Lower Urinary Tract Symptoms in Women with Systemic Lupus Erythematosus
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Lower Urinary Tract Symptoms in Women with
Systemic Lupus Erythematosus
Wei-Chia Lee, Kuang-Lun Lee1, Mao-Yuan Chen1,
Cheng-Yuan Chen1, Jun Chen, Hong-Jeng Yu
1
Department of Urology and Internal Medicine, National Taiwan University Hospital,
Taipei, Taiwan, R.O.C.
OBJECTIVE: Systemic lupus erythematosus (SLE) is a multisystem disease with a wide
spectrum of clinical and laboratory features. Involvement of the urinary bladder is rarely men-
tioned in the literature. We conducted this study to examine lower urinary tract function in fe-
male patients with SLE.
METHODS: We conducted a prospective study on 145 consecutive female SLE patients re-
ceiving regular treatments in the Rheumatology Department from October 1999 through June
2000. Each patient was interviewed with a questionnaire comprised of the International Prostate
Symptom Score (IPSS) and their clinical histories of SLE. Symptom scores were further corre-
lated with disease severity, which was determined by the SLE disease activity index (SLEDAI)
based on clinical and laboratory features. In addition, symptom scores obtained from 177
age-matched healthy females were used as a control.
RESULT: Total symptom score (6.24 ± 0.56 vs. 4.26 ± 0.36), irritative symptom score
(3.71± 0.32 vs. 2.88 ± 0.22), and obstructive symptom score (2.53 ± 0.33 vs. 1.38 ± 0.19) were all
significantly higher in the SLE group when compared to the control group. The symptom score
showed a significant correlation with disease activity (r = 0.30, p < 0.001), but not with disease
duration (p > 0.05). Overall, 45 (31.0%) patients reported an IPSS of > 7. Those who linked
their urinary symptoms to SLE (n = 29) had significantly higher symptom scores than those who
did not (n = 16). Thirty-eight (26.2%) patients reported being “mostly dissatisfied” with their
urination.
CONCLUSIONS: Our study suggests that a substantial number of women with SLE present
with various degrees of voiding dysfunction that is significantly associated with disease activity.
Whether voiding dysfunction is a clinical manifestation of lupus cystitis or secondary to other
factors remains to be elucidated. (J Urol R.O.C., 11:161-6, 2000)
Key words: Systemic lupus etrythemaosus, lower urinary tract symptoms, IPSS.
INTRODUCTION renal length and echogenicity has been reported in about
40% to 75% of patients with SLE [4,5]. Involvement of
Systemic lupus erythematosus (SLE) is an auto- the urinary bladder in SLE is rarely mentioned in the
immune disease entity with multiorgan involvement [1]. literature. Only severe cases presenting with interstitial
Polyarthritis and dermatitis are the most common clini- cystitis-like symptoms and signs (lupus cystitis) with
cal manifestations of SLE. Many of the clinical mani- coexisting obstructive uropathy have been reported
festations of SLE are a consequence of tissue damage sporadically [6-10]. Symptoms can be managed by ster-
from vasculopathy mediated by immune complexes oid pulse therapy and improved when the disease activ-
[2,3]. The prevalence of SLE varies throughout the ity is under control. In our clinical practice however,
world. In North American and northern Europe, it is patients with SLE who suffer from lower urinary tract
about 40 per 100,000 people. SLE predominately affects symptoms like frequency, urgency, and nocturia are not
young women, and diagnosis is most frequent during infrequently seen. Thus, it would be of interest to inves-
the second and third decades of life [1]. tigate the prevalence of lower urinary tract symptoms in
In the genitourinary tract, the kidney is the most patients with SLE and to assess the impacts on their
commonly involved organ in SLE. Apparent lupus ne- daily lives. In the present study, we used the Interna-
phritis manifesting as proteinuria, hematuria, abnormal tional Prostate Symptom Score (IPSS) [11] to estimate
Received: Feb. 8, 2001 Revised: March 5, 2001 Accepted: June 20, 2001
Address reprint requests and correspondence to: Dr. Hong-Jeng Yu,
Department of Urology, National Taiwan University Hospital, 7 South Chung-Shan Road, Taipei, Taiwan, 100 R.O.C.
