Covid-19 infection in children and adolescents and its association with type 1 diabetes mellitus (T1d) presentation and management.

Children seem to be affected by the new SARS-CoV-2 virus less severely than adults, with better prognosis and low mortality. Serious complications of COVID-19 infection in children include multisystem inflammatory response syndrome in COVID-19 infection (MIS-C), myo-or pericarditis and, less frequently, long COVID syndrome. On the other hand, adults with type 1 (T1D) or type 2 diabetes (T2D) are among the most vulnerable groups affected by COVID-19, with increased morbidity and mortality. Moreover, an association of SARS-CoV-2 with diabetes has been observed, possibly affecting the frequency and severity of the first clinical presentation of T1D or T2D, as well as the development of acute diabetes after COVID-19 infection. The present review summarizes the current data on the incidence of T1D among children and adolescents during the COVID-19 pandemic, as well as its severity. Moreover, it reports on the types of newly diagnosed diabetes after COVID infection and the possible pathogenetic mechanisms. Additionally, this study presents current data on the effect of SARS-CoV-2 on diabetes control in patients with known T1D and on the severity of clinical presentation of COVID infection in these patients. Finally, this review discusses the necessity of immunization against COVID 19 in children and adolescents with T1D.

Infections in Children With Cancer: The Role of the Presence or Absence of Neutropenia.

BACKGROUND: Infections in patients with cancer are a major cause of morbidity and mortality. In most cases, the presence of neutropenia renders them prone to infections to either common or opportunistic pathogens. A wide spectrum of bacterial, viral, or fungal agents is encountered in these patients. AIM: The aim of this study was to evaluate infection types and pathogens in pediatric patients with cancer with and without neutropenia. METHODS: A total of 37 pediatric patients with cancer (median age ± 25% quartile, 6.0 ± 2.0% years) with 70 febrile episodes were evaluated at fever's onset and 48 hours later with complete blood count, C-reactive protein, cultures of biological fluids, polymerase chain reaction, and antibody titers. RESULTS: Of 70 infections, 30 (42.85%) were bacterial, 13 (18.57%) were viral, 3 (4.28%) were fungal, 16 (22.85%) were fever of unknown origin, 18 (25.71%) were opportunistic, and 12 (17.14%) were mixed infections. Neutropenia was detected in 42 (60.0%) of 70 febrile episodes, mainly in patients with hematological malignancies [odds ratio, 2.81 (0.96-8.22); P = 0.059]. Neutropenic patients had higher prevalence of mucocutaneous infections (47.6% vs 7.14%; P = 0.004). Herpes simplex virus 1 infections occurred only in the neutropenic group (14.3%). CONCLUSIONS: Patients with cancer exhibited a high prevalence of bacterial (42.85%), opportunistic (25.7%), and mixed infections (17.14%). Patients with hematological malignancies and neutropenia presented higher frequency of mucocutaneous and herpes simplex virus 1 infections than the nonneutropenic ones.

Association Between Severity of Diabetic Ketoacidosis at Diagnosis and Multiple Autoimmunity in Children With Type 1 Diabetes Mellitus: A Study From a Greek Tertiary Centre.

OBJECTIVES: Type 1 diabetes mellitus is a chronic disorder associated with development of autoimmunity. In this work, we studied the relationship between severity of acidosis at diagnosis and future risk for autoimmunity development in children with type 1 diabetes. METHODS: We investigated the presence of associated autoimmunity in 144 children with type 1 diabetes (mean ± standard deviation: age, 12.44±4.76 years; diabetes duration, 4.41±3.70 years). We identified the presence of thyroid disease, celiac disease, autoimmune gastritis and adrenal autoimmunity, and retrospectively reviewed the files for presence of diabetic ketoacidosis at diagnosis. RESULTS: Autoimmunity prevalence was 16.7% for thyroid autoimmunity, 9.5% for celiac disease, 5% for gastric autoimmunity and 8.0% for multiple autoimmunities. There were strong associations between severe acidosis at diabetes diagnosis (pH<7.10) and development of thyroid autoimmunity (odds ratio [OR], 5.34; 95% confidence interval [CI], 1.90‒15.1; p<0.001), celiac disease (OR, 5.83; 95% CI, 1.19‒28.6; p=0.013), gastric autoimmunity (OR, 13.1; 95% CI, 1.22‒140; p=0.006) and multiple autoimmunity (OR, 26.7; 95% CI, 2.36‒301; p<0.01). The associations persisted after adjustment for sex, age at diabetes diagnosis, age at assessment, time since diabetes diagnosis and antiglutamic acid decarboxylase autoantibody status. CONCLUSIONS: The severity of acidosis at diagnosis is strongly associated with the development of associated autoimmune diseases in children with type 1 diabetes and could act as a predictive factor for multiple autoimmunity development. This association can be either due to effect of acidosis on immune system or to the presence of a more aggressive diabetes endotype.

