|Year : 2015 | Volume
| Issue : 2 | Page : 314-319
|Pediatric systemic lupus erythematosus in a single nephrology unit
Doaa Mohammed Youssef1, Doaa Mostafa Tawfek1, Abdelsalam Mohammed Mohammed1, Rania Mohammed1, Naglaa Ahmed Khalifa2
1 Department of Pediatric Nephrology, Zagazig University, Zagazig, Egypt
2 Department of Pathology, Zagazig University, Zagazig, Egypt
Click here for correspondence address and email
|Date of Web Publication||3-Mar-2015|
| Abstract|| |
Clinical manifestations of systemic lupus erythematosus (SLE) are widely variable, and its course is unpredictable. SLE that begins in childhood has been considered more severe than SLE with onset during adulthood. Our aim was to determine the presentation and the outcome of SLE of 26 children (20 females and 6 males, with a female to male ratio of 3.8:1) with SLE in our center, their ages ranging from 5 - 18 years and followed from 2005 till October 2011. They were diagnosed according to the American Rheumatism Association's revised criteria. Complete blood count, erythrocyte sedimentation rate, C3, urine analysis, 24-h urinary protein, antinuclear antibodies, anti-ds DNA and renal biopsy were obtained for the patients. We found that the most extra-renal manifestation of SLE was fever (57.7%), while lupus nephritis (LN) was the most commonly affected organ (50%). Hemolytic anemia was the most common hematological abnormality (80.8%), while immunological characteristics were positive in all the patients. Remission in patients without LN was more than 5.3-times the remission in LN patients. The outcome of the patients without LN was better than the patients with LN.
|How to cite this article:|
Youssef DM, Tawfek DM, Mohammed AM, Mohammed R, Khalifa NA. Pediatric systemic lupus erythematosus in a single nephrology unit. Saudi J Kidney Dis Transpl 2015;26:314-9
|How to cite this URL:|
Youssef DM, Tawfek DM, Mohammed AM, Mohammed R, Khalifa NA. Pediatric systemic lupus erythematosus in a single nephrology unit. Saudi J Kidney Dis Transpl [serial online] 2015 [cited 2019 Nov 13];26:314-9. Available from: http://www.sjkdt.org/text.asp?2015/26/2/314/152493
| Introduction|| |
Systemic lupus erythematosus (SLE) is a multisystem, inflammatory, autoimmune disease that can affect any organ system and is characterized by the presence of circulating anti-nuclear antibodies (ANA), especially antibodies to native (double-stranded) ds-DNA. 
The etiology of the SLE is now at least partially known, involving multiple genetic and environmental factors. The disease is character rized by a dysregulation of the immune system with polyclonal B-cell activation, which results in the production of self-reactive autoanti-bodies. 
Children and adolescents with SLE often present with non-specific constitutional symptoms.  While the incidence of childhood SLE is relatively low, renal involvement appears to be more common and severe in children than in adult SLE patients. It has been reported that more than 70% of children diagnosed with SLE develop lupus nephritis (LN) at the early stage of the disease. 
The criteria set developed by the American College of Rheumatology (ACR) is most widely utilized, and at least four criteria should be present to diagnose the SLE. 
A life-long and serious SLE disease is marked with a high morbidity and substantial mortality.  The choice of medications to treat the SLE depends on the severity of disease and the extent of organ damage. 
The causes of death vary with the disease duration; LN accounts for the highest percentage of deaths in those with less than five years of the disease, whereas vascular disease is the most important factor in the group who died later in the disease course. 
The aim of our study was to determine the characteristics of the presentation and the outcome of the SLE in children followed-up in our center.
| Patients and Methods|| |
We retro-prospectively studied 26 children (20 females and six males, ratio 3.1:1) fulfilling at least four of the American Rheumatism Association's revised criteria for the diagnosis of SLE. Their age ranged from five years to 18 years, with a mean of 11.3 ± 2.66 years. The mean duration of illness in this patient group was 3.5 ± 1.5 years.
