Primary Immunodeficiency

Publication Date: September 1, 2015

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...

...Gene...

...ical to maintain a high index of suspicion...

...2. Other conditions that can increase susceptibi...

...3. It is important to confirm the precise f...

...focused family history (eg, recurrent in...

...wise approach is recommended to evalua...

...on of specific immune responses is essen...

...DDs should be defined at the molecular genetic le...

SS 8. The possibility of an X-linked PIDD should b...

.... Carrier status should be determined for all...


...Figu...


...Table 1. Character...


...Table 2. Laboratory Tests...


.... Summary of Laboratory Findings in the Diag...


Treatment

...Treat...

...10. After diagnosis of a PIDD, it is important...


...S 11. Immunoglobulin replacement therapy is...


...ation with low IgG levels, IgA defic...


...ients receiving IgG therapy should have regular mo...


...e placement of permanent central venous access so...


...15. Aggressive and prolonged antimicro...


...rt- or long-term antimicrobial prophylaxi...


...g imaging and function should be mon...


SS 18. Surgical procedures undertaken wit...


...The recommended definitive therapy of ce...


...20. Only irradiated, CMV-negative, lymphocyt...


...ines should not be administered to patients...


...Inactivated or subunit vaccines can be...


...ducation for patients and families with PIDD...


...S 24. Patients with suspected or d...


...5. A coordinated multidisciplinary approa...


...Table 4....


...Table...


Combined B- and T-Cell Immunodeficiencies 

...Combined...

...Figure 2. Diagnosis of C...


...Severe combined immunodefi...

...26. SCID should be considered in the dif...

...Patients with SCID or suspected SCID sho...

...ents with SCID or suspected SCID should b...

...9. Patients with SCID should receive P...

...y signs of infection should be promptly investig...

.... Polyethylene glycol (PEG)-conjugated A...

...A suspicion of SCID should be considered an urgent...

...33. Patients with SCID should be immun...

...Table...

...Table 7...

...Other CID syn...

...34. Patients with CID with intermedi...

...5. All forms of ancillary or supportive therapy ad...

.... Patients with leaky SCIDPatients wit...

...Hyper-IgM syndrome (...

...nosis of a form of HIM should be considered in...

...40L expression should be evaluated by using...

.... CD40 expression should be measured by using...

...le patients with the HIM phenotype...

...PCP prophylaxis is indicated for all patie...

...ia in patients with CD40 or CD40L deficien...

...uld be considered for CD40L and CD40 deficiency. (...

...CID, unspecified ...

...y patient with abnormal serum immunoglobul...

...Well-Defined...

...osis of Wiskott-Aldrich Syndrome (WAS) sho...

...7. Patients suspected to have WAS s...

...ent of patients with WAS should include IgG replac...

...st be seriously considered for pat...

...Non-SC...

...her chromosomal repair disorders should be consid...

...1. Immunodeficiency, centromeric instability, and...

...2. Postmeiotic segregation increase...

...3. A diagnosis of radiosensitivity...

...genetic abnormalities, such as chromosomal tr...

...ts suspected to have AT should be screened by me...

...with radiography should be used cautiously i...

...ntibiotic prophylaxis, IgG replacement...

.... Management of malignancy in patients with AT and...

...em cell transplantation can be considered in...

...DiGeorge syndro...

...GS should be investigated in patients with...

...S 61. Periodic immunologic re-evaluat...

...nts suspected of having DGS should have molecul...

...Treatment of infants with complete DGS requires...

...Idiopathi...

...should be suspected in patients with...

...nagement of ICD4L is supportive and dictated...

...Immuno-osseous dyspl...

...muno-osseous dysplasias should be c...

...67. Medical management of immunoosseo...

...s indicated and has been successful for the corre...

...Comel-Netherton s...

...69. A diagnosis of Comel-Netherton...

...Hyper-IgE synd...

...70. A form of HIES should be considered in pat...

...71. The initial approach to HIES therapy should...

...2. Patients with DOCK8 deficiency and poor...

...of IVIG or IFN-γ in patients with type 1 autoso...

...S 74. HSCT should be considered fo...

...Hepatic veno-oc...

.... Mutations in the SP110 gene should be so...

...Dyskeratosis cong...

...76. DKC should be investigated in patien...

...Defects...

...rn errors of folate and vitamin B12 ma...

...fants with severe vitamin B12 or folate de...

...Immunodeficienc...

...born with MIA should be screened for CIDs. ( C )5...

...HSCT should be considered for treatment of MIA-S...


Predominantly Antibody Deficiencies 

...Predominantly...

A...

...Patients with very low or undetectable serum im...

...bulinemia should be managed aggressively with...

