BACKGROUND: Nintedanib, a tyrosine kinase inhibitor with antifibrotic properties, has been shown to significantly slow the progression of pulmonary fibrosis. The aim of this study is to assess the clinical characteristic...BACKGROUND: Nintedanib, a tyrosine kinase inhibitor with antifibrotic properties, has been shown to significantly slow the progression of pulmonary fibrosis. The aim of this study is to assess the clinical characteristics, longitudinal pulmonary function tests, serial high-resolution computed tomography (HRCT) findings, and the efficacy, tolerability, and outcomes of nintedanib treatment in patients with systemic autoimmune rheumatic disease-associated interstitial lung disease (SARD-ILD) within a Middle Eastern population. PATIENTS AND METHODS: This is a cohort study conducted between May 2015 and March 2024, all patients with SARD-ILD treated with nintedanib were analyzed. Demographic and clinical data were collected before the initiation of nintedanib. Serial changes in percentage predicted forced vital capacity (ppFVC) and percentage predicted diffusing capacity for carbon monoxide (ppDLCO), as well as HRCT findings, were recorded at 6, 12, and 24 months posttreatment initiation. Adverse events of nintedanib were documented. Descriptive statistics were employed for data analysis. RESULTS: A total of 47 patients with SARD-ILD received nintedanib. The most common diagnoses were systemic sclerosis (36.2%) and rheumatoid arthritis (17%). Over 24 months, patients showed stable or slightly improved ppFVC and ppDLCO values, and 89% had stable ILD on HRCT. Gastrointestinal adverse events were reported in 27.7% of patients. Five patients (10.6%) underwent lung transplantation, with an average time of 3.2 ± 2.2 years from treatment initiation to transplantation. CONCLUSION: Our findings indicate that nintedanib is well-tolerated, with no new safety concerns identified. In addition, we observed clinically meaningful improvements in pulmonary function tests by 6 months, which were sustained through 24 months.
BACKGROUND/OBJECTIVE: Relapses occur in 14% to 44% of patients with antineutrophil cytoplasm antibody-associated vasculitis (AAV). The French Vasculitis Study Group Relapse Score (FRS) was recently proposed to predict re...BACKGROUND/OBJECTIVE: Relapses occur in 14% to 44% of patients with antineutrophil cytoplasm antibody-associated vasculitis (AAV). The French Vasculitis Study Group Relapse Score (FRS) was recently proposed to predict relapse risk. This study aimed to identify relapse-associated factors and evaluate the FRS performance in a Mexican cohort. PATIENTS AND METHODS: We performed a medical records review study including patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) who were followed for ≥12 months at a Mexican tertiary care center. Demographic, clinical, laboratory, and treatment data were analyzed using descriptive statistics, survival analysis, and ROC curves. RESULTS: Among 147 patients (110 GPA, 37 MPA), the median age at diagnosis was 49 years (IQR: 36 to 59). Over a median follow-up of 93 months (IQR: 48 to 152), 90 patients (61%) relapsed. Cumulative relapse rates at 12, 24, 36, 48, and 60 months were 13.6%, 32.3%, 40.3%, 47.5%, and 58.0%, respectively. FRS scores of 1, 2, and 3 corresponded to median relapse-free survivals of 85, 68, and 33 months, with 5-year relapse risks of 40.5%, 48.4%, and 68.3%, respectively. Discrimination was significant (log-rank p < 0.0004). The C-statistic for FRS alone was 0.648 (95% CI: 0.586-0.710); for model 1 (adding cluster 4), 0.666 (95% CI: 0.605-0.728); and for model 2 (adding cluster 4 and rituximab as maintenance), 0.700 (95% CI: 0.643-0.757). An age cutoff of ≤50 years showed better accuracy (AUC: 0.67, p = 0.0006) for relapse prediction. CONCLUSIONS: In this cohort, relapses were frequent. Incorporating clinical clusters and rituximab therapy to the FRS may enhance its predictive performance.
