Healing Times of Pedal Ulcers in Diabetic Immunosuppressed Patients After Transplantation

Transcription

1 935 Healing Times of Pedal Ulcers in Diabetic Immunosuppressed Patients After Transplantation David R. Sinacore, PhD, PT ABSTRACT. Sinacore DR. Healing times of pedal ulcers in diabetic immunosuppressed patients after transplantation. Arch Phys Med Rehabil 1999;80: Objective: To compare the healing time of neuropathic plantar ulcers treated by total-contact casting (TCC) in diabetic, immunosuppressed patients after organ transplantation with the healing time of plantar ulcers in control nonimmunosuppressed patients. Design: A case-control design with the control group matched for age, race, sex, body dimensions (height, weight, and body mass index), presence of sensory neuropathy, foot deformity presence and location, and pedal ulcer area and depth. Setting: An outpatient physical therapy clinic in a regional tertiary-care hospital and academic medical center. Participants: Nine patients with chronic diabetes mellitus and a previous organ transplantation who were currently receiving lifelong immunosuppressive drug therapy were treated for a neuropathic plantar ulcer by means of TCC. Fourteen group-matched control subjects with diabetes mellitus and a plantar ulcer but who had never had an organ transplantation and were not taking immunosuppressive agents were also studied. Interventions: TCC with partial weight-bearing using an assistive device until ulcers healed. Main Outcome Measure: Healing time was defined as the number of days in the total-contact cast until the skin completely closed. Results: All diabetic foot ulcers healed with casting. Immunosuppressed/transplanted patients healed in a mean time of 111 _+ 25 days; ulcers of control subjects healed in days (p <.05). All patients returned to ambulation using prescribed therapeutic footwear. None of the patients required a lower extremity amputation throughout the follow-up period. Conclusions: TCC is a highly effective and rapid method of healing neuropathic pedal ulcers in diabetic immunosuppressed/ transplantation patients, although it may take several weeks longer than it would for patients who were not immunocomproraised by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation F OOT ULCERS ARE A COMMON and costly complication of diabetes mellitus and often lead directly to lower extremity amputation and long-term disability. There is little From the Program in Physical Therapy and Department of Medicine, Washington University School of Medicine, St. Louis, MO. Submitted for publication December 7, Accepted in revised form March 8, 1999, No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit upon the authors or upon any organization with which the authors are associated. Reprint requests to David R. Sinacore, PhD, PT, Program in Physical Therapy, Campus Box 8502, 660 South Euclid Avenue, St. Louis, MO by the American Congress of RehabiIitation Medicine and the American Academy of Physical Medicine and Rehabilitation /99/ /0 doubt that organ transplantation (kidney, liver, pancreas, heart, and lung) is responsible, in large part, for patients with chronic diabetes mellitus living much longer, healthier, and more productive lives. A consequence of organ transplantation, however, is the necessity of lifelong immunosuppressive therapy to prevent the transplanted organ from being rejected. Immunosuppressive agents are known to have several side effects, and it has long been suspected that wound healing is less likely, and more often delayed, in immunosuppressed, transplanted (IS/ TX) diabetic patients.l,2 Total-contact casting (TCC) has proven to be a highly effective and rapid ambulatory method of healing chronic plantar ulcers in individuals with diabetes and sensory neuropathy. 3-5 It has been reported that 90% of grade I and II plantar ulcers (Wagner 6 classification), treated by TCC, healed in an average of days. 4 The length of time that foot ulcers are present before casting is, on average, 9 months. 4 This underscores the relatively rapid rates of healing and effectiveness of casting. The mechanism underlying the effectiveness of TCC appears to be a reduction in plantar pressures per unit area over the entire foot. It is this reduction of plantar pressures that usually allows an ulcer to heal rapidly and completely. 