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Lupus
http://lup.sagepub.com/content/13/3/204
The online version of this article can be found at:
DOI: 10.1191/0961203303lu530xx
2004 13: 204Lupus
M H Houman, M Smiti-Khanfir, I Ben Ghorbell and M Miled
Systemic lupus erythematosus in Tunisia: demographic and clinical analysis of 100 patients
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- Mar 1, 2004Version of Record >>
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LUPUS AROUND THE WORLD
Systemic lupus erythematosus in Tunisia: demographic and
clinical analysis of 100 patients
MH Houman¤, M Smiti-Khan r, I Ben Ghorbell and M Miled
Department of Internal Medicine, La Rabta University Hospital, Tunis, Tunisia
There is a wide va riation in the n atural histor y of sy stemic lup us eryth ematosus (SLE) amo ng differen t
ethnic and geographicalgroups. Studies in Arabs are fewand those in North Africans and especially in
the Tunisian population do not exist. This study aims to demonstrate the demographic, clinical and
laboratory characteristics of SLE Tunisian patients and to identify those at high risk for renal and
neurops ychiatric involvements. One hun dred patients with SLE (American Co llege of Rheumatolog y
criteria), seen at the Department of Internal Medicine of the University Hospital La Rabta in Tunisia
over a 15-year period (1987 to 2001) were retrospectively enrolled. There were 92 women and eight
men with an average ag e at the onset o f disease of 32 y ears. Nineteen patients were aged over 50 years
at the moment of SLE diagnosis (late-onset SLE). Of the patients, 78% had articular involvement,53%
photosensitivity and 63% malar rash. Serositis occurred in 45 patients of whom 16 had pericarditisand
29 had pleuritis. Nephritis was diagnosed in 43% of the cases and consisted always of glomerular
nephritis, in three cases of which tubulo interstitiallesions were also obser ved. Comparison o f patients
with an d without renal i nvolvement showed that lupus nephritis was sign i cantly associated with
pericarditis (P0.03), arterial blood hypertension (P<0.0001), c ryoglobulinemi a (P0.07) and
antipho spholipid synd rome (P0.03). The SLEDAI at SLE diagnosis was signi cantly higher for
lupus nephritis pa tients. Twelve patient s with lupus nephri tis died compa red with th ree patients in t he
remaining group (P<0.0001). Neuropsychiatric manifestations were observed in 25% of the cases.
The mean age at SLE onset was signi cantly lower, the mean SLEDAI at SLE diagnosis and the
mortality were signi cantly higher in the neuropsychiatric group than in the remaining group.
Immunological features included antinuclear antibodies (100%), anti-DNA antibodies (56%), anti-
Sm antibodies (61%), anticardiolipin antibodies (62%), anti-b2GP1 (13%) anti-Rnp (23%) and
hypocomplementemia (48%). The frequencies of pulmonary hypertension (25 versus 2%,
P<0.00001) and vascular thrombosis (25 versus 2%, P<0.00001 ) were signi ca ntly hi gher in
patient s with positive anti b2GPI a ntibodies. The ve-year survival ra te in our series was 86%. The
most frequent causes of death were active SLE and infections. Lupus (2004) 13, 204 – 211.
Key words: Arab African; autoantibodies; demographics; nephritis; outcome; systemic lupus
erythematosus
Introduction
There is a wide variation in the natural history of
systemic lupus erythematosus (SLE) among different
ethnic and geographical groups.
1–3
These differences
are attributed mainly to differences in genetic and
cultural factors. Studies on Arab subjects are few and
those in North Africans, in particular Tunisians, are
nonexistent. This is, to our best knowledge, the rst
study that aims to demonstrate the demographic,
clinical and laboratory characteristics of SLE adult
Tunisian patients and to identify those at high risk for
renal and neuropsychiatric involvements through a
study of an homogeneous group of patients observed in
the same department. A better knowledge of the
prognostic factors for morbidity and mortality can
improve the management of SLE patients.
Patients and methods
We performed a retrospective review of the records of
the cases diagnosed as SLE in a tertiary referral centre
(Department of Internal Medicine, La Rabta University
Hospital in Tunis) over a 15-year period (19 87– 200 1).
¤Correspondence: Habib Hou man, Department of In ternal Medicine, La
Rabta University Hospital, 1007 Tunis, Tunisia.
E-mail: houman.habib@rns.tn
Received 29 June 2003; accepted 1 December 20 03
L u p u s (2004) 1 3,
204
–
211
www.lupus-journal.com
#
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Only patients with symptoms of at least one-year
duration, who ful lled at least four of the American
College of Rheumatology (ACR) criteria for the
classi cation of the disease revised in 1997
4
and
whose charts had suf cient clinical and laboratory data
were included. The records were analysed for age, sex,
presentation, diagnostic criteria, investigations, com-
plications and treatment. The main SLE clinical
manifestations evaluated in this study were de ned
according to the American Rheumatism Association
glossary committee.
