Many studies have suggested that late-onset lupus patients differ from those with early onset disease in their clinical presentation, pattern of organ involvement, and the severity of their disease.
Usually, the disease starts insidiously with the first clini- cal manifestations being vague. Arthralgias, myalgias, weak- ness, fatigue, fever, and weight loss are the most common initial clinical manifestations [4, 22]. More specific clinical features, such as malar rash [18, 20, 22] and other mucocuta- neous manifestations [15], arthritis [6, 18], and nephritis [15, 18], are less frequent at disease onset. Furthermore, the num- ber of the American College of Rheumatology criteria for the classification of SLE [26, 27] are usually fewer compared to those patients with earlier onset disease [10, 12]. These nonspecific signs and symptoms as well as the presence of other musculoskeletal, endocrine, and metabolic comorbidi- ties [12] can pose diagnostic problems. Indeed, the diagnosis of SLE in many of these older patients is delayed up to sev- eral years and established only after an extensive clinical evaluation and laboratory work-up is performed. This diag- nostic delay varies in different reports, but ranges from 1 to 5 years [4, 5, 10, 13, 15, 16, 21, 24, 25, 28, 29].
Table 15.2 [4–7, 10, 12–14, 16–24, 28–35] summarizes studies in which a comparison between the different clinical manifestations present in patients with late-onset lupus and those with earlier onset disease was performed. According to the meta-analysis by Ward and Polisson [9] patients with late-onset lupus have a lower frequency of mucocutaneous manifestations, including malar rash, photosensitivity, alope- cia and cutaneous vasculitis. They also tend to have Raynaud’s phenomenon, lymphadenopathy, renal and neuropsychiatric
Table 15.1 Frequency of late-onset lupus a
Authors and year of publication Country of origin Study type
Total number of
patients studied Frequency (%)
Dimant et al. (1979) [19]b USA Longitudinal cohort 234 7
Baker et al. (1979) [13] USA Medical records review 258 12
Catoggio et al. (1984) [4]c UK Longitudinal cohort 71 18
Shaikh and Wang (1985) [16] Malaysia Medical records review 425 4
Font et al. (1991) [6] Spain Longitudinal cohort 250 16
Costallat and Coimbra (1994) [14] Brazil Medical records review 272 4
Mak et al. (1998) [5] Hong Kong Medical records review 102 13
Formiga et al. (1999) [15] Spain Medical records review 100 12
Voulgari et al. (2002) [7]c Greece Medical records review 489 18
Mok et al. (2005) [17] Hong Kong Longitudinal cohortd 285 8
Bertoli et al. (2006) [12] USA Nested case-control study
within a longitudinal cohort
217 12
Lalani et al. (2010) [18] Canada Cross-sectional 1,528 11
a Defined as age ³50 years, except as noted
b ³51 years of age
c³55 and older
d New-onset disease
137 15 Systemic Lupus Erythematosus in Elderly Populations
Table 15.2 Disease manifestations in late-onset lupusa Authors and year
of publication
Country
of origin Ethnic group Study type
Total number of patients
studied Salient findings Dimant et al.
(1979) [19]
USA Caucasian and African American b
Longitudinal cohort
234 Lower frequency of oral ulcers, Raynaud’s phenomenon, cutaneous vasculitis, neuropsychiatric manifestations, leucopenia, and proteinuria; higher frequency of discoid lupus, photosensitivity and pulmonary fibrosis
Baker et al.
(1979) [13]
USA Caucasian
and African Americanb
Medical records review
258 Lower frequency of lymphadenopathy, Raynaud’s phenomenon, neuropsychiatric manifestations, alopecia, and skin rash;
higher frequency of pulmonary manifestations
Wilson et al.
(1981) [30]
USA Caucasian
and African Americanb
Longitudinal cohort
66 Lower frequency of significant renal involve- ment, pleuropericarditis, and arthritis Ballou et al.
(1982) [28]
USA Caucasian
and African Americanc
Medical records review
138 Similar frequency of major clinical manifesta- tions, including renal, central nervous system, and cutaneous manifestations. Older patients were less likely to be African American
Gossat and Walls (1982) [32]
Australia Caucasianb Medical records review
14c Lower frequency of serositis and thrombocy- topenia; higher frequency of neuropsychiat- ric manifestations and constitutional complaints, such as fever, weight loss, and malaise
Catoggio et al.
(1984) [4]
UK Caucasianb Longitudinal
cohort
71 Lower frequency of arthritis; higher frequency of interstitial lung disease
McDonald et al.
(1984) [33]
UK Caucasianb Longitudinal
cohort
10c High frequency of neurologic manifestations Hochberg et al.
(1985) [31]
USA Caucasian
and African American
Medical records review
150 Caucasian patients had lower frequency of nephritis and higher frequency of Sjögren’s syndrome. Insufficient data on African Americans
Font et al.
(1991) [6]
Spain Caucasianb Longitudinal
cohort
250 Lower frequency of arthritis, malar rash, photosensitivity, and renal involvement;
higher frequency of myositis Takayasu et al.
