LES en Niños Cuadro Clinico y DX 2024

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Lupus eritematoso sistémico (LES) de inicio infantil:

manifestaciones clínicas y diagnóstico
AUTOR: Deborah M Levy, MD, MS, FRCPC
EDITOR DE SECCIÓN: Marisa Klein-Gitelman, MD, MPH
EDITOR ADJUNTO: Siobhan M Caso, MD, MHS
Todos los temas se actualizan a medida que hay nueva evidencia disponible y nuestro proceso de revisión por pares se
completa.
Revisión de la literatura vigente hasta: marzo de 2024.

Este tema se actualizó por última vez: 24 de junio de 2022.
INTRODUCCIÓN
El lupus eritematoso sistémico (LES) es una enfermedad inflamatoria autoinmune crónica de

causa desconocida que puede afectar cualquier sistema orgánico, con mayor frecuencia la piel,
las articulaciones, los riñones y los sistemas nervioso, hematológico y cardiovascular. Se
caracteriza por la producción de múltiples autoanticuerpos. Aunque el LES en niños es
fundamentalmente la misma enfermedad que en adultos, con etiología, patogénesis y
hallazgos de laboratorio similares, existen algunas diferencias en la frecuencia y gravedad de
ciertas manifestaciones clínicas. En general, se acepta que los niños con LES tienen una mayor
gravedad de la enfermedad y una acumulación más temprana de daño por enfermedad que los
adultos con LES [ 1 - 5 ]. La atención de niños y adolescentes con LES es diferente a la de los
adultos debido al impacto de la enfermedad y su terapia en el crecimiento y desarrollo físico,
psicosocial y emocional. (Ver "Manifestaciones clínicas y diagnóstico del lupus eritematoso
sistémico en adultos", sección de 'Manifestaciones clínicas' .)
Aquí se revisan la epidemiología, las características clínicas, el diagnóstico y la clasificación del

LES de inicio en la infancia (LESc). El tratamiento, las complicaciones y el pronóstico del LESc se
analizan por separado. (Ver "Lupus eritematoso sistémico (LES) en niños: tratamiento,
complicaciones y pronóstico" .
EPIDEMIOLOGÍA
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La mejor estimación es que el LESc afecta a entre 5.000 y 10.000 niños en los Estados Unidos [ 6
] y afecta a las mujeres con más frecuencia que a los hombres (8 a 9:1), incluso en el grupo de
edad prepúber (4 a 5:1) [ 7- 9 ]. El LES puede ocurrir a cualquier edad, aunque es raro antes de
los cinco años y es cada vez más frecuente después de la primera década de la vida [ 7,10 - 12 ].
Entre el 10 y el 20 por ciento de todas las personas que desarrollan LES lo hacen en la niñez.
(Ver "Epidemiología y patogénesis del lupus eritematoso sistémico", sección sobre
'Epidemiología' ).
Worldwide, estimates of cSLE incidence are between 0.3 to 2.2 per 100,000 children-years, while
prevalence rates range widely from 3.3 to 9.7 per 100,000 children and adolescents, depending
upon the population studied and its ethnic distribution [13-24]. Persons of Asian, African,
Indigenous North American, and Hispanic/Latino ancestry are more frequently and more
severely affected than those of European ancestry [13,25-28].
PATHOGENESIS
The etiology of SLE remains unknown, but genetic, hormonal, immunologic, and environmental
factors are suspected to play a role. However, unique to cSLE is the identification of monogenic
forms of SLE, mainly due to defects in the complement system; type I interferon pathway;
aberrant nucleic acid repair, degradation, and sensing; or abnormal B cell development [29,30].
Many of the clinical manifestations are mediated directly or indirectly by antibody formation
and the creation of immune complexes. The etiology and pathogenesis of SLE are discussed in
greater detail separately. (See "Epidemiology and pathogenesis of systemic lupus
erythematosus".)
CLINICAL MANIFESTATIONS
The presenting manifestations of cSLE are diverse, and any organ system may be involved
( table 1) [31]. Many children and adolescents have an insidious onset of persistent fever,
weight loss, fatigue, and arthralgia with general deterioration over weeks to months. Major
organ involvement typically occurs within the first two to three years of disease onset. However,
some new patients have acute or even life-threatening symptoms at presentation due to
concomitant macrophage activation syndrome (MAS), severe renal disease, severe
neuropsychiatric manifestations, or acute thromboembolic disease. Children with earlier-onset
cSLE (<10 years of age) tend to have more severe disease activity and poorer prognosis [32,33].
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Children may have small joint arthritis and renal disease, both of which are commonly
overlooked before the diagnosis of SLE is established. The classic malar rash ( picture 1 and
picture 2) may be absent or overlooked when there are only subtle changes. The rash may
also appear as less conspicuous erythema or hypopigmentation in persons with darker skin
pigmentation. Thus, the malar rash must not be relied upon to suggest the diagnosis.
In reviews from multiple different countries, the most common presenting manifestations were
as follows [1,7,11,13,34-36]:
● Hematologic (55 to 77 percent) – Anemia, lymphopenia, leukopenia, and/or

thrombocytopenia
● Mucocutaneous (70 percent) – Malar rash, photosensitivity, oral or nasal ulcers, and/or
discoid rash
● Musculoskeletal (61 to 64 percent) – Arthritis, arthralgia, and/or serositis
● Renal abnormalities (27 to 59 percent) – Proteinuria, hematuria, and/or casts suggestive of

nephritis; nephrotic syndrome; and/or biopsy-proven lupus nephritis
● Fever (26 to 58 percent)
Pulmonary, thromboembolic, cardiac, neuropsychiatric, and gastrointestinal manifestations are

also reported [7,11,13,36].
Hematologic abnormalities, lupus nephritis, fever, ocular symptoms, seizures, and

lymphadenopathy are more common in cSLE than adult-onset SLE (aSLE), whereas Raynaud
phenomenon, pleuritis, and sicca symptoms (dry eyes, dry mouth) are more common
manifestations in aSLE [37,38]. (See "Clinical manifestations and diagnosis of systemic lupus
erythematosus in adults", section on 'Clinical manifestations'.)
Mucocutaneous — Skin and mucous membrane findings include the butterfly (malar) rash
( picture 1 and picture 2), oral and/or nasal ulcers, and nonscarring alopecia. However, the
classic skin findings may be absent in children at presentation. Although the classic malar rash
crosses the nasal bridge and spares the nasolabial folds, the rash also frequently affects the
chin and the ears or may present as a hypopigmented rash, especially in children with darker
pigmentation. Other skin manifestations in cSLE include a frequently diffuse maculopapular
rash, discoid lupus erythematosus (DLE), and cutaneous vasculitis [39].
Following the dermatology classification [40], cutaneous lesions can be classified into:
● Acute cutaneous (eg, malar rash, generalized maculopapular rash)

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● Subacute cutaneous (eg, annular subacute cutaneous lupus erythematosus [SCLE])

● Chronic cutaneous (eg, DLE, lupus profundus, chilblain lupus erythematosus [LE]) lesions
DLE (or chronic cutaneous lupus) occurs as an isolated syndrome in 90 to 95 percent of adults
with localized lesions and 70 to 85 percent of adults with generalized lesions. In children,
"isolated" DLE progresses to SLE in up to 25 percent of patients [41]. Acute cutaneous lesions
are most common in cSLE, and mucocutaneous involvement in SLE is reviewed in greater detail
separately. (See "Overview of cutaneous lupus erythematosus", section on 'Lupus
erythematosus-specific skin disease' and "Overview of cutaneous lupus erythematosus", section
on 'Lupus nonspecific skin disease' and "Overview of cutaneous lupus erythematosus", section
on 'Mucosal manifestations'.)
Thinning of the hair, especially in the frontotemporal areas, is common in cSLE, while diffuse
alopecia is less frequent. "Lupus hair" (thin, unruly hair that easily fractures) can occur in
addition to one or multiple localized patches of alopecia areata [42]. Telogen effluvium is also
seen, occurring up to three months following a flare of cSLE disease. (See "Overview of
cutaneous lupus erythematosus", section on 'Nonscarring alopecia'.)
Systemic — Low-grade fever, fatigue, anorexia, and lymphadenopathy are common

