Diagnostic delays in familial Mediterranean fever: a Juvenile Inflammatory Rheumatism (JIR) cohort study
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Published on: October 3, 2019
Rim Bourguiba1,2,3, Samuel Deshayes4, Gayane Amaryan5
1Internal Medicine Department, Tenon Hospital, Paris, France. rim.bourguiba@fmt.utm.tn.
Abstract:
Several studies reported that Familial Mediterranean Fever (FMF) diagnosis may be missed or delayed even in countries with a high FMF prevalence. Our aim was to study on a large cohort of European FMF patients the frequency and associated factors of diagnosis delay. Clinical data were extracted from the Juvenile Inflammatory Rheumatism (JIR)-cohort. All FMF patients fulfilled Livneh Criteria and had been sequenced for MEFV exon 10. FMF-diagnostic delay (d-FMF) was defined as the duration between the onset of the symptoms and the diagnosis of more than 10 years. 960 FMF patients were enrolled: delayed diagnosis (d-FMF) was noted in 200 patients (20%). d-FMF patients were significantly older compared to non d-FMF with a median age of 46.4 years old vs. 15.5 (p < 0.0001). Women displayed more d-FMF compared to men (56 vs. 47%, p = 0.03). Clinical presentation during attacks was not statistically significant except for erysipelas-like erythema, which was higher among d-FMF patients (33 vs. 22%, p = 0.0003). The presence of one or two pathogenic MEFV mutation was not different between patients. Compared to other FMF, d-FMF patients displayed significantly more AA amyloidosis (10 vs. 2.6%, p < 0.0001) and received more biotherapy (18 vs. 3.8%, p < 0.0001). Twenty percent of FMF patients had a diagnostic delay >10 years, including more women. The differential diagnosis of abdominal attacks with menstrual pain may be an explanation, and erysipelas-like erythema may not be recognized as FMF by all practitioners.
Insights
Familial Mediterranean Fever (FMF) diagnosis delays over 10 years affect 20% of European patients, particularly women. Delayed diagnosis is linked to more AA amyloidosis and increased biotherapy use, highlighting the need for earlier FMF identification.
Area of Science:
- Rheumatology
- Genetics
- Internal Medicine
Background:
- Familial Mediterranean Fever (FMF) is a genetic autoinflammatory disorder.
- Delayed diagnosis of FMF is a recognized clinical challenge, even in high-prevalence regions.
Purpose of the Study:
- To determine the frequency of diagnostic delay in a large cohort of European FMF patients.
- To identify factors associated with delayed FMF diagnosis.
Main Methods:
- Retrospective analysis of clinical data from 960 European FMF patients in the Juvenile Inflammatory Rheumatism (JIR)-cohort.
- Patients fulfilled Livneh Criteria and underwent MEFV exon 10 sequencing.
- Diagnostic delay (d-FMF) was defined as >10 years from symptom onset to diagnosis.
Main Results:
- Twenty percent (200/960) of FMF patients experienced diagnostic delay (>10 years).
- Delayed diagnosis was more common in women (56% vs. 47%) and older patients (median age 46.4 vs. 15.5 years).
- d-FMF patients had significantly higher rates of AA amyloidosis (10% vs. 2.6%) and received more biotherapy (18% vs. 3.8%). Erysipelas-like erythema was more frequent in d-FMF patients (33% vs. 22%).
Conclusions:
- A significant proportion of European FMF patients face diagnostic delays, impacting long-term outcomes.
- Factors like female sex and specific clinical features (erysipelas-like erythema) may contribute to delayed diagnosis.
- Earlier FMF diagnosis is crucial to prevent complications such as AA amyloidosis and reduce the need for intensive treatments.