(1992) [34]
Brazil Admixedb Medical records
review
199 Lower frequency of cutaneous manifestations and alopecia; higher frequency of muscular involvement
Costallat and Coimbra (1994) [14]
Brazil White and non-White
Medical records review
272 Lower frequency of nephrotic syndrome; higher frequency of pericarditis
Koh and Boey (1994) [29]
Singapore Asian (Chinese) and Caucasian
Medical records review
76 Higher frequency of peripheral neuropathy, myalgia and pancytopenia
Shaikh and Wang (1995) [16]
Malaysia Asian (Malay) Medical records review
425 Lower frequency of renal central nervous system involvement; and of relapses higher frequency of pulmonary involvement;
higher proportion of males Ho et al. (1998)
[22]
Hong Kong Asian (Chinese) Medical records review (Case- control study)
125 Lower frequency of major organ involvement;
and of major relapses Mak et al. (1998)
[5]
Hong Kong Asian (Chinese) Medical records review
102 Lower frequency of cutaneous manifestations;
higher frequency of serositis; similar frequency of major organ involvement Pu et al. (2000)
[21]
Taiwan Asian (Chinese) Medical records review (Case- control study)
194 Lower frequency of malar rash; higher frequency of discoid rash
Voulgari et al.
(2002) [7]
Greece Caucasiansb Medical records review
489 Lower frequency of malar rash
(continued)
Table 15.2 (continued) Authors and year of publication
Country
of origin Ethnic group Study type
Total number of patients
studied Salient findings Boddaert et al.
(2004) [10]
France Caucasian, African and Asian (Indian)
Medical records review (Case- control study)
161 Lower frequency of arthritis, malar rash and renal involvement
Sayarlioglu et al.
(2005) [24]
Turkey Caucasianb Medical records review
120 Similar clinical manifestations; lower frequency of fever; higher frequency of pulmonary fibrosis
Mok et al.
(2005) [17]
Hong Kong Asian (Chinese) Longitudinal cohort
285 Lower frequency of malar rash and photosensi- tivity; higher frequency of Raynaud’s phenomenon
Bertoli et al.
(2006) [12]
USA Caucasian, African American and Hispanic
Nested case-control study within a longitudinal cohort
217 Lower frequency of renal involvement; higher frequency of neurological involvement and vascular events
Padovan et al.
(2007) [35]
Italy Caucasian Longitudinal
cohort
255 Higher frequency of peripheral neuropathy Mak et al.
(2007) [23]
Hong Kong Asian (Chinese) Medical records review
287 Similar frequency of renal involvement Appenzeller et al.
(2008) [20] Brazil African Americans
and Caucasian Nested case-control
study 76 Lower frequency of arthritis, malar rash; higher frequency of hemolytic anemia and thrombocytopenia
Lalani et al.
(2010) [18]
Canada Caucasian, Asian, African- American, Native American, Hispanic, Jewish and Middle Eastern.
Cross-sectional 1,528 Lower frequency of renal involvement, malar rash, neurologic, hematologic, and immunologic manifestations
a Compared with younger-onset disease patients
b Assumed
c Number is for late-onset patients only
involvement less frequently. On the contrary, serositis, pulmonary involvement (particularly interstitial lung dis- ease), and Sjögren’s syndrome are more frequently found in this patient group. Although the published data may be influ- enced by selection and confounding biases as well as by the demographic characteristics of the patients studied, there is the overall sense that late-onset lupus patients have less major organ involvement, particularly renal involvement [6, 10, 12, 16, 18, 30, 31]. Disease relapses have also been found to be less frequent in these patients [16, 18, 22].
Late-onset lupus patients also seem to display a distinct autoantibody profile. As depicted in Table 15.3 [4–6, 10, 12, 14–22, 24, 28–30, 34–38], anti-DNA [6, 10, 15, 30], anti- RNP [4, 10, 36], and anti-Smith antibodies are found with low frequency in this patient group [12, 14, 36, 37], whereas rheumatoid factor [22, 25, 30, 36] and anti-Ro and anti-La antibodies tend to be positive more frequently [4, 5, 9, 14, 20]. The increased frequency of these antibodies may relate to the higher frequency of secondary Sjögren’s syndrome
reported in this patient group [9, 31, 39, 40]. Late-onset lupus patients also have hypocomplementemia less frequently, albeit not consistently compared to younger lupus patients [9, 15, 16, 19, 28–30, 36] which is not surprising given their less severe disease manifestations.
