2026-07-01 | Infertility in aa renal amyloidosis secondary to familial mediterranean fever
ABSTRACT Background and Objectives: Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease worldwide, affecting mainly Mediterranean populations. AA amyloidosis is its most severe complication, with renal involvement being the primary determinant of prognosis. While infertility has been historically associated with FMF, particularly before the colchicine era, the specific impact of AA amyloidosis on fertility outcomes remains poorly characterized1, 2 . This study aims to evaluate fertility in patients with FMF‑related AA amyloidosis compared to FMF patients without amyloidosis. Methods: Retrospective study of all FMF patients seen at our center over a 4‑year period (2015 to 2019). Diagnosis was established according to Livneh criteria3 . Fertility data were collected from medical records, including number of pregnancies, parity for women, and number of children for men. Patients with biopsy‑proven AA amyloidosis were compared to those without amyloidosis. Results: Eighty FMF patients were included, of whom 52 had histologically confirmed AA amyloidosis. Median age at diagnosis was 33.7 years (range 6 to 70). Median age at symptom onset was 6 years (range 4 to 45). Forty‑nine patients were homozygous or compound heterozygous for pathogenic MEFV mutations, while 31 were simple heterozygous. Median age at colchicine initiation was 38.1 years (range 28 to 70). Among men (44 patients, median age 42 years), mean number of children was 2 (range 0 to 7). Declared infertility was observed in 2 men (4.5%) within the AA amyloidosis group. Among women (36 patients, median age 37 years), mean number of pregnancies was 2.2 (range 0 to 9); 22% were under 25 years and 35% under 30 years. Infertility was diagnosed in 4 women (11.1%), all of whom had developed AA renal amyloidosis. Overall, 47 patients (58.8%) with secondary amyloidosis had children. AA amyloidosis complicating FMF significantly increased infertility risk compared to FMF patients without amyloidosis (11.5% versus 0%, p = 0.03). Conclusion: AA amyloidosis complicating FMF significantly increases infertility risk compared to FMF patients without amyloidosis. Early and sustained colchicine prescription can restore fertility rates to normal levels and prevent the development of systemic amyloidosis 4, 5 . Keywords: Familial Mediterranean fever; AA amyloidosis; infertility; colchicine; MEFV mutation; renal amyloidosis.
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2026-06-29 | Inflammation at the Crossroads: Familial Mediterranean Fever and Cardiovascular Risk.
The understanding between Familial Mediterranean Fever (FMF) and cardiovascular diseases (CVDs) remains unclear. The study's objective was to investigate the association between FMF and CVD. Based on a survey targeting individuals with FMF, the patients diagnosed with coronary artery disease, cerebrovascular disease, and hypertension were considered patients with CVD. Out of 522 patients, 201 had CVD. The mean ± standard deviation (SD) age was 53.00 ± 6.43 in patients without CVD and 57.60 ± 8.33 in patients with CVD. Hypertension was present in 188 patients (36%), coronary artery disease was observed in 51 patients (9.8%), and 10 patients (1.9%) had cerebrovascular disease. In patients with CVD, diabetes (30.3%) was the most common comorbidity. All patients consumed colchicine. Thirty-five patients with (17.2%) and 25 without CVD (7.8%) had colchicine resistance. 90% continued treatment with colchicine. 25 (12.4%) patients with CVD were using biological agents, as were 18 (5.7%) patients without CVD (p=0.006). The attack period average C-reactive protein (CRP) level was 61.3 (SD=53.1), while in remission, it had an average value of 3.39 (SD=4.28). CRP median was 3.00 (3.65) during attacks in the group with CVD, and 2.00 (2.5) in the group without CVD (p=0.011). CRP median was 2.8 (3.55) in patients with hypertension, and 2.00 (2.7) in patients without hypertension. FMF does not appear to increase the risk of CVD. Colchicine resistance was associated with the incidence of cardiovascular diseases. Colchicine and anti-interleukin-1 show promise in reducing the risk of cardiovascular diseases in patients with FMF.
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2026-06-29 | The integrative role of the microbiome in systemic immuno-inflammatory aberrations.
The human immune system maintains a delicate balance between protective immunity and self-tolerance. Disruption of this equilibrium leads to immune-mediated diseases (IMDs), a heterogeneous group of disorders including autoimmune, allergy, and autoinflammatory conditions [examples include familial Mediterranean fever (FMF) and cryopyrin-associated periodic syndromes (CAPS)]. Traditionally viewed as organ-specific pathologies, IMDs are now recognized as systemic disorders driven by chronic, self-sustaining low-grade inflammation. The microbiome, a key regulator of immune development and barrier function, acts as a central driver of this systemic inflammatory circuit. Dysbiosis impairs epithelial integrity, promotes microbial translocation, and triggers aberrant activation of pattern-recognition receptors, inflammasomes, and inflammatory signaling pathways. It skews cytokine networks toward pro-inflammatory phenotypes and disrupts the differentiation and function of critical immune cell populations, establishing a vicious cycle that propagates systemic inflammation and multi-organ comorbidities via gut-skin, gut-joint, and gut-lung axes. This review summarizes the roles of microbiome dysbiosis in IMD pathogenesis, highlights related biomarkers, and evaluates emerging therapeutic strategies targeting the host-microbiota axis. We advocate a systems immunology paradigm that integrates the microbiome as a core therapeutic target to restore immune homeostasis, achieve durable remission, and reduce the systemic comorbidity burden in patients with IMDs.
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