Vaccine Adherence and Postvaccination Serological Status of Pediatric Allogeneic Hematopoietic Stem Cell Transplant Recipients: A Single-center Experience.

Despite developing consensus guidelines addressing immunization after hematopoietic stem cell transplantation (HSCT), studies showed deviations from recommended immunization practices commonly occur. Difference between the ideal scenario presented in guidelines and real-life scenarios is one of the most recognized barriers to implementing recommended practices. Therefore, this study aimed to evaluate pediatric allogeneic HSCT recipients' adherence to revaccination schedule and evaluate the serological status after immunization. Transplant and vaccination records of children who were followed up at least 2 years after HSCT, postvaccination antibody results of vaccine-preventable diseases were evaluated retrospectively. Total of 173 patients have enrolled in this study. Median revaccination onset time was post-transplant 15 months. Adherence to revaccination program was 30% for inactive and 11.4% for live vaccines. Oral polio vaccine was given to 22 patients, and Bacille-Calmette-Guerin vaccine was applied to 3. Seropositivity after revaccination was >90% for Hepatitis B, Hepatitis A, pertussis, and measles, and it was 88.5% for rubella, 80% for mumps and varicella. Measles seropositivity was low in children with hemoglobinopathy. In subgroup assessments of pertussis, patients vaccinated with low antigen-containing pertussis vaccine (Tdap) had higher seropositivity of adenylate cyclase toxin. Our findings revealed the importance of careful monitoring of current practices in pediatric HSCT recipients.

Live-attenuated measles, mumps, and rubella booster vaccine in children diagnosed with rheumatic disease: A single-center study.

To evaluate the safety profile of measles, mumps and rubella (MMR) booster in children diagnosed with rheumatic diseases receiving biological agents. The study included retrospective safety data of children administered MMR booster dose receiving biologics or biologics with methotrexate. The files of 182 patients were accessed from the pediatric rheumatology biological therapy archive, and the vaccination status of these children was obtained by accessing electronic records. Of 182 patients, 14 patients were vaccinated with MMR booster dose. Thirteen of the patients were followed up with a diagnosis of juvenile idiopathic arthritis and one with colchicine-resistant familial Mediterranean fever. None of the patients had disease exacerbation after vaccination, and three patients had mild side effects consisting of rash, angioedema, joint pain, and fatigue.    Conclusion: This study supports the data regarding evidence of the safety of MMR booster dose administration in children with rheumatic diseases receiving bDMARDs. What is Known: • MMR booster is avoided in immunocompromised pediatric patients receiving bDMARDs except in specific conditions. What is New: • The MMR booster dose may be safe in children with PedRD receiving bDMARDs or bDMARDs with MTX. These bullets can be added to the manuscript.

Comorbidities and phenotype-genotype correlation in children with familial Mediterranean fever.

Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease manifesting with phenotypic heterogeneity. The phenotype-genotype correlation is not established clearly yet. Furthermore, some comorbidities such as vasculitis and inflammatory arthritis may accompany FMF. Herein, we aimed to define phenotype-genotype correlation and comorbid diseases of children with FMF. The medical records of 1687 children diagnosed and followed up as FMF were reviewed retrospectively. Disease severity was assessed by PRAS score. A total of 1687 children (841 girls, 846 boys) were involved in the study. The mean ± standard deviation of current age, age at symptom onset, and age at diagnosis were 13.1 ± 5.4, 5.4 ± 4, and 8 ± 4.2 years, respectively. Median (min-max) follow-up period was 3 (0.5-18) years. Among them, 118 (7%) patients had at least one concomitant disease and 72% of them were carrying at least one M694V mutation. Patients with a concomitant disease expressed a more severe course of disease when compared to ones without a concomitant disease (23.7% vs 8.8%, p < 0.001). Children carrying homozygous M694V mutation had significantly earlier age of disease onset and severe disease course (p < 0.001). Forty-four patients (2.6%) were colchicine resistant and most of them were carrying homozygous M694V mutation. Sixteen colchicine-resistant patients were treated with anakinra while 28 received canakinumab. Juvenile idiopathic arthritis (JIA) and immunoglobulin A vasculitis were the most commonly seen associated diseases and the patients with a concomitant disease demonstrated more severe course. This is the largest pediatric cohort studied and presented since now. We confirmed that carrying M694V mutation is associated both with a severe disease course and a predisposition to comorbidities.