manifestations of SLE at onset but do not differentiate the diagnosis of SLE from other systemic
illnesses. Persistent high fevers above 38.6°C (101.5°F) may occur; however, coexisting infection
and MAS should always be excluded in these cases.
Musculoskeletal — The most common musculoskeletal findings in children with SLE are
arthritis and arthralgias. The arthritis of cSLE affects both large and small joints. Contrary to
usual teaching, the arthritis of cSLE is not always painful and, in many cases, may be
asymptomatic and only noted on careful physical examination [43]. These manifestations are
reviewed in greater detail separately. (See "Arthritis and other musculoskeletal manifestations of
systemic lupus erythematosus", section on 'Joint involvement'.)
Additional bony abnormalities include osteopenia, osteoporosis, and osteonecrosis (avascular

necrosis) [44,45]. Low bone mineral density (BMD) is frequently observed at cSLE diagnosis and
does not improve throughout the disease course, even when glucocorticoids are tapered and
stopped [46,47]. In one case series of 64 consecutive children with SLE, dual x-ray
absorptiometry (DXA) scanning demonstrated lumbar spine osteopenia in 24 patients (38
percent), osteoporosis in 13 (20 percent), and decreased hip BMD in 12 patients (19 percent)
[44]. Osteoporosis in SLE is discussed in greater detail separately, and vitamin D deficiency is
discussed below. (See "Arthritis and other musculoskeletal manifestations of systemic lupus
erythematosus", section on 'Osteoporosis' and 'Laboratory findings' below.)
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Renal — Renal involvement in SLE may vary from the detection of hematuria and proteinuria on
routine examination to the presence of nephrotic syndrome or acute kidney injury. Some
degree of renal involvement is present in up to two-thirds of patients with cSLE evaluated at
major medical centers [48]. However, in a study of US children with SLE enrolled in Medicaid
from 2000 to 2004, only 37 percent had lupus nephritis [16]. A higher rate of lupus nephritis was
seen in adolescent-onset SLE compared with aSLE in one series [49]. Similar to aSLE patients
with lupus nephritis, Black patients have worse prognosis regardless of socioeconomic status.
(See "Acute kidney injury in children: Clinical features, etiology, evaluation, and diagnosis" and
"Lupus nephritis: Diagnosis and classification".)
Lupus nephritis is classified by histopathology and ranges from class I (normal or near normal)
to class VI (end-stage kidney disease), with proliferative nephritis (class III or class IV)
representing almost half of all renal lesions [50]. Proliferative lesions are the most severe and
require intensive immunosuppression as they are the most likely to progress to end-stage
kidney disease. If urinalysis demonstrates any proteinuria or if the sample is dilute and mild
proteinuria is not elucidated on dipstick, quantification of the urine protein is required. Spot
urine protein-to-creatinine ratio is an accurate alternative to a 24-hour collection. Orthostatic
proteinuria should be excluded in isolated proteinuria by examination of a first morning urine
sample.
A renal biopsy is required for accurate diagnosis of lupus nephritis. Indications include cSLE with
proteinuria or renal insufficiency as suggested by increased creatinine or decreased estimated
glomerular filtration rate (eGFR). Isolated hematuria is unusual in cSLE and therefore warrants a
biopsy to rule out other causes, if present. Absolute contraindications to biopsy include a
requirement for anticoagulation, uncorrected thrombocytopenia, or uncontrolled hypertension;
a relative contraindication is a solitary kidney [51]. (See "Lupus nephritis: Diagnosis and
classification".)
Hematologic — Hematologic abnormalities, including anemia, leukopenia, lymphopenia, and

thrombocytopenia, are common among children with SLE [52-58]. Isolated thrombocytopenia
(immune thrombocytopenia [ITP]) or Evans syndrome (immune thrombocytopenia and
concomitant autoimmune hemolytic anemia) may be diagnosed months to years prior to the
diagnosis of cSLE [59]. (See "Hematologic manifestations of systemic lupus erythematosus" and
'Laboratory findings' below and "Autoimmune hemolytic anemia (AIHA) in children:
Classification, clinical features, and diagnosis", section on 'Evans syndrome'.)
● Anemia – Anemia, defined as a hemoglobin concentration more than two standard

deviations below the mean for age and sex (defined as hemoglobulin ≤12 g/dL in several
studies), is present in 50 to 75 percent of affected children [55,56,60]. The most common
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types of anemia, which may occur separately or in combination, are iron deficiency
anemia, Coombs-positive autoimmune hemolytic anemia (AIHA), and anemia of chronic
disease [55,56,61]. Concomitant hemoglobinopathies, such as alpha or beta thalassemia
trait or sickle cell trait, may also contribute to anemia. (See "Approach to the child with
anemia" and "Anemia of chronic disease/anemia of inflammation" and "Iron deficiency in
infants and children <12 years: Screening, prevention, clinical manifestations, and
diagnosis" and "Autoimmune hemolytic anemia (AIHA) in children: Classification, clinical
features, and diagnosis" and "Overview of hemolytic anemias in children".)
● Leukopenia – Leukopenia, defined as a total white blood cell (WBC) count <4000/microL
[62,63], occurs in nearly two-thirds of children at some point during the course of illness
[53,54,60,64]. The decrease in WBC count is primarily due to a fall in absolute lymphocyte
count [7,11,64]. Neutropenia is less common in SLE. Lymphopenia and neutropenia may
be due to the underlying disease process or to treatment or infection. In the case of high-
dose glucocorticoid therapy, the total WBC count usually increases due to demargination
while the lymphocyte count decreases.
● Thrombocytopenia – The reported prevalence of thrombocytopenia varies from 10 to 50

percent [65-68]. Frequently, the degree of thrombocytopenia is mild (platelet counts
between 100,000 and 150,000/microL), and hemorrhage is rare [65], although platelet
counts under 10,000/microL with associated petechiae, purpura, and bleeding do occur.
ITP, although isolated thrombocytopenia by definition, may be the first manifestation of
cSLE, antedating this diagnosis by many years [69-73]. Thrombotic thrombocytopenic
purpura (TTP) is an uncommon, acute and life-threatening complication that may also be
the initial presenting feature of cSLE [74-76]. Antiphospholipid antibodies (aPLs) and other
autoantibodies are discussed below [65,77,78]. (See "Immune thrombocytopenia (ITP) in
children: Clinical features and diagnosis" and "Diagnostic approach to suspected TTP, HUS,
or other thrombotic microangiopathy (TMA)" and "Approach to the child with unexplained
thrombocytopenia".)
Neuropsychiatric — cSLE is associated with many neuropsychiatric syndromes and additional

unclassified neuropsychiatric manifestations (NPSLE) [79]. One or more neuropsychiatric
manifestations are reported in up to two-thirds of cSLE patients [80-88]. The most common
manifestation is headache, followed by cognitive impairment, psychosis, seizures, mood
disorders, anxiety disorders, and cerebrovascular disease. Less common manifestations include
acute confusional state, peripheral neuropathy, chorea (movement disorders), cranial nerve
palsy, and transverse myelitis. Neuropsychiatric symptoms can present with a gradual onset of
symptoms over weeks to months but, if untreated and severe, can result in significant
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impairment in thought, cognition, and even consciousness. Cognitive impairment in cSLE occurs
during a time of important brain development, and significant challenges remain in diagnosis
and management [89-91]. Neurologic manifestations of SLE are discussed in greater detail
separately. (See "Neurologic and neuropsychiatric manifestations of systemic lupus
erythematosus" and "Manifestations of systemic lupus erythematosus affecting the peripheral
nervous system".)
Appropriate attribution of neuropsychiatric manifestations to underlying SLE is important

because it influences the approach to treatment. Differentiating active SLE from underlying
infection, primary neuropsychiatric illness, a medication side effect, or other autoimmune
disease requires careful history taking, physical examination, and appropriate laboratory and
imaging studies that may include bloodwork, magnetic resonance imaging (MRI),
electroencephalogram (EEG), and lumbar puncture (LP) [92,93]. (See "Neurologic and
neuropsychiatric manifestations of systemic lupus erythematosus", section on 'Attribution of a
clinical syndrome to SLE'.)
Pulmonary — Most reviews of cSLE report respiratory findings in 30 to 50 percent of patients,

