[Coexistence of familial Mediterranean fever and seronegative spondyloarthritis: peculiarities of the course].

Familial Mediterranean fever (FMF) is an autosomal recessive disease distributed among populations of Mediterranean origin - Armenians, Sephardi Jews, Arabs, Turks. There are numerous clinical observations regarding combination of FMF, as a classical representative of autoinflammatory diseases, with systemic diseases of connective tissue. Seronegative spondyloarthritis (SpA) are the most interesting disorders from this point of view, as far as sacroiliitis - an essential feature of SpA, may also present as a part of joint syndrome in FMF. The main objective of this clinical study was the investigation of the peculiarities of courses of FMF and SpA in case of their coexistence. We studied 126 patients with FMF, SpA and coexistence of both. According to results, patients with the overlap of FMF with SpA had relatively milder course of disease in comparison with each disease separately. Comparative clinical and instrumental characteristics of FMF-associated disorders had shown that in FMF-SpA overlap the symptoms of both diseases are less severe.

Generation of iPSCs from a Patient with the M694V Mutation in the MEFV Gene Associated with Familial Mediterranean Fever and Their Differentiation into Macrophages.

Familial Mediterranean fever (FMF) is a systemic autoinflammatory disorder caused by inherited mutations in the MEFV (Mediterranean FeVer) gene, located on chromosome 16 (16p13.3) and encoding the pyrin protein. Despite the existing data on MEFV mutations, the exact mechanism of their effect on the development of the pathological processes leading to the spontaneous and recurrent autoinflammatory attacks observed in FMF, remains unclear. Induced pluripotent stem cells (iPSCs) are considered an important tool to study the molecular genetic mechanisms of various diseases due to their ability to differentiate into any cell type, including macrophages, which contribute to the development of FMF. In this study, we developed iPSCs from an Armenian patient with FMF carrying the M694V, p.(Met694Val) (c.2080A>G, rs61752717) pathogenic mutation in exon 10 of the MEFV gene. As a result of direct differentiation, macrophages expressing CD14 and CD45 surface markers were obtained. We found that the morphology of macrophages derived from iPSCs of a patient with the MEFV mutation significantly differed from that of macrophages derived from iPSCs of a healthy donor carrying the wild-type MEFV gene.

Perioperative care of the patient with a periodic fever syndrome.

Periodic fever syndromes are autoinflammatory disorders associated with recurrent fevers unrelated to infection. Little is known about the perioperative management of patients with these syndromes, and existing literature consists primarily of case reports and occasional case series. This narrative review discusses background information and diagnostic criteria for the three most common periodic fever syndromes: periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA), familial Mediterranean fever (FMF), and TNF receptor-associated periodic syndrome (TRAPS), and describes perioperative considerations for anesthesia providers when caring for the patient with a periodic fever syndrome. We include a systems-based framework in which to organize these considerations.

Relationship between sacroiliitis and inflammatory markers in familial Mediterranean fever.

OBJECTIVE: Familial Mediterranean fever is the most common monogenic autoinflammatory disease. This study aimed to evaluate the relationship between sacroiliitis observed in familial Mediterranean fever and hematological inflammatory markers. METHODS: In this study, 168 familial Mediterranean fever patients were examined. A total of 61 familial Mediterranean fever patients who had sacroiliac magnetic resonance imaging due to waist and hip pain were included in the study. According to the magnetic resonance imaging findings, patients were divided into two groups: with and without sacroiliitis. The relationship between hematological inflammatory markers and sacroiliitis was investigated. RESULTS: The frequency of sacroiliitis was found to be 13.6% in all familial Mediterranean fever patients and 37.8% in patients with low back pain who underwent sacroiliac magnetic resonance imaging. Neutrophil count, neutrophil/lymphocyte ratio, monocyte/lymphocyte ratio, and systemic immune-inflammatory index were significantly higher in the sacroiliitis group than in the other group, and this difference was found to be statistically significant (p<0.05). As a result of the receiver operating characteristic analysis, it was observed that neutrophil/lymphocyte ratio, monocyte/lymphocyte ratio, and systemic immune-inflammatory index were very sensitive parameters in determining sacroiliitis in patients with familial Mediterranean fever. CONCLUSION: It was observed that the frequency of sacroiliitis was increased in familial Mediterranean fever patients. It is predicted that hematological inflammatory markers such as neutrophil/lymphocyte ratio, monocyte/lymphocyte ratio, and systemic immune-inflammatory index can be used in the diagnosis of sacroiliitis.

