The effect of vitamin D supplementation on attacks in PFAPA syndrome patients with low vitamin D levels.

BACKGROUND-AIM: To evaluate the effect of vitamin D supplementation on the frequency and duration of attacks in patients of PFAPA syndrome with low vitamin D levels. METHODS: This retrospective study comprised PFAPA patients with vitamin D deficiency/insufficiency between 2018 and 2023. The frequency and duration of PFAPA attacks before and after vitamin D supplementation were noted. RESULTS: Seventy-one patients were included. Of the 71 patients, 24 (33.8%) had vitamin D insufficiency, and 47 (66.2%) had vitamin D deficiency. In patients with vitamin D insufficiency, mean attack frequency and mean attack duration before vitamin D supplementation were 4.3 ± 1.9/year and 2.2 ± 1.6 days, respectively, while mean attack frequency and mean attack duration after vitamin D supplementation were 3.5 ± 2.7/year per year and 1.3 ± 0.9 days respectively (p = 0.2, p = 0.2, respectively). In patients with vitamin D deficiency, mean attack frequency and mean attack duration before vitamin D supplementation were 7.4 ± 2.1/year and 2.2 ± 1.6 days, respectively, while mean attack frequency and mean attack duration after vitamin D supplementation were 3.3 ± 2.4/year and 1.3 ± 0.9 days respectively (p < 0.01, p = 0.04, respectively). When the vitamin D level and the frequency of attacks were compared, the cut-off value of vitamin D was found to be 29.7 nmol/L. CONCLUSIONS: In PFAPA patients with low vitamin D levels, the frequency and duration of PFAPA attacks were reduced with vitamin D supplementation. Especially at vitamin D level cut-off > 29.7 nmol/L, the frequency of attacks reduced significantly.

Deficiency of adenosine deaminase 2 as an unrecognized cause of early-onset stroke and cranial nerve palsy.

OBJECTIVE: The aim of this study is to evaluate the clinical, laboratory, and radiological findings and prognosis of patients with adenosine deaminase 2 deficiency (DADA2) and to highlight the conditions that DADA2 should be considered in the differential diagnosis in patients with neurological findings. METHODS: A case series of six DADA2 patients was presented in this retrospective, descriptive study. Clinical and laboratory data, treatment protocols, and prognosis of the patients were recorded. A diagnosis of DADA2 was established by ADA2 enzyme activity assay and/or ADA2 gene sequencing. RESULTS: Six patients with DADA2 were included in the study. The median age at symptom onset was 6.5 years (range 3.5-13.5 years). The median time to diagnosis from the initial presentation was 9 (3-72) months. Consanguinity was present in the families of 4 cases. The skin, nervous system, and musculoskeletal system were the most commonly involved systems. Vasculitis mimicking polyarteritis nodosa (PAN) was the predominant phenotype (n=4) in our case series. Four patients with PAN-like features had neurological involvement. Ischemic strokes were found in 3 patients, cranial nerve palsy in 2 patients, and seizures in 2 patients. The CECR1 gene was analyzed in all patients. We analyzed plasma ADA2 enzyme activity only in one patient. Anti-tumor necrosis factor (TNF)-α therapy was initiated. Inflammation was suppressed and remission was achieved in all patients. CONCLUSION: DADA2 should be considered in patients with PAN-like disease, a history of familial PAN/vasculitis, early-onset strokes/neurological involvement with systemic inflammation. Furthermore, anti-TNF-α therapy appears to be beneficial for the treatment of DADA2.

Biological Agent Switching in Patients With Juvenile Idiopathic Arthritis: A Tertiary Center Experience.

OBJECTIVE: The purpose of this study is to investigate the causes and outcomes of switching biological agents in juvenile idiopathic arthritis (JIA) patients using biological agents and compare the characteristics of patients whose biological agents are switched and those whose are not. METHODS: This medical records review study was conducted with 128 patients who were diagnosed with JIA at our clinic between January 2009 and January 2022 and were receiving biologic agents. Factors affecting the biologic agent switching were investigated. RESULTS: The JIA subtype with the most frequent switching in biological agents was systemic JIA (n = 13, 40.6%). Systemic JIA was followed by rheumatoid factor-negative polyarticular JIA and persistent oligoarticular JIA with 5 patients (15.6%), extended oligoarticular JIA and enthesitis-related JIA with 3 patients (9.3%), rheumatoid factor-positive polyarticular JIA with 2 patients (6.2%), and undifferentiated JIA with 1 patient (3.1%). Among the patients, 32 (25%) patients had their biological agent switched once, and 5 (3.9%) had theirs switched twice. The most frequently used biological agent was etanercept (n = 76, 59.3%), whereas the most frequently observed cases of biological agent switching were from an anti-TNF agent to another anti-TNF agent (40.6%). The reason for switching was unresponsiveness to the agent in 22 patients (68.8%), adverse effects in 6 patients (18.7%), drug intolerance in 1 patient (3.1%), and other reasons in 3 patients (9.3%). CONCLUSIONS: The most frequently used biological agent was etanercept; the most frequent cases of biological agents switching were from an anti-TNF agent to another anti-TNF agent.

