Familial Mediterranean fever is a hereditary syndrome -- an autosomal recessive disease -- characterized by recurrent episodes of fever and serositis, resulting in pain in the abdomen, chest, joints and muscles. It is primarily diagnosed in people of Jewish, Arabic, Turkish or Armenian ancestry and is caused by mutations in the gene encoding for pyrin. Abdominal familial Mediterranean fever attacks resemble the clinical presentation of 'acute abdomen', with severe abdominal pain and rigidity, but familial Mediterranean fever symptoms always resolve spontaneously. It is important to distinguish these regular pain episodes from small bowel obstruction due to adhesions to prevent life-threatening bowel strangulation.

Familial Mediterranean fever symptoms
Familial Mediterranean fever symptoms and signs are due to recurrent crises of fever and serosal inflammation, leading to abdominal, thoracic or articular pain. Erysipela -like erythema affecting mainly feet and legs and effort-induced myalgia are less frequently encountered symptoms. The major complication of familial Mediterranean fever is the development of renal amyloidosis.

Familial Mediterranean fever diagnosis
Standard laboratory tests of familial Mediterranean fever patients are non-informative, except for the high sedimentation rate and white blood cell count, but during and immediately after crises, diminished albumin concentrations and elevated fibrinogen, C-reactive protein, beta2 and alpha2 M globulins, haptoglobin and lipoprotein concentrations are noted. Studies have measured immunoglobulin (Ig) levels in the sera of familial Mediterranean fever patients and found elevated levels of IgA, IgM, IgG, and IgD. Familial Mediterranean fever crises are characterised by a massive influx of polymorphonuclear leukocytes into the inflamed regions. Moreover, the peritoneal fluid of familial Mediterranean fever patients contains abnormally low levels of the inhibitor of complement fragment C5a and interleukin 8. Failure to suppress inflammatory response to C5a may explain the typical inflammatory Familial Mediterranean fever crises.

Familial Mediterranean fever treatment
Familial Mediterranean fever symptoms include attacks of serositis, commonly involving the abdomen, chest or joints, typically accompanied by fever and elevated acute phase reactants. Attacks subside spontaneously within one to three days, without residue. Continuous treatment with colchicine, at a daily dose of 1 to 2 mg, reduces attack frequency, duration and intensity in the majority of patients, and also prevents the development of secondary amyloidosis, the most dreaded complication of the disease. In most cases, colchicine will prevent new painful attacks. This website is focused on natural treatment options as discussed below.

Familial Mediterranean fever treatment with herbs and natural supplements
Very little human research has been done with alternative medicine or natural supplements for FMF, hence no definite answers or treatment regimens can be provided. The following herbs have been evaluated with some positive responses, but more research is needed before we know the ideal dosages, frequency of use and long term side effects. Echinacea angustifolia & purpurea, Astragalus membranaceus, and Eleutherococcus senticosus (Siberian Ginseng herb), Andrographis paniculata, Schizandra chinensis, and Glycyrrhiza glabra (licorice). You can find these herbs for purchase here. See Astragalus herb and Schisandra herb.

Familial Mediterranean Fever - FMF - research Update
Plasma nitric oxide level in familial Mediterranean fever and its modulations by Immuno-Guard.
Nitric Oxide. 2003 Sep;9(2):103-10. Panossian A, Hambartsumyan M, Panosyan L, Abrahamyan H, Mamikonyan G, Gabrielyan E, Amaryan G, Astvatsatryan V, Wikman G. Pharmaceuticals and Nutraceuticals Expertise Research Institute, Yerevan, Armenia.
Familial Mediterranean fever is a recessively inherited inflammatory disorder, characterised by recurrent attacks of fever and serositis. Since nitric oxide (NO) is an important mediator of inflammation, the production of NO (assessed as the accumulation of nitrate and nitrite and measured by capillary electrophoresis) in blood plasma of Familial Mediterranean fever patients during acute attacks (active) and attack-free periods (inactive) of the disease has been determined and compared with NO levels found in healthy volunteers (control group C). Thirty-six Familial Mediterranean fever patients were involved in a placebo-controlled double-blind study (group A received the drug, group B the placebo) of the effects of Immuno-Guard, a novel herbal preparation which relieves the severity and longevity of Familial Mediterranean fever attacks on NO blood levels. Thirty-two Familial Mediterranean fever patients (group D) being permanently treated with colchicine were also examined with respect to their NO blood level. No significant differences were found between the NO levels in blood of inactive Familial Mediterranean fever patients and those of control group C, or between inactive colchicine-treated group D patients and inactive patients of groups A and B, a finding which is atypical for chronic inflammatory disorders. Significantly lower plasma NO levels were found in active Familial Mediterranean fever patients in groups A and B compared with inactive patients in those groups and with patients of group D and the control group C. The decrease of NO in blood of Familial Mediterranean fever patients may trigger the generation of fever by initiating the production of pro-inflammatory IL-6. Plasma NO levels in inactive Familial Mediterranean fever patients were significantly increased during attack-free periods following treatment with Immuno-Guard. The preparation has a normalising effect both on NO and IL-6 blood levels in Familial Mediterranean fever patients during attacks, demonstrating a relationship between the beneficial effect of Immuno-Guard in reducing the severity of inflammatory attacks in Familial Mediterranean fever patients and the increase in NO blood levels. Herbs found in Immuno-Guard: Echinacea angustifolia & purpurea, Astragalus membranaceus, and Eleutherococcus senticosus (Siberian Ginseng)

