[Methyldopa-induced autoimmune hemolytic anemia. Course and long-term observations on 11 patients]

Long-term studies on 11 patients suffering from methyldopa-induced autoimmune haemolytic anaemia suggest that this self limitable episode of disturbed immune tolerance is characterized by five main parameters: 1. The autoimmune pathogenic average daily drug dose: Unfortunately, it cannot be estimated exactly due to the individually rather variable absorption of methyldopa (7-62%). The lowest oral dose in our patients was 125 mg daily. 2. The period of autoimmune induction: between the start of the methyldopa administration and the beginning of autoantibody production. It has to be estimated somewhat shorter than the time up to the clinical manifestation of the haemolytic anaemia. This varied over a wide range from 2 to 52 months. 3. The period of the active autohemolysis: between the appearance of pathogenic autoantibodies and the withdrawal of methyldopa. It depends on the recognition of the cause of the disease. In our patients it varied between 2 and 32 weeks. 4. The period of the haematologic remission: between the withdrawal of methyldopa and the normalization of the red blood cell values. It ranged between 4 weeks and 4 months. Contrary to the other parameters, the clinical remission is almost uniform in all patients. It begins immediately when the drug is stopped. This fact suggests that the induction and maintenance of the disease needs a continuous application of methyldopa and its presence in blood and tissue. The normalization of the red blood cell turnover simultaneous with the cessation of therapy, although the direct antiglobulin test remains positive, reveals a change of the autoantibodies into those apathogenic variants known from the majority of methyldopa-induced autoimmunizations. 5. The period of immunologic remission: between the withdrawal of methyldopa and the definite extinction of autoantibody production. It varied between 4 and 12 months. Transition to or later development of an autonomous warm autoantibody anaemia were not observed. The disease remits spontaneously. Its prompt reversibility resembles the same phenomenon in autoantibody anaemias induced by infectious agents. An inhibition of methyldopa-sensitive suppressor-T-cells may initiate the disturbed tolerance disease.