Saudi Journal of Kidney Diseases and Transplantation

RENAL DATA FROM THE ARAB WORLD
Year
: 2008  |  Volume : 19  |  Issue : 6  |  Page : 1001--1008

Clinical and immunological manifestations of systemic lupus erythematosus: A study on 146 south Tunisian patients


Moez Jallouli1, Makram Frigui1, Mohamed Ben Hmida2, Sameh Marzouk1, Neila Kaddour1, Zouheir Bahloul1,  
1 Department of Internal Medicine, Hedi Chaker University Hospital, Sfax, Tunisia
2 Department of Nephrology, Hedi Chaker University Hospital, Sfax, Tunisia

Correspondence Address:
Moez Jallouli
Department of Internal Medicine, Hedi Chaker University Hospital, Sfax
Tunisia

Abstract

The objective of this study was to determine the main clinical and laboratory features as well as the morbidity and mortality of systemic lupus erythematosus (SLE) in a population of patients predominantly from the south of Tunisia. A retrospective review of a well documented population of 146 patients with SLE was undertaken. All patients fulfilled four or more criteria defined by the American College of Rheumatology. The mean age at presentation was 29.2 years (range 6-55) and the mean duration of follow-up was 62 months (range 0.25-374). Musculoskeletal (84.2%) and mucocutaneous (75.3%) were the most frequent clinical mani­festations. Antinuclear antibodies were detected in 97.3%, anti-DNA antibodies in 69.2% and anti-Sm in 39.2% of the patients. Anti-cardiolipin antibodies and lupus anticoagulant were ob­served respectively in 71.6% and 37.8% of the patients. The five-year survival rate in our series was 92%. Renal involvement and thrombocytopenia were associated with poor prognosis (p< 0.05). The clinical and immunological characteristics of our SLE patients are largely comparable to most major studies. Main differences included prominent major organ damage and high pre­valence of anti-Sm and anti-cardiolipin antibodies.



How to cite this article:
Jallouli M, Frigui M, Hmida MB, Marzouk S, Kaddour N, Bahloul Z. Clinical and immunological manifestations of systemic lupus erythematosus: A study on 146 south Tunisian patients.Saudi J Kidney Dis Transpl 2008;19:1001-1008


How to cite this URL:
Jallouli M, Frigui M, Hmida MB, Marzouk S, Kaddour N, Bahloul Z. Clinical and immunological manifestations of systemic lupus erythematosus: A study on 146 south Tunisian patients. Saudi J Kidney Dis Transpl [serial online] 2008 [cited 2021 Jan 16 ];19:1001-1008
Available from: https://www.sjkdt.org/text.asp?2008/19/6/1001/43484


Full Text

 Introduction



Systemic lupus erythematosus (SLE) is a multi­system autoimmune disease of unknown etio­logy characterized by the production of non­organ-specific autoantibodies directed to nuc­lear, cytoplasmic and cell surface antigens, which may lead to a wide range of tissue in­juries. The prevalence of clinical and immuno­logic manifestations varies significantly among different ethnic and geographical groups. Des­pite a large number of published reports, clini­cal and laboratory features are still an interes­ting matter of study, as there are important discrepancies. Few studies have been conducted on North Africans and Tunisians, in particular. In the current report; we present the main epidemiological, clinical and immunological features in a population essentially from the south of Tunisia. In addition, this investigation was meant to study the predictors of renal and neuropsychiatric involvement and to determine the impact of demographic factors, clinical manifestations, disease activity and serologic tests on survival.

 Patients and Methods



The patients included in this study were those attending the Department of Internal Medicine at the Hedi Chaker University Hospital, Sfax, Tunisia, from January 1996 to June 2006. All patients fulfilled four or more criteria for the diagnosis of SLE as defined by the American College of Rheumatology. Conventionally, the patients were seen at four monthly intervals. At each visit, the patient's history was re­viewed in addition to physical examination and routine laboratory tests.

The following data were collected: age, gender, age at onset of disease (defined as age at which the patient developed initial mani­festation(s) attributable to SLE) and age at diagnosis of SLE. The main clinical mani­festations were defined as described by the American Rheumatism Association glossary committee. Kidney biopsy results were docu­mented according to the World Health Orga­nization (WHO) classification system. Anti­nuclear antibodies (ANA) were evaluated by indirect immunofluorescence (IF) technique using either mouse liver or Hep-2 cells. Anti­DNA antibodies were assayed by IF using Crithidia luciliae as substrate and by enzyme linked immunosorbent assay (ELISA) if IF was negative. Anti-nucleosome antibodies and anti-extractible nuclear antigen antibodies (or anti-ENA: anti-Sm, anti-RNP, anti-SSA and anti-SSB) were detected by immunodot. Anti­cardiolipin antibodies were assessed by a stan­dardized ELISA technique. Complement and rheumatoid factor were assessed by nephe­lometry.

