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...
...l Considerations...
...is critical to maintain a high index of suspicio...
...onditions that can increase susceptibil...
...It is important to confirm the precise focus of...
...4. A focused family history (eg, recurrent infe...
SS 5. A stepwise approach is recommended to...
...aluation of specific immune responses is e...
...should be defined at the molecular gen...
...ssibility of an X-linked PIDD should be con...
SS 9. Carrier status should be deter...
...e 1. General Approach for the Diagno...
...aracteristic Clinical Presentations...
...e 2. Laboratory Tests of Immune Functio...
...3. Summary of Laboratory Findings in the Diagno...
Treatment
...eatmen...
...fter diagnosis of a PIDD, it is important...
...11. Immunoglobulin replacement the...
...12. In association with low IgG levels...
.... Patients receiving IgG therapy shou...
...The placement of permanent central...
...15. Aggressive and prolonged antimicrobial therapy...
...16. Short- or long-term antimicrobial prophylaxis...
...ing and function should be monitored re...
.... Surgical procedures undertaken with t...
...mended definitive therapy of cellular or combine...
...adiated, CMV-negative, lymphocyte-depleted ce...
...1. Live vaccines should not be admi...
...ctivated or subunit vaccines can be administer...
...n for patients and families with PIDDs is r...
.... Patients with suspected or diagnosed PIDDs ar...
...5. A coordinated multidisciplinary approa...
Table 4. Summary of Therapeutic Considerations f...
...le 5. Regimens for Prophylaxis of Bacte...
Combined B- and T-Cell Immunodeficiencies
...ined B- and T-Cell Immunodefici...
...osis of Combined or Syndromic Immunodeficienci...
...ned immunodeficiency (SCID)Â ...
...ld be considered in the differential diagnos...
...ents with SCID or suspected SCID should receive Ig...
...nts with SCID or suspected SCID shoul...
...ts with SCID should receive PCP prophylaxis. ( C )...
...Early signs of infection should be promptly inv...
...ene glycol (PEG)-conjugated ADA31. Polyeth...
...A suspicion of SCID should be considered an urgen...
...with SCID should be immunologically reconstit...
...able 6. Clinical and Laboratory Ma...
...ymphocyte Phenotype Classification of SCIDÂ ...
...ther CID syndrome...
...ents with CID with intermediate T-cell numbers...
...ms of ancillary or supportive therapy...
...s with leaky SCIDPatients with leaky SCID...
...yper-IgM syndrome (HIM) caused by...
...osis of a form of HIM should be considered in...
SS 38. CD40L expression should be evalua...
...expression should be measured by using...
...40. Female patients with the HIM phenotype...
...rophylaxis is indicated for all patients wit...
...nia in patients with CD40 or CD40L deficien...
...3. HSCT should be considered for C...
..., unspecified ...
.... Any patient with abnormal serum i...
...-Defined Syndromes with Immunode...
...sis of Wiskott-Aldrich Syndrome (WAS) should b...
...suspected to have WAS should have a defini...
...nt of patients with WAS should include IgG re...
...HSCT must be seriously considered for patients...
...CID DNA repair defec...
...and other chromosomal repair disorders should b...
...eficiency, centromeric instability, and...
.... Postmeiotic segregation increased 2...
...A diagnosis of radiosensitivity, immunodeficiency...
...S 54. Cytogenetic abnormalities, such as chromo...
...S 55. Patients suspected to have AT shou...
...ith radiography should be used cautiously in pa...
...Antibiotic prophylaxis, IgG replacement therapy, o...
...ment of malignancy in patients with...
...tem cell transplantation can be co...
...George syndrome (DGS)...
...hould be investigated in patients wit...
...ic immunologic re-evaluation is recommended...
...atients suspected of having DGS should h...
...3. Treatment of infants with complete DGS requ...
...c CD4 lymphopenia (ICD4L)...
...CD4L should be suspected in patients with opportu...
...Management of ICD4L is supportive and dic...
Immuno-osseous dysplasias
...The immuno-osseous dysplasias shou...
...Medical management of immunoosseous syndromes...
...s indicated and has been successful for th...
...l-Netherton syndrome...
...A diagnosis of Comel-Netherton syndrome (...
...er-IgE syndromes (HIES)...
...form of HIES should be considered in patients wit...
...itial approach to HIES therapy sho...
...atients with DOCK8 deficiency and poor antibody p...
...he use of IVIG or IFN-γ in patients...
...4. HSCT should be considered for both forms of HIE...
...c veno-occlusive diseas...
...S 75. Mutations in the SP110 gene shou...
Dyskeratosis congenita (...
...KC should be investigated in patients...
...amin B12 and folate metabolism...
...Inborn errors of folate and vitamin B12 malabso...
SS 78. Infants with severe vitamin B12 or folate...
...ency with multiple intestinal atresia (MIA)...
...tients born with MIA should be screened for CIDs....
...HSCT should be considered for treatment of...
Predominantly Antibody Deficiencies
...minantly Antibody Deficien...
...gammaglobulinemiaÂ...
...atients with very low or undetectable serum imm...
