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Erschienen in: Journal of Clinical Immunology 7/2019

01.08.2019 | Original Article

How to Identify Common Variable Immunodeficiency Patients Earlier: General Practice Patterns

verfasst von: Frederik V. Ilkjær, Line D. Rasmussen, Raquel Martin-Iguacel, Lena Westh, Terese L. Katzenstein, Ann-Brit E. Hansen, Thyge L. Nielsen, Carsten S. Larsen, Isik S. Johansen

Erschienen in: Journal of Clinical Immunology | Ausgabe 7/2019

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Abstract

Purpose

Diagnostic delay is a major problem concerning common variable immunodeficiency (CVID). We aimed to determine the pattern of general practitioner (GP) consultations in individuals diagnosed with CVID within 3 years before the diagnosis and whether the risk of diagnosis was associated with the frequency of consultations or character of examinations.

Methods

We conducted a nested case-control study, identifying 132 adult CVID patients and 5940 age- and gender-matched controls from national registers during 1997–2013. We used conditional logistic regression to calculate the odds ratios (OR) and 95% confidence intervals (95%CI).

Results

The median number of consultations among individuals with CVID was more than twice that of the controls in all 3 years (3rd, 10; 2nd, 11.5; and 1st, 15.4 vs. 4). We found a statistically significant association between the number of consultations and the risk of a subsequent CVID diagnosis, independent of age and gender, but strongest in the individuals < 40 years. In the 3rd year before diagnosis, having 9–15 consultations compared with 1–4 was associated with an OR (95%CI) of 5.0 (2.3–10.9), 2.4 (1.1–5.4), and 1.3 (0.3–5.3) for those aged 18–40, 41–60, and > 60, respectively. Several examinations (i.e., blood tests for inflammation/infection and pulmonary function test) were associated with increased odds of a subsequent CVID diagnosis.

