In Skin leiomyomas Botox Fails To Reduce pain
But significant improvements of Quality- Life Scores Can Seen...
Pain associated with cutaneous leiomyomas failed to improve with injections of botulinum toxin A (Botox) but patients' quality of life (QOL) did improve, a small clinical study showed.
The median pain score remained unchanged at 4 weeks in patients who received active treatment, as compared with an increase in the placebo group, but the difference did not achieve statistical significance. The level of self-reported pain also did not differ significantly between treatment groups.
But median scores on a validated skin-related QOL scale improved by 4.0 points with Botox versus no improvement with a placebo injection, reported Edward Cowen, MD, of the National Cancer Institute in Bethesda, Md., and colleagues online in JAMA Dermatology.
"These data suggest that botulinum toxin may reduce the intensity of pain associated with these lesions," the authors said in their discussion of the 18-patient trial. "We also found a marked improvement in skin-related quality of life and skin pain in the botulinum toxin arm compared with the placebo arm. These findings indicate that amelioration of chronic skin pain may improve quality of life by reducing skin pain and by improving social, emotional, and functional status."
Arising most often in the arrector pili, the smooth muscle tumors known as cutaneous leiomyomas cause pain in more than 90% of affected patients. The pain, so intense that some patients reportedly contemplate suicide, usually does not respond to medical management or responds inadequately.
The pain mechanisms remain poorly understood but might involve neuropeptide release, pressure on nerves within lesions, or alpha-adrenergic receptor-mediated contraction of the arrector pili, the authors noted. An accumulation of data has suggested that targeting nerve conduction pathways might provide pain relief for patients with cutaneous leiomyomas.
Clinical experience with botulinum toxin has included use as an analgesic agent in chronic pain syndromes, such as migraine. Botulinum toxin reduces nociception sensitization by inducing muscle relaxation. Some evidence has suggested that botulinum toxin may act directly on noncholinergic neurons to decrease levels of pain-transmission neuropeptides, such as substance P and CGRP.
Eligible patients had at least one symptomatic leiomyoma and associated pain of at least 4 on a visual analog scale (VAS) of 0 to 10. Patients were randomized to receive intralesional botulinum toxin A or saline at baseline, and treatment was administered to the most painful lesions.
Pain was assessed by means of standardized ice-provocation testing, and patients used the VAS to rate pain before and after ice provocation. Other assessments included the Brief Pain Inventory (BPI), Patient Global Impression of Change (PGIC) in pain, and the Dermatology Life Quality Index (DLQI).
The primary endpoint was the between-group difference in pain score from week 0 to week 4, as assessed by the BPI and by the VAS. Secondary endpoints, including skin-related QOL and safety, were assessed at weeks 4 and 12, at which point patients assigned to placebo could crossover to intralesional botulinum toxin and continue follow-up for an additional 12 weeks. Patients randomized to botulinum toxin injections remained in follow-up to week 24 but did not receive additional treatment.
The primary analysis included 18 patients, nine in each treatment arm. At baseline, average lesional pain was from 1.13 to 5.64 in response to ice provocation (P50% improvement in pain (four of nine versus two of nine), and patients in the botulinum toxin arm had less pre-ice provocation pain (0.00 versus 0.40 for placebo, P=0.06). Five patients in the placebo group versus one in the botulinum toxin group reported more pre-ice provocation pain by VAS from weeks 0 to 4.
Skin-related QOL improved significantly in the botulinum toxin group (P=0.007). Additionally, botulinum toxin significantly reduced skin pain (P=0.048) as assessed by the DLQI question, "Over the last week, how itchy, sore, painful, or stinging has your skin been?"
Scores for change in pain, pain severity, pain interference, or skin-related quality of life did not differ between groups across weeks 0 to 12, nor did PGIC scores from weeks 4 to 12.
The study had some limitations including a small sample size and "the inherent subjectivity" in how patients experience pain, which may have biased the results toward accepting the null hypothesis, the authors acknowledged.
The authors suggested that a larger randomized trial would be required to make a proper assessment of botulinum toxin's ability to reduce pain in cutaneous leiomyomas. Ideally, future trials should employ the more recently developed topical formulations of botulinum toxin to improve tolerability and adherence, they added.
The authors disclosed no other relevant relationships with industry.
- Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner