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Year : 2021  |  Volume : 1  |  Issue : 1  |  Page : 7-12

Clinical and serological features of patients with systemic lupus erythematosus in the eastern province of Saudi Arabia: A prospective cohort study

1 Department of Internal Medicine, Rheumatology Unit, King Fahad Military Medical Complex, Dhahran, Kingdom of Saudi Arabia
2 Department of Postgraduate Studies and Research, Prince Sultan Military College of Health Science, Dhahran, Kingdom of Saudi Arabia

Date of Submission30-Apr-2021
Date of Decision31-May-2021
Date of Acceptance14-Jul-2021
Date of Web Publication13-Nov-2021

Correspondence Address:
Dr. Khawla K Alghanim
Department of Internal Medicine, Rheumatology Unit, King Fahad Military Medical Complex, Dhahran 31932
Kingdom of Saudi Arabia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ara.ara_1_21

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Context: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that manifests differently across races. Aims: The aim of the study is to summarize the clinical and serological features of patients with SLE in Saudi Arabia and to determine the predictors of morbidity and mortality. Settings and Design: This was single-center prospective cohort study. Patients and Methods: We included SLE patients who met our selection criteria and followed prospectively and regularly between December 2016 and January 2020. We analyzed their symptoms, laboratory results, frequencies of clinical manifestations, causes of admission, and causes of death. We also assessed variables that predicted mortality. Statistical Analysis: Chi-square test was used to find the association between quantitative variables; survival analysis was done using Mantel–Cox method. Results: The mean age of the patients at diagnosis was 33.42 ± 12.9 years. The most common symptoms were arthritis (74.1%), malar rash (66.4%), and photosensitivity (64.7%). Renal involvement was seen in 17.2% of patients, with Class IV lupus nephritis (35%) being the most common. Patients aged ≤45 years had higher antinuclear antibody titers. Patients of African descents displayed higher rates of Class VI lupus nephritis and renal failure (25%). SLE caused deaths in 4.3% of patients, the main cause being infection (46.03%). There were obstetric complications in 27 (23.3%) patients; 28 (24.1%) vascular thrombosis events were noted, the most common being venous thrombosis (n = 21). Conclusions: Most patients were diagnosed at a young age. African patients displayed more severe disease in the form of renal symptoms, especially Class VI lupus nephritis. Infectious complications were the main cause of death.

Keywords: Antinuclear antibodies, antiphospholipid antibodies, lupus nephritis, systemic lupus erythematosus

How to cite this article:
Alghanim KK, Gasmelseed BG, Abdulhameed RS, Alrayes HA, Jebakumar AZ, Abozaid HS. Clinical and serological features of patients with systemic lupus erythematosus in the eastern province of Saudi Arabia: A prospective cohort study. Ann Rheumatol Autoimmun 2021;1:7-12

How to cite this URL:
Alghanim KK, Gasmelseed BG, Abdulhameed RS, Alrayes HA, Jebakumar AZ, Abozaid HS. Clinical and serological features of patients with systemic lupus erythematosus in the eastern province of Saudi Arabia: A prospective cohort study. Ann Rheumatol Autoimmun [serial online] 2021 [cited 2023 May 28];1:7-12. Available from: https://www.arajournal.org//text.asp?2021/1/1/7/330429

  Introduction Top

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease causing widespread inflammation and damage to multiple organs.[1]

SLE manifests differently across ethnicities, with varying clinical and serological features predominating in different patient groups. A study from Saudi Arabia found fever, fatigue, and malaise with musculoskeletal and mucocutaneous involvement as the common symptoms.[2] SLE prevalence appears to vary by ethnicity,[3] but prognosis has improved significantly because of early diagnosis and immunosuppressive therapies.[4]

We aimed to summarize the clinical and serological manifestations of SLE patients in Saudi Arabia of different ages and racial backgrounds and identify the predictors of morbidity and mortality.