Conclusion

The risk of a CVID diagnosis was highly related to both the number of consultations and the character of examinations performed by the GP. CVID should be a differential diagnosis among patients with multiple consultations, especially in patients < 40 years old.
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Literatur
1.
Zurück zum Zitat Selenius JS, Martelius T, Pikkarainen S, Siitonen S, Mattila E, Pietikainen R, et al. Unexpectedly high prevalence of common variable immunodeficiency in Finland. Front Immunol. 2017;8:1190.CrossRefPubMedPubMedCentral Selenius JS, Martelius T, Pikkarainen S, Siitonen S, Mattila E, Pietikainen R, et al. Unexpectedly high prevalence of common variable immunodeficiency in Finland. Front Immunol. 2017;8:1190.CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Gathmann B, Grimbacher B, Beaute J, Dudoit Y, Mahlaoui N, Fischer A, et al. The European Internet-based patient and research database for primary immunodeficiencies: results 2006-2008. Clin Exp Immunol. 2009;157(Suppl 1):3–11.CrossRefPubMedPubMedCentral Gathmann B, Grimbacher B, Beaute J, Dudoit Y, Mahlaoui N, Fischer A, et al. The European Internet-based patient and research database for primary immunodeficiencies: results 2006-2008. Clin Exp Immunol. 2009;157(Suppl 1):3–11.CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat Westh L, Mogensen TH, Dalgaard LS, Bernth Jensen JM, Katzenstein T, Hansen AE, et al. Identification and characterization of a Nationwide Danish Adult Common Variable Immunodeficiency Cohort. Scand J Immunol. 2017;85(6):450–61.CrossRefPubMed Westh L, Mogensen TH, Dalgaard LS, Bernth Jensen JM, Katzenstein T, Hansen AE, et al. Identification and characterization of a Nationwide Danish Adult Common Variable Immunodeficiency Cohort. Scand J Immunol. 2017;85(6):450–61.CrossRefPubMed
4.
Zurück zum Zitat Tuijnenburg P, Lango Allen H, Burns SO, Greene D, Jansen MH, Staples E, et al. Loss of function NFKB1 variants are the most common monogenic cause of CVID in Europeans. J Allergy Clin Immunol. 2018;142:1285–96.CrossRefPubMedPubMedCentral Tuijnenburg P, Lango Allen H, Burns SO, Greene D, Jansen MH, Staples E, et al. Loss of function NFKB1 variants are the most common monogenic cause of CVID in Europeans. J Allergy Clin Immunol. 2018;142:1285–96.CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat de Valles-Ibanez G, Esteve-Sole A, Piquer M, Gonzalez-Navarro EA, Hernandez-Rodriguez J, Laayouni H, et al. Evaluating the genetics of common variable immunodeficiency: monogenetic model and beyond. Front Immunol. 2018;9:636.CrossRefPubMedPubMedCentral de Valles-Ibanez G, Esteve-Sole A, Piquer M, Gonzalez-Navarro EA, Hernandez-Rodriguez J, Laayouni H, et al. Evaluating the genetics of common variable immunodeficiency: monogenetic model and beyond. Front Immunol. 2018;9:636.CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Yazdani R, Abolhassani H, Kiaee F, Habibi S, Azizi G, Tavakol M, et al. Comparison of common monogenic defects in a large predominantly antibody deficiency cohort. J Allergy Clin Immunol Pract. 2019;7(3):864–78.e9.CrossRefPubMed Yazdani R, Abolhassani H, Kiaee F, Habibi S, Azizi G, Tavakol M, et al. Comparison of common monogenic defects in a large predominantly antibody deficiency cohort. J Allergy Clin Immunol Pract. 2019;7(3):864–78.e9.CrossRefPubMed
7.
Zurück zum Zitat Gathmann B, Mahlaoui N, Gerard L, Oksenhendler E, Warnatz K, Schulze I, et al. Clinical picture and treatment of 2212 patients with common variable immunodeficiency. J Allergy Clin Immunol. 2014;134(1):116–26.CrossRefPubMed Gathmann B, Mahlaoui N, Gerard L, Oksenhendler E, Warnatz K, Schulze I, et al. Clinical picture and treatment of 2212 patients with common variable immunodeficiency. J Allergy Clin Immunol. 2014;134(1):116–26.CrossRefPubMed
8.