Health conditions of first-degree relatives of children with familial Mediterranean fever.

BACKGROUND: Given the strong genetic background of familial Mediterranean fever (FMF), the frequently reported co-existing diseases in children with FMF should also be investigated in other family members. Therefore, we aimed to examine the medical conditions of first-degree relatives (FDRs) of our pediatric patients with FMF in the present study. METHODS: Chronic diseases of FDRs of pediatric 449 FMF, 147 juvenile idiopathic arthritis (JIA) patients and 93 healthy controls (HC) were questioned during their routine clinical visits for 9 consecutive months. RESULTS: A total of 1975 FDRs of 449 FMF, 690 FDRs of 147 JIA patients, and 406 FDRs of 93 HC were included into the study. The most common medical conditions were non-atopic asthma (n=71, 3.6%), type 2 DM (n=14, 2%), and tonsillectomy history (n=12, 2.95%) in the FMF, JIA, and HC groups, respectively. Atopic diseases (FMF vs. JIA: p=0.013; FMF vs. HC: p=0.014), rheumatic diseases (FMF vs. JIA: p=0.030; FMF vs. HC: p=0.017), and surgical histories (FMF vs. JIA: p<0.01; FMF vs. HC: p=0.026), including adenoidectomy, tonsillectomy, and appendectomy, were significantly more common in the FMF group than in other groups. CONCLUSIONS: Our novel findings may contribute to understanding the hereditary burden of co-existing diseases in children with FMF and encourage further studies involving genetic screenings.

Risk for cancer development in familial Mediterranean fever and associated predisposing factors: an ambidirectional cohort study from the international AIDA Network registries.

Objective: Inflammation has been associated with an increased risk for cancer development, while innate immune system activation could counteract the risk for malignancies. Familial Mediterranean fever (FMF) is a severe systemic inflammatory condition and also represents the archetype of innate immunity deregulation. Therefore, the aim of this study is to investigate the risk for cancer development in FMF. Methods: The risk ratio (RR) for malignancies was separately compared between FMF patients and fibromyalgia subjects, Still's disease patients and Behçet's disease patients. Clinical variables associated with cancer development in FMF patients were searched through binary logistic regression. Results: 580 FMF patients and 102 fibromyalgia subjects, 1012 Behçet's disease patients and 497 Still's disease patients were enrolled. The RR for the occurrence of malignant neoplasms was 0.26 (95% Confidence Interval [CI.] 0.10-0.73, p=0.006) in patients with FMF compared to fibromyalgia subjects; the RR for the occurrence of malignant cancer was 0.51 (95% CI. 0.23-1.16, p=0.10) in FMF compared to Still's disease and 0.60 (95% CI. 0.29-1.28, p=0.18) in FMF compared to Behçet's disease. At logistic regression, the risk of occurrence of malignant neoplasms in FMF patients was associated with the age at disease onset (ß1 = 0.039, 95% CI. 0.001-0.071, p=0.02), the age at the diagnosis (ß1 = 0.048, 95% CI. 0.039-0.085, p=0.006), the age at the enrolment (ß1 = 0.05, 95% CI. 0.007-0.068, p=0.01), the number of attacks per year (ß1 = 0.011, 95% CI. 0.001- 0.019, p=0.008), the use of biotechnological agents (ß1 = 1.77, 95% CI. 0.43-3.19, p=0.009), the use of anti-IL-1 agents (ß1 = 2.089, 95% CI. 0.7-3.5, p=0.002). Conclusions: The risk for cancer is reduced in Caucasic FMF patients; however, when malignant neoplasms occur, this is more frequent in FMF cases suffering from a severe disease phenotype and presenting a colchicine-resistant disease.

Identifying high-risk neurological phenotypes in adult-onset classic monogenic autoinflammatory diseases: when should neurologists consider testing?