7,s Unfortunately, outcomes with TCC can be quite variable, depending on such factors as ulcer size, the presence of infection, nutritional aspects of patients, and perhaps drug interactions that can either delay or prevent wound healing. Any of these critical factors may complicate the ambulatory method of TCC and, therefore, should be investigated more thoroughly. Few studies have directly addressed the question of pedal ulcer healing in immunosuppressed diabetic individuals. The purpose of this case-control study was to examine the healing times and, secondarily, the short-term outcomes of a group of posttransplanration, immunosuppressed patients with diabetic neuropathic plantar ulcers of the foot who were treated by TCC, The group of IS/TX subjects were compared with matched control subjects who had no history of transplantation or use of immunosuppressive agents and who were casted throughout the same time interval. In addition, healing times of immunosuppressed subjects were compared with previously published healing times of subjects with diabetic pedal ulcers and fixed deformities of the foot treated with TCC. METHODS Subjects Nine patients (seven men, two women) with diabetes mellitus and an organ transplantation who were receiving lifelong immunosuppressive therapy and who had a neuropathic plantar ulcer of the foot were studied. A control group of 14 subjects (11 men, 3 women) were matched in several patient characteristics: age, race, sex, ulcer size and depth, and presence of foot deformity. All participants (patients and controls) had been referred to our outpatient physical therapy clinic for treatment of chronic pedal ulcers during the interval from June 1992 to December 1998 (6.5 years). General characteristics of the individuals studied are summarized in table 1. Individuals were included in the study only if they were treated by one of two Arch Phys Med Rehabi! Vol 80, August 1999

2 936 HEALING TIME OF PEDAL ULCER AFTER TRANSPLANTATION, Sinacore Table 1: Subject and Ulcer Characteristics IS/TX Control Patients Patients (n = 9) (n = 14) pvalue* Age (yrs) _ Sex (% male:% female) 78:22 71: Race (% white:% black) 89:11 79: Weight (kg) Height (cm) Body mass index (kg/m 2) 27 _ _ Type 1 :type 2 diabetes mellitus (%) 67:33 14: Duration of diabetes mellitus (years) _ Years since transplant 5 --_ 2 NA -- Immunosuppressive agents % Prednisone 67 NA -- % Cyclosporine 89 NA -- % Azathiopine 22 NA -- % Combination 100 NA -- History of ulceration %Y:%N 89:11 64: Sensory neuropathy.200 % Absent % Diminished % Protective Ulcer location (%HF:MF:FF) 33:67:0 0:25: initial ulcer area (cm 2) _ Initial ulcer depth (mm) 4.5 +_ _ Type 1 is insulin-dependent diabetes mellitus; type 2 is non-insulindependent diabetes mellitus. Absent sensation = unable to feel 6.10 (75g) monofilament; diminished sensation = able to feel 6.10 (75g) monofilament but unable to feel the 5.07 (10g) monofilament; protective sensation = able to feel the 5.07 (10g) monofilament on the plantar surface of the foot. * All p values for continuous variables from t test for independent samples; p values for categorical variables using X 2 test with 1 dr. physical therapists, each having more than 18 years of experience in casting. This criterion was used to reduce the potential for differences in healing outcomes because of the practitioner's level of skill. Most individuals had been referred by the same orthopedic surgeon, but some patients were referred from either a vascular surgeon or their diabetologist. All nine immunosuppressed patients had their organ transplantation within the previous 8 years. Seven patients had a renal transplantation, one had a liver transplantation, and one had a pancreas transplantation. The control subjects were similarly referred by the same physicians in our medical center and did not differ in most physical characteristics from the patients. In general, control subjects were older than the patients and a greater percentage of them had type 2 diabetes meilitus with a shorter duration of the disease (table 1). All participants gave their written informed consent for the TCC procedure, and the treatment protocol was approved by the Human Subjects Committee at our university medical school. Procedure Before initiating treatment of the ulcer, each participant's age, height, weight, race, type and duration of diabetes mellitus, and history of foot ulceration was recorded. In addition, a physical examination was performed to determine the location of ulceration, type and location of foot deformity, presence of palpable pedal pulses, and presence and level of neuropathy. 9 All participants had evidence of distal symmetric polyneuropathy indicated by inability to feel the 5.07 (10-g) Semmes- Weinstein monofilament on selected sites on the plantar surface, loss of ankle-jerk reflexes, or intrinsic muscular weakness. 9 Extrinsic muscular weakness (eg, of the gastrocnemius/soleus or tibialis anterior/extensor digitomm longus muscles) was, in general, minimal or absent. The reliability of this type of evaluation has been published previously. 9 Reliability indices for interrater assessments were.72 to.89 for the tests of sensory neuropathy, ulcerated areas and their depths, assessments of ankle reflexes, assessments of deformities of the foot, and assessments of range of motion. 