Zurück zum Zitat Resnick ES, Moshier EL, Godbold JH, Cunningham-Rundles C. Morbidity and mortality in common variable immune deficiency over 4 decades. Blood. 2012;119(7):1650–7.CrossRefPubMedPubMedCentral Resnick ES, Moshier EL, Godbold JH, Cunningham-Rundles C. Morbidity and mortality in common variable immune deficiency over 4 decades. Blood. 2012;119(7):1650–7.CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Slade CA, Bosco JJ, Binh Giang T, Kruse E, Stirling RG, Cameron PU, et al. Delayed diagnosis and complications of predominantly antibody deficiencies in a cohort of Australian adults. Front Immunol. 2018;9:694.CrossRefPubMedPubMedCentral Slade CA, Bosco JJ, Binh Giang T, Kruse E, Stirling RG, Cameron PU, et al. Delayed diagnosis and complications of predominantly antibody deficiencies in a cohort of Australian adults. Front Immunol. 2018;9:694.CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Graziano V, Pecoraro A, Mormile I, Quaremba G, Genovese A, Buccelli C, et al. Delay in diagnosis affects the clinical outcome in a cohort of cvid patients with marked reduction of iga serum levels. Clin Immunol. 2017;180:1–4.CrossRefPubMed Graziano V, Pecoraro A, Mormile I, Quaremba G, Genovese A, Buccelli C, et al. Delay in diagnosis affects the clinical outcome in a cohort of cvid patients with marked reduction of iga serum levels. Clin Immunol. 2017;180:1–4.CrossRefPubMed
11.
Zurück zum Zitat Quinti I, Soresina A, Spadaro G, Martino S, Donnanno S, Agostini C, et al. Long-term follow-up and outcome of a large cohort of patients with common variable immunodeficiency. J Clin Immunol. 2007;27(3):308–16.CrossRefPubMed Quinti I, Soresina A, Spadaro G, Martino S, Donnanno S, Agostini C, et al. Long-term follow-up and outcome of a large cohort of patients with common variable immunodeficiency. J Clin Immunol. 2007;27(3):308–16.CrossRefPubMed
12.
Zurück zum Zitat Ameratunga R, Brewerton M, Slade C, Jordan A, Gillis D, Steele R, et al. Comparison of diagnostic criteria for common variable immunodeficiency disorder. Front Immunol. 2014;5:415.CrossRefPubMedPubMedCentral Ameratunga R, Brewerton M, Slade C, Jordan A, Gillis D, Steele R, et al. Comparison of diagnostic criteria for common variable immunodeficiency disorder. Front Immunol. 2014;5:415.CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Odnoletkova I, Kindle G, Quinti I, Grimbacher B, Knerr V, Gathmann B, et al. The burden of common variable immunodeficiency disorders: a retrospective analysis of the European Society for Immunodeficiency (ESID) registry data. Orphanet J Rare Dis. 2018;13(1):201.CrossRefPubMedPubMedCentral Odnoletkova I, Kindle G, Quinti I, Grimbacher B, Knerr V, Gathmann B, et al. The burden of common variable immunodeficiency disorders: a retrospective analysis of the European Society for Immunodeficiency (ESID) registry data. Orphanet J Rare Dis. 2018;13(1):201.CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Sadeghi B, Abolhassani H, Naseri A, Rezaei N, Aghamohammadi A. Economic burden of common variable immunodeficiency: annual cost of disease. Expert Rev Clin Immunol. 2015;11(5):681–8.CrossRefPubMed Sadeghi B, Abolhassani H, Naseri A, Rezaei N, Aghamohammadi A. Economic burden of common variable immunodeficiency: annual cost of disease. Expert Rev Clin Immunol. 2015;11(5):681–8.CrossRefPubMed
15.
Zurück zum Zitat Hajjar J, Kutac C, Rider NL, Seeborg FO, Scalchunes C, Orange J. Fatigue and the wear-off effect in adult patients with common variable immunodeficiency. Clin Exp Immunol. 2018;194(3):327–38.CrossRefPubMedPubMedCentral Hajjar J, Kutac C, Rider NL, Seeborg FO, Scalchunes C, Orange J. Fatigue and the wear-off effect in adult patients with common variable immunodeficiency. Clin Exp Immunol. 2018;194(3):327–38.CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Rider NL, Kutac C, Hajjar J, Scalchunes C, Seeborg FO, Boyle M, et al. Health-related quality of life in adult patients with common variable immunodeficiency disorders and impact of treatment. J Clin Immunol. 2017;37(5):461–75.CrossRefPubMedPubMedCentral Rider NL, Kutac C, Hajjar J, Scalchunes C, Seeborg FO, Boyle M, et al. Health-related quality of life in adult patients with common variable immunodeficiency disorders and impact of treatment. J Clin Immunol. 2017;37(5):461–75.CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Tabolli S, Giannantoni P, Pulvirenti F, La Marra F, Granata G, Milito C, et al. Longitudinal study on health-related quality of life in a cohort of 96 patients with common variable immune deficiencies. Front Immunol. 2014;5:605.CrossRefPubMedPubMedCentral Tabolli S, Giannantoni P, Pulvirenti F, La Marra F, Granata G, Milito C, et al. Longitudinal study on health-related quality of life in a cohort of 96 patients with common variable immune deficiencies. Front Immunol. 2014;5:605.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Pedersen KM, Andersen JS, Sondergaard J. General practice and primary health care in Denmark. J Am Board Fam Med. 2012;25(Suppl 1):S34–8.CrossRefPubMed Pedersen KM, Andersen JS, Sondergaard J. General practice and primary health care in Denmark. J Am Board Fam Med. 2012;25(Suppl 1):S34–8.CrossRefPubMed