  Patients and Methods Top

We enrolled 320 SLE patients who followed prospectively over 4 years at King Fahad Military Medical Complex, Dhahran, between December 2016 and January 2020. The patients either fulfilled four 1997 Classification Criteria of the American College of Rheumatology for SLE or fulfilled at least three of the criteria and had a typical SLE renal biopsy lesion. We only included SLE patients with a minimum frequency of one visit per 3 months for at least 24 months of follow-up duration at the lupus clinic. We excluded patients younger than 14 years of age and those with overlap syndromes or history of cancer. In our hospital, patients with SLE are assigned a diagnosis-specific code, which can be used to identify their electronic medical records and extract data when required. We collected the data prospectively and analyzed their symptoms and laboratory results, clinical manifestation frequency, laboratory data, treatment, cause of admission, and cause of death. The demographic data included age, sex, age at diagnosis, disease duration, pregnancy history, and clinical manifestations. The laboratory tests included routine laboratory workup, antinuclear antibody (ANA) profile, antiphospholipid profile, lipid profile, and 24-h urinary protein. We performed renal biopsies only if there was any biochemical evidence of lupus nephritis. All patients with SLE who attained clinical remission were evaluated and examined every 3 months; SLE remission was characterized by a clinical SLE Disease Activity Index (SLEDAI) score of 0, a physician's global assessment score of <0.5, and prednisone levels of ≤5 mg/day.[5]

Patients were admitted and reassessed frequently for disease activity or complications. We included their symptoms starting from their first visit to our lupus clinic, first admission to the hospital, or first appearance of clinical symptoms. If there were multiple results, we considered the immunological and laboratory values of the first positive laboratory result.

The Saudi Arabian population comprises two major ethnicities: 90% Arab and 10% Afro-Asian.[6] We classified our patients into different groups based on their age (≤45 vs. ≥45 years) and ethnicity (Arab, African, and Asian) because we believe that these factors play an important role in disease expression and might affect patients' prognoses. We also reviewed the previous literature from the Kingdom of Saudi Arabia, the Arab medical literature, and the findings from other countries, and we compared them with our clinical findings.

Statistical analysis

Quantitative data are presented descriptively (mean and standard deviation [SD]). We employed frequency tables to examine other demographic variables and applied survival analysis to determine the survival rate with the log-rank test (Mantel–Cox method). Chi-square test was used to identify association between qualitative variables. We used the Statistical Package for the Social Sciences (SPSS), version 25 (IBM SPSS Statistics , Smart vision, Dubai, UAE), in this study and considered a P ≤ 0.05 (at a 95% confidence interval) to indicate statistical significance.

  Results Top

We included 116 SLE patients in this investigation who met our selection criteria. Of the 116 patients, there were Arab (n = 109), African (n = 6), and Asian (n = 1) [Figure 1]. Most patients were young (n = 76, ≤45 years) and female (n = 102, 87.9%), with a female-to-male ratio of 7:1. The mean patients' age was 41.03 years (SD ± 11.07), and the mean age at disease onset was 33.42 years (SD ± 11.75). The mean disease duration was 4.36 years.
Figure 1: Distribution of ethnic groups in Saudi Arabia

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Notably, 9.5% of the patients had a family history of lupus, and 11.1% had hypothyroidism. A small percentage (5.1%) of patients was smokers. Mortality in our cohort was 4.3%, with infection (mainly with Gram-negative–resistant organisms) being a major cause of death in four lupus patients and one lupus patient died with massive pulmonary thrombosis [Table 1].
Table 1: Patients' demographic data and comorbidities

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The most common presenting symptoms in our cohort were arthritis (74.1%), followed by a malar rash (66.4%) and photosensitivity (64.7%). We found renal involvement in 17.2% of the patients, with the most common type being Class IV lupus nephritis (35%). Notably, African patients had higher rates of Class VI lupus nephritis and renal failure (25%). The least-common manifestation was neurological (i.e. psychosis and memory disturbance) at 1.7% each. However, within this category, seizure (5.2%) was the most common complication. There were 28 vascular thrombosis events, the most common being venous thrombosis (n = 21); 80.95% of these patients tested positive for antiphospholipid antibodies (APLs). There were only three arterial thrombosis events; all three affected patients who tested positive for APLs. Twenty-seven patients had obstetric complications, and there were 32 obstetric events (25 events in the first trimester, four events in the second trimester, one preterm labor, and two intrauterine fetal deaths). However, only 29.62% of them had APLs. In addition, fever was not a common manifestation; it was reported only by 19 patients (16.3%) [Table 2].
Table 2: Clinical manifestations of systemic lupus erythematosus

