Hatice Dilara Karakaş

To determine the frequency of malnutrition, including undernutrition and overnutrition, in pediatric patients with familial Mediterranean fever (FMF), and to assess the impact of colchicine treatment on nutritional outcomes and factors associated with malnutrition. The medical records of patients with FMF who were followed up in our pediatric rheumatology clinic between 2011 and 2024 were reviewed. Patients were divided into 3 groups according to their nutritional status: normal, undernutrition and overnutrition. Demographic and clinical characteristics and disease severity were compared before and after treatment. The international severity scoring system for FMF (ISSF) was used to assess disease severity. This retrospective study included 532 (50.6% female) pediatric patients with a median (IQR) age at diagnosis of 6.5 (6) years. Malnutrition was detected in 32.7% of patients at the time of diagnosis, after colchicine treatment this rate declined to 20.7%, significant reductions in undernutrition (from 23.5% to 12.8%) and marginal improvements in overnutrition (from 9.2% to 7.9%) (p < 0.001) groups were observed. The ISSF was significantly higher in both the undernutrition and overnutrition groups compared to patients with normal nutritional status before and after colchicine treatment (p < 0.001). A severe disease phenotype and malnutrition at the time of diagnosis were identified as significant risk factors for persistent malnutrition (p < 0.001). Malnutrition, including undernutrition and overnutrition, is a common condition in pediatric FMF patients that can be improved with colchicine. The presence of malnutrition at diagnosis and a more severe disease phenotype seemed to be the most important determinants of persistent malnutrition.

A subset of genetic conditions, particularly skeletal dysplasias, comprises a heterogeneous group of inherited disorders characterized by abnormal bone development, joint stiffness, and short stature. Their musculoskeletal manifestations frequently mimic those of rheumatic diseases, especially Juvenile Idiopathic Arthritis (JIA), complicating accurate diagnosis. We conducted a comprehensive clinical, radiological, and molecular evaluation of 47 individuals (23 males, 24 females) from 22 distinct families who presented primarily with non‐inflammatory musculoskeletal complaints. Genomic investigations included targeted next‐generation sequencing panels, chromosomal microarray analysis, and multiplex ligation‐dependent probe amplification. Pathogenic or likely pathogenic variants were identified in all cases, establishing the following diagnoses: Hereditary Multiple Exostoses (n = 9), Camptodactyly‐Arthropathy‐Coxa Vara‐Pericarditis syndrome (n = 12), Progressive Pseudorheumatoid Dysplasia (n = 7), Trichorhinophalangeal Syndrome types I/II (n = 5), Spondyloenchondrodysplasia with Immune Dysregulation (n = 6), Pseudoachondroplasia (n = 3), Primary Hypertrophic Osteoarthropathy type 1 (n = 1), Ehlers–Danlos Syndrome (n = 2), Multicentric Osteolysis‐Nodulosis‐Arthropathy (n = 1), and Mucopolysaccharidosis type VI (n = 1). Certain genetic disorders may present with musculoskeletal manifestations that closely resemble those of rheumatic diseases. Therefore, a comprehensive evaluation for underlying genetic causes is essential in patients with non‐inflammatory skeletal findings, as it improves diagnostic precision and guides appropriate management strategies. This study aims to investigate the clinical and molecular features of patients with non‐inflammatory musculoskeletal involvement, with a particular focus on the phenotypic overlap between genetic disorders and rheumatic diseases. Furthermore, seven novel variants were identified, expanding the mutational spectrum associated with these rare conditions and contributing new insights to the existing literature.