20.
Zurück zum Zitat Schmidt M, Pedersen L, Sorensen HT. The Danish Civil Registration System as a tool in epidemiology. Eur J Epidemiol. 2014;29(8):541–9.CrossRefPubMed Schmidt M, Pedersen L, Sorensen HT. The Danish Civil Registration System as a tool in epidemiology. Eur J Epidemiol. 2014;29(8):541–9.CrossRefPubMed
21.
Zurück zum Zitat Andersen JS, Olivarius Nde F, Krasnik A. The Danish National Health Service Register. Scand J Public Health. 2011;39(7 Suppl):34–7.CrossRefPubMed Andersen JS, Olivarius Nde F, Krasnik A. The Danish National Health Service Register. Scand J Public Health. 2011;39(7 Suppl):34–7.CrossRefPubMed
22.
Zurück zum Zitat Lynge E, Sandegaard JL, Rebolj M. The Danish National Patient Register. Scand J Public Health. 2011;39(7 Suppl):30–3.CrossRefPubMed Lynge E, Sandegaard JL, Rebolj M. The Danish National Patient Register. Scand J Public Health. 2011;39(7 Suppl):30–3.CrossRefPubMed
23.
Zurück zum Zitat Thygesen LC, Daasnes C, Thaulow I, Bronnum-Hansen H. Introduction to Danish (nationwide) registers on health and social issues: structure, access, legislation, and archiving. Scand J Public Health. 2011;39(7 Suppl):12–6.CrossRefPubMed Thygesen LC, Daasnes C, Thaulow I, Bronnum-Hansen H. Introduction to Danish (nationwide) registers on health and social issues: structure, access, legislation, and archiving. Scand J Public Health. 2011;39(7 Suppl):12–6.CrossRefPubMed
24.
Zurück zum Zitat Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83.CrossRefPubMed Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83.CrossRefPubMed
25.
Zurück zum Zitat Arslan S, Ucar R, Caliskaner AZ, Reisli I, Guner SN, Sayar EH, et al. How effective are the 6 European Society of Immunodeficiency warning signs for primary immunodeficiency disease? Ann Allergy Asthma Immunol. 2016;116(2):151–5.e1.CrossRefPubMed Arslan S, Ucar R, Caliskaner AZ, Reisli I, Guner SN, Sayar EH, et al. How effective are the 6 European Society of Immunodeficiency warning signs for primary immunodeficiency disease? Ann Allergy Asthma Immunol. 2016;116(2):151–5.e1.CrossRefPubMed
26.
Zurück zum Zitat Chapel H, Lucas M, Lee M, Bjorkander J, Webster D, Grimbacher B, et al. Common variable immunodeficiency disorders: division into distinct clinical phenotypes. Blood. 2008;112(2):277–86.CrossRefPubMed Chapel H, Lucas M, Lee M, Bjorkander J, Webster D, Grimbacher B, et al. Common variable immunodeficiency disorders: division into distinct clinical phenotypes. Blood. 2008;112(2):277–86.CrossRefPubMed
27.
Zurück zum Zitat Berger M, Geng B, Cameron DW, Murphy LM, Schulman ES. Primary immune deficiency diseases as unrecognized causes of chronic respiratory disease. Respir Med. 2017;132:181–8.CrossRefPubMed Berger M, Geng B, Cameron DW, Murphy LM, Schulman ES. Primary immune deficiency diseases as unrecognized causes of chronic respiratory disease. Respir Med. 2017;132:181–8.CrossRefPubMed
28.
Zurück zum Zitat McCullagh BN, Comellas AP, Ballas ZK, Newell JD Jr, Zimmerman MB, Azar AE. Antibody deficiency in patients with frequent exacerbations of chronic obstructive pulmonary disease (COPD). PLoS One. 2017;12(2):e0172437.CrossRefPubMedPubMedCentral McCullagh BN, Comellas AP, Ballas ZK, Newell JD Jr, Zimmerman MB, Azar AE. Antibody deficiency in patients with frequent exacerbations of chronic obstructive pulmonary disease (COPD). PLoS One. 2017;12(2):e0172437.CrossRefPubMedPubMedCentral
Metadaten
Titel
How to Identify Common Variable Immunodeficiency Patients Earlier: General Practice Patterns
verfasst von
Frederik V. Ilkjær
Line D. Rasmussen
Raquel Martin-Iguacel
Lena Westh
Terese L. Katzenstein
Ann-Brit E. Hansen
Thyge L. Nielsen
Carsten S. Larsen
Isik S. Johansen
Publikationsdatum
01.08.2019
Verlag
Springer US
Erschienen in
Journal of Clinical Immunology / Ausgabe 7/2019
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-019-00666-9

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