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Increased non-articular tenderness in patients on steroid therapy
European
Journal
of Pain (1998) 2: 261-266
Increased non-articular steroid therapy
tenderness
in patients
on
Dan Buskila”, Elena Schleiferb, H. Selvyn Odesb and Lily Neumannc “Rheumatic Disease Unit, bGastroenterology Institute, “Department of Epidemiology, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
Increased non-articular tenderness and tender shins have been suggested to be associated with steroid therapy in patients with lupus. The aim of the present study was to extend this observation in a different disease, inflammatory bowel disease (IBD), and to examine the relationship between tenderness, dosage and duration of steroid therapy. Eighty-seven patients with IBD, 23 of them on steroid therapy, were assessed for disease activity and nonarticular tenderness. A count of 18 tender points was conducted by thumb palpation, and tenderness thresholds were assessed by dolorimetry at four shin sites, nine tender point sites and four control point sites. Patients on steroids were significantly more tender than subjects not on steroids: their mean tender point counts were 13.3 and 6.7 (p
INTRODUCTION
of pain and are not represented
Pain perception is a complex and externally inaccessible experience determined by the integration of complex neuronal processes modulated by central factors including neurotransmitters and neurohormones (Buskila et al., 1993a).Pain can be exaggerated or suppressed, but it is a personal experience, not accessible to objective evaluation. In contrast, specific tenderness occurs at deep sites unknown to the patient, because the sites are not central to areas Paper received 24 January 1998 and accepted in revised form 7 July 1998. Correspondence to: Dan Buskila, Department of Medicine B, Soroka Medical Center, P.O. Box 151, Beer Sheva 84101, Israel. 1090-3801/98/030261+06 $12.00/O 0 1998 European Federation of Chapters
of the International
in consciousness.
Tendernesscan be measured as the force required to produce it. One method to measure tenderness has been codified in the American College of Rheumatology (ACR) 1990 criteria (Wolfe et al., 1990)for the classification of fibromyalgia syndrome, which used a simple count of 18 tender points assessedby palpation. Another method for assessingtenderness uses a dolorimeter, a device which allows accurate measurement of the degree of pressure being placed over a standardized surface area (McCarty et al., 1968). Recent studies have demonstrated the existence of several factors affecting tenderness, namely, sex, age, diagnosis, ethnicity and medications (Buskila et al., 1990, 1992, 1993a, 1995; Smythe et al., 1991, 1993). Diffuse pain associated with steroid therapy Association
for the Study
of Pain
II.
was described soon after the introduction of cortisone and its analogs (Rothstein & Good, 1957),and more, specifically, a marked tenderness of the shins was described in the 1970s(Smythe, 1972). Indeed, Smythe et al. (1990) reported a quantitative study of tendernessmeasured by a dolorimeter in 54 patients, of whom 26 had receivedsteroid therapy for at least 3 years [most of them were patients with systemic lupus erythematosus (SLE)]. This study demonstrated the presenceof tender shins in those receiving steroid therapy, as well as increasedtendernessat tender point sites and at control sites. Our aim was to extend the observation of increased tendernessin subjects on steroid therapy in a different diseasemodel, inflammatory bowel disease (IBD), and to explore the relationship between tenderness,dosage and duration of steroid therapy. MATERIALS AND METHODS Subjects
Eighty-seven patients with IBD [59 with ulcerative colitis (UC) and 28 with Crohn’s disease (CD)] attending the Gastroenterology Outpatient Clinic of the Soroka Medical Center (where most IBD cases in southern Israel are followed) during the period January to August 1997 were entered into the study. The subjects were not selected or excluded by symptoms of pain. The CD and UC casesmet the strict case definition criteria of Lennard-Jones (1989), as adopted by the ‘European Collaborative Study on the Epidemiology of IBD’ (Shivananda & Mayberry, 1993),in which the Gastroenterology Clinic participates. Patients were categorized as steroid treated if they had taken at least 5 mg of prednisonejday for at least 3 months. Part of the non-steroid group had never had steroids; the rest had previous steroid therapy, but none in the past year. The study was approved by the Helsinki Ethics Committee of the Soroka Medical Center, with all participants giving their written consent after having received detailed information about the study. European
Journal
of Pain
(1998),
2
Disease
activity
BUSKILA
ET AL.
