Immediate-type hypersensitivity to succinylated corticosteroids.

BACKGROUND: Despite their frequent use, systemic corticosteroids have rarely elicited immediate-type reactions. OBJECTIVE: We report two male patients, aged 26 and 70 years, respectively, with severe immediate-type hypersensitivity secondary to the administration of corticosteroids esterified with succinate. METHODS: Skin tests, basophil activation tests and challenge tests were performed for diagnostic evaluation. RESULTS: In both patients, immediate-type skin test reactions were found to methylprednisolone sodium hemisuccinate (MSH) and prednisolone sodium hemisuccinate (PSH). In contrast, nonsuccinylated corticosteroids (including methylprednisolone and prednisolone in one patient) yielded no test reactions. Basophils from one patient exhibited a stimulated expression of the activation marker CD63 upon in vitro incubation with PSH or hydrocortisone sodium succinate, but not with hydrocortisone. Skin tests and basophil activation tests were negative in controls. One patient was challenged with the incriminated drugs. He developed flush, conjunctivitis, tachycardia and dyspnea 2 min after injection of MSH, and dyspnea shortly after intravenous administration of PSH. Oral and intravenous challenge tests with nonsuccinylated corticosteroids were tolerated well by both patients. CONCLUSIONS: These case reports should alert clinicians to rare, but severe immediate-type reactions to corticosteroids, related to the succinate moiety in our patients. In case of allergic reactions to corticosteroids, it is mandatory to identify the causative agent and find safe alternatives.

Prophylactic corticosteroid increases survival in experimental heat stroke in primates.

It has been suggested that endotoxins or lipopolysaccharides (LPS), may contribute to heat stroke pathophysiology. In this study, 11 anesthetised monkeys were divided into 2 groups. The steroid group (n = 5) had received a dose of MPSS (30 mg.kg-1, i.v.) before being heat-stressed and the control animals (n = 6) received saline equivolumetrically. The animals were heat-stressed to a rectal temperature of 43.5 degrees C in an environmental temperature of 41 +/- 0.3 degrees C and 100% relative humidity and then allowed to recover at room temperature. Blood samples for LPS and anti-LPS IgG analyses were taken both before treatment and before and after heat-stress. The administration of prophylactic MPSS increased the survival rate significantly from 33% to 100% (p less than 0.05). The plasma LPS level in the steroid group showed very little change after heat-stress, whereas in the non-surviving controls there was a significant increase in plasma LPS level (from 0.089 +/- 0.007 to 0.257 +/- 0.031 ng.ml-1) (p less than 0.005). The control animals that survived showed very little increase in plasma LPS levels, but had about 300% greater plasma Anti-LPS IgG levels. We conclude that pretreatment with MPSS improves the survival rate during heat stroke, possibly by suppressing the rise in plasma LPS concentration.