All the patients had medical history, clinical examination and laboratory investigations, which included complete blood count (CBC), erythrocyte sedimentation rate (ESR), urinalysis, 24-h urine protein, serum creatinine, immunological investigations [complement (C3) assay by nephrometry BN Prospic] and ANA and anti-ds DNA (using fluorescent microscope for the detection of autoantibodies). Percutaneous renal biopsy was performed only to cases resistant to our protocol of treatment for SLE; we only obtained biopsy for three cases, which frequently relapsed and was resistant to treatment. For monitoring of the lupus activity, C3 and anti-ds DNA were repeated.
| Statistical Analysis|| |
The data were tabulated and statistically analyzed using the SPSS version 15 software package. Data were expressed as mean ± standard deviation for numerical variables. The Student t-test and chi-squared test were used to determine the significance and compare the categorical variables. For all the tests, P-values less than 0.05 were considered to be statistically significant.
| Results|| |
[Table 1] shows the clinical characteristics of SLE at diagnosis. The most common extrarenal manifestation was fever (57.7%), followed by joint involvement and malar rash (50%), and the least frequently involved organ was the pericardium (3.8%). LN appeared to be the most common major organ affected (50%), especially in males.
|Table 1: The clinical characteristics of the SLE children at presentation.|
Click here to view
[Table 2] shows the hematological and immunological characteristics of SLE of children at presentation. Hemolytic anemia was the most common hematological abnormality (80.8%), and the anti-ds DNA, ANA and low C3 were positive in all the patients.
|Table 2: The hematological and immunological characteristics of SLE of children at presentation.|
Click here to view
[Table 3] shows the renal manifestations of patients with LN. The proteinuria (100%) was the most common renal manifestation, followed by hematuria (84.6%).
|Table 3: Renal manifestations of patients with lupus nephritis at presentation.|
Click here to view
[Table 4] shows the comparison of relapses of the disease in patients with and without LN. There was no significant difference inrequencies of relapses of SLE patients between both groups.
[Table 5] shows the outcome of patients at the latest follow-up. Remission in patients without LN was more than that in LN. There was only one patient with LN who had CRF. Only one case reached 18 years and was therefore transferred to adult nephrology unit to complete the course of treatment.
|Table 5: Outcome of patients with and without lupus nephritis at the latest follow-up.|
Click here to view
[Table 6] shows the prognostic significance of the initial demographical, clinical and laboratory data on the relapse rate in the study patients. The patients whose age was <10 years, those with hematuria and those with increased serum creatinine were at an increased risk of relapses than others.
|Table 6: The prognostic significance of the initial demographical, clinical and laboratory data on the relapse rate in the study patients.|
Click here to view
| Discussion|| |
We compared the clinical manifestations and laboratory variables of children with SLE at diagnosis with the local data as well as data from other countries. The disease was diagnosed before the age of 10 years in 28.5% of patients. The age at diagnosis of SLE is comparable to other studies involving Egyptian  and Western  children with SLE. Bogdanovic et al  found that the majority of SLE children were aged above 10 years and Tucker et al  reported that 23% of SLE children developed the disease before the age of 10 years.
The female-to-male ratio in our study was 3.8:1, with a female predominance, similar to reports from other countries. ,, On the other hand, our female-to-male ratio was much lower than that in other Egyptian studies (12:1).  Also, other studies from Spain,  Philippines,  Lebanon  and Serbia  described a wide range of female-to-male ratios (7 - 18:1), close to the ratios reported in adult SLE.
In our study, the most common extrarenal manifestations at diagnosis were fever, arthritis and malar rash. The frequency of joint involvement in our series (50%) was comparable to other studies involving Egyptian,  Indian  and European children,  but less common than in Arab , and American  children. Mucocutaneous manifestations of SLE are less common in Arab children. ,
However, in our study, the malar rash was found in 50% of the patients; it is closer to a Thailand study (53.5%) carried out by Pattaragarn et al  and an Egyptian study (46.2%) carried out by Bakr et al.  On the other hand, it was higher than another Egyptian study (38.2%) carried out by Salah et al,  but it was lower than the Philippine study (74.8%) carried out by Hamijoyo et al. 
Our patients had fewer central nervous system (CNS) manifestations (11.5%); this result is supported by Alsaeid et al  who reported a low frequency of neuropsychiatric abnormalities in Kuwaiti children with SLE. However, reports from Saudi Arabia,  Western countries  and the Philippine study  pointed to a higher frequency of CNS abnormalities.
The frequency of hemolytic anemia in our study was 80.8%, which is more than other studies performed by Bakr  (51%), the Indian study carried out by Chandrasekaran et al  (53%) and the Kuwaiti study (20%) carried out by AlSaeid et al. 
The serological features of SLE in our patients showed a 100% ANA positivity similar to the Kuwaiti study (100%) carried out by AlSaeid et al  and slightly higher than the Egyptian study (94.7%) carried out by Salah et al.  Also, the anti-dsDNA positivity was 100% in our study, slightly higher than that in the Egyptian study (95.5%) carried out by Bakr. 