of IBD
Disease activity was assessed by a gastroenterologist (HSO) who was unaware of the steroid treatment status and tenderness measurements of the subjects. The CD cases were scored for present level of disease activity by the Clamp/Softley modification of the Harvey/ Bradshaw Index (Myren et al., 1984). The possible range of this score is O-25, with 25 indicating active disease.Similarly, the UC cases were scoredby the Mayo Clinic System,modified to exclude findings at proctosigmoidoscopy (Odes, 1997). The possible range of the score is O-9, with 2 3 indicating active disease. Tenderness
assessment
Tenderness was assessedmanually and with a dolorimeter as described in detail elsewhere (Wolfe et al., 1990; Buskila & Neumann, 1997; Buskila et al., 1997)at tender point sites, control sites and shin sites. Tender points are specific, predictable anatomic sites that reveal tenderness upon physical examination which is lacking at control sites. A count of 18tender points at nine symmetrical siteswas performed by thumb palpation. Manual pressurewas demonstrated at a control site first. Subjects were told to expect a sensation of pressure but to indicate if it becamepainful. Definite tendernessat any of the points was considered to be present if some involuntary verbal or facial expression of pain occurred or a wince or withdrawal was observed. The amount of manual pressure applied over a tender point was about 4 kg/cm* (tested periodically with a dolorimeter). Thirteen point sites (nine tender point sites and four control sites)were further studied using a dolorimeter. The nine tender point sites were: the trapezius muscle (right and left), midpoint of the upper fold; the occiput (right), below the occipital prominence; cervical spine (right); the anterior aspect of the intertransverse spaces at C5-C7; the second costochondral junction (right), just lateral to the junctions, on the upper surface; the medial fat pad of both knees, overlying the medial collateral ligament; the lateral surface of the elbow (right), 2cm distal to the
TENDERNESS
AND
STEROIDS
lateral epicondyle; and 2 cm posterior to the greater trochanter (right). The four control sites were: the forehead (middle); the forearm (right distal third); the lateral surfaceof the knee (right); and the shaft of the third metatarsal (right). The four shin sites were medial (over the tibia) or lateral (over muscle) at thejunctions of the middle third with the upper and lower thirds, all on the right side. Threshold of tendernesswas measured using a Chatillon dolorimeter, model 719-20, which has a maximum scale of 9 kg, with a neoprene stopper footplate with a diameter of 1.4cm (McCarty et al., 1968). The site of maximum tenderness over tender point sites was determined by preliminary light pressure.The footplate of the dolorimeter was then placed appropriately, and, if necessary,its location was stabilized with the examiner’s non-dominant hand to prevent (often painful) shifting of the footplate under pressure,with care being taken not to add or subtract from the force applied. The dolorimeter was held close to the vertical position. Pressure was increased at the rate of about 1 kg/s. The subject was asked to say ‘yes’ when the sensation changed from pressure to definite pain. Preliminary measurements of the control sites were obtained not only to familiarize the subject with the process, but also to discourage anticipation of exaggerated responses. Patients were not told which were tender and which were control points, and the points were mixed together in the examination. All dolorimeter measurements of the 13 point sites, and the shin sites, as well as a total point count were done by one observer (ES), who was unaware whether the examined subject was on steroid therapy. Statistical
Analysis
The data are expressed as mean &- standard deviation (SD). Student’s t-tests and non-parametric Mann-Whitney tests were used to compare tendernessresults (mean point counts and mean dolorimeter thresholds) in various groups. Two-way analysis of variance was performed to examine the effectsof steroid therapy and gender
263
on measuresof tenderness.Pearson’scorrelation coefficients were used to assessthe relationship between tendernessand disease activity of UC and CD. RESULTS Eighty-seven IBD patients were recruited, 23 receiving steroid treatment and 64 not on steroids. In all subjects non-articular tendernesswas assessedmanually and by a dolorimeter. Table 1 displays the main sociodemographic and clinical characteristics of the two groups: gender distribution, age, educational level, employment status, duration and dosage of steroid treatment. The steroid group (n =23) did not differ significantly from the non-steroid group (n = 64) on any demographic variable (Table 1). In all subjects,a point count at 18tender points was conducted, and non-articular tendernesswas assessedby a dolorimeter at three site classes: tender point sites, control sites and shins (Table 2). IBD patients on steroids were significantly more tender than subjects not on steroids by all tenderness measures, namely, they had higher mean tender point counts and lower dolorimeter thresholds. Specifically, the mean tender point count (out of 18) was 13.3 vs 6.7 (p
Journal
of Pain
(1998),
2
D.
