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Cold agglutinin disease is an autoimmune disease where antibodies attach to red blood cells at low temperatures, causing hemolysis. There are two types, primary and secondary, with symptoms including anemia, discolored fingers and toes, and chronic fatigue. Prevention is the best treatment, but in severe cases, doctors may use monoclonal antibodies or immunosuppressant drugs.
Cold agglutinin disease is a type of autoimmune disease characterized by antibodies that agglutinate or attach to red blood cells (RBCs). It is a variant of autoimmune hemolytic anemia, in which agglutination leads to the death of red blood cells, an event known as hemolysis. Cold agglutinin disease is distinct from autoimmune hemolytic anemia, however, in that antibodies attach to red blood cells only at low temperatures, in the approximate range of 39.2 to 98.6°F (4 to 37°C). Therefore, such antibodies are referred to as cold agglutinins.
In 1903, the Austrian-born Jewish American physician and chemist Karl Landsteiner made the first description of the existence of cold agglutinins. It was in 1957, however, that a trio of medical researchers with the surnames Dacie, Crookston, and Christenson made the first report of cold agglutinin hemolysis, thus marking the first description of cold agglutinin disease. Eventually, the antibody most commonly associated with the medical condition became immunoglobulin (Ig), usually the IgA, IgG, or IgM variant.
There are two forms of cold agglutinin disease: primary disease and secondary disease. The primary type is described as idiopathic and chronic, meaning that its cause is unknown and that it is long lasting. Primary disease occurs from monoclonal antibodies or antibodies that come from the same cell. Secondary disease is usually triggered by another condition, usually another autoimmune disease, infection, or tumor. Furthermore, it is typically generated by both monoclonal and polyclonal antibodies, the latter coming from different cells.
Cold agglutinin disease is more common in the elderly, particularly people in their 60s and 80s. The secondary polyclonal form of the disease, in particular, often affects younger people. In terms of gender, females are more commonly affected than males.
The most common symptom of cold agglutinin disease is anemia, which is a reduction in the number of red blood cells or the amount of hemoglobin in the blood. Other common signs include painful, discolored toes and fingers; chronic fatigue; hemoglobinuria or the release of high concentrations of hemoglobin from the urine; and breathing problems. People with the primary form of cold agglutinin disease may have symptoms worsen during colder weather due to the low temperatures under which cold agglutinin disease works best.
The best treatment for cold agglutinin disease is prevention. This means that staying out of the cold or dressing warmly are the most effective measures people can take. In more extreme cases, however, doctors rely on the monoclonal antibody Rituximab, steroid hormones such as glucocorticoids, and immunosuppressant and immunomodulatory drugs. Such treatments are used sparingly, however, due to questionable effectiveness or their potentially harmful side effects.
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