Common variable immunodeficiency: Difference between revisions

Jump to navigation Jump to search
No edit summary
Line 321: Line 321:
  | doi = 10.1182/blood-2012-05-431064
  | doi = 10.1182/blood-2012-05-431064
  | pmid = 22936739
  | pmid = 22936739
}}</ref
}}</ref>


==Diagnosis==
==Diagnosis==

Revision as of 16:59, 21 August 2018

  • Prophylactic antibiotics for patients with recurrent sinopulmonary infections. Evidence in support of this approach is largely derived from benefits observed in retrospective studies of children with this and similar antibody deficiencies.
Common variable immunodeficiency
ICD-10 D83
ICD-9 279.06
OMIM 240500
DiseasesDB 3274
MeSH D017074

WikiDoc Resources for Common variable immunodeficiency

Articles

Most recent articles on Common variable immunodeficiency

Most cited articles on Common variable immunodeficiency

Review articles on Common variable immunodeficiency

Articles on Common variable immunodeficiency in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Common variable immunodeficiency

Images of Common variable immunodeficiency

Photos of Common variable immunodeficiency

Podcasts & MP3s on Common variable immunodeficiency

Videos on Common variable immunodeficiency

Evidence Based Medicine

Cochrane Collaboration on Common variable immunodeficiency

Bandolier on Common variable immunodeficiency

TRIP on Common variable immunodeficiency

Clinical Trials

Ongoing Trials on Common variable immunodeficiency at Clinical Trials.gov

Trial results on Common variable immunodeficiency

Clinical Trials on Common variable immunodeficiency at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Common variable immunodeficiency

NICE Guidance on Common variable immunodeficiency

NHS PRODIGY Guidance

FDA on Common variable immunodeficiency

CDC on Common variable immunodeficiency

Books

Books on Common variable immunodeficiency

News

Common variable immunodeficiency in the news

Be alerted to news on Common variable immunodeficiency

News trends on Common variable immunodeficiency

Commentary

Blogs on Common variable immunodeficiency

Definitions

Definitions of Common variable immunodeficiency

Patient Resources / Community

Patient resources on Common variable immunodeficiency

Discussion groups on Common variable immunodeficiency

Patient Handouts on Common variable immunodeficiency

Directions to Hospitals Treating Common variable immunodeficiency

Risk calculators and risk factors for Common variable immunodeficiency

Healthcare Provider Resources

Symptoms of Common variable immunodeficiency

Causes & Risk Factors for Common variable immunodeficiency

Diagnostic studies for Common variable immunodeficiency

Treatment of Common variable immunodeficiency

Continuing Medical Education (CME)

CME Programs on Common variable immunodeficiency

International

Common variable immunodeficiency en Espanol

Common variable immunodeficiency en Francais

Business

Common variable immunodeficiency in the Marketplace

Patents on Common variable immunodeficiency

Experimental / Informatics

List of terms related to Common variable immunodeficiency

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Mohsen Basiri M.D.

Synonyms and keywords: CVID; common variable hypogammaglobulinaemia; non-familial hypogammaglobulinaemia; acquired hypogammaglobulinemia; immunodeficiency, common variable; late-onset immunoglobulin deficiency

Overview

Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder. It is the most common form of severe antibody deficiency affecting both children and adults. The characteristic immune defect in CVID is impaired B cell differentiation with defective production of immunoglobulin. CVID is defined by low total serum concentrations of immunoglobulin G (IgG), as well as low immunoglobulin A (IgA) and/or immunoglobulin M (IgM), poor or absent response to immunization, and the absence of any other defined immunodeficiency state.

Most patients are diagnosed between the ages of 20 and 40 years. Delayed recognition is common.

Bacterial infections of the sinopulmonary tract, particularly sinusitis and pneumonia, are experienced by most patients with CVID. Opportunistic and unusual infections are uncommon, but do occur.

In addition to recurrent infections, patients with CVID have evidence of immune dysregulation leading to autoimmunity, a variety of inflammatory disorders, and malignant disease. Patients may suffer from chronic lung disease, gastrointestinal and liver disorders, granulomatous infiltrations, lymphoid hyperplasia, splenomegaly, or malignancy.