264
TABLE steroid
1. Demographic therapy.
and clinical
Steroids
Male/female ratio Age in years, mean (SD) Education in years, mean (SD) No. employed (%I Dosage of prednisone, mean (SD), mg range: Duration of prednisone treatment, mean (SD), months range:
14/9 39.3 11.5 12
TABLE
2. Measures
Tenderness
of tenderness
Data shows 3. Measures
as mean
(SD). Student’s
of tenderness
Steroid (n= 14) Tender point count (of 18) Dolorimeter thresholds (nine tender sites), kg Dolorimeter thresholds (four control sites), kg Shin site tenderness, kg Data shown
as mean
of Pain
(1998),
(n=64)
(610/o/39%) (16.9) ( 3.4) (52.2%)
28/36 46.4 13.2 36
(44%/56%) (16.4) ( 9.8) (56.3%)
(pzO.05). on steroid
and non-steroid
therapy.
Non-steroid (n=64)
p”
13.3 (2.6)
6.7 (4.4)
<0.001
3.3 (0.7)
6.1 (2.4)
co.oo1
3.9 (0.7) 3.8 (0.7)
6.5 (I .9) 6.7 (2.2)
<0.001
t-test and Mann-Whitney on steroid
Non-steroid (n=28)
test.
and non-steroid
IBD patients
Female p
12.4 (2.2)
5.4 (4.3)
co.oo1
3.2 (0.4)
6.7 (2.3)
3.8 (0.6) 3.8 (0.8)
7.1 (2.1) 7.6 (2.5)
Steroids (n=9)
therapy
by gender.
IBD patients Non-steroid (n=36)
p
14.9 (2.7)
7.6 (4.3)
<0.001
co.00 1
3.5 (0.9)
5.7 (2.4)
co.oo1
co.oo1 co.001
4.1 (0.7) 3.7 (0.9)
6.0 (1.6) 6.0 (1.7)
co.oo1 co.oo1
(SD).
measures of tenderness. Furthermore, 10 additional patients whose steroid treatment was discontinued less than a year ago, l-8 months (and therefore they were excluded from the study), had tendernessthresholds similar to those of patients who never were on steroids. In addition, we examined the relationship between tenderness,duration and dosageof steroid therapy, in subjectson steroids(n = 23). The range of steroid therapy was 3-72 months; thus, we Journal
Non-steroid
(n=23)
Steroids (n=23)
of IBD patients Male
and non-
16.1 (22.6) 3-72
in IBD patients
variable
on steroid
ETAL.
15.1 ( 9.8) 5-60
are not significant
Tender point count (of 18) Dolorimeter thresholds, kg (nine tender sites) Dolorimeter thresholds, kg (four control sites) Shin sites tenderness, kg
European
of IBD patients
Variable
Note, all differences
TABLE
details
BUSKILA
2
compared the tenderness of patients who were on steroids for less than a year (n = 13) with those for a year or more (n = 10). No significant differences were observed between these two groups regarding any tendernessmeasure.Moreover, when we examined eight patients who were on steroids for l-2 months (and therefore were not included in the study), they also exhibited increased tendernesscompared to patients not on steroid therapy.
TENDERNESS
AND
STEROIDS
TABLE steroid
4. Two-way therapy.
Tenderness Tender
Mean
Mean
Mean
265 analyses
of variance
measure
point
threshold
threshold
threshold
of tenderness
Source
measures,
of variation
by gender
and
Significance
count
of nine tender
of four control
Steroid therapy Gender Interaction
Steroid therapy Gender Interaction
Steroid therapy Gender Interaction
Steroid therapy Gender Interaction
sites
sites
of four shin sites
We also tested the association between disease activity and tenderness.Since the diseaseseverity scoresof UC and CD have different ranges and measure different aspects of disease, the mean scores of IBD patients (UC or CD) with and without steroids cannot be directly compared. The mean diseaseactivity scoresfor UC subjects on steroid therapy (n = 11) did not significantly differ from those not on steroid therapy (n= 48): 3.1+ 2.2 and 2.0+ 2.5, respectively (~~0.05). Similarly, no significant differenceswere observed regarding the severity scores of CD patients on steroids (n= 12) vs those not on steroids (n= 16):4.3 + 1.9 and 5.9+ 2.3, respectively (p>O.O5). Furthermore, no significant correlations were observedbetweentendernessthresholds and disease activity: in UC, the correlation was 0.158 (~~-0.05) and in CD, r=0.131 (p>O.O5). The steroid dosage ranged from 5-60 mg/day of prednisone. The 23 subjects on steroids were thus divided into two dosagegroups: above 10mg (inclusive) and below 10mg (n = 10 and n = 13, respectively). Patients with higher dosageswere more tender (i.e. had lower tendernessthresholds) than those with lower dosages:their mean tendernessthresholds at nine tender point sites were 3.OkO.5 and 3.5+0.7 kg, respectively(p=O.O57); and their mean tenderness thresholds at four control sites were 3.6 +0.6 and 4.2 +0.6 kg, respectively (p = 0.068).
