SEARCH

SEARCH BY CITATION

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Is there a need for a different term to refer to SLE among children and adolescents?
  5. When does adulthood start?
  6. Current status of nomenclature used in the medical literature
  7. Nomenclature used in the medical literature for chronic diseases in childhood
  8. Discussion
  9. AUTHOR CONTRIBUTIONS
  10. Acknowledgements
  11. REFERENCES
  12. Supporting Information

Objective

To propose a common nomenclature to refer to individuals who fulfill the American College of Rheumatology classification criteria for systemic lupus erythematosus (SLE) during childhood or adolescence.

Methods

The medical literature was reviewed for studies conducted in the target population between 1960 and December 2011 to obtain information about the terms used to refer to such children and adolescents. We reviewed the threshold ages used and disease features considered to discriminate these individuals from patients with onset of SLE during adulthood. Furthermore, the nomenclature used in other chronic diseases with onset during both childhood and adulthood was assessed.

Results

There was an astonishing variability in the age cutoffs used to define SLE onset prior to adulthood, ranging from 14–21 years, but most studies used age 18 years. The principal synonyms in the medical literature were SLE without reference to the age at onset of disease, childhood-onset SLE, juvenile SLE, and pediatric (or paediatric) SLE.

Conclusion

Based on the definition of childhood, in analogy with other complex chronic diseases commencing prior to adulthood, and given the current absence of definite genetic variations that discriminate adults from children, the term childhood-onset SLE is proposed when referring to individuals with onset of SLE prior to age 18 years.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Is there a need for a different term to refer to SLE among children and adolescents?
  5. When does adulthood start?
  6. Current status of nomenclature used in the medical literature
  7. Nomenclature used in the medical literature for chronic diseases in childhood
  8. Discussion
  9. AUTHOR CONTRIBUTIONS
  10. Acknowledgements
  11. REFERENCES
  12. Supporting Information

Various terms and definitions are used in the medical literature to refer to the subset of individuals that fulfill the American College of Rheumatology classification criteria for systemic lupus erythematosus (SLE) prior to adulthood (1). This results in several difficulties for health care providers, parents and families, researchers, and government agencies because information and research data about patients with SLE onset prior to adulthood are often not directly comparable due to differences in the age cutoffs chosen. Additionally, variation in the terminology can be confusing to patients and inhibits the review of the medical literature for information relevant to patients with SLE onset early in life.

The objective of this review was to appraise the medical literature in an attempt to propose a universally acceptable and sensible nomenclature to refer to individuals with SLE onset prior to adulthood. Excluded was the group of children who are diagnosed with neonatal lupus, a disease primarily afflicting the offspring of women who test positive for antibodies to the nuclear antigens Ro/La.

Significance & Innovations

  • International consensus on nomenclature to distinguish systemic lupus erythematosus (SLE) patients with adult onset from SLE patients with earlier onset is absent.

  • For patients with onset of SLE from infancy to age 18 years, we recommend the use of the term “childhood-onset SLE.”

Is there a need for a different term to refer to SLE among children and adolescents?

  1. Top of page
  2. Abstract
  3. Introduction
  4. Is there a need for a different term to refer to SLE among children and adolescents?
  5. When does adulthood start?
  6. Current status of nomenclature used in the medical literature
  7. Nomenclature used in the medical literature for chronic diseases in childhood
  8. Discussion
  9. AUTHOR CONTRIBUTIONS
  10. Acknowledgements
  11. REFERENCES
  12. Supporting Information

There are no known unique physiologic or genetic pathways that differentiate patients with SLE onset prior to adulthood from those with disease starting later in life. This raises the question whether the 10–20% of patients with disease onset during childhood should be diagnosed with a different, albeit related disease, or simply be referred to as having SLE. Most medical reports aimed at distinguishing patients whose disease onset was before adulthood by authors who study patients with disease onset later in life. Examples include numerous reports from the LUpus in MInorities, NAture versus nurture (LUMINA) cohort, where only rare reports separate out those with disease onset early in life (2). An example clearly distinguishing the different age at onset groups are the reports of the Grupo Latinoamericano de Estudio del Lupus Eritematoso cohort (3–8).

Evidence in favor of a separate term when referring to adults versus children with SLE may be that some deficiencies of early components of the classic complement pathway predispose to SLE onset at an early stage in life. These deficiencies have uncommonly resulted in SLE signs and symptoms that commence during adulthood. Furthermore, the female to male ratio is at 4:3, much lower in populations in which disease occurs in the first decade of life as compared to 9:1 in adult SLE (9–12). The above differences support the notion that there may be other, undiscovered inborn differences between adults and children with SLE. An additional indication in favor of introducing a separate term when referring to patients with SLE onset during childhood or adolescence may be the differences in patient phenotypes and the effectiveness and safety of pharmacologic interventions used for treatment. Children and adolescents often present with more acute and severe SLE features than adults based on studies providing direct comparisons (2, 13, 14). Most published research suggests a higher rate of renal, neurologic, and hematologic involvement among children and adolescents as compared to adults at the time of SLE diagnosis (2, 14–18). Indeed, the average disease activity of children and adolescents with SLE is significantly higher than those with adult-onset SLE (19), with the most pronounced differences in the renal and neurologic organ systems. Besides significantly more active disease at the time of disease onset, there is also more active disease, damage, and mortality over time among children and adolescents compared to adults with SLE (2, 19). The abovementioned phenotypic differences often result in more intensive medical therapy, and the pediatric population especially requires multidisciplinary care, families' education, and the promotion of school performance. Taken together, there appears to be compelling evidence that makes SLE with onset during childhood or adolescence deserving of a distinct designation.

