Iontophoretic Administration of Dexamethasone Sodium Phosphate for Acute Epicondylitis

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1 /103/ $02.00/0 THE AMERICAN JOURNAL OF SPORTS MEDICINE, Vol. 31, No American Orthopaedic Society for Sports Medicine Iontophoretic Administration of Dexamethasone Sodium Phosphate for Acute Epicondylitis A Randomized, Double-Blinded, Placebo-Controlled Study Robert P. Nirschl,* MD, Dennis M. Rodin, MD, Derek H. Ochiai, MD, and Craig Maartmann-Moe, MPT, for the DEX-AHE Study Group From the Nirschl Orthopedic & Sportsmedicine Clinic, Arlington, Virginia Background: A better treatment modality is needed to control the pain of medial or lateral epicondylitis (tennis elbow). Hypothesis: Dermal iontophoretic administration of dexamethasone sodium phosphate will be significantly more effective in controlling pain than a placebo in patients with medial or lateral elbow epicondylitis. Study Design: Randomized, double-blinded, placebo-controlled study. Methods: On six occasions, 1 to 3 days apart within 15 days, 199 patients with elbow epicondylitis received 40 ma-minutes of either active or placebo treatment. Results: Dexamethasone produced a significant 23-mm improvement on the 100-mm patient visual analog scale ratings, compared with 14 mm for placebo at 2 days and 24 mm compared with 19 mm at 1 month. More patients treated with dexamethasone than those treated with placebo scored moderate or better on the investigator s global improvement scale (52% versus 33%) at 2 days, but the difference was not significant at 1 month (54% versus 49%). Investigator-rated pain and tenderness scores favored dexamethasone over placebo at 2 days. Patients completing six treatments in 10 days or less had better results than those treated over a longer period. Conclusions: Iontophoresis treatment was well tolerated by most patients and was effective in reducing symptoms of epicondylitis at short-term follow-up American Orthopaedic Society for Sports Medicine Medial or lateral epicondylitis, or tennis elbow, is the most common disorder of the elbow in adults, with an incidence of 4 to 7 per 1000 per year seen in general practice. 10 The duration of an average episode is estimated to be between 6 months and 2 years. 16 Medial or lateral epicondylitis occurs in men more than women and tends to involve the subject s dominant side. Characteristically, symptoms of epicondylitis occur in patients more than 35 years of age whose activity level, sports, or occupation requires repetitive activity and who have a compromised fitness or conditioning level. The repetitive * Address correspondence and reprint requests to Robert P. Nirschl, MD, Nirschl Orthopedic & Sportsmedicine Clinic, Virginia Hospital Center Arlington, 1715 North George Mason Drive, Suite 504, Arlington, VA The names and institutions of investigators who participated in this study are listed in the Acknowledgments. Funding was received from commercial parties related to products named in this study. See Acknowledgments for funding information. strain on the tendons of the forearm muscles at the point at which they attach to the elbow leads to inflammation and ultimately to degenerative changes such as tendinosis, microtears, and fibrous tissue healing at these points. 13 Common pain-relieving treatments for epicondylitis include nonsteroidal antiinflammatory medications, splinting, braces, ultrasound, phonophoresis, electrical stimulation, and application of heat or cold. Injections may be required for drug administration because topical applications of nonsteroidal antiinflammatory medications and corticosteroids do not diffuse rapidly or adequately through the skin to a sufficient depth. Although injections have been effective in reducing the symptoms of epicondylitis, the benefits are often outweighed by the possible adverse effects. It is well documented that adverse events may occur after local steroid injection into joints and tendons, including tendon rupture, nerve injury, joint de- 189

2 190 Nirschl et al. American Journal of Sports Medicine struction, infection, chemical neuritis, skin atrophy, and skin pigmentation changes. 5,7,8,14,15 Iontophoresis is a drug delivery method that uses a small, external electric current to drive water-soluble ionic drugs through the skin. Iontophoresis can deliver drugs locally in high concentrations, which may provide therapeutic effects with fewer local side effects. 6 Iontophoresis of dexamethasone is routinely used in physical medicine and rehabilitation as a treatment modality for patients with various musculoskeletal inflammatory conditions. 