ABSTRACT

Some of Familial Mediterranean fever (FMF) patients suffer from several different musculoskeletal symptoms similar to spondyloarthropathy. Colchicine is generally ineffective in treating these symptoms, unlike its effects on serositis. Therefore, these patients can be classified into a different disease class: The musculoskeletal variant of FMF. Additionally, studies should be conducted on these patients to evaluate both the disease characteristics of this subgroup and treatment options for the variant.

Dear Editor,

Familial Mediterranean fever (FMF) is an auto-inflammatory disease characterized by recurrent fever and serositis attacks.^[1] Three quarters of the patients with FMF have some type of musculoskeletal symptoms.^[2] Herein, there may be two distinct clinical spectrums in the FMF patients with musculoskeletal involvement. Firstly, some FMF patients may suffer from recurrent attacks of acute, non-erosive, self-resolving monoarthritis such as serositis attacks.^[3] Others have musculoskeletal features, which are usually chronic and persistent. Here, 5% of patients may have permanent arthritis, especially in the large lower extremity joints.^[4] In addition, other musculoskeletal features including sacroilitis, spinal involvement and enthesitis are not uncommon in FMF patients.^[5,6] It was recently shown that exertional leg pain is also a sign of lower extremity enthesitis.^[7] All these musculoskeletal features are often found together and have been associated with more severe disease.^[8]  Therefore it would be speculated that, like Behçet syndrome,^[9] FMF patients with pronounced musculoskeletal symptoms can be classified under the musculoskeletal or spondyloarthropathy (SpA) subgroup of the disease. In addition, there are many studies in the literature presenting patients with both FMF and SpA.^[10,11] However, we do not currently know whether these patients are FMF patients with SpA or whether they suffer from FMF with predominant musculoskeletal features. Recently, it has been shown that ankylosing spondilitis (AS) patients with FMF have a different clinical picture than only AS patients.^[12] Moreover, FMF patients with dominant musculoskeletal features have higher disease activity scores and more frequent, intense and longer serositis attacks although these are not SpA signs.^[8] Also, FMF patients with SpA findings have lower frequency of HLAB27 positivity as compared to SpA patients.^[13] Lastly, FMF patients with AS have lower frequency of uveitis, as an example of extra articular features of SpA.^[12] Therefore, I speculate that some FMF patients may have SpA-like phenotypes through the MHC class I type additive immune system.^[14] According to several studies, M694 V mutations are the most frequent MEFV mutations in FMF patients with SpA findings or SpA diagnosis.^[11,15] Since colchicine is not always successful in treating musculoskeletal symptoms of FMF, other treatment options may be considered early in these patients. According to EULAR recommendations for the management of FMF, disease modifying anti-rheumatic drugs, intra-articular steroid injections and biologics may be applied to the patients with chronic arthritis.^[16] Therefore, those drugs may be administered to the patients with musculoskeletal features. Additionally, studies on FMF have been conducted on the whole group, without focusing on FMF patients with specific disease characteristics such as musculoskeletal symptoms. In addition, definitions of colchicine resistance do not include musculoskeletal features that are unresponsive to colchicine.^[9] Therefore, studies focusing on this FMF subgroup are needed to establish the treatment approach for musculoskeletal features of FMF patients.

Ethic

Peer-review: Externally peer-reviewed.