Associated autoimmune diseases in children and adolescents with type 1 diabetes mellitus (T1DM).

Type 1 diabetes (T1DM) is an autoimmune disease with aberrant immune responses to specific ß-cell autoantigens, resulting in insulin deficiency. Children and adolescents with T1DM may also develop organ-specific multiple autoimmunity in the context of APS (autoimmune polyendocrine syndrome) type 1, 2 or 3. The most frequently encountered associated autoimmune disorders in T1DM are autoimmune thyroid, followed by celiac, autoimmune gastric disease and other rare autoimmune conditions. There are limited previous studies on the prevalence of associated autoimmunity, especially multiple, in children with T1DM. The present review reports on the classification of autoimmune diabetes, and on the prevalence, pathogenesis, predictive factors and clinical presentation of pancreatic autoimmunity and of all associated autoimmune disorders in children with T1DM. The impact of associated autoimmunity on diabetes control and general health is also discussed, along with suggestions regarding screening strategies and follow-up for early detection and management of the autoimmunity.

Multiple autoimmunity, type 1 diabetes (T1DM), autoimmune thyroiditis and thyroid cancer: is there an association? A case report and literature review.

Type 1 diabetes mellitus (T1DM) is characterized by selective autoimmune destruction of pancreatic b-cells, resulting in insulin deficiency. Associated autoimmune disorders, such as celiac disease, autoimmune thyroiditis, and gastritis, can coexist in patients with T1DM. These disorders are characterized by the presence of antibodies against tissue transglutaminase (anti-tTG-IgA), thyroglobulin, and thyroid peroxidase (anti-TG, anti-TPO), as well as antibodies against gastric parietal cells. Children with T1DM may also develop organ-specific multiple autoimmunity, with the coexistence of one or more autoimmune disorders. Furthermore, there is a lot of controversy regarding the role of thyroid autoimmunity in the pathogenesis of thyroid cancer. We present a child with T1DM and multiple autoimmunity including autoimmune Hashimoto's thyroiditis (HT), who developed thyroid cancer. The literature on the prevalence of associated autoimmunity in children with T1DM and the prevalence, pathogenesis, and timely diagnosis of thyroid cancer among patients with HT is also reviewed.

Deep vein thrombosis and pulmonary embolism in a child with diabetic ketoacidosis and protein s deficiency: a case report.

INTRODUCTION: Diabetic ketoacidosis (DKA) is considered a hypercoagulable state, which may be exacerbated in patients with thrombophilia and lead to thrombosis. CASE REPORT: We report on a 5.5-year-old boy, who was admitted to the pediatric department with DKA due to newly diagnosed type 1 diabetes. Low-grade fever was reported for 6 days prior to admission and continued during DKA management, with negative septic screening. After DKA management, the child developed symptoms of iliofemoral deep vein thrombosis (DVT). A family history of protein S (PS) deficiency was revealed. He was initially treated intravenously with antibiotics and unfractionated heparin, which, after 2 days, was switched to low-molecular-weight heparin and vitamin K antagonist (VKA) due to poor anticoagulant response. On the 6th day of anticoagulant treatment, the patient presented with pulmonary embolism (PE); he continued with VKA and antibiotics, with significant clinical improvement. Prolonged fever was attributed to DVT and PE. The patient was discharged on oral anticoagulants and insulin. CONCLUSION: We report on a child with congenital PS deficiency and DKA who developed DVT and PE despite anticoagulant treatment. It is important in children presenting with DKA to seek thoroughly for a medical history of thrombophilia and to start early thromboprophylaxis in such cases in order to prevent a possible thrombosis.

Plasma high sensitivity C-reactive protein and its relationship with cytokine levels in children with newly diagnosed type 1 diabetes and ketoacidosis.

BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) and pro-inflammatory cytokines have been suggested as sensitive markers of endothelial dysfunction. Our aim was to monitor plasma hs-CRP levels at different time-points and in different degrees of ketoacidosis severity, its association with cytokine levels and its role as a marker of severe ketoacidosis complications. PATIENTS AND METHODS: We studied in 38 newly diagnosed children with type 1 diabetes and ketoacidosis, aged 7.7 ± 3.1 years, hs-CRP, white blood cell count (WBC), and plasma levels of cytokines IL-1ß (interleukin-1ß), IL-2, IL-6, IL-8, IL-10, TNF-α (tumor necrosis factor-α) prior to and during DKA management. RESULTS: On admission, the levels of WBC, PMN, IL-6 and IL-10 were elevated, but were all reduced within 120 h after ketoacidosis management. In the group with moderate/severe ketoacidosis, but not in mild ketoacidosis, hs-CRP levels were significantly reduced at 24h (p=0.021), WBC and IL-6 at 120 h (p=0.003), while IL-10 was prematurely reduced at 6-8h (p=0.008). Moreover hs-CRP was significantly associated with WBC (p=0.023) and IL-6 (p=0.028) on admission, with IL-6 (p=0.002) and IL-8 (p=0.014) at 24h and with IL-10 (p=0.027) at 120 h. The above were not observed in the group with mild ketoacidosis. CONCLUSIONS: In the children with moderate/severe diabetic ketoacidosis of our study, increased levels of hs-CRP and IL-6 were observed, together with leukocytosis and neutrophilia, without the presence of infection. As hs-CRP was found to be strongly associated with the inflammatory IL-6, the prolonged elevation of hs-CRP levels in children with severe ketoacidosis could serve as a marker for the development of its severe complications.

The prevalence and risk factors for coeliac disease among children and adolescents with type 1 diabetes mellitus.

AIMS: Our aim was to determine in children with T1DM the prevalence of positive antibodies against tissue transglutaminase (anti-tTG IgA) as indices of coeliac disease (CD), as well as its clinical presentation, its determinants and its association with thyroid (anti-TG, anti-TPO) and pancreatic b-cell autoimmunity (anti-GAD). METHODS: The study included 105 children and adolescents with T1DM, aged (mean±SD) 12.44±4.76 years, with a T1DM duration of 4.41±3.70 years. RESULTS: Fifty of our patients (47.6%) were positive for anti-GAD, 9/105 (8.6%) for anti-tTG IgA and 21/105(20%) for anti-thyroid antibodies. The anti-tTG IgA (+) children, in comparison with the rest of the study population, were of younger age (9.31 vs. 12.74 years, p=0.038), shorter diabetes duration (2.16 vs. 4.62 years, p=0.056) and had mild growth impairment (height SDS: -0.55 vs. +0.20, p=0.055). Univariate logistic regression analysis revealed that the presence of anti-tTG IgA (+) was associated with younger age and shorter T1DM duration. Only 5/9 (55.6%) children with high titres of anti-tTG IgA developed mild gastrointestinal symptoms or growth retardation and had histological findings typical of CD. CONCLUSIONS: The prevalence of anti-tTG IgA positivity among T1DM children was 8.6% and its occurrence was associated with younger age and short diabetes duration. Since CD presents in T1DM patients asymptomatically or with non-specific symptoms, periodic autoantibody screening is necessary for its early diagnosis.

Factors for thyroid autoimmunity in children and adolescents with type 1 diabetes mellitus.

INTRODUCTION: Type 1 diabetes mellitus (T1DM) is associated with an autoimmune reaction to thyroid antigens including thyroid peroxidase (anti-TPO) and thyroglobulin (anti-Tg). AIMS: We determined in children with T1DM the relationship of positive anti-thyroid antibodies to potential risk factors, including, age, gender, duration of diabetes, and glutamic acid decarboxylase antibodies (anti-GAD). MATERIALS AND METHODS: We studied 144 children and adolescents with T1DM. Their age was 12.3 +/- 4.6 (mean +/- SD) years, and duration of diabetes was 4.6 +/- 3.8 years. Anti-thyroid antibodies were determined using a luminescence method and anti-GAD using an enzyme-linked immunosorbent assay. RESULTS: The prevalence rates of anti-thyroid antibodies among the children with T1DM in our study were: anti-TPO (17.4%), anti-Tg (11.1%), and of both anti-thyroid antibodies (10.4%). The presence of serum anti-thyroid antibodies was positively associated with age (16.6 years in those with positive tests versus 12.0 years in those with negative tests, P = 0.027), duration of diabetes (7.4 versus 4.3 years, P = 0.031), and serum TSH (Thyroid-stimulating hormone) levels (4.8 versus 2.3 microIU/mL, P = 0.002). The presence of both anti-thyroid antibodies was associated with female sex (boys: 4/75 (5.3%), girls: 11/69 (15.9%), chi-square = 6.44, P = 0.04). Subclinical autoimmune thyroiditis (SAIT) was present in 55.5% of the patients with thyroid antibody-positivity and was positively associated with age (16.6 versus 12.0 years, P = 0.001) and diabetes duration (7.6 versus 4.2 years, P = 0.001). Multiple logistic regression analysis revealed that the development of anti-thyroid antibodies was predicted by: 1) the presence of anti-GAD (odds ratio (OR) 1.45, 95% confidence interval (CI) 1.09-1.92), 2) the presence of a second anti-thyroid antibody (OR 134.4, 95% CI 7.7-2350.3), and 3) older age (OR 22.9, 95% CI 1.13-463.2). CONCLUSIONS: Thyroid autoimmunity was associated with female gender, increasing age, long diabetes duration, the persistence of anti-GAD, and with TSH elevation, indicating subclinical hypothyroidism.