with pleuritis being the most common (30 to 35 percent of children with SLE) [7,64,94-96]. Chest
pain is the most common presenting symptom, whereas predominant complaints of shortness
of breath are rare [94,97,98]. Children with pleuritis typically complain of chest pain that is sharp
("stabbing"), often severe, exacerbated by deep inspiration, and usually well localized. The
diagnosis of pleuritis in a child with SLE is usually made with plain radiographs of the chest that
demonstrate pleural fluid on one or both sides. Significantly elevated C-reactive protein (CRP)
levels are frequently observed in patients with serositis (pleuritis and/or pericarditis) in contrast
to the normal or minimally elevated levels observed in patients with other manifestations of
active cSLE [99,100]. (See "Pulmonary manifestations of systemic lupus erythematosus in
adults".)
Subclinical lung disease (eg, restrictive lung disease or reduced diffusion capacity identified
through pulmonary function testing [PFT] with diffusing capacity for carbon monoxide [DLCO])
is present in as many as 60 to 70 percent of patients who are tested [95,97,101-103]. As such,
PFTs with DLCO should be performed whenever there are new or increasing complaints of
shortness of breath. (See "Overview of pulmonary function testing in children".)
Acute pulmonary hemorrhage [94,98,104-107] and pulmonary hypertension [98,108] are the
most severe forms of lupus-associated pulmonary involvement, although they occur
infrequently in children with SLE (<5 and <2 percent, respectively). Pulmonary hemorrhage is an
acute emergency. The clinical manifestations of acute pulmonary hemorrhage include fever,
cough, fatigue, pallor, tachypnea, and epistaxis or hemoptysis, although frank hemoptysis is
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frequently absent. Any child with SLE who experiences acute shortness of breath with a sudden
drop in hemoglobin should be evaluated promptly for pulmonary hemorrhage. Other
considerations for a patient with cSLE and hemoptysis are infection and pulmonary embolism.
(See "Hemoptysis in children".)
Pulmonary hypertension in cSLE is rare, and, although initially attributed to multiple

thromboses, the etiology is now thought to be multifactorial [108,109]. Symptoms include
dyspnea on exertion, fatigue, lethargy, chest pain, exertional syncope, cough, hemoptysis, and
hoarseness (caused by compression of the left recurrent laryngeal nerve by a dilated main
pulmonary artery). It should be suspected in any child with increasing tricuspid insufficiency on
echocardiogram and is confirmed by demonstrating increased pulmonary arterial systolic
pressure. (See "Pulmonary hypertension in children: Classification, evaluation, and diagnosis".)
Other rare pulmonary manifestations of SLE in children include shrinking lung syndrome [110-
112] and pneumonitis [94,98]. (See "Pulmonary manifestations of systemic lupus erythematosus
in adults".)
Thromboembolic — Thromboembolic disease can complicate SLE, particularly in the context of

aPLs. Although one-quarter to two-thirds of patients with cSLE are positive for aPLs, fewer than
half of these patients will have a thrombotic event (see 'Laboratory findings' below). In cSLE, the
lupus anticoagulant is the greatest risk factor for the subsequent development of thrombosis
[78], and the contribution of anticardiolipin antibodies and other aPLs (eg, anti-beta-2-
glycoprotein 1) antibodies is not as well delineated. Antiphospholipid syndrome (APS) is
diagnosed when a cSLE patient with aPLs has a thrombotic event [113,114]. In cSLE-associated
APS, venous thromboembolic events are far more common than arterial events. Deep vein
thrombosis (DVT) is most frequent, followed by cerebral sinus venous thrombosis (CSVT),
pulmonary embolus, and lastly arterial stroke [115]. (See "Clinical manifestations of
antiphospholipid syndrome" and 'Laboratory findings' below and "Clinical manifestations and
diagnosis of systemic lupus erythematosus in adults", section on 'Clinical manifestations'.)
Although lupus anticoagulant predisposes to thrombosis, bleeding in a patient with cSLE,

prolonged prothrombin time (PT), partial thromboplastin time (PTT), and a positive lupus
anticoagulant is probably due to antibodies to prothrombin (factor II) and is known as lupus
anticoagulant-hypoprothrombinemia syndrome (LAHPS) [116].
Cardiac — Pericarditis is the most common cardiac abnormality in children with SLE,
particularly within the first six months of diagnosis, and is clinically significant in nearly one-
quarter [7,98,117]. Other cardiovascular disease, such as myocarditis, valvular disease (eg,
endocarditis) [102,118,119], and coronary artery disease (CAD), are rare. (See "Coronary artery
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disease in systemic lupus erythematosus" and "Clinical manifestations and diagnosis of

myocarditis in children" and "Non-coronary cardiac manifestations of systemic lupus
erythematosus in adults".)
The prevalence of clinical heart disease among children with SLE ranges in various studies from
12 to 54 percent [98,117,119,120], and myopericardial manifestations occur at a rate 4.4-fold
higher in cSLE compared with aSLE [121]. Subclinical disease, detected by echocardiography or
found in autopsy studies, also occurs in many children [102,118,122,123]. In a retrospective
review of 40 children with SLE who had at least one echocardiogram, 68 percent of subjects (27
of 40) had abnormalities [102]. These abnormalities were persistent in 5 of 14 subjects who had
a second echocardiogram, of whom three were found to have moderately severe cardiac
defects.
The classic presentation of pericarditis is an acute, sharp, anterior chest pain, often
accompanied by dyspnea. Inspiration exacerbates the pain, which may be alleviated by an
upright forward leaning position. On physical examination, low-grade fever, tachycardia, and
tachypnea are commonly present. A pericardial rub also may be heard. Bloodwork frequently
demonstrates a significantly elevated CRP level [99,100]. Large pericardial effusions may
accumulate without symptoms until they cause cardiac tamponade [124-127]. These children
present with symptoms suggestive of heart failure and accompanied by findings of distant
heart sounds, pulsus paradoxus, hepatomegaly, and jugular venous distention. The diagnosis is
suggested by enlargement of the cardiac silhouette on chest radiographs (ie, water bottle-
shaped heart) and confirmed by echocardiography. (See "Acute pericarditis: Clinical
presentation and diagnosis".)
Children with SLE have an increased risk for early atherosclerosis and CAD that may not become
clinically apparent until they are young adults [128-131]. CAD directly impacts the long-term
prognosis of children with SLE, particularly since the first recognized manifestation of CAD in
children with SLE is often myocardial infarction [119,132,133]. (See "Coronary artery disease in
systemic lupus erythematosus".)
Heart failure in children with SLE is usually the result of renal or pulmonary compromise (eg,
hypertension, glomerulonephritis and/or nephrosis, and pulmonary disease) rather than
intrinsic cardiac disease. (See 'Renal' above and 'Pulmonary' above.)
Gastrointestinal — Gastrointestinal involvement occurs in approximately 20 percent of

