Investigations
1st investigations to order
FBC
Test
Order in any patient with prolonged spiking temperatures with concurrent arthralgia, rash, or sore throat.
Anaemia is seen in 27% to 69% of patients.[25][28][29][30]
Leukocytosis and elevated polymorphonuclear leukocytes ≥80% are classic findings in people with AOSD and are seen together in 73% to 100% of patients.[5]
Thrombocytosis is seen in 38% to 46% of patients.[7][30]
Thrombocytopenia occurred in 14% of patients with AOSD in one study.[29]
Result
anaemia, leukocytosis, neutrophilia; thrombocytosis or thrombocytopenia
renal panel
Test
Routine test. Renal dysfunction may infrequently be a complication (reported in around 7% of patients).[5]
Result
serum creatinine may be elevated
C-reactive protein (CRP)
erythrocyte sedimentation rate (ESR)
liver function tests
Test
One of the minor criteria in the Yamaguchi's classification criteria for AOSD.[48]
Result
abnormal, particularly elevations in aspartate and alanine aminotransferase
procalcitonin
Test
Highly sensitive to bacterial infection, so this test is carried out to help rule out this differential.[64]
Result
negative
blood cultures
Test
Part of an initial full septic screen to rule out infection.
Result
negative
chest x-ray
Test
Part of a full septic screen to rule out infection.
Result
no signs of chest infection
renal and liver ultrasound scan
Test
Part of a full septic screen to rule out infection.
Result
no signs of abdominal source of infection
echocardiogram
Test
Part of a full septic screen to rule out infection. May be done if pericarditis or myocarditis suspected as an uncommon finding in AOSD.
Result
normal unless pericarditis/myocarditis present
ECG
Test
May be done if pericarditis or myocarditis suspected.
Result
normal; with myocarditis there may be non-specific ST-segment and T-wave abnormalities; with pericarditis there may be upwards concave ST-segment elevation globally with PR depressions in most leads, J-point depression and PR elevation in leads aVR and V1
Investigations to consider
cardiac enzymes
Test
May be mildly elevated if myocarditis present.
Result
normal unless myocarditis present
cardiac MRI
Test
May be done if myocarditis suspected.
Result
normal; with myocarditis there may be global early enhancement and concurrent pericardial thickening or inflammation
serum ferritin
Test
Request in any patient with prolonged fevers in whom first-line infective screens have been unremarkable.
Hyperferritinaemia is common (89%) in people with AOSD.[47]
A highly sensitive though poorly specific marker of AOSD (though hyperferritinaemia alongside a low glycosylated ferritin can act as a specific marker).[1]
Levels can also be used to monitor disease activity and if >5000 ng/mL and/or climbing can help to identify the life-threatening complication macrophage activation syndrome.[6][63]
Result
Hyperferritinaemia (≥5 × ULN)
glycosylated ferritin
further tests as part of full septic screen
Test
This screen would include but is not limited to targeted cultures, interferon-gamma release assays (IGRAs) for diagnosing Mycobacterium tuberculosisinfection, and serology and polymerase chain reaction for specific infections.
Result
no evidence of infection
further tests as part of autoimmune/rheumatological screen
Test
This screen may include but is not limited to:
Rheumatoid factor, which is positive in 60% to 70% of people with rheumatoid arthritis.[65]
Anticyclic citrullinated peptide (ACPA), which is positive in 70% of those with rheumatoid arthritis.[66]
Antineutrophil cytoplasmic autoantibodies (ANCA), which when positive is strongly associated with certain forms of vasculitis.
Antinuclear antibodies (ANA), which are positive (though non-specific) in systemic lupus erythematosus.
HLA-B27, which may be positive in people with reactive arthritis.
Muscle MRI/biopsy demonstrating inflammatory features associated with dermatomyositis.
Result
no evidence of other rheumatological disease
fluorodeoxyglucose (FDG)-positron emission tomography (PET) whole-body scan
Test
Malignancy or occult infection typically must be ruled out before diagnosing and treating AOSD.
The characteristic pattern of AOSD along with the intensity of uptake has been shown to effectively differentiate it from other differentials.[6][67]
This investigation may not be available in all locations.
Result
pattern of symmetrical reactive lymph nodes in the neck and axilla with increased uptake in the spleen and bone marrow
whole-body CT scan
Test
May be used to help rule out malignancy or occult infection.
Result
pattern of symmetrical reactive lymph nodes in the neck and axilla; serous effusions
bone marrow biopsy
Test
May be done to exclude differentials and/or if the complication of MAS is suspected.
Result
no evidence of lymphoma or a myeloproliferative disorder, may show haemophagocytosis by activated macrophages if complicated by macrophage activation syndrome (MAS)
lymph node biopsy
Test
Lymph node biopsy can help to exclude differentials such as histiocytic disorders, lymphoproliferative diseases, and tuberculosis, all of which can present with fever of unknown origin. Lymphoma is a particularly important differential to exclude.[5]
Result
May reveal reactive hyperplasia or non-specific chronic inflammation
empirical corticosteroids
Test
In practice, as with most autoinflammatory conditions, once malignancy and infection has been ruled out a good response to corticosteroids is suggestive of the underlying aetiology.
Result
rapid improvement in symptoms
autoinflammatory gene profiling
Test
It is important to exclude inherited and acquired monogenic autoinflammatory diseases, which may have different treatment options. Autoinflammatory panels for genetic analysis exist and can identify pathogenic variants of the genes associated with specific autoinflammatory diseases such as NLRP3-AID and VEXAS syndrome.[6] Infevers: The registry of hereditary auto-inflammatory disorders mutations Opens in new window
Result
no pathogenic variants of genes associated with other autoinflammatory diseases
Emerging tests
cytokine profiles
Test
These profiles may be used in the future to better identify clinical subsets, those at risk of complications (e.g., increased likelihood of MAS with elevated IL-18), and predict the most effective targeted therapies.[53]
Result
elevated IL-18/1β levels in systemic AOSD; elevated IL-6 in articular AOSD
serum S100A12; serum calprotectin (S100A8/S100A9 dimer)
HLA genotyping
Test
There is an association of certain HLA subtypes with AOSD.
HLA-DQB1*06:02 (OR 2.70), HLA-DRB1*15:01 (OR 2.44), HLA-DRB1*11 (OR 2.3) and HLA-DQA1*01:02 (OR 1.97) have all demonstrated association with the disease against healthy controls and may have a potential role in diagnosis in the future although further research is required.[60][61]
Result
HLA association may be present
Use of this content is subject to our disclaimer