Various forms of primary and secondary hypogammaglobulinemia must be excluded before the diagnosis of CVID can be assigned.The diagnosis of CVID requires a suggestive clinical history, a reduced total serum concentration of IgG, plus low IgA or IgM, and poor responses to both protein- and polysaccharide-based vaccines.

Historical Perspective

In 1953, Charles Janeway was the first to describe the first case of CVID. The case was a 39-year-old who had recurrent infections, bronchiectasis, and meningitis.[1] However described in 1953, there were no standard criteria for CVID which caused confusion during diagnosis. In the decade from the 1990s, the European Society for Immunodeficiency (ESID) and Pan-American Group for Immunodeficiency (PAGID) determined diagnostic criteria, including minimum age of diagnosis and the need to rule out other diseases, to determine the disease. These criteria were published in 1999 and since that time, some aspects, like increasing the minimum age, have been modified.

Classification

Common variable immunodeficiency (CVID) is a heterogeneous immune disorder characterized by recurrent sinopulmonary infections, autoimmune diseases, granulomatous disease, and an enhanced risk of malignancy.

A phenotypic approach to clssify CVID has been suggested, based upon the type of complications the patient demonstrates. This method is from an analysis of the European Common Variable Immunodeficiency Disorders registry, in which 334 patients with CVID were followed for an average of 26 years . Five phenotypic categories were proposed:[2]

  1. Patients with no complications.
  2. Patients with autoimmune disease.
  3. Patients with lymphocytic organ infiltration i.e. lymphocytic enteropathy, granulomas, unexplained hepatomegaly, persistent lymphadenopathy, splenomegaly.
  4. Patients with predominant enteropathy
  5. Patients with lymphoid malignancy

Pathophysiology

The exact pathophysiology of CVID is not fully understood. CVID is a group of disorders with a common endpoint of defective immunoglobulin secretion and dysregulated immune functions. The clinical dissimilarity of CVID proposes that multiple immunoregulatory dysfunctions can result in the final common pathway of hypogammaglobulinemia. [3]


The immune defect in CVID is due to defective B cell differentiation into plasma cells, with the inability to produce immunoglobulin. CVID is associated with a high occurrence of autoimmune, inflammatory, and malignant disorders, whereas these conditions are not observed in X-linked agammaglobulinemia (XLA), a disease that affects early B cell development.

CVID appears to result from a number of gene defects. which may be either recessive in inheritance or autosomal dominant with variable penetrance. Some of these are due to defects of B cell signalling molecules but additional genes affecting immune regulation may also lead to the CVID phenotype.

Type Gene Immunoglobulin Deficiency Phenotype
ICOS deficiency ICOS Low IgG and IgA Recurrent infections, autoimmunity, gastroenteritis.
CD19 deficiency CD19 Low IgG and IgA Recurrent infections.

May be associated with glomerulonephritis.

CD81 deficiency CD81 Low IgG, low or normal IgA and IgM Recurrent infections.

May be associated with glomerulonephritis.

CD20 deficiency CD20 Low IgG, normal or elevated IgM, and IgA Recurrent infections.
CD21 deficiency CD21 Low IgG; impaired antipneumococcal response Recurrent infections.
TACI deficiency TNFRSF13B Low IgG and IgA and/or IgM Variable clinical expression
BAFF-receptor

deficiency

TNFRSF13C Low IgG and IgM Variable clinical expression
TWEAK deficiency TWEAK Low IgM and IgA; lack of antipneumococcal antibody Recurrent infections such as Pneumonia, bacterial infections, warts;

and thrombocytopenia; neutropenia

NF-kappa-B2

deficiency

NFKB2 Low IgG and IgA and IgM; very low B cells in some Recurrent infections; adrenal insufficiency;

ACTH deficiency; alopecia

NF-kappa-B1

deficiency

NFKB1 Low IgG and IgA and IgM; low B cells in some Recurrent infections
IKAROS IKZF1 Low IgG and IgA and IgM, very low B cells Recurrent infections

Causes

The cause of common variable immunodeficiency has not been identified. Genetic mutations can be recognized as the cause of CVID in about 10% of patients, and familial inheritance accounts for 10-25% of the affected population. Rather than arising from a single genetic mutation, CVID is due to numerous mutations that all are associated with dysfunction in antibody regulation and production.[4]

Differentiating Common Variable Immunodeficiency from other Diseases

CVID should be differentiated from the following diseases:

Epidemiology and Demographics

Prevalence

CVID has an estimated prevalence ranging from a low of 2 per 100,000 to a high of 4 per 100,000 with an average of 3 per 100,000.