When does adulthood start?

  1. Top of page
  2. Abstract
  3. Introduction
  4. Is there a need for a different term to refer to SLE among children and adolescents?
  5. When does adulthood start?
  6. Current status of nomenclature used in the medical literature
  7. Nomenclature used in the medical literature for chronic diseases in childhood
  8. Discussion
  9. AUTHOR CONTRIBUTIONS
  10. Acknowledgements
  11. REFERENCES
  12. Supporting Information

The most frequently used age at which adolescence ends is that proposed by the World Health Organization criteria, at 19 years, 11 months (20). Conversely, the National Institutes of Health and the American Academy of Pediatrics suggest that the pediatric age ends with the 21st birthday (21). From a sociologic point of view, the end of adolescence and the beginning of adulthood vary by geographic location, and even within a nation or culture, different ages are taken into account at which an adolescent is considered to be chronologically and legally mature.

From a developmental point of view, adolescence is a period to consolidate identity, develop a positive body image, establish social relationships, achieve independence and sexual identity, and move from school to tertiary education or work. Childhood ends with the onset of adolescence, which is associated with puberty and its dramatic alterations in hormone levels in both sexes.

Age 18 years is the threshold age at diagnosis with SLE that is most frequently used to define SLE with onset during childhood or adolescence in population-based research around the world (2, 4, 22–49). Nevertheless, age cutoffs used in studies of SLE range from 14–21 years (50–67). This is in line with some studies comparing pediatric versus adult populations with other chronic diseases, including asthma (68) and type 2 diabetes mellitus (69), which consider threshold ages of up to 20 years at diagnosis to define the pediatric subgroup. Conversely, a lower threshold for the age at diagnosis is used for some other chronic diseases. A prime example is juvenile idiopathic arthritis, which, according to the International League of Associations for Rheumatology classification, is defined as disease onset prior to the 16th birthday. This cut point is without strong genetic evidence that this is the most appropriate threshold age (70).

Similar to studies of pediatric lupus populations published to date, age 18 years at diagnosis is used to define patients with disease onset during childhood or adolescence with many other rheumatic diseases. Examples include studies of primary Sjögren's syndrome (71), juvenile-onset mixed connective tissue disease (72), and multinational studies of localized and systemic scleroderma (73, 74). Similarly, the classification criteria for primary childhood vasculitis (Henoch-Schönlein purpura, polyarteritis nodosa, granulomatosis with polyangiitis [Wegener's], Takayasu arteritis) of the European League Against Rheumatism/Paediatric Rheumatology International Trials Organisation/Pediatric Rheumatology European Society use a maximum age at diagnosis of 18 years (75). Likewise, recent multicenter studies in juvenile dermatomyositis (76–78), population-based research in rheumatic fever (79, 80) and Lyme disease (81), inflammatory bowel disease (82, 83), pain amplification syndromes (including juvenile fibromyalgia) (84, 85), panniculitis in childhood and adolescence (86), and pediatric-onset relapsing polychondritis (87) all chose the age threshold of 18 years to define the pediatric population under consideration.

In line with many other pediatric rheumatic diseases, and as done for most studies reporting on patients with SLE commencing before or after puberty, we propose to use age 18 years as the upper age at diagnosis. Although SLE with onset at age 17 years is probably not different from disease beginning at age 19 years, it is important to differentiate SLE in adolescents and adults.

A common definition of threshold age to define lupus with disease onset prior to adulthood is also important from a disease management point of view. The choice of age 18 years appears sensible because it is often also used by adult rheumatology services (2, 4, 38, 42, 43, 48). Although quite arbitrary, one might expect that patients ages 18 years or older would more likely be treated by adult rheumatologists, and the transfer of medical care from pediatric to adult health care in the short term could be avoided, therefore reducing the medical and psychosocial problems encountered during the transition process.

Current status of nomenclature used in the medical literature

  1. Top of page
  2. Abstract
  3. Introduction
  4. Is there a need for a different term to refer to SLE among children and adolescents?
  5. When does adulthood start?
  6. Current status of nomenclature used in the medical literature
  7. Nomenclature used in the medical literature for chronic diseases in childhood
  8. Discussion
  9. AUTHOR CONTRIBUTIONS
  10. Acknowledgements
  11. REFERENCES
  12. Supporting Information

When searching PubMed (details of the search terms are shown in Supplementary Appendix A, available in the online version of this article at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)2151-4658) for the vocabulary used to refer to patients with SLE with disease onset during childhood or adolescents, 4 principal terms are recognized, including SLE, juvenile SLE, pediatric (or paediatric) SLE, and childhood-onset SLE.

As shown in Figure 1, overall, the most commonly used terms in the literature to date (in order of frequency) are pediatric SLE, SLE, juvenile SLE, and childhood-onset SLE. More than 95% of articles about kidney involvement in children and adolescents use the term lupus nephritis (LN) without special emphasis on the young age of the study population (such as juvenile LN). A rationale for this might be that the renal histology is indistinguishable in those with early as compared to later onset of disease (88).

thumbnail image

Figure 1. Use of the terms in the medical literature over time. pSLE = pediatric systemic lupus erythematosus; cSLE = childhood-onset SLE; jSLE = juvenile SLE.

