What are the clinical signs of familial Mediterranean fever in children, adolescents, or young adults of Mediterranean ancestry?

Clinical Signs of Familial Mediterranean Fever

Familial Mediterranean fever presents with recurrent, self-limited attacks of fever (lasting 1-3 days) accompanied by painful inflammation of serosal surfaces—most commonly peritonitis, pleuritis, and arthritis—along with an erysipelas-like rash on the lower extremities. 1

Core Attack Features

Fever Pattern

• Short, recurrent febrile episodes lasting 1-3 days (not the quotidian pattern seen in other conditions) 1, 2
• Attacks are self-limited and resolve spontaneously 3, 4
• Fever may be more transient than the associated inflammatory symptoms 5

Serosal Inflammation (Most Common Presentations)

Peritonitis:

• Acute abdominal pain mimicking surgical emergencies 1, 2
• Can lead to unnecessary exploratory laparotomy if FMF not recognized 1
• Signs of peritoneal inflammation without other cause 2, 4

Pleuritis:

• Chest pain with signs of pleural inflammation 2, 4
• Unilateral chest involvement typical 5

Arthritis:

• Acute monoarticular synovitis, predominantly affecting knee, ankle, or hip 1, 2
• Joint attacks are self-limited during acute episodes 4, 5

Cutaneous Manifestations

• Erysipelas-like erythema appearing almost exclusively on the lower extremities 1, 5
• This distinctive rash accompanies fever attacks 2, 4

Less Common but Important Manifestations

Scrotal Involvement

• Acute scrotal pain and swelling from tunica vaginalis inflammation 2, 5
• Can mimic testicular torsion 2

Protracted Myalgia

• Severe, prolonged muscle pain requiring expert consultation 1
• May need glucocorticoids or IL-1 blockade for resolution 1

Chronic Complications (If Untreated)

• Chronic destructive polyarthritis can develop, particularly spondyloarthropathy patterns 1
• AA amyloidosis leading to renal failure—the most severe complication 3, 4, 5
• Sensorineural hearing loss (rare) 3
• Pericardial effusion (rare) 3

Demographic and Genetic Context

Population Characteristics

• Predominantly affects individuals of Mediterranean ancestry: Turkish, Armenian, Arab, and Sephardic Jewish populations 3, 2, 4
• Disease often starts in childhood or early adolescence 1, 3, 5
• Can occur in non-Mediterranean individuals and without family history, despite the name 5

Genetic Pattern

• Autosomal recessive inheritance with MEFV gene mutations 3, 4, 6
• Variable proportion of patients present with only heterozygous variants 3
• Three major mutations (M680I, M694V, V726A) account for most Turkish cases 6

Laboratory Findings During Attacks

Acute Phase Response

• Elevated inflammatory markers: CRP and serum amyloid A (SAA) protein during attacks 1
• Leukocytosis during acute episodes 4
• These markers should normalize between attacks in well-controlled disease 1

Monitoring for Subclinical Inflammation

• Persistent elevation of SAA or CRP between attacks indicates inadequate disease control 1
• Regular monitoring every 3-6 months essential to prevent amyloidosis 1, 7

Key Diagnostic Pitfalls to Avoid

Do not dismiss the diagnosis based on:

• Absence of family history (can occur sporadically) 5
• Non-Mediterranean ethnicity (increasingly recognized worldwide) 3, 2
• Atypical genetic findings (some patients have only one identified mutation) 3, 6

Critical differential considerations:

• Distinguish from Adult-Onset Still's Disease (which has quotidian fever pattern, not 1-3 day episodes) 1
• Differentiate from TRAPS (fever attacks last ~21 days with centrifugal rash and ocular involvement) 1
• Rule out surgical emergencies when peritonitis presents (patients with FMF are equally susceptible to appendicitis) 1

Attack Frequency and Pattern

• Attacks occur with variable frequency, but >3 attacks in 6 months is significant for treatment decisions 1
• Complete remission between attacks is characteristic 1
• Attack-free periods distinguish FMF from continuous inflammatory conditions 1