Age

  • The typical patient is after puberty and between 20 and 40 years age.
  • About 20% of patients are diagnosed in childhood.
  • In an analysis of the CVID data from the ESID about 35 percent of patients were diagnosed before 10 years of age; and in studies from United States centers, 20 percent of patients are diagnosed before the age of 20 years. The majority of patients are diagnosed between the ages of 20 and 45. [5] [6]

Gender

There is no gender predilection to common variable immunodeficiency.

Race

Race is not associated with an increased risk of common variable immunodeficiency. However, there is some evidence of higher prevalence among individuals of northern European descent.[7]

Natural History, Complications and Prognosis

Natural History

All patients have several histories of acute and recurrent infections. The majority of patients with CVID have evidence of immune dysregulation leading to autoimmunity, inflammatory disorders, and malignant disease. Accordingly, CVID Patients may suffer from chronic lung disease, gastrointestinal and liver disorders, granulomatous infiltrations of several organs, lymphoid hyperplasia, splenomegaly, or malignancy.[8]The clinical manifestations of CVID affect multiple organ systems, and patients often have the history of several specialists visits by the time they are recognized. It may be partly for this reason, delayed diagnosis of this condition is common. in the European Society for Immunodeficiencies (ESID) database, and other studies, there was an average of five to seven years between the beginning of symptoms and diagnosis[9][10]

Complications

Numerous complications are possible in CVID. They include:[11][12][13]

Prognosis

Prognosis with the advent of immune globulin treatment is generally good, and the incidence of death associated with acute bacterial infection in CVID decreased dramatically.[14] Afterwards, the leading causes of death are owing to complications of chronic lung disease and malignancies.

In the several large series of following patients with CVID, the leading causes of death were respiratory failure due to bronchiectasis, lymphoma, and liver disease.[15][16]

Diagnosis

History and Symptoms

Symptoms of CVID are:

Physical Examination

Head

Abdomen

Laboratory Findings

Diagnosis is often delayed; and diagnosis is often made in the second or third decade of life after referral to an immunologist. As with several other immune cell disorders, CVID may predispose to lymphoma or possibly stomach cancer. There also appears to be a predilection for autoimmune diseases, with a risk of up to 25%. Autoimmune destruction of platelets or red blood cells are the commonest of these.

Treatment

Medical Therapy

  • Immune Globulin Replacement Therapy

The mainstay of treatment for CVID is immune globulin replacement therapy. In addition, management requires precise monitoring for associated conditions, such as sinopulmonary, granulomatous, gastrointestinal, and autoimmune diseases, and malignancy.<ref>Charlotte Cunningham-Rundles (2010). "How I treat common variable immune deficiency". Blood. 116 (1): 7–15. doi:10.1182/blood-2010-01-254417. PMID 20332369. Unknown parameter |month= ignored (help)</ref>

Treatment

The mainstay of treatment for CVID is Immune globulin replacement therapy, an injection of human antibodies harvested from blood donations which may be administered either intravenously or subcutaneously:

  • Intravenous immunoglobulin (IVIG, most common treatment) .The routine initial dosing for IVIG is 300 to 600 mg/kg every three to four weeks.
  • Subcutaneous immunoglobulin G (SCIG, relatively new therapy), As an alternative to IVIG which is usually administered weekly or every other week. Dose depends on body weight and immune globulin requirements.
  • Intramuscular immunoglobulin (IMIG, less effective, painful).