A descriptive analysis was performed with the aid of the SPSS program to analyze the frequency of the clinical manifestations, im­munological findings, and requirement of pharmacologic treatment during the course of disease. Qualitative differences between sub­groups were analyzed with the Chi-Square and Fisher Exact Test. The Student t-test was used to evaluate means with equal and unequal variance of the study variables. The signi­ficance level (p = 0.003), arterial hypertension (p = 0.006), pleurisy (0.05) and leukopenia (0.009). In a multivariate ana­lysis, thrombocytopenia, decreased C3 level, hypertension and pleural effusion remained significant factors for the development of active renal disease.

A past or present neurological manifestation was observed in 28 cases (19.2%), mainly in the form of generalized tonic-clonic seizures, noted in 20 patients (13.7 %). Peripheral neu­ropathy occurred in four patients (2.75%). Comparison between patients with and without neurological manifestations showed that oral ulcerations (p = 0.003), pericarditis (p = 0.024), Raynaud's phenomenon (p = 0.037), thrombo­cytopenia (p = 0.003) and/or decreased C3 level (p = 0.017) were more commonly ob­served in patients with neurological manifes­tations. Of these variables, thrombocytopenia, pericarditis and oral ulcerations remained significant multivariate factors. Psychiatric features occurred in 26 patients (17.8%); they occurred before steroid therapy in nine pa­tients. The psychiatric manifestations essen­tially included depression (10 cases), acute confusional state (8 cases) and psychosis (6 cases).

A conventional magnetic resonance imaging scan performed in 30 patients was abnormal in 13 cases (43.3%). Cortical atrophy and small white matter hyperintensities were the most common findings (6 cases each).

Hematological manifestations (87%) were common in our series and included anemia in 78.75%, leukopenia in 47.9 %, lymphopenia in 47.3% and thrombocytopenia in 24.7% of the patients. Lymphadenopathy was observed in 34 patients (23.3%) and splenomegaly in 15 (10.3%).

Laboratory findings are presented in [Table 2]. Positive ANA were present in 97.3% of pa­tients, anti-DNA antibodies in 69.2%, anti-Sm antibodies in 39.2%, anti-cardiolipin antibodies in 71.6% and lupus anticoagulant in 37.8%. Fourteen patients (9.6%) met the diagnostic criteria for antiphospholipid syndrome. Anti­Sm antibodies were significantly associated with Raynaud's phenomenon (p = 0.027) and the presence of anti-RNP antibodies (p p = 0.039).

After the diagnosis of SLE, 24 pregnancies in 15 women were followed-up. Nine women had only one pregnancy, three had two and three others had three pregnancies. The mean dura­tion of the disease before the onset of the first pregnancy was 56 months (range 9-132). Among the 24 pregnancies, 12 (50%) resulted in live births, seven (29.15%) in therapeutic abortion and five (20.8%) in spontaneous abortion.

At some stage of the disease, anti-malarial drugs and steroids were added respectively in 87.8% and 94.5% of our patients. High-dose steroid treatment was administered to 111 patients (76%). In addition, intravenous pulse cyclophosphamide was required in 39 cases (26.7%), the main indication being prolife­rative GN (87.2%). Only one patient received treatment with mycophenolate mofetil.

The mean duration of follow-up was 62 months (range 0.25-374). Complete clinical, biological and immunological remission was obtained in 15 cases (10.2%). Sixty-one pa­tients (41.8%) relapsed in an average time of 30 months. Fatality occurred in 11 cases. Nine patients died within five years after the diag­nosis of SLE was made. The cause of death included florid SLE (4 cases), infections (4 cases), complications of renal biopsy (2 cases) and pulmonary hypertension secondary to an associated systemic scleroderma (1 case). Re­nal involvement (p = 0.02), [nephrotic syn­drome (p = 0.04), raised creatinine (p = 0.02)], thrombocytopenia (p = 0.02) and the presence of anti-cardiolipin antibodies (p = 0.05) were associated with poor prognosis.

Sixty-six patients (45.2%) developed 169 infections during the study period (range 1- 11). The mean interval between the occurrence of infection and the diagnosis of SLE was 29 months (range 0-166 months). Infection in­volved the urinary tract (51 infections), the skin (30 infections) and the lung (17 infec­tions). Severe infections (18%) were observed in 29 patients (20%).

