Adult Patients with Familial Mediterranean Fever - A Single-Center Case Series
Bibliographic record
Abstract
Objectives Describe the clinical characteristics of adult patients with FMF (Familial Mediterranean Fever) and identify potential challenges in the diagnosis and treatment in this population. Methods Patients over age 18 years meeting the Tel HaShomer diagnostic criteria for FMF were recruited from an autoinflammatory clinic in Toronto. Clinical records and data were reviewed and analyzed. Gene panel testing was performed at the Division of Genome Diagnostics, Hospital for Sick Children. All patients provided written consent to be included in a case series. Results A total of 22 patients were included (59% male). The cohort was composed of a variety of ethnicities including Middle Eastern (45%), Caucasian (18%), Southeast Asian and African (both 14%). The median ages at enrollment were 45 years, symptom onset (12.5 years), and diagnosis (35.5 years). Seven patients had first symptom onset after age 18. The median diagnostic delay was 7.5 years. A family history of FMF was present in 63% of patients. The most common trigger for flares was stress (41%). The most common symptoms were abdominal pain (95%), followed by fever (91%) and arthritis (72%). CRP was elevated during flares in 89% of patients. Notable comorbidities included spondyloarthropathy in 2 patients. Genetic testing was available in 20 patients. 14 were homozygous and 6 were heterozygous for variants in MEFV. The most common variants were V726A (7/20), M694V/M680I/E148Q (each in 4/20), and M694I (2/20). All were variants of uncertain significance, or likely/pathogenic by American College of Medical Geneticists classification. One patient carried 3 variants in MEFV (homozygous E148Q, and p369S), while 2 patients carried additional NOD2 variants (R791W, R702W). 86% of patients responded to colchicine, but 55% reported side effects. As such, IL-1 inhibitors such as anakinra or canakinumab were applied for to the provincial Exceptional Access Program in 8 patients. Funding for this medication was denied in 7 of them. Compassionate medication release was provided to 5 patients, for which 4 exhibited marked benefit. Conclusion FMF remains an underrecognized entity as demonstrated by the significant diagnostic delay (maximum 42 years) in our cohort. Moreover, it can present for the first time in adulthood (32% of our cohort). IL-1 blockade has been shown to be highly effective, but limited access to public funding remains a significant barrier. It will be important to continue to raise awareness for FMF and advocate for improved access to genetic testing as well as effective, evidence-based therapy.[1,2] [1.] Ozen S. Ann Rheum Dis 2015:1-8. [2.] Gattorno M. Int J Mol Sci 2023:1-24.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".