children with SLE. In one case series, 39 of 201 children with SLE had gastrointestinal
involvement [134]. Symptoms included pain due to ascites (n = 14), pancreatitis (n = 12), or
complications of treatment (n = 1) or infection (n = 1). Pancreatitis in particular has increased
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morbidity. Asymptomatic mild hepatitis (liver enzyme elevations two to three times the upper
range of normal) is a frequent finding at disease onset, although it is important to rule out
infectious causes of hepatitis [135,136].
Autoimmune hepatitis (AIH) may be diagnosed prior to cSLE diagnosis, with positive antismooth
muscle antibodies but without antiliver kidney microsomal antibodies [137]. Hepatomegaly may
differentiate primary AIH from cSLE-associated hepatitis, although the histopathology are
similar and are probably within a spectrum of disease. (See "Gastrointestinal manifestations of
systemic lupus erythematosus".)
LABORATORY FINDINGS
Common laboratory findings in children with SLE, in addition to the hematologic abnormalities
discussed above, include presence of autoantibodies such as antinuclear antibodies (ANAs),
double-stranded DNA (dsDNA) antibodies, antibodies to the extractable nuclear antigens (ENAs),
and antiphospholipid antibodies (aPLs) ( table 1). Vitamin D deficiency is frequent at
presentation in children and adolescents with SLE and may contribute to decreased bone
density and osteopenia [138]. These findings are in addition to elevated erythrocyte
sedimentation rate (ESR), a common marker of inflammation. C-reactive protein (CRP), however,
may be normal or only mildly elevated in active SLE and is often elevated only when a patient
with cSLE has concomitant infection, serositis, or macrophage activation syndrome (MAS).
Findings more specific to SLE include hypocomplementemia and urinary sediment
abnormalities. (See 'Hematologic' above and 'Renal' above and "Clinical manifestations and
diagnosis of systemic lupus erythematosus in adults", section on 'Laboratory testing'.)
In most series, 100 percent of children with SLE are ANA positive. Occasional cases of "ANA-
negative" SLE are described, although the concept is controversial, and an ANA-negative child
should be vigorously evaluated for alternative diagnoses. Rarely, false-negative ANAs are
observed when antibodies in high concentration fail to agglutinate unless multiple serum
dilutions are done (a prozone effect). Additional autoantibodies such as anti-dsDNA and anti-
Smith (anti-Sm) help to confirm the diagnosis of SLE but are not uniformly present. Antibodies
to Ro, La, and ribonucleoprotein (RNP) are found with varying frequency and are more frequent
in cSLE than in adult-onset SLE (aSLE). Although anti-Ro and anti-La antibodies occur in up to 30
percent of patients with cSLE, one study found that only 2.5 percent of patients with cSLE and
these antibodies have Sjögren's syndrome manifested by sicca symptoms including dry mouth,
dry eyes, and/or parotitis [139]. Antiribosomal P antibodies are found more frequently in
children than adults and are associated with active disease and neuropsychiatric, renal, or
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hepatic involvement [140,141]. However, they are not specific for particular manifestations and
do not provide prognostic value.
Antineutrophil cytoplasmic antibodies (ANCAs) are observed in SLE, but their presence is not
associated with disease activity or specific organ involvement [142].
All of these antibodies may also be found in children who do not fulfill classification criteria for
SLE. Some of these children will go on to develop SLE, others will develop other rheumatic
diseases, and some will remain asymptomatic. The diagnostic utility of these tests varies with
the population under study.
The prevalence of aPLs in children and adolescents with SLE has been evaluated in cross-
sectional cohort studies and ranges from 24 to 62 percent for lupus anticoagulant (LA) to 27 to
66 percent for anticardiolipin antibodies [77,78,115,143,144]. aPLs are associated with
thrombocytopenia, prolonged clotting times (eg, activated partial thromboplastin time [PTT]),
menorrhagia, unexplained thrombosis, and stroke [65]. However, aPLs are also found in many
children with SLE without these complications. Children and adolescents with SLE who have
aPLs should be presumed to have the same increased risk of developing a clotting disorder as
adults with aPLs [65,77,143], and they should be treated accordingly. (See 'Thromboembolic'
above and "Clinical manifestations of antiphospholipid syndrome".)
DIAGNOSIS
In addition to children with obvious manifestations of cSLE such as malar rash, polyarthritis,
serositis, and nephritis, the diagnosis should be suspected in any child with a gradual onset of
fever, anorexia, weight loss, and/or fatigue with persistent or worsening symptoms over several
weeks to months. Although fatigue is frequent, isolated chronic fatigue without other physical
findings at presentation of cSLE is rare. Additional suggestive clinical features include arthralgia,
discoid rash, alopecia, lymphadenopathy, peripheral edema, headache, cognitive impairment,
psychosis, seizures, mood disorders, anxiety disorders, and cerebrovascular disease (stroke).
Suggestive laboratory findings include persistent thrombocytopenia, hemolytic anemia,
lymphopenia, and leukopenia. A low index of suspicion for SLE in childhood is the primary
impediment to a proper diagnosis. Delayed diagnosis may be due to the frequent absence of
the typical findings of SLE at disease onset (eg, malar rash) or may be due to the high frequency
of nonspecific constitutional symptoms. The diagnosis is generally based upon clinical judgment
after excluding alternative diagnoses. In the absence of SLE diagnostic criteria, SLE classification
criteria are often used by clinicians to help identify some of the salient clinical features when
making the diagnosis. Serologic findings are important to suggesting the possibility of SLE. (See
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'Clinical manifestations' above and 'Classification criteria' below and 'Hematologic' above and
'Laboratory findings' above.)
Children who fulfill the American College of Rheumatology (ACR) criteria, Systemic Lupus
International Collaborating Clinics (SLICC) criteria, or 2019 European Alliance of Associations for
Rheumatology (EULAR; formerly known as European League Against Rheumatism)/ACR criteria
(see 'Classification criteria' below) are considered to have definite SLE. However, not all of the
manifestations required for a definite diagnosis may be present when the child is first seen, and
there are no official criteria for probable or possible SLE. A single manifestation of SLE, such as
thrombocytopenia, may predominate early in the course of the disease. Such children should be
carefully evaluated for the presence of additional manifestations of SLE, including an elevated
antinuclear antibody (ANA) titer [145]. If an elevated ANA titer is found, the patient should be
carefully evaluated for other manifestations of SLE [65,77,143]. Children with two or three
classification criteria may go on to develop a fourth over time, but others may ultimately
develop SLE without fulfilling the classification criteria. The key to proper care is to appropriately
treat the manifestations present when the child is first seen and to carefully follow for several
years those who present with fewer than four criteria for the development of additional findings
over time. (See 'Hematologic' above and 'Laboratory findings' above.)
Some children with SLE present acutely with a fever, rash, leukopenia, and thrombocytopenia;
findings that are suggestive of overwhelming infection [146,147] or macrophage activation
syndrome (MAS) [148]. The differentiation of SLE from intercurrent sepsis may be difficult and
may require simultaneous treatment for both conditions. (See 'Differential diagnosis' below and
"Sepsis in children: Definitions, epidemiology, clinical manifestations, and diagnosis" and "Septic
shock in children in resource-abundant settings: Rapid recognition and initial resuscitation (first
hour)" and "Systemic juvenile idiopathic arthritis: Course, prognosis, and complications", section
on 'Macrophage activation syndrome'.)
DIAGNOSTIC APPROACH
SLE is the "disease of a thousand faces." As such, a clinician should consider the diagnosis when
both specific and nonspecific signs and symptoms occur. Often there is a gestalt "sense" that
cSLE may be the underlying culprit, especially when a child or adolescent presents with a typical
constellation of mucocutaneous findings. However, even the most experienced clinicians have
been surprised when an unusual presentation eventually is diagnosed as cSLE. Because of the
myriad of presenting signs and symptoms, it is important to think of cSLE in order to proceed
with the appropriate testing in a timely way.
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As a start, suspect cSLE when a child or adolescent presents with any of the typical clinical
symptoms or laboratory findings shown in the table ( table 1). In particular, certain clinical
scenarios should prompt a further workup for cSLE. These include:
● The adolescent female with chronic thrombocytopenia

● The patient hospitalized with new-onset psychosis, acute confusional state, or atypical
anorexia nervosa
Although cSLE has a higher incidence in non-White females and usually has its onset after age
10 years, monogenic forms of cSLE are more likely in young patients (<5 years old) who have
severe disease and whose parents are consanguineous.
If cSLE is suspected, remember to look at the vital signs for evidence of hypertension, abnormal
heart rate, increased respiratory rate, or fever. A careful history should be followed by a physical
exam looking for alopecia (diffuse or circumscribed), malar rash, oral and nasal ulcers,
papilledema, lymphadenopathy (diffuse or localized), abnormal breath sounds, increased
respiratory effort, abnormal heart sounds and rhythm, hepatosplenomegaly, and peripheral
edema. A complete skin exam should be performed, looking for any rash on the scalp, face,
trunk, or extremities, and abnormalities of the nailfold capillaries such as hemorrhage or
dropout consistent with Raynaud syndrome. A musculoskeletal exam is important to examine
for arthritis and/or tenosynovitis, and a focused neurologic exam is imperative, especially in the
face of symptoms consistent with myositis, increased intracranial pressure, focal deficits, or
cranial or peripheral nerve abnormalities on history.
A basic laboratory workup should include a complete blood count (CBC) with differential,
creatinine, alanine aminotransferase (ALT), albumin, erythrocyte sedimentation rate (ESR), C-
reactive protein (CRP), complement components 3 and 4 (C3, C4), total immunoglobulin G (IgG),
immunoglobulin A (IgA), immunoglobulin M (IgM), and antinuclear antibodies (ANAs), in
addition to a urinalysis and a spot urine for protein and creatinine.
If ANA testing is positive and there are other signs or symptoms of cSLE, it is reasonable to
check for double-stranded DNA (dsDNA) antibodies and extractable nuclear antigens (ENAs).
The latter testing usually includes a panel of anti-Ro, anti-La, anti-Smith (anti-Sm), and anti-
ribonuclear protein (RNP) antibodies. Additionally, check for the presence of a lupus
anticoagulant, anticardiolipin (aCL) antibodies, direct antibody test (Coombs), and look for an
elevated reticulocyte count if the hemoglobin is reduced with signs of hemolysis. In the face of a
febrile or ill patient, ferritin and other markers of macrophage activation syndrome (MAS)
should be ascertained. (See "Clinical features and diagnosis of hemophagocytic
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lymphohistiocytosis" and "Systemic juvenile idiopathic arthritis: Course, prognosis, and