Objectives: This study aimed to evaluate the predictability of the homozygous M694V genotype in paediatric FMF patients and to develop a clinical scoring system to enhance disease management strategies. Methods: This nationwide, multicentre, cross-sectional study included 3981 paediatric FMF patients with biallelic pathogenic variants in exon 10 of the Mediterranean fever gene. Patients were divided into two groups: group 1 (homozygous M694V) and group 2 (other variants). Data were collected from 37 paediatric rheumatology and/or nephrology clinics across Türkiye, covering patients followed between 2014 and 2023. Results: Group 1 had significantly earlier symptom onset (≤3 years: 49.8% vs 43.9%, P < 0.001) and diagnosis (median age: 5 years vs 5.8 years, P < 0.001) compared with group 2. A higher prevalence of family history of FMF was observed in group 1 (P < 0.001). Clinical manifestations, including arthritis (27.5%), erysipelas-like erythema (ELE) (20.3%) and protracted febrile myalgia syndrome (PFMS) (3.6%), were significantly more frequent in group 1 (P < 0.001 for all). Colchicine resistance was also higher in group 1 (18.1% vs 5.1%, P < 0.001). Logistic regression analysis showed that ≤3 years of age at symptom onset, family history, arthritis, myalgia, PFMS, ELE and splenomegaly were independent predictors of the homozygous M694V genotype. A clinical scoring system was proposed based on these findings. Conclusion: This study provides valuable insights into the clinical predictors of the homozygous M694V genotype in paediatric FMF. The proposed scoring system will support clinicians in prognosis assessment and treatment planning, contributing to improved patient outcomes.

Objective: Familial Mediterranean fever (FMF) is the most prevalent hereditary autoinflammatory disease among children. Abdominal pain and various gastrointestinal system (GIS) manifestations may arise directly from FMF or concomitantly with FMF. This study aimed to evaluate GIS complaints and findings other than classic peritonitis attacks in patients with FMF and to interpret concomitant GIS and hepatic disorders in these patients. Methods: The medical and genetic findings of patients with FMF who attended our clinic between December 2011 and December 2021 were reviewed. Gastrointestinal system symptoms, liver function tests, abdominal images, and endoscopic and histopathological data were extracted from medical records. Results: A total of 576 pediatric patients (female, 52.3%) diagnosed with FMF were included. Among them, almost one-fifth displayed GIS complaints, such as abdominal pain, defecation problems, and dyspepsia, distinct from typical FMF attacks. High serum aminotransferase levels were detected in 18.4% of the patients, with viral infections being the most common cause of moderate/severe hypertransaminasemia. In addition, during follow-up, 26.9% of them were referred to the pediatric gastroenterology department. At least 1 gastroenterological and hepatobiliary disorder was detected in 17.5% of the patients because of organic and functional GIS disorders or hepatobiliary disorders, such as gastroesophageal reflux disease, esophagitis, functional dyspepsia, and inflammatory bowel diseases. Conclusion: Various GIS and hepatic disorders can be encountered in children with FMF. The spectrum of these complaints and pathologies can range from frequently observed health problems to more severe diseases.

Objective: Erysipelas-like erythema is the pathognomonic skin manifestation of familial Mediterranean fever although not frequently seen in the pediatric population. This study aims to describe the differences between patients presenting with and without erysipelas-like erythema and to examine the relation of erysipelas-like erythema with subclinical inflammation in a large pediatric cohort of familial Mediterranean fever patients. Materials and Methods: This retrospective study from a single pediatric rheumatology referral center included familial Mediterranean fever patients with a follow-up for at least 6 months in the last 5 years. Patients were grouped according to the presence of erysipelas-like erythema and subclinical inflammation. Results: Among 515 patients with familial Mediterranean fever, 35 patients (6.8%) were found to present with erysipelas-like erythema, and the earliest age for erysipelas-like erythema was 2.9 years. All erysipelas-like erythema lesions were defined on lower extremities with concurrent arthritis in 21 patients (60.0%). Compared to other patients in the cohort, patients presented with erysipelas-like erythema had significantly higher frequencies of acute arthritis, subclinical inflammation, and biallelic exon 10 mutations, and they used significantly higher doses of colchicine at the latest visits (all P ≤ .002). Patients with subclinical inflammation more frequently presented with erysipelas-like erythema compared to others without subclinical inflammation (21.7% vs. 2.9%, P < .001). Conclusion: Erysipelas-like erythema is an uncommon but important finding that can be a sign of severe disease course and subclinical inflammation in the pediatric population with familial Mediterranean fever. Cite this article as: Avar-Aydın PÖ, Özçakar ZB, Aydın F, Karakaş HD, Çakar N, Yalçınkaya F. Erysipelas-like erythema: A manifestation of severe disease phenotype in pediatric patients with familial mediterranean fever. Turk Arch Pediatr. 2022;57(6):599-602.

