Clinical manifestations and diagnosis of familial Mediterranean fever
- Stephen E Goldfinger, MD
Stephen E Goldfinger, MD
- Professor of Medicine Emeritus
- Harvard Medical School
- Section Editor
- Lawrence S Friedman, MD
Lawrence S Friedman, MD
- Section Editor — General Gastroenterology
- Professor of Medicine
- Harvard Medical School
- Tufts University School of Medicine
Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disorder characterized by recurrent bouts of fever and serosal inflammation. This topic will review the clinical manifestations and diagnosis of FMF. The epidemiology, genetics, pathophysiology, and management of FMF and an overview of periodic fever syndromes and other autoinflammatory diseases can be found elsewhere. (See "Familial Mediterranean fever: Epidemiology and pathogenesis" and "Management of familial Mediterranean fever" and "Periodic fever syndromes and other autoinflammatory diseases: An overview".)
Familial Mediterranean fever (FMF) is characterized by sporadic, unpredictable attacks of fever and serosal inflammation. Most patients with FMF experience their first attack in early childhood. The initial attack occurs before the ages of 10 and 20 years in 65 and 90 percent of cases, respectively . However, in rare cases the initial attack can occur in individuals older than 50 years of age.
Recurrent fever — Patients with FMF have recurrent episodes of fever and severe pain (due to serositis at one or more sites). The onset of pain and fever is usually abrupt, peaking soon after onset. Many patients have a stereotypic prodrome before their attacks . Episodes last for one to three days and then resolve spontaneously. In between attacks, patients are asymptomatic. The frequency of attacks is highly variable, even in a given patient, and it is unusual for a patient to describe a consistent triggering event. Vigorous exercise, exposure to cold, emotional stress, fatigue, surgery, and menstruation have been associated with an attack in some patients. However, many patients have no clear precipitant. Attacks during pregnancy usually abate during the second half. The intervals between episodes are irregular, ranging from one week to several months or years. 
Abdominal pain — Ninety-five percent of patients with FMF have episodic abdominal pain . Abdominal pain and tenderness may initially be localized and then progress to become more generalized. Guarding, rebound tenderness, rigidity, and an adynamic ileus are often present. These findings can be mistaken for an acute surgical abdomen. (See "Evaluation of the adult with abdominal pain".)
Chest pain — Painful FMF attacks are localized to the chest in approximately 45 percent of patients. Chest pain may be due to inflammation of the pleura or referred pain from subdiaphragmatic inflammation. Pleural inflammation typically manifests as unilateral chest pain that is worse with inspiration or coughing. Patients often have a small, transient pleural effusion. Episodes usually resolve within three days, but may last up to one week. Concomitant pericarditis can also be observed in patients with pleuritis.
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- CLINICAL MANIFESTATIONS
- Recurrent fever
- Abdominal pain
- Chest pain
- Joint pain
- Erysipelas-like skin lesion
- Other manifestations
- LABORATORY FINDINGS
- LONG-TERM COMPLICATIONS
- Secondary (AA) amyloidosis
- Small bowel obstruction
- When to consider the diagnosis
- Our diagnostic approach
- - Major criteria
- - Minor criteria
- - Supportive criteria
- Genetic testing
- DIFFERENTIAL DIAGNOSIS
- SUMMARY AND RECOMMENDATIONS