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Childhood-onset systemic lupus erythematosus (cSLE): Clinical manifestations and diagnosis

Childhood-onset systemic lupus erythematosus (cSLE): Clinical manifestations and diagnosis
Author:
Deborah M Levy, MD, MS, FRCPC
Section Editor:
Marisa Klein-Gitelman, MD, MPH
Deputy Editor:
Siobhan M Case, MD, MHS
Literature review current through: Apr 2025. | This topic last updated: Dec 12, 2024.

INTRODUCTION — 

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease of unknown cause that can affect any organ system, most frequently the skin, joints, kidneys, and the nervous, hematologic, and cardiovascular systems. It is characterized by the production of multiple autoantibodies. Although SLE in children is fundamentally the same disease as in adults, with similar etiology, pathogenesis, and laboratory findings, there are some differences in the frequency and severity of certain clinical manifestations. It is generally accepted that patients with childhood-onset SLE (cSLE) have greater disease severity and earlier accrual of disease damage than patients who develop SLE in adulthood [1-5]. In addition, the care of children and adolescents with SLE is different from that of adults because of the impact of the disease and its therapy on physical, psychosocial, and emotional growth and development. (See "Systemic lupus erythematosus in adults: Clinical manifestations and diagnosis", section on 'Clinical manifestations'.)

This topic reviews the epidemiology, clinical features, diagnosis, and classification of cSLE. The treatment, complications, and prognosis of cSLE are discussed separately. (See "Systemic lupus erythematosus (SLE) in children: Treatment, complications, and prognosis".)

EPIDEMIOLOGY — 

The best estimate is that cSLE affects between 5000 and 10,000 children in the United States [6] and affects females more often than males (8 to 9:1), even in the prepubertal age group (4 to 5:1) [7-9]. Worldwide, estimates of cSLE incidence are between 0.3 to 2.5 per 100,000 children-years, while prevalence rates range widely from 1.1 to 9.7 per 100,000 children and adolescents, depending upon the population studied [10-20]. (See "Systemic lupus erythematosus: Epidemiology and pathogenesis", section on 'Epidemiology'.)

SLE can occur at any age, although it is rare before five years of age and is increasingly prevalent after the first decade of life [7,21,22]. Between 10 to 20 percent of all persons who develop SLE do so in childhood. Children with earlier-onset cSLE (<10 years of age) tend to have more severe disease activity and poorer prognosis [23,24]. Fever, lymphadenopathy, hematologic abnormalities, lupus nephritis (LN), pericarditis, neuropsychiatric symptoms, and ocular symptoms are more common in cSLE than adult-onset SLE (aSLE), whereas Raynaud phenomenon, pleuritis, subacute cutaneous lupus, discoid lupus, and sicca symptoms (dry eyes, dry mouth) are more common manifestations in aSLE [25-27]. (See "Systemic lupus erythematosus: Epidemiology and pathogenesis", section on 'Age at onset' and "Systemic lupus erythematosus in adults: Clinical manifestations and diagnosis", section on 'Clinical manifestations'.)

Differences in the frequency of SLE and severity of disease have been reported by patient race, ethnicity, and ancestry, including more frequent and severe disease among children who identify as Asian, African, Indigenous North American, and Hispanic/Latino [10,28-30]. (See "Systemic lupus erythematosus: Epidemiology and pathogenesis", section on 'Geography and race/ethnicity'.)

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 [31,32] (see "Systemic lupus erythematosus: Epidemiology and pathogenesis", section on 'Genetic factors'). Many of the clinical manifestations are mediated directly or indirectly by antibody formation and the creation of immune complexes. (See "Systemic lupus erythematosus: Epidemiology and pathogenesis", section on 'Immune abnormalities'.)

The pathogenesis of SLE is discussed in greater detail separately. (See "Systemic lupus erythematosus: Epidemiology and pathogenesis".)

CLINICAL MANIFESTATIONS

Common presenting features — The presenting manifestations of cSLE are diverse, and any organ system may be involved (table 1). 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 patients have acute or even life-threatening symptoms at presentation due to concomitant macrophage activation syndrome (MAS), severe kidney disease, severe neuropsychiatric manifestations, concomitant thromboembolic disease, or thrombotic microangiopathy (TMA), such as thrombotic thrombocytopenic purpura (TTP).