Double-blind, placebo-controlled, randomized, pilot clinical trial of ImmunoGuard -- a standardized fixed combination of Andrographis paniculata Nees, with Eleutherococcus senticosus Maxim, Schizandra chinensis Bail. and Glycyrrhiza glabra L. extracts in patients with Familial Mediterranean Fever.
Phytomedicine. 2003 May;10(4):271-85. Amaryan G, Astvatsatryan V, Gabrielyan E, Panossian A, Panosyan V, Wikman G.
Republican Children's Familial Mediterranean fever Center, Yerevan State Medical University, Yerevan, Armenia.
Double blind, randomized, placebo controlled pilot study of ImmunoGuard -- a standardized fixed combination of Andrographis paniculata Nees., Eleutherococcus senticosus Maxim., Schizandra chinensis Bail., and Glycyrrhiza glabra L (licorice) , was carried out in two parallel groups of patients. The study was conducted in 24 (3-15 years of both genders) patients with Familial Mediterranean Fever (Familial Mediterranean fever), 14 were treated with tablets of series A (verum) and 10 patients received series B product (placebo). The study medication was taken three times of four tablets daily for 1 month. Daily dose of the andrographolide--48 mg. The primary outcome measures in physician's evaluation were related to duration, frequency and severity of attacks in Familial Mediterranean fever patients (attacks characteristics score). The patient's self-evaluation was based mainly on symptoms--abdominal, chest pains, temperature, arthritis, myalgia, erysipelas-like erythema. All of 3 features (duration, frequency, severity of attacks) showed significant improvement in the verum group as compared with the placebo. In both clinical and self evaluation the severity of attacks was found to show the most significant improvement in the verum group. Both the clinical and laboratory results of the present phase II (pilot) clinical study suggest that ImmunoGuard is a safe and efficacious herbal drug for the management of patients with Familial Mediterranean fever.

Familial Mediterranean Fever Questions
Q. I have familial Mediterranean fever and it appears my 4 year-old son has it too though he most likely has only one mutation (M694V) causing his symptoms. My son’s osteopath referred me to your web-site so that I may find a safe alternative to taking colchicine. I would like to ask the history and known side effects of ImmunoGuard / the herbal remedies that comprise it, indicated for FMF treatment, and if there is any research comparing its use, side effects and benefits to colchicine in FMF patients. I have been in contact with a research doctor at National Institutes of Health in Bethesda, Maryland since 1989 regarding my condition and have been on colchicine almost continuously since then. I have also directed my doctor to your web-site in the hopes that he may contact you with any questions.
     A. All the information we have on these topics is on our website and we try to update it as soon as we find more research on familial Mediterranean fever.

Q. My daughter is five years old and had been suffering from periodic fevers from April through September 2007. These fevers began with joint pain and 11 days of 102-104. As the months passed the duration of the fevers lessened and the joint pain became more severe with the last episode of fever being September 20. Within that period of time, I had made appointments with rheumatologists. One wanted to medicate and the other wanted to wait. I decided to wait and observe. In the meantime, after some discussion with people who had positive results in general with vitamin D, I did some research and began supplementing my daughters diet with vitamin D (at the beginning of September). The fevers did not recur until this month, January 2008 ( I thought viral, but there were no other symptoms so the doctor thinks it could be familial Mediterranean fever. We have done no other testing other than blood work ups. I realized that I had stopped giving her the vitamin D in the beginning of December and the fevers recurred mid January. Her bloods were tests in October of 2007 and I requested her levels of D be tested. the results were optimum (from what I am reading on the internet. Her level of 25 hydroxy... was 52. I am concerned with toxicity as well. This episode of fever and blood work, the idea of vitamin D did not enter my mind until 3 days after the blood was drawn to have the D levels tested again. I have been reading a lot about vitamin D deficiencies and auto immune diseaases and I was wondering if there was any specific research in regard to familial Mediterranean fever and vitamin D deficiencies. I was impressed with your article due to the attention paid to the natural remedies. I'm sure like all mothers I am exploring all natural options before pharmaceuticals. I have began the supplementation of Vitamin D again and will wait at least two months to see if the fevers cease again before administering the medication. Of course I am not abandoning science altogether and I am certainly not pretending to be a doctor, but I want the most natural "cure" or "treatment" for this disease (if it is familial Mediterranean fever) possible. Genetic testing is in the near future. The doctors were not quick to test because of the short history of fevers and lack of data.
   A. Familial Mediterranean fever, the most frequent of the periodic fever syndromes, is an autosomal recessive disease, predominantly affecting people of Mediterranean descent. The disease is caused by mutations in the MEFV gene, encoding the pyrin protein thought to be associated with the interleukin-1 related inflammation cascade. We are not aware of any research regarding the use of vitamin D as a treatment for familial Mediterranean fever. This condition is more common in the Middle East where people are exposed to a lot of sun and hence are not deficient in vitamin D.

Q. I am 60 years old and have had familial Mediterranean fever since infancy. I take colchicine which UCLA's familial Mediterranean fever clinic prescribed when I was 16 years old. It's when my familial Mediterranean fever was diagnosed after years of confusion! Doctors believe my sister died of the disease due to a bowel obstruction. This occurred before my birth. It was in 1945 and she was only 17 years old. Since familial Mediterranean fever is an "inflammation response" disease, do you know of any other medications or treatments for this condition?
   A. Certain herbs have been tried for this condition as discussed above. As a general rule, fish and vegetables reduce inflammation and you may consider increasing your intake of these foods while decreasing the ingestion of foods that have sugar.

This familial Mediterranean fever page was last updated in 2008.

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