DISCUSSION Our study demonstrated increased tendernessat the shins and tender point sites in IBD patients receiving steroid therapy. These findings are in accordance with the results of a prior study on the relationship between tendernessand steroids (Smythe et al., 1991).In that study, an increase of tendernessat shin sites associatedwith steroid therapy was confirmed, with a mean threshold of 3.0 kg in the steroid group, and in the nonsteroid group 5.6 kg. Similar increaseswere observedat the tender point and control point sites: 2.6 vs 4.1 kg, and 3.6 vs 5.6 kg, respectively. Likewise, in the presentstudy, we found a similar effect of steroid therapy on tenderness: at shin sites -3.8 vs 6.7 kg, at tender point sites -3.3 vs 6.1 kg, and at control point sites - 3.9 vs 6.5 kg. The increasedtendernessin the steroid group was observed for both sexes: men and women on steroids were significantly more tender than men and women not on steroids (Table 3). Furthermore, no correlation was observedbetween tendernessand duration of steroid treatment. A marked increase in tenderness was already noted after 3 months of steroid therapy. Even patients who were on steroids for l-2 months also exhibited increased tenderness. Thus, the effect of steroid therapy on tenderness European
Journal
of Pain
( 1998),2
266
D. BUSKILA
thresholds starts quite early in the course of the treatment. It seems,however, that the effect subsides rapidly after discontinuation of the steroid treatment. The tenderness threshold of patients who stopped taking steroids for at least a year was not different from those who were never on steroid therapy. Furthermore, patients whose steroid treatment was discontinued less than a year ago, l-8 months, had similar tendernessto patients who never were on steroids. In order to study the relationship between tendernessand steroid dosage, we have divided the 23 patients on steroids into two groups of comparable sizes, namely, those receiving 10 or more mg/day prednisone and those receiving less than lOmg/day. Despite the small comparison groups, increasedtendernesswas associatedwith increasedsteroid dosage. Sinceit seemsreasonableto assumethat dosage and duration of steroid treatment are somehow related to the severity of the IBD state, one may speculate that the increased tenderness demonstrated in subjects on steroids is related to the disease activity itself and not to the treatment with steroids. However, no such association was observedin our study. In the present study, we have demonstrated the relationship betweenincreasedtendernessand steroid therapy in IBD patients, in addition to the earlier observation in SLE (Smythe et al., 1991). These findings suggest that such a relationship is not diseasespecific, though further studies are neededto establish this association in other diseaseentities. What are the clinical implications of the effect of steroids on tenderness thresholds? The recognition of this association is relevant to every physician who cares for patients treated with steroids. Symptoms of increased tenderness at the shins, as well as at other soft tissue sites,may be misinterpreted by the physician unfamiliar with this association as part of the underlying disease. Future research is needed to further elucidate the possible role of steroid therapy on tenderness.
European Journal
of Pain
(19981,
2
ET AL.
REFERENCES Buskila D, Neumann L. Fibromyalgia syndrome (FM) and nonarticular tenderness in relatives of patients with FM. J Rheumatol 1997; 24: 941-944. Buskila D, Gladman DD, Langevitz P, Urowitz S, Smythe HA. Fibromyalgia in human immunodeficiency virus infection. J Rheumatol 1990; 17: 1202-1206. Buskila D, Langevitz P, Gladman DD, Urowitz S, Smythe HA. Patients with rheumatoid arthritis are more tender than those with psoriatic arthritis. J Rheumatol 1992; 19: 1115-1119. Buskila D, Pefer P, Harman-Boehm 1, Press J, Neumann L, Lunenfeld E, Gedalia A, Potashnik G, Sukenik S. Assessment of nonarticular tenderness and prevalence of fibromyalgia in hyperprolactinemic women. J Rheumatol 1993a; 20: 2112-2115. Buskila D, PressJ, Gedalia A, Klein M, Neumann L, Boehm R, Sukenik S. Assessment of nonarticular tenderness and prevalence of fibromyalgia in children. J Rheumatol 1993b; 20: 368-370. Buskila D, Neumann L, Press J, Zaks N, Gedalia A. Assessment of nonarticular tenderness of children in different ethnic groups. J Musculoskeletal Pain 1995; 3: 83390. Buskila D, Neumann L, Vaisberg G, Alkalay D, Wolfe F. Increased rates of fibromyalgia following cervical spine injury. Arthritis Rheumatism 1997; 40: 446-452. Lennard-Jones JE. Classification of inflammatory bowel disease. Stand J Gastroenteroll989; 24 (Suppl. 