Skin Inflammatory Reactions in Patients with Continuous Subcutaneous Injection of Foslevodopa-Foscarbidopa Hydrate: Histopathology

Abstract

Continuous subcutaneous injection of foslevodopa-foscarbidopa, a new device therapy for advanced Parkinson's disease, helps improve motor complications. In terms of safety, adverse events occurred in 94.3% of patients, and the most common side effects reported were “injection site erythema,” “injection site nodules,” and “cellulitis.”¹ Based on these results, it is clear that this drug causes a variety of skin problems, and the management of these problems is essential for its continued administration.

At our facility, we administered this treatment to 14 patients, and all patients developed redness or nodules. Here, we evaluated the pathology of the tender subcutaneous induration at the cannula insertion site in two of our patients.

One patient was a 44-year-old Japanese man with a body mass index (BMI) of 19.9. The patient realized the appearance of a tender induration at the cannula insertion site. A 3-cm dome-shaped nodule that had a normal color was observed in the right lower abdomen (Fig. 1A). Pathological findings revealed no abnormalities in the epidermis, and the infiltration of inflammatory cells, mainly lymphocytes, was observed in the adipose tissue partitions (Fig. 1B). The symptoms improved with the local injection of steroids.

The second patient was a 53-year-old Caucasian male with a BMI of 22.0. A tender subcutaneous induration appeared at the cannula insertion site. The patient presented with a 3 cm dome-shaped red mass in the right lower abdomen and a 2 cm red subcutaneous induration in the left lower abdomen (Fig. 1C). A skin biopsy was performed on the mass in the right lower abdomen. Pathological findings revealed the infiltration of inflammatory cells in the center of the partitions of the subcutaneous adipose tissue. The infiltrating inflammatory cells were mainly lymphocytes, and panniculitis was diagnosed (Fig. 1D). Four days after a local steroid injection, the rash and tenderness had improved.

The rashes appeared as subcutaneous indurations or dome-shaped nodules measuring 1 to 4 cm in size between the day of cannulation and the fourth day thereafter and were accompanied by mild to moderate pain. As in reactions to apomorphine subcutaneous injections, the pathological changes were panniculitis-like local inflammatory reactions.²

Although the severity of symptoms varied in the cases reported here, both yielded pathological findings of panniculitis, and reactive inflammation because of the administration of a high concentration of the drug in the adipose tissue was suspected.

The recommended preventive measures include clean cannulation and correct cannula insertion at a 90° angle to the body wall. As a first aid measure, cooling may have a specific effect. Possible treatment options include the topical application of betamethasone valerate or betamethasone butyrate, the oral administration of nonsteroidal anti-inflammatory drugs, and the subcutaneous injection of betamethasone acetate. The subcutaneous injection of betamethasone acetate is the most effective, with a tendency for symptoms to improve on the third day after treatment. Therefore, the subcutaneous injection of betamethasone acetate is worth trying in patients who complain of severe symptoms.

We believe that the appropriate management of cutaneous side effects is essential for the continuation of this therapy.

(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

N.N.: 1B, 3B

R.W.: 3B

N.H: 1A, 3B