3,9,11,17 Investigators have reported increased range of motion, improved function, and decreased pain in patients who had musculoskeletal conditions and who received treatment with iontophoresis of dexamethasone. The objective of this study was to evaluate the safety and effectiveness of dermal iontophoretic administration of dexamethasone sodium phosphate 0.4% injection compared with a placebo of saline solution for the treatment of acute epicondylitis in a multicenter, double-blinded, placebo-controlled study. MATERIALS AND METHODS Patients Patients were recruited from 11 centers across the United States. The study, including potential risks and benefits, was clearly explained to each patient. Institutional Review Board approval for the study was obtained at each site, and all patients gave written informed consent before participation. Patients were eligible for the study if they were between 18 and 75 years of age and had clinical signs leading to a diagnosis of medial or lateral humeral epicondylitis, if they had a duration of symptoms of 3 months or less during the most recent episode before the screening evaluation, and if the investigator s global evaluation of the severity of epicondylitis at screening and at the baseline evaluation was rated moderate or greater intensity. Patients were excluded from the study if they had recurrent injury of the subject area, bilateral or multiple affected areas, and had an injection of a steroid into the affected area within the past year or prior surgery to correct the problem. Other grounds for exclusion were use of nonsteroidal antiinflammatory medications, systemic and local corticosteroids, or analgesics within 3 days of study participation; involvement in a lawsuit or workers compensation claim for any medical condition; or history of rheumatoid arthritis, degenerative arthritis, polyarthritis, carpal tunnel syndrome, rotator cuff tendinitis, neurologic abnormalities in the affected area, muscular dysfunction, peripheral neuropathy, radial nerve entrapment, or fracture or tumor of the affected area. Study Design and Procedures Each patient was screened for study enrollment within 1 week ( 2 days) before the baseline visit. At the screening visit, each patient underwent a complete physical examination, including medical history, laboratory tests, and clinical evaluations. Patients who met the study inclusion criteria were invited to participate in the study and were scheduled for their first treatment within 7 days ( 2 days) of the screening visit. At the baseline evaluation, patient eligibility was confirmed by a thorough review of the patient s entire medical history, laboratory tests, and clinical evaluations obtained during the screening visit. Concomitant medications were reviewed, and patients and investigators completed clinical evaluations. Patients who continued to meet the eligibility criteria for the study were randomized to one of two treatment arms: dermal iontophoretic administration of dexamethasone sodium phosphate, 0.4% injection (American Regent Laboratories, Shirley, New York), or dermal iontophoretic administration of bacteriostatic sodium chloride injection, 0.9%. Patients were randomized according to a computer-generated randomization schedule, and randomization was stratified according to initial disease severity so that equal numbers of patients with a disease severity of very severe at baseline would receive each treatment. (Only one patient had a score of very severe and was randomized to the dexamethasone group.) Both the patients and the investigator were blinded as to study treatment. The study sponsor supplied the active and placebo solutions in indistinguishable 30-ml multipledose, glass bottles. A tear-off label with a code for active or placebo was affixed to each bottle of study medication. The sealed codes were kept by the study s statistician and could be broken in case of a medical emergency. Iontophoresis was administered by using the IOMED Phoresor Iontophoretic Drug Delivery System (IOMED, Inc., Salt Lake City, Utah). Either 2.5 ml of dexamethasone sodium phosphate 0.4% injection or 2.5 ml of placebo saline solution was instilled into a GelSponge pad (IOMED, Inc.) with a calibrated syringe immediately before application of the pad to the skin. The skin where both electrodes were to be located was prepared by briskly rubbing for 6 to 8 seconds with alcohol and then allowed to dry thoroughly. Electrodes were not applied to damaged skin. The hydrated drug electrode pad, connected to the negative lead clip, was positioned over the medial or lateral epicondyle at its most tender site. The dispersive electrode was connected to the positive lead clip to complete the circuit and was placed proximal or distal to the drug electrode over a major muscle (biceps, triceps, or on the forearm). Each patient received 40 ma-minutes of either the active or placebo treatment on six occasions. Patients