The diagnosis of SLE may be delayed due to overlooking certain signs, including nonpainful small-joint arthritis and kidney disease. In addition, a classic malar rash (picture 1 and picture 2) must not be relied upon to suggest the diagnosis since it may be absent or overlooked when there are only subtle changes; in particular, persons with darker skin pigmentation may have less conspicuous erythema or hypopigmentation.

In reviews from multiple countries, the most common presenting manifestations were as follows [1,7,10,21,33-35]:

●Constitutional (20 to 90 percent) – Fever, fatigue, anorexia, weight loss, and/or lymphadenopathy

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

●Mucocutaneous (60 to 80 percent) – Malar rash, alopecia, photosensitivity, oral or nasal ulcers, and/or discoid rash

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

●Kidney abnormalities (27 to 59 percent) – Proteinuria, hematuria, and/or casts suggestive of lupus nephritis (LN) and/or biopsy-proven LN; or nephrotic syndrome

●Serositis (20 to 30 percent) – Pleural effusion, symptomatic pleuritis, pericardial effusion, symptomatic pericarditis, and/or peritonitis

●Neuropsychiatric (5 to 30 percent) – Headache, psychosis, cognitive dysfunction, seizure, and/or acute confusional state

Mucocutaneous — The most frequent skin and mucous membrane findings include the butterfly (malar) rash (picture 1 and picture 2), oral and/or nasal ulcers, and nonscarring alopecia. However, these pathognomonic findings may be absent 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 common skin manifestations in cSLE include photosensitivity, diffuse maculopapular rash, discoid lupus erythematosus (DLE), and cutaneous vasculitis [36].

Following the dermatology classification [37], cutaneous lesions that are specific for SLE can be classified into:

●Acute cutaneous (eg, malar rash, generalized maculopapular rash) (see "Overview of cutaneous lupus erythematosus", section on 'Acute cutaneous lupus erythematosus')

●Subacute cutaneous (eg, annular subacute cutaneous lupus erythematosus [SCLE]) (see "Overview of cutaneous lupus erythematosus", section on 'Subacute cutaneous lupus erythematosus')

●Chronic cutaneous (eg, DLE, lupus profundus, chilblain lupus erythematosus [LE]) lesions (see "Overview of cutaneous lupus erythematosus", section on 'Chronic cutaneous lupus erythematosus')

In adults, DLE (or chronic cutaneous lupus) usually occurs as an isolated syndrome; only 5 to 10 percent of adults with localized DLE lesions and 15 to 30 percent of those with generalized lesions progress to having SLE. By contrast, up to 25 percent of children with "isolated" DLE progress to having SLE [38]. (See "Overview of cutaneous lupus erythematosus", section on 'Chronic cutaneous lupus erythematosus'.)

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 [36]. 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'.)

Other forms of mucocutaneous involvement in SLE are reviewed in greater detail separately. (See "Overview of cutaneous lupus erythematosus", section on 'Lupus nonspecific skin disease' and "Overview of cutaneous lupus erythematosus", section on 'Other manifestations'.)

Systemic — Low-grade fever, fatigue, anorexia, weight loss, 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. More information on lymphadenopathy in the setting of SLE is provided separately. (See "Systemic lupus erythematosus: Hematologic manifestations", section on 'Lymphadenopathy'.)

Musculoskeletal — The most common musculoskeletal findings in c 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 [39]. Myositis also occurs, manifesting as either muscle pain or weakness; weakness more frequently affects proximal muscles than distal ones, similar to the symptoms of juvenile dermatomyositis. The musculoskeletal manifestations of SLE are reviewed in greater detail separately. (See "Arthritis and other musculoskeletal manifestations of systemic lupus erythematosus", section on 'Joint involvement' and "Arthritis and other musculoskeletal manifestations of systemic lupus erythematosus", section on 'Muscle involvement'.)

Additional bony abnormalities include osteopenia, osteoporosis, and osteonecrosis (avascular necrosis) [40,41]. 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 [42,43]. 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) [40]. 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.)