170): 2-6. McCarty DJ, Gatter RD, Steele AD. A twenty pound dolorimeter for quantification of articular tenderness. Arthritis Rheum 1968; 11: 690497. Myren J, Bouchier IAD, Watkinson G, Softley A, Clamp SE, de Dombal FT. The O.M.G.E. multinational inflammatory bowel disease survey 19761982. A further report on 2,657 cases. Sand J Gastroenterol 1984; 19: l-27. Odes HS. 5-Aminosalicylic acid, l,OOO-mgcaplets versus 500-mg tablets, in maintenance of remission in ulcerative colitis. J Clin Gastroenterol 1997; 24: 287-288. Rotstein J, Good RA. Steroid pseudorheumatism. Arch Intern Med 1957; 99: 545-546. Shivananda S, Mayberry JF. Epidemiology of inflammatory bowel disease. Curr Opin Gastroenterol 1993; 9: 560-565. Smythe HA. Nonarticular rheumatism and the “fibrositis” syndrome. In: Hollander JL, McCarty DJ, editors. Arthritis and Allied Conditions, 8th ed. Philadelphia: Lea & Febiger, 1972. Smythe HA, Lee D, Rush P, Buskila D. Tender shins and steroid therapy. J Rheumatol 1991; 18: 1568-1572. Smythe HA, Buskila D, Gladman DD. Performance of scored palpation, a point count, and dolorimetry in assessingunsuspected nonarticular tenderness. J ZZheumatol 1993; 20: 352-357. Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, Tugwell P, and the Multicenter Criteria Committee. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Arthritis Rheum 1990; 33: 160-172.
Journal
of Pain (1998) 2: 261-266
Increased non-articular steroid therapy
tenderness
in patients
on
Dan Buskila”, Elena Schleiferb, H. Selvyn Odesb and Lily Neumannc “Rheumatic Disease Unit, bGastroenterology Institute, “Department of Epidemiology, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
Increased non-articular tenderness and tender shins have been suggested to be associated with steroid therapy in patients with lupus. The aim of the present study was to extend this observation in a different disease, inflammatory bowel disease (IBD), and to examine the relationship between tenderness, dosage and duration of steroid therapy. Eighty-seven patients with IBD, 23 of them on steroid therapy, were assessed for disease activity and nonarticular tenderness. A count of 18 tender points was conducted by thumb palpation, and tenderness thresholds were assessed by dolorimetry at four shin sites, nine tender point sites and four control point sites. Patients on steroids were significantly more tender than subjects not on steroids: their mean tender point counts were 13.3 and 6.7 (p
INTRODUCTION
of pain and are not represented
Pain perception is a complex and externally inaccessible experience determined by the integration of complex neuronal processes modulated by central factors including neurotransmitters and neurohormones (Buskila et al., 1993a).Pain can be exaggerated or suppressed, but it is a personal experience, not accessible to objective evaluation. In contrast, specific tenderness occurs at deep sites unknown to the patient, because the sites are not central to areas Paper received 24 January 1998 and accepted in revised form 7 July 1998. Correspondence to: Dan Buskila, Department of Medicine B, Soroka Medical Center, P.O. Box 151, Beer Sheva 84101, Israel. 1090-3801/98/030261+06 $12.00/O 0 1998 European Federation of Chapters
of the International
in consciousness.
Tendernesscan be measured as the force required to produce it. One method to measure tenderness has been codified in the American College of Rheumatology (ACR) 1990 criteria (Wolfe et al., 1990)for the classification of fibromyalgia syndrome, which used a simple count of 18 tender points assessedby palpation. Another method for assessingtenderness uses a dolorimeter, a device which allows accurate measurement of the degree of pressure being placed over a standardized surface area (McCarty et al., 1968). Recent studies have demonstrated the existence of several factors affecting tenderness, namely, sex, age, diagnosis, ethnicity and medications (Buskila et al., 1990, 1992, 1993a, 1995; Smythe et al., 1991, 1993). Diffuse pain associated with steroid therapy Association
for the Study
of Pain
II.