received current of up to 4.0 ma, depending on their sensitivity. Once the preset dose of 40 ma-minutes was delivered, the current automatically ramped down to 0 ma. Treatments were spaced 1 to 3 days apart, and all six iontophoresis treatments were completed within a 15-day ( 2 days) period. Two days after their last treatment, patients returned to the clinic, and efficacy assessments were completed by the patient and investigator. One month after their last iontophoresis treatment, patients completed a questionnaire that assessed efficacy and were contacted by telephone to ascertain whether any adverse events had occurred. Patients were not to begin concurrent use of other treatments for their condition. If a patient had been using a

3 Vol. 31, No. 2, 2003 Iontophoretic Administration of Dexamethasone for Epicondylitis 191 treatment before study enrollment, he or she was to continue use throughout the course of the study treatment. Patients were instructed to avoid activities that would increase the severity of their symptoms. Criteria for Evaluation Measurement of efficacy was based on a comparison between the scores at baseline and at the 2-day follow-up. The primary efficacy variables included the investigator s global evaluation of improvement ( 1, worsened, through 4, no symptoms), patient s global evaluation of improvement ( 1, worsened, through 4, no symptoms), and the patient s pain evaluation at the end of treatment (100 mm on a visual analog scale; 0, no pain, through 100, most pain imaginable). Secondary efficacy variables included the patient s assessment of symptoms (0, none, through 4, very severe), the investigator s assessment of symptoms (100 mm on a visual analog scale; 0, no pain, through 100, most pain imaginable), the investigator s assessment of disease severity (0, none, through 4, very severe), and the investigator s tenderness evaluation (0, no tenderness, through 4, very severe tenderness). A composite score based on the results of the primary efficacy variables was computed. This score ranged from 0 to 3 based on the sum of the following items: patient pain evaluation score on a visual analog scale (0 if improvement measured less than 10 mm; 1 if improvement was 10 mm or more), patient global evaluation of improvement score (0 if no improvement, 1 if any improvement), and investigator global evaluation of improvement (0 if no improvement, 1 if any improvement). Safety and tolerability were evaluated based on the frequency of adverse events and on the occurrence of local reactions to treatment. A post hoc analysis was undertaken to determine whether patients who received all six treatments in a shorter period had better results than those who received all six treatments over a longer period. Patients were grouped according to the number of days required to complete all six treatments. These analyses were not anticipated when the study was designed, and therefore these comparisons would be expected to be underpowered, with fewer patients per comparison. Determination of Sample Size A clinically significant response was defined as improvement in investigator and patient global evaluations and a reduction in patient pain after the sixth treatment. It was anticipated that there would be a 20% difference in response between groups (a 60% response in the active group versus a 40% response in the placebo group). The minimum sample size to detect such a difference with 80% power at a two-sided alpha level of 5% was determined to be 97 patients per group. Thus, this study was to have a total sample size of approximately 200 patients. Statistical Methods Comparability of treatment groups was evaluated by using two-way analysis of variance and Mantel-Haenszel summary chi-square tests for ordered and dichotomous data, adjusting for treatment center. Evaluation was made on the 2-day follow-up results by using the last observation carried forward for patients who dropped out of the study. Rating scale evaluations were analyzed by using Mantel-Haenszel summary chi-square tests for dichotomous or ordered categories, stratified on the basis of treatment center and baseline severity. Visual analog scales were compared by using a factorial analysis of variance with the factors of treatment center, treatment, and baseline severity. Secondary analyses included construction of a composite score of the three primary efficacy variables and investigation of time to effect. Local reactions to treatment were compared by treatment by using summary chi-square tests stratified on center. RESULTS Patient characteristics by treatment group are presented in Table 1. The presence of all symptoms was comparable between treatment groups. There were slightly more women than men in both treatment groups. The duration of