Because of the slow disease onset and, oftentimes, non- specific manifestations earlier in the course of the disease, late-onset lupus can be misdiagnosed. The differential diag- nosis [41] includes other inflammatory rheumatic diseases, such as rheumatoid arthritis, polymyalgia rheumatica, and different vasculitides. Other nonrheumatic entities, such as infections and malignancies, should also be ruled out. Given that elderly patients usually have a number of comorbid conditions for which pharmacological therapy is frequently required, the differential diagnosis should also include drug-induced lupus. The latter has many features in com- mon with SLE but characteristically develops in individuals who have no history of systemic autoimmune disease. The syndrome is characterized by the presence of arthralgias,
139 15 Systemic Lupus Erythematosus in Elderly Populations
Table 15.3 Serologic findings in late-onset lupusa Author and year of
publication Country of origin Study type
Total number of
patients studied Serologic findings
Dimant et al. (1979) [19] USA Longitudinal cohort 234 Lower frequency of
hypocomplementemia
Wilson et al. (1981) [30] USA Longitudinal cohort 66 Lower frequency of anti-DNA
antibodies and hypocomplement- emia; higher frequency of rheumatoid factor
Ballou et al. (1982) [28] USA Medical records review 138 Lower frequency of hypocomplement-
emiaSimilar frequency of anti-DNA antibodies
Catoggio et al. (1984) [4] UK Medical records review 71 Lower frequency of anti-RNP
antibodies; higher frequency of anti-Ro and anti-La antibodies
Maddison (1987) [36] UK Medical records review 112 Higher frequency of anti-La and
anti-Ro antibodies
Font et al. (1991) [6] Spain Longitudinal cohort 250 Lower frequency of anti-Ro antibodies
and high titers of anti-DNA antibodies; higher frequency of antiphospholipid antibodies Takayasu et al. (1992) [34] Brazil Medical records review 199 Similar frequency of positive auto-
antibodies Domenech et al. (1992)
[38]
UK Medical records review 247 Lower frequency of anti-DNA
antibodies
Cervera et al. (1993) [37] Spain Longitudinal cohort 1,000 Higher frequency of anti-DNA antibodies and rheumatoid factor;
lower frequency of other antibodies
Koh and Boey (1994) [29] Singapore Medical records review 76 Similar frequency of positive auto-antibodies; higher frequency of hypocomplementemia Costallat and Coimbra
(1994) [14]
Brazil Medical records review 272 Higher frequency of anti-DNA and
anti-Ro antibodies but lower frequencies of other antibodies Shaikh and Wang (1995)
[16]
Malaysia Medical records review 425 Lower frequency of positive
autoantibodies and hypocomplementemia
Mak et al. (1998) [5] Hong Kong Medical records review 102 Lower frequency of hypocomplement- emia; higher frequency of anti-La antibodies
Ho et al. (1998) [22] Hong Kong Medical records review 125 Higher frequency of anti-DNA and anti-Ro antibodies and of rheumatoid factor Formiga et al. (1999) [15] Spain Medical records review
(case-control study)
100 Lower frequency of anti-DNA
antibodies and hypocomplementemia
Pu et al. (2000) [21] Taiwan Medical records review 194 Similar frequency of antinuclear and anti-DNA antibodies and hypocomplementemia Boddaert et al. (2004) [10] France Medical records review
(case-control study)
161 Increased frequency of rheumatoid factor; lower frequency of anti-RNP, and anti-Sm antibodies;
lower levels of CH50 Sayarlioglu et al. (2005)
[24]
Turkey Medical records review 120 Similar autoantibody profile
Mok et al. (2005) [17] Hong Kong Longitudinal cohort 285 Similar autoantibody profile
Bertoli et al. (2006) [12] USA Nested case-control study within a longitudinal cohort
217 Lower frequency of anti-Smith antibodies
Padovan et al. (2007) [35] Italy Longitudinal cohort 255 Higher frequency of anti-DNA
antibodies and rheumatoid factor (continued)
Table 15.3 (continued) Author and year of
publication Country of origin Study type
Total number of
patients studied Serologic findings Appenzeller et al. (2008)
[20]
Brazil Nested case-control
study
76 Similar frequency of ANA; higher prevalence of anti SSA/Ro
Lalani et al. (2010) [18] Canada Cross-sectional 1,528 Lower frequency of anti-RNP,
anti-Sm antibodies and hypoco- mplementemiaSimilar frequency of anti-DNA antibodies
a Compared to younger-onset disease patients
myalgias, pleurisy, rash, and fever in association with the presence of antinuclear antibodies; central nervous system and renal involvement are rare. Although antinuclear anti- bodies occur in the majority of these patients, anti-double stranded DNA antibodies are rare [25]; the typical finding includes the presence of antihistone antibodies, which may be present in up to 95% of patients [42]. The absence of antinuclear antibodies should not preclude the diagnosis of drug-induced lupus; in these cases, the resolution of symp- toms within weeks (or months) of discontinuation of the offending drug is of particular value in the diagnosis of this condition [43]. Since first recognized almost 50 years ago in association with hydralazine therapy [44], numerous medi- cations have been added to the list of drugs associated with the induction of lupus. Depending mostly in the number of cases reported, such associations range from weak (only few cases reported) to strong (procainamide, hydralazine) [45, 46]. Typically, drug-induced lupus does not require specific treatment as the clinical and serological manifesta- tions of this condition usually subside once the suspected drug is discontinued [25].