BACKGROUND: Monogenic autoinflammatory disorders result in a diverse range of neurological symptoms in adults, often leading to diagnostic delays. Despite the significance of early detection for effective treatment, the neurological manifestations of these disorders remain inadequately recognized. METHODS: We conducted a systematic review searching Pubmed, Embase and Scopus for case reports and case series related to neurological manifestations in adult-onset monogenic autoinflammatory diseases. Selection criteria focused on the four most relevant adult-onset autoinflammatory diseases-deficiency of deaminase 2 (DADA2), tumor necrosis factor receptor associated periodic fever syndrome (TRAPS), cryopyrin associated periodic fever syndrome (CAPS), and familial mediterranean fever (FMF). We extracted clinical, laboratory and radiological features to propose the most common neurological phenotypes. RESULTS: From 276 records, 28 articles were included. The median patient age was 38, with neurological symptoms appearing after a median disease duration of 5 years. Headaches, cranial nerve dysfunction, seizures, and focal neurological deficits were prevalent. Predominant phenotypes included stroke for DADA2 patients, demyelinating lesions and meningitis for FMF, and meningitis for CAPS. TRAPS had insufficient data for adequate phenotype characterization. CONCLUSION: Neurologists should be proactive in diagnosing monogenic autoinflammatory diseases in young adults showcasing clinical and laboratory indications of inflammation, especially when symptoms align with recurrent or chronic meningitis, small vessel disease strokes, and demyelinating lesions.

Examination of cardiac functions during acute attack and remission period in children with familial Mediterranean fever.

Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disease characterized by recurring serosal inflammation. Cardiac involvement in FMF commonly manifests as pericarditis and pericardial effusion; however, there is limited research on myocardial function. This study aimed to assess cardiac functions during active inflammation and remission periods of FMF patients and investigate the cardiac effects of inflammation during the attack period. Thirty-eight FMF patients without additional cardiac diseases were included in the study. Demographic characteristics, clinical symptoms, family history, and MEFV gene analysis results were obtained retrospectively. Blood tests, blood pressure measurements, electrocardiogram evaluations, conventional echocardiography, and speckle tracking echocardiography were performed during the attack and remission periods. Disease severity was assessed using the Pras scoring system. During the attack period, FMF patients exhibited significantly higher leukocyte count, neutrophil count, C-reactive protein, and erythrocyte sedimentation rate compared to the remission period (p < 0.005). Speckle tracking echocardiography revealed decreased function in the inferior segments of the left ventricle during the attack period (p < 0.005). Right ventricular function was more affected in the moderate disease group. FMF patients with lymphopenia during the attack demonstrated more impaired right ventricular function compared to those with normal lymphocyte count. Conclusions: FMF patients experience cardiac abnormalities during active inflammation, highlighting the importance of monitoring cardiac functions in these patients. Speckle tracking echocardiography can provide valuable insights into cardiac involvement in FMF. These findings emphasize the cardiac impact of FMF inflammation and the significance of long-term cardiac function monitoring in the management of FMF patients. What is Known: • The current literature lacks studies investigating myocardial function in the pediatric population during the attack period of this particular disease. • Our objective was to assess the alterations in cardiac function during the attack and remission periods, considering clinical manifestations, disease severity, acute phase reactant levels, and mutation type. We also evaluated the pattern of cardiac involvement and the affected cardiac areas by comparing remission and attack periods. What is New: • Several studies have demonstrated a rise in the prevalence of ischemic cardiac disease and mortality among individuals with FMF. • Investigating cardiac involvement during the attack period in FMF patients can provide valuable insights for the prevention of long-term complications.

Canakinumab treatment real world evidence in 3 monogenic periodic fever syndromes in 2009-2022: an interim analysis using the French JIR cohort database.

BACKGROUND: Our study aimed to provide real-world evidence on the treatment patterns, effectiveness and safety of canakinumab in France in Familial Mediterranean Fever (FMF), Mevalonate Kinase Deficiency (MKD), and Tumor necrosis factor Receptor Associated Periodic Syndrome (TRAPS). METHODS: This study used the JIR cohort, a multicentre international registry created in 2013 to collect data on patients with juvenile inflammatory rheumatic diseases. French patients diagnosed with FMF, MKD or TRAPS and treated with canakinumab were included in this study. RESULTS: 31 FMF, 26 MKD and 7 TRAPS patients received canakinumab during the study period. Most of them initiated canakinumab at the recommended dose of 2 mg/kg or 150 mg, but less than half of FMF and MKD patients initiated it at the recommended frequency (every 4 weeks). Two years after initiation, the rate of patients still on treatment was 78.1% in FMF, 73.7% in MKD, and 85.7% in TRAPS patients. While the dose per injection remained globally the same over the course of the treatment, some adjustments of the dose intervals were observed. Six patients had a severe adverse event reported. Of those, three were possibly related to canakinumab. CONCLUSION: This interim analysis showed a good maintenance of canakinumab treatment 2 years after initiation and confirmed its safety profile in real-life practice in France in patients diagnosed with FMF, MKD and TRAPS. The high variety of dose and interval combinations observed in canakinumab treated patients let suppose that physicians adapt the posology to individual situations rather than a fixed treatment plan.

