Scandinavian Journal of Rheumatology
ISSN: 0300-9742 (Print) 1502-7732 (Online) Journal homepage: http://www.tandfonline.com/loi/irhe20
Pattern of SLE in Hong Kong Chinese: A Cohort Study K. L. Wong To cite this article: K. L. Wong (1992) Pattern of SLE in Hong Kong Chinese: A Cohort Study, Scandinavian Journal of Rheumatology, 21:6, 289-296, DOI: 10.3109/03009749209099244 To link to this article: http://dx.doi.org/10.3109/03009749209099244
Published online: 12 Jul 2009.
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Pattern of SLE in Hong Kong Chinese: A Cohort Study K. L. Wong University Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong
Wong KL. Pattern of SLE in Hong Kong Chinese: A Cohort Study. Scand J Rheumatol. 1992; 21: 289-296
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One hundred and fifty six Chinese patients with Systemic Lupus Erythematosus (SLE) were studied prospectively over 50 months. The patients in the retrospective group (Group I) were diagnosed before and in the prospective group (Group 11). at the time of entry into the study. The overall female to male ratio was 25: 1 with mean age at onset (t- SD) of 26 k 9.9 years. Neurological manifestation as the presenting feature was rare (3%), and none of the untreated patients presented with infection. Anti-nuclear antibody (ANA) was positive in 94% and anti double stranded-DNA antibody (anti DNA) 65%. New manifestations developed in 34 patients (26%) and 218 episodes of relapses occurred in 100 patients with a rate of 0.042 relapse per patient month. Five patients died during the study period with a 5 year survival of 97% and 10 year survival of 94% in the cohort. There was no significant difference in survival between Group I and Group I1 patients at 50 months (p = 0.72).
Keywords: cohort study, SLE, Hong Kong Chinese
Patients with Systemic Lupus Erythematosus (SLE) have been reported in different ethnic races (1-7). The disease has been claimed to be more severe in black (4, 8, 9) and Orientals (l), and the types of renal involvement differ in different studies (7, 9, 10, 11, 12, 13). The presenting features vary widely and the subsequent course are complicated by episodes of relapses and infections. SLE is a common autoimmune disease in Hong Kong Chinese and is a not uncommon cause of morbidity amongst females of reproductive age locally. We conducted a cohort study in our patients with SLE to quantify the clinical pattern at the time of presentation in a combined retrospective and prospective manner and tc determine whether there are any differences in the pattern, relapses and outcome of SLE patients during the study period.
Materials and methods The study was conducted over a period of 50 months (from February 1985 to March 1989). Patients were recruited during this period from unselected referrals from general practitioners, emergency admissions to Queen Mary Hospital, Hong Kong or outpatients at the Immunology/Rheumatology Clinic and Lupus Nephritis Clinic, University Department of Medicine, Hong Kong. The latter two clinics were responsible for treatment of
K. L. Wong, University Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong Received 16 September 1991 Accepted 25 September 1992 23 Rheumatology 21%
more than 95% of all the patients with SLE who were referred to the University Department of Medicine. All patients are Chinese and satisfy the revised criteria for the diagnosis of SLE (14) by April 1989. Patients entered into the study were followed up by a single observer (KLW), who would see them at least once every 6 months and at each relapse. These patients were divided into the retrospective group (Group I) if they were diagnosed before, and the prospective group (Group 11) if they were diagnosed at the time of entry into the study. Clinical features at the time of diagnosis was obtained from review of the records of patients in the retrospective group. The patients in this group were excluded if the clinical information at the time of diagnosis was inadequate or not accessible. All relapses and deaths were recorded. In tabulating the number of ARA criteria satisfied at presentation, the patients in the retrospective group were excluded from analysis if the results of ANA and/or anti DNA were not available.
Methods Biochemical and hematological data were obtained using standard hospital technique. ANA was measured using either mouse liver (before 1975) or peripheral blood leukocyte as substrate. Anti DNA was measured by Farr assay before 1978 (15), and later by indirect immunofluorescence using Crithidia luciliae as substrate (16). Anti-extractable nuclear antigen antibody (anti ENA) was measured by counter immunoelectrophoresis using rabbit thymus extract as substrate. 289
K . L. Wong 50
Table I: Clinical Features at time of Diagnosisa,
40
Manifestation
I
;.5 30 B ". O
d
20
10
0
3
2
4
5
7
6
No. of A R A criteria satisfied
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F7g. 1 . Number of revised A R A criteria satisfied at time of diagnosis. (Group I = retrospective group, Group I1 = prospective group; sec tcxt f o r details).
C3 and C4 were measured by radial immunodiffusion o r nephelometry. The activity of the disease at the time of diagnosis was assessed by symptoms and signs (alopecia, rash, serositis, arthralgia/arthritis, mucosal ulcers. neurological events, malaise not due t o any other cause, fundoscopic abnormalities, lymphadenopathy, splenomegaly) and laboratory findings (anti-DNA antibody, C3, C4, serum creatinine. urinary protein, hemoglobin, platelet count) as described (17). A score of 0 was given for absence of symptoms, signs o r normal laboratory values; 1 for moderate and 2 for severe symptoms, signs or laboratory abnormalities. The disease activity was classified as remission, mild, moderate and severe if the score was 0 , 1-10, 11-20 and > 20 respectively. SLE was considered to have relapsed if there were evidence of: acute synovitis, pleuritis o r pericarditis with radiographic o r echocardiographic changes, new neurologic or psychiatric symptoms, thrombocytopenia (< 100 x 10y/l), leucopenia (< 4 x 10y/l), hemolytic anemia (Coomb's test positive), new cutaneous lesion, active kidney disease (with abnormal urinalysis, increasing proteinuria of 2 1 g per day and/or low c3, C4) (18).
.I
1'
0 Croup
4
5
6
7
8
No. of ARA criteria satisfied
Fig. 2. Number of revised A R A criteria satisfied by April
290
53 71 16 4 35 75 92 a 70 +
34 56 10 2 62 80 98 56
Overall (n=1561 % 47 66 14 3 44 76 94** 65' '
see text for definition of Group I and II patients. Group I compared with Group 11, p < 0.05. * n = 101; * * n = 151; + n = 81, '' n = 131.
Analysis
Survival was analysed by the Kaplan-Myer life table method. Chi-square test, Fisher's exact test and Students' t test were used where appropriate. Results
One hundred and fifty six patients were recruited into this cohort study. Of these, 25 patients were Table II: Number of SLE Patients with Renal Involvement at Presentation. Clinical presentation *
Renal Biopsy WHO Class AP
NS
NE
ARF
Group I I 1 I Ill IV V unclassified not done
1 1 9 16 3 1 3
0 0 1 8 3 0 1
0
0 1
0 0 1 3 0 0 2
2 0 0 0 0
Total
34
13
1
6
2
56 (53)
0 0 0
0
CRF
0
0
Totala
1 1 13 27
11) (1) 112) (25) 6 (61 1 (1) 7 (7)
Clinical presentation *
Renal Biopsy WHO Class AP
NS
0 2 0 0 0
unclassified not done
0 1
0 0 1 7 4 0 0
Total
3
12
v
0
Group II (n=501 %
a
Group II I II 111 IV
I
Group I I
," 40
I9XY.
