rifampin and Porphyrias

Studies in 14 patients with unconjugated hyperbilirubinaemia caused by Gilbert's syndrome have revealed abnormalities of the enzymes of haem biosynthesis measured in peripheral blood cells. The activity of the penultimate enzyme of haem biosynthesis protoporphyrinogen (PROTO) oxidase was reduced at 3.1 +/- 2.6 nmol PROTO/g protein/h (mean +/- ISD) compared with 8.2 +/- 5.1 in controls (p less than 0.005). This was associated with a compensatory increase in the activity of the initial and rate controlling enzyme of the pathway delta-aminolaevulinic acid (ALA) synthase at 866 +/- 636 nmol ALA/g/protein/h compared with 156 +/- 63 in controls (p less than 0.001). Unlike variegate porphyria in which there is a genetic deficiency of PROTO oxidase there was no increased excretion of porphyrins or their precursors in Gilbert's syndrome. Accentuation and subsequent correction of the unconjugated hyperbilirubinaemia with rifampicin produced reciprocal changes in PROTO oxidase activity indicating that bilirubin may be inhibiting the activity of this enzyme.

Topics: 5-Aminolevulinate Synthetase; Adult; Bilirubin; Female; Flavoproteins; Gilbert Disease; Heme; Humans; Hyperbilirubinemia, Hereditary; Male; Middle Aged; Mitochondrial Proteins; Oxidoreductases; Oxidoreductases Acting on CH-CH Group Donors; Porphyrias; Porphyrins; Protoporphyrinogen Oxidase; Rifampin

With reference to an observation of porphyria variegata, which was complex and unusual as all such observations are, the direct responsibility of rifampicin is underscored. Porphyria variegata should be considered in two situations. The first of these is a dramatic acute neuroabdominal picture: the diagnosis of acute hepatic porphyria is established by the measurement of urinary porphyrins; the second step is to distinguish between the three acute hepatic porphyrias by looking for cutaneous manifestations and determining the respective proportions of coproporphyrins and protoporphyrins in the stools. In porphyria variegata, fecal protoporphyrins are significantly increased. The second situation is cutaneous involvement suggestive of late-onset cutaneous porphyria: porphyria variegata as well as hereditary coproporphyria in the cutaneous phase must be considered. Diagnosis can be established only through measuring fecal porphyrins. Porphyria variegata is a genetic enzymatic disorder inherited on an autosomal dominant basis. A study of the family is required in all cases, but the conventional methods for detecting heterozygotes for porphyria variegata are not satisfactory. Carriers will be unequivocally distinguished from healthy subjects only through measuring the defective enzyme activity.

Topics: Acute Disease; Adult; Chemical and Drug Induced Liver Injury; Feces; Humans; Liver Diseases; Male; Polyradiculoneuropathy; Porphyrias; Porphyrins; Rifampin; Skin Diseases

Topics: Adult; Humans; Male; Porphyrias; Rifampin; Skin Diseases

Topics: Animals; Humans; Porphyrias; Rats; Rifampin; Species Specificity

Topics: Animals; Disease Models, Animal; Furosemide; Humans; Porphyrias; Rats; Rifampin; Risk; Valproic Acid

A patient who developed porphyria cutanea tarda and disturbed liver function tests following treatment with rifampicin and isoniazid for a tuberculous psoas abscess is reported. The patient had normal liver function tests prior to receiving anti-tuberculosis chemotherapy, but was subsequently demonstrated to have cholelithiasis. Challenge testing with both drugs incriminated rifampicin as the agent precipitating porphyria cutanea tarda and disturbance of the liver function tests particularly the serum bilirubin. The association between rifampicin and porphyria cutanea tarda has not previously been described but might be expected because of the ability of rifampicin to induce various liver enzyme systems including delta aminolevulinic acid synthetase activity. This further illustration of rifampicin hepatotoxicity emphasizes the need for regular monitoring of liver function when rifampicin is prescribed. Rifampicin should be used with extreme caution in any patient with a previous history of porphyria cutanea tarda.

Topics: Drug Eruptions; Humans; Liver Function Tests; Male; Middle Aged; Porphyrias; Rifampin; Skin Diseases