Kidney — Kidney 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 kidney involvement is present in up to two-thirds of patients with cSLE evaluated at major medical centers [44]. However, in a study of United States children with SLE enrolled in Medicaid from 2000 to 2004, only 37 percent had LN [13]. A higher rate of LN was seen in adolescent-onset SLE compared with aSLE in one series [45]. (See "Lupus nephritis: Diagnosis and classification", section on 'Clinical features'.)

LN is classified by histopathology and ranges from class I (normal or near normal) to class VI (end-stage kidney disease), with focal and diffuse LN (class III or class IV) representing almost half of all kidney lesions [46]. Class III or IV LN (with endocapillary hypercellularity) are the most severe and require intensive immunosuppression as they are the most likely to progress to end-stage kidney disease. (See "Lupus nephritis: Diagnosis and classification", section on 'Histopathologic classification of LN'.)

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 kidney biopsy is required for accurate diagnosis of LN. Indications include cSLE with persistent proteinuria or kidney 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 [47]. (See "Lupus nephritis: Diagnosis and classification", section on 'Role of kidney biopsy'.)

Hematologic — Hematologic abnormalities, including anemia, leukopenia, lymphopenia, and thrombocytopenia, are common among children with SLE [48,49]. Isolated thrombocytopenia (immune thrombocytopenia [ITP]) or Evans syndrome (ITP and concomitant autoimmune hemolytic anemia [AIHA]) may be diagnosed months to years prior to the diagnosis of cSLE [50]. (See "Immune thrombocytopenia (ITP) in children: Clinical features and diagnosis" 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 [51]. The most common types of anemia, which may occur separately or in combination, are iron deficiency anemia, Coombs-positive AIHA, and anemia of chronic disease [52]. Concomitant hemoglobinopathies, such as alpha or beta thalassemia trait or sickle cell trait, may also contribute to anemia. (See "Systemic lupus erythematosus: Hematologic manifestations", section on 'Anemia' and "Approach to the child with anemia".)

●Leukopenia – Leukopenia, defined as a total white blood cell (WBC) count <4000/microL, occurs in nearly two-thirds of children at some point during the course of illness [53-56]. The decrease in WBC count is primarily due to a fall in absolute lymphocyte count [7,21,53]. 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. (See "Systemic lupus erythematosus: Hematologic manifestations", section on 'Leukopenia'.)

●Thrombocytopenia – The reported prevalence of thrombocytopenia varies from 10 to 50 percent [57-60]. Frequently, the degree of thrombocytopenia is mild (platelet counts between 100,000 and 150,000/microL) and hemorrhage is rare [57], 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 up to 10 years [61-63]. Thrombotic thrombocytopenic purpura (TTP) is an uncommon, acute, and life-threatening complication that may also be the initial presenting feature of cSLE [64-66]. (See "Systemic lupus erythematosus: Hematologic manifestations", section on 'Thrombocytopenia'.)

Antiphospholipid antibodies (aPLs) and other autoantibodies are discussed below [57,67,68]. (See 'Laboratory findings' below.)

Neuropsychiatric — Patients can develop varied manifestations of neuropsychiatric SLE (NPSLE) [69]. One or more neuropsychiatric manifestations are reported in up to two-thirds of cSLE patients [70-76]. 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. While NPSLE can present subacutely over weeks to months, it can result in significant impairment in thought, cognition, and even consciousness if it is severe and untreated. Cognitive impairment in cSLE occurs during a time of important brain development, and significant challenges remain in diagnosis and management [77-81]. 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) [75,76]. (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, including the following [7,53,82-84]:

●Pleuritis – Pleuritis is the most common pulmonary complication of cSLE, affecting 30 to 35 percent of patients [7,53,82-84]. Chest pain is the most common presenting symptom, whereas predominant complaints of shortness of breath are rare [85,86]. 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 CRP levels observed in patients with other manifestations of active cSLE [87,88]. (See "Pulmonary manifestations of systemic lupus erythematosus in adults", section on 'Pleural disease'.)

●Subclinical lung disease – 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 [83,89,90]. 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" and "Pulmonary manifestations of systemic lupus erythematosus in adults", section on 'Interstitial lung disease'.)

●Pulmonary hemorrhage – Acute pulmonary hemorrhage [86,91-94] is one of the most severe forms of SLE-associated pulmonary involvement, although it occurs infrequently in cSLE (<5 of patients). 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 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" and "Pulmonary manifestations of systemic lupus erythematosus in adults", section on 'Pulmonary hemorrhage'.)