complications", section on 'Macrophage activation syndrome'.)
When clinically indicated by history and/or physical exam, supplemental laboratory testing can
include measuring thyroid-stimulating hormone (TSH) levels for hypothyroidism, anti-tissue
transglutaminase acid (TTG) antibodies for concomitant celiac disease, and serum electrolytes if
there are concerns around fluid status or renal function. In the presence of fever, cytopenias, or
signs of MAS, look for viruses including Epstein-Barr virus (EBV) and cytomegalovirus (CMV) in
particular as these can precipitate and/or occur concomitantly with the onset of cSLE. Testing
for tuberculosis with a tuberculin skin test and/or interferon (IFN) gamma release assay (IGRA)
should be done in patients with appropriate risk factors. A patient with pleural or pericardial
symptoms warrants an electrocardiogram (ECG), echocardiogram, and chest radiograph, while
patients with lymphadenopathy and/or hepatosplenomegaly may benefit from abdominal
and/or neck ultrasound. Magnetic resonance imaging (MRI) of affected organs (in particular the
brain and/or spinal cord) should be obtained when there are significant central nervous system
(CNS) or peripheral nervous system (PNS) symptoms. If there is any suspicion of thrombosis,
then the appropriate investigation(s) (usually ultrasound depending upon location of the
suspected thrombosis) should be obtained urgently. Many of these investigations should be
ordered only after consulting with the appropriate subspecialty services. (See "Venous
thrombosis and thromboembolism (VTE) in children: Risk factors, clinical manifestations, and
diagnosis".)
REFERRAL
Pediatric rheumatology should be consulted when cSLE is suspected, especially in a hospitalized

patient. In some centers, pediatric nephrology is involved in the care of all patients with cSLE,
and other subspecialists including pediatric neurology, hematology, psychiatry, dermatology,
ophthalmology, cardiology, and pulmonology are frequently involved in the diagnosis and
management.
CLASSIFICATION CRITERIA
Three classification criteria exist: one from the American College of Rheumatology (ACR), last
revised in 1997, a set of criteria titled the Systemic Lupus International Collaborating Clinics
(SLICC) group classification criteria (based upon ACR criteria and published in 2012), and the
2019 European Alliance of Associations for Rheumatology (EULAR)/ACR classification criteria
[149]. Any of these criteria may be used to aid in the diagnosis of SLE in both children and adults
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( table 2 and table 3) [62,63,150-152], although the SLICC criteria are more sensitive,
especially early on in cSLE [153].
For the older ACR criteria, a patient is classified as having SLE if four or more of the criteria are
present, either serially or simultaneously during any interval of observation in the absence of
another explanation for the findings. Similarly, for the SLICC criteria, four or more of the criteria
are required for classification, but the criteria present must include at least one clinical and one
immunologic criterion. An alternative to the requirement of four criteria is positive antinuclear
antibodies (ANAs) or anti-double-stranded DNA antibodies (anti-dsDNA) in conjunction with
biopsy-proven lupus nephritis. Other factors, such as family history, age, duration of symptoms,
and evolution of findings, must be considered before classifying a child as having SLE since
none of the individual clinical or immunologic criteria for the classification of SLE are disease
specific. Some patients may have severe organ manifestations of SLE without fulfilling
classification criteria and must be treated urgently or emergently without waiting for other
criteria to develop. As an example, a child with a positive ANA, positive anti-Ro antibody,
hypocomplementemia, and acute confusional state probably has SLE but would only fulfill one
ACR and three SLICC classification criteria. (See "Clinical manifestations and diagnosis of
systemic lupus erythematosus in adults", section on 'Classification criteria' and 'Diagnosis'
above.)
The 2019 joint EULAR/ACR classification criteria are notably different in that a positive ANA is
required for further consideration of SLE [149,154,155]. As seen in the table ( table 3), the
criteria are weighted within domains, providing a clinician a sense of the relative likelihood of
SLE (versus another disease) depending upon the clinical or laboratory feature present within a
domain. A total score of 10 or greater classifies a patient as having SLE. As an example, a patient
with mucocutaneous features might have nonscarring alopecia (score 2), oral ulcers (score 2),
subacute cutaneous lupus or discoid lupus (either scores 4), or acute cutaneous lupus (ie, malar
rash; score 6). Only the highest score is counted within each domain, so a child with a malar
rash and an oral ulcer would score 6.
Only one study (using the proposed rather than final published criteria) has examined the
validity of these criteria in cSLE, suggesting that sensitivity is similar to prior classification
criteria, although specificity might be improved by using a higher cutoff score of 13 rather than
10 [156]. Although classification criteria are designed to classify similar patients for research
studies and not for clinical diagnosis, clinicians recognize the utility of these criteria to aid in
diagnosis. Further study will determine if these criteria are suitable for use to distinguish a
patient with cSLE from a patient with another systemic autoimmune disease such as
dermatomyositis or systemic sclerosis.
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DIFFERENTIAL DIAGNOSIS
Ten percent or more of "healthy" children have a positive antinuclear antibody (ANA) [157-159].
Thus, most children with a positive ANA and arthralgias in the absence of other supporting
manifestations do not have cSLE. (See "Measurement and clinical significance of antinuclear
antibodies".)
The major considerations in the differential diagnosis and evaluation of a child with a positive
ANA and multisystem illness are infection and other autoimmune and systemic inflammatory
diseases. However, children with malignancies such as acute lymphoblastic leukemia may also
have a positive ANA, and it may be challenging to differentiate these two entities as both can
present with fever, bicytopenia or pancytopenia, lymphadenopathy, hepatosplenomegaly,
weight loss, and fatigue. A bone marrow aspirate and biopsy may be required when other
features that are exclusively in cSLE (such as a malar rash, nephritis, psychosis, or multiple
autoantibodies) are absent. Night awakening due to pain and leukopenia with significant
neutropenia are symptoms suggestive of underlying malignancy rather than cSLE. (See
"Overview of the clinical presentation and diagnosis of acute lymphoblastic leukemia/lymphoma
in children".)
While the differential diagnosis remains wide, other, rarer nonmalignant diseases to consider
include Kikuchi-Fujimoto disease and Castleman disease:
● Kikuchi-Fujimoto disease most frequently presents with unilateral cervical

lymphadenopathy and systemic features of fever, cytopenias, and elevated inflammatory
markers. The constellation of symptoms can resemble SLE, and patients can also develop
concomitant macrophage activation syndrome (MAS) with hyperferritinemia. The histology
of the lymph node biopsy (required for the diagnosis) reveals necrotizing histiocytic
lymphadenitis. Children with Kikuchi-Fujimoto disease may have a self-limited episode,
although up to 25 percent will go on to develop SLE within weeks to years [160,161]. In our
practice, we follow children with Kikuchi-Fujimoto disease (especially in the presence of
any positive autoantibodies) longitudinally. (See "Kikuchi disease".)
● Castleman disease is a nonclonal lymphoproliferative disorder that presents with localized

