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
...iagnosis
...eneral Considerat...
...critical to maintain a high index of suspicion for...
...her conditions that can increase susc...
...portant to confirm the precise focus of infection...
...d family history (eg, recurrent infecti...
...S 5. A stepwise approach is recommended to...
...of specific immune responses is e...
...7. PIDDs should be defined at the mo...
...bility of an X-linked PIDD should be cons...
...Carrier status should be determined for all po...
...igure 1. General Approach for the Diagnosis of Pr...
...e 1. Characteristic Clinical Presentations of So...
...2. Laboratory Tests of Immune Function ...
...y of Laboratory Findings in the Diagnosis of...
Treatment
Treatme...
SS 10. After diagnosis of a PIDD, it is i...
...noglobulin replacement therapy is i...
...In association with low IgG levels, IgA defici...
...ents receiving IgG therapy should have r...
...placement of permanent central venous...
...ve and prolonged antimicrobial therapy shou...
...hort- or long-term antimicrobial prophylaxis s...
.... Lung imaging and function should be m...
...S 18. Surgical procedures undertaken with...
...ecommended definitive therapy of cellular...
...Only irradiated, CMV-negative, lymphocyte-depl...
...1. Live vaccines should not be administered t...
...ated or subunit vaccines can be administered to im...
...ion for patients and families with...
...ts with suspected or diagnosed PIDDs are re...
...dinated multidisciplinary approach to...
...y of Therapeutic Considerations for P...
...s for Prophylaxis of Bacterial Respirator...
Combined B- and T-Cell Immunodeficiencies
...ined B- and T-Cell Immunodeficiencies...
...ure 2. Diagnosis of Combined or Syndro...
...re combined immunodeficiency...
...ID should be considered in the differential diag...
...atients with SCID or suspected SCI...
...with SCID or suspected SCID should be prot...
...ents with SCID should receive PCP pr...
...signs of infection should be promptly in...
...thylene glycol (PEG)-conjugated AD...
...on of SCID should be considered an urgent...
...s with SCID should be immunologically reconsti...
...Clinical and Laboratory Manifestations of S...
...ymphocyte Phenotype Classification of S...
Other CID syndromes
...S 34. Patients with CID with interme...
...of ancillary or supportive therapy administered...
...ients with leaky SCIDPatients with...
...r-IgM syndrome (HIM) caused by defects of CD40L...
...S 37. The diagnosis of a form of HIM...
...0L expression should be evaluated by using...
...expression should be measured by using...
...male patients with the HIM phenoty...
...PCP prophylaxis is indicated for all...
...enia in patients with CD40 or CD40L deficiency s...
.... HSCT should be considered for CD40L and...
...ID, unspecified ...
...patient with abnormal serum immunoglobulin leve...
...ined Syndromes with Immunodefici...
...diagnosis of Wiskott-Aldrich Syndrome...
...s suspected to have WAS should have a definiti...
...48. Management of patients with WAS sh...
...9. HSCT must be seriously considered...
...DNA repair defects
...50. AT and other chromosomal repair disorders...
...munodeficiency, centromeric instabil...
...Postmeiotic segregation increased 2 (PMS...
...nosis of radiosensitivity, immunodeficiency,...
...ytogenetic abnormalities, such as chromoso...
.... Patients suspected to have AT should be...
...56. Imaging with radiography should be u...
...biotic prophylaxis, IgG replacement therap...
...58. Management of malignancy in patients...
...Stem cell transplantation can be consi...
...e syndrome (DGS)...
...S should be investigated in patients with thymic...
...61. Periodic immunologic re-evaluat...
...2. Patients suspected of having DGS should have...
...63. Treatment of infants with complete...
...opathic CD4 lymphopenia (ICD4L)...
...S 64. ICD4L should be suspected in patients...
...ement of ICD4L is supportive and dic...
...sseous dysplasias
...6. The immuno-osseous dysplasias s...
...l management of immunoosseous syndrom...
...indicated and has been successful for the cor...
...omel-Netherton syn...
...S 69. A diagnosis of Comel-Netherton syndro...
...-IgE syndromes (HIES)...
...form of HIES should be considered in...
SS 71. The initial approach to HIES thera...
...72. Patients with DOCK8 deficiency and poor a...
...S 73. The use of IVIG or IFN-γ in patie...
...should be considered for both forms of HIES....
...patic veno-occlusive...
...tions in the SP110 gene should be sought in patien...
...atosis congenita (DKC)...
.... DKC should be investigated in patient...
...s of vitamin B12 and folate meta...
...errors of folate and vitamin B12...
...Infants with severe vitamin B12 o...
Immunodeficiency with multiple intestinal atre...
...ents born with MIA should be screened for CIDs. (...
...T should be considered for treatment...
Predominantly Antibody Deficiencies
...antly Antibody Deficienci...
...gammaglobuline...
...nts with very low or undetectable serum immu...
...obulinemia should be managed aggressively w...
SS 83. Enteroviral meningoencephalitis in pati...