symptoms in the dexamethasone group averaged about 52 days, compared with 57 days for the placebo group (P 0.199). Half of the patients in both groups reported leisure activity as the cause of their condition (P 0.994). Work was reported to be the cause of the condition for 26% and 22% of the dexamethasone and placebo groups, respectively (P 0.687). All but four patients who received dexamethasone and all but five who received the placebo completed all six TABLE 1 Patient Characteristics for Both the Treatment and Placebo Groups Characteristic Dexamethasone group (N 99) Placebo group (N 100) Sex Women (N and %) 57 (58) 52 (52) Men (N and %) 42 (42) 48 (48) Age (years) Mean SD Range 17 to to 70 Symptom duration (days) Mean SD Range a 3to120 5to150 Prior treatments for epicondylitis (%) Any Physical therapy 2 5 Splinting b 5 15 Other treatment Prior medications for epicondylitis (%) Aspirin/ibuprofen Steroid injection 0 4 Other medication 8 13 a According to the protocol, symptom duration was to be 3 months or less; however, one patient in the dexamethasone group had symptoms for 120 days, and two patients in the placebo group had symptoms for 105 and 150 days. b Significant difference between treatment groups (P 0.05).

4 192 Nirschl et al. American Journal of Sports Medicine treatments. Reasons for withdrawal from the dexamethasone group included patient request (N 2), back injury during the study period (N 1), and atopic dermatitis at the drug site (N 1). Reasons for withdrawal from the placebo group included lack of efficacy (N 2), mild burning sensation (N 1), mild erythema (N 1), and severe elbow pain (N 1). The dose administered for all treatments was 40 maminutes. The majority of patients received treatments at a maximum current of 3 to 4 ma. Twenty-three patients in the dexamethasone group and 20 patients in the placebo group had a maximum current of 2 ma or 3 ma. The majority of patients had the dispersive electrode placed on their biceps muscle (64% in the dexamethasone group and 60% in the placebo group). Almost one-quarter of the patients had the dispersive electrode placed on their forearm (20% in the dexamethasone group and 22% in the placebo group). The median duration for patients to complete all six treatments for the dexamethasone group was 11 days (range, 7 to 16), and for the placebo group was 11 days (range, 7 to 18) (P 0.598). Efficacy Variables Table 2 summarizes results of primary and secondary analyses. Efficacy was based on a comparison between the baseline and 2-day follow-up scores. Patients receiving dexamethasone significantly improved in their visual analog scale score compared with the placebo group (P 0.012), and investigators rated overall symptomatic improvement as moderate or better for 52% of patients in the dexamethasone group compared with 33% in the placebo group (P 0.013). Forty-eight percent of the dexamethasone group and 41% of the placebo group had a score of moderate or better for the patient global evaluation of improvement (P 0.477). For the secondary efficacy variables, there was a significant improvement in the investigator pain evaluation score at the 2-day follow-up visit, in favor of the dexamethasone treatment group (P 0.019). There was also significant improvement, in favor of the dexamethasone group, for patients with a score of moderate or better on the investigators tenderness score (P 0.001). The number of patients with improvement in all three primary efficacy variables was significantly higher for the dexamethasone group than for the placebo group (60% versus 45%, P 0.039). Fifty-one patients completed all six treatments in 7 to 8 days (25 dexamethasone, 26 placebo), 36 in 9 to 10 days (18 dexamethasone, 18 placebo), 77 in 11 to 12 days (38 dexamethasone, 39 placebo), and 26 in more than 12 days (14 dexamethasone, 12 placebo). Although the result was not evaluated statistically, patients who completed all six treatments in 10 days or less showed better results than did patients who completed all six treatments over a longer period. The most marked differences between the treatment and placebo groups in those who received treatment in 10 days or less were in the investigator rating of global improvement, improvement in patient visual analog scale score, and improvement in investigator visual analog scale scores (Fig. 1). Patient reports of their outcome at 1 month after the sixth treatment were also obtained (Table 3). Of the 199 patients, 180 were interviewed by telephone. Patients were free to use other treatment modalities after the 2-day follow-up visit. Fifty-four percent of the treatment group scored moderate or better on their global evaluation of improvement. Improvement in patient symptoms was equal in both the dexamethasone group and the placebo group. Change