Appendectomy history is associated with severe disease and colchicine resistance in adult familial Mediterranean fever patients

Background/aim: Peritonitis attacks of Familial Mediterranean Fever (FMF) usually requires emergency medical admissions and it’s hard to distinguish a typical abdominal attack from surgical causes of acute abdomen. Therefore, history of abdominal surgery, particularly appendectomy, is very common in patients with FMF. However, history of appendectomy might also give some clues about the course of FMF in the adulthood. This study was to determine whether the history of appendectomy help to anticipate disease course of FMF in the adulthood. Materials and methods: All patients recruited from FMF in Central Anatolia (FiCA) cohort, comprising 971 adult subjects. All patients fulfilled the Tel Hashomer criteria. Demographic data, FMF disease characteristics, co-morbid conditions, past medical history, surgical history and disease complications were meticulously questioned and laboratory features and genotype data (if available) were recruited from patient files. Results: Appendectomy history was evident in 240 (24.7%) subjects. Disease onset was earlier and peritonitis is strikingly more prevalent (97.1% vs. 89.6%, p < 0.001) in appendectomized patients. These patients had reported almost two fold more frequent attacks in the last year compared to appendix intact patients (median 3.5 vs. 2 attacks, p = 0.001) without a difference in frequency of musculoskeletal and skin attacks. Severe disease was more common (10% vs. 5.9%, p = 0.038) due to involvement of more attack sites throughout the life and more frequent attacks. Appendectomy patients had used higher daily doses of colchicine to control disease (1.43 ± 0.6 mg vs. 1.27 ± 0.52 mg, p = 0.002) but colchicine resistance was also more common in these patients, 15% vs. 6.7% respectively, p < 0.001. Conclusion: Appendectomy history is common in FMF patients and associated with frequent serositis attacks in adulthood. These patients require higher colchicine doses with a lower rate of response and more need for Interleukin-1 antagonist therapies.Key words: Familial Mediterranean fever, appendectomy, surgery, prognosis, colchicine resistance

