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Severe Radiation-Induced Proctitis Treated With Botulinum Anatoxin Type A

Division of Internal Medicine, Cottolengo Hospital, Turin, Italy

To the Editor: Increasing use of radiation therapy (RT) in pelvic malignancy has led to a rise in the incidence of chronic radiation proctitis, which can vary from milder to severe forms, potentially affecting a patient’s quality of life. While pelvic RT clearly decreases local relapse, the risk benefit ratio of treatment should be carefully considered.¹ Rectal instillation of 4% formalin, local nitrates, and endoscopic therapy with argon plasma coagulation are the current treatment options, but their efficacy is not usually sustained; surgery is reserved for resistant bleeding, strictures, or fistulas.²

We report a case of severe radiation-induced proctitis successfully treated with botulinum anatoxin type A (Botox; Allergan Inc, Irvine, CA), when all other treatments were ineffective. A 75-year-old male patient, treated in 2001 for a rectum carcinoma by surgery and successive RT, was referred to our division for intensive anal-perineal pain. A large ulcer, histologically negative for cancer relapse, was present at the rectal-sigmoidal junction. The pain did not subside as a result of analgesic drugs, and the patient was treated at that time with an intraspinal morphine delivery system without relief. At a physical examination, the anal sphincter was hypertonic in response to local inflammation, fibrosis, and pain. We tried to treat the patient with botulinum anatoxin type A, aiming to interrupt the vicious circle between pain and muscular hypertonia. We obtained a written informed consensus from the patient, and we injected 100 U of diluted (in normal saline) botulinum anatoxin A all around the anal sphincter. After 24 hours, the pain decreased dramatically, and 48 hours later, the analgesic drug-delivery system was removed. The patient was again able to sit, and the performance status ameliorated. He described a transient worsening of the pre-existing anal incontinence, which improved in 4 days. Ten months later, the patient showed no symptoms. In September 2002, at an endoscopic check, the rectal-sigmoidal ulcer persisted, but was reduced in dimensions.

There are many papers that consider the use of botulinum anatoxin type A in patients with anismus, anal sphincter achalasia, and chronic anal fissure^3,4; the U.S. Food and Drug Administration has approved its use to treat blepharospasm, strabismus, hemifacial spasm, cervical dystonia, and glabellar (frown) lines. To our knowledge, there are no data about the treatment of radiation-induced proctitis with botulinum anatoxin A. The toxin causes paralysis by locking the presynaptic release of acetylcholine at the neuromuscolar junction. We hypothesized that the chemical denervation obtained with the toxin could be useful in this condition, where the internal sphincter hypertonia, induced and maintained by the chronic underlying fibrosis,⁵ was also responsible for pain. Given the rapid and long-lasting relief from symptoms and the safety of the procedure, we think that this case could be useful to confirm the impression of the potentially beneficial therapeutic role of botulinum anatoxin in various diseases where pain, alone or in combination with organ impairment, represents the principal finding of the pathologically elevated muscular tone. Data from clinical trials are needed to confirm our hypothesis.

REFERENCES

1. Greven KM, Lanciano RM, et al: Analysis of complication in patients with endometrial carcinoma receiving adjuvant irradiation. Int J Radiat Oncol Biol Phys 21:919–923, 1991[Medline]

2. Luna-Perez P, Rodriguez-Ramirez SE: Formalin instillation for refractory radiation-induced hemorrhagic proctitis. J Surg Oncol 80:41–44, 2002[CrossRef][Medline]

3. Brisinda G, Maria G et al. A comparison of injections of botulinum toxin and topical nitroglycerin ointment for the treatment of chronic anal fissure. N Engl J Med 341:65–69, 1999[Abstract/Free Full Text]

4. Mandal A, Robinson RJ: Indications and efficacy of botulinum toxin in disorders of the gastrointestinal tract. Eur J Gastroenterol Hepatol 13:603–609, 2001[CrossRef][Medline]

5. Haboubi NY, Schofield PF, et al: The light and electron microscopic features of early and late phase radiation-induced proctitis. Am J Gastroenterol 83:1140–1144, 1988[Medline]

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by De Micheli, C. Articles by Pascale, C. Search for Related Content PubMed PubMed Citation Articles by De Micheli, C. Articles by Pascale, C. Social Bookmarking                            What's this?