In our study, renal involvement was seen in 50% of the cases, comparable to the findings of the studies of Gulay and Dans;  Meunier et al  and Zappitelli et al  found that LN was present in 50-67% of the children. On the other hand, lower frequencies of renal involvement were reported in other Arab SLE studies.  However, a higher percentage (80.8%) was noted in an Egyptian study. 
Proteinuria (100%) and hematuria (84.6%) were the most common renal manifestations in our study, similar to Hoffman et al.  It was higher than the 41% and 24.3%, respectively, found in a study carried out by Gulay and Dans. 
Hypertension occurred in a higher percentage (76.9%) in our study than 40% found in other studies. ,
The clinical manifestations of our patients with LN were similar to those seen in the study of Western children  and the Egyptian studies. , However, none of the studies on Arab children described the details of the LN in them.
The wide variations among different studies in the prevalence of childhood SLE manifestations may be related to the differences in the genetic make-up of the patients who come from various ethnic groups, or to referral bias, as some studies were performed in the nephrology units and others in the rheumatology units. 
In our series, almost all the SLE patients without LN, in contrast with 69.2% of the LN patients, achieved remission. The profile of the outcome in our study was similar to that of a study of Caucasian LN children and better than that carried out by Bogdanovic et al  and Hagelberg et al.  Moreover, poor prognosis of Arab children with LN was described by Yalaoui et al.  Five of 16 Tunisian LN children died in the context of renal failure. In a Saudi report of 37 children with LN, four died and ten reached dialysis. 
One of the limitations of this study was that not all patients were able to perform the renal biopsy. This was primarily due to financial reasons, as the majority of our patients came from low-income families.
We conclude that renal involvement occurred in 50% of children with SLE. The outcome of patients without LN was better than that of patients with LN. We found male sex and age <10 years as the prominent risk factors affecting the outcome of the disease.
Conflict of interest: None declared.
| References|| |
Lattanzi B, Ravelli A. Systemic Lupus Erythematosus. Textbook of Clinical Pediatrics 2012; 2:1629-41.
Moser KL, Kelly JA, Lessard CJ, Harley JB. Recent insights into the genetic basis of systemic lupus erythematosus. Genes Immun 2009; 10:373-9.
Watson L. Diagnosis and management of juvenile-onset SLE. Paediatr Child Health 2011; 21:539-45.
Perfumo F, Martini A. Lupus nephritis in children. Lupus 2005;14:83-8.
Petri M. Review of classification criteria for systemic lupus erythematosus. Rheum Dis Clin North Am 2005;31:245-54.
Malleson P, Tekano J. Diagnosis and management of systemic lupus erythematosus in children. Pediatr Child Health 2008;18:2:61-9.
Mina R, Brunner HI. Pediatric Lupus - Are There Differences in Presentation, Genetics, Response to Therapy, Damage Accrual Compared to Adult Lupus? Rheum Dis Clin North Am 2010;3653-80
Manson JJ, Anisur Rahman A. Systemic lupus erythematosus. Orphanet J Rare Dis 2006;1:6.
Bakr A. Epidemiology treatment and outcome of childhood systemic lupus erythematosus in Egypt. Pediatr Nephrol 2005;20:1081-6.
Niaudet P, Salomon R. Systemic lupus Erythematosus. In: Avner ED, Harmon WE, Niaudet P, et al, eds. Pediatric Nephrology. Philadelphia: Lippincott & Williams-Wilkins; 2004. p. 865-86.
Bogdanovic R, Nikolic V, Pasic S, et al. Lupus nephritis in childhood: A review of 53 patients followed at a single center. Pediatr Nephrol 2002;19:36-44.
Tucker LB, Menon S, Schaller JG, Isenberg DA. Adult- and childhood-onset systemic lupus erythematosus: A comparison of onset, clinical features, serology, and outcome. Br J Rheumatol 1995;34:866-72.
Stichweh D, Arce E, Pascual V. Update on pediatric systemic lupus erythematosus. Curr Opin Rheumatol 2004;16:577-87.
Khoo JJ, Pee S, Thevarajah B, Yap YC, Chin CK. Lupus nephritis in children in Malaysia. J Paediatr Child Health 2005;41:31-5.
