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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2018

Open Access 01-12-2018 | Research

The burden of common variable immunodeficiency disorders: a retrospective analysis of the European Society for Immunodeficiency (ESID) registry data

Authors: Irina Odnoletkova, Gerhard Kindle, Isabella Quinti, Bodo Grimbacher, Viviane Knerr, Benjamin Gathmann, Stephan Ehl, Nizar Mahlaoui, Philippe Van Wilder, Kris Bogaerts, Esther de Vries, in collaboration with the Plasma Protein Therapeutics Association (PPTA) Taskforce

Published in: Orphanet Journal of Rare Diseases | Issue 1/2018

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Abstract

Background

Common variable immunodeficiency disorders (CVID) are a group of rare innate disorders characterized by specific antibody deficiency and increased rates of infections, comorbidities and mortality. The burden of CVID in Europe has not been previously estimated. We performed a retrospective analysis of the European Society for Immunodeficiencies (ESID) registry data on the subset of patients classified by their immunologist as CVID and treated between 2004 and 2014. The registered deaths and comorbidities were used to calculate the annual average age-standardized rates of Years of Life Lost to premature death (YLL), Years Lost to Disability (YLD) and Disability Adjusted Life Years (DALY=YLL + YLD). These outcomes were expressed as a rate per 105 of the CVID cohort (the individual disease burden), and of the general population (the societal disease burden).

Results

Data of 2700 patients from 23 countries were analysed. Annual comorbidity rates: bronchiectasis, 21.9%; autoimmunity, 23.2%; digestive disorders, 15.6%; solid cancers, 5.5%; lymphoma, 3.8%, exceeded the prevalence in the general population by a factor of 34.0, 7.6, 8.1, 2.4 and 32.6, respectively. The comorbidities of CVID caused 8722 (6069; 12,363) YLD/105 in this cohort, whereas 44% of disability burden was attributable to infections and bronchiectasis. The total individual burden of CVID was 36,785 (33,078, 41,380) DALY/105. With estimated CVID prevalence of ~ 1/ 25,000, the societal burden of CVID ensued 1.5 (1.3, 1.7) DALY/105 of the general population.
In exploratory analysis, increased mortality was associated with solid tumor, HR (95% CI): 2.69 (1.10; 6.57) p = 0.030, lymphoma: 5.48 (2.36; 12.71) p < .0001 and granulomatous-lymphocytic interstitial lung disease: 4.85 (1.63; 14.39) p = 0.005. Diagnostic delay (median: 4 years) was associated with a higher risk of death: 1.04 (1.02; 1.06) p = .0003, bronchiectasis: 1.03 (1.01; 1.04) p = .0001, solid tumor: 1.08 (1.04; 1.11) p < .0001 and enteropathy: 1.02 (1.00; 1.05) p = .0447 and stayed unchanged over four decades (p = .228).

Conclusions

While the societal burden of CVID may seem moderate, it is severe to the individual patient. Delay in CVID diagnosis may constitute a modifiable risk factor of serious comorbidities and death but showed no improvement. Tools supporting timely CVID diagnosis should be developed with high priority.
Appendix
Available only for authorised users
Footnotes
1
Today, there is no complete consensus regarding the definition of CVID. The discussion particularly concerns the presence of a decreased IgA level as an imperative diagnostic criterion. While ESID recommends diagnosis of CVID based on a marked decrease of IgG and a marked decrease of IgA (with or without low IgM levels; 2014), the international consensus “ICON” (2016) suggests less stringent diagnostic criteria: a marked decrease of IgG and at least one of IgM or IgA (3,7, Additional file 8). Patient inclusion was based solely on the diagnosis by their immunologists and not verified according to the diagnostic criteria due to limitations of the dataset.
 
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Metadata
Title
The burden of common variable immunodeficiency disorders: a retrospective analysis of the European Society for Immunodeficiency (ESID) registry data
Authors
Irina Odnoletkova
Gerhard Kindle
Isabella Quinti
Bodo Grimbacher
Viviane Knerr
Benjamin Gathmann
Stephan Ehl
Nizar Mahlaoui
Philippe Van Wilder
Kris Bogaerts
Esther de Vries
in collaboration with the Plasma Protein Therapeutics Association (PPTA) Taskforce
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2018
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-018-0941-0

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