We recently heard about the case of an 8-year-old Arabic patient who, following the recent article by Milledge et al,1 was offered a bone marrow transplantation (BMT) by a private institution to cure his familial Mediterranean fever (FMF). This boy has a very good general constitution but is still suffering from recurrent bouts of fever with abdominal pain, although he has been on colchicine 3 × 0.5 mg a day for 2 years. No alternative drug has been tried. This little boy has no evidence of amyloidosis. While, in this patient, 2 Met694Val mutations were identified in MEFV, the gene responsible for FMF, no MEFV screening was performed in his HLA-identical younger brother, the designated matched family donor.
We would like to stress the fact that BMT is a life-threatening and expensive procedure that has not proved to be a cure for FMF at this point. We recommend that the following issues be addressed in the rare FMF patients resistant to colchicine: (1) Does the patient indeed suffer from FMF? The diagnosis should be confirmed by a well-experimented clinician and/or by genetic testing. (2) Does he/she really take appropriate doses of colchicine? Is there any possibility of defective absorption of colchicine, allergy, or intolerance to colchicine? (3) Have all medical approaches been exhausted? If the patient truly does not respond to a maximal tolerated dose of colchicine (up to 2-2.5 mg a day, dose split up throughout the day), and if compliance is not involved, other treatments should be discussed, such as interferon α,2 and possibly thalidomide3 or anticytokines. (4) In any case, colchicine treatment should not be stopped because of the risk of developing amyloidosis.
Even when the patient is refractory to medical treatment and suffers from intractable and debilitating FMF, it is still debatable whether and when BMT should be considered. We agree that this treatment might possibly improve FMF symptoms, since this disease may be regarded as a hematopoietic disorder and BMT has sometimes shown to work in preliminary trials in other inflammatory disorders, such as rheumatoid arthritis. However, given the morbidity and mortality associated with BMT, and given that FMF is a self-limited disease with an overall good prognosis when colchicine is properly adjusted, we maintain that BMT has no role in the current treatment of FMF in the general medical community and should be contemplated only in the setting of a carefully conducted research protocol, if at all. Moreover, the ethical issue of offering this high-risk, unproven procedure to children is particularly troubling, even in the setting of a well-designed study.
