Dermatologic Therapy, Vol. 28, 2015, 210–215 Printed in the United States  All rights reserved

C 2015 Wiley Periodicals, Inc. V

DERMATOLOGIC THERAPY ISSN 1396-0296

ORIGINAL PAPERS

Use of transcutaneous electrical nerve stimulation for chronic pruritus Basma Mourad Mohammad Ali*, Doaa Salah Hegab*, & Hanan Mohammad El Saadany† *Dermatology and Venereology Department, Faculty of Medicine, Tanta University, and †Physical Medicine, Rheumatology & Rehabilitation Department, Faculty of Medicine, Tanta University, Tanta, Egypt

ABSTRACT: Pruritus is a distressing symptom in many dermatological as well as systemic conditions, and it is sometimes very chronic and relapsing. Transcutaneous electrical nerve stimulation (TENS) is an inexpensive form of analgesia that could also ameliorate itching. This study aimed to evaluate TENS efficacy in patients with pruritus due to some types of chronic eczema, and in patients with chronic hepatic disease. Ten patients with atopic dermatitis (AD), 20 patients with lichen simplex chronicus (LSC), and 16 patients with chronic liver disease having chronic distressing pruritus received three sessions of TENS weekly for 12 sessions, and the effect on the visual analogue scale (VAS) scores was recorded after 2 weeks of therapy, at treatment end, and after an additional month for follow up. There was a statistically significant decline in the mean VAS score for studied groups at weeks 2 and 4 of therapy compared to baseline, but the improvement was more significant in patients with AD, and LSC (p < 0.001 for both) than in those with chronic liver disease (p < 0.01) who also showed an early re-elevation of VAS score on follow up. TENS therapy holds promise as a palliative, alternative, safe and inexpensive treatment for patients with some chronic pruritic conditions. KEYWORDS: chronic, pruritus, transcutaneous electrical nerve stimulation

Introduction Management of patients with chronic intractable pruritus is a great challenge. Pruritus could be categorized into: pruritoceptive (itch primarily generated within the skin as in atopic dermatitis (AD), and lichen simplex), neurogenic (including systemic causes of itch as in hepatobiliary disorAddress correspondence and reprint requests to: Doaa Salah Hegab, MD, Faculty of Medicine, Dermatology and Venereology Department, Tanta University Hospitals, El Geish Street, Tanta 31111, Egypt, or email: [email protected].

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ders, and disordered processing of itch within the central nervous system), neuropathic (caused by an anatomical lesion of the peripheral or central nervous system), and psychogenic. These categories are not mutually exclusive, and two or more classes of itch may occur concurrently in the same patient (1). AD is a chronic relapsing inflammatory skin disease characterized by eczematous skin lesions, xerosis, and severe pruritus which may lead to lichenification (2). It affects 10–20% of children worldwide and approximately 2–3% of the adult population, and it affects quality of life of patients and their families. It could be a challenging

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disease to treat, and current treatment modalities can be associated with long term side effects (3). Lichen simplex chronicus (LSC) is a chronic condition characterized by lichenified plaques resulting from constant repetitive compulsive desire for scratching or rubbing the skin on a part of the body (4). It usually affects adults with mild preference for females with anxiety (5). Various treatments, including potent topical corticosteroids, doxepin cream, capsaicin cream, and intralesional corticosteroids are used for treatment of LSC, but in most patients, however, they do not permanently abolish the symptom (6,7). Pruritus is a consequence of all types of liver diseases, including those caused by inflammatory destruction of intra- and extrahepatic biliary structures leading to cholestasis and those associated with hepatocellular injury (8). Pruritus is one of the most common symptoms reported by people with hepatitis C (20%), and sometimes it could be the only symptom (9). It is more commonly found in people with advanced liver disease and cirrhosis, and it might be localized or generalized. Pruritus with hepatitis C can be related to high bilirubin levels, autoimmune disease, or dry skin, and can be a side effect of treatment with interferon/ribavirin (10). Indeed, the itch from liver disease can be so severe that it is an indication for liver transplantation even in the absence of liver failure (8,9). Transcutaneous electrical nerve stimulation (TENS) uses a pulsed electric current generated transcutaneously by a device, causing impulses to be carried along large-diameter afferent nerves. Subsequently, it produces presynaptic inhibition of nociceptive A delta and C fibers involved in the pain gates in the substantia gelatinosa and thus have an effect in pain control (11). Pain and pruritus are two sensations that share similarities both at the peripheral and central levels, and thus TENS could also provide antipruritic effect in itchy skin disorders (12). So far, TENS has been reported to offer pruritus relief in generalized pruritus (13), prurigo nodularis, mycosis fungoides (14), and burns (15). This work aimed to evaluate TENS efficacy in patients with pruritus due to some types of chronic eczema as AD, and LSC, and in patients with chronic hepatic disease.