was described soon after the introduction of cortisone and its analogs (Rothstein & Good, 1957),and more, specifically, a marked tenderness of the shins was described in the 1970s(Smythe, 1972). Indeed, Smythe et al. (1990) reported a quantitative study of tendernessmeasured by a dolorimeter in 54 patients, of whom 26 had receivedsteroid therapy for at least 3 years [most of them were patients with systemic lupus erythematosus (SLE)]. This study demonstrated the presenceof tender shins in those receiving steroid therapy, as well as increasedtendernessat tender point sites and at control sites. Our aim was to extend the observation of increased tendernessin subjects on steroid therapy in a different diseasemodel, inflammatory bowel disease (IBD), and to explore the relationship between tenderness,dosage and duration of steroid therapy. MATERIALS AND METHODS Subjects
Eighty-seven patients with IBD [59 with ulcerative colitis (UC) and 28 with Crohn’s disease (CD)] attending the Gastroenterology Outpatient Clinic of the Soroka Medical Center (where most IBD cases in southern Israel are followed) during the period January to August 1997 were entered into the study. The subjects were not selected or excluded by symptoms of pain. The CD and UC casesmet the strict case definition criteria of Lennard-Jones (1989), as adopted by the ‘European Collaborative Study on the Epidemiology of IBD’ (Shivananda & Mayberry, 1993),in which the Gastroenterology Clinic participates. Patients were categorized as steroid treated if they had taken at least 5 mg of prednisonejday for at least 3 months. Part of the non-steroid group had never had steroids; the rest had previous steroid therapy, but none in the past year. The study was approved by the Helsinki Ethics Committee of the Soroka Medical Center, with all participants giving their written consent after having received detailed information about the study. European
Journal
of Pain
(1998),
2
Disease
activity
BUSKILA
ET AL.
of IBD
Disease activity was assessed by a gastroenterologist (HSO) who was unaware of the steroid treatment status and tenderness measurements of the subjects. The CD cases were scored for present level of disease activity by the Clamp/Softley modification of the Harvey/ Bradshaw Index (Myren et al., 1984). The possible range of this score is O-25, with 25 indicating active disease.Similarly, the UC cases were scoredby the Mayo Clinic System,modified to exclude findings at proctosigmoidoscopy (Odes, 1997). The possible range of the score is O-9, with 2 3 indicating active disease. Tenderness
assessment
Tenderness was assessedmanually and with a dolorimeter as described in detail elsewhere (Wolfe et al., 1990; Buskila & Neumann, 1997; Buskila et al., 1997)at tender point sites, control sites and shin sites. Tender points are specific, predictable anatomic sites that reveal tenderness upon physical examination which is lacking at control sites. A count of 18tender points at nine symmetrical siteswas performed by thumb palpation. Manual pressurewas demonstrated at a control site first. Subjects were told to expect a sensation of pressure but to indicate if it becamepainful. Definite tendernessat any of the points was considered to be present if some involuntary verbal or facial expression of pain occurred or a wince or withdrawal was observed. The amount of manual pressure applied over a tender point was about 4 kg/cm* (tested periodically with a dolorimeter). Thirteen point sites (nine tender point sites and four control sites)were further studied using a dolorimeter. The nine tender point sites were: the trapezius muscle (right and left), midpoint of the upper fold; the occiput (right), below the occipital prominence; cervical spine (right); the anterior aspect of the intertransverse spaces at C5-C7; the second costochondral junction (right), just lateral to the junctions, on the upper surface; the medial fat pad of both knees, overlying the medial collateral ligament; the lateral surface of the elbow (right), 2cm distal to the
TENDERNESS
AND
STEROIDS
lateral epicondyle; and 2 cm posterior to the greater trochanter (right). The four control sites were: the forehead (middle); the forearm (right distal third); the lateral surfaceof the knee (right); and the shaft of the third metatarsal (right). The four shin sites were medial (over the tibia) or lateral (over muscle) at thejunctions of the middle third with the upper and lower thirds, all on the right side. Threshold of tendernesswas measured using a Chatillon dolorimeter, model 719-20, which has a maximum scale of 9 kg, with a neoprene stopper footplate with a diameter of 1.4cm (McCarty et al., 1968). The site of maximum tenderness over tender point sites was determined by preliminary light pressure.The footplate of the dolorimeter was then placed appropriately, and, if necessary,its location was stabilized with the examiner’s non-dominant hand to prevent (often painful) shifting of the footplate under pressure,with care being taken not to add or subtract from the force applied. The dolorimeter was held close to the vertical position. Pressure was increased at the rate of about 1 kg/s. The subject was asked to say ‘yes’ when the sensation changed from pressure to definite pain. Preliminary measurements of the control sites were obtained not only to familiarize the subject with the process, but also to discourage anticipation of exaggerated responses. Patients were not told which were tender and which were control points, and the points were mixed together in the examination. All dolorimeter measurements of the 13 point sites, and the shin sites, as well as a total point count were done by one observer (ES), who was unaware whether the examined subject was on steroid therapy. Statistical
Analysis
The data are expressed as mean &- standard deviation (SD). Student’s t-tests and non-parametric Mann-Whitney tests were used to compare tendernessresults (mean point counts and mean dolorimeter thresholds) in various groups. Two-way analysis of variance was performed to examine the effectsof steroid therapy and gender
263
on measuresof tenderness.Pearson’scorrelation coefficients were used to assessthe relationship between tendernessand disease activity of UC and CD. RESULTS Eighty-seven IBD patients were recruited, 23 receiving steroid treatment and 64 not on steroids. In all subjects non-articular tendernesswas assessedmanually and by a dolorimeter. Table 1 displays the main sociodemographic and clinical characteristics of the two groups: gender distribution, age, educational level, employment status, duration and dosage of steroid treatment. The steroid group (n =23) did not differ significantly from the non-steroid group (n = 64) on any demographic variable (Table 1). In all subjects,a point count at 18tender points was conducted, and non-articular tendernesswas assessedby a dolorimeter at three site classes: tender point sites, control sites and shins (Table 2). IBD patients on steroids were significantly more tender than subjects not on steroids by all tenderness measures, namely, they had higher mean tender point counts and lower dolorimeter thresholds. Specifically, the mean tender point count (out of 18) was 13.3 vs 6.7 (p
Journal
of Pain
(1998),
2
D.
