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

...gnosis...

...eneral Considerations...

...critical to maintain a high index...

...ther conditions that can increase suscepti...

...t is important to confirm the precis...

...S 4. A focused family history (eg,...

...tepwise approach is recommended to...

SS 6. Evaluation of specific immune responses is...

...7. PIDDs should be defined at the molecular gene...

...e possibility of an X-linked PIDD should be consi...

...er status should be determined for all poten...


...1. General Approach for the Diagnosis of...


...Characteristic Clinical Presentati...


...e 2. Laboratory Tests of Immune Function...


...ary of Laboratory Findings in the Diagnosis of An...


Treatment

Treatme...

...er diagnosis of a PIDD, it is important...


...mmunoglobulin replacement therapy is indic...


...association with low IgG levels,...


...3. Patients receiving IgG therapy should have re...


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


...ssive and prolonged antimicrobial therap...


...S 16. Short- or long-term antimicrobial...


...17. Lung imaging and function should be monit...


...l procedures undertaken with the aim of reduc...


...recommended definitive therapy of cellular or...


...irradiated, CMV-negative, lymphocyte-...


...ive vaccines should not be administe...


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


...23. Education for patients and families with...


...atients with suspected or diagnosed...


...nated multidisciplinary approach t...


.... Summary of Therapeutic Considerations fo...


...ns for Prophylaxis of Bacterial Resp...


Combined B- and T-Cell Immunodeficiencies 

...ned B- and T-Cell Immunodeficiencies ...

...Diagnosis of Combined or Syndromic Imm...


...mbined immunodeficiency (SCID) ...

...CID should be considered in the differential...

...ents with SCID or suspected SCID should re...

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

...tients with SCID should receive PC...

SS 30. Early signs of infection should be prom...

...lyethylene glycol (PEG)-conjugated ADA...

SS 32. A suspicion of SCID should be considered...

...with SCID should be immunologically recon...

...able 6. Clinical and Laboratory Manife...

...le 7. Lymphocyte Phenotype Classif...

...her CID syndromes...

...atients with CID with intermediate...

...orms of ancillary or supportive thera...

...6. Patients with leaky SCIDPatient...

...ome (HIM) caused by defects of CD40L and C...

.... The diagnosis of a form of HIM shou...

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

...expression should be measured by using flow cy...

...S 40. Female patients with the HIM phenoty...

...S 41. PCP prophylaxis is indicated for all patien...

...Neutropenia in patients with CD40 or...

...HSCT should be considered for CD40L and CD40...

...D, unspecified 

...45. Any patient with abnormal ser...

...Syndromes with Immunodeficiency...

...46. A diagnosis of Wiskott-Aldrich Syndr...

...nts suspected to have WAS should have a def...

...ent of patients with WAS should inc...

...be seriously considered for patients...

...DNA repair defects...

...d other chromosomal repair disorders shoul...

...nodeficiency, centromeric instabili...

...stmeiotic segregation increased 2 (P...

...diagnosis of radiosensitivity, immun...

...Cytogenetic abnormalities, such as chro...

...suspected to have AT should be screened by measu...

...56. Imaging with radiography should be used c...

...ntibiotic prophylaxis, IgG replacement ther...

...nagement of malignancy in patients...

...cell transplantation can be considered in selecte...

...rge syndrome (DGS)...

...60. DGS should be investigated in patien...

...odic immunologic re-evaluation is r...

...62. Patients suspected of having DG...

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

...c CD4 lymphopenia (ICD4L)...

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

...S 65. Management of ICD4L is supportive an...

...-osseous dysplasias...

...no-osseous dysplasias should be considered...

...ical management of immunoosseous syndromes shoul...

...indicated and has been successful for t...

...therton syndrome...

...osis of Comel-Netherton syndrome (SPINK5 gene...

...IgE syndromes (HIES)...

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

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

...atients with DOCK8 deficiency and poor...

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

...74. HSCT should be considered for both forms of H...

...tic veno-occlusive dise...

...S 75. Mutations in the SP110 gene s...

...keratosis congenita (DK...

...ould be investigated in patients with...

...ts of vitamin B12 and folate metabolism...

...born errors of folate and vitamin B12...

...nts with severe vitamin B12 or folate deficiency s...

Immunodeficiency with multiple intesti...

...s born with MIA should be screened for CI...

...SCT should be considered for treatment of M...


Predominantly Antibody Deficiencies 

...nantly Antibody Deficiencies ...

...ammaglobulinem...

...Patients with very low or undetectable seru...

...aglobulinemia should be managed aggressively...

.... Enteroviral meningoencephalitis in p...

...4. Lung transplantation should be considered...


...able immunodeficiency (CVID)...