●Pulmonary hypertension – Pulmonary hypertension in cSLE is rare, affecting <2 percent of patients, and can be severe [86,95]. Although it was initially attributed to multiple thromboses, the etiology is now thought to be multifactorial [95,96]. 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" and "Pulmonary manifestations of systemic lupus erythematosus in adults", section on 'Pulmonary hypertension'.)

Other rare pulmonary manifestations of SLE in children include shrinking lung syndrome [97-99] and pneumonitis [84,86]. (See "Pulmonary manifestations of systemic lupus erythematosus in adults", section on 'Acute pneumonitis' and "Pulmonary manifestations of systemic lupus erythematosus in adults", section on 'Shrinking lung syndrome'.)

Cardiac and vascular

●Cardiac disease – The prevalence of clinical heart disease among children with SLE ranges in various studies from 12 to 54 percent [86,100-102], and myopericardial manifestations occur at a rate 4.4-fold higher in cSLE compared with aSLE [27]. 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 [7,86,101]. Other forms of cardiovascular disease, such as myocarditis, valvular disease (eg, endocarditis) [27,89,100], and coronary artery disease (CAD), are rare. (See "Clinical manifestations and diagnosis of myocarditis in children" and "Systemic lupus erythematosus in adults: Coronary artery disease" and "Non-coronary cardiac manifestations of systemic lupus erythematosus in adults".)

•Pericarditis – 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 [87,88]. Large pericardial effusions may accumulate without symptoms until they cause cardiac tamponade [103,104]. 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 "Non-coronary cardiac manifestations of systemic lupus erythematosus in adults", section on 'Pericardial disease' and "Acute pericarditis: Clinical presentation and diagnosis".)

•Subclinical disease – Subclinical disease, detected by echocardiography or found in autopsy studies, also occurs in many children [89,105,106]. In a retrospective review of 40 children with SLE who had at least one echocardiogram, 68 percent of subjects (27 of 40) had abnormalities [89]. 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.

•Coronary artery disease – Children with SLE have an increased risk for early atherosclerosis and CAD that may not become clinically apparent until they are young adults [107-109]. 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 [100,110,111]. (See "Systemic lupus erythematosus in adults: Coronary artery disease".)

•Heart failure – Heart failure in children with SLE is usually the result of kidney or pulmonary compromise (eg, hypertension, glomerulonephritis and/or nephrosis, and pulmonary disease) rather than intrinsic cardiac disease. (See 'Kidney' above and 'Pulmonary' above.)

●Vasculitis – Children with SLE may develop vasculitis, most commonly small-vessel vasculitis with skin manifestations (eg, nonblanching, petechial rash, digital ulcerations, urticarial vasculitis) (see 'Mucocutaneous' above). Involvement of small and, rarely, medium-sized vessels in the lungs, central nervous system (CNS; including the retina), gastrointestinal system, and kidneys may lead to severe symptoms such as hemorrhage and organ damage [112-114].

●Thromboembolic disease – Thromboembolic disease can complicate SLE, particularly in the context of aPLs. The prevalence of aPLs in cSLE varies widely among reported cohorts, likely due to different thresholds for positivity and a range of methods for their detection. However, fewer than 10 percent of patients with cSLE experience one or more thrombotic events [115]. In cSLE, the lupus anticoagulant (LAC) is the greatest risk factor for the subsequent development of thrombosis [68], and the contribution of anticardiolipin antibodies (aCL) and other aPLs (eg, anti-beta2 glycoprotein I [anti-beta2GPI]) is not as well delineated. (See 'Laboratory findings' below.)

Antiphospholipid syndrome (APS) is diagnosed when a cSLE patient with aPLs has a thrombotic event or other associated microvascular, hematologic, or cardiac manifestations [116-118]. 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 embolism, and lastly arterial stroke [115]. Other nonthrombotic manifestations of APS in cSLE may include microvascular (eg, livedoid vasculopathy, chorea, nephropathy, pulmonary hemorrhage), hematologic (eg, thrombocytopenia), and cardiac valve involvement with aseptic vegetations (ie, Libman Sacks endocarditis). Appropriate monitoring may include routine pulmonary function testing, echocardiography, and involvement of other subspecialty colleagues. (See "Clinical manifestations of antiphospholipid syndrome" and "Antiphospholipid syndrome: Diagnosis".)

