r the reaction subsides spontaneously, as it commonly does. If the reaction is more severe or if neutropenia occurs, another drug should be tried or the medication withdrawn altogether. Usually a switch is made to another thiocarbamide, because cross-reactions do not necessarily occur between members of this drug family. Alternatively, the program of therapy may be changed to the use of RAI, which may be given after the patient has stopped taking the antithyroid drug for 48 – 74 hours, or the patient may be prepared for surgery by the administration of iodides and propranolol.
The incidence of agranulocytosis in a large series of patients was 0.4% . It occurs most frequently in older patients and those given large amounts of the drug (20-30 mg methimazole every eight hours) .
Reactions tend to be most frequent in the first few months of therapy but can occur at any time, with small doses of drug, and in patients of all ages . The most common reactions are fever and a morbilliform or erythematous rash with pruritus. Reactions similar to those of serum sickness, with migratory arthralgias, jaundice, lymphadenopathy, polyserositis, and episodes resembling systemic lupus erythematosus have also been observed . Pyoderma gangrenosum can occur (147.1). Neutropenia and agranulocytosis are the most serious complications. These reactions appear to be due to sensitization to the drugs, as determined by lymphocyte reactivity in vitro to the drugs . Occasionally agranulocytosis can develop even though the total WBC remains within normal ranges- a hazard to be remembered if differential counts are not done. Fortunately, even these problems almost always subside when the drug is withdrawn.
Aplastic anemia with marrow hypoplasia has been reported (perhaps 10 cases), again with spontaneous recovery in 2-5 weeks in 70%, but fatal outcome in 3 patients . Thrombocytopenia and/or anemia may accompany the neutropenia.
Vasculitis is a fortunately rare complication during treatment with antithyroid drugs.
Neutropenia-It is probably wise to see patients receiving the thiocarbamides at least monthly during the initiation of therapy and every two to three months during the entire program. Neutropenia can develop gradually but often comes on so suddenly that a routine white cell count offers only partial protection. A white cell count must be taken whenever there is any suggestion of a reaction, and especially if the patient reports malaise or a sore throat. A white cell count taken at each visit will detect the gradually developing neutropenia that may occur. While many physicians do not routinely monitor these levels, the value of monitoring is suggested by the study of Tajiri et al . Fifty-five of 15398 patients treated with antithyroid drugs developed agranulocytosis, and 4/5 of these were detected by routine WBC at office visits. Low total leukocyte counts are common in Graves’ disease because of relative neutropenia, and for this reason a baseline WBC and differential should be performed before starting anti-thyroid drugs. However, total polymorphonuclear counts below 2,000 cells/mm3 should be carefully monitored; below 1,200 cells/mm3 it is unsafe to continue using the drugs.
In the event of severe neutropenia or agranulocytosis, the patient should be monitored closely, given antibiotics if infection develops, and possibly adrenal steroids. There is no consensus on the use of glucocorticoids, since they have not been shown to definitely shorten the period to recovery. Administration of recombinant human granulocyte colony stimulating factor (75 µg/day given IM) appears to hasten neutrophile recovery in most patients who start with neutrophile counts > 0.1 X 109/L . Antithymocyte globulin and cyclosporin are also used [153.1]. Care must be taken to ensure against exposure to infectious agents, and some physicians prefer not to hospitalize their patients for this reason. If the patient is hospitalized, he or she should be placed in a special-care room with full bacteriologic precautions.
Patients may develop antineutrophil cytoplasmic antibodi