...2. Agammaglobulinemia should be managed aggressiv...
...roviral meningoencephalitis in patie...
...transplantation should be considered for patients...
...le immunodeficiency (CVID)Â ...
...e diagnosis of CVID should be consider...
...86. Grouping of patients with CVID based on ana...
...cted diseases, molecular defects, or...
...ould be managed aggressively with antimicrobia...
...estinal status should be monitored regularly i...
...90. Vigilance for possible autoimmune...
...nce for nonmalignant and malignant lymphopr...
...S 92. Autoimmune, lymphoproliferative, or ma...
...S 93. Stem cell transplantation can be co...
...s having hypogammaglobulinemia and thymoma should...
...S 95. In patients with Good syndrome,...
...lective IgA deficiency (SIGAD)...
...96. Subjects older than 4 years with a s...
...tients with serum IgA levels of less than the norm...
...s with SIGAD should be monitored over time for...
...ation use should be investigated in p...
...gressive antimicrobial therapy, prophylaxis, o...
...1. Atopic disease should be treated aggressi...
...e patients with SIGAD might benefit from IVIG re...
...ass deficiency (IGGSD)Â ...
...diagnosis of IGGSD should be considered for a p...
...The principles of management of IGGSD should fo...
...ntibody deficiency (SAD)Â ...
...diagnosis of SAD should be given to patients...
...ts with SAD might benefit from additional immuniz...
...8. Assessing Serotype-Specific Respon...
...hypogammaglobulinemia of infancy (THI)...
...07. Infants and young children with f...
...The principles of management of THI should f...
...mmunoglobulin class-switc...
...ents with immunoglobulin class-switch defec...
...principles of management of immunoglobulin c...
.... Autoimmune, lymphoproliferative,...
...hypogammaglobulinemia...
...Any patient with primary hypogammaglobul...
...gement of unspecified hypogammaglobulinemia...
...iseases of Immune Dysregula...
...re 3. Diagnosis of Diseases of Immune Dysregulat...
...iak-Higashi syndrome (...
...CHS should be suspected in patients with partial...
...mination of a peripheral blood smear sh...
.... The treatment of HLH in patients...
...iscelli syndrome (GS)...
...type 2 should be suspected in patients with pigm...
...ky-Pudlak syndrome (HPS)...
...118. HPS type 2 should be suspected...
...ilial hemophagocytic lymphohistiocyto...
.... FHL should be suspected in patients with fever,...
...atory screening for FHL should be performed befo...
...HLH should be treated with high-dose gluc...
...liferative syndromes...
...nked lymphoproliferative disease (XLP) should...
...ts with suspected XLP should be screened...
...IVIG should be given to patients with XLP and...
...ts with XLP and HLH should be treated with chem...
...s with autoimmunity...
...phoproliferative syndrome (ALPS) and...
...an ALPS-related disorder should be suspected...
...rement of T cells expressing the α/β T-cell...
...128. Treatment of ALPS should be tailored to...
...toimmune polyendocrinopathy–candi...
...129. APECED should be suspected in patients w...
...ients with clinical features consistent...
.... Immunosuppressive therapy should...
...specific genetic lesions should be...
...syndrome
...syndrome should be suspected in patie...
...osis of IPEX syndrome should be sought by enume...
.... Initial treatment of IPEX syndrome shoul...
...should be considered early in the course of I...
...her specific genetic lesions should be sought in...
...nt deficiency should be considered...
...hagocytic Cell Defects...
...re 4. Diagnosis of Phagocyte Defec...
...ts of neutrophil differentia...
...ngenital neutropenia...
...tients with recurrent bacterial respiratory tr...
...Patients with neutropenia should receive G-CSF...
...ould be considered for patients with...
...fects of neutrophil...
Leukocyte adhesion deficiency (LAD) types I, II, a...
...hould be suspected in patients with cellulitis...
...blood cell count should be the fir...
...4. LAD-I/II should be diagnosed by us...
...apy for LAD-I/II should be supportive a...
...cose supplementation can ameliorate the course...
...s curative for LAD-I and LAD-III and should be con...
...cific granule deficienc...
.... SGD should be considered in patients wi...
...nagement of SGD should be supportive, but HSC...
...es of defective neutrophil motility...
SS 150. Additional genetic lesions should be inves...
Defects of the respiratory burst
...ects of the respiratory bur...
...anulomatous disease (CGD)...
SS 151. CGD should be suspected in patients...
...surement of phagocyte oxidase activity shoul...
...153. Patients with CGD should be given...
...cyte transfusions should be considered as a last-r...
...atients with CGD, aggressive surgical d...
.... HSCT should be considered early...
Mendelian susceptibility to mycobacterial disease (MSMD)
...elian susceptibility to mycobacterial diseas...
...Patients with severe tuberculous or...
...nts suspected of having MSMD shoul...
.... Management of MSMD should includ...
...with partial IFNGR1/2 mutations and I...
...entical sibling HSCT can be conside...
Pulmonary alveolar proteinosis (PAP)
...ary alveolar proteinosis (PAP)...
...Patients with PAP should be tested fo...