Download figure to PowerPoint

SLE (or LN) without a clear distinction according to age at the time of disease onset is the term used to refer to children and adolescents in 43% of all case reports (with or without review of the medical literature rephrasing this). In this setting, the term childhood-onset SLE is the least commonly used, at less than 10%.

Conversely, in rheumatology journals, the term SLE is the least frequently used term when reporting on children and adolescents diagnosed with the disease (Figure 2). The terms pediatric SLE and juvenile SLE are the most frequently used, with pediatric SLE being used most frequently, particularly in recent years.

thumbnail image

Figure 2. Use of the terms in the rheumatology literature. cSLE = childhood-onset systemic lupus erythematosus; jSLE = juvenile SLE; pSLE = pediatric SLE.

Download figure to PowerPoint

Therefore, if one agrees that children and adolescents fulfilling the American College of Rheumatology SLE classification criteria (1) deserve a distinct designation, based on numbers alone and assuming that rheumatology journals are being the most precise in their reference of the population under investigation, pediatric SLE might be the most appropriate term for use in studies that report on individuals with disease onset of SLE during childhood.

However, to identify the most appropriate designation, one could also use an etymologic approach. The Oxford Dictionary defines juvenile as “not fully mature or immature or childish,” while pediatric is defined as “relating to the medical care of children” and childhood onset is defined as “onset during the time period of being a child.”

“Juvenile” may not be the most appropriate term, in spite of the frequent use in the pediatric rheumatology diseases, e.g., juvenile idiopathic arthritis (70), juvenile dermatomyositis (76–78), and juvenile fibromyalgia (84, 85). Although “pediatric” may be a more suitable term to define the threshold of age 18 years, this adjective is associated with children and may cause embarrassment among adults who had been diagnosed with SLE early in life. The term “childhood” includes prepubertal and postpubertal ages of children and adolescents. A caveat may be that this term is rarely used in specific cultures for those ages 15 years or older.

Nomenclature used in the medical literature for chronic diseases in childhood

  1. Top of page
  2. Abstract
  3. Introduction
  4. Is there a need for a different term to refer to SLE among children and adolescents?
  5. When does adulthood start?
  6. Current status of nomenclature used in the medical literature
  7. Nomenclature used in the medical literature for chronic diseases in childhood
  8. Discussion
  9. AUTHOR CONTRIBUTIONS
  10. Acknowledgements
  11. REFERENCES
  12. Supporting Information

Yet another approach to decide on a sensible common term when referring to individuals with onset of SLE prior to adulthood is to seek advice from other chronic pediatric diseases. It may be reassuring to some that rheumatology and lupus are not alone in their struggles to arrive at a standardized nomenclature for a chronic disease that can commence prior to adulthood.

In general, 4 distinct taxonomic categories of chronic diseases in childhood are acknowledged (Table 1). The first category represents well-characterized single diseases with onset in childhood. Each disease in this category has an established pathogenetic background and presents with distinctive clinical characteristics. These diseases are usually characterized by the adjective “juvenile,” displaying occurrence of the disease in a person that is not fully physically mature. Typical examples of this category are diseases such as juvenile myoclonic epilepsy and juvenile myelomonocytic leukemia.

Table 1. Nomenclature of chronic diseases in childhood
Single diseases with onset in childhoodComplex diseases with onset typically in childhoodComplex diseases with onset across different age groupsSingle and complex childhood diseases with onset in adults
Juvenile myoclonic epilepsyPediatric/childhood asthmaPediatric/childhood-onset epilepsyAdult-onset Still's disease
Juvenile myelomonocytic leukemiaPediatric/childhood leukemiaChildhood-onset schizophreniaAdult-onset Henoch-Schönlein purpura
Juvenile polyposis syndromeJuvenile idiopathic arthritisPediatric/childhood-onset depressionAdult Kawasaki disease
Juvenile xanthogranulomaJuvenile dermatomyositisCrohn's disease (A1, A2, A3)Adult-onset Alexander disease
Juvenile angiofibromaJuvenile localized sclerodermaPediatric/childhood-onset nephrotic syndromeAdult-onset metachromatic leukodystrophy
Juvenile ossifying fibromaType 1 diabetes mellitus (previously juvenile diabetes mellitus)Pediatric/childhood obesityAdult congenital heart disease

The second category represents complex chronic diseases with multifactorial pathogenesis and characteristic onset during childhood. Most of these diseases can be further subclassified according to genetic background or similarities of the underlying immunopathogenic mechanisms. These diseases are devoid of a distinguishing nomenclature and, if they start early in life, are most commonly referred to as “pediatric,” “childhood,” or “juvenile” diseases. Pediatric (or childhood) asthma and juvenile idiopathic arthritis are among the most common chronic childhood diseases falling into this category. With advances in biochemistry, genetics, and molecular biology, it is expected that the classification of these diseases will be reevaluated, with the goal of achieving homogeneity within the disease groups.

An example is type 1 diabetes mellitus, which was previously referred to as juvenile diabetes mellitus. An interesting alternative in the taxonomy of complex chronic diseases is the Montreal classification of Crohn's disease, designating as the A1 category early-onset disease before age 16 years, whereas the A2 and A3 categories account for age at diagnosis of 17–40 years and >40 years, respectively (89).

