Investigations

1st investigations to order

full blood count and differential

Test
Result
Test

Should be ordered in anyone suspected of having SLE.

Leukopenia is usually caused by lymphopenia rather than neutropenia.

Drugs and infection should be excluded as a cause of the cytopenias.

Result

anaemia, leukopenia, thrombocytopenia; rarely pancytopenia

activated partial thromboplastin time

Test
Result
Test

To be considered in anyone suspected of having SLE.

Result

may be prolonged in patients with antiphospholipid antibodies

urea and electrolytes

Test
Result
Test

Ordered in anyone suspected of having SLE.

Identifies those patients with SLE who have renal manifestations.

Result

elevated urea and creatinine

erythrocyte sedimentation rate and C-reactive protein

Test
Result
Test

Non-specific markers that may be elevated due to an acute phase response from any cause.

Patients with SLE have systemic inflammation. Erythrocyte sedimentation rate (ESR) may be elevated due to high levels of immunoglobulins.

Elevated ESR and C-reactive protein should prompt a search for infection but could also be due to active disease.

Result

elevated (non-specific)

antinuclear antibodies, double-stranded (ds)DNA, Smith antigen

Test
Result
Test

Done in anyone suspected of having SLE.

Antinuclear antibody (ANA) is positive in virtually all patients with SLE.[79] Clinically relevant ANAs are IgG antibodies.

Currently the most sensitive test for confirming the diagnosis of SLE when accompanied by typical clinical findings.

A positive ANA in itself is not diagnostic as it may be positive in other connective tissue diseases such as rheumatoid arthritis, systemic sclerosis, Sjogren's syndrome, thyroid disease, chronic infectious diseases, and inflammatory bowel disease, and in patients treated with certain drugs such as procainamide, hydralazine, isoniazid, and chlorpromazine.

ANAs in a low titre also occur in healthy people: 1 in 3 will have a positive ANA at the screening dilution of 1:40 and 1 in 20 will have an ANA titre of 1:160.[66] As ANA can be positive in so many conditions, the result of a positive ANA has to be interpreted in the light of the clinical history and symptoms.

Rarely, the ANA can be negative in SLE, especially in anti-Ro-antibody-positive lupus (Ro is also known as Sjogren's syndrome A or Sjogren's antibody). The American College of Rheumatology recommends the immunofluorescence ANA test using human epithelial type 2 (HEp-2) substrate as the gold standard for ANA testing.[67][68] Anti-dsDNA and anti-Smith antibodies are highly specific for SLE and often are confirmatory of the diagnosis, if present.[69][70] High titres of anti-dsDNA antibodies are markers of disease activity and high levels are predictors of worse outcome in lupus nephritis. 

Result

positive

urinalysis

Test
Result
Test

To assess renal involvement and should be done in anyone suspected of having SLE.

Result

haematuria, casts (red cell, granular, tubular, or mixed) or proteinuria

chest x-ray

Test
Result
Test

All patients presenting with cardiopulmonary symptoms should have a chest x-ray performed.

Result

pleural effusion, infiltrates, cardiomegaly

ECG

Test
Result
Test

All patients presenting with cardiopulmonary symptoms should have an ECG performed.[73]

Result

may exclude other causes of chest pain

Investigations to consider

blood and urine cultures

Test
Result
Test

Performed in febrile patients.

Result

may exclude infection

antiphospholipid antibodies

Test
Result
Test

Antiphospholipid antibodies should be ordered in patients with a history of venous or arterial thromboses, miscarriages, or in patients with a prolonged activated partial thromboplastin time.

Result

positive

Coombs test

Test
Result
Test

Ordered if initial blood count shows an anaemia as well as features of haemolysis such as elevated MCV and reticulocyte count.

Result

positive

24-hour urine collection for protein or spot urine for protein/creatinine ratio

Test
Result
Test

Performed if urinalysis is abnormal.

Result

proteinuria

complement levels

Test
Result
Test

Complement levels should be considered but are not necessary to diagnose SLE. They can be used if there are significant organ manifestations such as cerebritis or nephritis. Sequential rather than single measurements are necessary to be of value, in order to follow response to treatment or confirm worsening disease.

Low C4 levels are common as they may be due to C4 null alleles (genetically low levels), and thus C4 levels are not always helpful in monitoring the disease.

Active disease may result in low C3 levels, but increased synthesis due to an acute phase response may confound interpretation. Although activation products can be measured, they are not frequently available.

Result

complement consumption

creatine phosphokinase

Test
Result
Test

Performed in patients with myalgia and weakness. If elevated, an underlying inflammatory myositis should be considered.

Result

may be elevated

plain x-rays of affected joint(s)

Test
Result
Test

Done in patients suspected of having SLE with symptoms of arthralgia or arthritis.

Result

inflammation, non-erosive arthritis

renal ultrasound

Test
Result
Test

Done in patients with SLE and renal involvement: for example, patients with abnormal urinary sediment on urinalysis.

Result

to exclude other causes of renal impairment

chest computed tomography

Test
Result
Test

Done in patients with SLE complaining of respiratory symptoms and signs.

Result

lung fibrosis, effusions

pulmonary function tests

Test
Result
Test

Done in patients with SLE complaining of respiratory symptoms and signs indicating fibrosis.

Result

restrictive pattern

pleural aspiration

Test
Result
Test

Performed to identify cause of pleural effusion.

Result

exudate

brain magnetic resonance imaging

Test
Result
Test

May be done in patients with suspected cerebral lupus, although central nervous system involvement is typically diagnosed clinically.

Result

white matter changes

echocardiography

Test
Result
Test

Done in patients with symptoms and signs of pericarditis or pulmonary hypertension.

Result

pericarditis, pericardial effusion, pulmonary hypertension

skin biopsy

Test
Result
Test

Often not necessary to confirm the diagnosis of mucocutaneous manifestations as these are typically diagnosed clinically. Skin biopsy should be done if the diagnosis is in doubt.

Result

immune deposits at the dermal-epidermal junction on immunofluorescence or non-specific inflammation

renal biopsy

Test
Result
Test

A renal biopsy is the most sensitive and specific test for diagnosis of lupus nephritis. As it is invasive and not without risks, patients with renal involvement should be assessed by a nephrologist.

Result

immune deposits, mesangial hypercellularity; focal, segmental, or global glomerulonephritis

thyroid-stimulating hormone

Test
Result
Test

Thyroid-stimulating hormone is elevated in primary hypothyroidism.

Result

normal level usually excludes hypothyroidism

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