from baseline in the visual analog scale scores was higher in the dexamethasone group than in the placebo group. Side Effects Treatment-related adverse events from dexamethasone treatment included application site vesicles (N 2), blister (N 2), localized skin reaction (N 2), burning sensation (N 1), atopic dermatitis (N 1), erythema (N 1), hypersensitivity (N 1), pruritis (N 1), and skin irritation (N 1). Treatment-related adverse events after placebo treatment included pruritus (N 3), erythema (N 2), arthralgia (N 2), application site pain (N 1), application site pruritus (N 1), burning sensation (N 1), and elbow pain (N 1). One patient in the dexamethasone group withdrew because of a treatmentrelated adverse event, atopic dermatitis at the drug site. TABLE 2 Summary of Results for Efficacy Variables Baseline Score Compared with Score at 2-day Follow-up Visit Efficacy variable a Active (N 99) Placebo (N 100) P value Primary efficacy variables Patient s pain evaluation (VAS) b Mean improvement (in millimeters) % patients with investigator s global evaluation of improvement score of moderate or better % patients who rated global evaluation of improvement moderate or better Secondary efficacy variables Investigator s pain evaluation (VAS) mean improvement (in millimeters) % patients reporting symptom improvement % patients with improvement in investigator s disease severity assessment % patients with improvement in investigator s tenderness score % patients with improvement for all three primary efficacy variables a See text for explanation of rating scales. b Visual analog scale.

5 Vol. 31, No. 2, 2003 Iontophoretic Administration of Dexamethasone for Epicondylitis 193 Figure 1. Summary of efficacy results by length of time in which patients completed treatments. VAS, visual analog scale score. TABLE 3 Summary of Results for Efficacy Variables Baseline Score Compared with Score at 1 Month Efficacy variable a Primary efficacy variables Patient s pain evaluation (VAS) b mean improvement (in millimeters) % patient global evaluation of improvement score of moderate or better Secondary efficacy variables % patients reporting symptom improvement Active (N 90) a See text for explanation of rating scales. b Visual analog scale. Placebo (N 90) P value Three patients in the placebo group experienced treatment-related adverse events that led to withdrawal from the study. One patient experienced a mild burning sensation, one experienced mild erythema, and one experienced severe elbow pain. Drug electrode reactions occurred in approximately 75% of patients receiving dexamethasone and in approximately 60% of the patients receiving the placebo. The reactions were mild and did not alter compliance with the study. Erythema and bullae occurred in four patients who received dexamethasone and in none of those who received the placebo. Dispersive site reactions occurred less frequently than drug electrode reactions, and none of the patients experienced erythema and bullae at the dispersive electrode site. DISCUSSION The results of our study showed that six iontophoresis treatments of 40 ma-minutes of dexamethasone were effective in reducing symptoms of medial or lateral epicondylitis. There have been several studies on the use of

6 194 Nirschl et al. American Journal of Sports Medicine iontophoresis for administering dexamethasone, both alone and in combination with other drugs; typically a local anesthetic. 2,9,12,18,19 The results of these studies were generally positive, in favor of the treated group, regardless of whether a combination of dexamethasone and lidocaine or dexamethasone alone was used. Selection of the appropriate treatment regimen for iontophoresis of dexamethasone (number of treatments required, timing between treatments) has been based on clinical experience rather than on well-controlled studies. The number of treatments of dexamethasone iontophoresis for musculoskeletal disorders reported in the literature varies, depending on the disorder being treated, from 1 treatment for delayed-onset muscle soreness to 10 daily treatments for shoulder girdle myofascial syndrome. 4,12 In most studies, treatments were spaced about every other day. On the basis of our results, six treatments were adequate to achieve significant improvement in several efficacy variables for patients who had elbow epicondylitis. However, it is not apparent whether additional treatments or variations in the spacing of treatments would have resulted in more prolonged or greater relief of symptoms. It should be noted that this study was focused on pain control and that other treatment concepts, including therapeutic exercise and surgery, may be considered in chronic situations. 