The evaluation of anxiety, depression and quality of life scores of children and adolescents with familial Mediterranean fever.

This study aimed to evaluate the anxiety, depression and quality of life scores of children and adolescents diagnosed with familial Mediterranean fever (FMF) and compare these scores with the ones of healthy controls. The study group comprised of 130 children and adolescents diagnosed with FMF with a mean age of 12.6 ± 2.58 and control group comprised of 121 healthy controls with a mean age of 11.8 ± 2.84. Both groups were evaluated with child depression inventory (CDI), screen for child anxiety related emotional disorders (SCARED), pediatric quality of life inventory TM 4.0 (PedsQL™ 4.0) questionnaires. The severity of FMF was assessed by Pras scoring system as mild, moderate and severe disease. The comparisons of these three subgroups of FMF were made in terms of anxiety, depression and quality of life. Children and adolescents with FMF had significantly higher median scores of anxiety than healthy controls. The median scores of depression and quality of life were similar between both groups. Patients with a depression score of 19 or above had significantly higher scores of anxiety and longer duration of disease than the patients with a depression score below 19. While the patients with a severe course of FMF had higher median scores of depression and anxiety, they had significantly lower median scores of quality of life. According to our evaluation, patients with FMF had higher anxiety scores and as the disease become severe, not only anxiety scores but also features of depression become overt. An early apprehension of the mood changes of these patients may have a positive influence in the management of FMF. So, a close collaboration between child and adolescent psychiatrist and pediatric rheumatologist is essential for all over well-being of children and adolescents with FMF.

Faecal calprotectin levels during the first year of life in healthy children.

AIM: A high faecal calprotectin (FC) level is a non-invasive marker for inflammatory bowel disease. Nevertheless, healthy infants have elevated levels of FC with large variations. The aim of our study was to determine the levels of FC and associated factors in healthy infants aged 0-12 months. METHODS: Infants younger than 1 year of age were in the follow-up programme of the Well Child Unit. Data on the clinical characteristics, including birth, anthropometric measurements and feeding types of infants in the unit, were obtained from their personal health records. One fresh stool sample was collected from each infant. ELISA was used to measure FC. RESULTS: We included 84 infants younger than 1 year of age. The median FC value was 313 µg/g. The FC levels were greater in the youngest (0-30 days) group of infants than in the oldest (181-365 days) group (P < 0.001). The FC levels were higher in infants delivered by caesarean section than in those delivered vaginally (P = 0.016). The levels were also higher in infants who were solely breastfed than in those who received mixed feeding (breast milk and formula) during the first 6 months of life (P = 0.030). CONCLUSION: The FC levels in this group of infants were high, especially in the first month of life. Several birth and environmental factors influenced the FC values. Further studies with a larger cohort of infants and serial assessment of FC over time are required to better understand the patterns of this biomarker during infancy.

Very high IgE levels in children: when from pediatrician to immunologist?

BACKGROUND: Total serum immunoglobulin E (IgE) is increased in many situations such as allergic diseases, primary immunodeficiencies (PID), parasitosis, infections and malignancies. When IgE levels >1000 kU/L are suspected PID by pediatricians. We tried to define some clinical and laboratory parameters to distinguish PID from the others. METHODS: We evaluated 158 children between 1.7 - 17 years (Mean: 6.6 ±3.4) for allergic diseases, PID, parasitosis and others. Total IgE, specific IgE, immunoglobulin levels and skin prick tests were performed to all patients. Parasite investigations, viral serological tests and detailed immunologic tests were analyzed in only patients who had suspected complaints. Hyper IgE syndrome (HIES) scoring sheet was filled out for all patients. RESULTS: Among all patients, 114 were diagnosed as bronchial asthma, allergic rhino-conjunctivitis or atopic dermatitis. PID diagnosis was established in totally 32 patients. Immunological evaluations were normal in 126 patients. Eleven patients were accepted as parasitosis. Median HIES score was 18 (5-44 points). CONCLUSIONS: Pediatricians may use HIES scoring sheet when they suspect a patient with PID. If the patient has very low points, they may follow the patient. If there are about 18-20 points, they should get an opinion from an immunologist for detailed immunologic tests.