 Discussion



Important differences in clinical and immu­nological manifestations of SLE have been reported among various ethnic groups. Two previous studies on SLE in the Tunisian popu­lation have been reported earlier. [1],[12] Our series involved patients predominantly from the south of Tunisia.

As seen in our patients' records, SLE is generally a disease of patients in their third decade. The sex ratio in our series confirms the well-known female predominance in SLE. However, this ratio is different from that reported from Europe (10:1), [13] Japan (11:1) [4] or the United States (10:1). [5] The reason for this discrepancy was not obvious.

The frequency of major clinical and sero­logical manifestations in our patients, in com­parison to those of other populations is shown in [Table 3]. Articular and cutaneous manifes­tations were the most common clinical symp­toms in our patients as well as in the other reported series. Oral ulcers (19.2%) were seen more often when compared with patients in North Tunisia (4%). [1] However, the frequency was similar to that seen in the European, [3] African [6],[7] and Southeast American [5] cohorts (17-24%).

The prevalence of renal involvement in our study (59%) is among the highest reported, particularly when compared to the 39% preva­lence reported from the European population. [3] This frequency is lower than that reported from India (73%), [8] Senegal (74%) [7] or Curacao (78%). [9] Our renal biopsy findings were similar to that seen in studies reported by Cameron (72.5%), [10] Mery (68%) [11] and Le Thi Huong (54%). [12] We found that thrombocytopenia and arterial hypertension were significant predic­tors of the occurrence of lupus nephritis. Similar findings have been reported in the literature. [1],[12],[13],[14],[15] Although several previous stu­dies showed that renal involvement correlated with the presence of anti-DNA anti-bodies, [16],[17] we did not find any such association.

There is a major variation in the reported prevalence of patients with neuropsychiatric syndromes in association with SLE; they range from 18 to 69% in the literature. [18] Our cohort study included 42 patients with neuropsychia­tric manifestations. This was comparable with the populations from Europe (27%), [3] northern Tunisia (25%), [1] Senegal (32%), [7] South Ame­rica (26.35%), [19] Saudi Arabia (25.3%) [20] and India (28%). [21] In our study, the main risk fac­tors for the development of significant neuro­logical manifestations were pericarditis, oral ulcerations and thrombocytopenia. This is con­sistent with the results of Feinglass, [24] who showed a significant association between throm­bocytopenia and neuropsychiatric manifestations.

The main immunologic finding in our pa­tients was the high prevalence of anti-Sm antibodies (39.2%); this is in contrast to 10% prevalence reported among Europeans, [3] 16% among Puerto Ricans [25] and 13% among Southeast Americans. [5] A high prevalence was also observed in north Tunisia (61%), [1] South Africa (44.28%), [6] Martinique (37.1%) [26] and Saudi Arabia (40%). [20] In our series, the presence of anti-Sm antibodies was found more frequently in patients with Raynaud's phenomenon and anti-RNP antibodies. Asso­ciations between anti-Sm antibodies and Ray­naud's phenomenon have been reported pre­viously. [27],[28] On the other hand, the relation between anti-Sm antibodies and anti-RNP anti­bodies was demonstrated by Houman, Tickly and Molina. [1],[6],[29]

The level of anti-cardiolipin antibodies has been reported to be raised in 5-80% of patients with SLE. [1],[30] This large variation in the pre­valence of anti-cardiolipin antibodies can be explained by the difference in the assay kits used. We found anti-cardiolipin antibodies in 71.6% of our patients, probably the highest frequency observed in the literature. In con­trast, the antiphospholipid syndrome was found in only 9.6% versus 21% among Kuwaitis [31] and 32.4% among Afro-Caribbean. [26] Houman [1] and Mc Dounagh [32] have reported similar fre­quencies to those seen in our study, respec­tively 11 and 9%.

The treatment received by our patients co­rrelated well with the severity of their disease and the prevalence of major organ damage and, consequently, to the increased requirement of high dose steroids (76%) and immuno­suppressive drugs (26.7%).