Renal Articular Serosal Neurological Hematological Cutaneous ANA positive Anti DNA positive
Group I (n=106) %
NE
ARF
CRF
Totalb
0
0 0 0
0 0 0 1 0 0 0
0 0 0 0 1 0 0
0 (0) 2 14) 1 12) 8 (16) 5 (10)
0
1
1
17 (34)
0 0
0
0 (0) 1 (2)
"AP = asymptomatic proteinuria; NS = nephrotic syndrome; NE = acute nephriticsyndrome; ARF = acute renal failure; CRF = chronic renal failure. percent in parenthesis (n=106). percent in parenthesis (n=50).
S L E , C'hinesr, Hong Kong Table Ill: Number of Patients with Non-renal Involvement at Presentation.
Serosttis pericardial effusion pleural effusion peritonitis pericardial T pleural effusion
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Neurological psychosis seizures
Group I (n=106)
Group II (n=501
4 12 0
1 4 0
1
0
1
1 0
3
Overall (n- 156)
2 (1) 3 (21
Hematologicdl * AlHA LP TP AlHA + LP AlHA t TP TP t LP AlHA T LP + TP Cutaneous malar rash discoid photosensitivity oral ulcers alopecia Raynaud's vasculttis Others lymphadenopathy hepatomegaly splenomegaly myositis PLE
62
3 17
3 21 20 30 15 11 12 1 1
26 1 12 4 10 9 11
88 4 29 7
=
131 ). There was no statistical difference between the activity of the disease with respect t o group I and I1 patients ( p = 0.89, Chi-square; results not shown ) . A t the time of diagnosis. 43% o f the patients had never completed primary school. 3Y'%, had completed primary school, 26% had completed secondary school and 7% had completed post-sccondnry or tertiary education. Since it was not possible t o get data o n family income tor Group I patients at the time o f diagnosis. the family income at the time of entry into the study wits used t o reflect the socio-economic status for all the patients. Twenty four percent of patients had family income of < HK$25.000 per annum. 53% HK$25.000-49, 909,18'%, HK$SO.000-99.999 and 5% > HK$IOO,OOO (most people o f the lower social class in Hong Kong had family income below HK$7S,OOO per annum. personal communication).
(56)
(3)
(19) 14) 31 (20) 29 (19) 41 (26) 22 (14) 14 191 15 (10) 3 (2) 3 (2)
AlHA = dutoimmune hemolytic anemia, LP = leucopenia, TP = thrombocytoperiia ' * one patient could have > 1 cutaneous manifestation PLE = protein losing enteropathy ' percent in parenthesis +
n o t tested for ANA and/or anti DNA at the time of diagnosis. They were cxcludcci only from analysis involving the numhcr of revised A R A criteria sntisfied a t the time of diagnosis and the assessment of activity. One hundred and sixty patients in the retrospcctive group were excluded because of iniidequate informittion at the time of diagnosis. Thcrc were 150 females and six males in the cohort. giving ;I F:M ratio of 25: 1 . The mean age a t onsct was 26 years (SD rt 9.9 years) and mean duration o f follow up u;is 79.5 months (SD k 53.7 months: range, 4 - 2 3 months). Group I1 patients wcrc followed up ovcr a shorter period (25.3 -t 13.3 months: mean ? SD; range. 4-50 months). The clinical features at the time o f presentation were shown in Table I . 34131 (26%) had less than three criteria tor diagnosis o f SLE at the time of presentation (Figures 1 , 2). All patients had active SLE discasc :it the time of the diagnosis (mild, 23
22.0'%l;moderate. 37.3'%; severe. 2c).ti'%): n
Pattern of Clinical Involvement Renal Involvement
37% (73156) o f patients had evidence of renal involvement (Table 11). Thcrc was ;I marked diffcrencc in the incidcnce o f asymptomatic proteinurin between Group 1 and I 1 patients because of ;I change in policy: before February 1985. renal biopsies were performed if urinary protein excret i o n was > 0.5 g per day and/or in presence o f abnormal urinary sediments. During the study period. renal biopsies were performed only when urinary protein excretion exceeded 1 g per d a y o r in presence of abnormal urinary sediments. Thc nephrotic syndrome was one of the most common presentations (Group 1, 13/56; Group I1 17/17; overall 25/73) (Table V ) . Diffuse proliferative glomerulonephritis ( W H O Class IV) and mcmbranous glomcrulonephritis ( W H O Class V ) were most common in patients with nephrotic syndrome. Acute nephritic syndrome was rare. Seven patients had acute renal failure and ;dl of thosc in whom renal biopsies had been performed (Y5)had use proliferative glomeruloncpliritis ( W H O Class IV). Other Systemic Involvements
At present ii t i o n . ;I rt i c u 1;I r m ;In i t'e s t ;it i o n occur r c d in h6.0'%,of the patients (Group I . 71'%,;Group 11. 56'X)) (Table I ) . Scrositis was ;I relatively rare manifestation and present in 14% of paticnts. The majority were pleural cffusion (Table 111). N o patient presented with peritonitis. Neurological involvement was rare ( 3 % ) . Three episodes of seizure!, 29 1
K . L. Wong Table IV: Cumulative Frequency of Anti-extractable nuclear antigen antibodies (anti ENA) in SLE Patients. anti ENA
anti-Sm anti-RnP anti-Ro anti-La others anti-Sm t anti-RnP anti-RnP t anti-Ro anti-Ro t anti-La anti-Ro t others anti-Sm t anti-RnP t anti-Ro anti-RnP t anti-Ro t anti-La anti-Ro t anti-La t others
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Total
Group I (n=106)
Group II (n=50)
0
2 1
0 2 13 0 5 2 4 3 2 1 1 0
67
33
12 30 2 1 1 12 5 0
I
Group I
Overall (n=156) 0 14 43 2 6 3 16 8 2 2 3 1
(0) 19) (28) (1) (4) (2) (10) (5) (1) (1) (2) (1)
100 (64)
'percent in parenthesis.
and two episodes of psychosis occurred at presentation. 44% of the patients presented with hematological involvement. Leucopenia alone (20/156) or in combination (40/156) was the most common presentation. Cutaneous manifestations were evident in 76% of patients. Malar rash was most common and oral ulcers were rare (Table 111). Lymphadenopathy was present in 14% of the patients, hepatomegaly in 9% and splenomegaly in 10% respectively. Myositis and protein losing enteropathy were rare, each occurred in three patients (Table 111). Serological Tests
ANA was present in 94% of the patients at presentation and in 100% by.Apri1 1989. Anti DNA was present in 65% of the patients (Table I). 1 C3, 1 C4 or 1 C3 and 1 C4 were present in 74%, S9%, 57% of the patients respectively. There was no specific organ system that was associated with positive anti DNA, 1 C3 or 1 C4. Most patients had an elevation of C3 and C4 towards the normal range when the disease was inactive. However, 23% had normalisation of C3 and C4 when the disease was still active and 5% had persistent 1 C3 and/or 1 C4 when the disease was in clinical remission. There was no statistically significant difference when the activity of the disease was compared to presence of anti DNA, level of C3 and C4 (results not shown). As anti-ENA was only available since 1985, the results were expressed as cumulative prevalence (Table IV). 64% of patients had anti ENA. The most common anti ENA was anti-Ro/SSA (75/100). Anti-Sm antibody never oc292
Table V: Number of SLE patients with Relapses with respect to Organ Systems.
