May 2026 Research Update

Across these studies, researchers looked for easier ways to track inflammation or possible organ effects in familial Mediterranean fever (FMF), using routine blood counts, newer blood proteins, and an ultrasound-based stiffness scan. Several blood tests showed measurable differences (either versus healthy people, or between attacks and remission), but it is still unclear how well these markers reflect organ health or long-term outcomes. One imaging approach (organ stiffness testing) did not detect clear differences in children who were already in remission. [1] [2] [3] [4]

A retrospective study in 87 children suggested that routine complete blood count patterns differed by disease phase. Neutrophil counts were higher during attacks, while platelet distribution width (a measure of how variable platelet size is) was higher during remission and independently predicted remission, with a combined model showing moderate ability to separate attack from remission (area under the curve 0.78). [1]

Two pediatric case-control studies evaluated less common blood proteins that could reflect inflammation even during remission. Midkine was higher in children with FMF in remission than in healthy controls, and it related to anemia and some signs of ongoing low-level inflammation; pleiotrophin showed higher gene activity but blood levels were not clearly higher than controls. Serum gelsolin levels were higher in children with FMF than in children with juvenile idiopathic arthritis and healthy controls, and it helped distinguish FMF from juvenile idiopathic arthritis in this small study (area under the curve 0.82). [2] [5]

One cross-sectional study explored a kidney injury-related blood marker (serum Kidney Injury Molecule-1) in 50 people with FMF and 36 healthy controls. Levels were slightly higher in FMF than controls, and were lower in the subgroup treated with canakinumab compared with other FMF patients, but this marker did not move in step with common kidney checks like estimated filtration rate or urine protein level in this dataset. [3]

A prospective study tested whether shear-wave elastography (an ultrasound method that estimates tissue stiffness) could pick up hidden organ involvement during remission. Liver, spleen, and thyroid stiffness values were similar in children with FMF in remission and healthy controls, even though standard inflammation blood tests were higher in the FMF group. This suggests stiffness testing may miss subtle changes in this setting, or that there may be no measurable stiffness change during remission in many children. [4]

For patients and caregivers, this set of studies mainly adds background about tools researchers are evaluating to track FMF activity and possible organ effects between clinic visits. Routine blood count measures (like neutrophils and platelet distribution width) may help describe whether a child is in an attack or remission in research settings, while newer proteins (midkine, gelsolin, and Kidney Injury Molecule-1) are still exploratory and need more testing to understand what they mean over time and across different treatments. It also remains uncertain whether organ stiffness scans are useful for detecting early or low-level organ changes in FMF during remission, since one study found no clear differences versus healthy controls despite higher inflammation blood tests. [1] [2] [5] [3] [4]

This months studies add detail to how different changes in the MEFV gene can line up with different Familial Mediterranean fever (FMF) patterns, especially in children and teens. Overall, having two copies of some MEFV changes (such as M694V) tended to track with earlier start and higher severity, while uncertain gene changes were more often linked with less classic FMF symptoms but a similar overall burden of attacks. The research also reinforces that many people identified through clinic-based genetic testing have only one detected MEFV change, and not all symptom patterns fit neatly into one label. [6] [7] [8] [9]

In a large retrospective pediatric cohort (1,255 patients), symptom onset at age 2 years or younger was linked to longer time to diagnosis, more frequent attacks and fevers, higher disease severity, and more colchicine-resistant FMF. In the same study, M694V homozygosity was more common in early-onset disease, and having fever plus a family history of colchicine-resistant FMF were independent predictors of early onset. [6]

A separate genotype-phenotype comparison of 148 people with FMF found that M694V homozygosity was tied to earlier onset and higher severity scores, and it was also linked with more erysipelas-like erythema (a specific skin rash). At the same time, several common symptoms and related conditions (fever, abdominal pain, joint pain, vasculitis, family history, ankylosing spondylitis) did not differ across the genotype groups studied, and the authors noted that a single E148Q change could show FMF features similar to certain other MEFV changes. [7]

In a retrospective pediatric study of children with recurring inflammatory symptoms who were taking colchicine, those carrying MEFV variants of uncertain significance were less likely to have classic FMF features like serositis-related chest pain and arthritis, but more likely to have atypical symptoms including diarrhea, mouth sores, and swollen lymph nodes, along with longer-lasting attacks. Even so, age at onset and attack frequency were similar to children with two clearly disease-causing MEFV changes, and about half of the uncertain-variant group met FMF classification criteria. [8]

