Selcan Demir

Background: Gastrointestinal (GI) involvement is a clinically relevant but still incompletely characterized manifestation of pediatric Behcet’s disease (PedBD). This systematic review provides a focused analysis of GI involvement in PedBD (addressing its frequency, clinical symptomatology, anatomical/endoscopic features, and therapeutic management) as a dedicated sub-analysis of a broader systematic review. Methods: A systematic search of MEDLINE, EMBASE, CINAHL, CENTRAL, and ClinicalTrials.gov was conducted, following PRISMA 2020 guidelines. Observational studies reporting GI involvement in patients with PedBD (disease onset before 16 years of age) were included, and data on frequency, symptoms, anatomical/endoscopic findings, and treatment of GI-PedBD were extracted and synthesized. Results: Thirty studies were included. Most studies were not focused on GI manifestations in PedBD as a (primary) study aim. The frequency of GI involvement ranged widely across the selected articles with a median of approximately 15% among studies with ≥50 pediatric BD patients. Abdominal pain and diarrhea were the most consistently reported symptoms. Endoscopic data indicated frequent involvement of the ileocecal region and terminal ileum, with mucosal ulcers and erosions as the predominant findings. Therapeutic data specific to GI-PedBD were limited to two studies only. As an appendix to the systematic review in the discussion, relevant case reports were described: anti-TNF agents, particularly adalimumab, showed favorable outcomes in refractory cases. Conclusions: GI involvement in PedBD is not negligible and can be severe. Its clinical and endoscopic characterization remains incomplete due to substantial heterogeneity in reporting practices across studies. Anti-TNF agents may represent an effective therapeutic option, especially for refractory GI-PedBD. Prospective and multicenter studies with standardized GI assessment protocols are needed to better characterize this clinically relevant subgroup of PedBD patients.

Objective: Behçet’s disease (BD) is a variable-vessel vasculitis with multisystemic involvement. Although cytokine dysregulation has been extensively investigated, data on angiogenic and vascular marker profiles remain limited in pediatric BD. This exploratory study aimed to characterize circulating vascular and inflammatory mediator profiles in pediatric BD, compare them with deficiency of adenosine deaminase 2 (DADA2) and polyarteritis nodosa (PAN). It further aimed to assess whether these markers were associated with vascular or central nervous system (CNS) involvement in BD. Methods: Serum samples from BD (n=34), DADA2 (n=20), PAN (n=10), and healthy controls (n=8) were analyzed for thirteen vascular and inflammatory markers (TIE1, TIE2, FLT1, sT2, RAGE, CD40L, LIGHT, PlGF, TNF-α, IL-6, IL-10, IL-18, MCP-1) using a multiplex bead-based immunoassay. Statistical analyses included Kruskal–Wallis and Mann–Whitney U tests for group comparisons, logistic and linear regression for associations with clinical features, and Spearman correlation to explore interrelations among markers. Results: TIE2 levels were significantly reduced in BD compared with healthy controls (p=0.010). DADA2 patients exhibited a distinct angiogenic–inflammatory profile, with significantly elevated levels of TIE1, TIE2, FLT1, TNF-α, IL-10, IL-18, and MCP-1 (all p<0.010) compared with both BD and PAN. None of the circulating markers independently predicted vascular or CNS involvement in BD. Strong positive correlations among angiogenic mediators (FLT1, PlGF, LIGHT) suggested a coordinated vascular signaling pattern, particularly in DADA2. Conclusion: Although individual circulating mediators showed limited discriminatory performance across vasculitis subtypes, DADA2 displayed a more distinct vascular-inflammatory profile characterized by TNF-α- and TIE2-related pathways. In pediatric BD, reduced TIE2 may reflect altered endothelial homeostasis, although this finding should be interpreted cautiously. These results support the need for integrated multi-marker approaches and longitudinal sampling to better define vascular-immune phenotypes in pediatric vasculitis.

Objectives: Behçet’s disease (BD) is a multisystemic inflammatory disease, and its neurologic involvement represents serious manifestations. This study aimed to elucidate the neurologic manifestations of BD in a large paediatric population and to describe its outcomes and prognosis. Methods: This retrospective multicentre study included 75 paediatric patients diagnosed with neuro-Behçet’s disease (NBD). Demographic data, clinical features, neuroimaging findings, treatments and disability conditions were reviewed. Results: Neurologic manifestations were observed in 52 patients (69.3%) at initial presentation and in 23 patients (30.7%) at a median of 14 months (8–30) after diagnosis. The distribution of NBD subgroups was as follows: 56 patients (74.7%) with nonparenchymal, 15 patients (20%) with parenchymal and 4 patients (5.3%) with mixed forms. Headache, observed in 70 patients (93.3%), was the most common neurological symptom, being significantly more frequent in the non-parenchymal form (P = 0.028). Paresis, sensory loss and mood/mental health problems were significantly more frequent in the parenchymal form (P = 0.034, P = 0.016, P = 0.005, respectively). Neuroimaging revealed parenchymal lesions in 19 patients (25.3%), and vascular lesions were in 55 patients (73.3%). Azathioprine was the most commonly used immunosuppressor therapy (78.7%). The median follow-up duration of patients was 30 months (17.5–52.5), during which significant clinical improvement was observed, with no deaths reported. Conclusion: Paediatric NBD remains a significant issue in paediatric rheumatology. The non-parenchymal subgroup is the predominant form in children. Paediatric NBD should be confirmed and classified by MRI. The early aggressive immunosuppressive therapy provides clinical improvement. Activity and disability indexes are valuable for treatment and follow-up.

