Successful Treatment of Notalgia Paresthetica with Botulinum Toxin Type A

THE CUTTING EDGE

SECTION EDITOR: GEORGE J. HRUZA, MD; ASSISTANT SECTION EDITORS: MICHAEL P. HEFFERNAN, MD; CHRISTIE AMMIRATI, MD Successful Treatment of Notalgia Paresthetica With Botulinum Toxin Type A

Pamela Kirschner Weinfeld, MD; Division of Dermatology, Newton-Wellesley Hospital, Newton, Massachusetts

The Cutting Edge: Challenges in Medical and Surgical Therapeutics

Notalgia paresthetica is a chronic condition that, while not wrist, status post surgical repair; her only medication life threatening, produces symptoms that are incessant and was a multivitamin. She had no drug allergies. She had onerous to many patients. To date, there has been no ef- been treated previously with botulinum toxin type A in fective, long-lasting, noninvasive treatment for this con- the forehead and glabella for facial rhytids without ad- dition, which decreases the patient’s quality of life. verse reaction but without improvement in her pruritus. Her history and physical examination were indica- REPORT OF CASES tive of notalgia paresthetica.

CASE 1 THERAPEUTIC CHALLENGE

A 52-year-old white woman presented with a 2- to 4-year Common treatments for notalgia paresthetica that have history of pruritus of her upper back, which she de- provided variable relief to patients include local anes- scribed asa7onaseverity scale of 1 to 10. She reported thetics, topical corticosteroids, and topical capsaicin; how- scratching her back twice a day. She had tried moistur- ever, results with these treatments have been inconsis- izers and topical corticosteroids with no improvement. tent at best.1 With capsaicin, many patients reported She recalled that her father had had a similar itch on his burning, tingling, and pain with treatment, and most patients experienced a relapse of symptoms within a month.2 For editorial comment Oxcarbazepine was reported to reduce the severity of see page 1062 symptoms in a few cases; however, these patients reported only an improvement in their symptoms but not back for years that induced him to repeatedly scratch his resolution of them.3 One patient with a severe case of no- back on a doorpost. Her medical history was remark- talgia paresthetica was treated successfully with paraver- able only for gastroesophageal reflux disease, which was tebral nerve blocks, with bupivacaine and methylpred- responsive to ranitidine, and for rosacea, for which she nisolone acetate injected into the T3-T4 and T5-T6 used topical metronidazole. She had no drug allergies. intervertebral spaces.4 She remained symptom-free 1 year On physical examination, there was a 4ϫ4-cm hyper- after treatment. To date, there is no effective, long- pigmented patch on her right mid to upper back. Her pre- lasting, noninvasive treatment for patients with notal- sentation was consistent with notalgia paresthetica. gia paresthetica.

CASE 2 SOLUTION

A 39-year-old white woman presented with a 20-year The patients described in this article were treated with in- history of pruritus of her upper back. She described the tradermal injections of botulinum toxin type A using a itch asa5onaseverity scale of 1 to 10 and reported method similar to that used for postherpetic neuralgia.5 Spe- scratching her back on a doorpost 3 to 4 times a day. cifically, the area to be treated was demarcated based on She also described an altered sensation in the area when questioning and physical examination. Injection points were it was touched. Previous treatments, including topical marked 2 cm apart, and4Uofbotulinum toxin type A was class I steroids, pramoxine hydrochloride cream, 1%, injected superficially into each point, using a 3-mL dilu- and doxepin hydrochloride cream, 1%, had provided tion with preserved (0.9%) saline. The first patient was only minimal temporary relief. On physical examina- treated with a total of 16 U. She remains completely symp- tion, there was an approximately 4ϫ7-cm hyperpig- tom free to date (more than 18 months following treat- mented patch on her right mid upper back consistent ment), and the hyperpigmentation on her back is barely with the area of pruritus. Her medical history was sig- perceptible. The second patient was treated with 24 U and nificant only for bilateral de Quervain tendinitis of the had a considerable improvement in symptoms after her first

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 8), AUG 2007 WWW.ARCHDERMATOL.COM 980