...Lung transplantation should be consid...
...variable immunodeficiency (C...
...diagnosis of CVID should be considered in m...
SS 86. Grouping of patients with CVID b...
...ected diseases, molecular defects, o...
...should be managed aggressively with antimic...
...9. Gastrointestinal status should b...
...e for possible autoimmune diseases sh...
...1. Vigilance for nonmalignant and malig...
...92. Autoimmune, lymphoproliferative, or malignant...
.... Stem cell transplantation can be considere...
...ents having hypogammaglobulinemia and thymoma...
.... In patients with Good syndrome, thymom...
...tive IgA deficiency (SIGAD) ...
...ects older than 4 years with a serum IgA lev...
...Patients with serum IgA levels of less than t...
.... Patients with SIGAD should be moni...
...Medication use should be investigated in patien...
...ive antimicrobial therapy, prophylaxis, or bot...
...01. Atopic disease should be treated aggressively...
...S 102. Rare patients with SIGAD mig...
...lass deficiency (IGGSD) ...
...diagnosis of IGGSD should be considered fo...
...he principles of management of IGGS...
...pecific antibody deficiency (SAD) ...
...diagnosis of SAD should be given to patients...
...ents with SAD might benefit from additional immu...
...8. Assessing Serotype-Specific Responses...
...ient hypogammaglobulinemia of infancy (THI)...
...fants and young children with frequent v...
SS 108. The principles of management of THI s...
...globulin class-switch defe...
...atients with immunoglobulin class-switch def...
...principles of management of immunoglobulin...
...utoimmune, lymphoproliferative, or m...
...cified hypogammaglobulinemia...
.... Any patient with primary hypogammag...
...agement of unspecified hypogammaglobulinemia shou...
Diseases of Immune Dysregulati...
...Diagnosis of Diseases of Immune Dysregulation...
...-Higashi syndrome (CHS)...
SS 114. CHS should be suspected in p...
...tion of a peripheral blood smear should be the fir...
...atment of HLH in patients with CHS is identical in...
...syndrome (GS) type 2...
...2 should be suspected in patients with pigme...
...y-Pudlak syndrome (HPS)...
...e 2 should be suspected in patient...
...hemophagocytic lymphohistiocytosis (...
...should be suspected in patients with fever...
...Laboratory screening for FHL shou...
...121. HLH should be treated with high-dose gluco...
Lymphoproliferative syn...
...ed lymphoproliferative disease (XLP) should be sus...
.... Patients with suspected XLP should be scre...
...uld be given to patients with XLP and hypogamm...
...Patients with XLP and HLH should be treat...
...s with autoimmunity...
...mphoproliferative syndrome (ALPS)...
...S or an ALPS-related disorder should be su...
...urement of T cells expressing the α/β T-ce...
...Treatment of ALPS should be tailor...
...olyendocrinopathy–candidiasis–ectodermal d...
...D should be suspected in patients with immune-...
.... Patients with clinical features consistent with...
...suppressive therapy should be considered in patien...
...S 132. Other specific genetic lesions should be so...
...PEX syndrome
...133. IPEX syndrome should be suspected in patients...
...gnosis of IPEX syndrome should be sough...
...135. Initial treatment of IPEX syndrome...
...CT should be considered early in the cou...
...137. Other specific genetic lesions should be s...
...omplement deficiency should be considered in...
...ocytic Cell Defects...
...Diagnosis of Phagocyte Defects...
...fects of neutrophil differentiation
Severe congenital neut...
...Patients with recurrent bacterial respi...
...140. Patients with neutropenia should receive...
...141. HSCT should be considered for patien...
...f neutrophil motility...
...adhesion deficiency (LAD) types I, II, and III...
...ould be suspected in patients with cellulitis, abs...
...143. A blood cell count should be t...
...D-I/II should be diagnosed by using flo...
...apy for LAD-I/II should be supportive a...
...e supplementation can ameliorate the course of LA...
.... HSCT is curative for LAD-I and LAD-I...
...granule deficiency (SGD)...
...hould be considered in patients with recurrent sev...
...ent of SGD should be supportive, but HSCT might h...
...syndromes of defective neutrophil...
SS 150. Additional genetic lesions should be...
Defects of the respiratory burst
...f the respiratory burst...
...anulomatous disease (CGD)...
...should be suspected in patients with deep-seated g...
...asurement of phagocyte oxidase activity should be...
...3. Patients with CGD should be given prophylaxis...
...locyte transfusions should be considered as...
...patients with CGD, aggressive surgical debridemen...
...hould be considered early in the c...
Mendelian susceptibility to mycobacterial disease (MSMD)
...elian susceptibility to mycobacterial disease (...
...157. Patients with severe tuberculo...
...atients suspected of having MSMD s...
SS 159. Management of MSMD should include vig...
...Patients with partial IFNGR1/2 mut...
...A-identical sibling HSCT can be considered for t...
Pulmonary alveolar proteinosis (PAP)
...lveolar proteinosis (PAP)...
...ts with PAP should be tested for muta...