...viral meningoencephalitis in patient...

...splantation should be considered for patients w...


...Common vari...

SS 85. The diagnosis of CVID should be c...

...ing of patients with CVID based on analysis o...

...d diseases, molecular defects, or both should be...

SS 88. CVID should be managed aggressively wi...

...rointestinal status should be monitored regularly...

...ance for possible autoimmune diseases should be m...

...gilance for nonmalignant and malignant lymphoproli...

...une, lymphoproliferative, or maligna...

...cell transplantation can be conside...

...tients having hypogammaglobulinemia and thymoma sh...

...tients with Good syndrome, thymomas should be...


...Selective IgA...

...Subjects older than 4 years with a serum...

...97. Patients with serum IgA levels of less t...

...with SIGAD should be monitored over time...

...S 99. Medication use should be inv...

...gressive antimicrobial therapy, prophylaxis, or...

...1. Atopic disease should be treated...

...Rare patients with SIGAD might benefit from I...


...03. A diagnosis of IGGSD should be conside...

...principles of management of IGGSD shoul...


...Specific antibody...

...05. The diagnosis of SAD should be given to patie...

...with SAD might benefit from additional...


...Assessing Serotype-Specific Responses to Pne...


...Transient hypogammaglo...

...Infants and young children with freq...

SS 108. The principles of management of THI sh...


...Immunoglobulin class-s...

...ents with immunoglobulin class-switch defects shou...

.... The principles of management of immun...

...mune, lymphoproliferative, or malignant disea...


...Uns...

...atient with primary hypogammaglobulinemia a...

...agement of unspecified hypogammaglobulinemia sh...


...Diseases o...

...iagnosis of Diseases of Immune Dysre...


...Chediak-Higashi s...

...CHS should be suspected in patients wit...

...Examination of a peripheral blood smear...

...16. The treatment of HLH in patients with...


...Griscelli sy...

...GS type 2 should be suspected in pat...


...Hermansky-Pudlak s...

...ype 2 should be suspected in patients with hypo...


...Familial hemo...

...19. FHL should be suspected in patients with feve...

...Laboratory screening for FHL should be performe...

...S 121. HLH should be treated with high-dose glu...


...Lymphoproliferative syndro...

...X-linked lymphoproliferative disease (XLP) shou...

...with suspected XLP should be scree...

...S 124. IVIG should be given to patients w...

...125. Patients with XLP and HLH shou...


...Syndrome...

...Autoimmune l...

...n ALPS-related disorder should be s...

.... Measurement of T cells expressing the α/β T...

...ment of ALPS should be tailored to address life-...

...Autoimmune pol...

...S 129. APECED should be suspected in patients wit...

...ts with clinical features consistent...

...unosuppressive therapy should be considered in pa...

...ecific genetic lesions should be sough...

...IPEX...

.... IPEX syndrome should be suspected in patients...

...134. A diagnosis of IPEX syndrome should be sou...

...Initial treatment of IPEX syndrome...

...36. HSCT should be considered early in the course...

...S 137. Other specific genetic lesions s...

SS 138. Complement deficiency should be considered...

...Phagocytic Cell Defects...

...Diagnosis of Phagocyte Defects...

...Defects of n...

...Severe congeni...

...with recurrent bacterial respiratory tract and...

...ents with neutropenia should receive G-CSF ( C )5...

...should be considered for patients with severe chro...

...De...

...Leukocyte adhesion...

...42. LAD should be suspected in patients wi...

...143. A blood cell count should be the...

.../II should be diagnosed by using flow cytom...

...for LAD-I/II should be supportive...

...46. Fucose supplementation can amel...

...curative for LAD-I and LAD-III and should...

...Specific granule defici...

...SGD should be considered in patients with...

...ent of SGD should be supportive, but HSCT might h...


...Other syndrome...

...150. Additional genetic lesions should be investig...


Defects of the respiratory burst

...Defe...

...Chronic granulomato...

...51. CGD should be suspected in patients with deep-...

...Measurement of phagocyte oxidase activi...

...tients with CGD should be given prop...

...anulocyte transfusions should be considered as a l...

...5. In patients with CGD, aggressive surgical d...

...6. HSCT should be considered early in the cour...


Mendelian susceptibility to mycobacterial disease (MSMD)

...Mendelian susce...

...S 157. Patients with severe tuberculous or aty...


...8. Patients suspected of having MSMD should...


...nagement of MSMD should include vigilance for in...


...160. Patients with partial IFNGR1/2 mu...


SS 161. HLA-identical sibling HSCT c...


Pulmonary alveolar proteinosis (PAP)

...Pulmonary alveola...

...162. Patients with PAP should be tested...