9,1 Assessment of Ulcers/Fixed-Foot Deformity The size of each ulcer was determined by tracing the perimeter of the wound onto sterile, clear acetate at each visit. The area of each ulcer was determined from the tracings, using an Optimus Version 3.0 optical digitizer) and was expressed in square centimeters. The mean of three trials of digitizing each ulcer tracing was used in analysis. This method for determination of area has been shown to be quite reproducible, with repeated measures by the same operator differing by less than 3.6% and intrarater indices of reliability between trials of Depth was measured using a modified sliding ruler at the deepest point of the wound. All participants had Wagner grade I or II plantar surface ulcers. The ulcer size (area) and depth before initiating therapy was similar in patients and control subjects (table 1). The location of the ulcers in the immunosuppressed group, however (six [67%] in the midfoot and three [33%] in the hindfoot), varied from the controls. Significant fixed deformity of the foot was defined as rigid (nonreducible) subluxation or other bony malalignment, including complete or partial amputation of a ray or toe, medial longitudinal arch collapse, severe varus deformity (->4 ) of the hindfoot, rigid haflux abductovalgus, clawtoe, or hammer toe deformities. Two patients (22%) had previously had a foot amputated (one transmetatarsal amputation [TMA], the other fifth ray amputation). The location of the ulcer in the patient with TMA was at the lateral border of the foot beneath the remnant of the fifth metatarsal. The location of the ulcer in the patient with a fifth ray amputation was the lateral border of the fourth metatarsal. Many of the patients had more than one fixed deformity of their ulcerated foot. Four of the six midfoot ulcers were located on the medial pillar due to medial longitudinal arch collapse, whereas two ulcers were located on the lateral midfoot, caused by severe hindfoot varus deformity. In the control group, one subject had previously had a transmetatarsal amputation (ulcer located under remnant of second/third metatarsal) and one had a below-knee amputation on the contralateral extremity. The ulcers in the control group were located in the forefoot (75%) and in the midfoot (25%). There were no (0%) hindfoot ulcers among controls. The impact of this important source of variability was examined by subsequent statistical analysis. Immunosuppressive Agents All the organ transplantation patients were on lifelong immunosuppressive drug therapy. The type of immunosuppressive agents varied considerably among the patients studied. Prednisone, eyclosporine, and azathioprine were the most common agents, usually in some combination to prevent acute rejection and for chronic maintenance of the transplanted organ (table 1). Dosages of immunosuppressive agents varied significandy and were not recorded. None of the transplantation patients reported episodes of acute rejection during the period of casting. Arch Phys Med Rehabil Vol 80, August 1999

3 HEALING TIME OF PEDAL ULCER AFTER TRANSPLANTATION, Sinacore 937 Total-Contact Casting Casts were applied according to the method described elsewhere. 11 All casts were applied by one of two physical therapists-each with extensive clinical experience--in the same manner and using the same casting materials. Casts typically were changed at 1- to 2-week intervals until complete healing of the ulcer was achieved. Subjects were instructed to remain non-weight-bearing on the casted extremity for the first 24 hours, then were allowed partial weight-bearing using an assistive device while standing and walking. ]1 There was no attempt to assess the amount of weight-bearing or the amount of pressure on the casted foot throughout the study; however, adherence to weight-bearing instructions was routinely assessed and reenforced on subsequent visits for changing the cast. The time to healing (in days) was defined as the length of time needed for complete closure of the skin (ie, epithelialization) with no evidence of drainage or formation of a sinus tract. 11 Technically, the precise day the ulcer healed was unknown and may have occurred within any 7-day interval during regular changes in the cast according to our protocol. Short-Term Outcomes Typically, we follow up patients for 1 month after their plantar ulcers are healed, v Although this follow-up period is of short duration, it is adequate to determine if there is recurrence of the ulcer and to fit subjects for their protective footwear. 