Life quality, depression, and anxiety levels in parents of children with primary immunodeficiency.

BACKGROUND: Primary immune deficiencies (PID) encompasses genetic disorders that result in recurrent infections and immune dysregulation, often increasing the risk of malignancies. The aim of this study is to determine the quality of life, depression, and anxiety in parents of children with PID. METHODS: Various validated assessment tools, including the Beck Depression Inventory (BDI), State and Trait Anxiety Inventory (STAI), the 36-item Short Form Survey (SF-36), and a demographic form, were employed to gather data from 85 parents of 64 PID patients and 85 parents of 75 healthy children. RESULTS: The findings reveal that parents of PID patients exhibited higher BDI, STAI-S, STAI-T, and fatigue subdomain of SF-36 (p = .013, p = .013, p = .027, p = .000). Both parents had lower energy levels than the normal population, but mothers experienced higher levels of anxiety and depression. PID mothers' had higher scores than fathers of PID patients with healthy children in BDI, STAI-S, and STAI-T (p = .002, p = .010, p = .001). Mothers of PID patients reported lower scores in RLEP, E/F, EWB, P, and GH compared to fathers (p = .009, p = .005, p = .034, p = .001, p = .003). Additionally, the study found that STAI-T influenced all subdimensions of HRQOL. These results highlight the substantial emotional and psychological burden placed on parents caring for children with PID. CONCLUSION: The study underscores the importance of supporting caregivers to enhance the overall well-being of both parents and children with PID. Such support can potentially alleviate depression and anxiety levels among parents, ultimately improving their quality of life and aiding in the management of children with PID.

Clinical and Immunologic Features of a Patient With Homozygous FNIP1 Variant.

Agammaglobulinemia represents the most profound primary antibody deficiency, stemming from early cessation of B-cell development. Deficiency in folliculin-interacting protein 1 (FNIP1) is a novel inborn error of immunity characterized by a severe defect in B-cell development, agammaglobulinemia, variable neutropenia, and hypertrophic cardiomyopathy. FNIP1 plays a critical role in B-cell development and metabolic homeostasis, establishing a metabolic checkpoint that ensures pre-B cells possess sufficient metabolic capacity to undergo division while concurrently limiting lymphogenesis due to abnormal growth. Disruption of FNIP1 functionality affects the fundamental metabolic regulators adenosine monophosphate-activated protein kinase and mTOR, culminating in a severe B-cell deficiency alongside hypogammaglobulinemia, hypertrophic cardiomyopathy, preexcitation syndrome, and intermittent neutropenia. This case report presents an 11-month-old male patient with FNIP1 deficiency who, in addition to classical features, exhibited posterior cerebellar hypoplasia.

Malignancies and Lymphoproliferations in Children With Primary Immune Deficiency-A Single-center Experience.

Primary immune deficiencies (PIDs) are rare genetic disorders characterized by impaired immune function, leading to frequent infections and immune dysregulation. Studies have shown that individuals with PID are at an increased risk of developing malignancies and lymphoproliferative disorders compared with the general population. In this single-center study, we aimed to analyze the occurrence of malignancies and lymphoproliferations in children diagnosed with PID. We retrospectively analyzed the medical records of 550 pediatric patients diagnosed with PIDs at our center. Among them, 17 (3,0%) patients were identified with malignancy and/or benign lymphoproliferation. Eight of the 17 patients (47.0%) had immune dysregulatory diseases, whereas ataxia-telangiectasia was the second most common PID associated with malignancy and/or benign lymphoproliferation (n = 5, 29.4%). Lymphoma was the predominant malignancy (n = 11, 64.7%), and Epstein-Barr virus was identified as the most common viral agent associated with malignancy and/or benign lymphoproliferation in patients with PID (n = 8, 47.0%). Our study highlights the association between PID and malignancies/lymphoproliferations, with immune dysregulation syndromes being the most common subclass associated with malignancies/lymphoproliferations. Early diagnosis, multidisciplinary management, and regular surveillance are crucial in improving patient outcomes and saving lives.

Defective Treg generation and increased type 3 immune response in leukocyte adhesion deficiency 1.

In 15 Turkish LAD-1 patients and controls, we assessed the impact of pathogenic ITGB2 mutations on Th17/Treg differentiation and functions, and innate lymphoid cell (ILC) subsets. The percentage of peripheral blood Treg cells, in vitro-generated induced Tregs differentiated from naive CD4+ T cells were decreased despite the elevated absolute counts of CD4+ cells in LAD-1 patients. Serum IL-23 levels were elevated in LAD-1 patients. Post-curdlan stimulation, LAD-1 patient-derived PBMCs produced more IL-17A. Additionally, the percentages of CD18-deficient Th17 cells expanded from total or naïve CD4+ T cells were higher. The blood ILC3 subset was significantly elevated in LAD-1. Finally, LAD-1 PBMCs showed defects in trans-well migration and proliferation and were more resistant to apoptosis. Defects in de novo generation of Tregs from CD18-deficient naïve T cells and elevated Th17s, and ILC3s in LAD-1 patients' peripheral blood suggest a type 3-skewed immunity and may contribute to LAD-1-associated autoimmune symptoms.

Risk factors predisposing children to food allergies.

BACKGROUND: Food allergies are the most common cause of anaphylaxis in children, and their incidence is increasing globally. The aim of this study was to determine the risk factors leading to food allergies in childhood. METHODS: Children with food allergies and non-atopic healthy children were compared using a questionnaire that included prenatal, neonatal, and postnatal risk factors. RESULTS: A total of 314 subjects, 155 patients and 159 healthy children for the control group, were enrolled in the study. The median age of patients with a food allergy at diagnosis was 6 months (1-156 months), and 71 patients (45.8%) were males. The median age of the control group was 12 months (1-61 months), and 67.0% were males. Older maternal age (P = 0.023), birth by caesarean section (P = 0.001), birth in the summer or autumn (P = 0.011), crowded housing (P = 0.001), damp houses (P = 0.001), being fed with breast milk and complementary food (P = 0.001), use of synthetic bedding (P = 0.024), and being the oldest child in the family (P = 0.001) were the considered risk factors for an immunoglobulin-E (IgE)-mediated food allergy. A low frequency of yoghurt consumption by mother (P = 0.001) and use of wool bedding (P = 0.018) were identified as risk factors for non-IgE-mediated food allergies. Low socioeconomic status (P = 0.001) played a protective role against both IgE- and non-IgE-mediated food allergies whereas breastfeeding played a protective role against IgE-mediated food allergies (P = 0.030). CONCLUSION: The most important aspect of this study was that it separately identified prenatal, neonatal, and postnatal risk factors for IgE- and non-IgE-mediated food allergies.

A set of clinical and laboratory markers differentiates hyper-IgE syndrome from severe atopic dermatitis.

Hyper-IgE syndrome (HIES) patients may share many features observed in severe atopic dermatitis (SAD), making a diagnostic dilemma for physicians. Determining clinical and laboratory markers that distinguish both disorders could provide early diagnosis and treatment. We analyzed patients (DOCK8 deficiency:14, STAT3-HIES:10, SAD:10) with early-onset SAD. Recurrent upper respiratory tract infection and pneumonia were significantly frequent in HIES than SAD patients. Characteristic facial appearance, retained primary teeth, skin abscess, newborn rash, and pneumatocele were more predictable for STAT3-HIES, while mucocutaneous candidiasis and Herpes infection were common in DOCK8 deficiency, which were unusual in SAD group. DOCK8-deficient patients had lower CD3+ and CD4+T cells with a senescent phenotype that unique for this form of HIES. Both DOCK8 deficiency and STAT3-HIES patients exhibited reduced switched memory B cells compared to the SAD patients. These clinical and laboratory markers are helpful to differentiate HIES from SAD patients.

Prevalence of atopic diseases in children with papular urticaria.