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

...ing of patients with CVID based on analysis of B-c...

...diseases, molecular defects, or bot...

...D should be managed aggressively wi...

...rointestinal status should be monitored regu...

.... Vigilance for possible autoimmune diseases shoul...

...91. Vigilance for nonmalignant and malign...

...S 92. Autoimmune, lymphoproliferative...

...93. Stem cell transplantation can...

...having hypogammaglobulinemia and thymom...

...ents with Good syndrome, thymomas shoul...


...elective IgA deficiency (SIGAD)...

...older than 4 years with a serum IgA level...

...tients with serum IgA levels of less than th...

...98. Patients with SIGAD should be monitored ov...

...Medication use should be investigate...

...0. Aggressive antimicrobial therapy, prophylaxis...

...topic disease should be treated ag...

...e patients with SIGAD might benefit from...


IgG subclass deficiency (I...

...103. A diagnosis of IGGSD should b...

...The principles of management of IGGSD sh...


...tibody deficiency (SAD) ...

...The diagnosis of SAD should be given t...

...Patients with SAD might benefit from additio...


...ng Serotype-Specific Responses to Pn...


...ransient hypogammaglobulinemia of inf...

...Infants and young children with frequent...

...ciples of management of THI should follow th...


...unoglobulin class-switch...

...Patients with immunoglobulin class-switch defects...

...S 110. The principles of management of immunoglobu...

...mmune, lymphoproliferative, or malignant diseases...


Unspecified hypogammaglobu...

...112. Any patient with primary hypo...

...nagement of unspecified hypogammaglobulinemia s...


...iseases of Immune Dysregulation...

...iagnosis of Diseases of Immune Dysr...


...iak-Higashi syndrome (CH...

...hould be suspected in patients with partial...

...xamination of a peripheral blood smear should...

SS 116. The treatment of HLH in patients...


...riscelli syndrome (GS) typ...

...type 2 should be suspected in patients...


...nsky-Pudlak syndrome (HPS)

...ype 2 should be suspected in patients w...


...hemophagocytic lymphohistiocytosis...

...FHL should be suspected in patients wit...

...0. Laboratory screening for FHL should be perfor...

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


...hoproliferative syndr...

...linked lymphoproliferative disease...

...s with suspected XLP should be screened by u...

...hould be given to patients with XLP and hypogamm...

...ents with XLP and HLH should be treated wit...


...ndromes with autoim...

...phoproliferative syndrome (ALPS) and ALPS–re...

...r an ALPS-related disorder should be su...

...asurement of T cells expressing th...

...128. Treatment of ALPS should be tailored to...

...polyendocrinopathy–candidiasis–...

...ED should be suspected in patients with immune-med...

...tients with clinical features consi...

...uppressive therapy should be considered in...

...ecific genetic lesions should be so...

IPEX synd...

...syndrome should be suspected in patients with se...

...sis of IPEX syndrome should be sought by...

...S 135. Initial treatment of IPEX syn...

...hould be considered early in the co...

...Other specific genetic lesions should be so...

...38. Complement deficiency should be...

...hagocytic Cell Defects

...4. Diagnosis of Phagocyte Defects...

...f neutrophil differentiation...

...ngenital neutropenia...

...139. Patients with recurrent bacterial r...

...nts with neutropenia should receive G-CSF (...

...should be considered for patients with se...

...of neutrophil motilit...

...hesion deficiency (LAD) types I, II, and I...

...142. LAD should be suspected in pati...

...43. A blood cell count should be the first scre...

...144. LAD-I/II should be diagnosed by using flow...

SS 145. Therapy for LAD-I/II should be s...

...e supplementation can ameliorate the c...

...is curative for LAD-I and LAD-III a...

...fic granule deficiency...

...hould be considered in patients with recurrent...

...anagement of SGD should be supportive, but HSCT...


...syndromes of defective neutrophil...

...50. Additional genetic lesions should be investi...


Defects of the respiratory burst

...of the respiratory burst...

...hronic granulomatous disease (CGD...

...should be suspected in patients with deep-se...

...surement of phagocyte oxidase activity should be...

...53. Patients with CGD should be given pr...

...S 154. Granulocyte transfusions should...

SS 155. In patients with CGD, aggressi...

...should be considered early in the...


Mendelian susceptibility to mycobacterial disease (MSMD)

...elian susceptibility to mycobacterial...

...ts with severe tuberculous or atypical...


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


...ent of MSMD should include vigilance fo...


...ts with partial IFNGR1/2 mutations and IL-12p40...


...HLA-identical sibling HSCT can be c...


Pulmonary alveolar proteinosis (PAP)

Pulmonary alveolar proteino...

...Patients with PAP should be tested for mu...