Rheumatology 2013;52:2108–2115
doi:10.1093/rheumatology/ket160
Advance Access publication 2 May 2013
RHEUMATOLOGY
Review
Effect of gender on clinical presentation in systemic
lupus erythematosus
Grainne Murphy1 and David Isenberg1
R EV I E W
Abstract
The incidence of SLE is markedly increased in females of child-bearing age. Although males are protected
in terms of incidence of disease, it is unclear whether a distinct phenotype of male lupus exists in those
who do develop SLE. We sought to explore through a detailed literature review whether gender exerts an
influence on the clinical presentation and outcome of SLE. We found that males experience less of the
typical mucocutaneous and musculoskeletal symptoms commonly present at diagnosis in women. On the
other hand, there is limited evidence to support a negative prognostic association between male gender
and disease activity or mortality.
Key words: SLE, outcome measures, lupus nephritis, male gender.
Introduction
SLE is a multisystem autoimmune condition with diverse
clinical and immunological features [1]. It is characterized
serologically by autoantibodies targeting self-proteins,
notably ANAs, which are present in virtually all affected
individuals.
The pathogenesis of SLE remains incompletely understood but most likely involves the interaction of genetic,
hormonal and environmental factors [2, 3]. It is substantially more common in females of child-bearing age,
where the reported female:male ratio is 8–15:1 [4].
Pre-pubertal and post-menopausal ratios are much
lower at 2–6:1 and 3–8:1, respectively [5–10]. This striking
predominance in females probably relates to the effect of
endogenous sex hormones, which have complex effects
on the immune system [11, 12]. However, a full explanation for why the disease is so uncommon in men remains
elusive.
Another linked debate is whether there is a particular
type of lupus among males. Opinions have varied. One of
us has likened the existence of a distinct male lupus syndrome to the Loch Ness monster, i.e. often reported but
not proven [13]. Others have seemed more convinced that
lupus in males may take a more severe course [14], in
1
Department of Rheumatology, University College Hospital, London,
UK.
Submitted 19 November 2012; revised version accepted
14 March 2013.
Correspondence to: Grainne Murphy, Department of Rheumatology,
University College Hospital, 3rd Floor Central, 250 Euston Road,
London NW1 2PQ, UK. E-mail: [email protected]
particular with an increased incidence of renal disease,
serositis, thromboses and discoid skin disease. These
reports have been inconsistent and, like many studies of
SLE, are complicated by disparities in ethnicity, duration
of follow-up and selection bias.
We sought to explore this question through a critical
appraisal of the literature in an effort to clarify whether
there are true gender discrepancies in the presentation
and course of SLE and if this might be reflected by an
impact on survival and mortality. In particular, we also
focus on the issue of a disparity in the prevalence or prognosis of LN, a particularly contentious issue in the course
of lupus in men.
Clinical features
Presentation
One of the interesting issues to consider in studying
gender disparities in SLE is the nature of its initial presentation in male and female patients. The greater awareness
of SLE as a potential diagnosis, particularly in fertile
females, may lead to a greater delay in diagnosis in men
with similar symptoms. Alternatively, if men displayed an
atypical phenotype at presentation, a delay in diagnosis,
and thus treatment, might result. The consequence would
be a greater burden of inflammation and subsequent
damage over time.
Demographically it has been reported that male SLE
patients are older at disease onset [15]. However, this is
not strongly supported by the literature. In fact, there is
little evidence to support a discrepancy in either disease
onset (time of first SLE symptoms) or diagnosis (fulfilment
! The Author 2013. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: [email protected]
Comparison of male and female SLE
of four ACR criteria) by gender. While there is considerable variability, males have been reported to experience
first SLE-related symptoms at a mean age range of
26–38.4 years [9, 16] in comparison with females
(26.3–31.9 years) [17, 18]. The mean age range at diagnosis in males was 26–55 years [19, 20], with females being
diagnosed at a mean age of 27.9–42.6 years [20, 21]. Only
two studies reported a significantly older age of onset
in male subjects, one of which was a study of army veterans, which seems likely to be biased by its recruitment
policy [16, 20]. There is some suggestion that the age of
onset in males and females may differ in certain ethnicities. Specifically, two studies have reported an older
onset of SLE in males compared with females in the
Caucasian subpopulation of their cohorts [14, 22].
