Short summary

Efforts to reduce the diagnostic delay associated with Common Variable Immunodeficiency (CVID) are crucial. We aimed to assess the general practice (GP) patterns of undiagnosed CVID patients and a matched control cohort in 3 years before the CVID diagnosis and whether the risk of the CVID diagnosis was associated with the frequency of consultations or character of examinations. CVID patients visit the GP 2.5 times more three years before diagnose compared to the general population. And 95-100% of the undiagnosed CVID patients visit the GP every year and focus on finding the patients should be in the primary sector.

Rationale

With a prevalence ranging from 0.6 to 6.9/100.000  in Northern and Western Europe, Common Variable Immunodeficiency Disorder (CVID) is the most frequent symptomatic primary immunodeficiency disorder among adults (1-3). CVID is a heterogeneous group of diseases characterized by hypogammaglobulinemia,with monogenetic or complex causes  (REF )4-6). Although, most patients present themselves with increased susceptibility to mainly sino-pulmonary infections, and/or  autoimmune or granulomatous disease, unexplained polyclonal lymphoproliferation or cancer,  only a smaller percentage do not have an increased risk of infections (4-8).

Several studies have shown that for CVID patients, the diagnostic delay (i.e., time from symptom onset till diagnosis) is a major problem (4, 5, 9-11). In extension of that, a recent Danish cohort study of CVID patients (5) found a median diagnostic delay of seven years (IQR: 3 - 17), which was longer than that found in other studies.  The delay in diagnosis might be a result of several things. First, the general practitioners (GP) may have little knowledge of this rare disease; second, the heterogenic phenotype of CVID makes pattern recognition difficult; third, the diagnosis is not made by a simple test (positive/negative) but relies on clinical criteria as well as results of more tests (i.e. hypogammaglobulinemia, and poor vaccine response or a reduced number of switched memory B-cells (4-6)); Forth, the symptoms are often progressing with time along with a progressing  loss of antibodies. Efforts to reduce the diagnostic delay are crucial as a late diagnosis is correlated with higher morbidity, mortality and reduced quality of life, and an increased annual healthcare cost compared to early and appropriate diagnosis and management (7, 12-14). 

We hypothesized that CVID patients have an increased number of contacts with GP in the years before their CVID diagnosis, compared to the general population. We aimed to assess the fraction of CVID diagnosed patients who had contacts to their GP in the three-year period before the CVID diagnosis and investigate whether the risk of the CVID diagnosis was associated with the frequency of consultations or character of additional services provided at the GP.  

Description of the cohort

The Danish Adult Common Variable Immunodeficiency Cohort is a historical cohort study designed to identify and characterize Danish CVID patients older than 15 years from January 1994 through December 2013. It contains 179 CVID patients and it served as our case cohort.

For each case, 45 age-and gender-matched population controls were selected from the Danish Civil registration system. The controls had to be alive, older than 18 years at baseline, living in Denmark in the study period and not diagnosed with CVID before year 2013. Study inclusion (~baseline) for the cases and controls were the date of CVID diagnosis for the matched case.  

Data and biological material

Data is collected via three nationwide danish registries:

The Danish National Health Service Register

The Danish Civil registration system

The Danish Adult Common Variable Immunodeficiency Cohort 

and Data was obtained via Statistics Denmark from where information on socioeconomic status was available 

Collaborating researchers and departments

Department of Infectious Diseases, Odense University Hospital

• Professor Isik Somuncu Johansen
• PhD, DMSci Line Dahlerup Rasmussen
• Senior Consultant Raquel Martin-Iguacel

Department of Infectious Diseases, Aarhus University Hospital Skejby

• MD Lena Westh
• Professor Carsten Schade Larsen