Articular Serosal Renal Neurological Hematological Cutaneous Others relapses per patient months
Group II
30 1 44 4 10 68 8 0.042
Overall
6 2 9 2 2 26 6 0.043
36 3 53 6 12 94 14 0.042
curred alone and 32/75 anti RolSSA antibodies occurred in combination with other anti ENA antibodies. Clinical Sjogren's Syndrome was present in one patient in Group I and in two patients in Group 11. The patient in Group I was positive for anti-Ro/SSA, anti-La/SSB, and anti-RnP and in Group 11, one patient was negative for anti ENA and the other was positive for anti-Ro/SSA and anti-La/SSB . Relapses
New manifestations developed in 34 patients (26%) (results not shown). Two hundred and eighteen episodes of relapses occurred in 100 patients in this cohort with an overall relapse rate of 0.042 per patient month. There was no difference in the relapse rate between Group I and Group I1 patients. Cutaneous (43%) and renal (24%) relapses were most common. Neurological relapses were uncommon (six episodes) (Tables V, VI). Fifty six patients (36%) had no relapse during the study period and only ten patients had four or more relapses (Table V I ) . In order to compare the pattern of relapses before and during the study period, an organ system involvement which was more easily quantifiable Table VI: Number of SLE Patients with Relapses during the Study Period. No. of relapses
No. of patients Group I (n=106)
0
28 29 25 17 2 3 2
1 2 3 4 5 6 Total no of relapses a
Group II (n=50)
165
percent in parenthesis.
Overalla (n=156) 56 36 31 23 2 5 3
53
218
(36) (23) (20) (15) (1) (3) (2)
SLE, Chinese, Hong Kong Table VII: Pattern of Infections. Type of Infections
Treatment Group I
Group II
Overall
9 5 1 1 0 0 1 1 1
2 4 0 0 1 1 2 2 1
11 9 1 1 1 1 3 3 2
19
13
32
Herpes zoster Tuberculosis Candida Cryptococcus Staph. aureus Strept. pneumoniae Others Unidentified Mixed
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Total
was chosen as an index. This was intended to prove whether relapses occurred more or less frequently during the study period. Since renal relapses in the retrospective group is much better defined and data are more easily retrievable, it was chosen for such comparison. There were 56 renal relapses before and 45 relapses during this period. No renal relapse was present in 68 (64%) and 62 (59%) patients respectively (p = not significant). The distribution of the renal manifestation was similar with nephrotic relapse being most common (before the study period, 22/56 vs during the study period, 16/45) and so was the histological findings. The commonest renal histology before the study period was diffuse proliferative glomerulonephritis (WHO Class IV) (41%) and membranous glomerulonephritis (WHO Class V) (18%). Similar results were seen in Group I patients during the study period (44% diffuse proliferative glomerulonephritis and 21 % membranous glomerulonephritis respectively). To determine whether there is any difference in between patients recruited retrospectively (Group I) and prospectively (Group II), the pattern of renal relapse was compared to Group I patients. Thirteen episodes of renal relapse occurred in the Group I1 patients and no relapse in 82% of patients. Nephrotic relapses were still the most common presentation and diffuse proliferative glomerulonephritis (39%) and membranous glomerulonephritis (31%) were most common (results not shown).
At the time of diagnosis, 51% of the patients received low dose steroid therapy (I 20 mg of prednisone or equivalent per day), 28% a moderate dose of steroid (21-40 mg of prednisone or equivalent per day), 15% a high dose of steroid ( 2 40 mg of prednisone or equivalent per day) and 6Y'o received pulse methylprednisolone therapy (1 000 mg methylprednisolone intravenously daily per 3 days) as the predominant therapy. Other therapeutic modalities included non-steroidal anti-inflammatory drugs (NSAIDs) 35%, antimalarial drug (chloroquine or hydroxychloroquine) l o % , azathioprine 37%, cyclophosphamide 14Y0, plasma exchange 1% and cyclosporin A 1%. Cyclosporin A was used in this Group I1 patient for her severe retinal vasculitis. Subsequent therapy was modified according to the activity of the disease. At the time of relapse, 27 episodes (12%) required the use of low dose steroid, 42 episodes (19%) moderate dose of steroid, 78 episodes (36%) high dose of steroid and 11 episodes ( 5 % ) pulse methylprednisolone therapy. NSAIDs were used in 44 episodes (20%), antimalarial drug in 24 episodes (11Yo), azathioprine in 75 episodes (%yo), cyclophosphamide in 37 episodes (17%) and plasma exchange in 2 episodes (1"/o). Infections
Thirty two episodes of infection occurred in 27 patients. None of the untreated patients presented with infection (results not shown). The commonest causative organisms were Varicella-zoster virus (as Herpes zoster) (11) and tuberculosis (TB)(9) (Table VII). Two patients had mixed infection: Cytomegalovirus (CMV), Pneumocystis carinii (PCP) and Pseudomonas aeruginosa pneumonia (1); PCP and Pseudomonas aeruginosa pneumonia (1). The mean dose of steroid at time of infection for Group I was 30.5 mg of prednisone or equivalent per day (SD f 39.2 and median 15 mg per day); Group 11, 20.8 mg of prednisone or equivalent per day (SD k 11.0 and median 30 mg per day) and overall, 26.4 mg of prednisone or equivalent per day (SD f 30.7
Table VIII: Causes of Death.
Group I
Group II
No. of patients
Causes *
Disease status at time of death
1 1 1 1 1
pulmonary vasculitis cardiomyopathy severe cerebral atrophy (sequelae of CNS vasculitis) cardiomyopathy retinal vasculitis bronchopneumonia rifampicin induced thrombocytopenia with intracerebral hemorrhage miliary tuberculosis Candid septicemia aspiration pneumonia
severe remitted remitted mild mild
* CNS = central nervous system.
293
K. L. Wong
information at the time of diagnosis, 16 were dead from various causes by March 1989. T h e 5 year and 10 year survival for this group of patients were 92% and 87% respectively. There was no statistically significant difference in the survival rate for the patients who were excluded from the cohort.