Interestingly, the overall trend was to a shorter delay in
diagnosis of male patients, with a range of 6–46 months
between symptom onset and diagnosis in males and 8–58
years in females [21].
To address the clinical phenotype at presentation, a
number of groups have specifically assessed organ
involvement at disease onset. Although significant heterogeneity exists, the most consistent findings are a lower
incidence of musculoskeletal symptoms, RP, alopecia
and photosensitivity in men at diagnosis, with the suggestion of more prevalent serositis and discoid lupus.
Reduced arthralgia/arthritis has been reported in
Chinese (P = 0.02) [23], Greek (P = 0.004) [24] and
Caucasian (P < 0.03) [25] populations. Serologically only
anti-Ro antibodies have been shown to have a genderspecific association at diagnosis, being more frequently
positive in females (P = 0.049) [23]. Only one study
has found a greater incidence in nephropathy in men
at disease onset [24], inconsistent with findings from
an earlier Greek cohort [26]. Stefanidou et al. [24] also
found higher frequencies of thromboses (P < 0.01) and
gastrointestinal symptoms (P < 0.01) in men. Similarly,
no difference in renal biopsy frequency at diagnosis or
the resultant histology was shown in a Chinese SLE
cohort [23]. Interestingly, a study from Latin America suggested that males may display more constitutional symptoms at diagnosis [17]; this, however, has not been
reported in other geographic regions. Overall therefore,
despite the suggestion that men less frequently display
the typical mucocutaneous features of SLE at disease
onset, this has not been reflected by a delay in diagnosis
as outlined above.
Follow-up
The relative paucity of male patients with SLE has contributed to the difficulty in analysing the disease course in
males. This problem has been circumvented by the use of
case–control studies and a multicentre approach with
more recent reports describing larger inception cohorts.
Both ethnicity and age have a strong influence on SLE
expression; in particular, patients of African American extraction frequently exhibit more significant renal disease,
hypertension and discoid lupus and less photosensitivity
[27, 28]. In comparison with Caucasians, Hispanics also
have a greater incidence of arthritis [29]. Differences are
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also noted within ethnic subpopulations. For example,
Hispanics from Texas (of Mexican/Central American ancestry) more frequently suffer from serositis, renal involvement, psychosis and thrombocytopenia and less
frequently from photosensitivity and malar or discoid
rash than Puerto Rican Hispanics [30]. While this may reflect the complex interplay of genetics and environment, it
highlights the great difficulties in dissecting the role of
gender in altered disease phenotypes from what are typically heterogeneous populations.
It seems prudent to distinguish studies from different
geographical regions and ethnic populations to make
cohort comparisons more meaningful. This approach
may enable a better assessment of the role that gender
plays in disease expression within particular population
subgroups.
Asia
Previous studies have reported that Asian patients have
higher rates of renal involvement, more active renal disease and higher rates of nephritis-associated autoantibodies in comparison with predominant white populations
[31]. To characterize the gender-specific symptomatology
in Asian patients, Mok et al. [23] performed a case–control
study of 51 male and 201 female patients followed in
rheumatology or nephrology outpatients. After a median
disease duration of 103.6 months in males (101.6 months
in females), no significant differences in major organ involvement were identifiable, despite a trend towards less
RP, alopecia and arthritis in men. Importantly, there was
no evidence of increased damage using the SLICC/ACR
index and treatment modalities were not influenced by
gender. Interestingly, male subjects appeared to have a
lower number of disease flares per patient-year (P = 0.04).