1~,12 During the follow-up period, we encourage a gradual return to activity and to resumption of unassisted ambulation, as well as allow for an adequate period of footwear accustomization. Most ulcers recur within the first 1 to 3 months after initial healing.12,13 Statistical Analyses The mean, standard deviation, and 95% confidence interval (95% CI) for time to healing were computed for each group of patients. Age, height, weight, body mass index, diabetes mellitus duration, ulcer area and depth, and healing time for patients and controls were compared using Kruskal-Wallis one-way analysis of variance (ANOVA). Differences between groups with regard to categorical variables (ie, sex, race, type of diabetes mellitus, neuropathy level, partial weight-bearing compliance, previous ulcer history, ulcer location, and deformity location) measured at baseline were tested using chisquare analysis. An analysis of covariance (ANCOVA) was then used to control for the effect of the variables, which were different between the immunosuppressed patients and controls after selection of the control group at baseline. All statistical tests were performed using the SYSTAT Version 5.0 statistical package, b Descriptive statistics (means and standard deviations) for times to healing obtained from previously published reports were used to make comparisons with our findings. 14,15 An ANOVA of healing time between IS/TX patients in our study and 15 subjects with midfoot or hindfoot ulcers from previously published results was performed to further examine the impact of ulcer location and the presence of severe foot deformity. Ap --<.05 was set for all tests of significance. RESULTS There were no differences between patients and control subjects for most of the continuous and categorical variables measured at baseline (table 1). Therefore, the patient-control matching design was successful and the control group represented an adequate comparison of healing time in TCC. The initial ulcer size (area) and depth did not differ between the two groups before initiating casting. The location of the ulcers (X 2= 15.8, df= 1, p <.001), the type of diabetes mellitus (type 1 vs type 2; X 2 = 6.33, df = 1, p <.01), and the duration of diabetes (F = 5.47, df = 1,23, p <.05) among the patients and controls were different at baseline (table 1). Only the location of ulcers had a significant effect on healing time between the comparison groups (F = 8.4, df = 1,23, p <.01). The immunosuppressed group healed their pedal ulcers in a mean time of 1ll _+ 25 days (range = 129 days; 95% CI, 95 to 127 days) (fig 1). The matched control group healed their foot ulcers in days (range = 70 days; 95% CI, 38 to 56 days, F = 249, df = 1,23, p <.001) (fig 1). One month after initial healing, on follow-up, there were no amputations in either group of patients. All the immunosuppressed patients returned to ambulation using prescribed footwear or modifications of footwear. Two (22%) of the nine IS/TX patients required an assistive device (either two axillary crutches or a standard walker) to ambulate outside their homes after their ulcers healed. Only a single subject (1 [ 11%] of 9) in the IS/TX group reulcerated. This one subject had the TMA and reulcerated within the first week after initial wound closure. This patient was recasted and her ulcer healed, then remained healed after additional shoe modifications. In the control group, 28.5% of the patients reulcerated within the first month after initial healing. These patients were recasted for up to 6 weeks to heal their recurrent ulcer without complications. There were no amputations recorded in any of the control subjects within the follow-up period. DISCUSSION The results of this case-control study are different from those previously reported a because 100% of the small number of ulcers healed in the IS/TX group. Although persistent wound failure and higher rates of complications of ulcers may be expected when treating plantar ulcers in immunosuppressed patients by any method, we did not observe the often-held clinical suspicions of poorer outcomes. 2 In the only other report that directly addressed the effect of immunosuppressive agents on diabetic foot ulcer healing, Fletcher and associates ~ reported a much dimmer clinical picture of ulcer healing in immunosuppressed diabetic subjects after renal transplantation. They reported that of the 40 ulcers studied, only 50% healed. Furthermore, the average healing time was 214 days (median = 165; range 450) in those patients I ~- 140 I,- ~) 120 ~p.j 100 o m 80.E 40 =0 IS/TX GROUP CONTROL GROUP Fig 1. The mean healing time (days) of pedal ulcers in diabetic immunosuppressed patients after organ transplantation (IS/TX). The bar represents the mean; the line represents the standard deviation. Controls are group-matched subjects, *Significantly different among groups (p <.05). Arch Phys Med Rehabil Vol 80, August 1999