Novel Mutation in CECR1 Leads to Deficiency of ADA2 with Associated Neutropenia.

PURPOSE: Adenosine deaminase 2 (ADA2) have been reported to cause vasculitic diseases and immunodeficiency recently. Patients present with stroke episodes and rashes mimicking polyarteritis nodosa (PAN). We report a patient who has been followed up with severe neutropenia and found an unexpectedly revealed novel mutation in CECR1 affecting ADA2. METHODS: We reviewed medical records and clinical history of the patient. No mutations in other known neutropenia genes such as ELA, G6PC3, HAX1, AP3B1, LAMTOR2, VPS13B, VPS45, GFI1, JAGN1, or WAS could be detected. Sanger sequencing was used to confirm the genetic variants in the patient and relatives. RESULTS: Genetic analysis by exome sequencing revealed a novel mutation in the gene CECR1 (c.G962A; p.G321E) which segregated perfectly in the relatives. CONCLUSION: This is the first DADA2 patient presenting with severe neutropenia. We suggest that in patients with unexplained cytopenias combined with immunodeficiency, fevers of unknown origin and high inflammation markers, DADA2 should be considered.

Does familial Mediterranean fever affect cognitive function in children? Electrophysiological preliminary study.

OBJECTIVES: Familial Mediterranean fever (FMF) is a periodic autoinflammatory disease with subclinical inflammation occurring between attacks. The aim of the study was to prospectively evaluate the cognitive function of children diagnosed with FMF that were under colchicine therapy and compare them with healthy controls through electrophysiologically event-related potentials (ERPs) study. METHODS: Twelve children with FMF and 12 healthy controls were included in the study. During the electroencephalography recordings, all participants were instructed to discriminate rare stimuli (target stimuli) from frequent stimuli (standard stimuli) by pressing a botton on a mouse immediately following the target stimulus. P300, the cognitive component of ERP, was obtained in response to target stimuli and its amplitude and latency were measured. RESULTS: The amplitude of the P300 of the FMF patients was higher and the latencies of the P300 of the FMF patients were shorter than the amplitudes and latencies of control patients, respectively. The difference between the groups was statistically significant for amplitude but not for latency. CONCLUSIONS: Cognitive processing reflecting allocation of attention and visual processing speed seems not to be negatively affected in FMF patients with homozygous M694V mutations undergoing colchicine treatment. As this study is unique in its evaluation of the cognitive function of children with FMF, these findings may be helpful for counseling families and patients affected by the condition.

HAX-1 deficiency: Characteristics of five cases including an asymptomatic patient.

BACKGROUND: Mutations in the HAX-1 gene cause an autosomal recessive form of severe congenital neutropenia (SCN), which particularly manifests with recurrent skin, lung and deep tissue infections from the first few months of life. OBJECTIVE: We retrospectively evaluated the clinical and laboratory findings of the patients diagnosed with SCN carrying HAX1 gene mutations. METHODS: A total of five patients with SCN, carrying a HAX1 gene mutation, were evaluated in terms of clinical and laboratory findings. Mutation analysis of the candidate genes (HAX1, ELANE and CSF3R) was performed. RESULTS: All of the patients lived in Turkey; four of them were of Kurdish origin and one was Turkish. Of the five patients, three were girls and two were boys, and the mean age of the patients was 8.8 years old (range 4-15 years). The mean age of diagnosis was 25.8 months (range 2 months-5 years). The infections diagnosed included recurrent gingivitis, stomatitis, and skin and soft tissue abscesses. Developmental retardation and epilepsy were present in only one patient, whereas speech retardation was present in two. All of our patients had a HAX1 mutation, and are still alive and none of them has shown malignant transformation yet. CONCLUSION: Complete blood count should be performed and absolute neutrophil count should be evaluated in patients with recurrent severe infections. In the event that neutropenia is detected, they should be investigated in terms of SCN and mutation analysis should be performed.