Serologically only anti-Ro antibody status differed by
gender, present in 62% of females and 47% of men
(P = 0.05). Some similarities are found between these results and an earlier case–control study by Koh et al. In this
group, the incidence of renal disease and serositis was
similar between Oriental male and female patients with
SLE, but fewer males were seropositive for anti-Ro antibodies (P < 0.001) [32]. This group demonstrated an
increased frequency of arthritis and leucopenia in
females (P < 0.04). A more recent study of a Chinese
cohort failed to detect a significant difference in the clinical phenotype of male patients with SLE, although a trend
towards higher rates of renal involvement was reported
and SLEDAI scores were significantly high in the male
subgroup [33].
Thai males have also been shown to have less arthralgia than females in addition to less RP and alopecia
and more prevalent thrombocytopenia (P < 0.05 for all)
[18]. While the incidence of overt nephropathy did not
differ, there were significantly more male subjects with
increased creatinine levels over an average follow-up of
2 years (P = 0.006). A smaller study aimed primarily at dissecting the impact of gender on cutaneous manifestations
of SLE found no difference between male and female patients in non-cutaneous manifestations by retrospective
chart review [34].
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Europe
USA
Many large European studies have addressed the modifying effect of gender on disease expression. Even within
the same population, conflicting results are reported. Both
Stefanidou et al. [24] and Voulgari et al. [26] examined the
clinical phenotype of SLE in Greek patients. The latter
found that men had significantly more serositis
(P < 0.01), less photosensitivity (P < 0.05), oral ulcers
(P < 0.01), RP (P < 0.05), thrombocytopenia (P < 0.05) or
increased ESR (P < 0.01) in comparison with women
[26]. There was no overall increase in renal involvement
in men. In contrast, Stefanidou et al. [24] found that male
SLE patients had higher rates of nephropathy (P = 0.009),
myositis (P = 0.023) and tendonitis (P = 0.007) at follow-up,
with no discernible difference in the prevalence of cutaneous or mucosal features as reported by Voulgari et al.
[26]. These differences may be somewhat biased by the
recruitment process, with Stefanidou et al. basing their
study on patients attending rheumatology or nephrology
clinics, and by both disease duration and study type. It is
interesting, however, that despite using a patient group
specifically recruited from nephrology outpatients, which
might be expected to result in an overall higher prevalence
of nephropathy, both Voulgari et al. (24.6% males) and
Stefanidou et al. (27.1% males) report rates of renal involvement much lower than many reported studies. In
terms of overall disease activity, assessed by the ECLAM
index, and damage, assessed by the SLICC/ACR index,
Voulgari et al. showed no significant gender difference.
Focusing on Western European populations, four additional studies have been published addressing gender
and SLE [16, 22, 25, 35]. Lopez et al. [35] examined the
demographic and immunological features of a homogeneous cohort of SLE patients. Females were more commonly anti-Ro antibody positive (P = 0.047) and younger
(P < 0.01) at diagnosis. In patients of similar ethnicity, Font
et al. [25] failed to show a significant difference in onset
age or serology, but demonstrated a lower incidence of
arthritis and malar rash at follow-up (P < 0.01), with
increased frequencies of discoid and subacute cutaneous
lupus (P < 0.03). No difference in the incidence of nephropathy was detected. In contrast, a report from a Danish
cohort described an increased incidence of nephropathy,
including end-stage renal failure. The prevalence of serositis was also higher and photosensitivity less. Again this
study used a recruitment approach that included nephrology outpatients, which must be borne in mind when interpreting these results [16].
UK populations, which are more ethnically diverse, are
represented in a study by Renau et al. [22] using a retrospective approach. In contrast to the above, a trend towards an increase in renal failure and death was noted in
females with SLE, with a significant increase in oral ulceration (P < 0.05) and IgM aCLs in women (P < 0.05).
While these studies vary considerably by design and
duration of follow-up and are open to many biases, including selection bias, no clear patterns of gender-specific
disease expression have emerged in European
populations.
The significant ethnic diversity of the US population
makes discerning the impact of gender, independent of
ethnicity, more difficult. This problem is further complicated by differences in age of onset between ethnic populations [36, 37], given the known modifying effect this has
on disease expression [38–40]. However, several large
studies have been reported that have attempted to
circumvent these issues and correct for the effect of ethnicity on disease expression.