Materials and methods The study was approved by the local ethics committee of The Faculty of Medicine, Tanta Univer-

sity. The study included 10 patients with AD older than 7 years, 20 patients with LSC, in addition to 16 patients with chronic liver disease having chronic intractable pruritus who were collected from the outpatient clinics of Dermatology and Venereology Department and Internal Medicine Department – Tanta University Hospitals. An informed consent was obtained from every patient (from the parents in cases of children with AD). All included patients had chronic, relapsing pruritus, and all had received commonly used topical corticosteroids and systemic antihistaminics without satisfactory response. AD patients (group I) included six females (60%) and four males (40%), and their ages ranged from 7 to 25 years with a mean of 11.4 6 6.6. Diagnosis of patients with AD was done according to Hanifin and Rajka features (16). Appropriate cases must have at least three major and three minor characteristic features. The severity of AD was assessed according to the SCORAD index (17), and patients with severe AD (SCORAD > 50) in need for systemic therapy were excluded. Patients with LSC (group II) included fourteen females (70%) and six males (30%), and their ages ranged from 18 to 54 years with a mean of 31.3 6 9.4. Their inclusion criteria were as follows; a history of intermittent attacks of itching in localized area, age above 18 years, presence of at least one localized lichenified plaque of LSC on the following sites: neck, back, arm, or leg for a period of at least 1 year. Patients with intractable pruritus due to chronic liver disease (group III) (nine patients (56.25%) with chronic hepatitis C, and seven patients (43.75%) with liver cirrhosis) included five females (31.25%) and eleven males (68.75%) whose ages ranged from 30 to 60 years. The diagnosis of cirrhosis was based on; clinical examination, abdominal ultrasonography, and laboratory findings. The diagnosis of hepatitis C virus (HCV) was based on anti-HCV Abs (by third generation ELISA), and quantitation of HCV RNA by quantitative real-time polymerase chain reaction. All hepatic patients were subjected to full history taking and thorough clinical examination. In addition, routine biochemical panel, complete blood count, thyroid function tests, serum total immunoglobulin E, chest X-ray, urine and stool analysis, liver function tests, serology for HBsAg, and IHA for bilharzial antibodies were done. Exclusion criteria included patients with cardiovascular diseases including cardiac pacemaker insertion, neuropathies or loss of sensation at the treatment site, as well as those patients with

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Table 1. Baseline clinical characteristics of the studied groups of patients Group I n=10 Age in years, Mean(SD) Disease duration in years, Mean(SD) Gender, n(%) Female Male Lesional Leg location, n(%) Arm Back Neck

Group II n=20

Group III n=16

Tests 2

v or f

p-value

11.4(6.6)

31.3(9.4)

46.8(8.1)

54.369

< 0.001*

4.1(2.0) 6(60.0) 4(40.0) 4(40.0) 6(60.0) 0(0.0) 0(0.0)

4.5(2.4) 14(70.0) 6(30.0) 9(45.0) 4(20.0) 3(15.0) 4(20.0)

5.1(2.9) 5(31.3) 11(68.8) 6(37.5) 6(37.5) 4(25.0) 0(0.0)

0.569 5.544

0.570 0.063

10.974

0.089

*=sigmlicant. Group I5atopic dermatitis, group II5lichen simplex chronicus, group III5 hepatic itch.