5
The onset of SLE was de ned as
the time when the rst symptoms of SLE occurred.
Late-onset SLE is de ned by the occurrence of the rst
SLE manifestations after the age of 50 years.
Antinuclear antibodies were screened by indirect
immuno uorescence (IF) using either rate liver or
Hep-2 cell as substrate. Anti-DNA antibodies were
assayed by indirect immuno uorescence using
Crithidia luciliae as substrate, and by enzyme-linked
immunosorbent assay (ELISA) if indirect IF was
negative. Anti-RNP, Sm, SS-A and SS-B, anti-
cardiolipin and anti-b2 glycoprotein 1 antibodies
(anti-b2GP1) were assessed by a standardized ELISA
technique. Complement and rheumatoid factor were
assessed by nephelometry.
Renal biopsy specimens in patients with lupus
nephritis were routinely processed for standard analysis
by lig ht (LM) and immuno uorescence (IFM)
microscopy. They were analysed and classi ed
according to the 1982 World Health Organization
(WHO) classi cation for lupus glomerulonephritis.
Patients were usually seen at 1 +3 month intervals,
and organ involvement was assessed at each visit by
clinical and laboratory testing. Disease activity was
evaluated with the SLE index of activity (SLEDAI).
6
Chi-square and Fisher tests were used for statistical
analysis.
Results
One hundred records were analysed. The patients
originated from all parts of Tunisia: 48 were from the
north east, 35 from the north west and 17 from the
centre and the south. They comprised 92 females and
eight males. The average age at SLE diagnosis was 32
years and 19 patients were over 50 years old. The delay
of the diagnosis was on average 13 months (extremes of
one and 72 months). Eight patients (8%) had relatives
with SLE. The most common initial features of SLE
were arthritis or arthralgia (52%), skin involvements
(41%), fever (21%), serositis (8%), lymphopenia and
haemolytic anaemia (6%). The cumulative frequencies
of systemic involvement are presented in Table 1. It is
worth noting in particular, skin manifestations in our
series in the form of Rowell’s syndrome in two cases
and linear bullous IgA dermatosis in one case.
Forty-three patients (43%) had renal involvement at
some stage of their illness; for 41 of them this
complication occurred after SLE diagnosis with an
average duration of 15 months (extremes of one and
144 months). Renal disease consisted of glomerular
nephritis in all cases (43/43); three patients also pre-
sented tubulointerstitial lesions. Thirty- ve of the 43
lupus nep hritis patients (81.4%) underwent renal biopsy.
Biopsies were assigned to WHO classes as follows:
class II, ve patients; class III, 10 patients; class IV,
10 patients; class V, six patients. In the four remaining
cases, histological examination showed mixed mem-
branous-proliferative glomerulonephritis in two cases
and mixed membranous-mesangial glomerulonephritis
in the two others. No isolated interstitial nephritis
was seen.
Comparison of clinical and laboratory features of
SLE patients, with and without renal involvement,
showed that lupus nephritis was signi cantly associated
with pericarditis (P0.03), arterial blood hyperten-
sion (P<0.0001), cryoglobulinemia (P0.07) and
antiphospholipid syndrome (P0.03). The SLEDAI
at SLE diagnosis was signi cantly higher in patients
with lupus nephritis. Twelve patients with lupus
nephritis died, compared with three in the remaining
group (P<0.0001) (Table 2).
Central nervous system (CNS) was involved in
25 patients (25%), 24 had seizures and 18 psychiatric
Table 1 The cumulative frequencies of systemic
involvement in our series
Clinical featu res Frequencies (%)
Photosensitivity 53
Malar rash 63
Discoid rash 18
Raynaud’s phenomenon 19
Articular 78
Avascular necrosis 2
Myositis 2
Cardiac 18
Pericarditis 18
Myocarditis 2
Pulmonary 29
Pleuritis 29
Shrinking lung syndrome 2
Pulmonary hypertension 5
Haemolytic anaemia 6
Lymphopenia 50
Thrombocytopenia 12
Nephritis 43
Glomerular nephropathy 43 (100)
Tubulointerstitial nephropathy 3 (7)
Neuropsychiatric 25
Seizure 6 (24)
Psychosis 20 (80)
Venous thrombosis 6
Antiphospholip id syndrome 11
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manifestations. The average age at SLE onset was
signi cantly lower in patients with neuropsychiatric
disorders (P0.0012). Arterial hypertension was
signi cantly more common in these patients
(P<0.0001). The average SLEDAI at SLE diagnosis
and the mortality rate were also signi cantly higher in
this group of patients than in the remaining group
(P0.046 and 0.065, respectively). Infectious com-
plications were more common among these patients
(P0.00003) but they were also more frequently
treated with immunosuppressive drugs (P0.0006).
