Tests
1st tests to order
CBC
Test
Mostly elevated neutrophils due to acute inflammation. Thrombocytosis may occur as an acute-phase reaction.
Result
leukocytosis ± thrombocytosis
erythrocyte sedimentation rate
Test
Acute-phase reactant and might remain elevated in between attacks. Not specific or diagnostic.
Result
elevated
CRP
Test
Acute-phase reactant and might remain elevated in between attacks. Not specific or diagnostic.
Result
elevated
serum fibrinogen
Test
Acute-phase reactant and might remain elevated in between attacks. Not specific or diagnostic.
Result
elevated
serum amyloid A
Test
Acute-phase reactant and might remain elevated in between attacks. Not specific or diagnostic.
Result
elevated
LFTs
Test
If severely elevated could suggest acute viral hepatitis. May be mildly elevated during FMF attacks.
Should return to normal in between FMF attacks.
Result
rarely: elevated alanine aminotransferase and aspartate aminotransferase
urine analysis
Test
Proteinuria might be present during attacks, which should trigger an evaluation for the potentially fatal complication renal amyloidosis.
Hematuria may be suggestive of possible infection or other diagnosis (e.g., vasculitis).
Result
proteinuria; hematuria suggests infection or vasculitis
Tests to consider
LDH
Test
Due to acute inflammation. Not specific or diagnostic.
Result
elevated
chest x-ray
Test
Helpful to differentiate other causes of febrile illnesses. Not specific or diagnostic.
Result
usually normal
joint x-ray
Test
In rare cases may show chronic destructive arthritis, typically if hip or knee involvement. May be suggestive of other diagnosis.
Result
usually normal
abdominal CT
Test
This finding indicates serositis of the serosal lining of the abdomen (peritonitis). Helpful to exclude other causes of acute abdomen, but high level of suspicion of FMF must be maintained or diagnosis could be missed.
Result
may show fluid and/or inflammation
chest CT
Test
This finding indicates serositis of the pleura (pleuritis). Not specific or diagnostic, but may be helpful in suggesting diagnosis and/or excluding differential diagnoses.
Result
may show pleural effusion
echocardiogram
Test
This finding indicates serositis of the pericardium (pericarditis).
There is echocardiographic evidence to suggest that 27% of patients with disease duration >16 years have evidence of pericardial disease without any other known causative factors.[80][81]
Result
may show pericardial effusion; absence of left ventricular wall motion abnormalities
joint MRI
Test
In rare cases could show chronic destructive arthritis, typically if hip or knee involvement. May be suggestive of other diagnosis.
Result
usually normal
genetic testing
Test
Assess the patient for more common causes of fever, for example infection and malignancy, before ordering genetic testing.[70]
Not all mutations are known. The 4 most common are M680I, M694V, V726A, and M694I; these are present in over two-thirds of cases.[21]
Controversy exists as to the role of the amino acid substitution E148Q, where glutamine (Q) substitutes for glutamic acid (E). Initially this sequence variation was described as a disease-causing mutation with low penetrance and mild symptoms.[22][23][24] Subsequent studies suggest it may be no more than a benign polymorphism with a high frequency in the general population (up to 30% in some Asian populations).[25][26] The 2015 Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) guideline concludes that the E148Q variant is common, of unknown pathogenic significance, and as the only MEFV variant, does not support a diagnosis of FMF.[26] Physicians should closely monitor patients with a specifically homozygous E148Q genotype due to its possible association with amyloidosis.[27][28][29]
In a clinical context of FMF, the presence of 2 mutations on different alleles (homozygosity or compound heterozygosity) confirms the diagnosis.[54] When only 1 mutation is present, the diagnosis is unconfirmed; nevertheless, diagnosis should not be ruled out if the clinical presentation is typical, because some rare or unknown mutations do exist.[36][55] The registry of hereditary auto-inflammatory disorders mutations Opens in new window Those same ″true″ heterozygotes may display a complete clinical picture of FMF. It is also likely that some heterozygous patients, as in many recessive diseases, may have attenuated clinical signs. Even though the genetic diagnosis provides no final solution for every patient, it has become an important diagnostic tool for the confirmation of FMF diagnosis and, consequently, the provision of appropriate treatment, especially in children.[60]
To obtain genetic tests, physicians should contact their local laboratory provider (or local research laboratories at university centers). If there are existing genetic test results, do not order a duplicate test unless there is uncertainty about the existing result, for example the result is inconsistent with the patient’s clinical presentation or the test methodology has changed.[71]
Result
positive for mutation
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