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

Abstract

BackgroundCommon 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).ResultsData 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).ConclusionsWhile 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.Electronic supplementary materialThe online version of this article (10.1186/s13023-018-0941-0) contains supplementary material, which is available to authorized users.

Current Understanding and Recent Developments in Common Variable Immunodeficiency Associated Autoimmunity

“…Autoimmune diseases are one of the most common noninfectious complications, occurring in ∼20-30% of patients with CVID, with autoimmune cytopenias being the most common (9,22,23). In a European cohort of 2700 CVID patients taken from the ESID registry, autoimmune cytopenias were found to be 700 times more prevalent in CVID patients compared to the general population (9).…”

“…Among autoimmune cytopenias, autoimmune thrombocytopenia and autoimmune hemolytic anemia occur most frequently, either separately or concurrently as Evan's syndrome. Autoimmune neutropenia also occurs in CVID, although more rarely than thrombocytopenia or anemia (9,24). Importantly, the diagnosis of cytopenia precedes that of CVID by several years in up to 60% of patients (22).…”

“…Other rheumatologic manifestations include systemic lupus erythematosus, Sjogren's disease, Behcet's disease, and psoriasis (24,32). Among organ specific autoimmune manifestations, hypothyroidism was the most prevalent at 3.5%, followed by alopecia areata and vitiligo at 2.7%, and type 1 diabetes at 1.6% in an ESID registry of 2700 CVID patients (9). Autoimmunity may also underlie gastrointestinal complications of CVID, including inflammatory bowel disease, autoimmune enteropathy, and autoimmune gastritis (33).…”

“…Since the widespread adoption of this treatment, mortality of patients with CVID has decreased from 30% in the early 1990s (7) to 15% in the early 2000s (8), in a cohort of 240 patients in the United Kingdom and 334 patients from the ESID registry, respectively, all followed for approximately two decades. The improved survival in CVID patients has been attributed to the reduction of infectious complications thanks to the widespread use of immunoglobulin replacement and improved anti-microbial therapies (9)(10)(11)(12). While overall survival has improved, patients with CVID continue to have reduced survival compared to age-matched controls (13).…”

Prioritizing Research Challenges and Funding for Allergy and Asthma and the Need for Translational Research — The European Strategic Forum on Allergic Diseases

“…3. Необходима трансформация систем здравоохранения с целью перехода на широкое использование мобильных устройств и беспроводных технологий самооценки и самоконтроля пациента (так называемое цифровое здравоохранение), повышение медицинской грамотности населения и включение в круг регулируемых проблем вопросов окружающей среды (загрязнение микро-и макроокружения) и условий работы/учебы пациента [32][33][34][35].…”