CAD Diagnoses Climb With Cold of Winter Months, European Study Finds

Cold agglutinin disease (CAD) is more frequently diagnosed during winter months at multiple locations across Europe, supporting outdoor temperature as a disease trigger, researchers reported.

Findings also suggest that, in general, people living in places with milder weather may be less likely to experience CAD symptoms and, as such, are less likely to be diagnosed with the condition.

Their study, “Seasonal variation in the incidence of cold agglutinin disease in Norway, Denmark, and Italy,” was published as a correspondence to the editor in the American Journal of Hematology.

CAD is a rare autoimmune disorder caused by the production of self-reactive antibodies, called cold agglutinins, which bind and destroy red blood cells at low temperatures.

Prior research has indicated that the incidence of CAD is higher in Denmark and Norway than in Lombardy, a northern region of Italy.

“A possible explanation could be the climatic differences, particularly considering outdoor temperature,” the researchers wrote. In other words, because temperatures tend to be colder in Denmark and Norway than Italy, CAD symptoms might be more likely to manifest and the disease more likely to be diagnosed.

If true, then according to this proposed explanation the incidence of CAD in these countries should follow a seasonal pattern. It would also be expected that CAD diagnoses are more common when temperatures are lower in these countries.

To test this idea, researchers analyzed national databases from the three locations to identify CAD diagnoses, and extracted information about local monthly temperatures in these regions from publicly available sites over time.

Data gathered cover all cases of CAD identified in Norway and Lombardy between 2007 and 2018, as well as all diagnosed in Denmark from 1994 to 2016. In total, this amounted to 160 cases of CAD from Norway, 112 from Denmark, and 41 from Lombardy.

Using statistical analyses, investigators looked for trends in the frequency of CAD diagnoses in relation to the weather over time.

In all three locations analyzed, CAD was diagnosed more frequently in winter months than during the comparably warmer summer, which was what the researchers had expected to find.

“It is likely that the colder winter temperatures provoke latent disease to become apparent, thereby facilitating diagnosis,” they wrote.

The seasonal variation in CAD diagnoses was more dramatic in Italy, with over half of the patients being diagnosed in winter months (December, January, or February), while only 17% were diagnosed between May and September.

“This is probably related to the mild climate [in Italy], although occasional exposure to cold temperatures (sea/lake water, air conditioning, etc.) may still occur and cause symptoms,” investigators wrote.

Other hemolytic disorders — diseases that, like CAD, cause the destruction of red blood cells, but are usually not temperature-dependent — did not follow the same seasonal trends.

“We report decreased incidence of CAD during summertime in Norway, Denmark, and Italy. The seasonal variation supports that temperature triggered symptoms are the driving cause for initiating the diagnostic process,” they concluded.