Familial Mediterranean fever (FMF) is a genetic condition of inflammatory episodes that cause painful joints, pain in the abdomen, or pain in the chest, and is most often accompanied by a fever. This condition often shows up first in childhood with unexplained fever and aches and pains.
FMF is often misdiagnosed as various pain-related conditions such as fibromyalgia, myofascial pain syndrome, or gouty arthritis.
Genetics Home Reference explains “Familial Mediterranean fever is an inherited condition characterized by recurrent episodes of painful inflammation in the abdomen, chest, or joints. These episodes are often accompanied by fever and sometimes a rash or a headache. Occasionally inflammation may occur in other parts of the body, such as the heart; the membrane surrounding the brain and spinal cord; and in males, the testicles. In about half of affected individuals, attacks are preceded by mild signs and symptoms known as a prodrome. Prodromal symptoms include mildly uncomfortable sensations in the area that will later become inflamed or more general feelings of discomfort.”
FMF was classically thought of as an “autosomal recessive” genetic disease requiring the inheritance of two mutated genes.
But with the prevalence of genetic testing, new studies are showing that this is a disease with a range of symptoms sometimes showing up in those who are heterozygous (one copy) for the mutations and other times not affecting those who are homozygous (2 copies).
MEFV is the gene responsible for familial Mediterranean fever, and it codes for a protein called pyrin, which interacts with the immune system. Pyrin regulates interleukin-1 beta (IL1B), which is a cytokine important in inflammatory responses including fever.
While there are over 310 different MEFV mutations that have been identified and linked to familial Mediterranean fever, there are a few (E148Q, M680I, M694I, M694V, and V726A) that “may account for as much as 80% of FMF cases in classically affected populations”. [study]
It has also been found that up to 30% of FMF cases may be just heterozygous (one copy) for a MEFV mutation.
Since many who are heterozygous or homozygous have no symptoms, it is thought that there may be another genetic mutation also involved or environmental factors (or both). A recent study found that those with European ancestry usually have milder symptoms than those of Mediterranean ancestry. The gut microbiome may also be involved with changes to the microbiome found in those in acute attacks.
For those with frequent attacks, the long-term consequences can include amyloidosis and kidney failure, so definitely talk with your doctor if you have the genetic variants along with symptoms. There is a prescription medication, colchicine, that can help prevent the long-term consequences for those with frequent attacks.
Fever with achiness for a few days — sounds like just being frequently sick with a virus or something! Aching joints or muscles, pain in the abdomen, pain across the chest — could be a number of different rheumatoid-like illnesses. This made me wonder if there is an overlap between the diagnosis of other conditions such as fibromyalgia or arthritis with familial Mediterranean fever. Turns out there are studies showing overlap of conditions similar to FMF, although it isn’t clear if the MEFV gene variants make the original diagnosis more likely or if patients were misdiagnosed in the first place.
Check your 23andMe raw data for the following variants. (v.4 and v.5 ) These are some of the more common variants that can cause FMF; there are also other mutations that aren’t covered by 23andMe data. (Note that all are giving in the plus or forward orientation to match with 23andMe data)
Check your genetic data for rs61732874 (23andMe i4000409v4, v5; AncestryDNA):
Check your genetic data for rs3743930 ( 23andMe v4, v5; AncestryDNA):
Check your genetic data for rs104895083 (23andMe i4000403 v4, v5):
Check your genetic data for rs104895094 ( 23andMe i4000407 v4, v5):
Check your genetic data for rs28940580 ( 23andMe v4, v5):
Check your genetic data for rs28940578 (23andMe v4, v5; AncestryDNA):
Check your genetic data for rs61752717 (23andMe i4000406 v4, v5):
Check your genetic data for rs11466023 (23andMe v4, v5):
Check your genetic data for rs104895097 (23andMe i4000410 v4, v5; AncestryDNA):
Check your genetic data for rs28940579 (23andMe v4, v5; AncestryDNA):
There were several studies and clinical trials of ImmunoGard, a herbal-based supplement for familial Mediterranean fever which showed positive results.[ref][ref] I can’t find it sold online anywhere, though.
The ingredients of ImmunoGard included “Andrographolide (4 mg/tablet), Eleuteroside E, Schisandrins and Glycyrrhizin,”. Andrographolide is found in Andrographis extract, which is an herb used for boosting the immune system and included in some Lyme disease protocols. Schisandrins is from Eleutherococcus senticosus (Siberian ginseng), and glycyrrhizin is found in licorice.
Due to the increase in IL-1B, natural inhibitors of IL-1B such as quercetin or genistein may help.[ref] [ref] This is just a guess on my part, though, and I haven’t found any studies specific to FMF with either of these flavonoids. Quercetin is found in many fruits and vegetables as well as being available as a supplement. (Quercetin is a methyl donor, so use it with caution if you are sensitive to methyl supplements.)
A study of triggers of FMF attacks looked at stress, physical activity, and high-fat diet. It found that only stressful events were linked to FMF, and neither physical activity nor a high-fat diet was a trigger. So avoiding stress may help to decrease FMF attacks. [ref]
The gut microbiome may also contribute to both the likelihood of having FMF and the frequency of attacks. Here is a great open-access article on the topic: Probiotic Lactobacillus acidophilus Strain INMIA 9602 Er 317/402 Administration Reduces the Numbers of Candida albicans and Abundance of Enterobacteria in the Gut Microbiota of Familial Mediterranean Fever Patients The strain of probiotic used in the study is not one that I can find available online.