Figure. Case 2. A, Before second treatment with botulinum toxin type A. Note hyperpigmentation as well as erythema and recent scratch marks on her right mid upper back. B, One month after second treatment with botulinum toxin type A. Although there is some residual hyperpigmentation on the right mid upper back, the area of involvement is much smaller and somewhat faded. Erythema and scratch marks are absent.

treatment. Although prior to treatment she had been scratch- ciceptive afferent C fibers, and calcitonin gene-related pep- ing her back on a doorpost 3 to 4 times every day, after tide colocalizes with substance P in most sensory ganglia 3 months she reported scratching her back only twice a day. neurons.9 Botulinum toxin type A was also found to sup- After 18 months she reported that she was not even scratch- press the release of glutamate and noradrenaline.8 ing her back every day; however, she still felt some inter- Although the mechanism of the effect of botulinum toxin mittent pruritus. At that time, a second treatment of 48 U type A on pain and itch signals in human beings has not was given. Within a week she was symptom free and has been completely elucidated, botulinum toxin type A has remained so. The hyperpigmentation on her back de- been shown clinically to be effective for several pain syn- creased in size and color (Figure) but was still evident dromes, including postherpetic neuralgia and trigeminal 1 month after the second treatment. neuralgia.12,13 It has also been reported to be effective for the pruritus of lichen simplex chronicus.5 For posther- COMMENT petic neuralgia, injections of 2 to 5 U every 1 to 2 cm have been found to relieve patients’ pain. Up to 4 sessions, 1 to Notalgia paresthetica is a sensory neuropathy that can 4 weeks apart, may be necessary to achieve complete pain 14 A similar technique has been used for the treat- include symptoms of pruritus, tenderness, burning pain, relief. ment of painful scars, such as sternotomy scars, and for treat- and hyperalgesia.2 It is unilateral and usually occurs on 5 For lichen sim- the mid to upper back. There is often a hyperpigmented ment of reflex sympathetic dystrophy. plex chronicus, 20 U was injected into each lesion.5 patch over the affected area. Other names for this con- Interestingly, although the muscle paresis and blocked dition have included puzzling posterior pigmented pur- glandular secretion induced by botulinum toxin type A puric patches, hereditary localized pruritus, and puncta wear off after 3 to 6 months, the effect of botulinum toxin pruritica (itchy points).1 Patients often describe symptoms ranging from mild itching to severe, relentless itch- type A injection on these pain syndromes seems to be ing that drives them to rub their backs on doorposts and long term. It has been hypothesized that botulinum toxin walls when they cannot reach the area of skin to scratch. type A alters feedback loops leading to changes in pain 9 This may also be true for the pruritus of li- The cause of notalgia paresthetica is unknown. One study signaling. chen simplex chronicus, but follow-up beyond 4 months demonstrated an increase in the density of intradermal was not reported in the literature.5 nerves in a biopsy sample of involved skin.6 Another study Patients who develop notalgia paresthetica describe of- suggested that nerve root impingement may be caus- ten vexing and relentless symptoms that interfere with their ative because several patients had degenerative changes daily lives. Given the lack of effectiveness of topical treat- of the vertebrae corresponding with the affected derma- ments and the invasiveness of paravertebral nerve block, tome.7 A genetic basis has been suggested.3 Treatment options to date have been unsatisfactory. injection of botulinum toxin type A has provided these pa- Botulinum toxin type A is a purified protein that in- tients with a comparatively safe and effective, as well as hibits acetylcholine release at the neuromuscular junc- durable, treatment for their notalgia paresthetica. Given tion by cleaving SNAP-25 (synaptosomal-associated pro- the duration of their symptom improvement—more than teins of 25 kDa).8 This leads to paresis of muscle by 18 months—further research should be conducted to con- chemical denervation or blocked glandular secretion of the firm the effectiveness of this treatment. exocrine glands. In the laboratory, botulinum toxin type A has also been found to affect several neurotransmitters Accepted for Publication: October 16, 2006. involved in nociception. It has been found to inhibit re- Correspondence: Pamela Kirschner Weinfeld, MD, Di- lease of substance P from cultured embryonic dorsal root vision of Dermatology, Newton-Wellesley Hospital, 2000 ganglion neurons9,10 and to reduce stimulated release of Washington St, Newton, MA 02462 (pweinfeld@partners calcitonin gene-related peptide from cultured trigeminal .org). ganglia neurons.9,11 Substance P is released by primary no- Financial Disclosure: None reported.