Infections are common in SLE and affected 45.2% of our study patients. Most infections were mild (82%) involving principally the urinary tract and skin. Similar findings were observed in the literature. [33]

The survival of patients with SLE has clearly improved during the last four decades. Reports range from less than 50% survival in 1955 to more than 93% in the 1990's. Eleven patients (7.5%) died during follow-up in the present study. The five-year survival rate is 92% which is lower than that found in the European report (95%) but higher than that found in the north Tunisian report (86%). A bimodal distri­bution for SLE mortality was first described in 1976 by Urowitz et al. [34] Early deaths are largely due to active disease, while late deaths are associated with vascular events, infections and other complications not directly associated with lupus activity. In our series, active disease and infections were the two major causes of death and no patient died of cardiovascular complications or malignancies. These findings are comparable to those seen in northern Tuni­sians, [1] Chinese [41] and South Koreans. [35] Consis­tent with others studies, our data confirm an important increased risk of mortality among patients with renal involvement, [1],[36],[37],[38] thrombo­cytopenia [39],[40] and anti-cardiolipin antibodies. [1],[36]

 Conclusions



The clinical and immunological characteris­tics of our patients with SLE are largely com­parable to other study populations. In addition, the immunologic profile in our series is cha­racterized by the high prevalence of anti-Sm and anti-cardiolipin antibodies. Our data sug­gest that South Tunisian patients have more major organ damage such as renal and neuro­psychiatric disease.

