Cold agglutinin disease

Cold agglutinin disease (CAD) is a rare autoimmune disease characterized by the presence of high concentrations of circulating cold sensitive antibodies, usually IgM and autoantibodies that are also active at temperatures below 30 °C (86 °F), directed against red blood cells, causing them to agglutinate and undergo lysis. It is a form of autoimmune hemolytic anemia, specifically one in which antibodies bind red blood cells only at low body temperatures, typically 28–31 °C. Cold agglutinin disease (CAD) is a rare autoimmune disease characterized by the presence of high concentrations of circulating cold sensitive antibodies, usually IgM and autoantibodies that are also active at temperatures below 30 °C (86 °F), directed against red blood cells, causing them to agglutinate and undergo lysis. It is a form of autoimmune hemolytic anemia, specifically one in which antibodies bind red blood cells only at low body temperatures, typically 28–31 °C. When affected people's blood is exposed to cold temperatures (32 °F (0 °C; 273 K) to 50 °F (10 °C; 283 K)), certain proteins that normally attack bacteria (IgM antibodies) attach themselves to red blood cells and bind them together into clumps (agglutination). This eventually causes red blood cells to be prematurely destroyed (hemolysis) leading to anemia and other associated signs and symptoms. Cold agglutinin disease can be primary (unknown cause) or secondary, due to an underlying condition such as an infection, another autoimmune disease, or certain cancers. Treatment depends on many factors including the severity of the condition, the signs and symptoms present in each person, and the underlying cause. Cold agglutinin disease was first described in 1957. Symptoms of cold agglutinin disease (CAD) are often triggered or made worse by cold temperatures or a viral infection. Therefore, symptoms generally are worse during winter months. Symptoms may arise suddenly leading to abrupt onset of severe anemia and hemoglobinuria or develop more gradually and insidiously in the background without patient's consciousness and precaution. Most people with CAD have symptoms of hemolytic anemia (destruction of red blood cells, causing low levels of red blood cells). However, the number of symptoms and severity of symptoms may depend on how severe the anemia is. Signs and symptoms of hemolytic anemia may include: Many people with CAD also experience pain and bluish coloring of the hands and feet (acrocyanosis) or Raynaud's disease. These symptoms result from slow or poor circulation and can range from mild to disabling. Other signs and symptoms of CAD may include enlargement of the spleen (splenomegaly) and mottled discoloration of the skin (livedo reticularis). In people with secondary CAD (associated with another underlying condition), there may be additional signs and symptoms depending on the condition present. For example: Mycoplasma pneumoniae infection (the most common cause of secondary CAD) may cause respiratory symptoms. Various infections or cancers may cause enlarged or swollen lymph nodes.