4 938 HEALING TIME OF PEDAL ULCER AFTER TRANSPLANTATION, Sinacore who healed. This contrasted with a matched-control group without transplantation, where 71% of the foot ulcers healed in an average of 132 days (median = 100; range 420). Unfortunately, 50% of the nonhealing foot ulcers in the immunosuppressed group required an amputation within an average of 222 days (range 675 days). This contrasted with the matchedcontrol group where only 29% (15 of 52 ulcers) required a subsequent foot amputation between 1 and 572 days of follow-up. Fletcher 2 did not specify the methods of healing used in that study, but those results were not uncommon for methods before the popularization of TCC and a greater emphasis on pressure relief in the presence of sensory neuropathy. 4 Table 2 shows the outcome classification scheme originally proposed by Fletcher. 2 That study reported no cases (0%) having excellent outcomes; only 7% had good outcomes; 33% had fair outcomes; and the majority (58%) had poor outcomes in the immunosuppressed group. 2 This contrasted with their control group, in which 19% were rated as excellent; 27% were rated as good; 21% were rated as fair; and 33% were rated as poor. 2 According to the same outcome classification scheme, none of our IS/TX patients' pedal ulcers healed in <-60 days, so none (0%) would be rated as excellent; 89% would be rated as a good; and only 11% would be rated as a fair There were no (0%) IS/TX patients who could be rated a poor outcome using TCC. All our matched-control patients would be rated as excellent (79%) or good (21%) outcomes using TCC, as they all healed their pedal ulcers within 120 days without requiring a partial or complete foot amputation within the follow-up period. This comparison underscores the belief that TCC is a most effective therapy for Wagner grades I and II neuropathic plantar ulcers, including patients after transplantation who remain on lifelong immunosuppressive therapy. Walker and Helm 15 reported that the mean healing time of 25 nonforefoot ulcers (in patients without immunosuppression) was 42 ± 27 days. They reported significantly faster rates of healing for ulcers located in the forefoot ( days) but concluded that TCC was a highly effective method regardless of the location of the ulcer. In the absence of any reported immunosuppressive drug therapy, times to healing reported by Walker and Helm are consistent with the current control group and with previously published results using this method of treatment. 4 Unlike previous reports, 2,15 the results of our study suggest that immunosuppressive drag therapy influences time to healing to a significantly larger degree than do other characteristics, such as the ulcer size or depth. Table 2" Classification of Outcome Categories of Diabetic Pedal Ulcers Present Study Fletcher 2 Study IS/TX Control IS Control Patients Patients Patients Patients (n = 9} (n = 14) (n = 40) (n = 52) Outcome category* Excellent 0% 79% 0% 19% Good 89% 21% 8% 27% Fair 11% 0% 33% 21% Poor 0% 0% 59% 33% In the present study ulcers were treated by TCC; in the Fletcher 2 study ulcer treatment was not specified. * Classification of Outcomes according to Fletcher2: excellent, complete ulcer healing within 60 days with no surgical intervention; good, complete ulcer healing in 61 to 120 days with no surgical intervention; fair, complete ulcer healing between 121 and 365 days and/or surgery required; poor, complete ulcer healing in more than 365 days, which resulted in amputation. O~ " ,,J ~ 100 m 80 "o 1-6o isrrx CONTROL NON- NON- GROUP GROUP FOREFOOT- FOREFOOT NO WITH DEFORMITY DEFORMITY Fig 2. The mean healing time (days) of pedal ulcers in diabetic immunosuppressed patients after organ transplantation (IS/TX group), in control subjects (control group) from the present study, in nonforefoot ulcers with no fixed-foot deformity, and in nonforefoot ulcers with fixed-foot deformity. Neither group with nonforefoot ulcers was immunosuppressed. The bar represents the mean; the line represents the standard deviation. *Significantly different among groups (p <.05). (Data from nonforefoot ulcers with no foot deformity are from Walker and Helm15; data from nonforefoot ulcers with fixed-foot deformity are from Sinacore) 4} There is general consensus that high plantar pressures beneath ulcerated areas in subjects with absent or diminished pedal sensation can delay wound healing. 16 The presence of severe foot deformity typically causes higher plantar pressures even in the total contact cast. 17 The results of this study may be confounded by the location of the ulcers within the foot and the presence of more frequent and severe fixed-foot deformity in the IS/TX patients. Since the majority (75%) of ulcers in the control group were located in the forefoot, this factor may have accounted for the faster healing times with TCC. Severe, nonreducible foot deformity prolongs the healing of foot ulcers by TCC 14 or any other pressure-relieving methods. In this group of subjects, it appears that immunosuppressive therapy, combined with fixed-foot deformity, delays wound healing to an even further extent than foot deformity alone (fig 2). Sinacore 14 described healing rates of days for midfoot and days for hindfoot ulcers (average = 82 days) when significant foot deformity was present (fig 2). Immunosuppressed patients take approximately 3 to 4 weeks longer; however, there is considerable