Although LAC predisposes to thrombosis, patients with cSLE who have a positive LAC may also develop bleeding due to LAC-hypoprothrombinemia syndrome (LAHPS); these patients have a prolonged prothrombin time (PT) and partial thromboplastin time (PTT), and probably bleed due to antibodies to prothrombin (factor II) [119].

●Raynaud phenomenon – Patients with SLE can develop secondary Raynaud phenomenon, where regional blood flow to the digits and skin is disrupted due to a variety of mechanisms. Nailfold capillaroscopy is often abnormal [120], and episodes are typically triggered by cold exposure or emotional stress. Patients may develop episodic color changes, paresthesias, swelling of affected digits, tender or itchy erythematous subcutaneous nodules (pernio), and, in very severe cases, ulcerations due to ischemia of affected areas [121]. (See "Pathogenesis and pathophysiology of Raynaud phenomenon", section on 'Secondary Raynaud phenomenon' and "Clinical manifestations and diagnosis of Raynaud phenomenon".)

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 [122]. Symptoms included pain due to ascites (n = 14), pancreatitis (n = 12), or complications of treatment (n = 1) or infection (n = 1). Complications may include the following:

●Serositis – Primary acute SLE peritonitis (serositis) should be distinguished from peritonitis secondary to other causes including nephrotic syndrome, pancreatitis, and infarction or perforation from vasculitis or thrombosis [112].

●Pancreatitis – Although acute pancreatitis is uncommon, it is associated with significant morbidity and even mortality [123].

●Transaminitis and liver disease – 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 [124,125]. Autoimmune hepatitis (AIH) may be diagnosed prior to cSLE diagnosis, with positive anti-smooth muscle antibodies (ASMA) in the absence of anti-liver/kidney microsomal antibodies [126]. Hepatomegaly may differentiate primary AIH from cSLE-associated hepatitis, although the histopathology of both conditions is similar and they are probably within a spectrum of disease. (See "Gastrointestinal manifestations of systemic lupus erythematosus".)

Ophthalmologic — The most common ocular manifestation in cSLE is asymptomatic cotton-wool spots, which are suggestive of microangiopathic retinopathy and are seen most often in patients with LN [127]. Keratoconjunctivitis sicca (dry eyes) may occur in patients with or without secondary 'Sjögren's syndrome [128,129]. Vaso-occlusive retinopathy and retinal vasculitis are both rare and are associated with acute loss of vision. Central retinal vein thrombosis may occur, usually in the presence of aPL [130]. Rarely, episcleritis, scleritis, and symptomatic uveitis may develop.

In addition to ocular manifestations of SLE, patients may develop adverse ocular effects related to systemic glucocorticoid use, including subcapsular cataracts and glaucoma. (See "Major adverse effects of systemic glucocorticoids", section on 'Ophthalmologic effects'.)

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) including those directed against extractable nuclear antigens (ENAs), double-stranded deoxyribonucleic acid (dsDNA) antibodies, 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 [131]. 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 'Kidney' above and "Systemic lupus erythematosus in adults: Clinical manifestations and diagnosis", 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). ANA may also be negative when indirect immunofluorescence testing is done and anti-Ro and/or anti-La are the only ANAs present. (See "Measurement and clinical significance of antinuclear antibodies".)

Additional autoantibodies such as anti-dsDNA and anti-Smith (anti-Sm) help to confirm the diagnosis of SLE but are not uniformly present. Aside from anti-dsDNA antibodies, titers of individual antibodies are not useful biomarkers of disease activity. More information on specific autoantibodies is provided below:

●Anti-dsDNA antibodies – Anti-dsDNA antibodies may be a useful biomarker with decreasing titers correlating with treatment response, and increasing titers preceding disease flare in some patients [132]. (See "Antibodies to double-stranded (ds)DNA, Sm, and U1 RNP".)

●Anti-Ro/SSA and anti-La/SSB antibodies – Although anti-Ro/SSA and anti-La/SSB 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 [133]. (See "The anti-Ro/SSA and anti-La/SSB antigen-antibody systems".)