264
TABLE steroid
1. Demographic therapy.
and clinical
Steroids
Male/female ratio Age in years, mean (SD) Education in years, mean (SD) No. employed (%I Dosage of prednisone, mean (SD), mg range: Duration of prednisone treatment, mean (SD), months range:
14/9 39.3 11.5 12
TABLE
2. Measures
Tenderness
of tenderness
Data shows 3. Measures
as mean
(SD). Student’s
of tenderness
Steroid (n= 14) Tender point count (of 18) Dolorimeter thresholds (nine tender sites), kg Dolorimeter thresholds (four control sites), kg Shin site tenderness, kg Data shown
as mean
of Pain
(1998),
(n=64)
(610/o/39%) (16.9) ( 3.4) (52.2%)
28/36 46.4 13.2 36
(44%/56%) (16.4) ( 9.8) (56.3%)
(pzO.05). on steroid
and non-steroid
therapy.
Non-steroid (n=64)
p”
13.3 (2.6)
6.7 (4.4)
<0.001
3.3 (0.7)
6.1 (2.4)
co.oo1
3.9 (0.7) 3.8 (0.7)
6.5 (I .9) 6.7 (2.2)
<0.001
t-test and Mann-Whitney on steroid
Non-steroid (n=28)
test.
and non-steroid
IBD patients
Female p
12.4 (2.2)
5.4 (4.3)
co.oo1
3.2 (0.4)
6.7 (2.3)
3.8 (0.6) 3.8 (0.8)
7.1 (2.1) 7.6 (2.5)
Steroids (n=9)
therapy
by gender.
IBD patients Non-steroid (n=36)
p
14.9 (2.7)
7.6 (4.3)
<0.001
co.00 1
3.5 (0.9)
5.7 (2.4)
co.oo1
co.oo1 co.001
4.1 (0.7) 3.7 (0.9)
6.0 (1.6) 6.0 (1.7)
co.oo1 co.oo1
(SD).
measures of tenderness. Furthermore, 10 additional patients whose steroid treatment was discontinued less than a year ago, l-8 months (and therefore they were excluded from the study), had tendernessthresholds similar to those of patients who never were on steroids. In addition, we examined the relationship between tenderness,duration and dosageof steroid therapy, in subjectson steroids(n = 23). The range of steroid therapy was 3-72 months; thus, we Journal
Non-steroid
(n=23)
Steroids (n=23)
of IBD patients Male
and non-
16.1 (22.6) 3-72
in IBD patients
variable
on steroid
ETAL.
15.1 ( 9.8) 5-60
are not significant
Tender point count (of 18) Dolorimeter thresholds, kg (nine tender sites) Dolorimeter thresholds, kg (four control sites) Shin sites tenderness, kg
European
of IBD patients
Variable
Note, all differences
TABLE
details
BUSKILA
2
compared the tenderness of patients who were on steroids for less than a year (n = 13) with those for a year or more (n = 10). No significant differences were observed between these two groups regarding any tendernessmeasure.Moreover, when we examined eight patients who were on steroids for l-2 months (and therefore were not included in the study), they also exhibited increased tendernesscompared to patients not on steroid therapy.