The roles of SFKs in the regulation of proinflammatory cytokines and NLRP3 in familial mediterranean fever patients.

Familial Mediterranean Fever (FMF) is caused by mutations in pyrin, a protein produced in innate immune cells that regulates the development of interleukin (IL)-1ß by interacting with caspase-1 and other components of inflammasomes. Although overexpression of proinflammatory cytokines have been observed in FMF patients, no studies have been conducted on the role of Src family kinases (SFKs). The purpose of this study was to examine the impact of SFKs on the modulation of IL-1ß, IL-6, IL-8, TNF-α, and NLRP3 inflammasome in patients with FMF. The study included 20 FMF patients and 20 controls. Peripheral blood mononuclear cells (PBMCs) were isolated by density gradient centrifugation. Protein expression levels of SFKs members were measured by western blot. The effect of lipopolysaccharide-induced (LPS) activation and PP2- induced inhibition of SFKs on NLRP3 and IL-1ß, IL 6, IL-8, TNF-α were examined by western blot and flow cytometry respectively. Patients with FMF have considerably greater levels of Lck expression. In addition, patients had a substantially greater basal level of NLRP3 than the control group (*p = 0.016). Most importantly, the levels of IL-1 ß were elevated with LPS stimulation and reduced with PP2 inhibition in FMF patients. These results suggest that SFKs are effective in regulation of IL-1 ß in FMF patients.

Generating Concentration Gradients across Membranes for Molecular Dynamics Simulations of Periodic Systems.

The plasma membrane forms the boundary between a living entity and its environment and acts as a barrier to permeation and flow of substances. Several computational means of calculating permeability have been implemented for molecular dynamics (MD) simulations-based approaches. Except for double bilayer systems, most permeability studies have been performed under equilibrium conditions, in large part due to the challenges associated with creating concentration gradients in simulations utilizing periodic boundary conditions. To enhance the scientific understanding of permeation and complement the existing computational means of characterizing membrane permeability, we developed a non-equilibrium method that enables the generation and maintenance of steady-state gradients in MD simulations. We utilize PBCs advantageously by imposing a directional bias to the motion of permeants so that their crossing of the boundary replenishes the gradient, like a previous study on ions. Under these conditions, a net flow of permeants across membranes may be observed to determine bulk permeability by a direct application of J=PΔc. In the present study, we explore the results of its application to an exemplary O2 and POPC bilayer system, demonstrating accurate and precise permeability measurements. In addition, we illustrate the impact of permeant concentration and the choice of thermostat on the permeability. Moreover, we demonstrate that energetics of permeation can be closely examined by the dissipation of the gradient across the membrane to gain nuanced insights into the thermodynamics of permeability.

The evaluation of depression and anxiety levels of mothers of patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome and familial Mediterranean fever.

OBJECTIVE: Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome and familial Mediterranean fever (FMF) are autoinflammatory disorders typically characterized by recurrent fever attacks. These recurrent fever attacks can lead to depression and anxiety in mothers of these patients. This study aimed to compare the depression and anxiety levels in mothers of PFAPA and FMF patients. METHODS: This study is a cross-sectional observational study. 48 mothers of children with FMF and 70 mothers of children with PFAPA participated in the study. Mothers in these two groups were compared in terms of anxiety and depression by using the validated Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). RESULTS: Depression and anxiety scores of mothers were found to be similar in FMF and PFAPA groups. Moderate or high level of anxiety was seen in 32% of mothers of patients with PFAPA and 27% of mothers of patients with FMF. 23% of mothers of patients with PFAPA were evaluated as having moderate or severe depression, and 18% of mothers of patients with FMF were evaluated as having moderate depression. There was no statistically significant difference between the duration, frequency of attacks, recurrent hospitalizations, sociodemographic characteristics, and inventory scores. CONCLUSION: Depression and anxiety scores of mothers with children diagnosed with FMF and PFAPA are similar. These two diseases affect families psychosocially at similar levels. It is important to provide psychosocial support to families.