BACKGROUND: Cytomegalovirus (CMV) infection is prevalent in patients with anti-melanoma differentiation-associated 5 gene antibody-positive dermatomyositis (MDA5 + DM) and affects the prognosis. This study aimed to evalu...BACKGROUND: Cytomegalovirus (CMV) infection is prevalent in patients with anti-melanoma differentiation-associated 5 gene antibody-positive dermatomyositis (MDA5 + DM) and affects the prognosis. This study aimed to evaluate the efficacy of valganciclovir prophylaxis during MDA5 + DM treatment. METHODS: Adult patients with active MDA5 + DM were consecutively recruited from May 1, 2023 to December 31, 2023, and followed up for 6 months. Participants were categorized into 2 groups based on whether they received valganciclovir or not. The incidence of CMV infection and changes in disease activity were analyzed. RESULTS: This study included 49 patients with active MDA5 + DM. Prophylaxis with valganciclovir was administered to 18 patients, including 9 patients with rapidly progressive interstitial lung disease (RP-ILD). Of the remaining 31 patients, 15 had RP-ILD. During the follow-up, no CMV infection, discomfort, or abnormal laboratory findings associated with valganciclovir were observed during the prophylaxis period. Nine patients in the control group were infected with CMV ( p = 0.032). In the survival analysis, 2 and 9 patients with RP-ILD died in the valganciclovir and control groups, respectively ( p = 0.084). No significant difference in disease activity and glucocorticoid dosage was observed between two groups at 3 and 6 months. Furthermore, the use of biological and targeted synthetic disease-modifying antirheumatic drugs at the initiation of treatment was identified as a risk factor for CMV infection in active MDA5 + DM patients in the control group ( p = 0.007). CONCLUSION: Prophylaxis with valganciclovir can reduce the incidence of CMV infection during MDA5 + DM treatment. It exerts a potential auxiliary effect on MDA5 + DM treatment.
BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is life-threatening for immunocompromised patients. No consensus exists on PJP prophylaxis for immunosuppressed patients without HIV, transplant, or cancer. METHODS: We...BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is life-threatening for immunocompromised patients. No consensus exists on PJP prophylaxis for immunosuppressed patients without HIV, transplant, or cancer. METHODS: We retrospectively reviewed the electronic health records of adult immunosuppressed patients with PJP diagnosed between 1990 and 2020 at Mayo Clinic. Patients with HIV, solid organ transplants, or cancer were excluded. Demographic data, treatments, and outcomes were manually abstracted. RESULTS: The most common indications for immunosuppression were rheumatoid arthritis (19.7%), vasculitis (18.1%), and interstitial lung disease (ILD) not related to connective tissue disease (17.6%). Despite having high risk of PJP, 86.0% of patients did not receive PJP prophylaxis. Corticosteroids were the most common immunosuppressive agent used (84.5%), with 64.4% of patients receiving high-dose treatment. Nonbiologic disease-modifying antirheumatic drugs were used for 49.7%, including methotrexate (51.0%), azathioprine (22.9%), and hydroxychloroquine (11.5%). Biologics were prescribed for 25.4%, primarily rituximab (59.2%) and infliximab (22.4%). Hospitalization occurred for 76.7% of patients; 70.3% required intensive care unit (ICU) admission, and 46.6% received mechanical ventilation. The in-hospital mortality rate was 30.4% overall and 53.6% for patients on ventilation. Predictors of death included ILD [odds ratio (OR), 4.61; 95% CI, 1.75-13.00], ICU admission (OR, 3.60; 95% CI, 1.19-11.08), and ventilator use (OR, 3.46; 95% CI, 1.30-9.79). Biologic use was associated with lower odds of death (OR, 0.34; 95% CI, 0.11-0.89). CONCLUSIONS: Most patients in our cohort did not receive PJP prophylaxis, and outcomes were poor with high mortality rates. Standardized risk stratification and prophylaxis protocols are needed to improve outcomes.