●Antiribosomal P antibodies – Antiribosomal P antibodies are found more frequently in children than adults and are associated with active disease and neuropsychiatric, kidney, or hepatic involvement [134,135]. However, they are not specific for these manifestations and do not provide prognostic value. (See "Antiribosomal P protein antibodies".)

●Antineutrophil cytoplasmic antibodies (ANCAs) – ANCAs are observed in SLE, but their presence is not associated with disease activity or specific organ involvement [136]. (See "Clinical spectrum of antineutrophil cytoplasmic autoantibodies".)

The prevalence of aPLs in children and adolescents with SLE has been evaluated in cross-sectional cohort studies and ranges from 11 to 62 percent for lupus anticoagulant (LA), 19 to 87 percent for anticardiolipin antibodies (aCL), and 27 to 48 percent for anti-beta2GPI antibodies [137,138]. aPLs are associated with thrombocytopenia, prolonged clotting times (eg, activated partial thromboplastin time [PTT]), menorrhagia, unexplained thrombosis, and stroke [57]. However, aPLs are also found in many children with SLE without these complications. (See "Antiphospholipid syndrome: Diagnosis", section on 'Antiphospholipid antibody testing'.)

All of these autoantibodies 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.

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 or 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 '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 [139]. If an elevated ANA titer is found, the patient should be carefully evaluated for other manifestations of SLE. 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 or a score <10 (for the 2019 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 [140,141] or macrophage activation syndrome (MAS) [142]. 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, clinical manifestations, and diagnosis" and "Children with sepsis in resource-abundant settings: Rapid recognition and initial resuscitation (first hour)" and "Systemic juvenile idiopathic arthritis: 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.

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 examination 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 examination 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 secondary Raynaud phenomenon. A musculoskeletal examination is important to examine for arthritis and/or tenosynovitis, and a focused neurologic examination 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), IgA, IgM, and antinuclear antibodies (ANAs), in addition to a urinalysis and a spot urine for protein and creatinine.

If ANA testing is positive and/or there are other signs or symptoms of cSLE, it is reasonable to check for double-stranded DNA (dsDNA) antibodies and extractable nuclear antigens (ENAs). Although rare, ANA-negative SLE does occur and clinical judgment should prevail in pursuing further investigations (see "Measurement and clinical significance of antinuclear antibodies", section on 'Patients with a negative ANA by indirect immunofluorescence'). ENA testing usually includes a panel of anti-Ro, anti-La, anti-Smith (anti-Sm), and anti-ribonuclear protein (RNP) antibodies. Additionally, we check for the presence of a lupus anticoagulant (LAC), anticardiolipin (aCL), anti-b2GP1 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 lymphohistiocytosis" and "Systemic juvenile idiopathic arthritis: Complications", section on 'Evaluation and diagnostic testing'.)

When clinically indicated by history and/or physical examination, 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 kidney function. In the presence of fever, cytopenias, or signs of MAS, we 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 or prior to initiating immunosuppressive therapy. 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. Other subspecialists, including pediatric neurology, hematology, psychiatry, dermatology, ophthalmology, cardiology, and pulmonology, are also frequently involved in the diagnosis and management.

CLASSIFICATION CRITERIA — 

Three classification criteria exist: one from the American College of Rheumatology (ACR)issued in 1997 [143]; a set of criteria titled the Systemic Lupus International Collaborating Clinics (SLICC) group classification criteria, based upon ACR criteria and published in 2012 [144]; and the 2019 European Alliance of Associations for Rheumatology (EULAR)/ACR classification criteria [145]. Any of these criteria may be used to aid in the diagnosis of SLE in both children and adults (table 2 and table 3) [143,144,146,147], although the SLICC criteria are most sensitive, especially early on in cSLE [148,149]. (See "Systemic lupus erythematosus in adults: Clinical manifestations and diagnosis", section on 'Classification criteria'.)

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 (LN). 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 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 "Systemic lupus erythematosus in adults: Clinical manifestations and diagnosis", 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 [145,150,151]. 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.

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 juvenile dermatomyositis or systemic sclerosis.