An "On Demand" canakinumab regimen for treating children with Colchicine-Resistant familial Mediterranean fever - A multicentre study.

OBJECTIVES: Canakinumab, a human monoclonal antibody targeted at interleukin-1 beta, has demonstrated safety and efficacy in preventing familial Mediterranean fever (FMF) attacks among individuals with colchicine-resistant (crFMF). The manufacturer orders prescribe monthly subcutaneous injections. However, a subset of our patients is treated with an "canakinumab on demand " (COD) strategy, with wider intervals between drug administrations. Therefore, we aimed to compare disease activity and drug safety between COD and "canakinumab fixed frequency" (CFF) policies. METHODS: This retrospective study collected data from three Israeli paediatric rheumatology centres, of children with crFMF who were treated with canakinumab. Epidemiological and clinical parameters, cumulative drug dosages, and adverse events were compared between children treated by both policies. RESULTS: Twenty-five (49 %) children were treated according to COD policy and 26 according to CFF policy. Demographic parameters and most of the disease features did not differ significantly between the groups. Both groups showed significant reduction in attacks after canakinumab introduction. The median number (interquartile range) of attacks per month did not differ significantly between the COD and CFF groups (0.33 (0.08, 0.58) and 0.13 (0, 0.5), respectively, p = 0.485 (even though, per definition, COD patients presumably had an attack before receiving the second canakinumab dose). The mean monthly dose was lower for the COD than the CFF group (1.13 ± 1.13 vs. 3.16 ± 1.46 mg/kg, p < 0.001). Adverse events were similar between the groups. CONCLUSION: For individuals with crFMF, COD compared to CFF policy can achieve similar efficacy and safety, with a lower accumulated canakinumab dose, rendering it less immunosuppressive and less expensive.

Effects of intrauterine device use on attack frequency and severity in woman of reproductive age with familial Mediterranean fever.

AIM: Familial Mediterranean fever (FMF) is the most common inherited autoinflammatory disease in the world. There are known triggers to initiate an FMF attack, yet potential effects of intrauterine devices (IUD) in women of reproductive age have not been evaluated before. METHOD: Consecutive female patients with FMF who ever used IUD over the age of 18 were enrolled. Female patients with FMF were sub grouped according to the type of IUD they use. FMF attack frequency, severity, duration, presence of dysmenorrhea, severity of dysmenorrhea, having attacks during menstruation before and after IUD use were questioned. Demographic and clinical data were collected from hospital database. RESULTS: When all patients with IUD use were evaluated, it was found that the frequency of attacks increased after IUD insertion at 3rd and 12th months (median [min-max] attack frequency at 3rd month, 1 (0-3) vs 1 (0-6), p = 0.002, median [min-max] attack frequency at 12th month, 2 (0-12) vs 3.5 (0-18), p = 0.028). Attack severity measured by VAS pain was also significantly increased. Attack duration and menstrual pain was similar before and after IUD use. Attack frequency at 3rd and 12th months, attack severity and menstrual pain was all increased significantly in Cu-IUD users, whereas none of these parameters deteriorated in LNG-IUD group. CONCLUSION: IUD use, especially Cu-IUD, may increase the frequency and severity of attacks in female patients with FMF. Clinicians may benefit from considering LGN-IUD if IUDs are preferred as contraception in women of childbearing age with FMF.

Predicting genetic risk factors for AA amyloidosis in Algerian patients with familial Mediterranean fever.

