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immunodeficiency; immunodeficiency syndrome

Etiology: - humoral immune dysfunction - deficient antibody synthesis - IgG subclass deficiency - dysgammaglobulinemia - hypogammaglobulinemia - complement deficiency - cellular immune dysfunction - AIDS (HIV1 infection) - CD4 T-lymphocyte deficiency disorder - phagocytic disorder - neutrophil immunodeficiency syndrome - Chediak-Higashi syndrome - chronic granulomatous disease - asplenism - GATA2 deficiency - chronic mucocutaneous candidiasis - mixed cellular & humoral immune dysfunction - severe combined immune deficiency - Wiskott-Aldrich syndrome - common variable immunodeficiency - hyper IgE syndrome (Job's syndrome) - DiGeorge syndrome - Griscelli syndrome - LFA1 immunodeficiency disease - recurrent invasive pneumococcal disease - IRAK4 deficiency - immunosuppression - adult-onset congenital immunodeficiency syndromes [10] - chronic granulomatous disease - hyper IgE syndrome - GATA2 deficiency - common variable immunodeficiency Epidemiology: - prevalence of primary immunodeficiency is 1 in 1000 [13] Pathology: 1) Cellular immunologic dysfunction 1) associated conditions a) organ & bone marrow transplant patients - especially with severe mucositis b) AIDS patients c) therapy with glucocorticoids or cytotoxic agents d) lymphocytic neoplasms 2) characteristic pathogens: a) viruses 1] Herpes simplex 2] Herpes zoster/varicella 3] Cytomegalovirus 4] Epstein-Barr virus b) bacteria 1] Mycobacterium species 2] Legionella 3] Listeria monocytogenes 4] Salmonella 5] Nocardia c) fungi 1] Cryptococcus neoformans 2] Histoplasma capsulatum 3] Coccidioides immitis d) protozoa 1] Toxoplasma gondii 2] Pneumocystis carinii 3] Cryptosporidium parvum 2) Humoral immune dysfunction a) associated conditions - multiple myeloma - lymphoma - splenectomy - complement deficiency - properdin in males b) characteristic pathogens (recurrent infections) - encapsulated bacteria - Streptococcus pneumonia - Haemophilus influenzae - Pseudomonas aeruginosa - Neisseria (complement deficiency, late components) - N meningitidis - N gonorrhoeae - Mycoplasma 3) Neutrophil disorder - chronic granulomatous disease - invasive skin infections ... 4) Complement deficiency - infections with Neisseria sp, especially N gonorrhoeae Genetics: - > 400 genetic defects cause primary immunodeficiency [13] Laboratory: - see ARUP consult [2] Complications: - infections - noninfectious complications [13] - 43% of mortality - allergy - autoimmunity &/or inflammation in 1/3 of patients - cancer (7% of patients & 25% of mortality) [13] Management: - pneumococcal vaccination of all immunodeficient children 6-18 years of age with PCV13 (Prevnar) regardless of prior vaccination with pneumococcal polysaccharide vaccine [9]

Specific

asplenism cellular immune dysfunction DiGeorge syndrome; velocardiofacial syndrome; pharyngeal pouch syndrome dysgammaglobulinemia Griscelli syndrome humoral immune dysfunction hypogammaglobulinemia; immunoglobulin deficiency immunosuppression IRAK4 deficiency isolated immunodeficiency; pure immunodeficiency; immunodeficiency without anhidrotic ectodermal dysplasia LFA-1 immunodeficiency disease mixed cellular & humoral immune dysfunction recurrent invasive pneumococcal disease

General

chronic immunologic disease

References

  1. Medical Knowledge Self Assessment Program (MKSAP) 11, 14 American College of Physicians, Philadelphia 1998, 2006
  2. ARUP Consult: Immunodeficiency, Innate System, TLR-Signaling Defects The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/immunodeficiency-tlr-signaling-defects - Immunodeficiency Evaluation for Chronic Infections in Adults and Older Children Testing Algorithm https://arupconsult.com/algorithm/immunodeficiency-evaluation-chronic-infections-adults-and-older-children-testing-algorithm - Immunodeficiency Evaluation for Chronic Infections in Infants and Children Testing Algorithm https://arupconsult.com/algorithm/immunodeficiency-evaluation-chronic-infections-infants-and-children-testing-algorithm - ARUP consult: Primary Antibody Deficiency Panel, Sequencing and Deletion/Duplication. https://arupconsult.com/ati/Primary-Antibody-Deficiency-Panel
  3. Maarschalk-Ellerbroek LJ, Hoepelman IM, Ellerbroek PM. Immunoglobulin treatment in primary antibody deficiency. Int J Antimicrob Agents. 2011 May;37(5):396-404. PMID: 21276714
  4. Morimoto Y, Routes JM. Immunodeficiency overview. Prim Care. 2008 Mar;35(1):159-73 PMID: 18206723
  5. Nelson KS, Lewis DB. Adult-onset presentations of genetic immunodeficiencies: genes can throw slow curves. Curr Opin Infect Dis. 2010 Aug;23(4):359-64 PMID: 2058167
  6. Notarangelo LD. Primary immunodeficiencies. J Allergy Clin Immunol. 2010 Feb;125(2 Suppl 2):S182-94 PMID: 20042228
  7. Oliveira JB, Fleisher TA. Laboratory evaluation of primary immunodeficiencies. J Allergy Clin Immunol. 2010 Feb;125(2 Suppl 2):S297-305. PMID: 20042230
  8. Wood P; UK Primary Immunodeficiency Network. Primary antibody deficiencies: recognition, clinical diagnosis and referral of patients. Clin Med. 2009 Dec;9(6):595-9. PMID: 20095309
  9. Centers for Disease Control and Prevention (CDC) Use of 13-Valent Pneumococcal Conjugate Vaccine and 23-Valent Pneumococcal Polysaccharide Vaccine Among Children Aged 6-18 Years with Immunocompromising Conditions: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. June 28, 2013 / 62(25);521-524 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6225a3.htm
  10. Rothaus C A Man with Respiratory Failure Now@NEJM. Oct 16, 2015 http://blogs.nejm.org/now/index.php/a-man-with-respiratory-failure/2015/10/16/
  11. Uzzaman A, Fuleihan RL. Chapter 27: Approach to primary immunodeficiency. Allergy Asthma Proc. 2012 May-Jun;33 Suppl 1:S91-5. Review. PMID: 22794700
  12. Rubin LG, Levin MJ, Ljungman P et al for the Infectious Diseases Society of America. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014 Feb;58(3):309-18. PMID: 24421306 Free Article
  13. Alligon M et al. An appraisal of the frequency and severity of noninfectious manifestations in primary immunodeficiencies: A study of a national retrospective cohort of 1375 patients over 10 years. J Allergy Clin Immunol 2022 Jun; 149:2116-2125 PMID: 35031273 https://www.jacionline.org/article/S0091-6749(22)00039-2/fulltext
  14. National Institute of Allergy and Infectious Diseases (NIAID) Overview of the Immune System https://www.niaid.nih.gov/research/immune-system-overview