Familial Mediterranean fever: an animated, cited guide

This page needs JavaScript for its animations. The outline and key answers are below, and every claim in the full version carries a numbered citation.

Not medical advice. FMF Companion is an educational synthesis of published literature. It does not replace a clinician.

What is in it

What FMF is Who gets it, the numbers, and what an attack looks like.
The gene and inheritance MEFV, pyrin, the common variants and an animated Punnett square.
Pyrin, animated How pyrin guards RhoA, and what FMF variants change.
An attack, hour by hour 72 hours of fever, pain, CRP and SAA, site by site.
Colchicine inside the cell From the pill to the neutrophil to the microtubule.
Colchicine over months Why the benefit builds slowly, and what it prevents.
Dosing, safety and interactions What the guidelines and the label publish.
AA amyloidosis Serum amyloid A to fibril to kidney, over years.
Diagnosis and criteria Tel Hashomer, Livneh and the Eurofever/PRINTO calculator.
The differential TRAPS, MKD, CAPS, PFAPA, Behçet and the surgical abdomen.
The treatment ladder Colchicine first, then IL-1 blockade.
Living with FMF Pregnancy, surgery, school, triggers and monitoring.
Toward a cure What a cure would need, and the evidence for each route.
History and people 1908 to the discovery that pyrin senses RhoA.
Flashcards, quiz and glossary Revision for students.
Sources Every reference behind the app.

Part 4 · Treatment & the future

Toward a cure

No approved therapy cures FMF today. Colchicine and IL-1 blockade control it, for life. This module takes the question seriously anyway: where in the pathway could you intervene, what evidence exists for each route, and what stands in the way. Every claim carries an evidence label. Press play to send the signal down the pathway, then pick a route to drop a barrier in front of it.

Route

Signal flow

Schematic pathway, not to scale.

Replacing the marrow: what it would take

Months after transplant

Corrected myeloid cells at plateau

Hypothetical sequence drawn from transplant and gene-editing biology in other diseases. There is no FMF-specific human dataset behind these curves.

The routes, side by side

Route	What it would fix	Best evidence	Level	Main obstacle	Status

What a cure would have to achieve. Two things at once, not one. It would have to stop attacks, and it would have to switch off the quiet inflammation between them, because AA amyloidosis is driven by chronically raised SAA rather than by the attacks themselves. The 2024 EULAR/PReS update makes control of subclinical inflammation an explicit treatment target. A cure would also have to reach the right cells: MEFV messenger RNA in blood is restricted to myeloid cells, and the gene is switched on as CD34+ progenitors differentiate into granulocytes, which puts the target inside the bone-marrow stem and progenitor compartment. Pyrin protein has also been reported in dendritic cells and in synovial fibroblasts, so a purely blood-cell fix might leave a reservoir behind. ^35,54,203

Thirteen open questions

These are the gaps the literature itself leaves open, not rhetorical questions. Each one is a place where a study could change the picture.

What a next trial might look like

Read this part carefully. The three designs below are illustrations written for this page. They are not registered trials, not proposals from any investigator, and not advice. No trial of gene editing, RNA therapeutics, HSCT or a pyrin-targeted small molecule in FMF is registered as of the October 2026 sweep of ClinicalTrials.gov. ⁴²

The statin caution, and its limits. Statins deplete geranylgeranyl pyrophosphate, which stops RhoA from sitting in the membrane, and in cell experiments that activates the pyrin inflammasome; statin-induced IL-1β release was reversed by adding geranylgeranyl pyrophosphate back or by activating PKN. This is in-vitro mechanism. Its clinical relevance is unknown: no clinical study has looked at whether statins affect FMF, and patients with cardiovascular indications routinely receive them. Nobody should change or stop a medicine on the strength of this, and any question about a statin belongs with the prescriber. It appears here as one of the open questions, not as a recommendation. ²⁰⁷