Two recent cohorts have suggested that male patients
have an increase in renal disease independent of ethnicity
and age [14, 41]. Both used systematic follow-up and
included a large number of patients (618 and 1979 patients). Andrade et al. [41] correlated male gender with
reduced musculoskeletal symptoms and higher frequencies of LA antibodies. Tan et al. showed that men had
significantly increased disability, lymphopenia, thrombocytopenia and a spectrum of manifestations of renal disease (nephritic syndrome, proteinuria, haematuria, renal
insufficiency and failure) (P < 0.05) [14]. In addition to corroborating the lower risk of musculoskeletal involvement,
in the latter study men were protected from malar rash,
photosensitivity, oral ulcers, alopecia and RP (P < 0.05).
Serologically, in the Tan et al. study, men had a greater
prevalence of Coombs positivity, lupus anticoagulant, low
C3 anti-Sm, anti-dsDNA, anti-RNP and anti-La antibodies
than females (P < 0.05). These results are notably out of
line with any other study of male lupus. Both Tan et al. and
Andrade et al. also highlighted a potential association between gender and damage. Andrade et al. reported a
higher mean SDI in men at baseline and showed a positive
correlation between male sex and further damage accrual
[41]. Tan’s group showed evidence of increased neuropsychiatric, renal and cardiovascular damage in African
American and white males in comparison with females.
Interestingly, African American men were more likely
than Caucasians to have discoid lupus, alopecia, renal
involvement, anti-Sm antibodies and greater damage in
renal and cardiovascular domains. Looking specifically
at recently diagnosed disease (median duration from diagnosis to enrolment 13 months), the Carolina Lupus study
showed an increase in proteinuria and haematological
dyscrasias in men [42].
These data contrast notably with earlier studies that
failed to identify an association between gender and
renal disease. One of these studies included 2188 patients
identified through the US Veterans Administration database [20]. As would be expected, this cohort was significantly older than those in other studies. While no
difference in renal disease was observed, male patients
had higher rates of myocardial infarction and neoplasm.
Ward et al. [43] found that only an increased risk of seizures could be attributed to male gender, while Miller et al.
[6] associated serositis with male SLE and females had a
greater incidence of neurological involvement, thrombocytopenia and alopecia.
Clearly these studies have reported significantly differing results. It is of interest that it is the more recently
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Comparison of male and female SLE
performed studies that have suggested that renal disease
is more prevalent in men, even after adjusting for ethnicity.
Whether this truly reflects better detection or whether it is
the result of selection, referral bias or differences in other
demographic details is unclear.
Latin America
There have been two large studies examining the question
of disparate clinical phenotypes in men with lupus in Latin
America [17, 21]. The first, a multicentre study (GLADEL
cohort), found that men were significantly more likely to
experience constitutional symptoms, e.g. fever and
weight loss, in addition to having more cardiovascular disease (hypertension), proteinuria, cellular casts and haemolytic anaemia (P < 0.05) [17]. There was a nonsignificant
trend towards a higher frequency of glomerulonephritis
and no difference in the incidence of nephrotic syndrome
or serositis. Women, on the other hand, suffered from more
alopecia, photosensitivity, arthralgia and RP. Serologically
only IgG aCLs and low C3 demonstrated any gender predilection (more common in men). Despite 68% of male patients having aCLs, there was no significant increase in
vascular thromboses. Importantly, no significant difference
in the objective assessments of disease activity (SLEDAI
index), damage (SLICC index) or mortality was detected
following adjustment for confounders.
Interestingly, an earlier cross-sectional study also found
an elevated incidence of renal disease in male SLE patients (58% vs 44%) and suggested an increase in vascular thrombosis and protection from RP (P < 0.03) [21].
While no difference in the prevalence of IgG aCLs was
detectable in this cohort, they found that anti-dsDNA antibodies appeared to be more prevalent in the male subgroup (P = 0.002) [21].