Screening for associated autoimmunity in children and adolescents with type 1 diabetes mellitus (T1DM).

BACKGROUND/AIMS: Type 1 diabetes (T1DM) is associated with autoimmune thyroid, celiac, autoimmune gastric and Addison's disease. Our aim was to investigate the prevalence of associated autoantibodies in relation to the demographic and beta-cell autoantibody status (anti-GAD). METHODS: Antibodies against thyroid peroxidase (anti-TPO), thyroglobulin (anti-Tg), tissue transglutaminase (anti-tTG IgA), parietal cells (APCA) and adrenal tissue (AAA) were measured in 144 children with T1DM with a mean +/- SD age of 12.3 +/- 4.6 years and a diabetes duration of 4.6 +/- 3.8 years. RESULTS: The prevalence of antibody positivity among our patients was: anti-GAD 53.2%, anti-thyroid (anti-TPO 17.4%, anti-Tg 11.1%); anti-tTG IgA 7.6%, APCA 4.0%, and AAA 0%. Among the children with positive anti-thyroid antibodies, 60% developed autoimmune thyroiditis, while among those anti-tTG IgA positive, 62.5% developed biopsy-confirmed celiac disease. Female gender was more frequent among anti-tTG IgA-positive patients (OR 4.47, p = 0.068), while increasing age was associated with anti-Tg positivity (OR 22.9, p = 0.041). The presence of anti-thyroid antibodies was associated with the presence of anti-GAD (OR 1.45, p = 0.01) and parietal cell antibodies (OR 4.98, p = 0.09). CONCLUSION: Among T1DM patients, the prevalence rates of anti-thyroid and parietal cell antibodies increased with age and diabetes duration. As the presence of anti-GAD was associated with gastric and thyroid autoimmunity, it could serve as marker for the development of additional autoimmunity in adolescents with diabetes.

Prevalence of allergic symptoms among children with diabetes mellitus type 1 of different socioeconomic status.

The aim of the study was to assess the possible associations between allergies and type 1 diabetes mellitus (DM1), stratified by social class. We studied 127 children with DM1 with a median age of 10.8 yr and 150 controls of comparable age and sex distribution. The parents completed questionnaires on their education and occupation and on their children's history of allergic symptoms, breast-feeding, viral infections, and measles-mumps-rubella (MMR) vaccination. Lower family's social class was more frequently encountered among the DM1 families than in the controls (OR = 0.56, 95% CI: 0.35-0.92). The occurrence of any allergic symptoms among children with DM1 (35.45%) was not significantly different from the controls (38.78%), neither in the total group (OR = 0.87, 95% CI: 0.52-1.45) nor in the stratified analysis by social class. Similar findings were observed regarding the different types of allergic symptoms. In the univariate analysis, breast-feeding, the experience of viral infections, and MMR vaccination were found to be protective of DM1 presentation in both upper and lower social classes. In the multiple logistic regression analysis, the experience of more than 2 infections/yr (OR = 0.12, 95% CI: 0.04-0.34), the origin from middle and upper social classes (OR = 0.42, 95% CI: 0.22-0.80) and breast-feeding (OR = 0.58, 95% CI: 0.31-1.07) were protective of DM1 occurrence. In children with DM1, the presence of allergic symptoms was not associated with the development of DM1. Among the environmental factors, the origin from middle or upper social classes, breast-feeding, the experience of viral infections, and MMR vaccination were found to have a protective effect on DM1 presentation.