中華泌尿醫誌第十一卷第四期（89 年 12 月） 161Lower Urinary Tract Symptoms in Systemic Lupus Erythematosus
the lower urinary tract symptoms (LUTS) in 145 female daily lives. We defined the moment of the onset of dis-
patients with SLE. We correlated their urinary symp- ease as the time of clinical diagnosis of SLE, since the
toms with disease activity, which was determined by the first manifestation of disease is a less precise moment.
SLE disease activity index (SLEDAI). SLEDAI esti- Each patient received basic laboratory studies, including
mates 24 clinical attributes grouped into 9 organ sys- complete blood count, urinalysis, renal function test,
tems and derives a weighted score for each organ sys- anti-nuclear antibody (ANA), anti-DNA, C3, C4, and
tem based on clinical and laboratory features. The total renal sonographic examinations. Intravenous urography
score of SLEDAI ranges from 0 to 105 [12,13]. Further, (IVU) was also performed in patients who presented
to gain a better understanding of voiding dysfunction in with hydronephrosis on sonographic examinations or in
patients with SLE with respect to healthy individuals, those with severe urinary symptoms. The disease activ-
symptom scores were further compared to those of a ity was determined by SLEDAI, which is the sum of the
group of age-matched controls. score of 24 clinical variables. Each variable is scored
based on clinical or laboratory features. The total SLE-
SUBJECTS AND METHODS DAI score ranges from 0 to 105 [12]. Finally,
age-matched controls were selected from a data bank of
From October 1999 through June 2000, 151 pa- 583 females attending a health examination at National
tients with SLE received treatment in the Rhematology Taiwan University Hospital [14] for a comparison of
Department of National Taiwan University Hospital. urinary symptoms with the SLE group. Based on age,
Of these, 6 male patients were excluded due to the small menstruation, and birth histories, 177 subjects were se-
case number and the possible conflict of lower urinary lected.
symptoms induced by infravesical obstruction. Conse- Data are expressed as the mean ± standard error of
quently, 145 female patients were recruited into this the mean (SEM) and were analyzed using the Statistical
study. They were all interviewed by a single urologist Package for the Social Science (SPSS, Chicago, IL,
(WC Lee) with a questionnaire that consisted of the USA). Comparison of age, and obstructive, irritating
IPSS and clinical history of SLE. The IPSS question- and total symptom scores between patients with SLE
naire comprises 7 questions on LUTS (frequency, ur- and the controls were made by two-sample t- test.
gency, nocturia, intermittency, incomplete emptying, Chi-square test was used to compare the proportion of
weak stream, and hesitancy) and an additional question subjects whose daily lives were affected by their urinary
on general satisfaction of urinary conditions. Nocturia symptoms in each group. The associations of SLEDAI
was scored from 0 to 5 (5 or more times per night) as with disease duration on urinary symptoms were exam-
the actual voiding frequency per night. Other symptoms ined using correlation analysis with adjustment for age,
were scored on a frequency scale from 0 to 5: 0 (not at considering the possible confounding effect of age on
all); 1 (less than once every 5 times); 2 (less than half urinary symptoms. For all statistical tests, a p < 0.05
the time); 3 (about half the time); 4 (more than half the was considered significant.
time); and 5 (almost always). The scores were aggre-
gated to form a symptom index from 0 to 35. In this RESULTS
study, the sum of the obstructive symptom score (in-
complete emptying, intermittency, weak stream, and The mean age was 42.5 ± 1.1 years (range 20 to 69
hesitancy), irritative symptom score (frequency, ur- years). The disease duration ranged from 2 to 300
gency, and nocturia), and total symptom score were months (mean 96.0 ± 5.3 months). The duration of uri-
respectively calculated. Overall subjective satisfaction nary symptoms varied from 1 to 150 months (mean 15.8
with urinary conditions was scored from 0 (feel de- ± 2.5 months). The SLEDAI score ranged from 0 to 31
lighted) to 6 (feel terrible) to use as a quality of life (mean 7.6 ± 0.5).
