Sulfonamides agranulocytosis with

Severe reactions Severe reactions including deaths caused by sulfonamides have been associated with hypersensitivity reactions, agranulocytosis, aplastic anemia, other blood dyscrasias, and renal and hepatic damage. Irreversible neuromuscular and CNS changes and fibrosing alveolitis may occur. 

The hematopoietic toxicity includes agranulocytosis, thrombocytopenia and rarely aplastic anaemia and in patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, sulfonamides may cause intravascular haemolysis. 

The problems encountered most frequently with sulfonamide drugs include gastrointestinal distress, increased skin sensitivity to ultraviolet light, and allergic reactions. Serious disturbances in the formed blood elements, including blood dyscrasias such as agranulocytosis and hemolytic anemia, may also occur during systemic sulfonamide therapy. 

Agranulocytosis was not infrequent in the early sulfonamide era. The first cases were observed in association with sulfanilamide (84,85), Prontosil (84), sulfapyridine (85,86), sulfathiazole (87), sulfadiazine (87), and sulfasalazine (88). Even with topical silver sulfadiazine, agranulocytosis as a consequence of systemic absorption has been reported (89). 

Sulfonamides or sulfones usually account for most toxicity associated with coadministration of these antifolate drugs (see Chapter 43). The combination of pyrimethamine (25 mg) and sulfa-doxine (500 mg) (fansidar) causes severe and even fatal cutaneous reactions in up to 1 in 5000 people. This combination also has been associated with serum sickness-type reactions, urticaria, exfoliative dermatitis, and hepatitis. Pyrimethamine-sulfadoxine is contraindicated in individuals with previous reactions to sulfonamides, lactating mothers, and infants <2 months of age. Administration of pyrimethamine with dapsone (MALOPRIM, unavailable in the U.S.), occasionally has been associated with agranulocytosis. Higher doses pyrimethamine (75 mg daily) used along... 

Although rare, acute hemolytic anemia can occur. This may reflect an immune reaction or may be due to glucose-6-phosphate dehydrogenase deficiency. Agranulocytosis occurs in -0.1% of patients who receive sulfadiazine and also can occur with other sulfonamides. Although neutropenia may persist for weeks or months after sulfonamide is withdrawn, most patients recover spontaneously with supportive care. Pancytopenia with complete suppression of bone-marrow activity is extremely rare. It probably results from a direct myelotoxic effect and may be fatal. Reversible suppression of the bone marrow is quite common in patients with limited bone marrow reserve (e.g., patients with AIDS or those receiving myelosuppressive chemotherapy). 

Agranulocytosis occurs in 0.1 % of cases after sulfadiazine and also occurs after other sulfonamides. The myelotoxic effect is demonstrated as impaired development of the myeloblasts. Granulocytopenia is not related to the applied dosage and as a rule appears after 10 days treatment. Slight passing thrombocytopenia is frequent, but serious thrombocytopenia and aplastic anemia are rare. Isolated peripheral eosinophilia can be observed, disappearing rapidly after cessation of sulfonamides. It can also appear in combination with other signs of hypersensitivity (Thirkettle et al. 1963 Johnson and Korst 1961). 

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