Immunological features included antinuclear
antibodies in 100/100 patients (100%), anti-DNA
antibodies in 56/94 patients (59.9%), anti-Rnp
antibodies in 23/51 patients (45%), anti-Sm antibodies
in 41/67 patients (61.2%), anticardiolipin antibodies in
37/56 patients (66%), anti-b2GP1 in 8/58 (13.8%)
and hypocomplementemia in 48/79 (60.8%). There
were no clinical differences between patients with and
without anti-DNA antibodies. Anti-Sm antibodies were
more frequently observed in patients with than in those
without positive anti-DNA antibodies (51 versus 27%,
P0.02).
Because a relatively high percentage of patients
had the anti-Sm antibodies (group Sm 1), we compared
them with those without these antibodies (group Sm 2);
only pericarditis was more commonly observed in
group Sm 1 patients.
The frequency of neuropsychiatric manifestations
was signi cantly higher in patients with anticardio-
lipin antibodies (32 versus 9%, P0.001), while
cardiac involvement was signi cantly less common
in this group of patients (2.7% versus 23%,
P0.00021). In patients with positive anti-b2GP1
antibodies, the frequencies of pulmonary hypertension
(25 versus 2%, P<0.00001) and vascular thrombosis
(25 versus 2%, P<0.00001) were signi c antly higher
than in those with negative anti-b2GP1 antibodies.
However, skin involvement (50 versus 86%, P
0.016), nephritis (12.5 versus 50%, P<0.00001) and
death (0 versus 18%, P<0.00001) were signi cantly
less common in this group of patients. The anti-b2GP1
antibodies were signi cantly associated with the
presence of anticardiolipin antibodies (87.5 versus
58%, P0.06) (Table 3).
Nineteen patients had late-onset SLE. They were
four men and 15 women with an average age of 59
years (range, 50 –74 years). Female predominance
was signi cantly lower and the delay for SLE
diagnosis was signi cantly higher in this late-onset
SLE group than in the remaining group (16 versus 11
months, P<0.005). T he most common rst
manifestations were serositis and haematological
disorders (anaemia and lymphopenia) and hypocom-
plementemia was signi cantly more common in these
patients. They also were more exposed to infectious
complications (31 versus 18%).
Hydroxychloroquinewas prescribed in 98% of cases
and corticoids in 83% of them. Thirty-one patients were
handled with immunosuppressive therapy which was
cyclophosphamide in 23 cases and azathioprine in six
cases.
Table 2 Characteristics of SLE patients with (group R1) and without (group R2)
renal involvement
Group R1
(n43)
Group R2
(n57) P
Age (years) 32 35 0.54
Sex ratio F/M 37/6 55/2 0.08
Delay of diagnosis 9 months 15 months 0.62
Cardiac disorders 26% 12% 0.03
Arterial hypertension 33% 3.5% 0.00000 35
Pulmonary disorders 37% 23% 0.11
Neuropsychiatric disorders 26% 25% 0. 90
Antiphospho lipid syndrome 9% 2% 0.03
Haematological disorders 88% 75% 0.44
Anti-DNA antibody 65% 49% 0.23
Anti-Sm 49% 33% 0.13
Hypocomplementemia 51% 46% 0.67
Cryoglobulinemia 16 % 7% 0.07
Anticardiolipin antibody 42% 32% 0.32
Anti-b2GP1 4.5% 10.5% 0.12
Corticotherapy 100% 79% 0.25
Immunosuppressive therapy 51% 16% 0.00018
Infectious complications 26% 17% 0.21
SLEDAI 19.80 12.7 3 0.011
Death (average delay of SLE diagnosis) 28% (16 months) 5% (58 months) 0.0001
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Improvement of clinical features was noted in 58%
of the patients. Clinical, biological and immunological
complete remission was obtained in 10% of cases.
The average of the SLEDAI at the time of diagnosis
was 1 5.5 (range, 3 – 47); and after six an d 12 months o f
treatment, it decreased respectively to 4.3 (range, 0 –25)
and 3. 7 (range, 0 – 20 ).
Twenty-six patients (26%) developed a sepsis
during the course of SLE. Twenty-four of them (92%)
were under immunosuppressive therapy (prednisone
>20 mg and/or cyclophosphamide or azathioprine).
