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| Journal of the New Zealand Medical Association,
21-May-2004, Vol 117 No 1194
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Familial Mediterranean Fever: 36 years to diagnosis
Paul Casey, Mark Lane, and Rohan Ameratunga
Familial Mediterranean fever (FMF) is a rare cause of
recurrent abdominal pain in New Zealand, but it is more common in the Middle
East and Mediterranean regions. With increasing immigration to New Zealand from
these areas, it is a diagnosis that must be considered in patients presenting
with unexplained recurrent abdominal pain.
Case reportA 44-year-old woman was referred to
the Gastroenterology Service at Auckland Hospital with a history of chronic
recurrent abdominal pain. She was born in New Zealand but lived in South Africa
for 20 years. She subsequently returned to New Zealand.
Her symptoms began in childhood at 8 years of age when she
presented to hospital with fever and abdominal pain. On further questioning in
New Zealand, she described severe lower abdominal pain that typically occurred 3
to 4 days into menstruation—with fevers and abdominal distension. During
several of these painful episodes, she developed a well-demarcated erythematous
rash around her upper limbs, chest wall, and legs. Each episode would last
approximately 5 days and then resolve spontaneously.
She initially underwent appendicectomy. Subsequently, she
was diagnosed with peritonitis, which settled spontaneously. She continued to
have recurrent episodes of pain over the years increasing in frequency over the
last 6 years. Courses of prednisone (for a presumed autoimmune process) had
minimal effect. Investigations were unremarkable except for an elevated white
cell count of 13.5 and an elevated ESR of 32 on one occasion. Abdominal X-rays,
abdominal and pelvic ultrasound, and laparoscopy were normal with no evidence
for endometriosis.
Her sister had similar symptoms but with less frequent and
severe attacks. On further questioning, she indicated she was an Ashkenazi
Jew.
Once the possibility of a periodic fever syndrome was
considered, mutation analysis was performed for the Familial Mediterranean fever
gene (MEFV). The test was undertaken at Gene Dx and she was shown to be
homozygous for the V726A mutation of MEFV. Her sister also tested positive for
the same mutation.
She was commenced on colchicine prophylaxis and there has
been a marked improvement in the frequency and severity of her symptoms.
Familial Mediterranean Fever (FMF)FMF is an autosomal recessive
disease. It affects people predominantly from the Mediterranean
basin—including Sephardic Jews, Arabs, Turks, Armenians, and (less
commonly) Greeks and Italians. Ashkenazi Jews are also affected, although less
frequently.
Clinically, FMF manifests as short attacks of serositis
(peritonitis, pleuritis, or arthritis) and fever. The peritonitis often
resembles an acute surgical abdomen, and a history of previous exploratory
laparotomy is often given. Symptoms last from hours up to 4 days. Ninety percent
of patients have their first attack before age 20
years.1 An erysipelas-like skin rash can be
seen in up to 40% of cases.2
The frequency of attacks is variable. Defined triggers for
attacks are rare, but attacks related to the menstrual cycle are found in about
7% of cases.3
During attacks, white cell count and acute phase proteins
become elevated, but return to normal between attacks. Diagnosis is based on
clinical findings of episodic fever, serositis, and absence of an alternative
cause in a person from an at risk population. Although clinical diagnostic
criteria have been proposed,4 mutation analysis
of the MEFV is required for definitive
diagnosis.5
The most important long-term complication in FMF is the
development of secondary amyloidosis. Renal involvement with proteinuria and
eventually renal failure is the predominant presentation of FMF related
amyloidosis. In spite of 36 years of recurrent serositis, our patient did not
have clinical evidence of amyloidosis.
The pathophysiology of FMF appears to involve abnormal
recruitment and activation of neutrophils at serosal surfaces. This may be a
consequence of the action of the gene product of the MEFV gene, pyrin. Pyrin may
have a role in dampening neutrophil activation.
The treatment of choice is colchicine. Colchicine is known
to impair neutrophil function in gout, and its beneficial effect in FMF is
likely to be via the same mechanism. Furthermore, colchicine reduces the
frequency and severity of attacks. Colchicine also prevents amyloidosis, and can
reverse proteinuria even after amyloidosis is
established.6
This case illustrates the difficulty in making a diagnosis
of FMF in a low prevalence area. Chronic or recurrent abdominal pain is a common
problem presenting to medical practitioners. With increased immigration to New
Zealand from the Middle East in recent years, this is a disease which should be
considered, particularly in patients of Mediterranean or Middle Eastern
extraction.
Author information:
Paul Casey, Registrar, Department of Gastroenterology; Mark Lane, Consultant;
Rohan Ameratunga, Consultant, Department of Clinical Immunology, Auckland Main
Hospital, Auckland
Correspondence: Dr
Rohan Ameratunga, Department of Clinical Immunology, Auckland Main Hospital,
Private Bag, Auckland. Fax: (09) 307 2826. email: rohana@adhb.govt.nz
References:
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