BACKGROUND/OBJECTIVE: The framework for the study centered on the treatment decisions made by physicians during their medical encounters with patients with rheumatic diseases. Our primary objective was to analyze, from a...BACKGROUND/OBJECTIVE: The framework for the study centered on the treatment decisions made by physicians during their medical encounters with patients with rheumatic diseases. Our primary objective was to analyze, from a bioethical perspective, the underlying latent factors that influence these treatment decisions, focusing on the physician motivations behind them. METHODS: This cross-sectional study was carried out at an outpatient clinic where 14 certified rheumatologists and 10 trainees worked (February 2023-February 2024). Standardized data from 703 patient-physician encounters regarding the physician's treatment choice, their motivations, and patients' disease activity level were obtained. Exploratory factorial analysis defined how motivations integrate latent factors and structure treatment choices in various health care scenarios, defined by the physician choice and degree and the patient level of disease activity. RESULTS: The patients were primarily middle-aged women with long-standing rheumatic diseases. Certified rheumatologists and trainees were primarily females. The factorial analysis revealed a 4-factor structure in the majority of the health care scenarios; these latent factors accounted for 54.6% to 65.4% of total variance. The first factor ("Medications shortage and uncertainty") explained the largest percentage of total variance of the treatment choice; this factor violates justice principle. The second factor ("Patient-centered") was associated with motivations related to the patient's sociodemographics, clinical aspects, and preferences, which is related to autonomy principle. The third factor ("Accessibility and affordability") impacts justice principle. The fourth factor ("Evidence-based medicine and experience") was related to beneficence and nonmaleficence principles. CONCLUSIONS: Making treatment decisions is influenced by factors that shape the ethical lattice physicians based their decisions upon.
BACKGROUND/OBJECTIVE: The DANGER (Death in ANCA Glomerulonephritis-Estimating the Risk) score was developed to assess mortality risk in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). This...BACKGROUND/OBJECTIVE: The DANGER (Death in ANCA Glomerulonephritis-Estimating the Risk) score was developed to assess mortality risk in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). This study aimed to validate score in a cohort of Latin American patients. METHODS: This cohort study included patients with AAV evaluated between 2000 and 2022. The DANGER score was calculated, and its performance evaluated using the c-statistic and time-dependent area under the receiver operating characteristic curve. Multivariable Cox regression analysis was performed to identify variables that could enhance the score's predictive accuracy. RESULTS: We included 154 patients, 104 (68%) female, with a median age of 52 years (interquartile range [IQR], 38-61 years) and creatinine of 2.5 mg/dL (IQR, 1.7-2.5 mg/dL). Over a median follow-up of 74 months (IQR, 32-126 months), 24 patients died, with mortality rates of 6.5%, 8.6%, and 11.9% at 1, 2, and 5 years, respectively. The leading cause of death was infection. Mortality rates at 1 and 3 years in the low-, intermediate-, and high-risk categories were 1.0% and 3.1%, 14.0% and 16.8%, and 40.0% and 70.0%, respectively. The overall c-statistic for the DANGER model was 0.81 (95% confidence interval [CI], 0.73-0.90), with areas under the receiver operating characteristic curve of 0.81 (95% CI, 0.70-0.91), 0.78 (95% CI, 0.67-0.89), and 0.80 (95% CI, 0.70-0.90) at 1, 3, and 5 years, respectively. A revised model incorporating age, creatinine, C-reactive protein, and pulmonary involvement had a c-statistic of 0.86 (95% CI, 0.79-0.94). CONCLUSIONS: The DANGER score has good predictive accuracy for mortality in AAV patients with kidney involvement. In younger patients, the score may be modified to include variables such as C-reactive protein and severe pulmonary involvement to enhance its performance.