A retrospective study of 366 Jordanian adolescents with FMF described how often different common MEFV changes appeared in that clinic population. Just over half were mutation-positive on the tested panel, and the most frequent changes were E148Q, V726A, and M694V, mostly in people with only one copy of the change (heterozygous), while M694I showed higher homozygosity and one tested change (I692del) was not seen. [9]

One case report described a person with recurrent aseptic meningitis (Mollaret meningitis) who carried a newly reported single-copy MEFV change (L560F). Lab testing in immune cells suggested this variant increased inflammatory signaling markers after stimulation compared with normal MEFV, and the patient improved clinically with colchicine, but this is evidence from one person and may not apply broadly. [10]

For patients and caregivers, these studies mainly help explain why FMF can look different from one person to another, including differences in age when symptoms begin, how severe attacks are, and whether symptoms look classic (chest pain from lining inflammation, arthritis) or more atypical (diarrhea, mouth sores, swollen lymph nodes). Right now, this is mostly background information that supports conversations about why symptoms and gene results may not perfectly match, especially when only one MEFV change is found or when the change is classified as uncertain. Important uncertainties remain, including how to interpret many single-copy or uncertain MEFV results and how well these patterns apply outside the specific clinics and countries studied.

Across two clinical studies in children with familial Mediterranean fever (FMF), colchicine treatment response and treatment-related monitoring needs looked variable. One study suggested that higher disease-activity risk scores at diagnosis were linked to not meeting a 6-month improvement target, but prediction was only modest. Another study found blood anemia measures improved over 6 months while some vitamin levels decreased, suggesting a mix of benefits and potential monitoring questions during treatment. [11] [12]

In a retrospective cohort of 168 newly diagnosed children treated with colchicine for at least 6 months, about 65% met the study's FMF50 response definition at 6 months. Higher PREDICT-crFMF and TURPAID scores at diagnosis were linked to being a non-responder, and the M694V gene variant in two copies was also an independent predictor of non-response. Overall, the ability of these scores to separate responders from non-responders was modest. [11]

In a prospective study of 46 children starting colchicine, hemoglobin and iron levels increased by 6 months, while ferritin decreased. Vitamin B12 and folate levels also decreased over the same period. This pattern is consistent with reduced inflammation-related anemia alongside possible lowering of certain micronutrients during follow-up. [12]

For families using colchicine, these studies add context for what may be followed over time: symptom improvement can vary across children, and some research tools may only partly flag who might respond less by 6 months. Separately, short-term follow-up data suggest some blood measures can move in opposite directions (for example, anemia measures improving while vitamin B12 and folate fall), but it is still uncertain how often this happens and how it relates to symptoms in day-to-day life. [11] [12]

Two papers looked beyond standard colchicine therapy, but the evidence is early. One report described two children with overlapping inflammatory diseases who improved on a combination of two immune-targeting medicines, with no infections reported during short follow-up. Another was lab research using blood cells from FMF patients, identifying a molecular switch (JMJD3) that reduced inflammation signals when blocked, which may inform future drug development but is not a treatment study. [13] [14]

In a case report of two pediatric patients, one child with juvenile idiopathic arthritis, eye inflammation (uveitis), and FMF had low disease activity after anakinra was added to adalimumab, and no adverse events were observed over 6 months. Because this describes individual patients without a comparison group, it cannot show how often similar results would happen in other children, and it does not establish overall safety for broader use. [13]

In an in vitro study using peripheral blood immune cells from FMF patients, treating cells with GSK-J4 (which inhibits JMJD3) lowered NF-kB and NLRP3 pathway signals and reduced inflammatory cytokines. Similar reductions were seen when JMJD3 was decreased using gene-silencing methods. These results suggest JMJD3 may play a role in FMF-related inflammation, but the work was done in cells in the lab rather than in patients. [14]

This set of studies mainly matters as background on possible future directions and on rare, complex situations where more than one immune condition is being treated at the same time. The dual-biologic case report offers a description of what happened in two children under structured monitoring, but it cannot predict benefits or risks for most people with FMF. The JMJD3 lab study helps explain inflammation pathways in FMF and points to a potential drug target, but it does not yet show whether blocking JMJD3 is safe or effective in real-world patients. [13] [14]

Together, these studies suggest a spectrum of kidney involvement in familial Mediterranean fever (FMF), from subtle changes seen on kidney ultrasound to clear disease patterns on kidney biopsy. The overall message is that kidney issues in FMF can show up in different ways, and amyloidosis remains a key concern among people who reach the point of needing a biopsy. [15] [16]

In a case-control study of adults with FMF who did not have obvious kidney disease, kidney Doppler ultrasound showed higher measures of resistance to blood flow (renal resistance index and pulsation index) than in healthy controls. These measures were even higher in FMF patients who had low-grade protein in the urine, suggesting possible early kidney blood-flow changes before more noticeable kidney problems. [15]

