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Cutaneous Field Stimulation in the Treatment of Severe Itch
Joanna Wallengren, MD, PhD;
Frank Sundler, PhD
Arch Dermatol. 2001;137:1323-1325.
ABSTRACT
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Objective To evaluate the efficacy of cutaneous field stimulation of C fibers for the treatment of itchy skin and its effect on peripheral nerve fibers as shown in skin biopsy specimens.
Design We conducted an open-label uncontrolled study of 19 patients with itching. Each patient applied a flexible plate containing electrodes to the itchy area for 20 minutes at a time once daily for 5 weeks to stimulate nerve fibers with a constant current (0.8 mA). Skin biopsy specimens were collected before treatment and at the end of treatment and were immunostained for calcitonin gene–related peptide and protein gene product 9.5.
Setting University hospital in Lund, Sweden.
Patients Sixteen patients with notalgia paresthetica or brachioradial pruritus and 3 with generalized itch.
Interventions Cutaneous field stimulation and punch biopsies of the itchy skin.
Main Outcome Measures Visual analog scale for assessment of itching and counting the immunoreactive nerve fibers in 3-mm biopsy specimens.
Results Patients with localized itching experienced a reduction in mean values on the visual analog scale (from 78% before treatment to 42% by the end of the fifth week). The number of protein gene product 9.5– immunoreactive nerve fibers in the epidermis was reduced by 40% by the end of treatment compared with baseline values.
Conclusions Cutaneous field stimulation is an effective alternative for the treatment of localized itching. The reduction in itching is accompanied by degeneration of the epidermal nerve fibers, as evidenced by the loss of protein gene product 9.5 immunoreactivity.
INTRODUCTION
ITCHING IS transmitted by C fibers in the dermoepidermal junction area. Recently, a new technique termed cutaneous field stimulation (CFS), which electrically stimulates thin afferent fibers, including nociceptive C fibers, was reported to inhibit histamine-induced itching.1 We evaluated the effects of long-term CFS treatment in patients with severe itching, as well as the possible effects on the peripheral nerves involved. To map the distribution of sensory nerve fibers in skin treated with CFS, biopsy specimens were taken before and after treatment.
PATIENTS AND METHODS
A total of 19 patients with severe pruritus were enrolled in the study. Sixteen had localized itching, and 3 others complained of generalized pruritus. Patients were advised to apply the CFS device (Figure 1) once daily 20 to 30 minutes at a time during the following 5 weeks and to evaluate their symptoms before the treatment and at home at the end of each week using a visual analog scale (VAS). Full-thickness skin biopsy specimens were obtained from the itchy skin of 10 patients before and at the end of the 5 weeks of treatment by means of a 3-mm punch. Details on the processing of biopsy specimens have been presented previously.2 The number of immunoreactive fibers in each section was counted using a Leica Aristoplan epifluorescence microscope (x16 objective) (Leica Lasertechnik GmbH, Heidelberg, Germany). The mean of the counts in the 3 sections was used to represent each specimen.
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Figure 1. Cutaneous field stimulation device, consisting of a flexible electrode rubber plate (8 x 8 cm) to be fastened on a patch of itchy skin, a flat reference electrode (5 x 5 cm) to be placed on the same part of the body, and a stimulator (a 9-V battery). The pulse amplitude is adjustable from 0 to 10 A to control the intensity of the stimulus.
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RESULTS
Seventeen (89%) of the 19 patients with severe itching completed the study and the protocol (Table 1). Three patients (17%) with generalized pruritus did not find any relief on the most itchy areas when CFS was applied. One patient with prurigo nodularis left the study within a week because CFS was not helping, and another patient who completed the study but not the protocol reported no significant improvement. One patient with mycosis fungoides involving itch that was evaluated initially at 100% left the study with the VAS unchanged. One patient with brachioradial pruritus discontinued treatment after 3 weeks and went on treating the itch with capsaicin cream (0.025%).3 The results of the treatment are presented in Table 1. The patients with localized itching reported improvement. The mean VAS values are shown in Figure 2. A follow-up of the first 14 patients 3 to 12 months after treatment revealed a relapse in all patients but 2 (patients 2 and 5). Biopsy specimens were taken from 14 patients before CFS treatment and from 10 (patients 1-10) after treatment. Nerve fiber density in the whole-skin biopsy samples as measured by protein gene product immunoreactivity was unchanged after CFS treatment compared with baseline values. The density of the epidermal nerve fibers was reduced (Figure 3) in 7 patients (patients 3, 4, 6, 8, 10, 12, and 13), of whom all but 3 (patients 6, 10, and 12) improved with treatment. In the biopsy specimens taken after treatment, bundles of nerve fibers were regularly observed just beneath the epidermal or dermal layers (Figure 4).