Immune globulin replacement therapy reduces the number of infections and decreases antibiotic use and hospitalizations.[17] This therapy is not a cure, but it strengthens immunity in hypogammaglobulinemic patients, which helps to prevent recurrent upper respiratory infections, and fewer serious infections and days of hospitalization among patients with primary immunodeficiency . However, immune globulin therapy does not completely eliminate infections in most patients, and the sinopulmonary and gastrointestinal systems, in particular, remain susceptible.[18]

IG therapy should not be used if the patient has anti-IgA antibodies but in these cases, products low in IgA can be used; subcutaneous delivery also is a means of permitting such patients to have adequate antibody replacement.

IVIG treatment can be received by patients with a complete IgA deficiency if the IgA is completely removed from the treatment.

Some CVID patients may experience reactions to IG therapies; reactions may include:

Reactions can be minimized by taking an antihistamine and/or hydrocortisone and some paracetamol/acetaminophen/anti-inflammatory (naproxen, advil, aspirin) prior to treatment; patients should also be thoroughly hydrated and continue to drink water before, after and during treatment (if possible).

  • Antimcrobial Therapy

Antibiotics may be administered prophylactically, as well as for the treatment of acute infections or exacerbations of chronic infections.

  • Prophylactic antibiotics do not routinely administer to all patients with CVID. In CVID patients with ongoing lung disease, and with recurrent sinopulmonary infections, this approach is helpful.
  • Antibiotics are required for management of acute infections among patients with immunodeficiency. CVID patients typically do not clear common infections without the use of proper antibiotics. Thus, immediate recognition and treatment with antibiotics can help prevent chronic infections and infectious complications. It is important to ensure that the infection has treated completely at the end of a course of antibiotics, as patients with immunodeficiency sometimes necessitate longer duration of therapy. Antibiotic resistance does not seem to be a serious problem in patients with CVID, for causes which are not clearly understood, then the same antibiotics continue to be useful, regardless of prolonged or frequent exposure.[19]

Prevention

  • There are no primary preventive measures available for common variable immunodeficiency.
  • Secondary and tertiary prevention strategies following CVID include avoidance measures, vaccination, prophylactic antibiotics, immune globulin therapy, and when infections do occur, broader spectrum and more prolonged antibiotics are often recommended.
  • Avoidance: to reduce exposure to others with potentially contagious illnesses: proper hand-washing and use of alcohol-based disinfectants should be provided to patients and their families; Co-sleeping among family members should be minimized, and immunization of family members and close contacts is required.
  • Careful attention should be paid to patient's oral hygiene and dental health.
  • The efficiency of killed or inactivated vaccines in patients with CVID has not been evaluated extensively. It means patients with CVID have impaired responses to vaccination, however, vaccination might augment T cell immunity to viral agents, in addition to inducing the formation of specific antibodies. Certain live vaccines i.e. oral polio, smallpox, live-attenuated influenza vaccine, yellow fever, or live oral typhoid vaccines should not be given to patients with CVID , particularly those with significantly impaired T cell function.[20]

