndrome (HIM) caused by defects of CD40L a...
...The diagnosis of a form of HIM should b...
...D40L expression should be evaluated...
...ession should be measured by using flo...
...emale patients with the HIM phenotype shou...
...S 41. PCP prophylaxis is indicated for all pa...
...ia in patients with CD40 or CD40L...
...43. HSCT should be considered for CD40L and CD4...
..., unspecifiedÂ
...y patient with abnormal serum immunoglo...
...Syndromes with Immunodeficiency...
...sis of Wiskott-Aldrich Syndrome (WAS) should b...
SS 47. Patients suspected to have WAS should...
...ement of patients with WAS should include...
...ust be seriously considered for pati...
...DNA repair defect...
...ther chromosomal repair disorders s...
...eficiency, centromeric instability, and faci...
...Postmeiotic segregation increased 2...
SS 53. A diagnosis of radiosensitivity, immu...
...54. Cytogenetic abnormalities, such as chromo...
...ents suspected to have AT should be screen...
SS 56. Imaging with radiography should be use...
...biotic prophylaxis, IgG replacement the...
...58. Management of malignancy in patie...
...cell transplantation can be conside...
DiGeorge syndrome (D...
...S should be investigated in patients with...
...odic immunologic re-evaluation is recomm...
...S 62. Patients suspected of having DGS should...
...ent of infants with complete DGS requir...
...ic CD4 lymphopenia (ICD4L)...
...4. ICD4L should be suspected in patients wit...
...agement of ICD4L is supportive and dicta...
...no-osseous dysplas...
...muno-osseous dysplasias should be conside...
...l management of immunoosseous syndromes shoul...
...is indicated and has been successful...
...el-Netherton syndrome...
...diagnosis of Comel-Netherton syndro...
...er-IgE syndromes (HIES)...
...of HIES should be considered in patients with r...
.... The initial approach to HIES therapy should be...
...72. Patients with DOCK8 deficiency and...
...The use of IVIG or IFN-γ in patie...
...HSCT should be considered for both forms of...
Hepatic veno-occlusive disease
...Mutations in the SP110 gene should be sought in...
...eratosis congenita (DK...
SS 76. DKC should be investigated in patient...
...fects of vitamin B12 and folate me...
...rors of folate and vitamin B12 malabsorption s...
SS 78. Infants with severe vitamin B12 or folate...
...odeficiency with multiple intestinal at...
.... Patients born with MIA should be scre...
...SCT should be considered for treatment of MIA-SC...
Predominantly Antibody Deficiencies
...nantly Antibody Deficiencies ...
...gammaglobuline...
SS 81. Patients with very low or undetectable seru...
...aglobulinemia should be managed aggres...
...ral meningoencephalitis in patients with agammaglo...
SS 84. Lung transplantation should be consi...
...mon variable immunodeficiency (CVI...
...The diagnosis of CVID should be cons...
SS 86. Grouping of patients with CVID ba...
...lected diseases, molecular defects, or bo...
SS 88. CVID should be managed aggressively with an...
...89. Gastrointestinal status should be mon...
...e for possible autoimmune diseases should be...
...ilance for nonmalignant and malignant l...
...utoimmune, lymphoproliferative, or malignant dis...
...S 93. Stem cell transplantation can b...
...94. Patients having hypogammaglobulinemia and thy...
...ts with Good syndrome, thymomas should be excised...
...e IgA deficiency (SIGAD)Â ...
...S 96. Subjects older than 4 years with a serum I...
...7. Patients with serum IgA levels of l...
...nts with SIGAD should be monitored over time for t...
SS 99. Medication use should be in...
...ve antimicrobial therapy, prophylaxi...
...ic disease should be treated aggress...
...S 102. Rare patients with SIGAD might benefit fr...
IgG subclass deficienc...
...A diagnosis of IGGSD should be consider...
...4. The principles of management of...
...ic antibody deficiency (SA...
...5. The diagnosis of SAD should be...
.... Patients with SAD might benefit from a...
...e 8. Assessing Serotype-Specific Res...
...nsient hypogammaglobulinemia of inf...
...ts and young children with frequent viral and bact...
...principles of management of THI should follow t...
...globulin class-switch defects...
.... Patients with immunoglobulin class-swit...
...principles of management of immunoglobulin cla...
...Autoimmune, lymphoproliferative, or mali...
...pecified hypogammaglobu...
...tient with primary hypogammaglobulinemia a...
...gement of unspecified hypogammaglobulinem...
...of Immune Dysregulation...
...gure 3. Diagnosis of Diseases of Immune Dysreg...
...hediak-Higashi syndrome (C...
...should be suspected in patients with partial...
...ation of a peripheral blood smear should...
...The treatment of HLH in patients with CHS...
...i syndrome (GS) type 2...
...S type 2 should be suspected in patients with...
...rmansky-Pudlak syndrom...
...PS type 2 should be suspected in patients with...
...mophagocytic lymphohistiocytosis (FHL) syndrome...
...ld be suspected in patients with fever, hepa...
...120. Laboratory screening for FHL should be p...
...should be treated with high-dose gluco...
...phoproliferative syndromes
...linked lymphoproliferative disease (XL...
...3. Patients with suspected XLP shou...
...uld be given to patients with XLP and h...
...with XLP and HLH should be treated with chemo...
...omes with autoimmu...
...lymphoproliferative syndrome (ALPS) and ALPS–r...
...ALPS-related disorder should be suspe...
...Measurement of T cells expressing the α/β T-cel...
...ment of ALPS should be tailored to a...
...toimmune polyendocrinopathy–candidiasis–...
...hould be suspected in patients with immune-me...
...nts with clinical features consistent with aut...
...suppressive therapy should be consider...
...132. Other specific genetic lesions...
...syndrome...
...drome should be suspected in patients...
...4. A diagnosis of IPEX syndrome should...
...135. Initial treatment of IPEX syndro...
...136. HSCT should be considered early in t...
.... Other specific genetic lesions should be soug...
...mplement deficiency should be considered in the...
...cytic Cell Defects...
...gnosis of Phagocyte Defects...
...eutrophil differentiation...
...ngenital neutropenia...
...39. Patients with recurrent bacterial respirator...
...with neutropenia should receive G-...
...ould be considered for patients with se...
...fects of neutrophil motility...
...e adhesion deficiency (LAD) types I,...
...S 142. LAD should be suspected in patients...
...43. A blood cell count should be the...
...LAD-I/II should be diagnosed by using flow cytom...
...py for LAD-I/II should be supportiv...
...146. Fucose supplementation can a...
...curative for LAD-I and LAD-III and sh...
...ecific granule deficie...
...ould be considered in patients with recu...
...gement of SGD should be supportive,...
...ndromes of defective neutrophil mo...
...dditional genetic lesions should be inv...
Defects of the respiratory burst
...the respiratory burst...
...ranulomatous disease (CGD)...
...51. CGD should be suspected in pat...
...Measurement of phagocyte oxidase activity shou...
.... Patients with CGD should be given proph...
...ranulocyte transfusions should be consid...
...5. In patients with CGD, aggressive...
...should be considered early in the course...
Mendelian susceptibility to mycobacterial disease (MSMD)
...sceptibility to mycobacterial disease (MSMD)...
...atients with severe tuberculous or atypi...
...nts suspected of having MSMD should hav...
...Management of MSMD should include v...
...160. Patients with partial IFNGR1/2 mutation...
...tical sibling HSCT can be considered...
Pulmonary alveolar proteinosis (PAP)
...alveolar proteinosis (P...
...162. Patients with PAP should be tested f...