Renal involvement
The presence of LN impacts significantly on prognosis in
SLE. Underrecognition or delayed treatment may increase
the risk of chronic kidney disease and careful screening
for early nephritis/nephropathy is essential. A number of
studies have reported an increased incidence of renal disease in men with SLE [14, 21]. However, a greater number
of studies have failed to support this.
The prevalence of renal disease varies widely among
studies and may depend on the definition of renal involvement used. While a number of groups from different geographic regions have shown that male subjects had an
increased incidence of proteinuria [14, 17], cellular casts
or renal insufficiency (elevated serum creatinine) [14, 17],
this was not associated with an increase in end-stage
renal failure or patients requiring transplantation. Indeed,
only two studies were able to demonstrate an increase in
renal failure in male subjects [14, 16]. Interestingly, there is
no evidence to suggest a predilection for any particular
histological class of LN in males [23]. Moreover, the use of
cytotoxics, commonly required to treat LN, has not been
shown to associate with male gender.
De Carvalho et al. [44] specifically addressed the question of gender outcomes in LN and found no increase in
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mortality in men with LN. While they found no genderspecific pattern of histological class, male patients had
higher activity scores and higher serum creatinine. No difference was detectable in histological chronicity scores
or in the requirement for dialysis/transplantation. More
recently, Wang et al. [45] reported that Chinese males
had significantly lower ratios of complete and partial remission and had higher serum creatinine. However, using
multivariate analysis, male gender was not found to be
associated with an adverse renal outcome.
The association between male gender and nephropathy
in SLE remains tenuous at best. There is limited evidence
from many geographic regions, perhaps most consistently
in Latin America and more recently in the USA, to suggest
a weak association. It is known that multiple other confounding factors such as hypertension (known to be
increased in males), ethnicity and onset age also influence
renal disease and not all studies make the appropriate
statistical adjustment to account for such variables.
Morbidity/mortality
Life expectancy of patients with SLE is reduced in comparison with that of an age-matched general population
[46]. The suggestion by some that a number of aspects of
disease thought to carry a worse prognosis, notably renal
disease, are amplified in men might suggest that mortality
rates would be increased in men with SLE.
Interestingly among those studies that have addressed
this outcome measure, the most consistent finding is that
the overall mortality rates in men are comparable to those
in women. Of the studies that have addressed mortality
rates, four found no difference overall between male and
female patients [17, 21, 22, 44] and three suggested an
increase in mortality in male patients [14, 20, 45]. Tan et al.
[14] showed that the mortality rate was significantly elevated in male lupus patients, with a mortality rate of
11.5% in comparison with 6.2% in the female cohort.
Prete et al. [20] also found an elevated mortality rate in
males, but only within the first year after diagnosis. It
should be highlighted that the latter study of the US veteran population included an older population, and the
male cohort was significantly older than the female
cohort. Specifically men had increased rates of myocardial infarction and neoplasia [20]. Finally, Wang et al. [45]
reported higher rates of mortality in men with LN; however, this study had a small number of male subjects,
which limits its power to detect a statistically relevant
effect. The causes of death outlined in both these and
other studies, which did not detect a difference by
gender, included both SLE-specific and other causes.
The low overall numbers do not permit a conclusive analysis of whether SLE-specific mortality is more associated
with male gender and this needs to be addressed in prospective cohorts of greater duration.
Given the magnified cardiovascular risk recognized in
SLE patients [47], it is an interesting variable to study as it
may confer an increased risk over a longer time frame
than may be captured within current studies. Many use
the term cardiovascular disease as an all-embracing term
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to encompass a spectrum of disease from arterial hypertension to angina/myocardial infarction. A number of
studies have shown that cardiovascular disease is amplified in men with SLE [16]. In particular, in a few studies
male gender has been associated with greater hypertension [14, 16, 21], angina, MI and even CVA [24] in early
disease. Whether this reflects the general enhanced cardiovascular risk in the male population or is further magnified by the inflammatory state of SLE in men is unknown.