BACKGROUND: To compare the clinical features and disease severity of classic polyarteritis nodosa (PAN) with its monogenic form, deficiency of adenosine deaminase 2 (DADA2), in pediatric patients, in order to distinguish...BACKGROUND: To compare the clinical features and disease severity of classic polyarteritis nodosa (PAN) with its monogenic form, deficiency of adenosine deaminase 2 (DADA2), in pediatric patients, in order to distinguish overlapping vasculitic phenotypes. METHODS: This cross-sectional study included 36 pediatric patients with PAN-like vasculitis, comprising 22 with classic PAN (14 systemic, 8 cutaneous) and 14 with DADA2, followed up at our tertiary referral pediatric rheumatology department between August 2016 and February 2025. Demographic features, clinical manifestations, treatment choices, and outcomes were compared between the groups. RESULTS: DADA2 patients had significantly earlier symptom onset (median 4 vs. 11 years, p = 0.002) and higher rates of parental consanguinity ( p < 0.001) compared with systemic PAN (sPAN) patients. The most common clinical features in sPAN were constitutional symptoms (100%), followed by cutaneous (78.6%), musculoskeletal (57.1%), and renal involvement (57.1%). Growth retardation (14.3% vs. 57.1%, p = 0.018) and livedo racemosa (7.1% vs. 50%, p = 0.012) were more common in DADA2, whereas fatigue (92.9% vs. 35.7%, p = 0.002), renal involvement (57.1% vs. 0%, p < 0.011), diastolic hypertension (78.6% vs. 7.1%, p < 0.001), and purpura (35.7% vs. 0%, p = 0.014) predominated in PAN. Neurological manifestations were observed in 4 PAN patients (2 peripheral, 2 central) and 1 DADA2 patient with ischemic stroke. Biologic therapy was required in 4 PAN patients, whereas 11 of 14 DADA2 patients were treated with anti-tumor necrosis factor agents. CONCLUSION: Anti-TNF therapy remains the mainstay of treatment in DADA2 and is effective in preventing disease progression. In contrast, classic sPAN may require escalation to biologic agents in refractory cases or when neurologic or end-organ involvement is present.
OBJECTIVE: We aim to evaluate the clinical features, first-year treatment response, and frequency of adverse events in Mexican patients receiving Janus kinase inhibitor (JAK-i) using data from the Mexican Adverse Events...OBJECTIVE: We aim to evaluate the clinical features, first-year treatment response, and frequency of adverse events in Mexican patients receiving Janus kinase inhibitor (JAK-i) using data from the Mexican Adverse Events Registry (BIOBADAMEX). METHODS: We included all BIOBADAMEX patients from 2022 to 2024 and described the sociodemographic, clinical, treatment characteristics and adverse events of the approved JAK-i in Mexico: tofacitinib, baricitinib, and upadacitinib. We assessed the JAK-i efficacy comparing baseline and the 1-year response mean disease activity scores. RESULTS: A total of 222 patients were included, 39.6% received tofacitinib, 47.3% baricitinib, and 13.1% upadacitinib. The most common diagnosis was rheumatoid arthritis (77%). Sixty-eight percent of patients had comorbidities, 6% had prior history of malignancy, and 57% previously used a biologic. Mean age at JAK-i initiation was 49.6 (±13.9) years with an overall latency period of 9.4 years. DAS28 (Disease Activity Score in 28 joints) reduced from 4.7 (±1.2) at baseline to 2.99 (±1.2) in the first year ( p = 0.001), and Bath Ankylosing Spondylitis Disease Activity Index from 4.8 (±3.9) to 2 (±1.5). JAK-i withdrawal was 29%; nonmedical reasons were the main motive. Sixty-five adverse events were reported; all were nonsevere with only 1 case of herpes zoster and no reports of malignancy or thrombosis. Differences in clinical and treatment characteristics between JAK-i were found. CONCLUSIONS: Our study showed older age for JAK-i initiation, a lower overall latency period, and lower use of prior biologic disease-modifying antirheumatic drug when compared with existing data in the literature. The main motive for JAK-i withdrawal was nonmedical reasons. Adverse events were nonsevere; interestingly, there was only 1 case of herpes zoster and no reports of malignancy or thrombosis.