Sozeri B, Mir S, Mutlubas F, et al. Retrospective analysis of the outcome of pediatric lupus nephritis, single center Study. Ege Journal of Medicine/Ege Týp Dergisi 2009;48:181-7.
Alonso MD, Llorca J, Martinez-Vazquez F, et al. Systemic lupus erythematosus in northwestern Spain: A 20-year epidemiologic study. Medicine (Baltimore) 2011;90:350-8.
Hamijoyo L, Bernal C, Navarra S. Comparison of the clinical presentation of childhood/ adoloscent-onset with adult-onset systemic lupus erythematosus. Philippine Rheumatology Association, 16th Annual Meeting; 2009.
Uthman IW, Muffarij AA, Mudawar WA, Nasr FW, Masri AF. Lupus nephritis in Lebanon. Lupus 2001;10:378-81.
Salah S, Lotfy HM, Sabry SM, El Hamshary A, Taher H. Systemic lupus erythematosus in Egyptian children. Rheumatol Int 2009;29:1463-8.
Das SK, Ray A, Jana CK. Lupus Nephritis: epidemiology. Clinicopathological profile of renal changes in systemic lupus erythematosus. J Indian Med Assoc 2011;108:761-3.
Alsaeid K, Kamal H, Haider MZ, Al-Enezi HM, Malaviya AN. Systemic lupus erythematosus in Kuwaiti children: Organs involvement and serological findings. Lupus 2004;13:613-7.
Habib GS, Saliba WR. Systemic lupus erythematosus among Arabs. Isr Med Assoc J 2002; 4:690-3.
Iqbal S, Sher MR, Good RA, Cawkwell GD. Diversity in presenting manifestations of systemic lupus erythematosus in children. J Pediatr 1999;135:500-5.
Brik R, Padeh S, Mukamel M, et al. Systemic lupus erythematosus in children in Israel. Harefuah 1995;129:233-5, 296, 295.
Bahabri S, Al Sabban EA, Al Rashed A, et al. Juvenile systemic lupus erythematosus in 60 Saudi children. Ann Saudi Med 1997;17:612-5.
Pattaragarn A, Sumboonnanonda A, Parichatikanond P, Supavekin S, Suntornpoch V, Vongjirad A. Systemic lupus erythematosus in Thai children: Clinicopathologic findings and outcome in 82 patients. J Med Assoc Thai 2005;88 Suppl 8:232-41.
Bruns A, Meyer O. Neuropsychiatric manifestations of systemic lupus erythematosus. Joint Bone Spine 2006;73:639-45.
Gulay CB, Dans LF. Clinical presentations and outcomes of Filipino juvenile systemic lupus erythematosus. Pediatric Rheumatol Online J 2011;9:7.
Chandrasekaran AN, Rajendran CP, Ramakrishnan S, Madhavan R, Parthiban M. Childhood systemic lupus erythematosus in South India. Indian J Pediatr 1994;61:223-9.
Bader-Meunier B1, Armengaud JB, Haddad E, et al. Initial presentation of childhood-onset systemic lupus erythematosus: A French multicenter study. J Pediatr 2005;46:648-53.
Zappitelli M, Duffy CM, Bernard C, Gupta IR. Evaluation of activity, chronicity and tubulointerstitial indices for childhood lupus nephritis. Pediatr Nephrol 2008;23:83-91.
Hoffman IE, Lauwerys BR, De Keyser F, et al. Juvenile-onset systemic lupus erythematosus: Different clinical and serological pattern than adult-onset systemic lupus erythematosus. Ann Rheum Dis 2009;68:412-5.
Hersh AO, von Scheven E, Yazdany J, et al. Differences in long-term disease activity and treatment of adult patients with childhood- and adult-onset systemic lupus erythematosus. Arthritis Rheum 2009;61:13-20.
Danchenko N, Satia JA, Anthony MS. Epidemiology of systemic lupus erythematosus: A comparison of worldwide disease burden. Lupus 2006;15:308-18.
Hagelberg S, Lee Y, Bargman J, et al. Longterm follow up of childhood lupus nephritis. J Rheumatol 2002;29:2635-42.
Yalaoui S, Gorgi Y, Meddeb S, et al. Lupus in children in Tunisia. Rev Med Interne 1993; 14:765-71.
Dr. Doaa Mohammed Youssef
Department of Pediatric Nephrology, Zagazig University, Zagazig
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]
| Article Access Statistics|
| Viewed||3129 |
| Printed||28 |
| Emailed||0 |
| PDF Downloaded||494 |
| Comments ||[Add] |