The third category represents diseases with typical onset in childhood that may occasionally also develop in adults. These diseases are generally characterized by the adjective “adult” or “adult-onset.” Typical examples of this category are diseases such as adult-onset Still's disease and adult Kawasaki disease.

The fourth category is represented by complex chronic diseases without a characteristic age at onset. These diseases are diagnosed in both pediatric and adult populations, and usually patients with disease onset in childhood continue to have disease manifestations in adulthood. Generally, the pathogenetic backgrounds of the childhood- and adult-onset disease are similar, although certain age-related factors may significantly change the clinical presentation in different age groups. There is no standardized nomenclature for these diseases, and a wide range of adjectives are used to characterize these diseases, including “pediatric” or “pediatric-onset” and “childhood” or “childhood-onset.” Typical examples of this category are pediatric or childhood-onset epilepsy and pediatric or childhood obesity. As per the current state of the medical knowledge, SLE also seems to belong to this category of diseases.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Is there a need for a different term to refer to SLE among children and adolescents?
  5. When does adulthood start?
  6. Current status of nomenclature used in the medical literature
  7. Nomenclature used in the medical literature for chronic diseases in childhood
  8. Discussion
  9. AUTHOR CONTRIBUTIONS
  10. Acknowledgements
  11. REFERENCES
  12. Supporting Information

SLE is a multifactorial complex autoimmune disease that is diagnosed in individuals of all ages. At present and in an effort to enhance the comparability of studies in this population, we propose the use of the term “childhood-onset SLE” to refer to individuals with onset of SLE after infancy but by the age of 18 years.

As is evidenced by the nomenclature used for juvenile idiopathic arthritis, nomenclature in medicine is dynamic and generally reflects the state of medical knowledge. If future research yields data to support that the group of children and adolescents is genetically distinct from adults with SLE, then juvenile SLE would be the more appropriate term to use. Although some maturation processes, such as those of the neurocognitive brain development, continue beyond age 18 years, most are completed by age 18 years, particularly growth and sexual development (90). Therefore, we chose age 18 years as the upper age of diagnosing childhood-onset SLE. There are no data to support that a higher or even a lower age cutoff would be more appropriate, i.e., that the disease course of adolescents with disease onset at age 15 or 17 years is more similar to that of adult-onset SLE than to that of patients with SLE onset during childhood. If future epidemiologic research provides such evidence, then the age threshold needs to be revisited.

It is hoped that this review will result in a more homogeneous approach to defining the group of individuals with SLE onset during childhood or adolescence and provide them with a common designation for the disease with which they are diagnosed.