other inflammatory skin diseases or systemic diseases causing pruritus like metabolic or chronic kidney diseases. In addition, pregnant females and breast-feeding mothers were also excluded. All patients included in the study abstained from using antihistamines and topical corticosteroids 2 weeks before TENS sessions, and during the study period. Patients were treated by exposure of the most itchy distressing skin lesion to TENS for three sessions per week (one every other day), for a maximum of 12 sessions or until symptomatic cure at the Physical medicine, Rheumatology & Rehabilitation Department of Tanta University Hospitals. The duration of each session was 30 minutes, with high frequency (50–100 Hz) and pulse width 40–75 ls given from a dual-channel portable TENS unit with 4 3 5 cm surface carbon electrodes. TENS was applied to the same itchy lesion through the treatment sessions for every patient. Patient-reported treatment assessment Improvement or deterioration in pruritus was recorded by the patient- or the nursing parent in cases of children- interview with the same dermatologist using a horizontal visual analogue scale (VAS) score for evaluation of pruritus severity at baseline, mid treatment (second week), end of treatment (fourth week), and after an additional month for follow up. The scale ranged from 0 (no pruritus) to 10 (most severe pruritus). Physician-reported treatment assessment Objective clinical evaluation was done by another dermatologist for the lesions at the beginning of

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the study, followed by rating the pruritus at the end of therapy (4 weeks) on a six-point scale (21 5 worsening of itch, 0 5 no improvement, 1 5 mild improvement, 2 5 moderate improvement, 3 5 marked improvement, 4 5 complete improvement). Assessment of safety and tolerability The patients were asked to report any side effects as local erythema at site of electrode application, irritation, swelling, numbness, or dysaesthesia at each session.

Statistical analysis Statistical presentation and analysis was conducted using the mean, standard deviation, and Fisher’s exact v2 tests. Mann–Whitney U-test was carried out to compare the scales between the groups by Statistics Package for Social Sciences (SPSS) version18. ANOVA test was used for comparison among different times in the same group in quantitative data. p-value less than 0.05 was considered statistically significant.

Results Clinical data of the included patients are provided in Table 1. All included patients completed the treatment and returned for follow up. Analysis of patient-reported changes in VAS score FIGURE 1a summarizes the VAS scores for patients of the three studied groups at the baseline of the study, at mid treatment (after 2

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FIG. 1. (a) Effect of TENS treatment on itch intensity expressed by VAS during treatment and at follow up after 1 month of last session. (b) Physician-reported clinical scoring of improvement in patients of the three studied groups at the end of treatment sessions. Group I 5 atopic dermatitis, group II 5 lichen simplex chronicus, group III 5 hepatic itch.

Table 2. Outcomes of transcutaneous electrical nerve stimulation on VAS score of the studied groups of patients Paired t-test

VAS score

Group I n=10

Group II n=20

Group III n=16

t

P*

Base line, mean(SD) At 2 weeks, mean(SD) At 4 weeks, mean(SD) Follow up, mean(SD) p†

7.1(1.5) 4.5(1.1) 1.8(1.3) 2.7(1.3) < 0.001‡

7.7(1.3) 4.9(1.5) 2.5(1.7) 3.3(1.6) < 0.001‡

7.1(1.5) 4.8(0.9) 2.8(0.8) 4.0(1.0)

1.050 0.352 1.734 2.990

0.359 0.705 0.189 0.061

< 0.01§

Group I5atopic dermatitis, group II5lichen simplex chronicus, group III5hepatic itch. *Two-tailed p-values from Mann-Whitney U-test assessments for between the groups of atopic dermatitis, lichen simplex chronicus and hepatic pruritus. † Two-tailed P-values from Friedman analysis of variance (ANOVA) assessments for among baseline, week 2, week 4 treatment, and after 1 month for follow up. ‡ There was statistically significant difference between baseline and other weeks (2, 4, and follow up) (p < 0.001 for all). § There was statistically significant difference between baseline and both week 2 and week 4 of treatment (p < 0.01) but a statistically insignificant difference between baseline and follow up after 1 month of the end of sessions (p=0.062)

weeks), at the end of treatment (4 weeks of TENS therapy), and after 1 month of the end of sessions (follow up). All patients included had relief of their pruritus at varied degrees. The mean reductions in VAS scores after 2 and 4 weeks of TENS were statistically significant compared to baseline (p < 0.001 in groups I and II, and p < 0.01 in group III), (Table 2). After 1 month of follow up, the mean difference in VAS scores from baseline were still significant in the first two groups (p < 0.001), and it was insignificant statistically in the third group (p 5 0.062), (Table 2). Analysis of physician-reported changes in VAS score The clinical scoring of improvement on TENS sessions as reported by the examining dermatologist is shown in FIG. 1b.