BACKGROUND: Papular urticaria is a hypersensitivity reaction characterized by chronic and recurrent papular erythema. It occurs as a result of the bites of mosquitoes, fleas, bed bugs, and other insects; and it is generally seen in children. This study examines the prevalence of atopic diseases in patients with papular urticaria. METHODS: The medical records of 130 pediatric patients with the diagnosis of papular urticaria between August 2017 and August 2019, whose disease progression was followed in two tertiary care centers, were reviewed retrospectively. The patients were divided into two groups: under 5 and above 5 years old. The prevalence of the atopic disease in children with papular urticaria was compared with those in age-matched controls without papular urticaria. RESULTS: The study included 130 patients who were diagnosed with papular urticaria (64 males, 66 females, median age: 60 months). The prevalences of atopic disease, recurrent wheezing, and atopic dermatitis were higher in the group under 5 years old with papular urticaria than in the same-age control group (p=0.001, 0.002, and 0.001, respectively). The prevalences of atopic disease, asthma, allergic rhinitis, and atopic dermatitis were higher in the group above 5 years old with papular urticaria than in the same-age control group (p=0.001, 0.001, 0.001, and 0.007, respectively). CONCLUSIONS: Many children with papular urticaria are atopic children. These patients should be assessed not only in terms of papular urticaria but also in terms of comorbid atopic diseases.

An examination of the relationship between regulatory T cells and symptom flare-ups in children and adolescents diagnosed with chronic tic disorder and Tourette syndrome.

BACKGROUND: Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder characterized by several motor and phonic tics. AIMS: In this study, we aimed to compare activated regulatory T cell (Treg) values between patients with TS/chronic tic disorder (CTD) and age- and sex-matched healthy controls (HCs). MATERIALS AND METHOD: Patients with TS/CTD and age- and sex-matched HCs were included in the study. The severity of the disease was evaluated using the Yale Global Tic Severity Scale. CD4+CD25+CD127low Tregs from the patient group and the control group were compared using flow cytometry. RESULTS: The study included 48 patients diagnosed with TS/CTD (36 males and 12 females, mean age: 11.58 ± 2.61) and 24 HCs (18 males and 6 females, mean age: 11.63 ± 2.60). The TS/CTD group had significantly higher activated regulatory T percentile with respect to the T helper value compared to the HCs (p = 0.010). Lymphocyte count, T lymphocyte count, T lymphocyte percentage, T-helper lymphocyte count, and T-helper lymphocyte percentage were lower in the patient group compared to the control group (p = 0.024, 0.003, 0.007, <0.001, <0.001, respectively). The comparison of three groups (mild, moderate-severe, and HCs) revealed that T lymphocyte number and percentage and the T helper number and percentage were significantly higher in the HC group compared to the moderate-severe group, whereas the activated Treg percentage with respect to the T helper value was significantly higher in the moderate-severe group compared to the HC group (0.002, 0.026, <0.001, <0.001, 0.027, respectively). CONCLUSION: Our results suggest that Tregs may have a role in the pathogenesis of TS/CTD.

Characteristics of persistent diaper dermatitis in children with food allergy.

BACKGROUND/OBJECTIVES: Diaper dermatitis is often caused by irritant contact occurring beneath the diaper of an infant, and it is aggravated by factors such as dampness, friction, urea, and feces. Food-allergic patients are known to exhibit various skin lesions ranging from urticaria to eczema. This study aims to determine the relationship between persistent diaper dermatitis and food allergy. METHODS: A retrospective chart review was conducted of pediatric patients with a diagnosis of persistent diaper dermatitis between August 2015 and November 2017. RESULTS: The study included 157 patients diagnosed with persistent diaper dermatitis (67 male, 72 female; median age: 13 months). Diaper dermatitis was more common and included the whole perineum in children who had multiple food allergies (P = 0.001). In children with multiple food allergies, the course of diaper dermatitis was more severe, and the condition did not respond to topical treatment (P = 0.025). A longer elimination diet was required for patients with Type I reactions and persistent diaper dermatitis (P = 0.018). In patients with Type II and mixed reactions, diaper dermatitis was more diffuse and covered the whole perineum (P = 0.025). In patients with Type II and mixed reactions, diaper dermatitis was more severe and did not respond to topical treatment (P = 0.025). CONCLUSIONS: Persistent diaper dermatitis lasting longer than a month may be associated with food allergy. The diaper rash may also be the only indicator of the food allergy. Elimination of the responsible food may allow these patients to recover from persistent diaper dermatitis.