REFERENCES

  1. Top of page
  2. Abstract
  3. Introduction
  4. Is there a need for a different term to refer to SLE among children and adolescents?
  5. When does adulthood start?
  6. Current status of nomenclature used in the medical literature
  7. Nomenclature used in the medical literature for chronic diseases in childhood
  8. Discussion
  9. AUTHOR CONTRIBUTIONS
  10. Acknowledgements
  11. REFERENCES
  12. Supporting Information
  • 1
    Hochberg MC, for the Diagnostic and Therapeutic Criteria Committee of the American College of Rheumatology. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus [letter]. Arthritis Rheum 1997; 40: 1725.
  • 2
    Tucker LB, Uribe AG, Fernandez M, Vila LM, McGwin G, Apte M, et al. Adolescent onset of lupus results in more aggressive disease and worse outcomes: results of a nested matched case-control study within LUMINA, a multiethnic US cohort (LUMINA LVII). Lupus 2008; 17: 31422.
  • 3
    Shinjo SK, Bonfa E, Wojdyla D, Borba EF, Ramirez LA, Scherbarth HR, et al, on behalf of the Grupo Latino Americano de Estudio del Lupus Eritematoso (GLADEL). Antimalarial treatment may have a time-dependent effect on lupus survival: data from a multinational Latin American inception cohort. Arthritis Rheum 2010; 62: 85562.
  • 4
    Ramirez Gomez LA, Uribe Uribe O, Osio Uribe O, Grisales Romero H, Cardiel MH, Wojdyla D, et al. Childhood systemic lupus erythematosus in Latin America: the GLADEL experience in 230 children. Lupus 2008; 17: 596604.
  • 5
    Garcia MA, Marcos JC, Marcos AI, Pons-Estel BA, Wojdyla D, Arturi A, et al. Male systemic lupus erythematosus in a Latin-American inception cohort of 1214 patients. Lupus 2005; 14: 93846.
  • 6
    Alarcon-Segovia D, Alarcon-Riquelme ME, Cardiel MH, Caeiro F, Massardo L, Villa AR, et al, on behalf of the Grupo Latinoamericano de Estudio del Lupus Eritematoso (GLADEL). Familial aggregation of systemic lupus erythematosus, rheumatoid arthritis, and other autoimmune diseases in 1,177 lupus patients from the GLADEL cohort. Arthritis Rheum 2005; 52: 113847.
  • 7
    Gamarra AI, Matteson EL, Rodriquez AI, Rodriguez MI, Restrepo Suarez JF. An historical review of systemic lupus erythematosus in Latin America. Med Sci Monit 2004; 10: RA17185.
  • 8
    Pons-Estel BA, Catoggio LJ, Cardiel MH, Soriano ER, Gentiletti S, Villa AR, et al. The GLADEL multinational Latin American prospective inception cohort of 1,214 patients with systemic lupus erythematosus: ethnic and disease heterogeneity among “Hispanics”. Medicine (Baltimore) 2004; 83: 117.
  • 9
    Danchenko N, Satia JA, Anthony MS. Epidemiology of systemic lupus erythematosus: a comparison of worldwide disease burden. Lupus 2006; 15: 30818.
  • 10
    Malleson PN, Fung MY, Rosenberg AM. The incidence of pediatric rheumatic diseases: results from the Canadian Pediatric Rheumatology Association Disease Registry. J Rheumatol 1996; 23: 19817.
  • 11
    Nossent HC. Systemic lupus erythematosus in the Arctic region of Norway. J Rheumatol 2001; 28: 53946.
  • 12
    McCarty DJ, Manzi S, Medsger TA Jr, Ramsey-Goldman R, LaPorte RE, Kwoh CK. Incidence of systemic lupus erythematosus: race and gender differences. Arthritis Rheum 1995; 38: 126070.
  • 13
    Tucker LB, Uribe AG, Fernandez M, Apte M, McGwin G Jr, Vila LM, et al. Clinical differences between juvenile and adult onset patients with systemic lupus erythematosus (SLE): results from a multiethnic longitudinal cohort [abstract]. Arthritis Rheum 2006; 54 Suppl: S1623.
  • 14
    Font J, Cervera R, Espinosa G, Pallares L, Ramos-Casals M, Jimenez S, et al. Systemic lupus erythematosus (SLE) in childhood: analysis of clinical and immunological findings in 34 patients and comparison with SLE characteristics in adults. Ann Rheum Dis 1998; 57: 4569.
  • 15
    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: 86672.
  • 16
    Costallat LT, Coimbra AM. Systemic lupus erythematosus: clinical and laboratory aspects related to age at disease onset. Clin Exp Rheumatol 1994; 12: 6037.
  • 17
    Tucker LB. Making the diagnosis of systemic lupus erythematosus in children and adolescents. Lupus 2007; 16: 5469.
  • 18
    Rood MJ, ten Cate R, van Suijlekom-Smit LW, den Ouden EJ, Ouwerkerk FE, Breedveld FC, et al. Childhood-onset systemic lupus erythematosus: clinical presentation and prognosis in 31 patients. Scand J Rheumatol 1999; 28: 2226.
  • 19
    Brunner HI, Gladman DD, Ibanez D, Urowitz MD, Silverman ED. Difference in disease features between childhood-onset and adult-onset systemic lupus erythematosus. Arthritis Rheum 2008; 58: 55662.
  • 20
    McIntyre P, World Health Organization. Adolescent friendly health services: an agenda for change. Geneva: Department of Child and Adolescent Health and Development; 2003. URL: http://whqlibdoc.who.int/hq/2003/WHO_FCH_CAH_02.14.pdf.
  • 21
    Brookman RR. The age of “adolescence” [letter]. J Adolesc Health 1995; 16: 33940.
  • 22
    Hashkes PJ, Wright BM, Lauer MS, Worley SE, Tang AS, Roettcher PA, et al. Mortality outcomes in pediatric rheumatology in the US. Arthritis Rheum 2010; 62: 599608.