PDF

___

1. Masters SL, Simon A, Aksentijevich I, Daniel L. Kastner. Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease. Annual Review of Immunology 2009; 27:621–668 doi.org/10.1146/annurev. immunol.25.022106.141627
2. Ben-Chetrit E, Touitou I. Familial Mediterranean fever in the world. Arthritis Care & Research 2009; 61 (10): 1447-1453. doi. org/10.1002/art.24458
3. Onen F. Familial Mediterranean fever. Rheumatol International 2006; 26 (6): 489-496. doi.org/10.1007/s00296-005-0074-3
4. Sohar E, Gafni J, Pras M, Harry Heller. Familial Mediterranean fever. A survey of 470 cases and review of the literature. The American Journal of Medicine 1967; 43 (2): 227-253. doi. org/10.1016/0002-9343(67)90167-2
5. Livneh A, Langevitz P. Diagnostic and treatment concerns in familial Mediterranean fever. Best Practice & Research Clinical Rheumatology 2000; 14 (3): 477-498. doi.org/10.1053/ berh.2000.0089
6. Maconi G, Obici L, Carmagnola S, Guzetti S. Autoinflammatory diseases as a cause of acute abdominal pain in the emergency department. Clinical Experimental Rheumatology 2018; 36 (110), S39-S43
7. Rentea RM, Peter SDS, Snyder CL. Pediatric appendicitis: state of the art review. Pediatric Surgery International 2017; 33 (3): 269-283. doi: 10.1007/s00383-016-3990-2
8. Tufan A, Lachmann HJ. Familial Mediterranean fever, from pathogenesis to treatment: a contemporary review. Turkish Journal of Medical Sciences 2020; 50 (SI-2): 1591-1610. doi: 10.3906/sag-2008-11
9. Kasifoglu T, Cansu DÜ, Korkmaz C. Frequency of abdominal surgery in patients with familial Mediterranean fever. Internal Medicine 2009; 48: 523-526. doi.org/10.2169/ internalmedicine.48.1602
10. Tunca M, Akar S, Onen F, Korkmaz C, Keser G et al. Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study. Medicine (Baltimore) 2005; 84: 1-11. doi. org/10.1097/01.md.0000152370.84628.0c
11. Livneh A, Langevitz P, Zemer D, Zaks N, Kees S et al. Criteria for the diagnosis of familial Mediterranean fever. Arthritis & Rheumatism 1997; 40 (10): 1879-1885. doi.org/10.1002/ art.1780401023
12. Ter Haar NM, Annink KV, Al-Mayouf SM, Amaryan G, Frenkel J et al. Development of the autoinflammatory disease damage index (ADDI). Annals of the Rheumatic Diseases 2017; 76 (5): 821-830. doi.org/10.1136/annrheumdis-2016-210092
13. Demirkaya E, Acikel C, Hashkes P, Gattorno M, Ozen S et al. Development and initial validation of international severity scoring system for familial Mediterranean fever (ISSF). Annals of the Rheumatic Diseases 2016; 75 (6): 1051-1056. doi. org/10.1136/annrheumdis-2015-208671
14. Tufan A, Babaoglu MO, Akdogan A, Calguneri M, Kiraz S et al. Association of drug transporter gene ABCB1 (MDR1) 3435C to T polymorphism with colchicine response in familial Mediterranean fever. The Journal of Rheumatology 2007; 34 (7): 1540-1544.
15. Ozen S, Batu ED, Demir S. Familial Mediterranean fever: recent developments in pathogenesis and new recommendations for management. Frontiers in Immunology 2017; 8: 253. doi. org/10.3389/fimmu.2017.00253
16. Berkun Y, Ben-Chetrit E, Klar A, Ben-Chetrit E. Peritoneal adhesions and intestinal obstructions in patients with familial Mediterranean fever-are they more frequent? Seminars in Arthritis Rheumatism 2007; 36: 316-321. doi.org/10.1016/j. semarthrit.2006.11.002
17. Kallinich T, Haffner D, Niehues T, Huss K, Lainka E et al. Colchicine use in children and adolescents with Familial Mediterranean Fever: literature review and consensus statement. Pediatrics 2007; 119: e474-483. doi.org/10.1542/ peds.2006-1434
18. Satiş H, Armağan B, Bodakçi E, Ataş N, Tufan A et al. Colchicine intolerance in FMF patients and primary obstacles for optimal dosing. Turkish Journal of Medical Sciences 2020; 50 (5): 1337-1343. doi: 10.3906/sag-2001-261
19. Ben-Chetrit E, Levy M. Familial Mediterranean Fever. Lancet 1998; 351: 659-664. doi.org/10.1016/S0140-6736(97)09408-7
20. Rasmussen T, Fonnes S, Rosenberg J. Long-term complications of appendectomy: a systematic review. Scandinavian Journal of Surgery 2018; 107 (3): 189-196. doi: 10.1177/1457496918772379
21. Wu MC, Tsou HK, Lin CL, Wei JC. Incidence and risk of sepsis following appendectomy: a nationwide populationbased cohort study. Scientific Reports 2020; 10 (1): 10171. doi: 10.1038 /s41598-020-66943-5
22. Gershoni-Baruch R, Brik R, Lidar M, Shinawi M, Livneh A. Male sex coupled with articular manifestations cause a 4-fold increase in susceptibility to amyloidosis in patients with familial Mediterranean fever homozygous for the M694VMEFV mutation. The Journal of Rheumatology 2003; 30 (2): 308-312.
23. Babaoglu H, Armagan B, Bodakci E, Satis H, Tufan A et al. Factors associated with amage in patients with familial Mediterranean fever. Clinical Experimental Rheumatology 2020; 38 Suppl 127 (5): 42-48.