The most frequent infectious locations were pulmonary
and urinary for, respectively, six and ve patients.
The total follow-up duration was on average 28 months
(range, 1– 176 months). Figure 1 represents the survival
actuarial curve in our series. During the follow-up care
period, 15 patients died. These were 13 women and
two men, with an average age at the moment of SLE
diagnosis of 35.2 years. Ten of them (66%) died during
the two rst years after SLE diagnosis. At the moment of
death, the average duration of SLE evolution was 25
months (range, 1– 144 months). The most frequent
causes of deaths were active SLE in nine cases (60%) and
infections in six cases (40%). Most patients who died
of active SLE had frequently uncontrollable or
progressive multisystemic disease. The most frequent
infections were bacterial sepsis of pulmonary and urinary
origin. The delay of diagnosis was longer in patients who
died. The SLEDAI at the time of SLE diagnosis was
signi cantly higher in this patient group. Renal and
neuropsychiatric involvements, as well as arterial
hypertension and antiphospholipid syndrome (APLS)
Table 3 Clinical and laboratory features in patients with and without anti-b2
glycoprotein 1 ant ibodies
anti-b2GP1( )
group (n8)
anit-b2GP1()
group (n50) P
Age (years) 37 32 0.7
Skin involvement 50% 86% 0.0 16
Renal 12.5% 50% 0.00002
Articular 87. 5% 78% 0.6
Pericarditis 12.5% 10% 0.68
Pleuritis 25% 16% 0.2 0
Pulmonary hypertension 25% 2% 0.000029
Neuropsychiatric 25% 24% 0.89
Neurological
Psychiatric
Haematological 75% 84% 0.5 9
Vascular thrombosis 25% 2% 0.000029
Anti-DNA antibodies 62.5% 64% 0.88
Anti-Sm antibodies 62. 5% 50% 0.36
Anticardiolipin antibodies 87.5% 58% 0.06
Antiphospholip id syndrome 12.5% 12% 0.9 8
SLEDAI 11.25 17.39 0.28
Death 0 18% 0.06
anti-b2GP1 anti-b2 glycoprotein 1 antibodies.
Figure 1 Actuarial curve of survival.
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were signi cantly more frequent in patients who died. In-
fections were also more common in this group of patients
(Table 4). The ve-year survival rate in our series was
86%.
Discussion
In this present study we describe the frequency and
characteristics of the main SLE clinical and laboratory
features, and the mortality rate and causes of death in
100 Tunisian patients diagnosed and treated in the same
tertiary referral university centre.
The Tunisian population results from a signi cant
intermingling of different populations throughout
history, mainly composed of Berbers, Arabs, Turks
and south Europeans. Clinical features have been des-
cribed in various ethnic groups including Caucasian,
1
Asian,
1,3
Hispanic,
1
black Americans and Africans
1,7,8
and Arabs from the Middle East,
9–13
but no literature
exists on SLE features of North African patients, in
particular from Tunisia. Racial differences in prevalence
and features of SLE suggest that ethnic factors may be
important in the expression and severity of disease.
Prevalence of SLE has been found to be up to eight
times higher in African-American and Afro-Caribbean
populations than in people of European descent.
11
Incidence and prevalence of SLE in Tunisia as well as in
other African and Arab countries cannot be clari ed for
lack of national epidemiological enquiries. Age of SLE
onset and sex ratio in our patients were similar to those
from other racial groups.
1,2,9 –13
Eight patients (8%)
had relatives with SLE. Generally, about 10% of SLE
patients have familial SLE. A high familial rate (24%)
has been reported by Habib and Saliba in their study
of SLE among Arabs in Israel.
15
Unfortunately,
there are no data on familial SLE from other south
Mediterranean, African and Arab countries.
Our patients had clinical disease spectra similar to
those described in SLE patients from other ethnic
groups, especially from black African,
8,16
Arab,
9– 13
Asiatic,
14,17
Hispanic and Caucasian patients.
1,18
The frequencies of major clinical and serological
manifestations of our patients, compared to these other
populations are represented in Table 5. Articular and
cutaneous manifestations were the most common
symptoms in our patients as well as in the other
reported series. Frequency of malar rash in our patients
was similar to that in patients from South Africa,
8,16
the
Middle East,
9– 13
and Asia (Vietnamese,
14
Chinese,
3
and Japanese
17
populations) but clearly higher than in
European, Indian and Senegalese patients.
2,8,18
This
difference may be due to the higher levels of sunshine
in Tunisia compared to Europe, and on the other hand,
to the less dark skin of Tunisian people compared to
Senegalese and Indians. Oral ulcers were signi cantly
less frequent in our series (4%) and the European
cohort (8.9%) than in the other ethnic groups (16 –
40%). We are unable to explain these ndings.