DIFFERENTIAL DIAGNOSIS — 

Ten percent or more of "healthy" children have a positive antinuclear antibody (ANA) [152-154]. 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", section on 'Nonrheumatologic causes of a positive ANA'.)

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 occur 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 [155,156]. 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 [157,158]. (See "HHV-8-negative/idiopathic multicentric Castleman disease" and "Unicentric Castleman disease".)

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 phenomenon, puffy fingers, and myositis are predominant, in the presence of high-titer anti-ribonucleoprotein (RNP) antibodies and in the absence of kidney 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 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 "Systemic lupus erythematosus in adults: Clinical manifestations and diagnosis", 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 kidney 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), including those directed against extractable nuclear antigens (ENAs), double-stranded DNA (dsDNA) antibodies, and antiphospholipid antibodies (aPLs) (table 1). Vitamin D deficiency is frequent at presentation. (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 "Systemic lupus erythematosus in adults: Clinical manifestations and diagnosis", section on 'Our diagnostic criteria'.)

●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.

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  110. Soep JB, Mietus-Snyder M, Malloy MJ, et al. Assessment of atherosclerotic risk factors and endothelial function in children and young adults with pediatric-onset systemic lupus erythematosus. Arthritis Rheum 2004; 51:451.
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Topic 6420 Version 35.0

References

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77 : Initial validation of the Pediatric Automated Neuropsychological Assessment Metrics for childhood-onset systemic lupus erythematosus.

78 : Neurocognitive impairment in childhood-onset systemic lupus erythematosus: measurement issues in diagnosis.

79 : A proposed framework to standardize the neurocognitive assessment of patients with pediatric systemic lupus erythematosus.

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81 : Disparities in Psychiatric Diagnosis and Treatment for Youth with Systemic Lupus Erythematosus: Analysis of a National US Medicaid Sample.

82 : Respiratory manifestations of systemic lupus erythematosus: old and new concepts.

83 : Subclinical pulmonary abnormalities in childhood-onset systemic lupus erythematosus patients.

84 : Pulmonary involvement in patients with childhood-onset systemic lupus erythematosus.

85 : Pulmonary involvement in childhood-onset systemic lupus erythematosus: a report of five cases.

86 : Cardio-pulmonary involvement in juvenile systemic lupus erythematosus.

87 : High-sensitivity C-reactive protein and erythrocyte sedimentation rate in systemic lupus erythematosus.

88 : Extremely high levels of C-reactive protein in patients with acute lupus serositis.

89 : Echocardiography and pulmonary function testing in childhood onset systemic lupus erythematosus.

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91 : Pulmonary complications of childhood rheumatic disease.

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99 : Symptoms of shrinking lung syndrome reveal systemic lupus erythematosus in a 12-year-old girl.

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102 : Juvenile- and adult-onset systemic lupus erythematosus: a comparative study in a large cohort from the Spanish Society of Rheumatology Lupus Registry (RELESSER).

103 : Cardiac tamponade as the initial presentation of systemic lupus erythematosus: a case report and review of the literature.

104 : Cardiac tamponade as an initial manifestation of systemic lupus erythematosus in a child.

105 : Cardiovascular involvement in systemic lupus erythematosus: an autopsy study of 27 patients in India.

106 : Use of echocardiography at diagnosis and detection of acute cardiac disease in youth with systemic lupus erythematosus.

107 : Endothelial progenitor cell phenotype and function are impaired in childhood-onset systemic lupus erythematosus.

108 : Early determinants of atherosclerosis in paediatric systemic lupus erythematosus.

109 : Laboratory markers of cardiovascular risk in pediatric SLE: the APPLE baseline cohort.

110 : Assessment of atherosclerotic risk factors and endothelial function in children and young adults with pediatric-onset systemic lupus erythematosus.

111 : Endothelial function analysis and atherosclerotic risk factors in adolescents with systemic lupus erythematosus.

112 : Clinical characteristics and prognosis of childhood-onset lupus mesenteric vasculitis as the initial presentation-a case-control study.

113 : Vasculitis in systemic lupus erythematosus: Prevalence and clinical characteristics in 670 patients.

114 : Cutaneous Involvement in Systemic Lupus Erythematosus: A Review for the Rheumatologist.