A case series of intracardiac thrombi and vascular involvement in pediatric Behçet's disease.

To evaluate the general characteristics of pediatric Behçet's disease (BD) patients with thrombus and to present the clinical features, treatment responses and prognosis of patients with intracardiac thrombus. The clinical characteristics and outcomes of 15 patients with thrombus among 85 pediatric BD patients followed in the Department of Pediatric Rheumatology were evaluated retrospectively. Of the 15 BD patients with thrombus, 12 (80%) were male, 3 (20%) were female. The mean age at diagnosis was 12.9 ± 1.1 years. Thrombus was present at the time of diagnosis in 12 patients (80%), while thrombus developed in three patients within the first three months after diagnosis. The most common site of thrombus was the central nervous system (n = 9, 60%), followed by deep vein thrombus (n = 6, 40%) and pulmonary artery thrombus (n = 4, 26.6%). Three male patients (20%) developed intracardiac thrombus. The overall intracardiac thrombus rate in the 85 patients was 3.5%. Two of the three patients had thrombus in the right, and one had thrombus in the left heart cavity. In addition to steroids, 2 of the 3 patients received cyclophosphamide, while the patient with thrombus localized in the left heart cavity was given infliximab. In the follow-up, the two patients with thrombus in the right heart cavity were switched to infliximab because of resistance to cyclophosphamide. Complete resolution was observed in 2 of the 3 patients on infliximab; a significant reduction in the thrombus of the other patient was achieved. Intracardiac thrombus is a rare presentation of cardiac involvement in BD. It is usually observed in males and in the right heart. Although steroids and immunosuppressive agents such as cyclophosphamide are recommended as first-line treatment, favorable outcomes can be achieved with anti-TNFs in resistant cases.

Intussusception as a rare manifestation of immunoglobulin A vasculitis: Risk factors and treatment.

AIM: To identify the risk factors associated with intussusception in children with immunoglobulin A vasculitis (IgAV)-gastrointestinal (GI) tract involvement and to evaluate the outcomes of medical treatment and surgical intervention and the course of patients with intussusception. METHODS: This retrospective study was conducted in 157 patients under 18 years of age who were followed up with the diagnosis of IgAV-GI tract involvement between January 2015 and September 2022. The characteristics of the patients who developed intussusception were evaluated in detail. RESULTS: One hundred and fifty-seven patients with GI tract involvement were included in the study. The mean age of patients with IgAV-GI tract involvement was 8.7 ± 3.7 years. The female-to-male ratio was 1:1.5. Intussusception was detected in 14 patients (8.9%). Two patients (14.3%) underwent surgery, and the remaining 12 patients (85.7%) had their medical therapy intensified. Patients with GI tract involvement were divided into two groups as with (n = 14) and without (n = 143) intussusception. There was a statistically significant difference between the groups in the time from the onset of the first symptom of IgAV to the onset of steroids (P = 0.001). There were no statistically significant differences between the groups in age at onset of IgAV, gender distribution, erythrocyte sedimentation rate and C-reactive protein levels. CONCLUSIONS: The time from the onset of the first symptom of IgAV to the start of steroids is a risk factor for the development of intussusception in patients with IgAV-GI tract involvement. In these patients, medical treatment usually reduces intussusception without the need for surgical intervention.

Chronic non-bacterial osteomyelitis in children: Outcomes, quality of life.

BACKGROUND: Chronic non-bacterial osteomyelitis is a chronic sterile inflammatory bone condition. We aimed to describe patients' clinical and radiographic findings and to evaluate their response to therapy and their quality of life. METHODS: This cross-sectional study included 18 patients from a single center in Turkey whose clinical, radiological features, and outcomes were reviewed retrospectively. The quality of the patients' lives after treatment was compared with healthy controls using the Pediatric Quality of Life Inventory 4.0. RESULTS: The median age of disease onset was 12 years (IQR 10-14 years) and 11 (61.1%) patients were male. The median follow-up duration was 15 months (IQR 12-22 months). The persistent form of chronic non-bacterial osteomyelitis was the most common pattern in 15 (83.3%) patients and a recurrent pattern was defined in three (16.7%) patients. The lesions were multifocal in all patients and 15 (83.3%) patients had symmetric distribution in whole-body magnetic resonance imaging. The most common sites of arthritis were the knee and sacroiliac joints. Methotrexate was used in 16 (88.9%) patients as first-line therapy. However, some patients were unresponsive to the first-line therapy and needed tumor necrosis factor-α inhibitors (55.6%) and bisphosphonates (16.7%). We observed remission in only four (22.2%) patients, and three (16.7%) patients were unresponsive. The patients had a significantly poorer quality of life than controls (P = 0.005). CONCLUSIONS: Chronic non-bacterial osteomyelitis is an insidious disease that requires detailed analysis for diagnosis and whole-body magnetic resonance imaging is an effective tool for its diagnosis. Despite the advanced treatment, patients with chronic non-bacterial osteomyelitis have a poor quality of life.

