Investigations
1st investigations to order
full blood count with differential
Test
Should be ordered in all patients with suspected systemic lupus erythematosus.
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
To be considered in all patients with suspected systemic lupus erythematosus.
Result
may be prolonged in patients with antiphospholipid antibodies
urea and electrolytes
Test
Ordered in all patients with suspected systemic lupus erythematosus (SLE).
Identifies those patients with SLE who have renal manifestations.
Result
elevated urea and creatinine
erythrocyte sedimentation rate and C-reactive protein
Test
Non-specific markers that may be elevated due to an acute phase response from any cause.
Patients with systemic lupus erythematosus 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
Ordered in all patients with suspected systemic lupus erythematosus (SLE).
The American College of Rheumatology recommends the immunofluorescence ANA test using human epithelial type 2 (HEp-2) substrate for ANA testing.[80][81]
A positive ANA in itself is not diagnostic because 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.
A low or high (although less common) titre ANA can occur in healthy people.[82]
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). Anti-dsDNA and anti-Smith antibodies are highly specific for SLE and often are confirmatory of the diagnosis, if present.[83][84] 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
To assess renal involvement and should be performed in all patients with suspected systemic lupus erythematosus, even in the absence of symptoms.
Result
haematuria, casts (red cell, granular, tubular, or mixed) or proteinuria
chest x-ray
Test
All patients with suspected systemic lupus erythematosus presenting with cardiopulmonary symptoms should have a CXR performed.
Result
pleural effusion, infiltrates, cardiomegaly
ECG
Test
All patients with suspected systemic lupus erythematosus presenting with cardiopulmonary symptoms should have an ECG performed.[90]
Result
may exclude other causes of chest pain
Investigations to consider
blood and urine cultures
Test
All patients presenting with persistent fever should have an appropriate symptom-targeted infection screen.
Result
may exclude infection
antiphospholipid antibodies
Test
Antiphospholipid antibodies should be ordered in patients with systemic lupus erythematosus, and thereafter in those with an adverse pregnancy history or arterial/venous thrombotic events.[85]
Result
positive
Coombs test
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
Performed if urinalysis is abnormal, which is defined as abnormal proteinuria assessed by dipstick protein ≥2+ (any level of specific gravity); dipstick protein 1+ (low specific gravity); spot PCR >500 mg/g (50 mg/mmol); urine sediment positive for acanthocytes (≥5%), red blood cell casts or white blood cell casts.[87]
Result
proteinuria
complement levels
Test
Complement levels can be used in the setting of 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
creatinine phosphokinase
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
Done in all patients with systemic lupus erythematosus with symptoms of arthralgia or arthritis.
Result
inflammation, non-erosive arthritis
renal ultrasound
Test
Done in patients with systemic lupus erythematosus and renal involvement: for example, patients with abnormal urinary sediment on urinalysis.
Result
to exclude other causes of renal impairment
CT chest
Test
Done in patients with systemic lupus erythematosus complaining of respiratory symptoms and signs.
Result
lung fibrosis, effusions
pulmonary function tests
Test
Done in patients with systemic lupus erythematosus complaining of respiratory symptoms and signs indicating fibrosis.
Result
restrictive pattern
pleural aspiration
Test
Performed to identify cause of pleural effusion.
Result
exudate
brain magnetic resonance imaging
Test
May be done in patients with suspected cerebral lupus, although central nervous system involvement is typically diagnosed clinically.
Result
white matter changes
echocardiogram
Test
Done in patients with symptoms and signs of pericarditis or pulmonary hypertension.
Result
pericarditis, pericardial effusion, pulmonary hypertension
skin biopsy
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
kidney biopsy
Test
A kidney biopsy should be considered if proteinuria of ≥500 mg/d is confirmed by 24-hour urine collection, or if there is evidence of decreased glomerular filtration rate.[86][87] ACR guideline for screening, treatment, and management of LN.[86][87]
Result
immune deposits, mesangial hypercellularity; focal, segmental, or global glomerulonephritis
thyroid-stimulating hormone
Test
Thyroid-stimulating hormone is elevated in primary hypothyroidism and should be excluded as an underlying cause for fatigue.
Result
normal level usually excludes hypothyroidism
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