Pediatric Systemic Lupus Erythematosus Clinical Presentation

The most frequent presenting symptoms of systemic lupus erythematosus (SLE) are prolonged fever and malaise with evidence of multisystem involvement. Children often present with a history of fatigue, joint pain, rash, and fever. However, children may also present with various acute symptoms, including memory loss, psychosis, transverse myelitis, hemoptysis, edema of the lower extremities, headache, and painful mouth sores.

Eleven criteria from the American College of Rheumatology (ACR) are used for the classification of lupus in adults. ^[13] The same criteria can serve as a guideline in children. Any 4 criteria are sufficient for classificantion and should be sought in the history. (Of note, ANA is almost always present but is not diagnostic.)

The ACR’s diagnostic criteria for SLE include the following:

• Malar rash

• Naso-oral ulcers

• Photosensitive rash

• Discoid rash

• Arthritis

• Pleuritis or pericarditis

• Proteinuria (>500 mg/d) or evidence of nephritis in urinalysis

• Hemolytic anemia, thrombocytopenia, leukopenia, or lymphopenia

• Seizure or psychosis

• Positive ANA finding

• Positive anti–double-stranded DNA, anti-Smith, or antiphospholipid antibody/lupus anticoagulant

The Systemic Lupus International Collaborative Clinics recently published a modification of the ACR criteria. ^[14] Lupus patients meet 4 criteria with at least one clinical and one immunologic criterion or with biopsy-proven nephritis in association with positive ANA and anti-dsDNA. These criteria were thought to improve clinical relevance and specificity of criteria, as well as incorporate current understanding of lupus immunology.

Clinical criteria

1. Acute cutaneous lupus including the following:

• Lupus malar rash (do not count if malar discoid)

• Bullous lupus

• Toxic epidermal necrolysis variant of SLE

• Maculopapular lupus rash

• Photosensitive lupus rash (in the absence of dermatomyositis)

OR subacute cutaneous lupus (nonindurated psoriaform and/or annular polycyclic lesions that resolve without scarring, although occasionally with postinflammatory dyspigmentation or telangiectasias

2. Chronic cutaneous lupus including the following:

• Classic discoid rash

• Localized (above the neck)

• Generalized (above and below the neck)

• Hypertrophic (verrucous) lupus

• Lupus panniculitis (profundus)

• Mucosal lupus

• Lupus erythematosus tumidus

• Chilblains lupus

• Discoid lupus/lichen planus overlap

3. Oral ulcers in the absence of other causes such as vasculitis, Behçet disease, herpesviruses, inflammatory bowel disease, reactive arthritis, or acidic foods

• Palate

• Buccal

• Tongue

• Nasal

4. Nonscarring alopecia (diffuse thinning or hair fragility with visible broken hairs) in the absence of other causes such as alopecia areata, drugs, iron deficiency, or androgenic alopecia

5. Synovitis involving 2 or more joints, characterized by swelling or effusion OR tenderness in 2 or more joints and at least 30 minutes of morning stiffness

6. Serositis in the absence of other causes such as infection, uremia, and Dressler pericarditis

• Typical pleurisy for more than 1 day

• OR pleural effusions

• OR pleural rub

• Typical pericardial pain (pain with recumbency improved by sitting forward) for more than 1 day

• OR pericardial effusions

• OR pericardial rub

• OR pericarditis by electrocardiography

7. Renal, as follows:

• Urine-to-creatinine ratio (or 24-hour urine protein) representing 500 mg protein/24 hours

• OR red blood cell casts

8. Neurologic, as follows:

• Seizures

• Psychosis

• Mononeuritis multiplex in the absence of other known causes such as primary vasculitis

• Myelitis

• Peripheral or cranial neuropathy in the absence of other known causes such as primary vasculitis, infection, and diabetes mellitus

• Acute confusional state in the absence of other causes, including toxic/metabolic/uremia/drugs

9. Hemolytic anemia

10. Leukopenia (< 4,000/µL at least once) in the absence of other known causes such as Felty syndrome, drugs, or portal hypertension

OR lymphopenia (< 1,000/µL at least once) in the absence of other known causes such as corticosteroids, drugs, or infection

11. Thrombocytopenia (< 100,000/µL) at least once in the absence of other known causes such as drugs, portal hypertension, or thrombotic thrombocytopenic purpura

Immunologic criteria

1. ANA level above laboratory reference range

2. Anti-dsDNA antibody level above laboratory reference range (or >2-fold the reference range if tested by enzyme-linked immunosorbent assay [ELISA])