(unicentric) or diffuse (multicentric) lymphadenopathy, with concomitant systemic features
including fever, cytopenias, and elevated inflammatory markers. Differentiation from SLE
may rely on lymph node biopsy and the detection of autoantibodies, which should be
absent in Castleman disease [162,163]. (See "HHV-8-negative/idiopathic multicentric
Castleman disease" and "Unicentric Castleman disease".)
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Viral infections in particular are associated with the transient appearance of ANA. Parvovirus
and the herpesviruses, in particular Epstein-Barr virus (EBV) and cytomegalovirus (CMV), can
present with symptoms suggestive of cSLE (fever; cytopenias; organ involvement including liver,
lung, and joints; and additional constitutional symptoms). Infection with these viruses may also
occur concomitant with the initial presentation and diagnosis of cSLE, suggesting a possible role
in the pathogenesis of cSLE. Viral testing including serologic or polymerase chain reaction (PCR)
testing in addition to evaluation of the clinical course can usually differentiate infection from
cSLE. Other infections (eg, bacterial, mycobacterial) are less likely to be confused for cSLE, but
appropriate cultures and other testing should differentiate the underlying etiology.
Other systemic autoimmune rheumatic diseases such as mixed connective tissue disease
(MCTD), primary Sjögren's syndrome, juvenile dermatomyositis, scleroderma, and some
systemic vasculitides (granulomatosis with polyangiitis and polyarteritis nodosa), may present
with a positive ANA and multisystem findings. The majority of these can be excluded by a
careful history, physical examination, selected laboratory tests, and, when required,
histopathologic evaluation of the appropriate tissues (eg, muscle, skin, kidney, salivary gland).
MCTD is rare in children and adolescents, and differentiation from cSLE may initially be
challenging. However, the diagnosis can usually be made if the clinical symptoms of Raynaud,
puffy fingers, and myositis are predominant, in the presence of high-titer anti-ribonucleoprotein
(RNP) antibodies and in the absence of renal disease. (See "Juvenile dermatomyositis and other
idiopathic inflammatory myopathies: Diagnosis" and "Juvenile systemic sclerosis (scleroderma):
Classification, clinical manifestations, and diagnosis" and "Vasculitis in children: Incidence and
classification", section on 'Polyarteritis nodosa' and "Mixed connective tissue disease".)
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Systemic lupus
erythematosus".)
SUMMARY AND RECOMMENDATIONS
● Overview – Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory

disease of unknown cause that can affect any organ, most commonly the skin and mucous
membranes, joints, kidneys, and central nervous system (CNS). Hematologic
manifestations (cytopenias) and serositis are also frequent. Childhood-onset SLE (cSLE) is
fundamentally the same disease as in adults, with similar etiology, pathogenesis, clinical
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manifestations, and laboratory findings. However, the frequency of specific manifestations

varies between cSLE and adult-onset SLE (aSLE), and the disease may be more severe in
children, especially if diagnosis is delayed. (See 'Introduction' above and 'Pathogenesis'
above and 'Clinical manifestations' above and "Clinical manifestations and diagnosis of
systemic lupus erythematosus in adults", section on 'Clinical manifestations'.)
● Clinical manifestations – The most common initial symptoms are the gradual onset of
fever, weight loss, and fatigue, often with progression of symptoms for several weeks to
months prior to diagnosis ( table 1). Nonpainful arthritis of the small joints and renal
disease are commonly overlooked before the diagnosis of SLE is established. The classic
malar rash is present in only approximately one-third of individuals at the onset of disease
and therefore must not be relied upon to suggest the diagnosis. Hematologic,
neuropsychiatric, and pulmonary manifestations are also common at presentation. (See
'Clinical manifestations' above.)
● Laboratory findings – Common laboratory findings in children with SLE, in addition to the
hematologic abnormalities, include hypocomplementemia and the presence of
autoantibodies, such as antinuclear antibodies (ANAs) double-stranded DNA (dsDNA)
antibodies, antibodies to the extractable nuclear antigens (ENAs), and antiphospholipid
antibodies (aPLs) ( table 1). Vitamin D deficiency is frequent at presentation but is not
pathognomonic for cSLE. (See 'Laboratory findings' above.)
● Diagnosis – Three sets of classification criteria are available ( table 2 and table 3): one
from the American College of Rheumatology (ACR), last revised in 1997; a set of criteria
published in 2012 titled the Systemic Lupus International Collaborating Clinics (SLICC)
group classification criteria (based upon ACR criteria); and the 2019 European Alliance of
Associations for Rheumatology (EULAR; formerly known as European League Against
Rheumatism)/ACR classification criteria for SLE. Any of these criteria may be used to aid in
the diagnosis of SLE in both children and adults. A patient is classified as having SLE if four
or more of the ACR criteria are present or if four or more of the SLICC criteria, including at
least one clinical and one immunologic criterion, are present either serially or
simultaneously during any interval of observations in the absence of another explanation
for the findings. For the 2019 criteria, presence of a positive ANA is a required entry
criterion, following which a score is calculated based upon domains of clinical and
laboratory features. A total score of 10 or greater is required for classification. (See
'Diagnosis' above and 'Classification criteria' above and "Clinical manifestations and
diagnosis of systemic lupus erythematosus in adults", section on 'Our diagnostic criteria'.)
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● Differential diagnosis – The differential diagnosis of children with a positive ANA and
multisystem disease includes infection, malignancy, and other rheumatic diseases. (See
'Differential diagnosis' above.)
ACKNOWLEDGMENT
The editorial staff at UpToDate acknowledge Thomas JA Lehman, MD, who contributed to earlier
versions of this topic review.
Use of UpToDate is subject to the Terms of Use.
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69. Hepburn MJ, English JC 3rd, Keeling JH 3rd. Autoimmune idiopathic thrombocytopenic
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113. Groot N, de Graeff N, Avcin T, et al. European evidence-based recommendations for
diagnosis and treatment of paediatric antiphospholipid syndrome: the SHARE initiative.
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114. Ma J, Song H, Wei M, He Y. Clinical characteristics and thrombosis outcomes of paediatric
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117. Azhar AS, Awlia OM, Muzaffer MA. Cardiovascular complications in paediatric-onset
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118. Gazarian M, Feldman BM, Benson LN, et al. Assessment of myocardial perfusion and
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127. Saz EU, Ulger Z, Balkan S, et al. Cardiac tamponade as a first manifestation of possible
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Topic 6420 Version 32.0
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GRAPHICS
Características clínicas y de laboratorio sugestivas de lupus eritematoso

sistémico (LES) de inicio en la infancia
Manifestaciones clínicas
Fiebre persistente
Fatiga
Anorexia
Pérdida de peso
Artralgia
Artritis
Serositis (pleuritis, pericarditis, peritonitis)
erupción malar
erupción discoide
Alopecia
Úlceras orales y nasales.
Fotosensibilidad
Linfadenopatía
Edema periférico
Características del sistema nervioso central (SNC)*
Descubrimientos de laboratorio
Trombocitopenia persistente (plaquetas <150.000/ml)
Anemia hemolítica (Hgb ≤12 g/dL) ¶
Linfopenia (linfocitos <1500/mL)
Leucopenia (leucocitos <4000/ml)
hematuria
Proteinuria
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Hipocomplementemia (C3 y C4 bajos)
Autoanticuerpos (ANA, anti-dsDNA, anti-Smith, anti-RNP, anti-La/SSB, aCL, anticoagulante lúpico)
Elevación de enzimas hepáticas/hepatitis (no necesariamente específica de LES)
Aumento de la VSG (pero PCR normal, excepto en algunos escenarios)
Otras características de apoyo:
Hipergammaglobulinemia (IgG)
hipoalbuminemia
Se debe sospechar LES en un niño con cualquiera de estas características clínicas o de laboratorio.
Hgb: hemoglobina; WBC: glóbulo blanco; ANA: anticuerpo antinuclear; anti-dsDNA: anti-ADN bicatenario;
anti-RNP: anti-ribonucleoproteína; anti-LA/SSB: antígeno B anti-síndrome de Sjögren; aCL:
anticardiolipina; VSG: velocidad de sedimentación globular; PCR: proteína C reactiva; IgG:
inmunoglobulina G.
* Las características del SNC incluyen dolores de cabeza, deterioro cognitivo, psicosis (alucinaciones
visuales y auditivas, distorsiones), estado de confusión agudo (que se asemeja a un delirio), convulsiones,
derrames cerebrales, corea, desmielinización, hipertensión intracraneal idiopática, trastornos del estado
de ánimo, trastornos de ansiedad y meningitis aséptica. [1]
¶ Prueba de antiglobulina directa (DAT) especialmente positiva.
Referencia:
1. Nomenclatura y definiciones de casos del Colegio Americano de Reumatología para los síndromes de lupus
neuropsiquiátrico. Artritis Reumática 1999; 42:599.
Gráfico 64565 Versión 5.0
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Lupus eritematoso cutáneo agudo
En este paciente con lupus eritematoso sistémico se presentan eritema malar y edema sutil.
Reproducido con permiso de: www.visualdx.com . Copyright VisualDx. Reservados todos los derechos.
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Lupus eritematoso cutáneo agudo
En un paciente con LES se presenta una erupción eritematosa y edematosa en el área malar. Obsérvese
la preservación de los pliegues nasolabiales.
LES: lupus eritematoso sistémico.
Reproducido con permiso de: www.visualdx.com . Copyright VisualDx. Reservados todos los derechos.
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Criterios de clasificación del lupus eritematoso sistémico
[1,2] [3]
Criterios ACR Criterios SLICC
(4 de 11 criterios)* (4 of 17 criteria, including at least 1 clinical criterion

