6 months after the infection has resolved. Mild to moderate primary (unknown cause) cold agglutinin disease can also be associated with a good prognosis if excessive exposure to the cold is avoided. Those with cold agglutinin disease caused by HIV infection or certain types of cancer generally have a poor prognosis due to the nature of the underlying condition. Epidemiology Cold agglutinin disease most commonly affects adults who are of middle age and older. Some studies also report a slight bias in favor of females in the incidence of cold agglutinin disease, particularly in older populations. People with infectious mononucleosis, lymphoproliferative diseases, or mycoplasma pneumonia are more susceptible to this condition. Cold agglutinin disease represents an estimated 16–32% of autoimmune hemolytic anemia, whose annual incidence is estimated to be between 1/35,000-1/80,000 in North America and Western Europe. In patients with infectious mononucleosis, more than 60% of whom develop cold agglutinins disease. Primary cold agglutinin disease In single-center series, primary CAD has been found to account for 13–15% of the cases of AIHA. In a population-based clinical study of primary CAD in Norway, the prevalence was found to be 16 per million in habitants and the incidence rate 1 per million inhabitants per year. Little is known about possible geographic variations. Median age of CAD patients was 76 years and median age at onset of symptoms was approximately 67 years. The male/female ratio has been reported to be 0.5–0.6 which is not very different from a male/female ratio of 0.72 in an age-matched general population. The frequency of auto-immune disorders other than CAD does probably not differ from what is to be expected in an elderly population with some female predominance. as about 12.5 years from diagnosis and median age at death was 82 years, which implies a life expectancy in these patients similar to that of an age-matched general population. More than 90% of patients with primary CAD have Cold-induced circulatory symptoms ranging from moderate acrocyanosis to severe Raynaud phenomena precipitated even by very slight cold exposure. History Cold hemagglutination was first reported by Landsteiner in 1903 and found to occur in human beings in 1918. The association of cold hemagglutination with hemolysis was described in 1937 by Rosenthal and Corten. During the 1960s, Dacie and Schubothe published systematic descriptions of 16 CAD patients each. The auto antibodies responsible for hemagglutination at low temperatures, cold agglutinins (CA), may be found