Nephritis is in general the most important predictor
of poor outcome.
19
Renal manifestations of SLE are
variable in clinical presentation and prognosis, ranging
from mild asymptomatic proteinuria to rapidly
progressive glomerulonephritis leading to end-stage
renal disease.
20
In only two cases did renal involvement
occur before SLE diagnosis. This is probably due to a
bias of recruitment; in fact, such patients are taken care
of in a nephrology department of our district. In our
series, comparison of clinical and laboratory features of
SLE patients with and without renal involvement (Table
4) showed that lupus nephritis was signi cantly
associated to pericarditis (P0.03), arterial blood
Table 4 Comparison of clinical and laboratory features of dead (group D1) and survival
patients (group D2)
Group D1
(15 patien ts)
Group D2
(85 patient s) P
Age (years) 35.2 33.38 0.86
Sex F/M 13/2 F/6 0.63
Delay of diagnosis (months) 5.66 14.11 0.09
SLEDAI 24.38 14.5 <0.0001
Renal involvement 80% 36% 0.001
Renal failure 46% 14% 0.0004
Cardiac 20% 17% 0.78
Arterial hypertension 33% 13% 0.012
Neuropsychiatric involvement 40% 22% 0.04
Haematologic disorders 93% 79% 0.49
Hypocomplementemia 46% 48% 0.96
Anti-DNA antibodies 60% 56% 0.85
Anti-Sm antibodies 33 % 42% 0.37
Anticardiolipine antibodies 33% 55% 0.0 49
Antiphospholip id syndrome 2 0% 5% 0.0087
Immunosuppressive therapy 26% 25% 0.97
Infectious complications 40% 23 .5% 0.084
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Table 5 Frequencies of clinical and laboratory features of SLE patients among different ethnicities
Our
series Uthman
11
Alballa
9
Ka
8
Tickly
16
Phan
14
Hopkinson
2
LUMINA
1
(USA) Cervera
18
Thumboo
3
Population Tunisian Lebanese Saudi Senegalese South
African
Vietnamese English Hispanic Afro-
American
Caucasian European Malayan Indian Chinese
Number of patients 100 100 87 19 111 23 147 70 88 71 1000 63 28 381
F/M 92/8 86/14 78/9 19/0 — 21/2 136/11 66/4 78/10 58/13 92/908 57/6 24/4 354/27
Median age 32 25 28.5 28 — 38 35.1 34.2 35.4 42.8 29 32 30 31
Photosensitivity (%) 53 16 26 10 33 44 51 93 92 94 18.7 29 14 32
Malar rash (%) 63 52 56 37 55 61 30 — — — 26.4 64 26 63
Discoid lupus (%) 18 19 18 31 29 9 10 — — — 5.4 18 20 7
Oral ulcers (%) 4 40 16 21 22 30 37 — — — 8.9 26 25 19
Aricular (%) 78 95 90.8 95 62 61 91 93 94 89 41.3 54 68 62
Serositis (%) 45 40 56.3 58 28 30 37 — — — 12.9 22 19 21
Nephritis (%) 43 50 63.2 74 49 26 22 62 59 32 22.2 55 49 56
Neuropsychiatric (%) 25 19 25.3 32 17 22 9 68 67 59 13.6 10 28 14
Haematologic (%) 81 47 78 84 61 61 — 90 86 77 12.8 78 83 79
ANA (%) 100 87 98 100 — 100 97 98.6 97.7 97.4 96 90.5 91.7 93.4
Anti-DNA (%) 56 50 93 78 — 57 54 44.3 40.9 21.1 78 86 85.8 85.6
Anti-Sm (%) 61.2 — 40 — — 36 3 4.5 9.5 4.4 10 34.5 27 26.1
Anti-Rnp 45 — — — — 54 — — — — 13 50 39.1 38.1
Anticardiolipin (%) 37 — — — — 22 — 7 10.9 4.8 24 — — —
Number of ACR
criteria
5 (4–9) — — — — — — 6 (4– 9) 6 (4– 10) 6 (4– 9) — — — —
ANA, antinuclear antibodies.
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hypertension (P<0.0001), cryoglobulinemia (P
0.07) and antiphospholipid syndrome (P0.03);
however, it did not correlate to any antibodies,
especiall y to anti-DNA. The SLEDAI at SLE
diagnosis was signi cantly higher in patients with
lupus nephritis. Twelve patients with lupus nephritis
died, compared with three patients in the remaining
group (P<0 .0001). A comparative Euro pean study of
two groups of SLE patients with or without nephritis
showed that patients with renal involvement suffered
more commonly from malar rash, psychosis, lympha-
denopathy, myocarditis, pericarditis and hypertension
(as in our series), and anaemia, low serum complement
and raised anti-DNA antibodies were more frequent in
the lupus nephritis group.