(QOL) index. The distribution of individual voiding symptom
The clinical history of SLE included the duration scores in the SLE patients is shown in Table 1. If an
of SLE, treatments given, duration of urinary symptoms, individual symptom score of ≥ 2 was chosen as a cutoff
whether the patients linked their urinary symptoms to value, 32.8% of patients had frequency, 44.2% had
SLE, and whether the urinary symptoms affected their nocturia, and 17.3% had urgency. In contrast, the fre-
Table 1. Distribution of individual urinary symptoms among 145 SLE patients
Distribution of IPSS (%)
Symptom 0 1 2 3 4 5
Frequency 52.7 14.5 6.9 5.2 6.2 14.5
Nocturia 41.4 14.5 13.8 0.7 8.3 21.4
Urgency 74.5 8.3 9.7 0.7 2.8 4.1
Weak stream 69.0 6.2 13.8 0 3.4 7.6
Incomplete emptying 74.5 11.7 5.5 1.4 4.1 2.8
Hesitancy 77.9 7.6 6.2 0.7 4.1 3.4
Intermittency 77.2 6.2 8.3 4.1 1.4 2.8
162 J UROL ROC Vol.11 No.4, Dec.
2000WC Lee, KL Lee, MY Chen, et al
quencies of obstructive symptoms such as hesitancy which did not significantly differ from that of the con-
(14.4%), intermittency (16.6%), weak stream (24.8%), trol group (21.2%, p > 0.05). Dysuria was a complaint
and incomplete emptying (13.8%) were relatively lower. of 12% of patients. Pyuria (WBC > 5/ high power field)
Overall, 45 (31.0%) patients reported an IPSS of > 7, was seen in 25%, hematuria (RBC > 5/ high power field)
and 38 (26.2%) reported being “mostly dissatisfied” in 32%, and proteinuria (urine protein ≥ 30 mg on
(QOL score ≥ 4) with their urination. In contrast, 32 multistrip test) in 24% of patients. Twenty- six (18%)
(18.1%, p < 0.05 compared to the SLE group) women in patients had an abnormal renal sonography of which 6
the control group reported an IPSS of > 7, and 23 (4.1%) had hydronephrosis of various degrees. Of these,
(12.9%, p < 0.05 compared to the SLE group) reported contracted bladder with bilateral ureterovesical junction
being “mostly dissatisfied” with their urination. Table 2 stenosis was seen in 2 patients with IVU. IVU was also
compares differences in symptom scores between the performed in another 8 patients with moderate to severe
SLE and control groups. Total urinary symptom score, urinary symptoms. Small bladder capacity with no evi-
irritative symptom score, and obstructive symptom dence of upper urinary tract abnormality was seen in 2
score were all significantly higher in the SLE group. patients. Taken together, 4 (2.8%) of this study group
Of the 45 patients with an IPSS > 7, those (n = 29) had an overt abnormal appearance of the urinary blad-
who linked their urinary symptoms to SLE had a sig- der.
nificantly higher IPSS than did those (n = 16) who did
not (Table 3). With adjustment for age, IPSS correlated DISCUSSION
significantly with SLEDAI (r = 0.30, p < 0.001) and
duration of urinary symptoms (r = 0.35, p < 0.001), but SLE is a disease of unknown etiology in which
not with duration of SLE (r = 0.06, p > 0.05). Figure 1 tissue and cells are damaged by the deposition of patho-
depicts the distribution of IPSS in relation to SLEDAI. genic autoantibodies and immune complexes. The
In the SLE group, 17.9% reported various degrees commonly involved sites are skin, kidney, hematologi-
of urinary incontinence in the preceding 12 months, cal, and central nervous systems [1,2]. Through many
Table 2. Comparison of IPSS between the SLE and control groups
Age (yr) Irritative score Obstructive score Total score
SLE (n=145) 42.5 ± 1.1 3.71 ± 0.32 2.53 ± 0.33 6.24 ± 0.56
Control (n=177) 44.8 ± 0.9 2.88 ± 0.22 1.38 ± 0.19 4.26 ± 0.36
p valuea 0.302 < 0.001 < 0.001 < 0.001
a
Comparisons were made by two-sample t-test.
Values represent the mean ± SEM.
