Eighteen female and 20 male patients were included in the cohort. The mean age of the patients in the cohort was 12.8 ± 4.8 years. The mean time to diagnosis was 15.2 ± 12.9 months in females and 22.8 ± 22.1 months in males, and no significant difference was found in the time to diagnosis (p = 0.204). The mean disease follow-up was 6.8 ± 4.7 years.

Of 38 patients, 13 (34%) had a consanguineous marriage between their parents. In 31 (81.6%) of the patients, there was a family history of a relative diagnosed with FMF.

Patients were divided into 7 different groups according to MEFV mutation type. Only two of our 38 patients had no MEFV mutation. Patients without a MEFV gene analysis were not enrolled in the study. The most frequent MEFV mutation was M694V homozygous, detected in 15 patients, followed by M694V heterozygous in 4 patients. M694V allele was detected in 19 (50%) of our patients.

The mean Pras score of the cohort was 6.1 ± 1.7. The mean Pras score was 5.7 ± 1.2 in males and 6.5 ± 2.1 in females. There was no significant difference in disease severity between genders. No significant difference between genders was noted (p = 0.144).

Patients with a score of 3–5 points were included in the mild disease activity group; 6–8 points were included in the moderate disease activity group; and 9 points or more were included in the severe disease activity group. In addition, no significant difference was found between genders in any of the groups according to this Pras score.

Of the laboratory tests obtained, leukocyte count, neutrophil count, C-reactive protein level, and erythrocyte sedimentation rate were found to be significantly higher in the attack period compared to the remission period (p < 0.005).

During the attack period, the mean leukocyte count, 12200.0 ± 4740.8/mm3; the neutrophil count, 9360.5 ± 4204.3/ mm3; and the ESR, 25.4 ± 12.5 mm/h were measured, while in the remission period, these values were 7550.0 ± 2040.1/mm3, 4189.5 ± 1951.8/mm3, and 11.2 ± 6.2 mm/h, respectively. In all parameters, the measurements in the attack period were significantly higher compared to the remission period (p = 0.0001). The laboratory findings of patients divided into three groups (mild, moderate, and severe) according to the Pras scoring system were compared, taking into account the severity of the disease. Comparative leukocyte and neutrophil levels were presented for the attack and remission periods in Fig. 2.

Leukocyte, lymphocyte, and neutrophil levels between the attack and remission periods

CRP was measured at 98.9 ± 210.1 (median 48.0) in the attack period and at 14.6 ± 18.1 (median 7.5) in the remission period. A statistically significant difference was found between the attack and remission periods (p < 0.05). The changes in ESR and CRP levels, based on the disease groups, are shown in Fig. 3.

ESR and CRP levels between the attack and remission periods

During the attack period, the lymphocyte count was measured to be 1863.2 ± 1040.4/mm3, whereas it was 2663.2 ± 895.5/mm3 during the remission period. A significant decrease in lymphocyte count was observed during the attack period compared to the remission period (p = 0.0001). In our study, a lower limit of 1500/mm3 was defined for lymphopenia. Among the 38 patients evaluated during an attack, 14 had lymphocyte counts below the normal range, and eight of them had lymphocyte values < 1000/mm3. In this group of patients with lymphopenia (14 patients), only two were receiving biologic agents regularly (anakinra, canakinumab). During the remission period, the lymphocyte counts of patients who experienced lymphopenia during the attack returned to the normal range (Fig. 2).

There was no significant difference between platelet count and ProBNP values measured in the attack and remission periods in relation to disease activation (p > 0.005).

No statistically significant difference was observed in the mean values of acute phase markers and blood count measurements between the mild and moderate disease groups (p > 0.05). The schematic representation shows the comparison of measurements among the disease groups and all patients collectively (Figs. 2 and 3).

According to Pras scoring, ECG findings of the mild and moderate disease groups in the attack and remission periods were compared. In the mild group, the heart rate was 102.2 ± 20.2/min, the PR interval was 136.5 ± 14.6/ms, and the QRS width was 83.5 ± 7.0/ms in the attack period, while it was 82.2 ± 12.5/min, 135.9 ± 18.4/ms, and 83.2 ± 8.5/ms in the remission period, respectively. There was a significant difference between the attack and remission periods in the mild disease group (p < 0.05).

In the moderate disease group, the heart rate was 111.7 ± 24.7/min, the PR interval was 134.7 ± 23.4/ms, and the QRS width was 80.5 ± 12.2/ms during the attack period, and 84.1 ± 17.7/min, 128.9 ± 18.2/ms, and 83.2 ± 9.5/ms during the remission period, respectively. There was a significant difference between attack and remission periods in the moderate disease group (p < 0.05).

When ECG changes of mild and moderate disease groups were compared with each other, no significant difference was found between the 2 groups (p > 0.05).

A significant difference was found in the mean durations of e-wave deceleration in the conventional echocardiographic evaluations between the attack (mean: 161.61 ± 46.0 ms) and remission (mean: 188.32 ± 41.1 ms) periods (p = 0.046). In conventional echocardiography measurements, no significant change was found between the attack and remission periods in parameters other than early deceleration time (p > 0.05).

During the attack period, speckle tracking echocardiographic evaluation demonstrated impaired function in the inferior segments of the left ventricle (Table 1).

In Speckle echocardiographic evaluation, when mild and moderate disease groups were compared, the apical inferior segment was 13.8 ± 6.2 in the mild disease group and 18.3 ± 7.2 in the moderate disease group. There was a significant correlation with disease activity in the apical inferior segment (p < 0.05).

The mid-anterior segment measured 14.6 ± 5.7 in the mild disease group and 18.4 ± 6.1 in the moderate disease group. There was a significant difference between mild and moderate disease severity in the mid-anterior segment (p < 0.05). There was no significant difference in disease severity in other segments except these two segments (p > 0.05).

An assessment of these affected regions showed that right ventricular function was more affected in the moderate disease group. The affected regions are marked in red in Fig. 4.

Affected cardiac segments during an attack

In patients with lymphopenia, it was observed that the right ventricular function was more severely affected during the attack phase compared to patients with normal lymphocyte count. The change in TAPSE measurements between the attack and remission periods was − 16.1 ± 6.9% in the patients with lymphopenia during the attack and 3.7 ± 23.9% in the patients without lymphopenia. Statistically significant difference between the mean measurements was found (p = 0.019).

Speckle tracking echocardiography evaluations were compared between the patients who received anakinra treatment during the attack (17 patients) and the patients who received only symptomatic treatment (21 patients). The percentage change between the attack and remission period in the measurement of the three-chamber basalinferolateral segment in the patients who received only symptomatic treatment during the attack was 84.5 ± 96.1%. Meanwhile, the change between the attack and remission period in the patients who received anakinra was 20.8 ± 51.3%. A significant difference was observed between the two groups (p = 0.041).