In a retrospective biopsy series of adults with several non-lupus rheumatic diseases, amyloidosis was the most common kidney tissue diagnosis overall, and it was especially common in the FMF subgroup (61.3%). The biopsy staining pattern supported AA (inflammation-related) amyloidosis, based on positive serum amyloid A staining and no evidence of a monoclonal antibody pattern. [16]

For patients and caregivers, this month highlights that kidney involvement in FMF can be discussed at more than one level: early, indirect signals (like ultrasound blood-flow measures, especially when small amounts of urine protein are present) and later, tissue-level diagnoses when a biopsy is done. These studies do not show that an abnormal ultrasound result predicts future kidney failure, and the biopsy study only represents people sick enough to need a biopsy, so it cannot tell how common amyloidosis is in all people with FMF. [15] [16]

Taken together, this month's papers suggest familial Mediterranean fever (FMF) can affect health even during attack-free times, in ways that touch the heart, daily activity, sexual health, and related inflammatory conditions. Most evidence came from cross-sectional or retrospective studies, so these results describe patterns seen in groups but cannot prove what causes what. Several findings also varied by age group (children vs adults) and by factors such as season, region, and emotional well-being. [17] [18] [19] [20] [21]

In one moderate-sized study of adults taking long-term colchicine, people with FMF had higher P-wave dispersion on a standard electrocardiogram (a measure that reflects how evenly electrical signals travel through the upper heart chambers) than matched people without FMF. Higher P-wave dispersion was linked to FMF status, and also showed links with age and blood inflammation markers in the analysis. [17]

In children ages 9 to 14, weekly questionnaires over 3 months showed lower physical activity levels in those with FMF than in matched healthy peers. Lower activity was also linked with exercise-related leg pain, older age, and higher disease activity scores during the same period. [18]

In a study of 50 adult men assessed during attack-free periods, erectile dysfunction was reported in over half of participants, and it tracked more closely with anxiety, depression, and FMF-related quality of life than with clinical FMF measures. This points to sexual health and emotional health being closely connected for some men living with FMF. [19]

A systematic review that combined 10 observational studies found that vitamin D levels were lower on average in people with FMF than in healthy controls, but results differed widely across studies. Differences were not seen in summer in the studies that reported season, and there were regional differences (for example, lower levels reported in Egyptian versus Turkish groups), while parathyroid hormone and C-reactive protein did not differ overall. [20]

In a retrospective pediatric inflammatory bowel disease (IBD) cohort, rheumatologic diseases were common, and FMF was the most frequent among them. Children with IBD plus a rheumatologic disease had lower bowel disease activity at diagnosis but were more likely to need biologic therapy during follow-up; within the FMF subgroup, bowel disease activity was lower at diagnosis and higher at the last follow-up than in children without rheumatologic disease. [21]

For patients and caregivers, these studies add context that FMF may be linked to measurable differences between attacks, including heart electrical patterns, everyday movement in children, and sexual and emotional well-being in adult men, as well as interactions with other inflammatory conditions like IBD. Most results are best viewed as background information that may help explain why some symptoms or concerns can show up even when fever attacks are controlled, rather than as proof of a direct cause. Important uncertainties remain because several studies were small, single-center, or based on group averages, and the vitamin D review showed large differences by season and region.

Across the available research this month, a major life-disrupting event (a large earthquake) was linked to a clear, temporary worsening of familial Mediterranean fever (FMF) control in children, with the biggest increase seen where regular access to colchicine was disrupted. Over the following months, attack rates generally trended back down toward pre-disaster levels, suggesting the effect was not permanent but could be substantial in the short term. [22]

In a multicentre study of 963 children with FMF in Turkiye, monthly attack counts rose after the February 2023 earthquake compared with the year before. The increase was larger in earthquake-affected areas than outside the zone, and it was most pronounced in regions reported to have limited colchicine access. [22]

The same study also found that, month by month after the earthquake, attack counts and the chance of having at least one attack gradually declined from the immediate post-disaster peak. The authors noted that the study did not directly measure stress, infections, or environmental exposures, so it cannot pinpoint why attacks increased, only that the pattern was seen at the population level. [22]

For patients and caregivers, this evidence mainly adds background understanding: major disruptions like natural disasters may be followed by a noticeable, short-term increase in FMF attacks in some children, especially when access to regular medicines is interrupted. It is still uncertain how much of the effect is due to medication supply problems versus stress or other exposures, because these were not directly measured in this study. [22]