Objective: Interleukin-1 inhibitors are effective agents used in colchicine resistance or intoler- ance during the treatment of familial Mediterranean fever. This study aims to review the char- acteristics of patients treated with interleukin-1 inhibitors and their long-term follow-up in a large pediatric cohort of familial Mediterranean fever patients. Materials and Methods: The study was conducted in a pediatric rheumatology reference cen- ter. The patients treated with interleukin-1 inhibitors for at least 6 months were included and compared to other patients with familial Mediterranean fever. Clinical and laboratory charac- teristics of the cohort were recorded. Results: Among 542 patients with familial Mediterranean fever, 6.1% (n = 33) were treated with interleukin-1 inhibitors. Colchicine resistance was the reason in 82.8% and renal amyloidosis in 17.2% of the patients. Patients with interleukin-1 inhibitors had earlier disease onset and higher frequencies of acute arthritis, chest pain, and erysipelas-like erythema with pathogenic exon 10 mutations of the MEFV gene (all P < .04). All patients diagnosed with renal amyloidosis also received interleukin-1 inhibitors. Six patients were switched from anakinra to canakinumab or vice versa to control ongoing disease activity. Attack frequency was reduced in all patients. Conclusion: Interleukin-1 inhibitors are used in a relatively small number of pediatric patients with familial Mediterranean fever. Patients presenting with earlier disease onset, acute arthri- tis, chest pain, and erysipelas-like erythema and carrying pathogenic exon 10 mutations of the MEFV gene may show a higher need for interleukin-1 inhibitors. In pediatric familial Mediterranean fever patients who are resistant to colchicine, interleukin-1 inhibitors seem to be highly effective agents. Cite this article as: Avar Aydın PÖ, Özçakar ZB, Aydın F, Karakaş HD, Çakar N, Yalçınkaya F. The characteristics of pediatric patients with familial mediterranean fever treated with anti-interleukin-1 treatment. Turk Arch Pediatr. 2022;57(4):448-452.

Introduction Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease that can present with various forms of arthritis. This retrospective study aims to evaluate the characteristics of patients with arthritis in a large pediatric cohort of FMF patients. Methods The demographic and clinical data were extracted from electronic medical records. Patients with arthritis were grouped as arthritis of FMF and arthritis of FMF-associated diseases. Results A total of 541 patients were followed with a diagnosis of FMF in the last 5 years. Acute arthritis of FMF (n: 138) was the most common cause. It showed a recurrent course in the majority with a longer duration than other attack symptoms. Significantly higher frequencies of biallelic exon 10 and M694V mutations, erysipelas-like erythema, and protracted febrile myalgia were detected in these patients, particularly in those older than 2 years of age. Sacroiliitis of FMF was the second most common cause (n: 19). Patients with acute arthritis and sacroiliitis of FMF needed higher doses of colchicine. One patient with neonatal-onset FMF and M694V homozygosity was diagnosed with protracted arthritis. Arthritides of FMF-associated diseases including IgA vasculitis (n: 10), juvenile idiopathic arthritis (n: 9), chronic nonbacterial osteomyelitis (n: 5), and inflammatory bowel disease (n: 2) were detected in 26 patients. Conclusions Arthritis is an important clinical finding of FMF mostly associated with M694V mutations. The frequency of protracted arthritis is declined, whereas sacroiliitis of FMF and arthritis of associated diseases expand the spectrum of arthritis. This study represents the changing face and current perspectives of arthritis in FMF. Key Points • Arthritis is an important clinical finding of familial Mediterranean fever (FMF) that can present in various forms • Arthritis is most likely associated with M694V mutations • The frequency of protracted arthritis is declined whereas sacroiliitis of FMF and arthritis of associated diseases expand the spectrum of arthritis in FMF