Clinical features and outcomes of childhood polyarteritis nodosa: A single referral center experience.

OBJECTIVES: The aims of this study were to describe the clinical features, comorbidities and outcome of systemic childhood polyarteritis nodosa (PAN) and to evaluate PAN-like diseases in differential diagnosis. METHODS: The study group consisted of patients who were diagnosed as PAN in a referral center in Turkey. The files of all patients were reviewed retrospectively. Disease activity was evaluated with pediatric vasculitis activity score (PVAS). RESULTS: A total of 19 (13 boys/six girls) patients were enrolled in the study. The mean age of patients was 10.37 ± 3.6 years. The mean duration of follow-up was 5.73 ± 3.74 years. Eight patients (42.1%) were also diagnosed with familial Mediterranean fever (FMF). The cutaneous involvement was higher in patients with PAN than those with FMF-associated PAN (p = .03). The median (min-max) PVAS at diagnosis was 5 (3-7). There was no correlation between PVAS scores at the time of diagnosis and age, clinical findings and relapse. CECR1 mutation was detected in one patient leading to deficiency of adenosine deaminase 2. CONCLUSION: The clinical presentation is variable in children with PAN. PAN-like diseases characterized by necrotizing vasculitis should be considered. The possibility of FMF should be kept in mind if inflammation cannot be controlled.

Effect of anti-interleukin-1 treatment on quality of life in children with colchicine-resistant familial Mediterranean fever: A single-center experience.

AIM: The aim of this study is to evaluate the clinical parameters, acute-phase reactants, side effects, genetic mutations among colchicine-resistant Familial Mediterranean fever (FMF) patients who received anti-interleukin-1 (anti-IL-1) treatment. We also evaluate the quality of life and school attendance among colchicine-resistant FMF patients, in relation to treatment with anti-IL-1. INTRODUCTION: Familial Mediterranean fever is the most common inherited autoinflammatory disorder. Although the main treatment of FMF is colchicine, a small group of patients are resistant to colchicine treatment. Anti-IL-1 treatment is promising in colchicine-resistant patients due to excessive IL-1ß production in pathogenesis. The aim of this study is to evaluate the quality of life and school attendance rates among colchicine-resistant FMF patients after anti-IL-1 treatment. METHODS: This is a single center retrospective study of 25 pediatric colchicine-resistant FMF patients treated with anti-IL-1 treatment. Autoinflammatory Disease Activity Index (AIDAI) was used for disease activity assessment. School attendance rates were evaluated before and after treatment. RESULTS: There were 25 patients with FMF (11 M/14 F) who were treated with anakinra or canakinumab for various indications (colchicine-resistant recurrent febrile attacks in 20, colchicine-related side effects in 2, subclinical inflammation in 3 patients). Only 3 patients developed side effects with anakinra (2 headache, 1 urticarial rash). There was a significant decrease in the frequency of attacks, acute-phase reactants (erythrocyte sedimentation rate and C-reactive protein), AIDAI and physician's and patient's global assessment scores and improvement in school attendance rates. At the last follow-up, all patients were in remission, and only 3 had subclinical inflammation. CONCLUSION: Anti-IL-1 treatment is quite effective in children with colchicine-resistant FMF patients, proven with improved AIDAI scores and school attendance rates. In the long term by lowering disease activation even development of amyloidosis may be prevented.

Cytopathologic diagnosis in pleural effusion and cyto-histopathologic correlation.

OBJECTIVE: Cytological examination of pleural fluids is a fast, efficient and non-invasive diagnostic method. Identification of malignant effusions bears critical importance in treatment and prognosis. The aim of this study was to investigate the distribution of cytopathologic diagnoses in pleural effusions and the cyto-histopathologic correlation rates. MATERIAL AND METHOD: A total of 298 pleural fluid cases diagnosed from 2008 to 2009 in our laboratory were retrospectively identified as the study group. Evaluation results were classified in 5 groups as inconclusive, benign, atypical, suspicious and malignant, and compared with the biopsy results. RESULTS: Of the total 298 pleural fluid cases, 114 (38.3%) were females and 184 (61.7%) were males. The age range was between 15 and 89 with a mean value of 58.4 +/- 17.8. Of the cases, 3 (1%) were diagnosed as inadequate, 246 (82.6%) benign, 8 atypical, 10 suspicious, and 31 malignant by cytology. Among the cases who were diagnosed as malignant, 24 (8.1%) were reported as metastatic carcinoma and 7 (2.3%) as malignant mesothelioma. Of the 8 cases reported as atypical, biopsy results of 2 showed malignant mesothelioma, and of the 10 cases reported as suspicious, 1 case whose biopsy result was obtained was diagnosed as epidermoid carcinoma metastasis. CONCLUSION: Cytological examination is the most valuable diagnostic method for pleural effusions which may have various etiological causes. The most common cause of pleural effusions in our region is metastatic carcinomas including those from the lung, breast and ovarian tumors, followed by malignant mesothelioma.