1.00
0.95 C
8
- Group
0.90
---
P
I
Group I I
- Overall
Discussion
0.85
0.80
I 0
I
I
50
100
I
I
150
200
I 2 50
Month
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Fig. 3. Ovcrall survival of SLE patients.
and median 15 mg per day) respectively. Eleven patients were on azathioprine but only one was on cyclophosphamide. There is no statistically significant difference in the mean dose of prednisone in patients who had Herpes zoster and tuberculosis (t test). Comparison with other infections were not performed because of the small number of other infections. Of all the infections, only two patients died of causes directly related to the infection: bronchopneumonia (one) (Group I); miliary T B , Candida septicemia, aspiration pneumonia (one) (Group 11). Causes of Death and Outcome
Five patients died during this period: four in Group I and one in Group 11 (Table VIII). None of them died during the first presentation. Three patients had severe generalised disease before death, two of them had the disease treated and remitted, but died from the sequelae of the disease. Two other patients had mild disease at the time of death. Twelve patients (8%) had creatinine clearance of < 5 0 ml/min. at the end of the study period (Group I, 9 and Group 11, 3). Four of the Group I patients had creatinine clearance of < 10 ml/min and was maintained on dialysis (peritoneal dialysis, 3; hemodialysis, 1). None of these patients were transplanted. O n e of the group I1 patients was peritoneally dialysed for chronic renal failure with creatinine clearance of 8 ml/min. for 7 months during this period. Dialysis was stopped because of partial recovery of creatinine clearance to 46 ml/ min. Her creatinine clearance remained at around 35-38 ml/min. at the end of the study period. The overall prognosis of the patients was very good with five year survival of 97% and 10 year survival of 94% (Figure 3). The survival at 50 months was comparable between Group I and Group I1 (p = 0.72) (result not shown). Of the 160 patients who were excluded because of inadequate 294
SLE in Chinese patients has been reported in China, Taiwan, Singapore and Malaysia (2, 7, 19. 20, 21). Their behaviour with respect to the outcome is varied and most data are from retrospective studies. Our cohort study may be able to remedy some of the limitations on data collection of retrospective studies. The sex ratio is higher than usual and probably coincidental, since another cross sectional study over the same period revealed a female:male ratio of about 1O:l (22). Thirty-four of 131 p?t’tents (26%) had insufficient A R A criteria for diagnosis of SLE at the time of presentation. This is not uncommon in reported series. The clinical features at the time of presentation are comparable between our retrospective (Group I) and prospective (Group 11) patient groups except for the renal and hematological involvement. For the former, asymptomatic proteinuria was most common among patients in Group I. This is probably an artefactual distribution because of the difference in policy (vide supra). When the histological changes was further analysed as to the manner of presentation, there was not much difference between the Group I and Group I1 patients. This suggests that there is no difference in the relative proportion of patients with renal presentations. The observation on hematological features is probably valid as further breakdown shows consistently higher proportions of all types of hematological changes in Group I1 patients (Table 111). Neurological manifestation as the initial presentation was rare. This is in accordance with our prospective study on the neurological manifestation of SLE patients (23). Eight of 36 patients in the latter study had primary lupus involvement and none presented with neurological manifestation. This is in contrast t o most studies which reported a much higher incidence (25”/0 to 5 0 % ) ( 5 , 13, 21). Neurological relapses was again uncommon (six episodes) and this further supports the observation that primary neurological manifestation is uncommon among our patients (Table VI). A N A was positive in 92% and 98% of patients in Group I and Group I1 respectively. Anti D N A was positive in 70% and 56% respectively and was lower than what had reported by Boey et al (7). but similar to the results of Worrall et al (24). Since
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S L E , Chinese, Hong Kong
our cohort is much more ethnically homogenous, these observations is probably applicable to our Chinese patients with SLE. However. this level of low positivity may also be related to the methods used to detect the anti DNA which are specific but relatively insensitive. Anti-Ro was the most prevalent anti-ENA antibody and occurred in 48% ( 7 9 156) of patients. The latter is comparable with the results in Japan ( 2 5 ) or Singapore (7) suggesting anti-Ro/SSA is a common anti-ENA in Orientals. The prevalence of anti-Sm was low and is not likely to be of much diagnostic help in the diagnosis of SLE in our locality. Relapses were fairly common (0.042 per patient month), and was more frequent than what has been reported (13). The similar incidences o f renal relapses in patients in Group I and Group I1 suggested that there was not much change of pattern in the relapses in patients recruited before or at the time of entry into this study. When the relapses during the study period in Group I patients was compared to the relapses before the study period, the pattern of relapses was again similar, indicating that the pattern was consistent through these years of follow up. Despite the high frequency of relapses, most relapses responded to treatment (results not shown), Only one patient had severe SLE at the time of death. Correlation of these relapses to mortality is not performed as the number of deaths is too small. Infections have always been the major concern in management of SLE patients. The number of episodes of infections is relatively small (32 episodes in 27 patients). Few patients (two) died as result of infection. It has been argued that steroids or immunosuppressive treatments are the prime factors predisposing SLE patients to infections. In this cohort, the mean dose of prednisone for those who had infections was 26.4 f 30.7 mg/day. Only half of these patients received prednisone 2 15 mg/day. The number of patients on azathioprine and cyclophosphamide were also small (11 and 1 patient respectively). Our study cannot answer the question of whether prednisone or immunosuppressive agents will predispose patients to infections. Considering the number of SLE patients on cyclophosphamide in our Department, the number of patients on cyclophosphamide with infection was unexpectedly low (results not shown). A better designed prospective study controlling SLE disease activity, dosage of prednisone and immunosuppressive therapy may be able to answer whether steroid or immunosuppressive therapy increase the risk of infections. Only five patients died during this period (Table VIII). This mortality rate is low when comparing with major series (2.4.6.21). Since all the patients
were recruited from the available SLE patients in our Department. there is less bias with respect to the pattern of referral. The better survival rate may be explained by a more cautious immunosuppressive regimen given to the patients during the period of observation in patients with evidence of active renal disease, or inclusion of patient with no evidence of renal involvement at presentation. There is also a possibility of a recruitment bias in this cohort since about two thirds of the patients belongs to the retrospective group. Those with aggressive disease may have died before they were recruited into this study. The absence of statistically significant difference in survival between patients in the retrospective group (Group I) and the prospective group (Group 11) at 50 months suggests that the incidence of aggressive disease probably is similar in both groups and these findings may be applicable to the whole population of Chinese patients with SLE. Acknowledgement The author would like to thank Ms T Tong for her expert secretarial assistance and Mr M Leung f o r statistical analysis.
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14. Tan EM, Cohen AS, Frics J F et al. The 1982 revised criteria for thc classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271-7. 15. Pincus T, Schur PH, Ross JA, Decker JL, Tala1 N. Measurement of serum DNA-binding activity in systemic lupus erythematosus. N Engl J Med 1969; 281: 701-5. 16. Slatcr NGP, Cameron JS, Lessof MH. The crithidia luciliae kinctoplast immunofluorescence test in systemic lupus crythematosus. Clin Exp Immunol 1976; 25: 480-6. 17. Wong KL, Wong RPO. Limitation of serum soluble interleukin-2 receptor in defining the activity in patients with SLE. Ann Rheum Dis 1991, 50: 706-9. 18. Wong KL, Chan FY, Lee CP. Outcome of pregnancy in patients with SLE: a prospective study. Arch Int Med 1991, 151: 269-73.