variability, as evidenced by the large standard deviation in healing time in the IS/TX patients. The location of ulcers and the presence of severe fixed-foot deformity in the IS/TX group was different from the matched control group. Ulcer location and the presence of fixed-foot deformity explain a significant portion of the variance in healing time in TCC when patients and control subjects were pooled. (R =.86, R 2 =.73). To determine the independent effect of ulcers located in the midfoot and hindfoot in the presence of fixed-foot deformity in the IS/TX group, we performed an ANCOVA using previously published healing times of 15 patients with ulcers localized only in the midfoot or hindfoot 14 to healing times for the IS/TX group. For this analysis, ulcer location (either midfoot or hindfoot) was used as the covariate. The IS/TX group still took significantly longer to heal in a TCC than subjects with ulcers located in the midfoot or hindfoot but without immunosuppression/transplantation (F = 8.5, df = 1,23, p <.0]) (fig 2). Arch Phys Med Rehabil Vol 80, August 1999

5 HEALING TIME OF PEDAL ULCER AFTER TRANSPLANTATION, Sinacore 939 Throughout the casting period, all participants were instructed to partial weight-bear with an assistive device (defined as using two axillary crutches or a standard walker) during all periods of ambulation. Partial weight-bearing with an assistive device can help decrease plantar pressures and reduce complications, such as new cast abrasions, 4 thereby promoting faster healing times with casting. Encouraging all patients to use partial weight-bearing with assistive devices is an important, although often overlooked, key to successful outcome with all ambulatory healing methods. As in our previous reports of patient compliance 14,18 only two (22%) of the IS/TX patients and three (21%) of the controls were judged to adhere to using their assistive device for partial weight-bearing relief. Because of the small number of compliant patients studied, no secondary analysis could be performed; therefore, the impact of partial weight-bearing compliance could not be fully determined. However, since partial weight-bearing adherence may reduce healing time with TCC, all patients with diabetic pedal ulcers should be encouraged to partial weight-bear, using assistive devices to help reduce plantar pressures. TM Limitations As with any case-control study, there may be some uncontrolled confounding variables (bias) that are not readily apparent, but that may influence ulcer healing outcomes. One of these variables may be the extent and severity of vascular disease. The impact of vascular disease may provide an alternative explanation for the significantly longer healing times observed in the IS/TX group. Ischemia and advanced vascular disease are known to contribute to more frequent wound failure and poorer outcomes, 19 although it is highly unlikely that the longer healing times in the group of IS/TX patients solely result from more profound macrovascular disease. Although large-vessel and small-vessel disease were not directly assessed in this study, pedal blood flow (determined by presence of palpable pulses) in both groups of patients was adequate to permit complete ulcer healing. Furthermore, Fletcher 2 reported similar pulse volume recordings in immunosuppressed and immuno~ competent diabetic subjects, implying no differences in the severity of macrovascular disease among patients undergoing renal transplantation. Alternatively, since small-vessel (microvascular) disease is typically associated with more severe renal disease requiring transplantation, our IS/TX patients may have had more extensive impairment of their smaller pedal vessels. Because we did not measure either large- or small-vessel disease, both large- and small-vessel blood flows may have been functionally reduced in the IS/TX group compared to the matched group of control subjects. In general, it is a combination of high plantar pressures and increasing ischemic disease that may delay healing of ulcers, with many methods used to treat chronic ulcers on the foot, particularly with the use of TCC. The direct contribution of these factors must await further controlled studies. The results of this study have importance for individuals with diabetes mellitus and chronic ulcers of the foot, because the ambulatory method of TCC is prolonged due to the presence of immunosuppressive agents. Depending on other factors present, such individuals will typically spend a longer period of time in a cast and may have to restrict weight-bearing activities to a larger degree to help reduce plantar pressures and promote wound healing. Further study of the numerous factors that can influence time to healing of diabetic, neuropathic plantar ulcers treated with TCC is necessary. In addition to determining those factors that result in successful patient outcomes, it is necessary to document