Cyclic manner of neutropenia in a patient with HAX-1 mutation.

Introduction: Severe congenital neutropenia (SCN) includes a group of genetic disorders which cause to arrest of neutrophil maturation. SCN can be associated with heterogenous group of genetic defects in ELANE, GFI1, HAX1, G6PC3, JAGN1, VPS45 or activating mutations in the Wiskott-Aldrich syndrome (WAS) gene. Aim: Here we report a patient who has a HAX1 mutation presented with cyclic manner. Case Report: A 6 year old female patients was admitted with recurrent apthous stomatitis. We followed the patient as cyclic neutropenia according to complete blood count results 2 times for 6 weeks. After persistant neutropenia developed during a severe varicella infection, we analysed HAX1 mutation, the result was interesting and incompatible with reported cyclic neutropenia patients. Conclusion: We suggest that HAX1 deficiency should be thought in patients who have normal neutrophil counts in the between of infections.

The value of the clinical history for the diagnosis of immediate nonsteroidal anti-inflammatory drug hypersensitivity and safe alternative drugs in children.

BACKGROUND: Diagnosing hypersensitivity reactions that develop as a result of nonsteroidal anti-inflammatory drugs (NSAID) with a history is mostly misleading, and skin tests and/or provocation tests are needed for a definitive diagnosis. OBJECTIVE: To determine the frequency of actual NSAID hypersensitivity and whether there are any parameters in the history to predict NSAID hypersensitivity. In addition, to determine safe alternative drugs for children who are diagnosed with actual NSAID hypersensitivity. METHODS: Children with a history of NSAID hypersensitivity were evaluated by an allergist. Safe alternatives in children with a confirmed NSAID hypersensitivity were found by oral provocation tests. RESULTS: Sixty-four patients who were admitted with a suspicion of immediate-type reaction to NSAIDs were included in the study. The median age of the patients was 6 years old (range, 1-17 years), and 37 of the patients (57.8%) were boys. We performed skin tests for suspected NSAID in 35 patients (54.7%). Of these, two had positive results. Provocation tests were performed with 62 patients whose skin test results were negative or for whom skin tests were not available. During the provocation tests, 16 patients (25.8%) developed reactions. Low- and high-dose acetaminophen, nimesulide, and tolmetin sodium were used to find safe alternative drugs. Two patients developed reactions to high-dose acetaminophen but no reaction to nimesulide and tolmetin sodium. When statistically significant parameters were analyzed in a logistic regression model, the presence of multiple NSAIDs hypersensitivity in the patient history (odds ratio 26.6 [95% confidence interval, 1.47-481.63]; p = 0.026) and the emergence of a reaction within an hour (odds ratio 26.4 [95% confidence interval, 1.73-403.11]; p = 0.019) were found as the independent factors to predicted actual NSAID hypersensitivity. CONCLUSION: The emergence of a reaction within an hour of taking the drug and the presence of multiple NSAIDs hypersensitivity history increased the possibility of actual NSAID hypersensitivity. Nimesulide, low-dose acetaminophen, and tolmetin sodium could be used as safe alternative drugs in patients with multiple NSAIDs hypersensitivity.

The Platelet Parameters as Inflammatory Markers in Preschool Children with Atopic Eczema.

BACKGROUND: Mean platelet volume has been frequently used as an inflammatory marker in various diseases associated with inflammation. In this study, we compared platelet parameter levels between preschool children with and without atopic eczema (AE). METHODS: Preschool children with AE and age-matched healthy children were included in the study. Complete blood count was assessed in children with AE while platelet parameters were compared between children with and without AE. RESULTS: One hundred twenty eight pediatric patients (78 boys, mean age: 14 months) diagnosed with AE and 128 healthy patients (71 boys, mean age: 12 months ) were included in the study. There were no statistically significant differences between the genders (p = 0.375) and ages (p = 0.273) of both groups. WBC (p = 0.952), Hb (p = 0.370), MCV (p = 0.314) and RDW values (p = 0.124), and platelet counts (p = 0.198) of both groups were similar. In the AE group, while the MPV value was found to be higher (p = 0.003), mean PDW value (p = 0.025) and PLT/MPV ratio were found to be lower (p = 0.021). In addition, there was no correlation between the severity of AE and MPV (rho; 0.1, p = 0.257), PDW (rho; -0.1, p = 0.269) and PLT/MPV (rho; 0.07, p = 0.432) ratio. CONCLUSIONS: In patients with AE, as a sign of inflammation, PDW value and PLT/MPV ratio decrease while MPV value increases. This study has also shown that there is no association between the severity of AE and platelet parameters.