296
19. Feng PH, Boey ML. Systemic lupus erythematosus in Chinese. The Singapore experience. Rheumatol Int 1982; 2: 151-4.
20. Chou CT, Lee FT,Schumacher H . Modification of a screening technique to evaluate systemic lupus erythematosus. J Rheumatol 1986; 13: 8069. 21. Boey ML, Ng SC, Feng PH. Mortality in Orientals with systemic lupus erythematosus. A reappraisal. Singapore Med J 1987; 28: 318-20. 22. Wong KL, Hawkins BR, Wong RWS. Immunogenetics in Chinese patients with SLE. Scand J Rheumatol 1991, 20: 1104. 23. Wong KL, Yu YL, Woo EKW, Wong RWS. Neurological manifestation of SLE: a prospective study. Q J Med 1991, 81(294) : 857-70. 24. Worrall JG, Snaith ML, Batchelor JR, Isenberg DA. SLE: a rheumatological view. Analysis of clinical features, serological and immunogenetics of 100 SLE patients during long term follow up. Q J Med 1990, 74(273): 319-30. 25. Yokugoro R, Tsunematsu T. Application to Japanese patients of the 1982 American Rheumatism Association revised criteria for the classification of SLE. Arthritis Rheum 1985; 28: 693-8.
ISSN: 0300-9742 (Print) 1502-7732 (Online) Journal homepage: http://www.tandfonline.com/loi/irhe20
Pattern of SLE in Hong Kong Chinese: A Cohort Study K. L. Wong To cite this article: K. L. Wong (1992) Pattern of SLE in Hong Kong Chinese: A Cohort Study, Scandinavian Journal of Rheumatology, 21:6, 289-296, DOI: 10.3109/03009749209099244 To link to this article: http://dx.doi.org/10.3109/03009749209099244
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Date: 09 May 2016, At: 04:22
Pattern of SLE in Hong Kong Chinese: A Cohort Study K. L. Wong University Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong
Wong KL. Pattern of SLE in Hong Kong Chinese: A Cohort Study. Scand J Rheumatol. 1992; 21: 289-296
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One hundred and fifty six Chinese patients with Systemic Lupus Erythematosus (SLE) were studied prospectively over 50 months. The patients in the retrospective group (Group I) were diagnosed before and in the prospective group (Group 11). at the time of entry into the study. The overall female to male ratio was 25: 1 with mean age at onset (t- SD) of 26 k 9.9 years. Neurological manifestation as the presenting feature was rare (3%), and none of the untreated patients presented with infection. Anti-nuclear antibody (ANA) was positive in 94% and anti double stranded-DNA antibody (anti DNA) 65%. New manifestations developed in 34 patients (26%) and 218 episodes of relapses occurred in 100 patients with a rate of 0.042 relapse per patient month. Five patients died during the study period with a 5 year survival of 97% and 10 year survival of 94% in the cohort. There was no significant difference in survival between Group I and Group I1 patients at 50 months (p = 0.72).
Keywords: cohort study, SLE, Hong Kong Chinese
Patients with Systemic Lupus Erythematosus (SLE) have been reported in different ethnic races (1-7). The disease has been claimed to be more severe in black (4, 8, 9) and Orientals (l), and the types of renal involvement differ in different studies (7, 9, 10, 11, 12, 13). The presenting features vary widely and the subsequent course are complicated by episodes of relapses and infections. SLE is a common autoimmune disease in Hong Kong Chinese and is a not uncommon cause of morbidity amongst females of reproductive age locally. We conducted a cohort study in our patients with SLE to quantify the clinical pattern at the time of presentation in a combined retrospective and prospective manner and tc determine whether there are any differences in the pattern, relapses and outcome of SLE patients during the study period.
Materials and methods The study was conducted over a period of 50 months (from February 1985 to March 1989). Patients were recruited during this period from unselected referrals from general practitioners, emergency admissions to Queen Mary Hospital, Hong Kong or outpatients at the Immunology/Rheumatology Clinic and Lupus Nephritis Clinic, University Department of Medicine, Hong Kong. The latter two clinics were responsible for treatment of
K. L. Wong, University Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong Received 16 September 1991 Accepted 25 September 1992 23 Rheumatology 21%
more than 95% of all the patients with SLE who were referred to the University Department of Medicine. All patients are Chinese and satisfy the revised criteria for the diagnosis of SLE (14) by April 1989. Patients entered into the study were followed up by a single observer (KLW), who would see them at least once every 6 months and at each relapse. These patients were divided into the retrospective group (Group I) if they were diagnosed before, and the prospective group (Group 11) if they were diagnosed at the time of entry into the study. Clinical features at the time of diagnosis was obtained from review of the records of patients in the retrospective group. The patients in this group were excluded if the clinical information at the time of diagnosis was inadequate or not accessible. All relapses and deaths were recorded. In tabulating the number of ARA criteria satisfied at presentation, the patients in the retrospective group were excluded from analysis if the results of ANA and/or anti DNA were not available.
Methods Biochemical and hematological data were obtained using standard hospital technique. ANA was measured using either mouse liver (before 1975) or peripheral blood leukocyte as substrate. Anti DNA was measured by Farr assay before 1978 (15), and later by indirect immunofluorescence using Crithidia luciliae as substrate (16). Anti-extractable nuclear antigen antibody (anti ENA) was measured by counter immunoelectrophoresis using rabbit thymus extract as substrate. 289
K . L. Wong 50
Table I: Clinical Features at time of Diagnosisa,
40
Manifestation
I
;.5 30 B ". O
d
20
10
0
3
2
4
5
7
6
No. of A R A criteria satisfied
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F7g. 1 . Number of revised A R A criteria satisfied at time of diagnosis. (Group I = retrospective group, Group I1 = prospective group; sec tcxt f o r details).
C3 and C4 were measured by radial immunodiffusion o r nephelometry. The activity of the disease at the time of diagnosis was assessed by symptoms and signs (alopecia, rash, serositis, arthralgia/arthritis, mucosal ulcers. neurological events, malaise not due t o any other cause, fundoscopic abnormalities, lymphadenopathy, splenomegaly) and laboratory findings (anti-DNA antibody, C3, C4, serum creatinine. urinary protein, hemoglobin, platelet count) as described (17). A score of 0 was given for absence of symptoms, signs o r normal laboratory values; 1 for moderate and 2 for severe symptoms, signs or laboratory abnormalities. The disease activity was classified as remission, mild, moderate and severe if the score was 0 , 1-10, 11-20 and > 20 respectively. SLE was considered to have relapsed if there were evidence of: acute synovitis, pleuritis o r pericarditis with radiographic o r echocardiographic changes, new neurologic or psychiatric symptoms, thrombocytopenia (< 100 x 10y/l), leucopenia (< 4 x 10y/l), hemolytic anemia (Coomb's test positive), new cutaneous lesion, active kidney disease (with abnormal urinalysis, increasing proteinuria of 2 1 g per day and/or low c3, C4) (18).
.I
1'
0 Croup
4
5
6
7
8
No. of ARA criteria satisfied
Fig. 2. Number of revised A R A criteria satisfied by April
290
53 71 16 4 35 75 92 a 70 +
34 56 10 2 62 80 98 56
Overall (n=1561 % 47 66 14 3 44 76 94** 65' '
see text for definition of Group I and II patients. Group I compared with Group 11, p < 0.05. * n = 101; * * n = 151; + n = 81, '' n = 131.
