Cyclosporine for treatment of acute generalized exanthematous pustulosis: a retrospective analysis.

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Acute generalized exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction, typically to a medication, that is characterized by fever, neutrophilia, and a disseminated non-follicular pustular eruption. AGEP is typically self-resolving upon withdrawal of the offending agent, however it is not without complications and distributive shock due to systemic inflammatory response can lead to hemodynamic instability and organ failure1-2. These patients have been successfully treated with systemic corticosteroids3. Cyclosporine use in patients with AGEP has been limited to only a few case reports4, 5. To date, no studies have evaluated the utility of cyclosporine in the management of AGEP. We report the largest cohort of patients with AGEP treated with cyclosporine and compare them to patients treated with systemic glucocorticoids.This was a retrospective study of adults admitted to Massachusetts General Hospital or Brigham and Women's Hospital with a diagnosis of AGEP from 2009-2019. The patients were identified via a query of electronic medical record systems at both hospitals, and their records were reviewed to find those who received cyclosporine, matched to approximately 3 age- (+/- 5 years) and sex-matched controls per case that received systemic glucocorticoids, amounting to a total of 23 controls. The patients were followed daily while inpatient, and within 2 weeks of discharge. Time from treatment initiation to first noted improvement (defined by defervescence, or symptomatic improvement), time to cessation of pustule formation, time to resolution of erythema, and length of hospital stay were analyzed.The data from patients who received cyclosporine and systemic glucocorticoids was analyzed, with characteristics of the study population presented in Table 1. There was a high prevalence of patients who met SIRS criteria in patients treated with cyclosporine (62.5%), as well as in those with glucocorticoids (61%), implying that this cohort consisted of more severe cases of AGEP. The time from drug eruption onset to cessation of pustule formation was similar in both the cyclosporine group (2.5 days) and corticosteroid group (3 days). Patients treated with cyclosporine were able to achieve initial noted clinical improvement in 1.5 days, and had comparable durations of hospitalization and time to resolution of erythema as patients who received glucocorticoids. No patients had major adverse side effects from cyclosporine or glucocorticoids.To date, this represents the largest cohort of patients with AGEP successfully treated with cyclosporine. Cyclosporine appears to be non-inferior to glucocorticoids with regards to cessation of the eruption and providing clinical improvement. In this cohort, the patients who received cyclosporine were those with relative contraindications to systemic corticosteroids, such as diabetes, history of steroid use with poor tolerance (i.e. delirium, emotional lability, etc.). As cyclosporine was administered primarily based on provider preferences in the setting of the aforementioned comorbidities, some selection bias was unavoidable in this cohort. The small sample size and retrospective nature also limit this study. Nevertheless, cyclosporine appears to be a non-inferior therapeutic alternative to glucocorticoids in the appropriate patient who presents with AGEP, and future prospective studies are needed to further examine its utility in AGEP.

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