Cutaneous leukocytoclastic vasculitis associated with anti-tuberculosis drugs.

Leukocytoclastic vasculitis (LCV), a disease characterized by inflammation of the small vessels, presents with palpable purpura, especially in the lower extremities. Its etiology is known to include drugs, infection, collagen tissue disease, and malignancy, but LCV caused by anti-tuberculosis drugs is very rarely seen. This report describes the case of a 12-year-old girl who developed LCV with rifampicin and ethambutol while undergoing anti-tuberculosis treatment due to extensive pulmonary involvement.

Novel NLRP12 mutations associated with intestinal amyloidosis in a patient diagnosed with common variable immunodeficiency.

Heterozygous mutations in the NLRP12 gene have been found in patients with systemic auto-inflammatory diseases. However, the NLRP12-associated periodic fever syndromes show a wide clinical spectrum, including patients without classical diagnostic symptoms. Here, we report on a 20-year-old female patient diagnosed with common variable immunodeficiency (CVID), who developed intestinal amyloidosis and carried novel compound heterozygous mutations in NLRP12, identified by whole exome and transcriptome sequencing. CVID is a primary immunodeficiency characterized by low serum immunoglobulins, recurrent bacterial infections and development of malignancy, but it also presents with a magnitude of autoimmune features. Because of the unspecific heterogeneous clinical features of the disease, a delay in diagnosis is common. Secondary, inflammatory (AA type) amyloidosis has infrequently been observed in CVID patients. Based on our case observation and a critical review of the literature, we suggest that NLRP12 mutations might account for a small fraction of CVID patients with severe auto-inflammatory complications.

Relationship between hypogammaglobulinemia and severity of atopic dermatitis.

BACKGROUND: Atopic dermatitis is an itchy, inflammatory, chronic, or chronically relapsing skin disease. The disease occurs in people who have an "atopic tendency" or may appear as a clinical sign of primary immunodeficiency. OBJECTIVES: To determine the relation between severity of atopic dermatitis and hypogammaglobulinemia. METHODS: One hundred sixty pediatric patients with atopic dermatitis (98 boys and 62 girls, 1-60 months old, median age 14.5 months) and 95 healthy children (57 boys and 38 girls, median age 16 months; control group) were included in the study. In patients with atopic dermatitis, the severity of disease was determined by the SCORing Atopic Dermatitis index. Serum immunoglobulin levels of all patients and children in the control group were measured by nephelometry on admission. RESULTS: The incidence of hypogammaglobulinemia was higher in patients with atopic dermatitis than in the control group (P = .009). The main reason for this difference was the low level of IgG in the atopic dermatitis group (P = .024). Analysis of the relation between hypogammaglobulinemia and the severity of atopic dermatitis showed no statistically significant difference between the group with mild to moderate atopic dermatitis and the group with severe atopic dermatitis with respect to hypogammaglobulinemia (P = .859), IgG (P = .068), IgA (P = .410), and IgM (P = .776) values. CONCLUSION: Hypogammaglobulinemia was more frequent in patients with atopic dermatitis compared with the control group, mostly owing to the low IgG level. Hypogammaglobulinemia is not associated with the severity of atopic dermatitis.

Management of subglottic hemangioma with propranolol.

Subglottic hemangioma is a rare but life- threatening condition which requires intervention. It generally starts proliferating in the first and second months of lifespan and whether there is a respiration problem or not, it causes biphasic stridor. Its diagnosis generally requires direct laryngoscopy or direct screening through bronchoscopy. This case report presents a 45-day-old girl who had subglottic hemangioma presenting with wheezing and stridor. Our case took propranolol with a dose of 2 mg/kg/day and within 48 h after the start of the treatment, obstructive symptoms started to alleviate considerably.