Analysis
Survival was analysed by the Kaplan-Myer life table method. Chi-square test, Fisher's exact test and Students' t test were used where appropriate. Results
One hundred and fifty six patients were recruited into this cohort study. Of these, 25 patients were Table II: Number of SLE Patients with Renal Involvement at Presentation. Clinical presentation *
Renal Biopsy WHO Class AP
NS
NE
ARF
Group I I 1 I Ill IV V unclassified not done
1 1 9 16 3 1 3
0 0 1 8 3 0 1
0
0 1
0 0 1 3 0 0 2
2 0 0 0 0
Total
34
13
1
6
2
56 (53)
0 0 0
0
CRF
0
0
Totala
1 1 13 27
11) (1) 112) (25) 6 (61 1 (1) 7 (7)
Clinical presentation *
Renal Biopsy WHO Class AP
NS
0 2 0 0 0
unclassified not done
0 1
0 0 1 7 4 0 0
Total
3
12
v
0
Group II (n=501 %
a
Group II I II 111 IV
I
Group I I
," 40
I9XY.
Renal Articular Serosal Neurological Hematological Cutaneous ANA positive Anti DNA positive
Group I (n=106) %
NE
ARF
CRF
Totalb
0
0 0 0
0 0 0 1 0 0 0
0 0 0 0 1 0 0
0 (0) 2 14) 1 12) 8 (16) 5 (10)
0
1
1
17 (34)
0 0
0
0 (0) 1 (2)
"AP = asymptomatic proteinuria; NS = nephrotic syndrome; NE = acute nephriticsyndrome; ARF = acute renal failure; CRF = chronic renal failure. percent in parenthesis (n=106). percent in parenthesis (n=50).
S L E , C'hinesr, Hong Kong Table Ill: Number of Patients with Non-renal Involvement at Presentation.
Serosttis pericardial effusion pleural effusion peritonitis pericardial T pleural effusion
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Neurological psychosis seizures
Group I (n=106)
Group II (n=501
4 12 0
1 4 0
1
0
1
1 0
3
Overall (n- 156)
2 (1) 3 (21
Hematologicdl * AlHA LP TP AlHA + LP AlHA t TP TP t LP AlHA T LP + TP Cutaneous malar rash discoid photosensitivity oral ulcers alopecia Raynaud's vasculttis Others lymphadenopathy hepatomegaly splenomegaly myositis PLE
62
3 17
3 21 20 30 15 11 12 1 1
26 1 12 4 10 9 11
88 4 29 7
=
131 ). There was no statistical difference between the activity of the disease with respect t o group I and I1 patients ( p = 0.89, Chi-square; results not shown ) . A t the time of diagnosis. 43% o f the patients had never completed primary school. 3Y'%, had completed primary school, 26% had completed secondary school and 7% had completed post-sccondnry or tertiary education. Since it was not possible t o get data o n family income tor Group I patients at the time o f diagnosis. the family income at the time of entry into the study wits used t o reflect the socio-economic status for all the patients. Twenty four percent of patients had family income of < HK$25.000 per annum. 53% HK$25.000-49, 909,18'%, HK$SO.000-99.999 and 5% > HK$IOO,OOO (most people o f the lower social class in Hong Kong had family income below HK$7S,OOO per annum. personal communication).
(56)
(3)
(19) 14) 31 (20) 29 (19) 41 (26) 22 (14) 14 191 15 (10) 3 (2) 3 (2)
AlHA = dutoimmune hemolytic anemia, LP = leucopenia, TP = thrombocytoperiia ' * one patient could have > 1 cutaneous manifestation PLE = protein losing enteropathy ' percent in parenthesis +
n o t tested for ANA and/or anti DNA at the time of diagnosis. They were cxcludcci only from analysis involving the numhcr of revised A R A criteria sntisfied a t the time of diagnosis and the assessment of activity. One hundred and sixty patients in the retrospcctive group were excluded because of iniidequate informittion at the time of diagnosis. Thcrc were 150 females and six males in the cohort. giving ;I F:M ratio of 25: 1 . The mean age a t onsct was 26 years (SD rt 9.9 years) and mean duration o f follow up u;is 79.5 months (SD k 53.7 months: range, 4 - 2 3 months). Group I1 patients wcrc followed up ovcr a shorter period (25.3 -t 13.3 months: mean ? SD; range. 4-50 months). The clinical features at the time o f presentation were shown in Table I . 34131 (26%) had less than three criteria tor diagnosis o f SLE at the time of presentation (Figures 1 , 2). All patients had active SLE discasc :it the time of the diagnosis (mild, 23
22.0'%l;moderate. 37.3'%; severe. 2c).ti'%): n
Pattern of Clinical Involvement Renal Involvement
37% (73156) o f patients had evidence of renal involvement (Table 11). Thcrc was ;I marked diffcrencc in the incidcnce o f asymptomatic proteinurin between Group 1 and I 1 patients because of ;I change in policy: before February 1985. renal biopsies were performed if urinary protein excret i o n was > 0.5 g per day and/or in presence o f abnormal urinary sediments. During the study period. renal biopsies were performed only when urinary protein excretion exceeded 1 g per d a y o r in presence of abnormal urinary sediments. Thc nephrotic syndrome was one of the most common presentations (Group 1, 13/56; Group I1 17/17; overall 25/73) (Table V ) . Diffuse proliferative glomerulonephritis ( W H O Class IV) and mcmbranous glomcrulonephritis ( W H O Class V ) were most common in patients with nephrotic syndrome. Acute nephritic syndrome was rare. Seven patients had acute renal failure and ;dl of thosc in whom renal biopsies had been performed (Y5)had use proliferative glomeruloncpliritis ( W H O Class IV). Other Systemic Involvements
At present ii t i o n . ;I rt i c u 1;I r m ;In i t'e s t ;it i o n occur r c d in h6.0'%,of the patients (Group I . 71'%,;Group 11. 56'X)) (Table I ) . Scrositis was ;I relatively rare manifestation and present in 14% of paticnts. The majority were pleural cffusion (Table 111). N o patient presented with peritonitis. Neurological involvement was rare ( 3 % ) . Three episodes of seizure!, 29 1
K . L. Wong Table IV: Cumulative Frequency of Anti-extractable nuclear antigen antibodies (anti ENA) in SLE Patients. anti ENA
anti-Sm anti-RnP anti-Ro anti-La others anti-Sm t anti-RnP anti-RnP t anti-Ro anti-Ro t anti-La anti-Ro t others anti-Sm t anti-RnP t anti-Ro anti-RnP t anti-Ro t anti-La anti-Ro t anti-La t others
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Total
Group I (n=106)
Group II (n=50)
0
2 1
0 2 13 0 5 2 4 3 2 1 1 0
67
33
12 30 2 1 1 12 5 0
I
Group I
Overall (n=156) 0 14 43 2 6 3 16 8 2 2 3 1
(0) 19) (28) (1) (4) (2) (10) (5) (1) (1) (2) (1)
100 (64)
'percent in parenthesis.