  • 23
    Avcin T, Cimaz R, Silverman ED, Cervera R, Gattorno M, Garay S, et al. Pediatric antiphospholipid syndrome: clinical and immunologic features of 121 patients in an international registry. Pediatrics 2008; 122: e11007.
  • 24
    Gutierrez-Suarez R, Ruperto N, Gastaldi R, Pistorio A, Felici E, Burgos-Vargas R, et al, for the Pediatric Rheumatology International Trials Organization (PRINTO). A proposal for a pediatric version of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index based on the analysis of 1,015 patients with juvenile-onset systemic lupus erythematosus. Arthritis Rheum 2006; 54: 298996.
  • 25
    Hiraki LT, Benseler SM, Tyrrell PN, Harvey E, Hebert D, Silverman ED. Ethnic differences in pediatric systemic lupus erythematosus. J Rheumatol 2009; 36: 253946.
  • 26
    Parodi A, Davi S, Pringe AB, Pistorio A, Ruperto N, Magni-Manzoni S, et al, for the Lupus Working Group of the Paediatric Rheumatology European Society. Macrophage activation syndrome in juvenile systemic lupus erythematosus: a multinational multicenter study of thirty-eight patients. Arthritis Rheum 2009; 60: 338899.
  • 27
    Silva CA, Hilario MO, Febronio MV, Oliveira SK, Almeida RG, Fonseca AR, et al. Pregnancy outcome in juvenile systemic lupus erythematosus: a Brazilian multicenter cohort study. J Rheumatol 2008; 35: 14148.
  • 28
    Silva CA, Hilario MO, Febronio MV, Oliveira SK, Terreri MT, Sacchetti SB, et al. Risk factors for amenorrhea in juvenile systemic lupus erythematosus (JSLE): a Brazilian multicentre cohort study. Lupus 2007; 16: 5316.
  • 29
    Avcin T, Benseler SM, Tyrrell PN, Cucnik S, Silverman ED. A followup study of antiphospholipid antibodies and associated neuropsychiatric manifestations in 137 children with systemic lupus erythematosus. Arthritis Rheum 2008; 59: 20613.
  • 30
    Campos LM, Omori CH, Lotito AP, Jesus AA, Porta G, Silva CA. Acute pancreatitis in juvenile systemic lupus erythematosus: a manifestation of macrophage activation syndrome? Lupus 2010; 19: 16548.
  • 31
    Deen ME, Porta G, Fiorot FJ, Campos LM, Sallum AM, Silva CA. Autoimmune hepatitis and juvenile systemic lupus erythematosus. Lupus 2009; 18: 74751.
  • 32
    Faco MM, Leone C, Campos LM, Febronio MV, Marques HH, Silva CA. Risk factors associated with the death of patients hospitalized for juvenile systemic lupus erythematosus. Braz J Med Biol Res 2007; 40: 9931002.
  • 33
    Febronio MV, Pereira RM, Bonfa E, Takiuti AD, Pereyra EA, Silva CA. Inflammatory cervicovaginal cytology is associated with disease activity in juvenile systemic lupus erythematosus. Lupus 2007; 16: 4305.
  • 34
    Fernandes EG, Savioli C, Siqueira JT, Silva CA. Oral health and the masticatory system in juvenile systemic lupus erythematosus. Lupus 2007; 16: 7139.
  • 35
    Hari P, Bagga A, Mahajan P, Dinda A. Outcome of lupus nephritis in Indian children. Lupus 2009; 18: 34854.
  • 36
    Hersh AO, Trupin L, Yazdany J, Panopalis P, Julian L, Katz P, et al. Childhood-onset disease as a predictor of mortality in an adult cohort of patients with systemic lupus erythematosus. Arthritis Care Res (Hoboken) 2010; 62: 11529.
  • 37
    Hiraki LT, Benseler SM, Tyrrell PN, Hebert D, Harvey E, Silverman ED. Clinical and laboratory characteristics and long-term outcome of pediatric systemic lupus erythematosus: a longitudinal study. J Pediatr 2008; 152: 5506.
  • 38
    Hoffman IE, Lauwerys BR, De Keyser F, Huizinga TW, Isenberg D, Cebecauer L, et al. Juvenile-onset systemic lupus erythematosus: different clinical and serological pattern than adult-onset systemic lupus erythematosus. Ann Rheum Dis 2009; 68: 4125.
  • 39
    Jesus AA, Liphaus BL, Silva CA, Bando SY, Andrade LE, Coutinho A, et al. Complement and antibody primary immunodeficiency in juvenile systemic lupus erythematosus patients. Lupus 2011; 20: 127584.
  • 40
    Jesus AA, Silva CA, Carneiro-Sampaio M, Sheinberg M, Mangueira CL, Marie SK, et al. Anti-C1q antibodies in juvenile-onset systemic lupus erythematosus. Ann N Y Acad Sci 2009; 1173: 2358.
  • 41
    Jurencak R, Fritzler M, Tyrrell P, Hiraki L, Benseler S, Silverman E. Autoantibodies in pediatric systemic lupus erythematosus: ethnic grouping, cluster analysis, and clinical correlations. J Rheumatol 2009; 36: 41621.
  • 42
    Kisiel BM, Kosinska J, Wierzbowska M, Rutkowska-Sak L, Musiej-Nowakowska E, Wudarski M, et al. Differential association of juvenile and adult systemic lupus erythematosus with genetic variants of oestrogen receptors α and β. Lupus 2011; 20: 859.
  • 43
    Mok CC, Wong SN, Ma KM. Childhood-onset disease carries a higher risk of low bone mineral density in an adult population of systemic lupus erythematosus. Rheumatology (Oxford) 2012; 51: 46875.
  • 44
    Moorthy LN, Peterson MG, Hassett AL, Baratelli M, Chalom EC, Hashkes PJ, et al. Relationship between health-related quality of life and SLE activity and damage in children over time. Lupus 2009; 18: 6229.
  • 45
    Pereira T, Abitbol CL, Seeherunvong W, Katsoufis C, Chandar J, Freundlich M, et al. Three decades of progress in treating childhood-onset lupus nephritis. Clin J Am Soc Nephrol 2011; 6: 21929.