Microcephaly in Infants: A Retrospective Cohort Study from Turkey

Objective: Microcephaly (MC) is a clinical finding mostly reflecting deficiency of brain growth. The aim of this retrospective cohort study was to assess risk factors and follow-up features of children with MC. Methods: Children's personal health records (n=7580) followed between 2002 and 2020 in the Unit of a Well Child Clinic were assessed retrospectively. The case group comprised children with MC. MC was defined as head circumference (HC) standard deviation score (SDS) value ≤-2 SDS. Age and sex-matched children with normal HC were selected as the control group. Results: Children with MC (n=49) had more disadvantaged sociodemographic characteristics, such as young maternal and paternal age and low maternal and paternal education. Breastfeeding was more common among controls (n=98). Resolution of MC was observed in 26 (53.1%) children with MC, whether it was mild (HC SDS between -2 and -2.9) or severe (HC SDS ≤3). Children with persistent MC had poorer developmental milestones than controls and cases with resolution. Sociodemographic features or developmental milestones in mild and severe MC did not differ. Conclusion: These results suggest that the use of a definition of MC of ≤-2 SDS would be appropriate in order not to miss cases on follow-up. Greater sociodemographic equality may prevent some cases of MC. Further studies are needed evaluating socioeconomic factors on MC.

Vaccination coverage of children with rheumatic diseases compared with healthy controls: a retrospective case-control study.

OBJECTIVE: To reveal the vaccination status of patients with pediatric rheumatic disease (PedRD) and to compare this with healthy controls. METHODS: The electronic health records of the Ministry of Health regarding the vaccination status of children with PedRD followed in a tertiary hospital were analyzed cross-sectionally and compared with their healthy controls. The missing vaccines were reported according to individual, age-appropriate schedule and causes of skipped vaccines in both groups were investigated with an online survey. RESULTS: The vaccination rate of patients in the last examination was 71.4% (90/126) and 95.7% (110/115) in healthy controls (p < 0.001). Measles-mumps-rubella vaccine, diphtheria, the administration rates of the second dose of tetanus-acellular pertussis-inactivated polio and Haemophilus influenzae type B, chickenpox, and hepatitis A vaccines were significantly lower in patients than in controls (p values 0.004, 0.02, 0.01, 0.013, respectively). The pre-diagnosis incomplete vaccination proportion was significantly higher in the patient group (16.6%) than in healthy controls (4.3%) (p = 0.002). In the patient group, the proportion of incomplete live-attenuated vaccines after diagnosis (25%) was more than pre-diagnosis (61.1%) (p = 0.04), while the proportion of incomplete non-live vaccines before and after diagnosis was similar (47.2% and 50%, respectively) (p = 0.73). The major reasons for missed vaccines were physicians' recommendations (15.6%), the presence of PedRD diagnosis (12.5%), and the drugs used (12.5%). CONCLUSION: Vaccination coverage of PedRD patients has been shown to lag behind the routine vaccination schedule (71.4%). In addition to new recommendations, electronic health system records for vaccination may be appropriate for the follow-up of these patients, and the addition of reminder alerts may be useful to reduce the rate of missed vaccinations.

Miliaria rubra and thrombocytosis in pseudohypoaldosteronism: case report.