Contreras-Yáñez I, Guaracha-Basañez GA, Sánchez-Peralta ES
… +5 more, Alarcón-Jarquín MI, Ledón-Llanes L, Sánchez-Hernández A, Flores-Alvarado DE, Pascual-Ramos V
BACKGROUND: Mistreatment adversely affects outcomes from patients with rheumatic diseases (RMDs). We previously observed that half of Mexican outpatients with RMDs perceived mistreatment. The study examines the factors a...BACKGROUND: Mistreatment adversely affects outcomes from patients with rheumatic diseases (RMDs). We previously observed that half of Mexican outpatients with RMDs perceived mistreatment. The study examines the factors associated with mistreatment. METHODS: This cross-sectional study was conducted at 2 academic urban centers for RMDs located in Mexico (June 28, 2023, to January 10, 2025). Consecutive outpatients completed the Mistreatment Scale adapted for RMDs, and additional patients reported outcome measures. Sociodemographic, disease-related variables, comorbid conditions, and treatment-related data were recorded using standardized formats. Mistreatment was defined when an individual's scale score was ≥1. If attributed to a specific RMD, it was classified as mistreatment related to RMD; this applied when a participant showed all patterns of mistreatment with a score of at least 1, linked to the underlying RMD. Participants showing 2 or more distinct patterns fall under the multiple mistreatment category. Multivariate regression analysis was used. RESULTS: We included 746 outpatients with RMDs. Most frequent diagnoses were rheumatoid arthritis (n = 251 [34%]) and systemic lupus erythematosus (n = 240 [32%]). In the 728 patients where the mistreatment construct could be assessed, 358 (49.2%) experienced mistreatment. Among them, 109 patients (30.4%) scored mistreatment related to RMD subcategory and n = 167 (46.6%) multiple mistreatment. We found that mistreatment and its categories were linked to distinctive variables across various human spheres, including sociodemographics, physical functioning, social relationships, and psychoaffective spheres. CONCLUSIONS: Nearly 50% of the patients with RMD had the perception of mistreatment. This was linked to multiple variables including sociodemographics, physical functioning, social relationships, and mental health.
Quiñones M, Dowell S, Perez Alamino R
… +10 more, Swearingen CJ, Treadwell E, Garcia-Valladares I, Lawrence-Ford T, Lawrence-Elliott C, Ince A, Sherrer Y, Mosley-Williams A, Yazici Y, Kerr GS
OBJECTIVE: To identify differences in disease activity parameters that influence assessment, management, and outcomes of ethnic minority (EM) rheumatoid arthritis (RA) patients. METHODS: RA patients enrolled in the Ethni...OBJECTIVE: To identify differences in disease activity parameters that influence assessment, management, and outcomes of ethnic minority (EM) rheumatoid arthritis (RA) patients. METHODS: RA patients enrolled in the Ethnic Minority Rheumatoid Arthritis Consortium registry between 2010 and 2018 were studied. Comparisons among self-identified racial and ethnic subsets and associations with RA disease activity measures and thresholds for randomized controlled trial (RCT) inclusion criteria were estimated using univariable analytical methods. RESULTS: An observational cohort of 1315 RA patients of mean disease duration of 10.3 years was studied and comprised 380 (28.9%) Black, 178 (13.5%) Hispanic, and 126 (9.6%) Asian individuals. Compared with White participants, Black participants had lower socioeconomic status and, along with Hispanic participants, reported less years of education and tobacco use but greater disease activity and comorbidity. All 3 ethnic subsets had more prevalent seropositive RA with Black and Hispanic participants having less use of RA therapies compared with Asian participants who had the highest disease-modifying antirheumatic drug use. Composite disease activity measures that included a laboratory parameter found greater numbers to be in remission compared with patient-reported measures alone in the entire cohort. However, Black participants were less frequently in remission across all measures (approximately 2-fold for Disease Activity Score-28 joints with C-reactive protein vs. Disease Activity Score-28 joints with erythrocyte sedimentation rate) and more frequently met the RCT inclusion criteria. CONCLUSION: In a real-world EM RA cohort, subjective disease activity measures were discordant with objective parameters. Further, in Black participants, achieving remission criteria was dependent on laboratory assay chosen but frequently met active disease threshold eligibility for RCTs. Standardization of RA disease measures in EM patients is needed to achieve parity with current thresholds of optimum RA care.