the influence of factors that can either delay wound healing or predict persistent wound failure and the likelihood for subsequent amputation of the lower extremity. This study demonstrates that foot-ulcer healing rates are prolonged by the pharmacologic therapy that organ transplant patients are taking to prevent acute rejection and maintain transplant viability. As Fletcher 2 concluded, immunosuppressed diabetic patients take more time and more effort, so the treating physician (or physical therapist) must be prepared to expend that effort before undertaking care for these patients. Although the small number of individuals studied prevented a more detailed analysis, none of the combination of immunosuppressive agents appeared to delay ulcer healing more than any other combination of agents. As newer and more effective immunosuppressive agents are developed for organ transplantation patients, diabetic ulcer healing rates should be continually reexamined. Defining all the factors involved in healing diabetic pedal ulcers with TCC is clearly necessary in future controlled studies. CONCLUSIONS Chronic immunosuppressive drug therapy prolongs the healing time of diabetic pedal ulcers using TCC, but immunosuppression after organ transplantation does not cause any more frequent wound failure or subsequent complications such as foot amputation. Health care providers, such as physicians, physical therapists, and other specialists involved in rehabilitation, should inform their patients, members of the patients' family, employers of patients, and third-party payers to expect longer times in healing plantar ulcers due to chronic immunosuppressive therapy; however, in contrast with previously held clinical suspicions, they appear to be no more at risk for wound failure complications using TCC. References 1. Ehrlichman RJ, Seckel BR, Bryan DJ, Moschella CJ. Common complications of wound healing. Surg Clin North Am 1991;71: Fletcher F, Ain M, Jacobs R. Healing of foot ulcers in immunosuppressed renal transplant patients. Clin Orthop Re1 Res 1993;296: Sinacore DR, Mueller MJ, Diamond JE, Blair VP, Drury D, Rose SJ. Diabetic plantar ulcers treated by total contact casting. Phys Ther 1987;67: Sinacore DR. Total contact casting for diabetic neuropathic ulcers. Phys Ther 1996;76: Mueller MJ, Diamond JE, Sinacore DR, Delitto A, Blair VP, Dmry DA, et al. Total contact casting in treatment of diabetic plantar ulcers: controlled clinical trial. Diabetes Care 1989;12: Wagner FW Jr. The insensitive foot. In: Kiene RH, Johnson KA, editors. American Academy of Orthopaedic Surgeons Symposium on the Foot and Ankle. St Louis (MO): CV Mosby Co; p Lavery LA, Vela SA, Lavery DC, Quebedeaux TL. Total contact casts: pressure reduction at ulcer sites and the effect on the contralateral foot. Arch Phys Med Rehabil 1997;78: Shaw JE, Hsi WL, Ulbrecht JS, Norkitis A, Becker MB, Cavanagh PR. The mechanism of plantar unloading in total contact casts: implications for design and clinical use. Foot Ankle Int 1997;18: Diamond JE, Mueller MJ, Delitto A, Sinacore DR. Reliability of a diabetic foot evaluation. Phys Ther 1989;69: MueUer MJ, Diamond JE, Delitto A, Sinacore DR. Insensitivity, limited joint mobility and plantar ulcers in patients with diabetes mellitus. Phys Ther 1989;69: Sinacore DR, Mueller MJ. Total-contact casting in the treatment of neuropathic ulcers. In: Levin ME, O'Neal LW, Bowker JH, editors. The diabetic foot. 5th ed. St Louis (MO): Mosby-Yearbook; p Arch Phys Nled Rehabil Vol 80, August 1999

6 940 HEALING TIME OF PEDAL ULCER AFTER TRANSPLANTATION, Sinacore 12. Mueller MJ, Allen BT, Sinacore DR. Incidence of skin breakdown and higher amputation after transmetatarsal amputation: implications for rehabilitation. Arch Phys Med Rehabil 1995;76: Brand PW. The diabetic foot. In: Rifkin HA, editor. Diabetes mellitus: theory and practice. 3rd ed. New Hyde Park (NY): Medical Examination Publishing Co, Inc; p Sinacore DR. Healing times of diabetic ulcers in the presence of fixed deformities of the foot using total-contact casting. Foot Ankle Int 1998;19: Walker SC, Helm PA. Total contact casting and chronic diabetic neuropathic foot ulcerations: healing rates by wound location. Arch Phys Med Rehabil 1987;68: Armstrong DG, Lavery LA. Elevated peak pressures in patients who have Charcot arthropathy. J Bone Joint Surg Am 1998;80A: Martin RL, Conti SF. Plantar pressure analysis of diabetic rockerbottom deformity in total contact casts. Foot Ankle Int 1996;17: Sinacore DR. Acute neuropathic (Charcot) arthropathy in patients with diabetes mellitus: healing times by foot location. J Diabetes Complications 1998;12: Pecoraro RE, Reiber GE, Burgess EM. Pathways to diabetic limb amputation: basis for prevention. Diabetes Care 1990;13: Suppliers a. Optimus Corp North Creek Parkway, Suite 101, Bothell, WA b. Systat Inc., 1800 Sherman Avenue, Evanston, IL Arch Phys Med RehabiI Vol 80, August 1999