and two episodes of psychosis occurred at presentation. 44% of the patients presented with hematological involvement. Leucopenia alone (20/156) or in combination (40/156) was the most common presentation. Cutaneous manifestations were evident in 76% of patients. Malar rash was most common and oral ulcers were rare (Table 111). Lymphadenopathy was present in 14% of the patients, hepatomegaly in 9% and splenomegaly in 10% respectively. Myositis and protein losing enteropathy were rare, each occurred in three patients (Table 111). Serological Tests
ANA was present in 94% of the patients at presentation and in 100% by.Apri1 1989. Anti DNA was present in 65% of the patients (Table I). 1 C3, 1 C4 or 1 C3 and 1 C4 were present in 74%, S9%, 57% of the patients respectively. There was no specific organ system that was associated with positive anti DNA, 1 C3 or 1 C4. Most patients had an elevation of C3 and C4 towards the normal range when the disease was inactive. However, 23% had normalisation of C3 and C4 when the disease was still active and 5% had persistent 1 C3 and/or 1 C4 when the disease was in clinical remission. There was no statistically significant difference when the activity of the disease was compared to presence of anti DNA, level of C3 and C4 (results not shown). As anti-ENA was only available since 1985, the results were expressed as cumulative prevalence (Table IV). 64% of patients had anti ENA. The most common anti ENA was anti-Ro/SSA (75/100). Anti-Sm antibody never oc292
Table V: Number of SLE patients with Relapses with respect to Organ Systems.
Articular Serosal Renal Neurological Hematological Cutaneous Others relapses per patient months
Group II
30 1 44 4 10 68 8 0.042
Overall
6 2 9 2 2 26 6 0.043
36 3 53 6 12 94 14 0.042
curred alone and 32/75 anti RolSSA antibodies occurred in combination with other anti ENA antibodies. Clinical Sjogren's Syndrome was present in one patient in Group I and in two patients in Group 11. The patient in Group I was positive for anti-Ro/SSA, anti-La/SSB, and anti-RnP and in Group 11, one patient was negative for anti ENA and the other was positive for anti-Ro/SSA and anti-La/SSB . Relapses
New manifestations developed in 34 patients (26%) (results not shown). Two hundred and eighteen episodes of relapses occurred in 100 patients in this cohort with an overall relapse rate of 0.042 per patient month. There was no difference in the relapse rate between Group I and Group I1 patients. Cutaneous (43%) and renal (24%) relapses were most common. Neurological relapses were uncommon (six episodes) (Tables V, VI). Fifty six patients (36%) had no relapse during the study period and only ten patients had four or more relapses (Table V I ) . In order to compare the pattern of relapses before and during the study period, an organ system involvement which was more easily quantifiable Table VI: Number of SLE Patients with Relapses during the Study Period. No. of relapses
No. of patients Group I (n=106)
0
28 29 25 17 2 3 2
1 2 3 4 5 6 Total no of relapses a
Group II (n=50)
165
percent in parenthesis.
Overalla (n=156) 56 36 31 23 2 5 3
53
218
(36) (23) (20) (15) (1) (3) (2)
SLE, Chinese, Hong Kong Table VII: Pattern of Infections. Type of Infections
Treatment Group I
Group II
Overall
9 5 1 1 0 0 1 1 1
2 4 0 0 1 1 2 2 1
11 9 1 1 1 1 3 3 2
19
13
32
Herpes zoster Tuberculosis Candida Cryptococcus Staph. aureus Strept. pneumoniae Others Unidentified Mixed
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Total
was chosen as an index. This was intended to prove whether relapses occurred more or less frequently during the study period. Since renal relapses in the retrospective group is much better defined and data are more easily retrievable, it was chosen for such comparison. There were 56 renal relapses before and 45 relapses during this period. No renal relapse was present in 68 (64%) and 62 (59%) patients respectively (p = not significant). The distribution of the renal manifestation was similar with nephrotic relapse being most common (before the study period, 22/56 vs during the study period, 16/45) and so was the histological findings. The commonest renal histology before the study period was diffuse proliferative glomerulonephritis (WHO Class IV) (41%) and membranous glomerulonephritis (WHO Class V) (18%). Similar results were seen in Group I patients during the study period (44% diffuse proliferative glomerulonephritis and 21 % membranous glomerulonephritis respectively). To determine whether there is any difference in between patients recruited retrospectively (Group I) and prospectively (Group II), the pattern of renal relapse was compared to Group I patients. Thirteen episodes of renal relapse occurred in the Group I1 patients and no relapse in 82% of patients. Nephrotic relapses were still the most common presentation and diffuse proliferative glomerulonephritis (39%) and membranous glomerulonephritis (31%) were most common (results not shown).
At the time of diagnosis, 51% of the patients received low dose steroid therapy (I 20 mg of prednisone or equivalent per day), 28% a moderate dose of steroid (21-40 mg of prednisone or equivalent per day), 15% a high dose of steroid ( 2 40 mg of prednisone or equivalent per day) and 6Y'o received pulse methylprednisolone therapy (1 000 mg methylprednisolone intravenously daily per 3 days) as the predominant therapy. Other therapeutic modalities included non-steroidal anti-inflammatory drugs (NSAIDs) 35%, antimalarial drug (chloroquine or hydroxychloroquine) l o % , azathioprine 37%, cyclophosphamide 14Y0, plasma exchange 1% and cyclosporin A 1%. Cyclosporin A was used in this Group I1 patient for her severe retinal vasculitis. Subsequent therapy was modified according to the activity of the disease. At the time of relapse, 27 episodes (12%) required the use of low dose steroid, 42 episodes (19%) moderate dose of steroid, 78 episodes (36%) high dose of steroid and 11 episodes ( 5 % ) pulse methylprednisolone therapy. NSAIDs were used in 44 episodes (20%), antimalarial drug in 24 episodes (11Yo), azathioprine in 75 episodes (%yo), cyclophosphamide in 37 episodes (17%) and plasma exchange in 2 episodes (1"/o). Infections
Thirty two episodes of infection occurred in 27 patients. None of the untreated patients presented with infection (results not shown). The commonest causative organisms were Varicella-zoster virus (as Herpes zoster) (11) and tuberculosis (TB)(9) (Table VII). Two patients had mixed infection: Cytomegalovirus (CMV), Pneumocystis carinii (PCP) and Pseudomonas aeruginosa pneumonia (1); PCP and Pseudomonas aeruginosa pneumonia (1). The mean dose of steroid at time of infection for Group I was 30.5 mg of prednisone or equivalent per day (SD f 39.2 and median 15 mg per day); Group 11, 20.8 mg of prednisone or equivalent per day (SD k 11.0 and median 30 mg per day) and overall, 26.4 mg of prednisone or equivalent per day (SD f 30.7
Table VIII: Causes of Death.
Group I
Group II
No. of patients
Causes *
Disease status at time of death
1 1 1 1 1
pulmonary vasculitis cardiomyopathy severe cerebral atrophy (sequelae of CNS vasculitis) cardiomyopathy retinal vasculitis bronchopneumonia rifampicin induced thrombocytopenia with intracerebral hemorrhage miliary tuberculosis Candid septicemia aspiration pneumonia
severe remitted remitted mild mild
* CNS = central nervous system.