Objectives The aim of this study was to describe the cutaneous manifestations of patients with autoinflammatory bone diseases and to evaluate the relationship between cutaneous manifestations, bone involvement, and systemic inflammation in Turkish children. Methods This retrospective multicenter study was conducted in nine pediatric rheumatology centers between the years 2013 and 2023 in patients with a diagnosis of autoinflammatory bone disease with cutaneous manifestations. Demographic data, laboratory findings, cutaneous manifestations, bone involvement, and treatments were recorded. Results Two hundred and sixty-nine autoinflammatory bone disease patients were evaluated. Fifty-one patients with cutaneous manifestations (46 CRMO and five Majeed syndrome) were included in this study. The mean diagnostic delay was 16.1 ± 11.7 months in those with cutaneous manifestations and 25.3 ± 9.9 months in those with bone involvement (p = 0.02). The most common skin lesions were acne (n = 26), pustules (n = 23), and papules (n = 10). Patients with acne had more frequent male sex and higher ESR and CRP levels (p = 0.01, p = 0.03, and p = 0.04, respectively). Patients with pustules had a younger age at symptom onset and age at diagnosis and higher ESR and CRP levels (p = 0.04, p = 0.04, p = 0.04, p = 0.02, p = 0.03, respectively). In patients with CRMO, the mean time to remission was 2.1 ± 0.7 years for cutaneous manifestation and 2.9 ± 1.4 years for bone involvement (p = 0.04). Conclusion Skin lesions may appear before bone lesions in autoinflammatory bone diseases, serving as an important early warning sign for diagnosis. Lesions such as acne and pustules are more common in these conditions and may contribute to the severity of inflammation in autoinflammatory bone diseases. Key Points • Skin lesions, most commonly acne and pustules, are frequently observed in autoinflammatory bone diseases. • It would be appropriate to closely monitor skin involvement to manage the disease and inflammation.

Introduction/objectives Syndrome of undifferentiated recurrent fever (SURF) is an autoinflammatory disorder that is recognised in an increasing number of patients. In this study, we aimed to assess the data of SURF patients from the main reference centres in our country. Methods Data for this retrospective multicentre observational cohort study were obtained from the records of SURF patients aged 0–18 years who were followed up in 10 pediatric rheumatology clinics in Türkiye between 2010 and June 2023. Patients with recurrent fever that could not be explained by periodic fever, aphthous stomatitis, pharyngitis and adenopathy (PFAPA) and hereditary recurrent fevers and had no other cause were included in the study. Results Of the 134 patients included in the study, 74 (55.2%) were male. The median age at diagnosis was 67 months. The most common symptom was abdominal pain in 98 (73.1%), arthralgia in 82 (61.2%), malaise in 77 (57.5%). The age at symptom onset was ≤ 5 years in 109 patients (81.3%). Pharyngitis was more common symptom in children aged ≤ 5 years (p = 0.008), headache, arthralgia, chest pain were more common findings in children > 5 years (p = 0.008, p = 0.032, p = 0.045). There were 113 patients receiving colchicine alone or in combination therapy and 74.3% of them achieved complete or partial remission. The presence of abdominal pain (p = 0.021, OR = 0.254) increased the remission rate with colchicine. Conclusion SURF patients present with a wide range of clinical manifestations. Distinguishing between SURF and PFAPA is not concrete. Further omics studies will enlighten whether there is a true group of SURF. Key Points • SURF is an autoinflammatory disease that is becoming increasingly recognised. • The clinical manifestations of SURF are quite heterogeneous. • Colchicine and anti-IL-1 treatment is effective in most SURF patients. • It is controversial whether it should be called SURF or PFAPA-like syndrome, especially in children aged ≤ 5 years.

Objective: This nationwide, multicenter study was conducted to assess the demographic and clinical features, treatment regimens, and prognosis of primary Sjögren disease (SjD) in childhood. Methods: This retrospective study included a total of 81 patients < 18 years of age from 21 pediatric rheumatology centers. Among these, 51 patients fulfilled the diagnosis of childhood SjD according to the 2016 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria. The remaining 30 patients—who did not fully meet these criteria but exhibited clinical and laboratory findings suggestive of SjD—were categorized as at risk for childhood SjD to highlight diagnostic challenges and the spectrum of early presentations, based on comprehensive clinical evaluation by experienced pediatric rheumatologists. Results: The cohort consisted of 81 patients (85.2% female, 14.8% male) with a median age at symptom onset of 11.4 years and a median follow-up of 24 months. Common clinical manifestations included dry mouth, dry eyes, arthralgia, fatigue, and parotitis. Fifty-one of the 81 patients met the 2016 ACR/EULAR classification criteria, whereas the remaining 30 were classified as an at-risk group. The most common clinical findings in the at-risk group were xerostomia (90%), arthralgia (56.7%), fatigue (50%), and dry eyes (43.3%). Dry mouth and peripheral nervous system involvements were found to be higher in patients categorized as at risk ( P = 0.03 and P = 0.02, respectively). Conclusion: The current classification criteria for childhood SjD appear to be inadequate, highlighting the need for pediatric-specific criteria that more accurately reflect the distinct clinical patterns observed in children.

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.