the Diagnosis and Treatment of Familial Mediterranean Fever during Childhood and Adolescence

Health Question

Recommendation & its Grade

Level of Evidence

Source Guidelines

1-When to suspect FMF?

Recurrent febrile episodes associated with abdominal and/or chest pain caused by serositis (peritonitis, pericarditis or pleurisy) and arthritis/synovitis of large joints, accompanied by erysipeloid erythema. (D)

D

Brazilian(25)

2- How to diagnose FMF?

The presence of at least 2 of the following 5 criteria after exclusion of other causes can diagnose FMF with high sensitivity:

Fever axillary temperature of >38ᵒC, 6–72 h of duration, ≥3 attacks

Abdominal pain 6–72 h of duration ≥3 attacks

Chest pain 6–72 h duration≥ 3 attacks

Arthritis 6–72 h duration ≥3 attacks, oligoarthritis

Family history of FMF*(26)

GPP

3- What is the role of genetic study in FMF diagnosis?

Genetic testing can support the clinical diagnosis but cannot exclude it**(27)

GPP

4- What is the essential laboratory work up for FMF?

Laboratory tests are not specific, demonstrating high serum levels of inflammatory proteins in the acute phase of the disease, but also often showing high levels even between attacks. SAA serum levels may be especially useful in monitoring the effectiveness of treatment. (C)

C

Brazilian

Health Question

Recommendation

Source (Guidelines)

Page

Level of Evidence

GR

1-Who should start treatment?

Ideally, FMF should be diagnosed and initially treated by a physician with experience in FMF.

EULAR(28)

645

5

D

2-What are the ultimate goals of treatment of FMF?

The ultimate goal of treatment in FMF is to obtain complete control of unprovoked attacks and minimize subclinical inflammation in between attacks.

EULAR

645

4

C

3-When to start treatment with colchicine?

Treatment with colchicine should be started as soon as a clinical diagnosis is made.

EULAR

646

1b

A

4-Should asymptomatic Individuals with MEFV gene pathogenic mutations start treatment?

Genetic testing is ideally requested and interpreted by immunology/rheumatology specialist.** (27)

Asymptomatic individuals with homozygous pathogenic mutations, particularly M694V, should be evaluated and followed up by an expert for possible intervention.**(27)

GPP

GPP

5-How is colchicine given?

Dosing can be in single or in divided doses, depending on tolerance and compliance.

EULAR

646

5

D

6-What are the indications for increasing the dose of colchicine?

The persistence of attacks or subclinical inflammation represents an indication to increase colchicine dose.

EULAR

646

3

C

7-What is the treatment of amyloidosis?

FMF treatment needs to be intensified in AA amyloidosis using the maximal tolerated dose of colchicine and supplemented with biologics as required.

EULAR

646

2b

C

8-How to monitor toxicity of Colchicine?

Colchicine toxicity is a serious complication that should be given adequate consideration and be prevented.

Liver enzymes should be monitored regularly in patients with FMF treated with colchicine; if liver enzymes are elevated greater than twofold the upper limit of normal, colchicine shouldbe reduced, and the cause further investigated.

In patients with decreased renal function, the risk of colchicine toxicity is very high and therefore evidence of toxicity should routinely be sought, and the colchicine dose reduced accordingly.

EULAR

EULAR

EULAR

647

647

647

4

5

4

C

D

C

10-How to treat patients with chronic arthritis?

Chronic arthritis in a patient with FMF might need additional medications, such as DMARDs, intra-articular steroid injections or biologics.

EULAR

645

2b

C

11-How to treat febrile myalgia

In protracted febrile myalgia, glucocorticoids lead to the resolution of symptoms; NSAID and IL-1-blockade might also be a treatment option. NSAIDs are suggested for the treatment of exertional leg pain.

EULAR

645&648

2b

C

12-Should colchicine be stopped during pregnancy or lactation?

Colchicine should not be discontinued during conception, pregnancy or lactation; current evidence does not justify amniocentesis.

EULAR

648

3

C

13-Should colchicine be stopped before conception in men?

In general, men do not need to stop colchicine prior to conception; in the rare case of azoospermia or oligospermia proven to be related to colchicine, temporary dose reduction or discontinuation may be needed.

EULAR

648

3

C

14-When to add biologic treatment?

Compliant patients not responding to the maximum tolerated dose of colchicine can be considered non-respondent or resistant; alternative biological treatments are indicated in these patients.

EULAR

646-647

2b

B

15-For how long should treatment be continued?

If a patient is stable with no attacks for more than 5 years and no elevated APR, dose reduction could be considered after expert consultation and with continued monitoring.

EULAR

648-649

5

D