TENDERNESS
AND
STEROIDS
TABLE steroid
4. Two-way therapy.
Tenderness Tender
Mean
Mean
Mean
265 analyses
of variance
measure
point
threshold
threshold
threshold
of tenderness
Source
measures,
of variation
by gender
and
Significance
count
of nine tender
of four control
Steroid therapy Gender Interaction
Steroid therapy Gender Interaction
Steroid therapy Gender Interaction
Steroid therapy Gender Interaction
sites
sites
of four shin sites
We also tested the association between disease activity and tenderness.Since the diseaseseverity scoresof UC and CD have different ranges and measure different aspects of disease, the mean scores of IBD patients (UC or CD) with and without steroids cannot be directly compared. The mean diseaseactivity scoresfor UC subjects on steroid therapy (n = 11) did not significantly differ from those not on steroid therapy (n= 48): 3.1+ 2.2 and 2.0+ 2.5, respectively (~~0.05). Similarly, no significant differenceswere observed regarding the severity scores of CD patients on steroids (n= 12) vs those not on steroids (n= 16):4.3 + 1.9 and 5.9+ 2.3, respectively (p>O.O5). Furthermore, no significant correlations were observedbetweentendernessthresholds and disease activity: in UC, the correlation was 0.158 (~~-0.05) and in CD, r=0.131 (p>O.O5). The steroid dosage ranged from 5-60 mg/day of prednisone. The 23 subjects on steroids were thus divided into two dosagegroups: above 10mg (inclusive) and below 10mg (n = 10 and n = 13, respectively). Patients with higher dosageswere more tender (i.e. had lower tendernessthresholds) than those with lower dosages:their mean tendernessthresholds at nine tender point sites were 3.OkO.5 and 3.5+0.7 kg, respectively(p=O.O57); and their mean tenderness thresholds at four control sites were 3.6 +0.6 and 4.2 +0.6 kg, respectively (p = 0.068).
DISCUSSION Our study demonstrated increased tendernessat the shins and tender point sites in IBD patients receiving steroid therapy. These findings are in accordance with the results of a prior study on the relationship between tendernessand steroids (Smythe et al., 1991).In that study, an increase of tendernessat shin sites associatedwith steroid therapy was confirmed, with a mean threshold of 3.0 kg in the steroid group, and in the nonsteroid group 5.6 kg. Similar increaseswere observedat the tender point and control point sites: 2.6 vs 4.1 kg, and 3.6 vs 5.6 kg, respectively. Likewise, in the presentstudy, we found a similar effect of steroid therapy on tenderness: at shin sites -3.8 vs 6.7 kg, at tender point sites -3.3 vs 6.1 kg, and at control point sites - 3.9 vs 6.5 kg. The increasedtendernessin the steroid group was observed for both sexes: men and women on steroids were significantly more tender than men and women not on steroids (Table 3). Furthermore, no correlation was observedbetween tendernessand duration of steroid treatment. A marked increase in tenderness was already noted after 3 months of steroid therapy. Even patients who were on steroids for l-2 months also exhibited increased tenderness. Thus, the effect of steroid therapy on tenderness European
Journal
of Pain
( 1998),2
266
D. BUSKILA
thresholds starts quite early in the course of the treatment. It seems,however, that the effect subsides rapidly after discontinuation of the steroid treatment. The tenderness threshold of patients who stopped taking steroids for at least a year was not different from those who were never on steroid therapy. Furthermore, patients whose steroid treatment was discontinued less than a year ago, l-8 months, had similar tendernessto patients who never were on steroids. In order to study the relationship between tendernessand steroid dosage, we have divided the 23 patients on steroids into two groups of comparable sizes, namely, those receiving 10 or more mg/day prednisone and those receiving less than lOmg/day. Despite the small comparison groups, increasedtendernesswas associatedwith increasedsteroid dosage. Sinceit seemsreasonableto assumethat dosage and duration of steroid treatment are somehow related to the severity of the IBD state, one may speculate that the increased tenderness demonstrated in subjects on steroids is related to the disease activity itself and not to the treatment with steroids. However, no such association was observedin our study. In the present study, we have demonstrated the relationship betweenincreasedtendernessand steroid therapy in IBD patients, in addition to the earlier observation in SLE (Smythe et al., 1991). These findings suggest that such a relationship is not diseasespecific, though further studies are neededto establish this association in other diseaseentities. What are the clinical implications of the effect of steroids on tenderness thresholds? The recognition of this association is relevant to every physician who cares for patients treated with steroids. Symptoms of increased tenderness at the shins, as well as at other soft tissue sites,may be misinterpreted by the physician unfamiliar with this association as part of the underlying disease. Future research is needed to further elucidate the possible role of steroid therapy on tenderness.
European Journal
of Pain
(19981,
2
ET AL.
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