Familial Mediterranean Fever (FMF) is primarily a clinical diagnosis, relying on a careful patient history, physical examination, and specific diagnostic criteria. These criteria, combined with laboratory findings, guide the diagnostic process.

Key Clinical Indicators:
The diagnosis is strongly suggested by the presence of:
* Recurrent, short-duration (1-4 days) episodes of fever.
* Attacks of serositis, manifesting as abdominal pain, chest pain (pleuritis or pericarditis), or joint pain (arthralgia, arthritis affecting hips, knees, ankles).
* History of scrotal, skin (erysipelas-like erythema), or muscle involvement.
* A positive response to colchicine therapy in preventing attacks.
* An ethnic background known to be susceptible to FMF.
* A family history of FMF.

Laboratory Findings:
During FMF attacks, inflammatory markers are typically elevated and then rapidly normalize after the attack subsides. These include:
* Increased white blood cell count (leukocytosis), often with neutrophil dominance.
* Elevated Erythrocyte Sedimentation Rate (ESR).
* High C-reactive protein (CRP) levels.
* Increased fibrinogen levels.
* Occasionally, elevated serum haptoglobin (indicating red blood cell destruction) and albumin in urine (with or without microscopic hematuria) may be observed, potentially signaling kidney involvement.

Genetic Analysis:
Genetic testing for MEFV gene mutations can support a clinical diagnosis but is not definitive. It's important to note that a significant percentage (around 10%) of patients who meet clinical diagnostic criteria may not show any identifiable MEFV mutations.

Differential Diagnosis and Supporting Tests:
To exclude other conditions, or to support the diagnosis, specific tests may be performed:
* Synovial fluid analysis in joint attacks may show sterile fluid with elevated nucleated white cells.
* Electrocardiogram (ECG) might reveal diffuse ST-segment elevation in cases of pericarditis.
* Abdominal Computed Tomography (CT) scans are often used to rule out other causes of acute abdominal pain.

Comprehensive Diagnostic Criteria (based on the provided major, minor, and supportive categories):

Major Criteria (Presence of recurrent attacks affecting these areas):
* Abdomen
* Joints (hip, knee, ankle)
* Chest (unilateral pleuritis or pericarditis)
* Scrotum
* Skin
* Muscles
* Isolated fever

Minor Criteria:
* Recurrent attacks affecting abdomen, joints, or chest.
* Exertion-induced leg pain.
* Positive response to colchicine.
* Nephropathic amyloidosis.

Supportive Criteria:
* Family history of FMF.
* Vulnerable ethnic origin.
* Early onset (under 20 years of age).
* Severe attacks requiring bed rest.
* Presence of high white blood cell count or elevated acute phase reactants during attacks.
* History of laparotomy or appendectomy without pathological findings.
* Episodic proteinuria or hematuria.
* Parental consanguinity.