The Effect of Serum Vitamin D Level on Allergic Rhinitis Symptoms in Children.

Background: Allergic rhinitis (AR) is a chronic disease that is becoming increasingly common worldwide and has a negative impact on school performance, work performance, and quality of life. The aim of this study was to investigate the effect of vitamin D on the symptoms of AR in children. Methods: Serum vitamin D levels of children with AR and age-matched healthy controls were compared using the high-pressure liquid chromatography method. The relationship between serum vitamin D levels and symptoms and severity of AR was then examined. Results: The study included 137 patients diagnosed with AR (76 males, 61 females; median age: 11 years). Serum vitamin D levels were lower in the patient group than in the control group (P = 0.001), lower in all aeroallergen groups (mites, pollen, and multiple inhalants) than in the healthy control group (P = 0.001), and lower in both the perennial AR group and the seasonal AR group than in the control group (P = 0.001). Spearman correlation analysis showed that there was no correlation between symptom score and vitamin D level (rs = -0.099; P = 0.25). Conclusions: We found no correlation between serum vitamin D level and symptoms and severity of AR. Serum vitamin D levels were lower in children with AR than in healthy children.

A novel ITGB2 variant with long survival in patients with leukocyte adhesion defect type-I.

Leukocyte adhesion deficiency is an autosomal recessive primary immunodeficiency that has been divided into three types: LAD1 (beta-2 integrin (CD18) family deficiency/defect), LAD2 (absence of fucosylated carbonhydrate ligands for selectins) and LAD3 (defective activation of all beta integrins). However, recently LAD4 has been described in cystic fibrosis patients, with a defect in integrin activation reported in monocytes. LAD-I is the most common type and prevalence of 1 in 1,000,000 live births. Clinical features of LAD patients are recurrent bacterial and fungal infections, omphalitis with delayed umbilical stump separation, significant leukocytosis especially neutrophilia during infection periods, impaired pus formation, and delayed traumatic or surgical wound healing. Flow cytometry is considered a useful tool for rapid diagnosis of the disease. The study of CD18 and CD11 (a, b, c) expression patterns in peripheral blood leukocytes helps to distinguish different phenotypes of LAD-I. In general, patients with ≥ 2% CD18 expression tend to have a less severe infection and often survive until adulthood, whereas < 2% CD18 expression often results in death in infancy. In this case report, three siblings, 10, 15, and 17 years old, diagnosed with leukocyte adhesion defect type 1 in adolescence age group, are presented.

Effects of modifying visual inhaler spacer usage instructions on correct usage rate of untrained users.

BACKGROUND: Pressurized metered-dose inhalers (pMDIs) used with spacers are considered the method of choice for delivery of inhaled drugs in preschool-age children. The aim of this study was to determine the effects of modifying the visual inhaler spacer usage guidelines on the correct usage rate. METHODS: The parents and caregivers of patients <6 years old who were prescribed inhalers with spacers for the first time were included in our study. The participants were randomly divided into a modified visual inhaler spacer usage guidelines group and an unmodified visual inhaler spacer usage guidelines group. All study participants underwent face-to-face interviews and completed questionnaires. RESULTS: A total of 510 participants with a median age of 31 (range, 20-46) years were included in this study. The modified visual guidelines group included 254 (49.6%) participants, and the unmodified visual guidelines group included 256 (50.4%) participants. One hundred sixty-five (65.2%) of the 254 participants in the modified visual guidelines group correctly demonstrated the inhaler spacer technique. In contrast, only 21 (8.2%) of the 256 participants in the unmodified visual guidelines group correctly demonstrated the inhaler spacer technique (p < 0.001). When comparing the inhaler spacer usage steps between the 2 groups, the modified visual guidelines group demonstrated the steps more correctly and more quickly (p < 0.001). CONCLUSION: The current visual inhaler spacer usage guidelines are insufficient. We believe that improving the visual inhaler spacer usage guidelines, in particular, will increase the correct usage rate and decrease the number of usage errors.