References

  1. Janeway CA, Apt L, Gitlin D. Agammaglobulinemia. Trans Assoc Am Physicians 1953;66:200-2. PMID 13136263
  2. Helen Chapel, Mary Lucas, Martin Lee, Janne Bjorkander, David Webster, Bodo Grimbacher, Claire Fieschi, Vojtech Thon, Mohammad R. Abedi & Lennart Hammarstrom (2008). "Common variable immunodeficiency disorders: division into distinct clinical phenotypes". Blood. 112 (2): 277–286. doi:10.1182/blood-2007-11-124545. PMID 18319398. Unknown parameter |month= ignored (help)
  3. C. Cunningham-Rundles & C. Bodian (1999). "Common variable immunodeficiency: clinical and immunological features of 248 patients". Clinical immunology (Orlando, Fla.). 92 (1): 34–48. doi:10.1006/clim.1999.4725. PMID 10413651. Unknown parameter |month= ignored (help)
  4. Park, Miguel A; Li, James T; Hagan, John B; Maddox, Daniel E; Abraham, Roshini S (2008). "Common variable immunodeficiency: a new look at an old disease". The Lancet. 372 (9637): 489–502. doi:10.1016/S0140-6736(08)61199-X. ISSN 0140-6736.
  5. C. Cunningham-Rundles & C. Bodian (1999). "Common variable immunodeficiency: clinical and immunological features of 248 patients". Clinical immunology (Orlando, Fla.). 92 (1): 34–48. doi:10.1006/clim.1999.4725. PMID 10413651. Unknown parameter |month= ignored (help)
  6. R. A. Hermaszewski & A. D. Webster (1993). "Primary hypogammaglobulinaemia: a survey of clinical manifestations and complications". The Quarterly journal of medicine. 86 (1): 31–42. PMID 8438047. Unknown parameter |month= ignored (help)
  7. L. Hammarstrom, I. Vorechovsky & D. Webster (2000). "Selective IgA deficiency (SIgAD) and common variable immunodeficiency (CVID)". Clinical and experimental immunology. 120 (2): 225–231. PMID 10792368. Unknown parameter |month= ignored (help)
  8. L. Hammarstrom, I. Vorechovsky & D. Webster (2000). "Selective IgA deficiency (SIgAD) and common variable immunodeficiency (CVID)". Clinical and experimental immunology. 120 (2): 225–231. PMID 10792368. Unknown parameter |month= ignored (help)
  9. C. Cunningham-Rundles & C. Bodian (1999). "Common variable immunodeficiency: clinical and immunological features of 248 patients". Clinical immunology (Orlando, Fla.). 92 (1): 34–48. doi:10.1006/clim.1999.4725. PMID 10413651. Unknown parameter |month= ignored (help)
  10. Benjamin Gathmann, Nizar Mahlaoui, Laurence Gerard, Eric Oksenhendler, Klaus Warnatz, Ilka Schulze, Gerhard Kindle, Taco W. Kuijpers, Rachel T. van Beem, David Guzman, Sarita Workman, Pere Soler-Palacin, Javier De Gracia, Torsten Witte, Reinhold E. Schmidt, Jiri Litzman, Eva Hlavackova, Vojtech Thon, Michael Borte, Stephan Borte, Dinakantha Kumararatne, Conleth Feighery, Hilary Longhurst, Matthew Helbert, Anna Szaflarska, Anna Sediva, Bernd H. Belohradsky, Alison Jones, Ulrich Baumann, Isabelle Meyts, Necil Kutukculer, Per Wagstrom, Nermeen Mouftah Galal, Joachim Roesler, Evangelia Farmaki, Natalia Zinovieva, Peter Ciznar, Efimia Papadopoulou-Alataki, Kirsten Bienemann, Sirje Velbri, Zoya Panahloo & Bodo Grimbacher (2014). "Clinical picture and treatment of 2212 patients with common variable immunodeficiency". The Journal of allergy and clinical immunology. 134 (1): 116–126. doi:10.1016/j.jaci.2013.12.1077. PMID 24582312. Unknown parameter |month= ignored (help)
  11. L. Hammarstrom, I. Vorechovsky & D. Webster (2000). "Selective IgA deficiency (SIgAD) and common variable immunodeficiency (CVID)". Clinical and experimental immunology. 120 (2): 225–231. PMID 10792368. Unknown parameter |month= ignored (help)
  12. R. A. Hermaszewski & A. D. Webster (1993). "Primary hypogammaglobulinaemia: a survey of clinical manifestations and complications". The Quarterly journal of medicine. 86 (1): 31–42. PMID 8438047. Unknown parameter |month= ignored (help)