Table 3. Comparisons of patients who linked their urinary symptoms to SLE (group A) or those who did not
(group B)
Score Age (yr) Disease duration (mo)
Group A (n = 29) 14.47 ±1.48 37.35 ±2.04 78.94 ±12.18
Group B (n = 16) 8.07±0.39 41.06 ±1.31 85.75 ±6.97
a
p value < 0.001 0.180 0.987
a
Comparisons were made by two-sample t-test.
Values represent the mean ±SEM.
Fig. 1 Linear regression analysis of SLEDAI versus IPSS scores.
中華泌尿醫誌第十一卷第四期（89 年 12 月） 163Lower Urinary Tract Symptoms in Systemic Lupus Erythematosus
investigations, this disease can now be diagnosed based with an IPSS of > 7 was higher in the SLE group
on clinic manifestations and a series of biochemistry (31.0% vs. 18.5%, p < 0.001). And third, the proportion
studies, including ANA, anti-DNA, C3, C4, and so on of patients with a QOL score of ≥ 4 was also higher in
[15]. There are no absolute guides to the management of the SLE group (26.2 vs. 12.9%, p < 0.001). That pa-
SLE. Treatment is determined to a great extent by indi- tients who linked their urinary symptoms to SLE (e.g.,
vidual disease manifestations and disease activities, they believed their urinary symptoms were caused by
which can be estimated by some index systems derived SLE) had significantly higher symptom scores than
from the clinical and laboratory features [1-3,12,15]. those who did not may provide indirect evidence of
SLEDAI is one of the validated indices reported to pro- SLE-induced voiding dysfunction in these patients. The
vide a global assessment of disease activity in SLE question raised then is whether the higher incidence of
[12,13]. The maximum theoretical score is 105, but in voiding dysfunction is one of the clinical manifestations
practice, few patients have scores greater than 45. In of lupus cystitis or secondary to other factors. Aside
general, half of the patients have values of 10 or less, from lupus cystitis, several factors like bacterial cystitis,
and only 25% of patients have a value of 20 or more cyclophosphamide-induced cystitis and neurogenic
[12]. In general, the disease activity can be controlled, dysfunction secondary to transverse myelopathy are
but not cured by NSAIDS or immunosuppressive agents known to cause bladder dysfunction in patients with
[1-3]. In this study, only 13 (9.1%) patients had a SLE- SLE [10]. None of our patients during the study period
DAI score ≥ 20, indicating that most of our patients had been treated with cyclophosphamide or had clinical
presented with milder disease activities during this evidence of transverse myelopathy; therefore, it was
study. unlikely that these 2 factors played an important role in
Extrarenal involvement of the genitourinary tract in the voiding dysfunction of these patients. On the other
SLE is less well understood. Theoretically, the immune hand, inflammation of the lower urinary tract may have
complexes can deposit in any systemic organs including been an important factor as 25% of our patients pre-
the urinary bladder, yet involvement of the urinary sented with pyuria during the investigation.
bladder in SLE is rarely mentioned in published reports. Typical pictures of lupus cystitis include a con-
To date, only patients with severe lupus cystitis have tracted bladder with severe irritative symptoms, such as
been sporadically reported [6-10]. Otherwise, bladder frequency, nocturia, and urgency [6-10]. Similarly, a
involvement in patients with SLE has never been exten- great proportion of our patients complained of fre-
sively studied. It is not clear whether the low incidence quency and nocturia (Table 1). If an individual symp-
of bladder involvement in SLE is a fact or has simply tom score of ≥ 2 was chosen as the cutoff value, 32.8%
been overlooked. Perhaps similar to other organs such of patients had frequency and 44.2% had to wake up at
as lung (interstitial pneumonia and fibrosing alveolitis) least twice per night to void. These findings may also
and muscle (myositis or a non-specific proximal myo- provide indirect evidence for possible bladder involve-
pathy) [1], involvement of the bladder in SLE tends to ment in these patients. In addition to the irritative
be mild and may easily to be overshadowed by other symptom score, the obstructive score was also higher in
more-dramatic clinical features of the disease. patients with SLE. Obstructive symptoms like a weak
In the present study we used urinary symptoms and urinary stream, intermittency, and hesitancy are not un-
laboratory data to evaluate lower urinary tract function commonly seen in elderly females [14]. The major fac-
in female patients with SLE. To avoid sampling bias, tor responsible for these obstructive symptoms may be
we sampled, on an unselected basis, all patients with age-related detrusor under-activity rather than bladder
SLE attending the rheumatological clinic during a outlet obstruction [14]. As the mean age in females with
7-month period. The presence of voiding dysfunction SLE was younger (mean age: 42.5 years), it is unlikely
was evaluated by the IPSS, which has been widely used that the obstructive symptoms were a factor of age.