and 1 immunologic criterion; ¶ OR biopsy-proven lupu
nephritis Δ )
Criterion Definition Criterion Definition
Clinical criteria
Malar rash Fixed erythema, flat or raised, Acute cutaneous Lupus malar rash (do not
over the malar eminences, lupus count if malar discoid);
tending to spare the bullous lupus; toxic epiderma
nasolabial folds necrolysis variant of SLE;
maculopapular lupus rash;
photosensitive lupus rash (in
the absence of
dermatomyositis); OR
subacute cutaneous lupus
Photosensitivity Skin rash as a result of (nonindurated psoriasiform
unusual reaction to sunlight, and/or annular polycyclic
by patient history or clinician lesions that resolve without
observation scarring, although
occasionally with
postinflammatory
dyspigmentation or
telangiectasias)
Discoid rash Erythematosus raised patches Chronic cutaneous Classic discoid rash; localized
with adherent keratotic scaling lupus (above the neck); generalized
and follicular plugging; (above and below the neck);
atrophic scarring may occur in hypertrophic (verrucous)
older lesions lupus; lupus panniculitis
(profundus); mucosal lupus;
lupus erythematosus
tumidus; chilblains lupus; OR
discoid lupus/lichen planus
overlap
Nonscarring Diffuse thinning or hair

alopecia fragility with visible broken
hairs (in the absence of other
causes, such as alopecia
areata, drugs, iron deficiency,
and androgenic alopecia)
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Oral ulcers Oral or nasopharyngeal Oral or nasal Palate, buccal, tongue, OR

ulceration, usually painless, ulcers nasal ulcers (in the absence o
observed by a clinician other causes, such as
vasculitis, Behçet syndrome,
infection [herpesvirus],
inflammatory bowel disease,
reactive arthritis, and acidic
foods)
Arthritis Nonerosive arthritis involving Joint disease Synovitis involving 2 or more

2 or more peripheral joints, joints, characterized by
characterized by tenderness, swelling or effusion OR
swelling, or effusion
Tenderness in 2 or more
joints and at least 30 minutes
of morning stiffness
Serositis Pleuritis – Convincing history Serositis Typical pleurisy for more than
of pleuritic pain or rubbing 1 day, pleural effusions, or
heard by a clinician or pleural rub, OR
evidence of pleural effusion
OR
Pericarditis – Documented by Typical pericardial pain (pain

ECG, rub, or evidence of with recumbency improved by
pericardial effusion sitting forward) for more than
1 day, pericardial effusion,
pericardial rub, or pericarditis
by electrocardiography in the
absence of other causes, such
as infection, uremia, and
Dressler syndrome
Renal disorder Persistent proteinuria greater Renal Urine protein-to-creatinine

than 500 mg/24 hours or ratio (or 24-hour urine
greater than 3+ if quantitation protein) representing 500 mg
not performed OR protein/24 hours, OR
Cellular casts – May be red Red blood cell casts

cell, hemoglobin, granular,
tubular, or mixed
Neurologic Seizures OR psychosis – In the Neurologic Seizures; psychosis;

disorder absence of offending drugs or mononeuritis multiplex (in th
known metabolic absence of other known
derangements (uremia, causes, such as primary
ketoacidosis, or electrolyte vasculitis); myelitis; periphera
imbalance) or cranial neuropathy (in the
absence of other known
causes, such as primary
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vasculitis, infection, and

diabetes mellitus); OR acute
confusional state (in the
absence of other causes,
including toxic/metabolic,
uremia, drugs)
Hematologic Hemolytic anemia – With Hemolytic anemia Hemolytic anemia

disorder reticulocytosis OR
Leukopenia or Leukopenia (<4000/mm 3 at
Leukopenia – Less than lymphopenia least once) (in the absence of
4000/mm 3 total on 2 or more other known causes, such as
occasions OR Felty syndrome, drugs, and
Lymphopenia – Less than portal hypertension), OR
1500/mm 3 on 2 or more Lymphopenia (<1000/mm 3 at
occasions OR least once) (in the absence of
Thrombocytopenia – Less than other known causes, such as
100,000/mm 3 (in the absence glucocorticoids, drugs, and
of offending drugs) infection)
Thrombocytopenia Thrombocytopenia
(<100,000/mm 3 ) at least once
in the absence of other
known causes, such as drugs,
portal hypertension, and
thrombotic thrombocytopeni
purpura
Immunologic criteria
ANA An abnormal titer of ANA by ANA ANA level above laboratory

immunofluorescence or an reference range
equivalent assay at any point
in time and in the absence of
drugs known to be associated
with "drug-induced lupus"
syndrome
Immunologic Anti-DNA – Antibody to native Anti-dsDNA Anti-dsDNA antibody level

disorders DNA in abnormal titer OR above laboratory reference
range (or >2-fold the
Anti-Sm – Presence of
reference range if tested by
antibody to Sm nuclear
ELISA)
antigen OR
Positive antiphospholipid
antibody on:
Anti-Sm Presence of antibody to Sm
1. An abnormal serum nuclear antigen
level of IgG or IgM
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anticardiolipin Antiphospholipid Antiphospholipid antibody

antibodies OR positivity as determined by
2. A positive test result for any of the following: Positive
lupus anticoagulant test result for lupus
using a standard anticoagulant; false-positive
method OR test result for rapid plasma
3. A false-positive reagin; medium- or high-titer
serologic test for anticardiolipin antibody level
syphilis known to be (IgA, IgG, or IgM); or positive
positive for at least 6 test result for anti-beta 2-
months and confirmed glycoprotein I (IgA, IgG, or
by Treponema pallidum IgM)
immobilization or
fluorescent treponemal
antibody absorption
test
Low complement Low C3; low C4; OR low CH50
Direct Coombs Direct Coombs test in the

test absence of hemolytic anemia
ACR: American College of Rheumatology; SLICC: Systemic Lupus International Collaborating Clinics; SLE:
systemic lupus erythematosus; ECG: electrocardiogram; ANA: antinuclear antibodies; Anti-Sm: anti-Smith
antibody; IgG: immunoglobulin G; IgM: immunoglobulin M; Anti-dsDNA: anti-double-stranded DNA;
ELISA: enzyme-linked immunosorbent assay; IgA: immunoglobulin A.
* For the ACR criteria, no distinction is made between clinical and immunologic criteria in determining
whether the required number has been met. The classification is based upon 11 criteria. For the purpose
of identifying patients in clinical studies, a person is said to have SLE if any 4 or more of the 11 criteria are
present, serially or simultaneously, during any interval of observation.
¶ For the SLICC criteria, criteria are cumulative and need not be presently concurrently. A patient is
classified as having SLE if he or she satisfies 4 of the clinical and immunologic criteria used in the SLICC
classification criteria, including at least 1 clinical criterion and 1 immunologic criterion.
Δ Alternatively, according to the SLICC criteria, a patient is classified as having SLE if he or she has biopsy-
proven nephritis compatible with SLE in the presence of ANAs or anti-dsDNA antibodies.
References:
1. Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis
Rheum 1982; 25:1271.
2. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus
erythematosus (letter). Arthritis Rheum 1997; 40:1725.
3. Petri M, Orbai AM, Alarcón GS, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics
classification criteria for systemic lupus erythematosus. Arthritis Rheum 2012; 64:2677.
Graphic 86633 Version 12.0
19/4/24, 14:49 A hoy
2019 European Alliance of Associations for Rheumatology (EULAR)/American

College of Rheumatology (ACR) classification criteria for systemic lupus
erythematosus
The entry criterion is necessary to classify SLE.