3. Anti-Sm: Presence of antibody to Sm nuclear antigen

4. Antiphospholipid antibody positivity as determined by any of the following

• Positive test result for lupus anticoagulant

• False-positive test result for rapid plasma reagin

• Medium- or high-titer anticardiolipin antibody level (IgA, IgG, or IgM)

• Positive test result for anti-B2-glycoprotein I (IgA, IgG, or IgM)

5. Low complement, as follows:

• Low C3

• Low C4

• Low CH50

6. Direct Coombs test in the absence of hemolytic anemia

Patients should be evaluated for traditional risk factors of atherosclerosis, including smoking history, family history of atherosclerosis, and physical activity. Risks should be stratified and treated.

The diagnosis of SLE is not difficult in a child who presents with many manifestations, such as malar rash, pleuritic chest pain, nephritis, and a positive ANA finding. Some patients present over longer periods and require careful consideration. Occasionally, patients do not fulfill the classification criteria, a definite classification is never made, or the patient may have an overlap syndrome with manifestations of several rheumatic diseases.

Treatment should never be delayed in patients who do not fulfill classification criteria, particularly when patients are seriously ill.

A detailed physical examination is a critical tool in the diagnosis of systemic lupus erythematosus (SLE). Most of the ACR classification criteria are associated with physical findings. ^[13] The following is a description of more common clinical manifestations.

Rash occurs in 70-80% of patients. The characteristic rash is a malar, or butterfly, rash, including both cheeks and the nasal bridge sparing the nasolabial fold. The rash varies from an erythematous blush to a thickened epidermis to a scaly rash. (See the image below.)

Other common rashes include vasculitic macular eruptions, particularly on the distal extremities and often in the subungual region, with visible microinfarcts from small vessel vasculitis; purpura; livedo reticularis, which is often associated with antiphospholipid antibodies; alopecia, which is usually frontal or hairline; and Raynaud phenomenon, which is characterized by sequential color changes in the fingers and toes.

Less common rashes include subacute psoriasiform or annular skin lesions, often associated with anti-Ro antibodies and bullous lesions, a rare but potentially life-threatening condition as bullae can cover large surfaces and oral mucosa, with loss or skin integrity and compromise of the airway. Other diagnostic skin findings include discoid rash, which is less common in childhood; a photosensitive rash; and mucous membrane changes that range from vasculitic erythema to large, deep ulcers on the palate and nasal mucosa.

Musculoskeletal findings include arthritis, arthralgia, tendonitis, and myositis. Deforming arthritis is unusual and, if present, is usually secondary to a Jaccoudlike arthropathy. This arthritis can lead to ligament damage and severely lax joints.

Avascular necrosis of bone is a frequent complication, occurring in about 25% of children with SLE over time. It is most common in children with SLE who are receiving daily corticosteroids, although it can also occur in children with SLE who are not being treated with corticosteroids and in children receiving corticosteroids for conditions other than SLE.

Patients often present with lymphadenopathy and hepatosplenomegaly. Many have chronic abdominal pain secondary to recurrent vascular insults to the intestinal tract and/or chronic pancreatitis, which may be a result of treatment with corticosteroids or from the SLE itself. Other abdominal findings can include pain secondary to peritoneal serositis or small-vessel vasculitis. The latter can be associated with severe bleeding and necrosis of tissue and is clearly life threatening.

Cardiac involvement includes pericarditis, murmurs associated with valvulitis, carditis, and cardiac failure from myocarditis or infarction. Pulmonary auscultatory findings may be abnormal secondary to pleuritis, infiltrates, or hemorrhage.

Neurologic manifestations can involve the central and the peripheral nervous systems. Clinical findings associated with classification criteria include seizure and psychosis; however, patients may present with stroke, pseudotumor cerebri, cerebral venous thrombosis, aseptic meningitis, chorea, global cognitive deficits, mood disorders, transverse myelitis, and peripheral neuropathy, as well as many less common neurologic findings.

As many as 40% of children may have neurologic disease, and perhaps even more when psychiatric manifestations and cognitive abnormalities are considered. Quantification of cognitive function with formal neuropsychiatric testing may be advisable.

Renal disease is manifested by hypertension, edema of the lower extremities, retinal changes, and clinical manifestations associated with electrolyte abnormalities, nephrosis, or acute renal failure. Renal disease is more frequently observed in children than in adults.

Patients with lupus may present with the clinical findings of endocrine disease, such as hyperthyroidism and Addisonian crisis.