21
Another comparative
study reported a higher frequency of neuropsychiatric
manifestations in the lupus nephritis group.
22
Frequencies of neuropsychiatric (NP) manifestations
in SLE vary from 7 to 69% depending on inclusion
criteria and ethnic origin. However, to what degree these
neuropsychiatric conditions can be explained on the basis
of chronic illness, or as part of the disease spectrum of
SLE, is a matter of debate.
23
In our study, 25% of the
patients had neuropsychiatric manifestations. The mean
age at SLE onset was signi cantly lower; the mean
SLEDAI at SLE diagnosis and the mortality were
signi cantly higher in the neuropsychiatric group than in
the remaining group. Several previous studies showed
that neuropsychiatris (NP) manifestations are signi -
cantly associated with antiphospholipid antibodies (aPL),
especially IgG anticardiolipin (aCL) and lupus antic-
oagulant (LAC).
24–26
Our patients with NP manifestations did not show
such association, but had arterial hypertension more
frequently than did the patients without NP manifesta-
tions. A history of cyclophosphamide treatment was
signi cantly associated with NP manifestations in our
series, similar to that was reported in Chinese patients.
26
The pro le of antibodies in Tunisian patients is
similar to that seen in other ethnic groups, but in some
cases at a higher frequency. The frequency of anti-Sm
antibodies (61%) is particularly high. Frequency of
these antibodies has been noted to vary between
patients with different racial backgrounds.
27
A high
frequency was also observed in the South African
16
(44.28%), the Saudi
9
(40%) and the Vietnamese popu-
lations
14
(36%). Anti-Sm antibodies were also reported
to occur signi cantly more frequently in African-
Americans than in Latin-Americans and white patients
in the USA and in Mullato/black patients than
Brazilian-whites and Caucasians patients in Brazil.
28–30
In our series, the presence of these antibodies was
signi cantly associated with pericarditis and Rnp
antibodies, while in the South African population it
was associated with psychosis.
Raised blood levels of antiphospholipid (aPL)
antibodies in autoimmune diseases and especially in
SLE, in which levels of these autoantibodies are raised
in 20 – 60% of patients, have been associated with
recurrent venous and arterial thromboses, fetal loss,
thrombocytopenia and neurological disorders.
31
In 1990, three independent groups reported that, in
primary antiphospholipid syndrome (PAPS) patients,
anticardiolipin antibodies (aCL) need a circulating
plasma protein as a cofactor, which binds to the
cardiolipin antigen in solid-phase ELISA assays. This
cofactor has been identi ed as b2-glycoprotein 1
(b2GP1).
32–34
Several studies have reported that
anti-b2GP1 was a more speci c biological marker
for thrombotic events than aCL.
35
Our results indicate
that aCL antibodies are more prevalent than anti-
b2GP1 antibodies in SLE patients (66 and 13%,
respectively).
In our series, the frequency of neuropsychiatric
disorders was signi cantly higher in patients with
anticardiolipin antibodies, while in patients with
positive anti-b2GP1 antibodies, the frequencies of
vascular thrombosis and pulmonary hypertension were
signi cantly higher than in those with negative anti-
b2GP1 antibodies. Similar to that observed by Loizou
et al.,
36
there was no association between anti-b
2
GP1
antibodies and kidney disease.
Traditionally, SLE has been considered a disease of
young women and onset of SLE in later life is
uncommon and constitutes just 6 – 18% of the lup us
population.
7,37,38
Nineteen of our patients (19%)
developed the rst manifestations of SLE after the
age of 50 years. Some authors have found no diff-
erences in the female/male ratio related to aging, but
our study suggests that female predominance is not so
pronounced in the elderly onset group (4/1 versus 15/1
in the remaining group) similar to that observed in the
Euro-Lupuscohort.
18
The clinical expression of SLE in
elderly patients differs in several aspects from the
disease in young adults.
39
In our late-onset SLE
patients, the most common rst manifestations were
serositis and haematological disorders (anaemia and
lymphopenia) and the delay for SLE diagnosis was
signi cantly higher than in the remaining group of
patients. The explanation for this apparent age-related
variability in the expression of the disease is still
unclear, but it has been postulated that the less
exuberant expression of SLE both clinically and
immunologically in older patients may re ect senes-
cence of the immune system.