References

1Houman MH, Smiti-Khanfir M, Ben Ghorbell I, Miled M. Systemic lupus erythematosus in Tunisia: Demographic and clinical analysis of 100 patients. Lupus 2004;13:204-11.
2Louzir B, Othmani S, Ben Abdelhafidh N. Systemic lupus erythematosus in Tunisa. A multicentric study. About 295 cases. Rev Med Interne 2003;24:768-74.
3Cervera R, Khamashta A, Font J; the Europeen working Party on systemic lupus erythema­tosus. Systemic lupus erythematosus: Cli-nical and immunological patterns of disease expre­ssion in a cohort of 1000 patients. Medicine 1993;72:113-24.
4Johnson E, Gordon C, Hobbs FD, Bacon PA. Undiagnosed systemic lupus erythematosus in the community. Lancet 1996;347:367-9.
5Cooper GS, Parks CG, Treadwell EL, et al. Differences by race, sex and age in the clinical and immunologic features of recently diag­nosed systemic lupus erythematosus patients in the southeastern United States. Lupus 2002; 11;161-7.
6Tickly M, Burgin S, Mohanlal P, Belligan A, George J. Auto antibodies in black South African with systemic lupus erythematosus: Spectrum and clinical associations. Clin Rheumatol 1996;15:261-5.
7Ka MM, Diallo S, Kane A, et al. Systemic lupus erythematosus and lupus syndromes in Senegal: a retrospective study of 30 patients seen over 10 years. Rev Rheum Engl Ed 1998;65:471-6.
8Malaviya AN, Chandrasekaren AN, Kumar A, Shamar PN. Systemic lupus erythematosus in India. Lupus 1997;6:690-700.
9Nossent JC. Systemic lupus erythematosus on the Caribbean Island of Curacao: an epide­miological investigation. Ann Rheum Dis 1992;51:1197-201.
10Cameron JS, Turner DR, Ogg CS, et al. Systemic lupus with nephritis: A long term study. Q J Med 1979;48:1-24.
11Mery JP. Etude critique du traitement des nephropathies lupiques. Ann Med Interne 1977;28:9-16.
12Le Thi Huong DU, Papo T, Beaufils H, et al. Renal involvement in systemic lupus erythe­matosus: a study of 180 patients from a single centre. Medicine 1999;78:148-66.
13Thumboo J, Fong KY, Chia HP, et al. Clinical predictors of nephritis in systemic lupus erythematosus. Ann Acad Med Singapore 1998;27:16-20.
14Bastian HM, Roseman JM, McGwin Jr G, Alarcon GS, Friedman AW, Fessler BJ. Systemic lupus erythematosus in three ethnic groups, XII: Risk factors for lupus nephritis after diagnosis. Lupus 2002;11:152-60.
15Miller MH, Urowitz MB, Gladman DD. The significance of thrombocytopenia in systemic lupus erythematosus. Arthritis Rheum 1983; 26:1181-6.
16Swaak AJ, Huysen V, Nossent JC, Smeenk RJ. Antinuclear antibody profiles in relation to specific disease manifestations of systemic lupus erythematosus. Clin Rheumatol 1990;9( suppl.1):56-73.
17Waldman M, Madaio MP. Pathogenic autoantibodies in lupus nephritis. Lupus 2005;14:19-24.
18Jennekens FGI, Kater L. The central nervous system in systemic lupus erythematosus, Part 1, Clinical syndromes: A literature investigation. Rheumatology 2002;4:605-18.
19Garcia MA, Marcos JC, Marcos AI, et al. Male systemic lupus erythematosus in a Latin­American inception cohort of 1214 patients. Lupus 2005;14:938-46.
20Alballa SR. Systemic lupus erythematosus in Saudi patients. Clin Rheumatol 1995;14:342-6.
21Thumboo J, Fong KY, Chong HH, et al. The effects of ethnicity on disease patterns in 472 orientals with systemic lupus erythematosus. J Rheumatol 1998;25:1299-304.
22Mok CC, To CH, Mak A. Neuropsychiatric Damage in Southern Chinese Patients with Systemic Lupus Erythematosus. Medicine 2006;85:221-8.
23Mikdashi J, Handwerger B. Predictors of neuropsychiatric damage in systemic lupus erythematosus: Data from the Maryland lupus cohort. Rheumatology 2004;43:1555-60.
24Feinglass EJ, Arnett FC, Dorsch CA, Zizic TM, Stevens MB. Neuropsychiatric manifes­tations of systemic lupus erythematosus: Diagnosis, clinical spectrum, and relationship to other features of the disease. Medicine 1976;55:323-39.
25Vila LM, Mayor AM, Valentin AH, Garcia­Soberal M, Vila S. Clinical and immunological manifestations in 134 Puerto Rican patients with systemic lupus erythematosus. Lupus 1999;8:279-86.
26Deligny C, Thomas L, Dubreuil F, et al. Sys­temic lupus erythematosus in Martinique: an Epidemiological study. Rev Med Interne 2002; 23:21-9.
27Al-Attia HM, Al Ahmed YH. Mucocutaneous disease in Arabs with systemic lupus erythe-matosus: Clinical expression and relevance to autoantibodies. Lupus 1998;7:535-9.
28Lopez-Longo FJ, Gonzalez-Fernandez CM, Rodriguez-Mahou M, et al. Clinical expresion of systemic lupus erythematosus with anti-U1­RNP and anti-Sm antibodies. Rev Clin Esp 1997;197:329-35.
29Molina JF. Ethnic differences in the clinical expression of systemic lupus erythematosus: a comparative study between African-Americans and Latin Americans. Lupus 1997;6:63-7.
30Haddouk S, Ben Ayed M, Baklouti S, Hachicha J, Bahloul Z, Masmoudi H. Autoantibodies in systemic lupus erythematosus: spectrum and clinicqal associations. Pathol Biol 2005;53: 311-7.
31Al-Jarallah K, Al-Awadi A, Siddiqui H, et al. Systemic lupus erythematosus in Kuwait­hospital based study. Lupus 1998;7:434-8.
32McDonagh J E, Isenberg DA. Development of additional autoimmune diseases in a popu­lation of patients with systemic lupus erythe­matosus. Ann Rheum Dis 2000;59:230-2.
33Zonana-Nacach A, Camargo-Coronel A, Yanez P, Sanchez L, Jimenez-Balderas FJ, Fraga A. Infections in outpatients with sys­temic lupus erythematosus: a prospective study. Lupus 2001;10:505-10.
34Urowitz MB, Bookman AA, Koehler BE, Gordon DA, Smythe HA, Ogryzlo MA. The bimodal mortality pattern of systemic lupus erythematosus. Am J Med 1976;60:221-5.
35Chun BC, Bae SC. Mortality and cancer incidence in Korean patients with systemic lupus erythematosus: Results from the Hanyang lupus cohort in Seoul, Korea. Lupus 2005; 14(8):635-8.
36Gomez J, Suare A, Lopez P, Mozo L, Diaaz JB, Gutierrez C. Systemic lupus erythematosus in Asturias, Spain: Clinical and serologic features. Medicine 2006;85:157-68.
37Manger K, Manger B, Repp R, et al. Definition of risk factors for death, end stage renal disease, and thromboembolic events in a monocentric cohort of 308 patients with systemic lupus erythematosus. Ann Rheum Dis 2002;61:1065-70.
38Ginzler EM, Diamond HS, Weiner M, et al. A multicenter study of outcome in systemic lupus erythematosus: I, Entry variables as predictors of prognosis. Arthritis Rheum 1982;25:601-11.
39Exner T, Triplett DA, Taberner D, Machin SJ. Guidelines for testing and revised criteria for lupus anticoagulants. SSC Subcommittee for the standardization of Lupus Anticoagulants. Thromb Haemost 1991;65:320-2.
40Reveille JD, Bartolucci A, Alarcon GS. Negative impact of increasing age at onset, black race, and thrombocytopenia, as well as causes of death. Arthris Rheum 1990;33:37-48.
41Manger K, Manger B, Repp R, et al. Definition of risk factors for death and stage renal disease, and thromboembolic events in a monocentric cohort of 338 patients with systemic lupus erythematosus. Ann Rheum Dis 2002;61:1065-70.