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Most of our patients were seropositive and had ANA positivity (91.4%) by indirect immunofluorescence antibodies technique; 76 young patients (≤45 years old) had a high titer of 1:320 or more, whereas only 29.3% of the patients tested positive for anti-double–stranded DNA (dsDNA) antibodies, the most specific antibodies for diagnosing SLE. A significant number of patients had low complement C3 levels (56%). We found APLs in 40.1% of patients. Leukopenia was the most common hematological finding (54.3%), followed by lymphopenia (38.3%) and thrombocytopenia (13.8%) [Table 3].
Table 3: Laboratory findings in patients with systemic lupus erythematosus

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The most frequently used treatment was hydroxychloroquine (97.4%), followed by oral prednisolone (≥10 mg once daily) during their disease course (66.4%) and azathioprine (42.2%). The drugs used least often were cyclosporine and tacrolimus (0.9% each) [Table 4].
Table 4: Treatment for systemic lupus erythematosus

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Among the 116 patients, 63 were admitted to the hospital for various reasons, most commonly infections (46.03%), specifically bacterial pneumonia (n = 7), and urinary tract infection (n = 3). Gram-negative–resistant organisms such as  Escherichia More Details coli and Klebsiella pneumoniae were predominant. Two patients developed herpes zoster due to the ingestion of high doses of prednisolone for SLE. Two patients were admitted for medication-related side effects that included acute pancreatitis and erosive gastropathy. Three young patients (≤40 years) were admitted due to myocardial infarction. One patient was admitted ten times because of anasarca secondary to pulmonary hypertension, which improved after valve replacement [Table 5].
Table 5: Causes for hospital admission

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Different factors affected the mortality of patients with SLE. Of the 116 patients, five patients ≤45 years died. Two factors were significantly associated with mortality: lymphopenia and leukopenia. All five patients had lymphopenia, and four of them had leukopenia. Their P values were 0.04 and 0.02, respectively [Table 6].
Table 6: Risk ratios for mortality using the Cox proportional hazards model

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There were 25 patients with lupus nephritis, with most manifesting Classes IV, V, or VI disease severity. Interestingly, most Class IV patients were Arab (n = 5), whereas most Class VI patients were African (n = 4). In all these African patients, lupus nephritis progressed to end-stage renal disease [Figure 2].
Figure 2: Classes of lupus nephritis among different ethnic groups

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Most of our patients were in remission or had mild disease activity (83.6%) with a SLEDAI of ≤4 at 6 months. Only 5.2% of patients had severe SLE because of lupus nephritis, whereas 62.1% were in remission [Figure 3].
Figure 3: Systemic lupus erythematosus disease activity index-2K at 6 months

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Most patients, across all age groups (older and younger than 45 years), had an ANA titer of at least 1:320. Among younger patients, 93.4% of the patients had a titer of at least 1:320, and only 6.6% had titers below 1:320. Among older patients, 85% of patients had an ANA titer of 1:320 or more, whereas 15% had titers of <1:320.

  Discussion Top

We collected data on the clinical and immunological features of SLE in patients of different ethnicities who presented at our hospital over 4 years. We found that SLE is prevalent among younger patients (≤45 years). The sex ratio in our cohort (female: male = 7:1) conforms to the well-known female predominance of SLE; in this patient population, 87.9% were female and 12.1% were male. There are reportedly nine women for every man affected with SLE.[7] The mean age of the patients in this cohort was 41.03 ± 11.6 years, and the mean age at disease onset was 35.3 ± 12.9. SLE generally manifests in young child-bearing women aged 15–44 years.[8] This is in line with the current observations since most of these patients were between 20 and 40 years of age (62.9%).

Most of these patients were of Arab descents (n = 109; 94%); the rest were Africans (5.2%) and Asians (0.9%). The prevalence rate of SLE is higher in these groups than in Caucasians.[9] Only 9.2% of these patients reported a family history of SLE. According to the Centers for Disease Control and Prevention (CDC), most patients with SLE do not have a positive family history, contrary to the general perception that autoimmune diseases are hereditary.

Most of these patients tested positive for ANAs (91.4%), whereas only 29.3% had anti-dsDNA antibodies. Up to 75% of patients with SLE exhibit co-existing hypertension;[9] however, in the current study, this rate was low (20.7%). Most patients (93.4%) with ANA titers of 1:320 or more (positive) were younger than 45 years; 84% of patients with an ANA titer of 1:320 were older than 45. Although the level is not correlated with disease severity, this finding shows that a negative or low ANA titer cannot rule out SLE.

