Flu-like symptoms and associated immunological response following therapy with botulinum toxins

We aimed to define the frequency and risk factors associated with flu-like symptoms (FLS) and other systemic symptoms following treatment with botulinum toxins (BoNT) and correlate them with the immunological response as determined by blood cytokines. The study involved prospective clinical and serological evaluation for cytokine analysis in patients receiving BoNT for movement disorders. We interviewed 218 patients about FLS following BoNT injections and prospectively studied 117 patients (females 67.5 %; mean age 59.74 ± 12.39 years) treated with BoNT in a total of 143 treatment cycles. While no patient reported any FLS at baseline, the symptom complex was subsequently reported in 19 patients (16.3 %) and in 20 (14 %) treatment cycles, with at least one systemic symptom reported in 49 (42 %) patients in 59 (41.3 %) treatment cycles. FLS and at least one symptom were reported more frequently by women (P = 0.006 and P = 0.049, respectively) and by younger patients: 55.6 versus 61.7 years (P = 0.022). Although the symptoms were usually considered mild, they were rated as moderate to serious after 18 (12 %) cycles. The following interleukins showed increased levels at 7-10 days after the BoNT injections: IL-1β, IL-8, GROα, eotaxin, MCP-1 and 2, RANTES, TARC, and inducible protein 10 (IP10), but only the latter showed significantly increased levels in patients with FLS: 69 versus 3 pg/ml (P = 0.007). FLS and other systemic symptoms occur after about 14 % of treatment visits in patients receiving BoNT. IP10 levels correlate with the presence and severity of FLS.