Previous evidence also emphasizes the importance of
capturing information on SLE-related damage as a prognostic indicator, with elevated damage scores associated
with greater mortality [48]. Of the many studies that have
included information on damage, only one showed an association between male gender and damage at baseline,
with a shorter time to accrual of further damage [41].
Certainly the evidence from research to date is that despite the suggestion of greater frequencies of particular
organ involvement in male subjects of certain ethnicities,
this is not reflected in the limited information on mortality
and morbidity captured by the SLICC index.
clinical characteristics may be differentially expressed
(Table 1 presents a summary of clinical and demographic
findings from main studies summarized in Table 2). There
is consistent evidence for a reduced incidence of RP, alopecia, malar rash and arthralgia/arthritis in men at presentation and in the subsequent disease course. In
contrast, it cannot be reliably said that there is a definite
increased incidence of nephropathy, thrombotic episodes, damage or, most importantly, a greater mortality
risk. Prognostically it appears evident from the available
literature that disease severity in male lupus is little different overall than in female patients.
There is no doubt that males are protected, in incidence, from SLE, and this has been ascribed to many
things. In particular, the role of oestrogen and other gonadal hormones in the alteration of immune cell function
has been explored [49–52]. Other alternate theories
abound, including an X-chromosome hypothesis (as supported by the increased incidence of SLE in patients
with Klinefelter’s syndrome) [53], various somatic genetic
polymorphisms [54] and disparities within the Toll-like receptor and interferon pathway [55, 56]. Interestingly,
despite the strong evidence implicating sex hormones in
SLE pathogenesis, there is limited evidence to suggest
an altered hormonal milieu in men with lupus [57, 58].
While some have documented biochemical hypoandrogenism in this cohort [59], this is complicated by concomitant corticosteroid therapy, which can have a similar
effect [60]. While it may be a contributing factor, more
work is required to clarify the true reasons for the protection of the male gender from SLE.
Discussion
The debate as to whether there truly is a different disease
course in men with SLE has continued. Complicated by
low patient numbers, studies that fail to correct for differences in disease duration, ethnicity, co-morbidities or
that have potential selection bias may lead to a
skewed representation of the clinical phenotype in men.
Nonetheless there are suggestions that a number of
TABLE 1 Summary of studies that have found differences in organ involvement between male and female patients with
SLE
Increased in men
Musculoskeletal
Photosensitivity
Malar rash
RP
Discoid lesions
Oral ulcers
Alopecia
Any renal disease
CNS disease
Serositis
Thrombocytopenia
Disease activity
[19]
Decreased in men
[14,
[14,
[14,
[14,
Comment
17, 18, 24, 25, 32, 40]
17, 19, 24, 26]
25]
17, 19, 18, 21, 23, 24, 26]
[23, 25, 33]
[14, 22, 26]
[6, 14, 17, 18, 19, 23, 24]
[14, 16,17, 18, 21, 41]
[42]a
[6, 16, 19, 26]
[14, 18, 41]
Damage
[14, 40] (baseline)
Mortality
Thromboses
GI
Cardiovascular
Other
[14, 20, 44]
[14, 21, 24]
[24]
[14,16, 17, 24] (CVA)
[17] (constitutional symptoms)
[6]
[6, 26]
Recorded in five other studies. No
change in [17, 23, 26, 40, 43]
Recorded in three other studies
with no significant effect of
gender [17, 23, 26]
No change in [17, 21, 22, 43]
Flares/severe flares [23]
The results depict studies where significant (P < 0.05) differences were detected. aSeizures.