18
Survival studies among our patients revealed a ve-
year survival rate of 86%, which is lower than American
and European reports (over 93%). This could be related
to delay in diagnosis due to lack in awareness of the
disease, referral bias where only serious patients are
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sent to our tertiary referral centre, patients failing to
comply with treatment and follow-up recommendation,
or a truly more severe disease among Tunisians, or a
combination of these genetic, environmental and/or
sociocultural factors.
Active disease and infections were the two major
causes of death in our series. As infections in SLE are
often due to or in uenced by the therapy employed, a
balance between bene ts and side effects should be
considered very carefully when selecting the medi-
cation to control SLE.
Acknowledgement
The authors wish to thank N Abderrahim for his
previous help and assistance.
References
1 Alarcon GS, Friedman AW, Straaton KV et al. Systemic lupus
erythematosus in three ethnic groups: III A comparison of
characteristics early i n the natural history of the LUMINA cohort.
Lupus 1999 ; 8: 197 – 209.
2 Hopkinson ND, Doherty M, Powell RJ. Clinical features and race-
speci c incidence/prevalence rates o f systemic lupus eryth emato sus in a
geographically complete cohort of p atients. Ann Rheum Dis 1994; 53:
675–680.
3 Thumboo J, Fong KY, Chng HH et al. The effects of ethnicit y on disease
patterns in 472 orientals with systemic lupus erythematosus. J
Rheumatol 19 98; 25: 1299 – 1304 .
4 Smith EL, Rhmerling S. The American College of Rheumatology
criteria for the classi cation of sy stemic lupus erythematosus. Strengths,
weaknesses and op portunities for imp rovement. Lupus 1999; 8:
586–595.
5 American Rheumatism Association glossary committee. Signs and
symptoms. Dictionary o f the Rheumatic Disease 1982; 1: 1 – 80.
6 Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH.
Derivation of the SLEDAI. A disease activity ind ex for lupus patients.
The Committee on Prognosis Studies in SLE. Arthritis Rh eum 1992; 35:
630–640.
7 Ballou SP, Khan MA, Kushner I. Clinical features of systemic lupus
erythematosus – differences related to race and age onset. A rthritis
Rheum 1982; 2 5: 55–60.
8 Ka MM, Diallo S , Kane A et al. Systemic lupus erythematosus and
lupus syndr omes in Seneg al. A retrospective study of 30 patients seen
over 10 years. Rev Rheum E ngl Ed 1998; 65: 471– 476.
9 Alballa SR. Systemic lupus erythematosus in Saudi patients. Clin
Rheumatol 19 95; 14: 342 – 346.
10 Al-Rawi ZS, Al Shaarbaf H, Al Raheem E, Khalifa ST. Clinical features
of early cases of systemic lupu s erythematosus in Iraqi patients. Br J
Rheumatol 19 83; 22: 165 – 171.
11 Uthman I, Nasr F, Kassak K, Masri A. Systemic lupus erythematosus in
Lebanon. Lupus 1 999; 8: 713 – 715.
12 Al-Jarallah K, Al-Awadi A, Siddiqui H et al. Systemic lupu s
erythematosus in Kuwait – hospital based study. Lupus 19 98; 7:
434 –438.
13 Al-Maini MH, El-Ageb EM, Al-Wahaibi SS, Al-Farsi Y, Richens ER.
Demographic, autoimmune, and clinical pro les of patients with
systemic lupus ery thematosus in Oman. Rheumatol Int 2003; 2 3:
186–191.
14 Phan JC, Bush TM, Do nald F, Ward M. Clinical and laboratory features
of patients of Vietnamese descent with systemic lupus erythematosus.
Lupus 1999 ; 8: 521 – 524.
15 Habib GS, Saliba WR. Systemic lupus erythematosus among Arabs.
IMAJ 2002; 4: 6 90– 6 93.
16 Tickly M, Burgin S, Mohanlal P, Belligan A, George J. Auto antibo dies
in black South African with systemic lupus erythematosus: Spectrum
and clinical associations. Clin R heumatol 1996; 15: 261 – 265.
17 Yokohari R, Tsun ematsu T. Application to Japanese patients o f the 1982
American Rheumatism Association revised criteria for the classi cation
of systemic lupus eryth ematosus. Arthritis Rheu m 1995; 28: 693–698.
18 Cervera R, and the European Working Party on Systemic Lupus
Erythematosus. Lessons from the “Euro-Lupus Cohort”. Ann Med
Interne 2002; 1 53: 530–536.
19 Wallace DJ, Podell T, Weiner J et al. Systemic lupu s erythematosus –
survival pattern s. Experience with 609 patien ts. JAMA 1981; 245: 934–
938.
20 Dooley MA, Falk RJ. Immunosuppressive therapy of lup us nephritis.
Lupus 1998 ; 7: 630 – 634.