for quantitative evaluation of subjective LUTS in be- Nevertheless, the obstructive symptoms in these patients
nign prostatic hyperplasia (BPH) [11]. Taking advan- might also have been caused by weak detrusor function
tage of its ease in understanding and quantitative nature, in which muscle fibers are damaged by the deposition of
IPSS has also been used to estimate the severity of uri- pathogenic autoantibodies and immune complexes, as
nary symptoms in patients with other disease as well as occurs in other organs [1-4]. Urodynamic study and
in females [14-18]. As the LUTS in a cohort of apparent bladder biopsies are indicated to investigate this notion.
healthy Taiwanese females assessed by IPSS has been There was a significant association between symp-
previously reported [14], the use of IPSS in this study tom score and disease activity, but not disease duration.
made it possible not only to quantitate the LUTS in fe- This result differs from the clinical presentation of lupus
male patients with SLE but also to compare it with nephritis in which the incidence and severity are associ-
healthy controls. ated with disease duration [4,5]. In accordance with
Three findings in this study suggest that patients previous reports, a large proportion of our patients
with SLE have a relatively higher incidence of voiding showed varying degrees of hematuria (25%) and pro-
dysfunction when compared to the control group. First, teinuria (32%), indicating that the kidney was one of the
the mean total symptom score was significantly higher most common visceral organs affected by SLE in our
in the SLE group. Second, the proportion of patients patients. [1-4].
164 J UROL ROC Vol.11 No.4, Dec.
2000WC Lee, KL Lee, MY Chen, et al
Patients with severe lupus cystitis always present the pathogenesis of interstitial cystitis, obstructive
with contracted bladder with bilateral ureterovesical uropathy, and intestinal malabsorption in a patient
junction stenosis and severe hydroureteronephrosis with systemic lupus erythematosus. Am J Med
[6-10]. In our group, 2 patients (1.4%) presented with 1981;70:875-81.
typical lupus cystitis, another 2 showed milder in- 7.Boye E, Morse M, Huttner I, et al. Immune com-
volvement with diminished bladder capacity, but not plex-mediated interstitial cystitis as a major manifes-
hydroureteronephrosis. Taken together, 2.8% of our tation of systemic lupus erythematosus. Clin Immunol
patients might have had apparent lupus cystitis, which is Immunopathol 1979;13:67-76.
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number of female patients with SLE have voiding dys- sus. Ann Intern Med 1983;98:323-26.
function that may be associated with the disease. Ac- 9.Oravisto KJ, Alfthan OS, Jokinen EJ. Interstitial cysti-
cordingly, it is tempting to speculate that the prevalence tis: clinical immunologic findings. Scand J Urol
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tract problem. Biopsy provides the most reliable infor- tions of the International Consensus Committee con-
mation about the type and severity of bladder involve- cerning: 1. Prostate symptom score (I-PSS) and
ment. However, it is not advisable to determine the pa- quality of life assessment, 2. Diagnostic work-up of
thology of bladder tissue in SLE patients with coexist- patients presenting with symptoms suggestive of
ing voiding dysfunction of mild or moderate degree. prostatism, 3. Patients evaluation for research studies,
and 4. BPH treatment. In: Cockett ATK, Aso Y,
CONCLUSION Chatelain C, et al, eds. Proceedings of the First In-
ternational Consultation on Benign Prostatic Hyper-
To the best of our knowledge, the impact of SLE plasia. Paris: Scientific Communication,
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Our results indicate that a substantial number of SLE 12.Bombardier C, Gladman DD, Urowitz MB, et al.
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