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 8), AUG 2007 WWW.ARCHDERMATOL.COM 981

©2007 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 Additional Contributions: Allergan Inc, Irvine, Califor- 12. Tu¨rk U, Ilhan S, Alp R, Sur H. Botulinum toxin and intractable trigeminal neuralgia. nia, provided the botulinum toxin type A used in this Clin Neuropharmacol. 2005;28(4):161-162. 13. Allam N, Brasil-Neto JP, Brown G, Tomaz C. Injections of botulinum toxin type A study. produce pain alleviation in intractable trigeminal neuralgia. Clin J Pain. 2005; 21(2):182-184. REFERENCES 14. Smith KC, Alam M. Botulinum toxin for pain relief and treatment of headache. In: Carruthers A, Carruthers C, eds. Botulinum Toxin. Philadelphia, PA: Elsevier Saunders; 2005:101-111. 1. Wallengren J, Klinker M. Successful treatment of notalgia paresthetica with topical capsaicin: vehicle-controlled, double-blind, crossover study. J Am Acad Dermatol. 1995;32(2, pt 1):287-289. 2. Odom RB, James WD, Berger TG. Andrew’s Diseases of the Skin. 9th ed. Phila- Submissions delphia, PA: WB Saunders Co; 2000:64. 3. Savk E, Bolukbasi O, Akyol A, Karaman G. Open pilot study on oxcarbazepine for Clinicians, residents, and fellows are invited to submit the treatment of notalgia paresthetica. J Am Acad Dermatol. 2001;45(4):630- cases of challenges in management and therapeutics to 632. this section. Cases should follow the established pat- 4. Goulden V, Toomey PJ, Highet AS. Successful treatment of notalgia paresthetica with a paravertebral local anesthetic block. J Am Acad Dermatol. 1998; tern. Manuscripts should be prepared double-spaced with 38(1):114-116. right margins nonjustified. Pages should be numbered 5. Heckmann M, Heyer G, Brunner B, Plewig G. Botulinum toxin type A injection in consecutively with the title page separated from the text the treatment of lichen simplex: an open pilot study. J Am Acad Dermatol. 2002; (see Instructions for Authors [http://archderm.ama-assn 46(4):617-619. .org/misc/ifora.dtl] for information about preparation of 6. Inaloz HS, Kirtak N, Erguven HG, Karakok M, Inaloz S. Notalgia paresthetica with the title page). Clinical photographs, photomicro- a significant increase in the number of intradermal nerves. J Dermatol. 2002; graphs, and illustrations must be sharply focused and sub- 29(11):739-743. mitted as separate JPG files with each file numbered with 7. Savk E, Savk O, Bolukbasi O, et al. Notalgia paresthetica: a study on pathogenesis. the figure number. Material must be accompanied by the Int J Dermatol. 2000;39(10):754-759. 8. Dressler D, Saberi FA, Barbosa ER. Botulinum toxin: mechanisms of action. Arq required copyright transfer statement (see authorship Neuropsiquiatr. 2005;63(1):180-185. form [http://archderm.ama-assn.org/misc/auinst_crit 9. Aoki KR. Review of a proposed mechanism for the antinociceptive action of botu- .pdf]). Preliminary inquiries regarding submissions for linum toxin type A. Neurotoxicology. 2005;26(5):785-793. this feature may be submitted to George J. Hruza, MD 10. Welch MJ, Purkiss JR, Foster KA. Sensitivity of embryonic rat dorsal root ganglia ([email protected]). Manuscripts should be submitted via neurons to clostridium botulinum neurotoxins. Toxicon. 2000;38(2):245-258. our online manuscript submission and review system 11. Durham PL, Cady R, Cady R. Regulation of calcitonin gene-related peptide se- (http://manuscripts.archdermatol.com). cretion from trigeminal nerve cells by botulinum toxin type A: implications for migraine therapy. Headache. 2004;44(1):35-42.

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 8), AUG 2007 WWW.ARCHDERMATOL.COM 982