21 Le Thi Huong D, Papo T, Beau ls H et al. Renal involvement in
systemic lupus eryth ematosus: a study of 1 80 patients from a single
center. Medicine 1999; 78: 148 – 166.
22 Pisetsky DS, Wallace DJ, Nessim S, Metzger Al, Klinenberg JR. Lupus
erythematosus in the 1980 s: a survey of 570 patients. Semin Arthritis
Rheum 1991; 2 1: 55–64.
23 Omdal R. Some controversies of neuropsychiatric systemic lupus
erythematosus. Scand J Rheumatol 2002; 3 1: 192– 1 97.
24 Afeltra A, Garzia P, Mitterhofer AP et al. Neuropsychiatric lupus
syndromes: Relationship with antiphospholipid antib odies. Neurology
2003; 61: 108 – 110.
25 Sanna G, Bertolaccini ML, Cuadrado MJ et al. Neuropsy chiatric
manifestations i n systemic lupus eryth ematosus: prevalence and associ-
ation with ant iphospholipi dantibodies. J Rheumato l2003;30: 985 – 992.
26 Mok CC, Lau CS, Wong RW. Neuropsychiatric manifestations and their
clinical associations in southern Chinese patients with systemic lupus
erythematosus. J Rheumatol 2001; 28: 76 6– 77 1.
27 Boey ML, Peebles CL, Tsay G, Feng PH, Tan EM. Clinical and
autoantibody correlations in orientals with systemic lupus erythemato-
sus. Ann Rheum Dis 1988; 47: 91 8– 92 3.
28 Molina JF, Molina J, Garcia C, Ghara AE, Wilson WA, Esponisa LR.
Ethnic differences in th e clinical expression of systemic lup us
erythematosus: a comparative study between African-Americans and
Latin Americans. Lupus 19 97; 6: 63 – 67.
29 Arn ett FC, Hamilto n RG, Roebber MG, H arley JB, Reichlin
M. In creased frequencies of Sm and nRNP autoantibodies in American
blacks compared to whites with systemic lupus erythematosus.
J Rheumatol 198 8; 15: 1773–1776.
30 Zimmermann AF, d e Messias IJ, Utiyama SR et a l. Clinical,
autoimmune and demo graphic pro le in systemic lupu s erythematosus
(SLE) patients from southern Brazil. J Investig Allergo l Clin Immunol
1997; 7: 24 – 31.
31 Alarcon-Segovia D, Deleze M, Oria CV et al. Antiphospho lipid
antibodies and the antiphosphol ipid syndrome in systemic lupus
erythematosus. A prospective analysis of 500 consecut ive patient s.
Medicine 198 9; 68: 353 – 365.
32 McNeil HP, Simpson RJ, Chesterman CN, Krilis SA. Antiphospholipid
antibodies are directed against a complex antigen that includes a lipid-
binding inhibitor of coagulation: ß
2
-glycoprotein I (apolipoprotein H).
Proc Natl Acad Sci USA 1990; 87: 4120– 4124.
33 Galli M, Confurius P, Maassen C et al. Anticardiolip in antibodies
(ACA) directed no tto card iolipin but to a plasma cofactor. Lancet 1990;
335: 1544–1547.
34 Mat suura E, Igarashi Y, F ujimoto M, Ich ikawa K, Koike T.
Anticardiolipin cofactor(s) and differential diagn osis of autoimmune
disease. Lancet 1990; 336: 177– 17 8.
35 Tsutsumi A, Matsuura E, Ichikawa K et al. Anti bodies to ß
2
-
glycoprotei n I and clinical manifestations in patients with systemic
lupus erythemato sus. Arthritis Rh eum 199 6; 39: 1466 – 1474.
36 Loizou S, Samarkos M, Norsworthy PJ, Cazabon JK, Walport J,
Davies KA. Signi cance of anticardiolipin and anti-ß2-glycopro tein I
antibodies in lupus nephritis. Rheumat ology 2000; 39: 962 – 968.
37 Ward MM, Polisson RP. A meta-analysis of th e clinical manifestations of
older-onset systemic lupus erythematosus. Arthritis Rheum 1989; 32:
1226 –1 232.
38 Mak SK, Lam EKM, Wong AKM. Clinical pro le of patients with late-
onset SLE: not a benign subg roup. Lupus 1998; 7: 23 –2 8.
39 Ho CTK, Mok CC, Lau CS, Wong RWS. Late onset systemic
lupus erythematosus in southern Chin ese. Ann Rh eum Dis 1998; 57:
437–440.
S L E i n T u n is ia
M H Houman
et al.
211
Lupus
at BROWN UNIVERSITY on December 19, 2012lup.sagepub.comDownloaded from
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