Familial life-long persistent fever of unknown origin responding to dexamethasone and uronic acids

Abstract

A patient of Lebanese ethnic origin was found to have a persistent temperature of 102 °F. with no diurnal variation. He gave a history of persistent life-long fever in himself and a twin brother. His family history was notable for multiple consanguineous marriages. Thorough study uncovered no apparent cause for his fever. Thyroid and adrenal function were normal as was the urinary etiocholanolone excretion. Sweat function also was normal. There was a further increase in his temperature after the administration of killed typhoid bacilli. His temperature could be decreased in twelve hours by the oral administration of dexamethasone and within one to five hours by the oral administration of glucuronic acid, its precursors, its metabolites and galacturonic acid. These various uronic acids, including the nonphysiologic galacturonic acid, are inhibitors of beta-glucuronidase. It is postulated that in this patient the defect in beta-glucuronidase is such that larger than normal physiologic amounts of natural inhibitors are necessary to inhibit beta-glucuronidase action. Beta-glucuronidase, therefore, is thought to be more active than normal, converting nonpyrogenic conjugated etiocholanolone to the pyrogenic free form. Glucuronic acid had no effect on etiocholanolone-induced fever in normal male volunteer subjects. It is suspected that beta-glucuronidase is important in regulating body temperature by controlling the level of free intrahepatic etiocholanolone and that this patient has a hitherto unknown defect of this mechanism.