Arthritis was the most frequently reported clinical manifestation. A meta-analysis of 3000 Arab patients with SLE characteristics revealed arthritis to be the most common symptom.[10] Retrospective studies in Jeddah[11] and Tabuk[12] revealed similar results. In contrast, an Egyptian cohort reported mucocutaneous involvement as the most common SLE symptom (90.8% of patients).[13] The least-common reported clinical manifestation in the current study was neurological (i.e., psychosis). This is similar to that in the Jeddah study, except that their least-frequently reported neurological condition was myelitis.[11]

The drug treatment for SLE is similar across various hospitals in different regions and countries. According to the CDC recommendations,[11] antimalarial drugs such as hydroxychloroquine should be used as the cornerstone of SLE management.[12] Hydroxychloroquine is most frequently used to manage SLE at our hospital. The least-used drugs are tacrolimus and cyclosporine. In contrast, in hospitals in Jeddah, mycophenolate mofetil is the least-used drug.

The patients with SLE in this study sought hospital admission for several reasons. In our hospital, 58 of the 116 patients had been admitted to the hospital, most commonly for an infection followed by lupus nephritis. In contrast, in Jeddah, the most common cause of hospital admission was active SLE, which mainly presented as active arthritis.[8] Another Egyptian study showed that bacterial infections were common in patients with SLE (43.8%),[13] and this study produced similar findings.

The mortality rate in this study was low (4.3%; 5/116 patients). Two factors were significantly associated with mortality: leukopenia and lymphopenia (P = 0.04 and 0.02, respectively). This contrast with the results of a case–control study carried out in a tertiary center in Mexico City, in which the factors significantly responsible for mortality were heart involvement, lung involvement, and severe thrombocytopenia; the odds ratios of these factors were 15.6, 9.6, and 5.6, respectively.[14] A Canadian study reported that significant factors associated with mortality were renal damage, thrombocytopenia, a SLEDAI ≥20 at presentation, lung involvement, and patients' age ≥50 years.[15]

SLE disease activity is often measured using the SLEDAI, which indicates treatment efficacy. A multiethnic cohort comprising Hispanic, African-American, and Caucasian individuals showed that most patients had a high SLEDAI, which meant that they were in the active phase of the disease (47%).[16] In this study, most patients were in remission (62.1%) or had mild disease activity (22.4%).

There is a strong association between lupus nephritis and ethnicity. A prospective, multiethnic cohort has shown that lupus nephritis patients were mostly African, Asian, and Hispanic men.[17] The Arabs in the current study had Class IV (n = 5), Classes V (n = 3), and Class VI lupus nephritis (n = 3). In contrast, two African patients had Class IV lupus nephritis, three had Class V, and four had Class VI disease. One Asian patient did not develop lupus nephritis.

Another large cohort study conducted in Riyadh, Saudi Arabia, consisting of 624 patients, showed results consistent with those observed in the current study, such as the common presentation being arthritis (80.4%). The mean age of the patients was 34 years; however, in this study, it was 41 years. Similar drugs were also used to manage SLE, resulting in high remission rates.[18]

The study's major limitations were the relatively small study cohort; some less-common disease manifestations (especially those involving the cardiac and central nervous systems) were not reported. Because this study was conducted at King Fahad Military Medical Complex, Dhahran, this cohort is mostly Arab. In addition, the current study is from a single center covering only the Eastern Province of the Kingdom of Saudi Arabia. The results may therefore not be generalizable to patient populations of different nationalities or to patients treated at other hospitals.

  Conclusions Top

SLE is more common among younger patients (younger than age 45) who display high ANA titers. Among patients with active infections, leukopenia and lymphopenia are associated with higher mortality rates. These findings will help consolidate the literature on SLE and help physicians to better predict the outcomes of their patients with SLE.

Availability of data and material

We have electronic medical records to extract all the information needed for our study.

Ethical policy and institutional review board statement

This study was approved by the appropriate ethics committee. Written informed consent was obtained from the patients for study participation and publishing of their data.

Code availability

We used the ICD-10 code (M32.1) for patients with SLE at our hospital, which helped us to use electronic medical records to extract all the information needed for this study.


We thank Editage for editing our paper and the Saudi Society for Rheumatology for providing financial support for editing our paper.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

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Wang F, Wang CL, Tan CT, Manivasagar M. Systemic lupus erythematosus in Malaysia: A study of 539 patients and comparison of prevalence and disease expression in different racial and gender groups. Lupus 1997;6:248-53.  Back to cited text no. 3
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  [Figure 1], [Figure 2], [Figure 3]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]


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