Entry criterion:
ANA at a titer of ≥1:80 on HEp-2 cells or an equivalent positive test (ever).*
At least 1 clinical criterion required to classify SLE. Additional additive (clinical or

immunology) criteria are counted toward the total score.
Additive criteria:
Do not count a criterion if there is a more likely explanation than SLE.
Occurrence of a criterion on ≥1 occasion is sufficient.
Criteria need not occur simultaneously.
Within each domain (eg, mucocutaneous, complement proteins), only the highest-weighted
criterion is counted toward the total score if more than 1 is present. ¶
Clinical domains and criteria Weight
Constitutional
Fever 2
Hematologic
Leukopenia 3
Thrombocytopenia 4
Autoimmune hemolysis 4
Neuropsychiatric
Delirium 2
Psychosis 3
Seizure 5
Mucocutaneous
Nonscarring alopecia 2
Oral ulcers 2
Subacute cutaneous or discoid lupus 4
Acute cutaneous lupus 6
Serosal
Pleural or pericardial effusion 5
19/4/24, 14:49 A hoy
Acute pericarditis 6
Musculoskeletal
Joint involvement 6
Renal
Proteinuria >0.5 g per 24 hours 4
Renal biopsy Class II or V lupus nephritis 8
Renal biopsy Class III or IV lupus nephritis 10
Immunology domains and criteria Weight
Antiphospholipid antibodies
Anti-cardiolipin antibodies or anti-beta-2GP1 antibodies or lupus 2

anticoagulant
Complement proteins
Low C3 or low C4 3
Low C3 and low C4 4
SLE-specific antibodies
Anti-dsDNA antibody Δ or anti-Smith antibody 6
A total score of ≥10 and ≥1 clinical criterion are required to classify SLE.
Total score
SLE: systemic lupus erythematosus; ANA: antinuclear antibody; HEp-2: human epithelial type 2; anti-beta-
2GP1: anti-beta-2 glycoprotein 1; anti-dsDNA: anti-double-stranded DNA.
* If ANA is absent, do not classify as SLE.
¶ Additional criteria within the same domain will not be counted.
Δ In an assay with 90% specificity against relevant disease controls.
From: Aringer M, Costenbader K, Daikh D, et al. 2019 European League Against Rheumatism/American College of Rheumatology
classification criteria for systemic lupus erythematosus. Arthritis Rheumatol 2019; 71(9):1400-1412.
https://onlinelibrary.wiley.com/doi/full/10.1002/art.40930. Copyright © 2019 American College of Rheumatology. Adapted with
permission of John Wiley & Sons Inc. This image has been provided by or is owned by Wiley. Further permission is needed before it
can be downloaded to PowerPoint, printed, shared or emailed. Please contact Wiley's permissions department either via email:
permissions@wiley.com or use the RightsLink service by clicking on the 'Request Permission' link accompanying this article on
Wiley Online Library (https://onlinelibrary.wiley.com/).
Graphic 122388 Version 3.0
19/4/24, 14:49 A hoy
Contributor Disclosures
Deborah M Levy, MD, MS, FRCPC Grant/Research/Clinical Trial Support: AstraZeneca [Systemic lupus
erythematosus]; GlaxoSmithKline [Systemic lupus erythematosus]; Roche [Systemic lupus erythematosus
nephritis]; SOBI [Systemic lupus erythematosus macrophage activation syndrome]. All of the relevant
financial relationships listed have been mitigated. Marisa Klein-Gitelman, MD,
MPH Grant/Research/Clinical Trial Support: AbbVie [JIA]; BMS [JIA]; CARRA [JIA, lupus, JDM]; LFA [Lupus];
PCORI/NIH/Spondylitis Society [ERA]; Pfizer [Childhood polyarticular arthritis]; PRINTO/PRCSG [JIA]; UCB
[Childhood polyarticular arthritis]. Consultant/Advisory Boards: FDA Arthritis Advisory Committee
[Arthritis]. Other Financial Interest: AstraZeneca [Blossom study international coordinating investigator].
All of the relevant financial relationships listed have been mitigated. Siobhan M Case, MD, MHS No
relevant financial relationship(s) with ineligible companies to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must
conform to UpToDate standards of evidence.
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Reimpresión oficial de UpToDate ®

Lupus eritematoso sistémico (LES) de inicio infantil:

Revisión de la literatura vigente hasta: marzo de 2024.

El lupus eritematoso sistémico (LES) es una enfermedad inflamatoria autoinmune crónica de

Aquí se revisan la epidemiología, las características clínicas, el diagnóstico y la clasificación del

● Hematologic (55 to 77 percent) – Anemia, lymphopenia, leukopenia, and/or

● Musculoskeletal (61 to 64 percent) – Arthritis, arthralgia, and/or serositis

● Renal abnormalities (27 to 59 percent) – Proteinuria, hematuria, and/or casts suggestive of

● Fever (26 to 58 percent)

Pulmonary, thromboembolic, cardiac, neuropsychiatric, and gastrointestinal manifestations are

Hematologic abnormalities, lupus nephritis, fever, ocular symptoms, seizures, and

● Acute cutaneous (eg, malar rash, generalized maculopapular rash)

● Subacute cutaneous (eg, annular subacute cutaneous lupus erythematosus [SCLE])

Systemic — Low-grade fever, fatigue, anorexia, and lymphadenopathy are common

Additional bony abnormalities include osteopenia, osteoporosis, and osteonecrosis (avascular

Hematologic — Hematologic abnormalities, including anemia, leukopenia, lymphopenia, and

● Anemia – Anemia, defined as a hemoglobin concentration more than two standard

● Thrombocytopenia – The reported prevalence of thrombocytopenia varies from 10 to 50

Neuropsychiatric — cSLE is associated with many neuropsychiatric syndromes and additional

Appropriate attribution of neuropsychiatric manifestations to underlying SLE is important

Pulmonary — Most reviews of cSLE report respiratory findings in 30 to 50 percent of patients,

Pulmonary hypertension in cSLE is rare, and, although initially attributed to multiple

Thromboembolic — Thromboembolic disease can complicate SLE, particularly in the context of

Although lupus anticoagulant predisposes to thrombosis, bleeding in a patient with cSLE,

disease in systemic lupus erythematosus" and "Clinical manifestations and diagnosis of

Gastrointestinal — Gastrointestinal involvement occurs in approximately 20 percent of

● The adolescent female with chronic thrombocytopenia

lymphohistiocytosis" and "Systemic juvenile idiopathic arthritis: Course, prognosis, and

Pediatric rheumatology should be consulted when cSLE is suspected, especially in a hospitalized

● Kikuchi-Fujimoto disease most frequently presents with unilateral cervical

● Castleman disease is a nonclonal lymphoproliferative disorder that presents with localized

SOCIETY GUIDELINE LINKS

SUMMARY AND RECOMMENDATIONS

● Overview – Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory

manifestations, and laboratory findings. However, the frequency of specific manifestations

Use of UpToDate is subject to the Terms of Use.

37. Livingston B, Bonner A, Pope J. Differences in clinical manifestations between childhood-

53. Schaller J. Lupus in childhood. Clin Rheum Dis 1982; 8:219.

refractory cytopenia in childhood-onset systemic lupus erythematosus. Lupus 2015; 24:966.

systemic lupus erythematosus in a 12-year-old girl. Pediatr Pulmonol 2013; 48:1246.

140. Reichlin M, Broyles TF, Hubscher O, et al. Prevalence of autoantibodies to ribosomal P

Arthritis Rheum 1999; 42:69.

144. Berube C, Mitchell L, Silverman E, et al. The relationship of antiphospholipid antibodies to

149. Aringer M, Costenbader K, Daikh D, et al. 2019 European League Against

in Childhood-onset Systemic Lupus Erythematosus. J Rheumatol 2019; 46:731.

161. Pepe F, Disma S, Teodoro C, et al. Kikuchi-Fujimoto disease: a clinicopathologic update.

Características clínicas y de laboratorio sugestivas de lupus eritematoso

Serositis (pleuritis, pericarditis, peritonitis)

Úlceras orales y nasales.

Características del sistema nervioso central (SNC)*

Trombocitopenia persistente (plaquetas <150.000/ml)

Anemia hemolítica (Hgb ≤12 g/dL) ¶

Linfopenia (linfocitos <1500/mL)

Leucopenia (leucocitos <4000/ml)

Hipocomplementemia (C3 y C4 bajos)

Autoanticuerpos (ANA, anti-dsDNA, anti-Smith, anti-RNP, anti-La/SSB, aCL, anticoagulante lúpico)

Elevación de enzimas hepáticas/hepatitis (no necesariamente específica de LES)