At 4 weeks of therapy, 50% of AD patients and 45% of LSC patients showed marked improvement, while most of the patients with hepatic causes of pruritus (62.5%) showed only mild to moderate improvement. In all studied groups, the clinical efficacy of TENS treatment did not have any statistically significant relation with either the gender of patient, or location of treated lesion (p > 0.05 for all). Regarding the assessment of safety and tolerability; the side effects reported by the patients were minimal and limited to mild local erythema in two patients of group I, and four patients of group III which did not require withdrawal of TENS therapy. Additionally, mild irritation and numbness during application of the electrodes which relieved spontaneously after few minutes were reported in one patient of group I, three patients of group II, and five patients of group III. Overall, a good tolerability was obtained in

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all studied groups with no significant reported side effects.

Discussion Findings from this study demonstrate that treatment with TENS is associated with considerable beneficial impact in measures of VAS score in AD, LSC, and to a less degree in liver disease-induced pruritus and is characterized by great safety. This significant reduction of pruritus led to improvement of the inflammatory lesions of the skin and so, the dermatologist-reported outcomes of clinical efficacy also came parallel. It is obvious that the efficacy of TENS began as early as the second week of treatment sessions in all studied groups and this might suggest a placebo-like effect in early treatment phases. However the noticed improvement which was maintained to a considerable degree even after 1 month of treatment end minimizes the role of this possible placebo-effect of TENS in patients with AD, and LSC. Patients with hepatic pruritus showed a less significant improvement of their VAS scores through the treatment sessions than AD and LSC patients, and also an earlier reelevation of their VAS score, where the difference between their baseline VAS and its levels after 1 month of TENS end (at follow up) was insignificant. These results could be attributed to the complexity of pruritus pathogenesis in hepatic patients which is attributed at least inpart, to increased central opioidergic tone aided by a multitude of coexistent peripheral cofactors (8). A previous study had found that scratching activity was significantly suppressed in association with placebo tablet in a controlled, double-blind study on hepatic patients. Their findings supported the exploration of the placebo effect of treatment modalities on the itch sensation in patients with this complication of liver disease (18). As Egypt has the highest prevalence of HCV in the world, estimated nationally at 14.7% among the 15–59 years age group (19), the development of a palliative, safe therapy for pruritus in chronic liver disease is a research priority in our country. This study suggests that TENS might offer a supportive relieving tool for those patients. It should be noted that TENS efficacy for pain relief has been well established but the exact mechanism is unclear. Some possible explanations have been proposed such as neuromodulation via presynaptic inhibition in the dorsal horn of the spinal cord (gate control theory), endogenous pain control (via endorphins, enkephalins,

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and dynorphins), direct inhibition of an abnormally excited nerve, and restoration of afferent input (20). TENS could theoretically provide antipruritic effect in itchy skin disorders and the results of the current study came in agreement with these theories, but we should consider that the follow up duration was quietly short, and that a longer-term evaluation would be valuable. The results of the current study were in accordance with other studies conducted on patients with AD (12,21–23), and LSC (24,25), but there are very few data about the use of TENS to alleviate pruritus in chronic hepatic patients. Conversely, other authors have compared the efficacy of cutaneous field stimulation (25 minutes, 16 electrodes, 4 Hz per electrode, up to 0.8 mA) and TENS (100 Hz, up to 26 mA) on AD chronic itch. They reported that both treatments augmented the itch sensation during ongoing stimulation; however, after cessation of cutaneous field stimulation, but not TENS, the itch sensation was significantly depressed for up to 7 hours (26). Moreover, Ozawa et al., had found that neuroselective TENS (5 Hz alternating current) preferentially evoked body area-specific different responses, where it induced itch at the dorsal surface of the hand and ankle, and a sensation without itch at the head and neck site (27). € ksek et al., had found that back lesions Yu showed low current perception and less response to TENS than lesions on legs. They attributed their findings to body area–specific factors that could affect the perception sensitivities or to the difference in vascular supply between different sites (25). In the current study, the location of the lesion treated by TENS did not impart any effect on the clinical response to sessions and this finding could be attributed to the fact that most of our patients (76%) had received TENS for lesions on legs or arms and only 8.7% of patients had lesions on the neck and 15.2% had lesions on the back. € ksek et al., report had detected a Although Yu better response to TENS in female patients than males which was attributed by the authors to the difference in pain threshold between females and males (25), the results of the current study showed that gender of the patient did not affect the clinical response in a significant manner.