17 Our patients who completed all six treatments in 10 days or less showed better results than those who completed the six treatments over a longer period. This analysis was not anticipated when the study was designed, and therefore these comparisons would be expected to be underpowered, that is, having fewer patients per comparison. Accordingly, these differences, though qualitatively large and consistent across efficacy parameters, may not be statistically significant. Results obtained at 1 month proved not to be statistically significant, which may be due to two factors. The first is that patients were only contacted by telephone and not examined by an investigator. The second, and more important, factor is that patients were not restricted from using other treatment modalities after the 2-day follow-up visit. They may have included use of antiinflammatory medications, steroid injections, or therapeutic exercises. Obviously, those patients who used additional modalities during the month could have altered assessment of symptoms compared with those patients who had iontophoresis only. A study design in which use of other subsequent treatment modalities is prohibited and in which patients receive physical examinations at 1 month after initial treatment may provide data as to how long the efficacy of iontophoresis actually lasts. The results of the current study, however, are significant in the short term. The early onset of pain relief may provide patients enough comfort to proceed with a physical therapy rehabilitative exercise program. Although corticosteroid injections have been the traditional mainstay of treatment for lateral or medial epicondylitis, there are limited clinical data that address the effectiveness and adverse effects of this treatment modality. 20 In an attempt to answer some of these questions, Assendelft et al. 1 performed a systematic overview of corticosteroid injections for lateral epicondylitis. On the basis of their review of 12 randomized clinical trials, the authors concluded that the evidence regarding the efficacy of corticosteroid injections was not conclusive. They noted that, although corticosteroid injections appear to be relatively safe and have a short-term effect (2 to 6 weeks), important questions regarding the optimal timing, dosage, injection technique, injection volume, and composition of the injection fluid remain unanswered. Although complications associated with intraarticular and soft tissue steroid injections are relatively uncommon, when a complication does occur, it can result in severe and disabling consequences for the patient. It is for this reason that elite-level competitive athletes may be hesitant to use corticosteroid injections. Anecdotal reports from athletes and coaches alike indicate a general apprehension regarding use of corticosteroid injection therapy because of the potential harmful consequences. Many athletes opt for more conservative treatment, such as iontophoresis, because the adverse events encountered with hypodermic injection are avoided completely. The majority of side effects reported in the present study were confined to the drug electrode site and were considered mild to moderate in severity. These findings are consistent with those of other studies that have investigated the effects of iontophoresis, which have shown few, if any, adverse effects from iontophoresis of dexamethasone. In conclusion, iontophoresis treatment with dexamethasone was well tolerated by the majority of the patients and was effective in reducing symptoms of medial and lateral epicondylitis, particularly when treatments were completed in 10 days or less. In this study, we assessed only pain control, but we anticipate that iontophoresis treatment will better enable patients to tolerate therapeutic exercises and, therefore, will accelerate the rehabilitative process for elbow epicondylitis. A second study that couples these two treatment regimens should be performed in the future. ACKNOWLEDGMENTS This study was supported by a grant from Iomed, Inc., Salt Lake City, Utah. We gratefully acknowledge the collaborators who contributed to this study: Maria Greenwald, MD, Advances in Medicine, Rancho Mirage, California; Craig Weisenhutter, MD, Couer d Alene Arthritis Clinic, Couer d Alene, Idaho; E. F. Shaw Wilgis, MD, Curtis National Hand Center, Baltimore, Maryland; Eric Peters, MD, Arizona Arthritis Clinic, Paradise Valley, Arizona; H. Malin Prupas, MD, Arthritis Consultants, Reno, Nevada; Robert Heidt, MD, Wellington Orthopedics, Cincinnati, Ohio; Thomas Lorish, MD, Providence Medical Center, Portland, Oregon; Stuart Silverman, MD, Osteoporosis Medical Center, Beverly Hills, California; Alan Kivitz, MD, Altoona Center for Clinical Research, Duncansville, Pennsylvania; and Benjamin Levine, MD, Park Nicollet Clinic, Minneapolis, Minnesota.

