Hypersensitivity folic acid

Few adverse reactions are associated with the administration of folic acid and leucovorin. Rarely, parenteral administration may result in allergic hypersensitivity. 

Allergic hypersensitivity occurs rarely with parenteral form. Oral folic acid is nontoxic. 

Nausea and mucosal ulcers are the most common toxicities. Progressive dose-related hepatotoxicity in the form of enzyme elevation occurs frequently, but cirrhosis is rare (< 1%). Liver toxicity is not related to serum methotrexate concentrations, and liver biopsy follow-up is only recommended every 5 years. A rare hypersensitivity-like lung reaction with acute shortness of breath is documented, as are pseudolymphomatous reactions. The incidence of gastrointestinal and liver function test abnormalities can be reduced by the use of leucovorin 24 hours after each weekly dose or by the use of daily folic acid, although this may decrease the efficacy of the methotrexate. This drug is contraindicated in pregnancy. 

Sulfasalazine has a high incidence of adverse effects, most of which are attributable to systemic effects of the sulfapyridine molecule. Slow acetylators of sulfapyridine have more frequent and more severe adverse effects than fast acetylators. Up to 40% of patients cannot tolerate therapeutic doses of sulfasalazine. The most common problems are dose-related and include nausea, gastrointestinal upset, headaches, arthralgias, myalgias, bone marrow suppression, and malaise. Hypersensitivity to sulfapyridine (or, rarely, 5-ASA) can result in fever, exfoliative dermatitis, pancreatitis, pneumonitis, hemolytic anemia, pericarditis, or hepatitis. Sulfasalazine has also been associated with oligospermia, which reverses upon discontinuation of the drug. Sulfasalazine impairs folate absorption and processing hence, dietary supplementation with 1 mg/d folic acid is recommended. 

Dapsone (Avlosulfon) is a member of a class of chemical agents known as the sulfones. Dapsone is especially effective against M. leprae and is used with rifampin as the primary method of treating leprosy. Dapsone appears to exert its antibacterial effects in a manner similar to that of the sulfonamide drugs that is, dapsone impairs folic acid synthesis by competing with PABA in bacterial cells. Primary adverse effects associated with dapsone include peripheral motor weakness, hypersensitivity reactions (skin rashes, itching), fever, and blood dyscrasias, such as hemolytic anemia. 

The frequency and severity of the adverse effects of sulfonamides correspond to those seen with other antibacterial agents (2-5%). Dose-related effects, which tend to be more troublesome than serious, include gastrointestinal symptoms, headache, and drowsiness. Crystalluria can occur, but urinary obstruction is rare. Hematological adverse effects due to folic acid antagonism occur primarily in combination with trimethoprim. Hemolytic anemia occurs in patients with enzyme deficiencies and abnormal hemoglobins. Hypersensitivity... 

Severe adverse drug reactions with trimethoprim and co-trimoxazole are rare (12-14). This also applies to children (15). The adverse effects of co-trimoxazole correspond to those expected from a sulfonamide (16). In HIV-infected patients, adverse effects of co-trimox-azole are more frequent and more severe (17-19). Hematological disturbances due to co-trimoxazole include mild anemia, leukopenia, and thrombocytopenia, which may be due to folic acid antagonism. Serious metabolic disturbances that are associated with trimethoprim include hyperkalemia and metabolic acidosis. Trimethoprim can cause hypersensitivity reactions. However, with co-trimoxazole, the sulfonamide is generally believed to be more allergenic (12). Generalized skin reactions predominate. Other effects, such as anaphylactic shock, are extremely rare (20-22). Carcinogenicity due to trimethoprim or co-trimoxazole has not been reported. 

Laws CL (1941) Sensitization to thiamine hydrochloride. JAMA 117 176 Levander-Lindgren M (1957) Hypersensitivity to folic acid in a case of erythroblastomato-sis. Acta Med Scand 157 233-234 Lind J (1953) In A treatise of the scurvy. Millow, London... 

Mitchell DC, Vilter RW, Vilter CF (1949) Hypersensitivity to folic acid. Ann Intern Med 31 1102-1105... 

Methotrexate is a folic acid antagonists that indirectly suppresses the synthesis of purine and is particularly effective in rapidly proliferating cell populations such as cancer. It depresses the primary and secondary antibody response, the homograft reaction, the graft-versus-host response, and the development of hypersensitivity. Methotrexate is used in the treatment of certain cancers. It is very toxic in long-term use, especially to the liver. The toxic effect of methotrexate is reversed by use of... 

The most common side effect of oral treatment with 15 mg folic acid in humans is mild gastrointestinal disturbance, Irritability malaise, hyperexcitability, disturbed sleep, and vivid dreams (Hunter et al, 1970). Hypersensitivity reactions do occur on occasion with certain patients (Mitchell et al, 1949). 

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