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Comparison of male and female SLE
TABLE 2 Summary of main clinical and demographic findings of comparative studies of male and female lupus
Gender-specific clinical features
(P < 0.05)
Country (ethnicity)
Study type
Size (%
male)
Age at
onset
Features
increased
in men
Features
increased
in women
Musculoskeletal
Serology
US (multi-ethnic) [40]
Prospective
cohort
618
(10.2)
37.1 (M),
36.5 (F)
Renal
LAC (M)
US (multi-ethnic) [41]
Case control
265
(9)
NA
Proteinuria,
lymphopenia,
# platelets
Greek [26]
Retrospective
580
(14)
34.6 (M),
31.4 (F)
Photosensitivity,
RP,
oral ulcers,
anaemia
Asian [32]
Retrospective
147
(41.5)
28.2 (M),
NA (F)
Arthritis,
leucopenia
Anti-Ro
(F)
UK (multi-ethnic) [22]
Retrospective
484
(9.3)
30.9 (M),
29.1 (F)
Oral ulcers
IgM aCL
(F)
Latin America [17]
Inception cohort
1213
(10.1)
27 (M),
29.2 (F)
Constitutional
symptoms,
proteinuria,
any renal,
haemolytic
anaemia
Arthralgia,
alopecia,
photosensitivity,
RP,
any cutaneous
Low C3,
RP
dsDNA (M)
6 antibodies
assayed,
P > 0.05
Latin America [21]
Cross-sectional
1316
(8.1)
26 (M),
28 (F)
Renal
Thai (Asian) [18]
Retrospective
case–control
111
(33.3)
34.6 (M),
34.4 (F)
# Platelets,
Alopecia,
" serum creatinine arthralgia,
RP,
psychosis
Oriental [23]
Retrospective
control
252
(20.2)
31 (M),
31.9 (F)
Danish [45]
Retrospective
513
(11.5)
46.2 (M),
36.2 (F)
Serositis,
nephropathy,
hypertension
Greek [24]
Retrospective
743
(7.9)
34 (M),
31 (F)
Nephropathy,
tendonitis,
myositis
Spanish [25]
Prospective
261
(11.5)
34 (M),
31 (F)
US (multi-ethnic) [14]
Retrospective
1979
(7.9)
US [6]
Prospective
control
US [27]
Inception
IgG aCL
(M)
7 antibodies
assayed,
P > 0.05
RP,
alopecia
Anti-Ro
(F)
Photosensitivity
3 antibodies
assayed,
P > 0.05
Discoid LE,
subacute
cutaneous LE
Arthritis,
malar rash
6 antibodies
assayed,
P > 0.05
49.8 (M),
37.6 (F)
Hypertension,
renal disease,
thrombotic
episode,
hypertension,
disability,
lymphopenia
Malar rash,
photosensitivity,
oral ulcers,
alopecia,
RP,
arthralgia
Anti-Sm,
DAT,
LAC,
antidsDNA,
low C3
(M)
100
(50)
45 (M),
44 (F)
Serositis
Neurological,
alopecia,
# platelets
361
(17.2)
44.7 (M),
35.2 (F)
Seizures
Findings with a significant difference between genders are reported (P < 0.05). Not all studies report figures adjusted for
multiple comparisons. DAT: direct antiglobulin test; F: female; LAC: lupus anticoagulant; M: male; NA: not applicable.
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Conclusion
Despite the suggestion by many that men with lupus demonstrate a distinct disease profile and a more aggressive
disease course, notably of LN, this has not been consistently found in the literature and has not translated into
significant differences in objective indices of disease
activity, damage or mortality. While some of the more typical mucocutaneous features of SLE appear to affect
females preferentially, the frequency of such manifestations varies widely between studies and still remains
the most prevalent of lupus manifestations in men.
Moreover, certain lupus features, such as thrombocytopenia and neurological involvement, have been shown by
some to be more prevalent and others to be reduced in
male lupus sufferers. Too few studies have consistently
provided evidence for correction of the effect of notable
confounders, such as ethnicity, duration of follow-up, age
of onset and comorbidites, or indeed for multiple comparisons that would likely alter the significance of studies with
weaker results. It is evident that a clear gender effect on
SLE phenotype remains elusive.
Rheumatology key messages
The age of onset is similar in male and female
patients with lupus.
. Men with lupus display decreased musculoskeletal
symptoms, photosensitivity, oral ulcers and RP than
women.
. There is no clear association between gender and
mortality or disease activity in SLE.
.
Disclosure statement: The authors have declared no
conflicts of interest.
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