Pseudohypoaldosteronism type 1 (PHA1) is a disease involving a state of renal tubular unresponsiveness to the action of aldosterone and characterized by excessive salt loss in the urine, hyperkalemia, and metabolic acidosis. In kidney, PHA1 may occur primarily by mutations in the subunits of the sodium channel or in the mineralocorticoid receptors, and secondarily by several renal disorders. Miliaria rubra and thrombocytosis are reported in a 6-month-old girl with PHA1. In patients with PHA1, miliaria rubra-like cutaneous eruptions are suggested to occur due to obstruction of eccrine sweat glands through inflammation caused by excessive sodium excretion in sweat during hyponatremic crises. The presence of thrombocytosis in patients with PHA1 has not been previously reported. A hypothesis is proposed suggesting that sympathetic activation which provides vascular tonus during sodium excretion in sweat and salt-depletion crisis may play a role in the development of eruptions and thrombocytosis in patients with PHA1.

Effects of selenium supplementation in the early stage of autoimmune thyroiditis in childhood: an open-label pilot study.

AIM: The aim of the study was to evaluate the role of selenium (Se) in childhood autoimmune thyroiditis regarding its effect on thyroid-stimulating hormone (TSH), free thyroxine (fT4), thyroid peroxidase antibodies (TPOAb), thyroglobulin antibody (TgAb), and thyroid morphology. METHODS: Newly diagnosed 23 euthyroid children (mean age, 12.3 +/- 2.4 years) with Hashimoto thyroiditis (HT) received only 50 microg L-selenomethionine per day for 3 months. The baseline basal urinary iodine level, serum Se, TSH, fT4, TPOAb, and TgAb concentrations, and thyroid morphology by ultrasound were detected. We reanalyzed the TPOAb and TgAb changes at the 3rd month and then compared the thyroid morphology with 30 healthy individuals (mean age, 12.1 +/- 2.1 years) at the 6th month. RESULTS: Serum TPOAb, TgAb, and thyroid echogenicity were unchanged with Se supplementation. A prominent decrease in thyroid volume was noteworthy; 35% of patients showed a thyroid volume regression rate of > or = 30%. CONCLUSION: In terms of TPOAb and TgAb, Se may not benefit in the euthyroid period of HT, but Se supplementation seems to lead a favorable response in thyroid volume regression.

Hepatitis B Vaccination in Children With Ongoing Cancer Treatment: A Safety and Efficacy Study of Super-Accelerated Vaccination Scheme.

OBJECTIVE: Children with cancer have an increased risk for hepatitis B virus (HBV) infections due to chemotherapy-induced secondary immunodeficiency and frequent blood transfusions. The aim of this study is to evaluate the efficacy and safety of hepatitis B vaccination during the intensive induction chemotherapy in children with cancer found to be seronegative for hepatitis B on admission. MATERIALS AND METHODS: Children newly diagnosed with cancer were evaluated for the presence of hepatitis B surface antigen (HBsAg) and antibody on admission. The children negative for both were included in the study. A super-accelerated vaccination scheme (3 booster doses at days 1-5, 8-12, and 28-33) was administered to these seronegative children concurrently with induction chemotherapy. Antibody response was checked 4-8 weeks after the last vaccination and 6 months after the end of the treatment. RESULTS: Eleven out of 122 children were seronegative for hepatitis B on admission (9%). Acute lymphoblastic leukemia, lymphoma, and solid tumors were diagnosed in 5, 4, and 2 children, respectively. Complete seroconversion was achieved in 4-8 weeks after the last vaccination with high titers of anti-HBs antibody, and all patients remained antibody-positive until 6 months after the completion of chemotherapy. CONCLUSION: The risk of transfusion-related infections increases with a number of transfused products and donor exposures, and it is more significant for immunosuppressed children with hematologic and oncologic malignancies. Hepatitis B vaccination could safely be applied with brisk and sustained responses in this vulnerable population, based on the local epidemiological data.

A rare case of syndromic severe congenital neutropenia: JAGN1 mutation.

