Reply to: “Neutrophil-Rich Infusion Site Reactions after Continuous Subcutaneous Application of Foslevodopa/Foscarbidopa”

Abstract

We extend our gratitude to Dr. Weise and colleagues for their insightful comments regarding our manuscript published in Movement Disorders. We greatly appreciate their consideration of additional adverse skin reactions caused by foslevodopa-foscarbidopa (LDP/CDP). In response, we would like to clarify the following points.

The case reported by Dr. Weise (similar to the case we reported in our study) involved a clinical finding of a dome-shaped nodule accompanied by tenderness, and pathological findings revealed inflammation observed from the deep dermis to the subcutaneous panniculitis. The difference between our cases is that the inflammatory cell infiltration observed in Dr. Weise's case mainly involved neutrophils and that observed in our case mainly involved lymphocytes. This difference is thought to be due to the differences in findings depending on the stage of panniculitis. In erythema nodosum and erythema induratum of Bazin, which are representative conditions of panniculitis, infiltrative inflammatory cells include lymphocytes, histiocytes, and neutrophils; in particular, in early lesions, the infiltration of inflammatory cells, which are mainly composed of neutrophils, is observed.¹ According to a review of factitial panniculitis, which is a subcutaneous tissue injury caused by various injections, neutrophilic panniculitis is observed in the acute phase. Lymphocytic infiltration is observed in the later phase.² Because the cause of skin disorders induced by LDP/CDP is unknown, this difference in inflammatory cell infiltration is fascinating, and we would like to reexamine the pathological findings in more cases to understand the pathology of this disorder.

Based on the results of clinical trials of LDP/CDP, the most frequent adverse events on the skin have been reported to be “injection site erythema,” “injection site pain,” and “cellulitis.”³ In our experience with actual cases, skin disorders can be generally divided into three manifestations: injection site erythema, injection site nodules, and injection site cellulitis. Injection site erythema is a skin reaction that occurs when LDP/CDP cannot be injected perpendicular to the skin surface, and we hypothesize that this skin reaction can be avoided by providing injection instructions. Additionally, injection site nodules are thought to be manifestations of panniculitis caused by irritation from the drug. Injection site cellulitis is associated with secondary infection due to the injection procedure, and the clinical findings are similar to those of the aforementioned findings of panniculitis; therefore, evaluating the presence or absence of the inflammatory findings in blood tests is necessary. However, we believe this outcome can be avoided by performing clean procedures. We believe that the accumulation and examination of cases are necessary to develop treatment strategies based to a greater degree on medical evidence.

(1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical analysis: A. Design, B. Execution, C. Review and critique; (3) Manuscript preparation: A. Writing the first draft, B. Review and critique.

N.Y.: 1A, 1B, 1C, 3A

R.W.: 3B

N.N.: 3B

N.H: 3B

The authors have nothing to disclose.