Assessing causality by means of the Naranjo scale in a paediatric patient with life threatening respiratory failure after alemtuzumab administration: a case report

Nori J L Smeets,Charlotte M H H T Bootsma-Robroeks,Saskia N De Wildt,Ruud J R Eijk

doi:10.1186/s12887-021-02698-w

Abstract

BackgroundAlemtuzumab is a T cell depleting antibody agent used as induction immunosuppressant therapy in solid organ transplant recipients. In addition, it is being increasingly used to treat severe or glucocorticoid-resistant graft rejection. Despite the effectiveness of the treatment, severe adverse events have been reported related to alemtuzumab administration. We present a similar event illustrating the severity of this adverse drug reaction (ADR) and we highlight the structure causality assessment provides in approaching such a case.Case presentationWe report a case of life-threatening respiratory failure after alemtuzumab administration in a 17 year old paediatric kidney transplant recipient. He developed near fatal severe respiratory and circulatory failure based on acute respiratory distress syndrome (ARDS) with diffuse alveolar oedema and haemoptysis hours after his second alemtuzumab administration. As it was questionable whether alemtuzumab could be regarded as the origin of his reaction and in order to assess the causality of this reaction as well as to structure clinical reasoning, we applied a widely used ADR probability scale to systematically review our case.Discussion and conclusionsOur case shows a severe ADR after alemtuzumab administration. It illustrates the importance of proper causality assessment, the structure it provides and the benefit of a clinical pharmacology consultation when a severe reaction is suspected to be an ADR. By taking our case as an example, we demonstrate the added value of structured causality assessment to clinical reasoning and in generating differential diagnoses.

Highlights

Alemtuzumab is a T cell depleting antibody agent used as induction immunosuppressant therapy in solid organ transplant recipients
Our case shows a severe adverse drug reaction (ADR) after alemtuzumab administration. It illustrates the importance of proper causality assessment, the structure it provides and the benefit of a clinical pharmacology consultation when a severe reaction is suspected to be an ADR
By taking our case as an example, we demonstrate the added value of structured causality assessment to clinical reasoning and in generating differential diagnoses

Summary

Discussion and conclusions

This report shows a case of a severe respiratory and circulatory failure based on ARDS with diffuse pulmonary oedema and haemoptysis. Organ-specific scores exist and have a higher validity [10], the Naranjo scale remains one of the most accessible and most frequently used ADR probability scale in case of a single-drug-event [11]. We used this scale and demonstrate that, by applying this simple tool and asking predefined questions, proper causality assessment leads to better substantiated clinical reasoning and might help in generating differential diagnoses. This could be considered as a first and accessible step for any clinician encountering a possible ADR.

Background

Did the reaction reappear when a placebo was given?

10. Was the adverse event confirmed by any objective evidence?