J Clin Rheumatol
· 2025 Dec · PMID 40768558
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OBJECTIVE: The study objectives were to compare the characteristics of patients with giant cell arteritis (GCA) from nonrural and rural areas and to identify factors associated with delayed GCA diagnosis. METHODS: In thi...OBJECTIVE: The study objectives were to compare the characteristics of patients with giant cell arteritis (GCA) from nonrural and rural areas and to identify factors associated with delayed GCA diagnosis. METHODS: In this historical cross-sectional analysis, adults meeting the 2022 European Alliance of Associations for Rheumatology/American College of Rheumatology GCA classification criteria and followed at the University of Iowa rheumatology clinics from 2/1/2000 to 2/7/2024 were included. Geographic categories were defined using the 2010 Rural-Urban Commuting Area (RUCA) codes. Characteristics of nonrural (RUCA 1-3) and rural (RUCA 4-10) GCA patient groups were compared. Bivariable analyses were performed between each predictor and time to GCA diagnosis with simple linear regression. Multivariable linear regression models were fitted to identify the best predictors of time to GCA diagnosis. RESULTS: In total, 317 subjects with GCA were included in this study (mean age, 72 years; 74.8% women). Nonrural (n = 172) and rural (n = 145) subjects had similar disease manifestations, including abrupt headache, vision loss, and jaw claudication. The mean time to GCA diagnosis was significantly longer in rural compared with nonrural GCA subjects (130 ± 185 vs. 45 ± 45 days, p < 0.0001). A significantly higher rate of hospitalizations was observed among rural subjects (24.1% vs. 12.2%, p = 0.0075). Bivariable analyses identified 4 variables associated with time to GCA diagnosis. In multivariable linear regression analyses, RUCA code (β = 13.99, 95% confidence interval, 9.23 to 18.75), age, and headache provided the best fit (adjusted R2 = 0.1196, Akaike corrected information criterion = 3082, p < 0.001). CONCLUSION: Rurality was identified as the strongest predictor of delayed diagnosis in GCA. Rural patients also experienced delays in undergoing temporal artery biopsy and a higher proportion of hospitalizations.
Chloroquine has been linked to numerous adverse effects impacting several organ systems in the body. The dermatologic adverse effects of chloroquine have not been extensively analyzed in the current literature. A recent...Chloroquine has been linked to numerous adverse effects impacting several organ systems in the body. The dermatologic adverse effects of chloroquine have not been extensively analyzed in the current literature. A recent publication reviewed these effects of hydroxychloroquine, a medication with a similar composition and use as chloroquine. We conducted a narrative review of the English literature on this topic to better understand the dermatologic toxicity of chloroquine. Many of the dermatologic adverse effects associated with chloroquine use identified in this review were well tolerated or resolved after discontinuation of treatment. The most commonly reported adverse dermatologic effect of chloroquine was pruritus, with at least 464 distinct cases across 29 studies. All dermatologic reactions to chloroquine occurred within 3 months of drug initiation. Due to the varying reporting styles and methodology of studies, this analysis demonstrates the need for future studies to better elucidate the risks for dermatologic adverse effects of chloroquine regarding underlying conditions and treatment regimens. Future research should aim to identify all possible dermatologic adverse effects so that clinicians may confidently determine the risk to their patients.
OBJECTIVES: Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disorder. Data regarding the reported triggers of this rare disease are scarce. This study aimed to analyze the demographic dat...OBJECTIVES: Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disorder. Data regarding the reported triggers of this rare disease are scarce. This study aimed to analyze the demographic data, clinical findings during the attacks, reported triggering, and self-reported management strategies of pediatric patients with FMF with exon 10 MEFV mutations. METHODS: Patients diagnosed with FMF according to the Eurofever/PRINTO classification criteria, with heterozygous, homozygous, and compound heterozygous mutations in exon 10 of the Mediterranean fever ( MEFV ) gene, and with a follow-up of more than 6 months were included in the study. RESULTS: The study included 266 patients (53% female, n = 141). Reported triggers were identified in 189 patients (93.6%), and the most common trigger was fatigue (n = 141; 69.8%). The others were as follows: prolonged standing (49.5%), emotional stress (47%), cold exposure (42.6%), insomnia (36.6%), menstruation (18.5%), high-fat food consumption (15.8%), exercise (15.3%), long-term travel (13.4%), starvation (11.9%), sunlight exposure (5.4%), and physical trauma (2.5%). Self-reported management strategies were used by 89.1% (n = 180) of the patients, primarily nonsteroidal anti-inflammatory drugs (75.2%, n = 152). The others were sleep (50.5%), fluid intake (39.1%), massage (31.2%), hot water compress (30.7%), warm shower (23.3%), fat-free diet (8.4%), and sweet food consumption (5.4%). Long-term travel was found to be a significantly more commonly reported trigger for attacks with arthritis/arthralgia ( p = 0.036) and erysipelas-like erythema ( p = 0.001). CONCLUSIONS: This is the first study focused on reported triggers in childhood FMF. Although our study offers unique findings, the data require validation with clinical and laboratory evidence.