293
K. L. Wong
information at the time of diagnosis, 16 were dead from various causes by March 1989. T h e 5 year and 10 year survival for this group of patients were 92% and 87% respectively. There was no statistically significant difference in the survival rate for the patients who were excluded from the cohort.
1.00
0.95 C
8
- Group
0.90
---
P
I
Group I I
- Overall
Discussion
0.85
0.80
I 0
I
I
50
100
I
I
150
200
I 2 50
Month
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Fig. 3. Ovcrall survival of SLE patients.
and median 15 mg per day) respectively. Eleven patients were on azathioprine but only one was on cyclophosphamide. There is no statistically significant difference in the mean dose of prednisone in patients who had Herpes zoster and tuberculosis (t test). Comparison with other infections were not performed because of the small number of other infections. Of all the infections, only two patients died of causes directly related to the infection: bronchopneumonia (one) (Group I); miliary T B , Candida septicemia, aspiration pneumonia (one) (Group 11). Causes of Death and Outcome
Five patients died during this period: four in Group I and one in Group 11 (Table VIII). None of them died during the first presentation. Three patients had severe generalised disease before death, two of them had the disease treated and remitted, but died from the sequelae of the disease. Two other patients had mild disease at the time of death. Twelve patients (8%) had creatinine clearance of < 5 0 ml/min. at the end of the study period (Group I, 9 and Group 11, 3). Four of the Group I patients had creatinine clearance of < 10 ml/min and was maintained on dialysis (peritoneal dialysis, 3; hemodialysis, 1). None of these patients were transplanted. O n e of the group I1 patients was peritoneally dialysed for chronic renal failure with creatinine clearance of 8 ml/min. for 7 months during this period. Dialysis was stopped because of partial recovery of creatinine clearance to 46 ml/ min. Her creatinine clearance remained at around 35-38 ml/min. at the end of the study period. The overall prognosis of the patients was very good with five year survival of 97% and 10 year survival of 94% (Figure 3). The survival at 50 months was comparable between Group I and Group I1 (p = 0.72) (result not shown). Of the 160 patients who were excluded because of inadequate 294
SLE in Chinese patients has been reported in China, Taiwan, Singapore and Malaysia (2, 7, 19. 20, 21). Their behaviour with respect to the outcome is varied and most data are from retrospective studies. Our cohort study may be able to remedy some of the limitations on data collection of retrospective studies. The sex ratio is higher than usual and probably coincidental, since another cross sectional study over the same period revealed a female:male ratio of about 1O:l (22). Thirty-four of 131 p?t’tents (26%) had insufficient A R A criteria for diagnosis of SLE at the time of presentation. This is not uncommon in reported series. The clinical features at the time of presentation are comparable between our retrospective (Group I) and prospective (Group 11) patient groups except for the renal and hematological involvement. For the former, asymptomatic proteinuria was most common among patients in Group I. This is probably an artefactual distribution because of the difference in policy (vide supra). When the histological changes was further analysed as to the manner of presentation, there was not much difference between the Group I and Group I1 patients. This suggests that there is no difference in the relative proportion of patients with renal presentations. The observation on hematological features is probably valid as further breakdown shows consistently higher proportions of all types of hematological changes in Group I1 patients (Table 111). Neurological manifestation as the initial presentation was rare. This is in accordance with our prospective study on the neurological manifestation of SLE patients (23). Eight of 36 patients in the latter study had primary lupus involvement and none presented with neurological manifestation. This is in contrast t o most studies which reported a much higher incidence (25”/0 to 5 0 % ) ( 5 , 13, 21). Neurological relapses was again uncommon (six episodes) and this further supports the observation that primary neurological manifestation is uncommon among our patients (Table VI). A N A was positive in 92% and 98% of patients in Group I and Group I1 respectively. Anti D N A was positive in 70% and 56% respectively and was lower than what had reported by Boey et al (7). but similar to the results of Worrall et al (24). Since
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S L E , Chinese, Hong Kong
our cohort is much more ethnically homogenous, these observations is probably applicable to our Chinese patients with SLE. However. this level of low positivity may also be related to the methods used to detect the anti DNA which are specific but relatively insensitive. Anti-Ro was the most prevalent anti-ENA antibody and occurred in 48% ( 7 9 156) of patients. The latter is comparable with the results in Japan ( 2 5 ) or Singapore (7) suggesting anti-Ro/SSA is a common anti-ENA in Orientals. The prevalence of anti-Sm was low and is not likely to be of much diagnostic help in the diagnosis of SLE in our locality. Relapses were fairly common (0.042 per patient month), and was more frequent than what has been reported (13). The similar incidences o f renal relapses in patients in Group I and Group I1 suggested that there was not much change of pattern in the relapses in patients recruited before or at the time of entry into this study. When the relapses during the study period in Group I patients was compared to the relapses before the study period, the pattern of relapses was again similar, indicating that the pattern was consistent through these years of follow up. Despite the high frequency of relapses, most relapses responded to treatment (results not shown), Only one patient had severe SLE at the time of death. Correlation of these relapses to mortality is not performed as the number of deaths is too small. Infections have always been the major concern in management of SLE patients. The number of episodes of infections is relatively small (32 episodes in 27 patients). Few patients (two) died as result of infection. It has been argued that steroids or immunosuppressive treatments are the prime factors predisposing SLE patients to infections. In this cohort, the mean dose of prednisone for those who had infections was 26.4 f 30.7 mg/day. Only half of these patients received prednisone 2 15 mg/day. The number of patients on azathioprine and cyclophosphamide were also small (11 and 1 patient respectively). Our study cannot answer the question of whether prednisone or immunosuppressive agents will predispose patients to infections. Considering the number of SLE patients on cyclophosphamide in our Department, the number of patients on cyclophosphamide with infection was unexpectedly low (results not shown). A better designed prospective study controlling SLE disease activity, dosage of prednisone and immunosuppressive therapy may be able to answer whether steroid or immunosuppressive therapy increase the risk of infections. Only five patients died during this period (Table VIII). This mortality rate is low when comparing with major series (2.4.6.21). Since all the patients
were recruited from the available SLE patients in our Department. there is less bias with respect to the pattern of referral. The better survival rate may be explained by a more cautious immunosuppressive regimen given to the patients during the period of observation in patients with evidence of active renal disease, or inclusion of patient with no evidence of renal involvement at presentation. There is also a possibility of a recruitment bias in this cohort since about two thirds of the patients belongs to the retrospective group. Those with aggressive disease may have died before they were recruited into this study. The absence of statistically significant difference in survival between patients in the retrospective group (Group I) and the prospective group (Group 11) at 50 months suggests that the incidence of aggressive disease probably is similar in both groups and these findings may be applicable to the whole population of Chinese patients with SLE. Acknowledgement The author would like to thank Ms T Tong for her expert secretarial assistance and Mr M Leung f o r statistical analysis.
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