115 : Factors associated with thrombosis in pediatric patients with systemic lupus erythematosus.

116 : European evidence-based recommendations for diagnosis and treatment of paediatric antiphospholipid syndrome: the SHARE initiative.

117 : Clinical characteristics and thrombosis outcomes of paediatric antiphospholipid syndrome: analysis of 58 patients.

118 : The 2023 ACR/EULAR Antiphospholipid Syndrome Classification Criteria.

119 : Lupus anticoagulant hypoprothrombinemia syndrome associated with systemic lupus erythematosus in children: report of two cases and systematic review of the literature.

120 : Capillaroscopy in the daily clinic of the pediatric rheumatologist.

121 : Raynaud's Phenomenon.

122 : Abdominal manifestations in childhood-onset systemic lupus erythematosus.

123 : Clinical features, severity and outcome of acute pancreatitis in systemic lupus erythematosus.

124 : Gastrointestinal system manifestations in juvenile systemic lupus erythematosus.

125 : Hepatic manifestations in juvenile systemic lupus erythematosus.

126 : Autoimmune hepatitis in 847 childhood-onset systemic lupus erythematosus population: a multicentric cohort study.

127 : Ocular Manifestations in Children with Juvenile-Onset Systemic Lupus Erythematosus.

128 : Evaluation of Dry Eye Disease in Children With Systemic Lupus Erythematosus and Healthy Controls.

129 : Prevalence of dry eye in patients with systemic lupus erythematosus: a meta-analysis.

130 : Update on ophthalmic manifestations of systemic lupus erythematosus: pathogenesis and precision medicine.

131 : Hypovitaminosis D is associated with greater body mass index and disease activity in pediatric systemic lupus erythematosus.

132 : An update on autoantibodies in systemic lupus erythematosus.

133 : Anti-RO/SSA and anti-La/SSB antibodies: Association with mild lupus manifestations in 645 childhood-onset systemic lupus erythematosus.

134 : Are anti-ribosomal P protein antibodies relevant in systemic lupus erythematosus?

135 : Machine learning identifies clusters of longitudinal autoantibody profiles predictive of systemic lupus erythematosus disease outcomes.

136 : Systemic lupus erythematosus and related disorders of childhood.

137 : Prevalence of clinically meaningful antiphospholipid antibodies in patients with systemic lupus erythematosus varies by race and ethnicity.

138 : Pediatric antiphospholipid syndrome.

139 : Development of autoantibodies before the clinical onset of systemic lupus erythematosus.

140 : Acute viral infections in patients with systemic lupus erythematosus: description of 23 cases and review of the literature.

141 : Cytomegalovirus in pediatric systemic lupus erythematosus: prevalence and clinical manifestations.

142 : Features, Treatment, and Outcomes of Macrophage Activation Syndrome in Childhood-Onset Systemic Lupus Erythematosus.

143 : Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus.

144 : Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus.

145 : 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus.

146 : Performance of the new SLICC classification criteria in childhood systemic lupus erythematosus: a multicentre study.

147 : Comparison between three systems of classification criteria in juvenile systemic lupus erythematous.

148 : Comparison of Sensitivities of American College of Rheumatology and Systemic Lupus International Collaborating Clinics Classification Criteria in Childhood-onset Systemic Lupus Erythematosus.

149 : Evaluating performance of the 2019 EULAR/ACR, 2012 SLICC, and 1997 ACR criteria for classifying adult-onset and childhood-onset systemic lupus erythematosus: A systematic review and meta-analysis.

150 : Reply.

151 : Multicriteria decision analysis process to develop new classification criteria for systemic lupus erythematosus.

152 : Prevalence of positive antinuclear antibodies in healthy children.

153 : Prevalence of antinuclear antibodies in schoolchildren during puberty and possible relationship with musculoskeletal pain: a longitudinal study.

154 : Frequency of antinuclear antibodies in healthy children and adolescents.

155 : Kikuchi-Fujimoto Disease: analysis of 244 cases.

156 : Kikuchi-Fujimoto disease: a clinicopathologic update.

157 : Rare diseases that mimic Systemic Lupus Erythematosus (Lupus mimickers).

158 : Histologic and Laboratory Characteristics of Symptomatic and Asymptomatic Castleman Disease in the Pediatric Population.