7 Vol. 31, No. 2, 2003 Iontophoretic Administration of Dexamethasone for Epicondylitis 195 REFERENCES 1. Assendelft WJJ, Hay EM, Adshead R, et al: Corticosteroid injections for lateral epicondylitis: A systematic overview. Br J Gen Pract 46: , Banta CA: A prospective, nonrandomized study of iontophoresis, wrist splinting, and antiinflammatory medication in the treatment of early-mild carpal tunnel syndrome. J Occup Med 36: , Bertolucci LE: Introduction of antiinflammatory drugs by iontophoresis: Double blind study. J Orthop Sports Phys Ther 4: , Delacerda FG: A comparative study of three methods of treatment for shoulder girdle myofascial syndrome. J Orthop Sports Phys Ther 4: 51 54, Genovese MC: Joint and soft-tissue injection. A useful adjuvant to systemic and local treatment. Postgrad Med 103: , Glass JM, Stephen RL, Jacobson SC: The quantity and distribution of radiolabeled dexamethasone delivered to tissue by iontophoresis. Int J Dermatol 19: , Gottlieb NL, Riskin WG: Complications of local corticosteroid injections. JAMA 243: , Gray RG, Gottlieb NL: Intra-articular corticosteroids. An updated assessment. Clin Orthop 177: , Gudeman SD, Eisele SA, Heidt RS Jr, et al: Treatment of plantar fasciitis by iontophoresis of 0.4% dexamethasone. A randomized, double-blind, placebo-controlled study. Am J Sports Med 25: , Hamilton PG: The prevalence of humeral epicondylitis: A survey in general practice. J R Coll Gen Pract 36: , Harris PR: Iontophoresis: Clinical research in musculoskeletal inflammatory conditions. J Orthop Sports Phys Ther 4: , Hasson SH, Henderson GH, Daniels JC, et al: Exercise training and dexamethasone iontophoresis in rheumatoid arthritis. Physiother Canada 43(2): 11 14, 29, Kraushaar BS, Nirschl RP: Tendinosis of the elbow (tennis elbow). Clinical features and findings of histological, immunohistochemical, and electron microscopy studies. J Bone Joint Surg 81A: , Mackinnon SE, Hudson AR, Gentili F, et al: Peripheral nerve injection injury with steroid agents. Plast Reconstr Surg 69: , McConnell JR, Bush DC: Intraneural steroid injection as a complication in the management of carpal tunnel syndrome: A report of three cases. Clin Orthop 250: , Murtagh JE: Tennis elbow. Aust Fam Physician 17: 90 95, Nirschl RP: Elbow tendinosis/tennis elbow. Clin Sports Med 11: , Pellecchia GL, Hamel H, Behnke P: Treatment of infrapatellar tendinitis: A combination of modalities and transverse friction massage versus iontophoresis. J Sport Rehabil 3: , Schiffman EL, Braun BL, Lindgren BR: Temporomandibular joint iontophoresis: A double-blind randomized clinical trial. J Orofac Pain 10: , Schnatz P, Steiner C: Tennis elbow: A biomechanical and therapeutic approach. J Am Osteopath Assoc 93: , 1993