Renal amyloid-associated (AA) amyloidosis is a harmful complication of familial Mediterranean fever (FMF). Its occurrence involves polymorphisms and mutations in the Serum Amyloid A1 (SAA1) and Mediterranean Fever (MEFV) genes, respectively. In Algeria, the association between SAA1 variants and FMF-related amyloidosis was not investigated, hence the aim of this case-control study. It included 60 healthy controls and 60 unrelated FMF patients (39 with amyloidosis, and 21 without amyloidosis). All were genotyped for the SAA1 alleles (SAA1.1, SAA1.5, and SAA1.3), and a subset of them for the - 13 C/T polymorphism by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Comparisons between genotype and allele frequencies were performed using Chi-square and Fisher tests. The SAA1.1/1.1 genotype was predominant in amyloid FMF patients, compared to non-amyloid FMF patients (p = 0.001) and controls (p < 0.0001). SAA1.1/1.5 was higher in non-amyloid patients (p = 0.0069) and in controls (p = 0.0082) than in patients with amyloidosis. Bivariate logistic regression revealed an increased risk of AA amyloidosis with three genotypes, SAA1.1/1.1 [odds ratio 7.589 (OR); 95% confidence interval (CI): 2.130-27.041] (p = 0.0018), SAA1.1/1.3 [OR 5.700; 95% CI: 1.435-22.644] (p = 0.0134), and M694I/M694I [OR 4.6; 95% CI: 1.400-15.117] (p = 0.0119). The SAA1.1/1.5 genotype [OR 0.152; 95% CI: 0.040-0.587] (p = 0.0062) was protective against amyloidosis. In all groups, the - 13 C/C genotype predominated, and was not related to renal complication [OR 0.88; 95% CI: 0.07-10.43] (p = 0.915). In conclusion, in contrast to the - 13 C/T polymorphism, the SAA1.1/1.1, SAA1.1/1.3 and M694I/M694I genotypes may increase the risk of developing renal AA amyloidosis in the Algerian population.

Factors triggering familial mediterranean fever attacks, do they really exist?

Several possible factors are hypothesized to trigger familial Mediterranean fever (FMF) attacks; however, there is no consensus on this matter. We aimed to identify these triggering factors and analyze their relationship with the Mediterranean fever gene mutation status. We prepared a questionnaire that included the most commonly mentioned possible trigger factors of familial Mediterranean fever. We administered a questionnaire to 882 patients. We used a questionnaire assessing the following: psychological stress, consumption of tea and coffee, relationship with menses, menopause and post-menopausal alleviation, seasonal changes, traveling for long durations, relocation, starvation, sleeplessness, cold exposure, fatigue, wind exposure, and humidity. The most frequent triggering factor for familial Mediterranean fever attacks was psychological stress (75.2%). Cold exposure was a statistically significant trigger in patients with exon 10 mutations. Humidity was a statistically significant trigger in patients with exon 2 mutations. Seasonal changes, traveling for long durations, relocation, and cold exposure were statistically significant triggers of familial Mediterranean fever attacks in patients with homozygous M694V mutations. Identifying trigger factors can lead to better preventive measures and personalized therapies to decrease familial Mediterranean fever attacks. Patients can significantly decrease the number of familial Mediterranean fever attacks they experience by managing psychological stress and avoiding physical factors such as cold exposure and fatigue. Determining the relationship between trigger factors and patients' Mediterranean fever gene mutation status can lead to personalized therapy for the prevention of familial Mediterranean fever attacks.

Study on crack resistance of self-healing microcapsules in asphalt pavement by multi-scale method.

Self-healing microcapsules in the asphalt pavement must be kept intact under vehicle load to ensure there is enough rejuvenator in capsules when cracks appear in asphalt pavement. In this paper, the crack resistance of self-healing microcapsules in asphalt pavement was evaluated. Firstly, an expanding multi-scale analysis was conducted based on proposed mesoscopic mechanical models with the aim to determine the mechanical parameters for the following contracting multi-scale analysis. Secondly, the periodic boundary condition was introduced for the contracting multi-scale analysis and the stress field of the capsule wall was obtained. Finally, the effects of the design parameters of the microcapsule on its crack resistance in asphalt pavement were investigated. The results showed that the incorporation of microcapsules has almost no effect on the elastic constants of the asphalt mixture. The core could be simplified as an approximately incompressible solid with the elastic constants determined by the proposed mesoscopic mechanical model. With the increase of the modulus of the capsule wall, the mean maximum tensile stress of the capsule wall increased from 0.372 MPa to 0.465 MPa, while with the decrease of the relative radius of the capsule core, the mean maximum tensile stress of the capsule wall increased from 0.349 MPa to 0.461 MPa. The change in the mean maximum tensile stress of the capsule wall caused by the change of capsule diameter was within 5%. The relative radius of the capsule core and the elastic modulus of capsule wall were two key parameters in capsule design. Besides, the microcapsules with the wall made of resin would not crack under the vehicle load before microcracks occurred in asphalt pavement.