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Details of Patients Treated With Cutaneous Field Stimulation*
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Figure 2. Localized itch in response to cutaneous field stimulation showing mean values on the visual analog scale (n = 16). For statistical evaluation we used the t test for paired data. Asterisk indicates P=.01; dagger, P .001.
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Figure 3. Nerve fiber density in biopsy specimens from whole-skin samples and the epidermis (epidermal nerve fibers) before and after cutaneous field stimulation treatment (n = 10). After treatment, the number of epidermal nerve fibers was reduced (t test for paired data).
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Figure 4. Skin biopsy specimen (patient 13) immunostained for protein gene product 9.5 before (A) and after (B) cutaneous field stimulation treatment. Arrows indicate nerve fibers (original magnification x200).
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COMMENT
In this open trial, localized itching responded to CFS treatment, and pruritus was reduced by 49% at the end of the fifth week compared with baseline. In patients with back pain, Deyo et al4 found that scores for pain severity, pain frequency, and functional status improved an average of 20% to 40% after the application of sham transcutaneous electrical nerve stimulation, despite the chronicity of pain (average duration, 4 years). Cutaneous field stimulation reduced the number of epidermal nerve fibers in all patients but 3, and this reduction was paralleled by relief of itch. This indicates that the treatment actually influences specific active components necessary for perceiving itch. Protein gene product 9.5 is a cytoplasmatic protein rather than a transmitter stored in vesicles or granules. Thus, the disappearance of protein gene product immunoreactivity indicates a degeneration of nerve fibers in the epidermis. The appearance of thick bundles of protein gene product–immunoreactive nerve fibers just beneath the epidermis after treatment with CFS may indicate nerve regeneration.
In the present study, itch relapsed gradually after the discontinuation of CFS, indicating nerve fiber regeneration into the epidermis. Nerve proliferation in the form of bundles is seen during the process of healing of wounds in which peripheral nerves have been damaged.2 Recently, topical treatment with capsaicin was reported to induce a loss of epidermal nerve fibers together with a reduction in pain.5 It appears that CFS is a viable treatment for localized itching. Generalized pruritus in mycosis fungoides did not respond to CFS. This may be related to the widespread nature of itching and the difficulties in using CFS at many skin locations. Chronic lichenified patches of prurigo nodularis did not respond to CFS either. This may be a result of the epidermal layer being severely hypertrophic in prurigo nodularis, making it difficult for the electrodes to reach to the dermoepidermal junction.
AUTHOR INFORMATION
Accepted for publication May 23, 2001.
This work was supported by grants from the Skane County Councils for Research and Development Foundation, Kristianstad; the Asthma and Allergy Foundation; and the Åke Wiberg Foundation Stockholm, Sweden.
We thank Doris Persson for help with immunocytochemistry.
Corresponding author and reprints: Joanna Wallengren, MD, Department of Dermatology, Lund University Hospital, SE-221 85 Lund, Sweden (e-mail: Joanna.Wallengren{at}derm.lu.se).
From the Departments of Dermatology (Dr Wallengren) and Neuroendocrine Cellbiology (Dr Sundler), Lund University Hospital, Lund, Sweden.
REFERENCES
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1. Nilsson HJ, Levinsson A, Schouenborg J. Cutaneous field stimulation (CFS): a new powerful method to combat itch. Pain. 1997;71:49-55.
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2. Wallengren J, Chen D, Sundler F. Neuropeptide-containing C-fibres and wound healing in rat skin: neither capsaicin nor peripheral neurotomy affect the rate of healing. Br J Dermatol. 1999;140:400-408.
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3. 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.
4. Deyo RA, Walsh NE, Martin DC, Schoenfeld LS, Ramamurthy S. A controlled trial of transcutaneous electrical nerve stimulation (TENS) and exercise for chronic low back pain. N Engl J Med. 1990;322:1627-1634.
ABSTRACT
5. Nolano M, Simone DA, Wendelschafer-Crabb G, Johnson T, Hazen E, Kennedy WR. Topical capsaicin in humans: parallel loss of epidermal nerve fibers and pain sensation. Pain. 1999;81:135-145.
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