  • 46
    Rygg M, Pistorio A, Ravelli A, Maghnie M, Di Iorgi N, Bader-Meunier B, et al, for the Paediatric Rheumatology International Trials Organisation (PRINTO). A longitudinal PRINTO study on growth and puberty in juvenile systemic lupus erythematosus. Ann Rheum Dis 2012; 71: 5117.
  • 47
    Silva CA, Deen ME, Febronio MV, Oliveira SK, Terreri MT, Sacchetti SB, et al. Hormone profile in juvenile systemic lupus erythematosus with previous or current amenorrhea. Rheumatol Int 2011; 31: 103743.
  • 48
    Wang CH, Yao TC, Huang YL, Ou LS, Yeh KW, Huang JL. Acute pancreatitis in pediatric and adult-onset systemic lupus erythematosus: a comparison and review of the literature. Lupus 2011; 20: 44352.
  • 49
    Spadoni M, Jacob C, Aikawa N, Jesus A, Fomin A, Silva C. Chronic autoimmune urticaria as the first manifestation of juvenile systemic lupus erythematosus. Lupus 2011; 20: 7636.
  • 50
    Brunner HI, Huggins J, Klein-Gitelman MS. Pediatric SLE: towards a comprehensive management plan. Nat Rev Rheumatol 2011; 7: 22533.
  • 51
    Mina R, Brunner HI. Pediatric lupus: are there differences in presentation, genetics, response to therapy, and damage accrual compared with adult lupus? Rheum Dis Clin North Am 2010; 36: 5380.
  • 52
    Abdwani R, Hira M, Al-Nabhani D, Al-Zakwani I. Juvenile systemic lupus erythematosus in the Sultanate of Oman: clinical and immunological comparison between familial and non-familial cases. Lupus 2011; 20: 3159.
  • 53
    Ahmadzadeh A, Derakhshan A, Ahmadzadeh A. A clinicopathological study of lupus nephritis in children. Saudi J Kidney Dis Transpl 2008; 19: 75660.
  • 54
    Ali US, Dalvi RB, Merchant RH, Mehta KP, Chablani AT, Badakere SS, et al. Systemic lupus erythematosus in Indian children. Indian Pediatr 1989; 26: 86873.
  • 55
    Ataei N, Haydarpour M, Madani A, Esfahani ST, Hajizadeh N, Moradinejad MH, et al. Outcome of lupus nephritis in Iranian children: prognostic significance of certain features. Pediatr Nephrol 2008; 23: 74955.
  • 56
    Aytac MB, Kasapcopur O, Aslan M, Erener-Ercan T, Cullu-Cokugras F, Arisoy N. Hepatitis B vaccination in juvenile systemic lupus erythematosus. Clin Exp Rheumatol 2011; 29: 8826.
  • 57
    Bader-Meunier B, Armengaud JB, Haddad E, Salomon R, Deschenes G, Kone-Paut I, et al. Initial presentation of childhood-onset systemic lupus erythematosus: a French multicenter study. J Pediatr 2005; 146: 64853.
  • 58
    Brunner HI, Feldman BM, Bombardier C, Silverman ED. Sensitivity of the Systemic Lupus Erythematosus Disease Activity Index, British Isles Lupus Assessment Group Index, and Systemic Lupus Activity Measure in the evaluation of clinical change in childhood-onset systemic lupus erythematosus. Arthritis Rheum 1999; 42: 135460.
  • 59
    Campos LM, Kiss MH, D'Amico EA, Silva CA. Antiphospholipid antibodies and antiphospholipid syndrome in 57 children and adolescents with systemic lupus erythematosus. Lupus 2003; 12: 8206.
  • 60
    Campos LM, Kiss MH, Scheinberg MA, Mangueira CL, Silva CA. Antinucleosome antibodies in patients with juvenile systemic lupus erythematosus. Lupus 2006; 15: 496500.
  • 61
    Huang JL, Yao TC, See LC. Prevalence of pediatric systemic lupus erythematosus and juvenile chronic arthritis in a Chinese population: a nation-wide prospective population-based study in Taiwan. Clin Exp Rheumatol 2004; 22: 77680.
  • 62
    Huang JL, Yeh KW, Yao TC, Huang YL, Chung HT, Ou LS, et al. Pediatric lupus in Asia. Lupus 2010; 19: 14148.
  • 63
    Klein A, Cimaz R, Quartier P, Decramer S, Niaudet P, Baudouin V, et al. Causes of death in pediatric systemic lupus erythematosus. Clin Exp Rheumatol 2009; 27: 5389.
  • 64
    Salah S, Lotfy HM, Mokbel AN, Kaddah AM, Fahmy N. Damage index in childhood-onset systemic lupus erythematosus in Egypt. Pediatr Rheumatol Online J 2011; 9: 36.
  • 65
    Salah S, Lotfy HM, Sabry SM, El Hamshary A, Taher H. Systemic lupus erythematosus in Egyptian children. Rheumatol Int 2009; 29: 14638.
  • 66
    Takei S, Maeno N, Shigemori M, Imanaka H, Mori H, Nerome Y, et al. Clinical features of Japanese children and adolescents with systemic lupus erythematosus: results of 1980-1994 survey. Acta Paediatr Jpn 1997; 39: 2506.
  • 67
    Tsai YC, Yeh KW, Yao TC, Huang YL, Kuo ML, Huang JL. Mannose-binding lectin expression genotype in pediatric-onset systemic lupus erythematosus: associations with susceptibility to renal disease and protection against infections. J Rheumatol 2011; 38: 142935.
  • 68
    Scott KM, Von Korff M, Alonso J, Angermeyer MC, Benjet C, Bruffaerts R, et al. Childhood adversity, early-onset depressive/anxiety disorders, and adult-onset asthma. Psychosom Med 2008; 70: 103543.
  • 69
    Schober E, Rami B, Grabert M, Thon A, Kapellen T, Reinehr T, et al. Phenotypical aspects of maturity-onset diabetes of the young (MODY diabetes) in comparison with type 2 diabetes mellitus (T2DM) in children and adolescents: experience from a large multicentre database. Diabet Med 2009; 26: 46673.