BACKGROUND: Neutrophils are essential innate cells to fight bacterial and fungal pathogens. Jagunal homolog 1 (JAGN1) mutations were recently defined as rare genetic defects causing severe congenital neutropenia. JAGN1 participates in the secretory pathway and is required for granulocyte colony-stimulating factor receptormediated signalling. This gene is required for normal ultrastructure and granulation of endoplasmic reticulum of myeloid progenitor cells. Its defect is related to increased predisposition to apoptosis. In the literature, a few cases have been reported with congenital anomalies such as cardiac and renal anomalies. CASE: Here we report a patient in which JAGN1 deficiency was found after several years. Apart from syndromic facial appearance we were unable to detect any other systemic malformations. CONCLUSION: The causes of multisystemic features of mutations in JAGN1 gene remain unknown. JAGN1 mutations must be considered in patients with severe congenital neutropenia especially with facial dismorphism even in the absence of systemic manifestations.

Assessment of Hearing Function in Children with Inflammatory Bowel Disease.

OBJECTIVES: Inflammatory bowel disease (IBD), a chronic pathology that affects many organ systems, appears after dysregulated immune response in genetically predisposed patients. Inner organ involvement has been shown in various autoimmune diseases because of its immunosensitivity. In this study, we aimed at showing sensorineural hearing loss (SNHL) as a result of possible subclinical inflammation in patients with IBD during the remission period. MATERIALS AND METHODS: We included 32 children with IBD and 31 healthy volunteers with comparable sex and age. Detailed ear-nose-throat examination was conducted for all, and patients were excluded if they had a history of ear infectionor trauma. Thereafter, the results of pure tone audiometry (PTA), high-frequency audiometry, and distortion product otoacoustic emissions testing were compared between the groups. RESULTS: There were no differences in terms of age, sex, and PTA values between controls and children with IBD. No statistical differences were found between responses at 250; 500; 2,000; 4,000; DP1000; DP1400; DP2000; DP2800;and DP4000 Hz as well as the signal-to-noise ratio (SNR) at 1,000 Hz when the controls and children with IBD (p>0.05 for all) were compared. However, the mean responses at 1,000; 8,000; 10,000; 12,500; 16,000; SNR1400; SNR2000; SNR2800; and SNR4000Hz of the children with IBD were significantly higher than those of the controls (p<0.05 for all). CONCLUSION: Initial SNHL appears at high frequencies in pediatric patients with IBD.

Serum amyloid A as a biomarker in differentiating attacks of familial Mediterranean fever from acute febrile infections.

OBJECTIVE: To determine the capability of serum amyloid A (SAA) in differentiating attacks of familial Mediterranean fever (FMF) from acute febrile upper respiratory tract infections. METHOD: Children diagnosed with FMF during febrile attacks were recorded as the patient group. The control group consisted of children with febrile upper respiratory tract infections. Complete blood count, serum amyloid A (SAA), C-reactive protein (CRP), and erythrocyte sedimentation rate were recorded in both groups during febrile episodes. RESULTS: The cohort consisted of 28 children with FMF attack and 28 previously healthy children with acute febrile infection. While CRP and SAA levels were elevated in both groups, elevations during FMF attacks were significantly higher in the FMF group than in the control group. Median CRP was 85 mg/L in the FMF attack group and was 36 mg/L in the control group (p = 0.001). Median SAA was 497.5 mg/L in the FMF attack group and was 131.5 mg/L in the control group (p < 0.001). Correlation analyses showed that SAA and CRP were positively correlated in the FMF attack group (r = 0.446, p = 0.01). The best cut-off value for SAA in differentiating FMF attack from an acute febrile infection was 111.5 mg/L (sensitivity 100%, specificity 65.1%, area under curve (AUC) = 0.78, confidence interval 0.66-0.90, p < 0.001). CONCLUSION: Serum amyloid A is a sensitive but not specific marker for demonstrating inflammation in FMF. SAA levels rise substantially in febrile upper respiratory tract infections.Key Points• SAA levels rise substantially in febrile upper respiratory tract infections.• SAA is a sensitive but not specific method for demonstrating inflammation.• SAA cut-off value for discriminating FMF attacks from febrile infection is 111.5 mg/L (sensitivity 100%, specificity 65.1%).