Conclusion TENS considerably alleviated chronic pruritus associated with AD, and LSC, while it improved

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pruritus with chronic hepatic disease to a less degree. It is a promising, simple, safe, tolerable, and nonexpensive technique for patients with chronic pruritus. It is advisable to be tried as an adjuvant, alternative treatment for chronic itchy conditions in which long treatment periods by drugs are not recommended. Based on the results of the current study, larger scale studies are recommended to assess the therapeutic effect of TENS on pruritus associated with different cutaneous as well as internal diseases and to detect its impact on patient’s quality of life.

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12. Tang WYM, Chan LY, Lo KK, Wong TW. Evaluation on the antipruritic role of transcutaneous electrical nerve stimulation in the treatment of pruritic dermatoses. Dermatology 1999: 199: 237–241. 13. Monk BE. Transcutaneous electronic nerve stimulation in the treatment of generalized pruritus. Clin Exp Dermatol 1993: 18: 67–68. 14. Greaves MW. Recent advances in pathophysiology and current management of itch. Ann Acad Med Singapore 2007: 36: 788–792. 15. Whitaker C. The use of TENS for pruritus relief in the burns patient: an individual case report. J Burn Care Rehabil 2001: 22: 274–276. 16. Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venreol 1980: 92: 44–47. 17. [No authors listed]. Severity scoring of atopic dermatitis: the SCORAD index. Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology 1993: 186 (1): 23–31. 18. Bergasa NV. The itch of liver disease. Semin Cutan Med Surg 2011: 30 (2): 93–98. 19. Mohamoud YA, Mumtaz GR, Riome S, Miller D, AbuRaddad LJ. The epidemiology of hepatitis C virus in Egypt: a systematic review and data synthesis. BMC Infect Dis 2013: 13: 288. 20. DeSantana JM, Walsh DM, Vance C, Rakel BA, Sluka KA. Effectiveness of transcutaneous electrical nerve stimulation for treatment of hyperalgesia and pain. Curr Rhematol Rep 2008: 10: 492–499. 21. Bjørna˚ H, Kaada B. Successful treatment of itching and atopic eczema by transcutaneous nerve stimulation. Acupunct Electrother Res 1987: 12 (2): 101–112. 22. Buddenkotte J, Steinhoff M. Pathophysiology and therapy of pruritus in allergic and atopic diseases. Allergy 2010: 65 (7): 805–821. 23. Chen CJ, Yu HS. Acupuncture, electrostimulation, and reflex therapy in dermatology. Dermatol Ther 2003: 16 (2): 87–92. 24. Engin B, Tufekci O, Yazici A, Ozdemir M. The effect of transcutaneous electrical nerve stimulation in the treatment of lichen simplex: a prospective study. Clin Exp Dermatol 2009: 34: 324–328. € ksek J, Sezer E, Aksu M, Erkokmaz U. Transcutaneous 25. Yu electrical nerve stimulation for reduction of pruritus in macular amyloidosis and lichen simplex. J Dermatol 2011: 38 (6): 546–552. 26. Nilsson HJ, Psouni E, Carstam R, Schouenborg J. Profound inhibition of chronic itch induced by stimulation of thin cutaneous nerve fibres. J Eur Acad Dermatol Venereol 2004: 18 (1): 37–43. 27. Ozawa M, Tsuchiyama K, Gomi R, Kurosaki F, Kawamoto Y, Aiba S. Neuroselective transcutaneous electric stimulation reveals body area-specific differences initch perception. J Am Acad Dermatol 2006: 55 (6): 996–1002.

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Use of transcutaneous electrical nerve stimulation for chronic pruritus.

Pruritus is a distressing symptom in many dermatological as well as systemic conditions, and it is sometimes very chronic and relapsing. Transcutaneou...
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