Treatment of notalgia paresthetica with botulinum toxin A: A double-blind randomized controlled trial

To the Editor: Notalgia paresthetica (NP) is a chronic sensory neuropathy affecting the interscapular area, especially the T2-T6 dermatomes and characterized by pruritus on the upper back with cutaneous signs associated with rubbing and scratching.^,  Botulinum toxin A (BTX-A) could have beneficial effects on localized pruritus, possibly by preventing the release of substance P, a mediator involved in pain and itch.^,  One publication reports complete resolution of pruritus in 2 patients with NP treated with BTX-A. We conducted a randomized, placebo-controlled, double-blind clinical trial to study the efficacy and safety of BTX-A in patients with NP in a Canadian dermatology research clinic between July 2010 and November 2011. After signing informed consent, 20 patients with NP for at least 1 year, stable for 3 months before baseline and resistant to topical therapy, were randomized (1:1) to either BTX-A (Xeomin, Merz Pharmaceuticals, Frankfurt, Germany) in saline or saline alone (placebo) (Fig 1). Baseline characteristics are shown in Table I. A sample size of 20 had a power of 0.8 to detect a difference in change from baseline of 1.7 in visual analogue score (VAS) for pruritus between the two groups, assuming a mean baseline VAS of 8 and standard deviation (SD) of 1.27. ANOVA for repeated measures was used to analyze the primary endpoint. Differences between the 2 groups at week 8 were analyzed with a post hoc contrast (Fisher's least significant difference) that compared the estimated means from the ANOVA (the observed means for a factorial plan) of groups for each time point with no adjustment for the multiplicity of test. Patients with NP with mild pruritus that was not bothersome or with presence of severe excoriations, erosions, or significant scarring were excluded to avoid injecting in open wounds. Spine imaging and skin biopsies were not performed. Patients in the BTX-A group received injections of 0.1 mL (50 U/mL) for every 1 to 2 cm² of hyperpigmented area; if there was no hyperpigmentation, the pruritic area as delimited by the patient was injected (maximum intradermal dose of 200 U BTX-A). Patients in the placebo group received a corresponding volume of saline. Patients who received placebo at baseline received BTX-A at week 12 and all patients continued the study until week 24. The non-blocked randomization sequence prepared using a proprietary software was sealed in sequentially numbered envelopes by the sponsor. Everyone except the pharmacist who assigned interventions remained blinded until week 12. The primary endpoint was the change from baseline (CFB) in pruritus VAS (10 cm) at week 8. Secondary endpoints included CFB in pruritus at week 12, CFB in area of hyperpigmentation, and global efficacy evaluated by the investigator and by the patients on a 5-point scale (worsening to excellent improvement). Patients without hyperpigmentation at baseline were not included in the hyperpigmentation analysis.

All patients but 1 from each group completed the study (1 received intraarticular corticosteroid and had to be withdrawn and the other withdrew consent). The mean dose of BTX-A received was 142 U. There was no statistically significant mean difference in pruritus VAS between patients treated with BTX-A (−0.72 ± 2.97) and those given placebo (−0.91 ± 3.8) 8 weeks after the treatment (P = .902; 95% CI: −3 to 3.4) (Fig 2). Similarly, there was no significant difference between the groups in hyperpigmentation (Fig 2) or investigator and patient global efficacy (not shown). Adverse events were mostly mild and determined to be not related to BTX-A (not shown).

In conclusion, this study was not able to confirm the beneficial effect of BTX-A injected intradermally at doses of at most 200 U to reduce pruritus in patients with notalgia paresthetica. Conclusions of this study are limited by the small population size.