  13. Elena S. Resnick, Erin L. Moshier, James H. Godbold & Charlotte Cunningham-Rundles (2012). "Morbidity and mortality in common variable immune deficiency over 4 decades". Blood. 119 (7): 1650–1657. doi:10.1182/blood-2011-09-377945. PMID 22180439. Unknown parameter |month= ignored (help)
  14. Elena S. Resnick, Erin L. Moshier, James H. Godbold & Charlotte Cunningham-Rundles (2012). "Morbidity and mortality in common variable immune deficiency over 4 decades". Blood. 119 (7): 1650–1657. doi:10.1182/blood-2011-09-377945. PMID 22180439. Unknown parameter |month= ignored (help)
  15. Helen Chapel, Mary Lucas, Martin Lee, Janne Bjorkander, David Webster, Bodo Grimbacher, Claire Fieschi, Vojtech Thon, Mohammad R. Abedi & Lennart Hammarstrom (2008). "Common variable immunodeficiency disorders: division into distinct clinical phenotypes". Blood. 112 (2): 277–286. doi:10.1182/blood-2007-11-124545. PMID 18319398. Unknown parameter |month= ignored (help)
  16. Isabella Quinti, Carlo Agostini, Stefano Tabolli, Grazia Brunetti, Francesco Cinetto, Antonio Pecoraro & Giuseppe Spadaro (2012). "Malignancies are the major cause of death in patients with adult onset common variable immunodeficiency". Blood. 120 (9): 1953–1954. doi:10.1182/blood-2012-05-431064. PMID 22936739. Unknown parameter |month= ignored (help)
  17. Paula Jane Busse, Samiya Razvi & Charlotte Cunningham-Rundles (2002). "Efficacy of intravenous immunoglobulin in the prevention of pneumonia in patients with common variable immunodeficiency". The Journal of allergy and clinical immunology. 109 (6): 1001–1004. PMID 12063531. Unknown parameter |month= ignored (help)
  18. Benjamin Gathmann, Nizar Mahlaoui, Laurence Gerard, Eric Oksenhendler, Klaus Warnatz, Ilka Schulze, Gerhard Kindle, Taco W. Kuijpers, Rachel T. van Beem, David Guzman, Sarita Workman, Pere Soler-Palacin, Javier De Gracia, Torsten Witte, Reinhold E. Schmidt, Jiri Litzman, Eva Hlavackova, Vojtech Thon, Michael Borte, Stephan Borte, Dinakantha Kumararatne, Conleth Feighery, Hilary Longhurst, Matthew Helbert, Anna Szaflarska, Anna Sediva, Bernd H. Belohradsky, Alison Jones, Ulrich Baumann, Isabelle Meyts, Necil Kutukculer, Per Wagstrom, Nermeen Mouftah Galal, Joachim Roesler, Evangelia Farmaki, Natalia Zinovieva, Peter Ciznar, Efimia Papadopoulou-Alataki, Kirsten Bienemann, Sirje Velbri, Zoya Panahloo & Bodo Grimbacher (2014). "Clinical picture and treatment of 2212 patients with common variable immunodeficiency". The Journal of allergy and clinical immunology. 134 (1): 116–126. doi:10.1016/j.jaci.2013.12.1077. PMID 24582312. Unknown parameter |month= ignored (help)
  19. A. Samuelson, S. Borrelli, R. Gustafson, L. Hammarstrom, C. I. Smith, J. Jonasson & A. A. Lindberg (1995). "Characterization of Haemophilus influenzae isolates from the respiratory tract of patients with primary antibody deficiencies: evidence for persistent colonizations". Scandinavian journal of infectious diseases. 27 (4): 303–313. PMID 8658061.
  20. William T. Shearer, Thomas A. Fleisher, Rebecca H. Buckley, Zuhair Ballas, Mark Ballow, R. Michael Blaese, Francisco A. Bonilla, Mary Ellen Conley, Charlotte Cunningham-Rundles, Alexandra H. Filipovich, Ramsay Fuleihan, Erwin W. Gelfand, Vivian Hernandez-Trujillo, Steven M. Holland, Richard Hong, Howard M. Lederman, Harry L. Malech, Stephen Miles, Luigi D. Notarangelo, Hans D. Ochs, Jordan S. Orange, Jennifer M. Puck, John M. Routes, E. Richard Stiehm, Kathleen Sullivan, Troy Torgerson & Jerry Winkelstein (2014). "Recommendations for live viral and bacterial vaccines in immunodeficient patients and their close contacts". The Journal of allergy and clinical immunology. 133 (4): 961–966. doi:10.1016/j.jaci.2013.11.043. PMID 24582311. Unknown parameter |month= ignored (help)

External links


Template:WikiDoc Sources