  • 70
    Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 2004; 31: 3902.
  • 71
    Cimaz R, Casadei A, Rose C, Bartunkova J, Sediva A, Falcini F, et al. Primary Sjogren syndrome in the paediatric age: a multicentre survey. Eur J Pediatr 2003; 162: 6615.
  • 72
    Kotajima L, Aotsuka S, Sumiya M, Yokohari R, Tojo T, Kasukawa R. Clinical features of patients with juvenile onset mixed connective tissue disease: analysis of data collected in a nationwide collaborative study in Japan. J Rheumatol 1996; 23: 108894.
  • 73
    Zulian F, Athreya BH, Laxer R, Nelson AM, Feitosa de Oliveira SK, Punaro MG, et al. Juvenile localized scleroderma: clinical and epidemiological features in 750 children. An international study. Rheumatology (Oxford) 2006; 45: 61420.
  • 74
    Martini G, Foeldvari I, Russo R, Cuttica R, Eberhard A, Ravelli A, et al, for the Juvenile Scleroderma Working Group of the Pediatric Rheumatology European Society. Systemic sclerosis in childhood: clinical and immunologic features of 153 patients in an international database. Arthritis Rheum 2006; 54: 39718.
  • 75
    Ozen S, Pistorio A, Iusan SM, Bakkaloglu A, Herlin T, Brik R, et al. EULAR/PRINTO/PRES criteria for Henoch-Schonlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: final classification criteria. Ann Rheum Dis 2010; 69: 798806.
  • 76
    Guseinova D, Consolaro A, Trail L, Ferrari C, Pistorio A, Ruperto N, et al. Comparison of clinical features and drug therapies among European and Latin American patients with juvenile dermatomyositis. Clin Exp Rheumatol 2011; 29: 11724.
  • 77
    Ravelli A, Trail L, Ferrari C, Ruperto N, Pistorio A, Pilkington C, et al. Long-term outcome and prognostic factors of juvenile dermatomyositis: a multinational, multicenter study of 490 patients. Arthritis Care Res (Hoboken) 2010; 62: 6372.
  • 78
    Sato JO, Sallum AM, Ferriani VP, Marini R, Sacchetti SB, Okuda EM, et al. A Brazilian registry of juvenile dermatomyositis: onset features and classification of 189 cases. Clin Exp Rheumatol 2009; 27: 10318.
  • 79
    Da Silva CH. Rheumatic fever: a multicenter study in the state of Sao Paulo. Pediatric Committee—Sao Paulo Pediatric Rheumatology Society. Rev Hosp Clin Fac Med Sao Paulo 1999; 54: 8590.
  • 80
    Moraes AJ, Soares PM, Leal MM, Sallum AM, Lotito AP, Silva CA. Aspects of the pregnancy and post delivery of adolescents with rheumatic fever. Rev Assoc Med Bras 2004; 50: 2936. In Portuguese.
  • 81
    Al-Sharif B, Hall MC. Lyme disease testing in children in an endemic area. WMJ 2011; 110: 22833.
  • 82
    Long MD, Crandall WV, Leibowitz IH, Duffy L, del Rosario F, Kim SC, et al. Prevalence and epidemiology of overweight and obesity in children with inflammatory bowel disease. Inflamm Bowel Dis 2011; 17: 21628.
  • 83
    Radzikowski A, Banaszkiewicz A, Lazowska-Przeorek I, Grzybowska-Chlebowczyk U, Wos H, Pytrus T, et al. Immunogenecity of hepatitis A vaccine in pediatric patients with inflammatory bowel disease. Inflamm Bowel Dis 2011; 17: 111724.
  • 84
    Kashikar-Zuck S, Ting TV, Arnold LM, Bean J, Powers SW, Graham TB, et al. Cognitive behavioral therapy for the treatment of juvenile fibromyalgia: a multisite, single-blind, randomized, controlled clinical trial. Arthritis Rheum 2012; 64: 297305.
  • 85
    Zapata AL, Moraes AJ, Leone C, Doria-Filho U, Silva CA. Pain and musculoskeletal pain syndromes related to computer and video game use in adolescents. Eur J Pediatr 2006; 165: 40814.
  • 86
    Moraes AJ, Soares PM, Zapata AL, Lotito AP, Sallum AM, Silva CA. Panniculitis in childhood and adolescence. Pediatr Int 2006; 48: 4853.
  • 87
    Belot A, Duquesne A, Job-Deslandre C, Costedoat-Chalumeau N, Boudjemaa S, Wechsler B, et al. Pediatric-onset relapsing polychondritis: case series and systematic review. J Pediatr 2010; 156: 4849.
  • 88
    Rush PJ, Baumal R, Shore A, Balfe JW, Schreiber M. Correlation of renal histology with outcome in children with lupus nephritis. Kidney Int 1986; 29: 106671.
  • 89
    Satsangi J, Silverberg MS, Vermeire S, Colombel JF. The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut 2006; 55: 74953.
  • 90
    Uddin LQ, Supekar KS, Ryali S, Menon V. Dynamic reconfiguration of structural and functional connectivity across core neurocognitive brain networks with development. J Neurosci 2011; 31: 1857889.

Supporting Information

  1. Top of page
  2. Abstract
  3. Introduction
  4. Is there a need for a different term to refer to SLE among children and adolescents?
  5. When does adulthood start?
  6. Current status of nomenclature used in the medical literature
  7. Nomenclature used in the medical literature for chronic diseases in childhood
  8. Discussion
  9. AUTHOR CONTRIBUTIONS
  10. Acknowledgements
  11. REFERENCES
  12. Supporting Information

Additional Supporting Information may be found in the online version of this article.

FilenameFormatSizeDescription
ACR_21757_sm_Appendix.doc22KSupplementary Data Appendix A

Please note: Wiley Blackwell is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.