Neurological involvement in patients with primary immunodeficiency

Introduction: Primary immunodeficiency diseases (PID) are defined by recurrent infections, allergies, autoimmunity, and malignancies. Neurologic symptoms are one of the major components of some immunodeficiency syndromes, such as Ataxia-Telangiectasia (AT), Nijmegen breakage syndrome (NBS), and Purine Nucleoside Phosphorylase (PNP) deficiency, which are considered as the primary involvement. Various pathological mechanisms, DNA repair disorders, metabolic abnormalities, and autoimmune phenomena have also been linked with neurological conditions. Materials and method: We retrospectively assessed the neurological involvement in 108 patients out of 6000 with PID in this study. Results: The female/male ratio of the cases was 49/59, and the median age was 13 years (min = 1; max = 60). Neurological problems were detected at a median age of 7 years (min = 0.5; max = 30). Di George Syndrome (DGS) and CVID (common variable immunodeficiency) were the most common diseases in our cohort (n = 31, 30% and n = 30, 27%, respectively). The most frequent outcomes were cognitive delay (n = 63, 58%), epilepsy (n = 25, 23%), and ataxia (n = 20, 18%). Central nervous system involvement was found in 99% of the patients (n = 107), and peripheral nervous system complication was found in only one patient with CVID and chronic inflammatory demyelinating polyneuropathy (CDIP). Cranial MRI was found to be abnormal in 74% (n = 80) of the patients. MRI findings included cerebellar atrophy (n = 33, 34%), white matter lesion (n = 27, 28.4%), cerebral atrophy (n = 21, 22.3%), gray matter lesion (n = 6, 6.3%), hydrocephalus (n = 5, 5,3%), and pituitary gland lesion (n = 3, 3.2%), intracranial hemorrhage (n = 3, 3%), intracranial vasculitis (n = 3, 2.7%), and arterio-venous malformation (n = 1, 0,9%) (AU)

Neurological involvement in patients with primary immunodeficiency.

INTRODUCTION: Primary immunodeficiency diseases (PID) are defined by recurrent infections, allergies, autoimmunity, and malignancies. Neurologic symptoms are one of the major components of some immunodeficiency syndromes, such as Ataxia-Telangiectasia (AT), Nijmegen breakage syndrome (NBS), and Purine Nucleoside Phosphorylase (PNP) deficiency, which are considered as the primary involvement. Various pathological mechanisms, DNA repair disorders, metabolic abnormalities, and autoimmune phenomena have also been linked with neurological conditions. MATERIALS AND METHOD: We retrospectively assessed the neurological involvement in 108 patients out of 6000 with PID in this study. RESULTS: The female/male ratio of the cases was 49/59, and the median age was 13 years (min = 1; max = 60). Neurological problems were detected at a median age of 7 years (min = 0.5; max = 30). Di George Syndrome (DGS) and CVID (common variable immunodeficiency) were the most common diseases in our cohort (n = 31, 30% and n = 30, 27%, respectively). The most frequent outcomes were cognitive delay (n = 63, 58%), epilepsy (n = 25, 23%), and ataxia (n = 20, 18%). Central nervous system involvement was found in 99% of the patients (n = 107), and peripheral nervous system complication was found in only one patient with CVID and chronic inflammatory demyelinating polyneuropathy (CDIP). Cranial MRI was found to be abnormal in 74% (n = 80) of the patients. MRI findings included cerebellar atrophy (n = 33, 34%), white matter lesion (n = 27, 28.4%), cerebral atrophy (n = 21, 22.3%), gray matter lesion (n = 6, 6.3%), hydrocephalus (n = 5, 5,3%), and pituitary gland lesion (n = 3, 3.2%), intracranial hemorrhage (n = 3, 3%), intracranial vasculitis (n = 3, 2.7%), and arterio-venous malformation (n = 1, 0,9%). Primary involvement (a component of the disease) was 60% (n = 65), and secondary (infection or autoimmunity) and tertiary involvements (structural or incidental lesions) contributed 20% (n = 20) each in the patients. CONCLUSION: In this study, we describe the various neurologic findings of patients with PID. The neurologic presentation may represent the initial manifestation of certain types of PID. Early diagnosis and treatment are essential to prevent or reduce further neurologic damages.

Therapeutic modalities and clinical outcomes in a large cohort with LRBA deficiency and CTLA4 insufficiency.

BACKGROUND: LPS-responsive beige-like anchor (LRBA) deficiency (LRBA-/-) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) insufficiency (CTLA4+/-) are mechanistically overlapped diseases presenting with recurrent infections and autoimmunity. The effectiveness of different treatment regimens remains unknown. OBJECTIVE: Our aim was to determine the comparative efficacy and long-term outcome of therapy with immunosuppressants, CTLA4-immunoglobulin (abatacept), and hematopoietic stem cell transplantation (HSCT) in a single-country multicenter cohort of 98 patients with a 5-year median follow-up. METHODS: The 98 patients (63 LRBA-/- and 35 CTLA4+/-) were followed and evaluated at baseline and every 6 months for clinical manifestations and response to the respective therapies. RESULTS: The LRBA-/- patients exhibited a more severe disease course than did the CTLA4+/- patients, requiring more immunosuppressants, abatacept, and HSCT to control their symptoms. Among the 58 patients who received abatacept as either a primary or rescue therapy, sustained complete control was achieved in 46 (79.3%) without severe side effects. In contrast, most patients who received immunosuppressants as primary therapy (n = 61) showed either partial or no disease control (72.1%), necessitating additional immunosuppressants, abatacept, or transplantation. Patients with partial or no response to abatacept (n = 12) had longer disease activity before abatacept therapy, with higher organ involvement and poorer disease outcomes than those with a complete response. HSCT was performed in 14 LRBA-/- patients; 9 patients (64.2%) showed complete remission, and 3 (21.3%) continued to receive immunosuppressants after transplantation. HSCT and abatacept therapy gave rise to similar probabilities of survival. CONCLUSIONS: Abatacept is superior to immunosuppressants in controlling disease manifestations over the long term, especially when started early, and it may provide a safe and effective therapeutic alternative to transplantation.

A Comprehensive Assessment of Long-Term Complications in Patients with Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.

INTRODUCTION: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap syndrome are rare severe hypersensitivity reactions that lead to epithelial sloughing. Studies investigating the chronic multisystem effects of these syndromes and assessing patients in terms of quality of life (QOL), depression, and anxiety in the pediatric population are limited. In this study, we aimed to investigate the long-term effects of these diseases from a multisystem perspective. METHOD: Sixteen pediatric patients diagnosed with SJS, TEN, and SJS/TEN overlap syndrome were evaluated between September 2020 and March 2021. Physical and eye examinations were performed. To evaluate QOL and psychological status, Children's Dermatology Life Quality Index (CDLQI), Screen for Child Anxiety-Related Emotional Disorders (SCARED), and Children's Depression Inventory (CDI) were conducted. The patients' general characteristics, symptoms, and examination findings at their first admission were retrospectively obtained from the hospital's electronic records. RESULTS: Nineteen percent of the patients were female (n = 3). There were 7 patients (44%) with the diagnosis of SJS, 5 patients (31%) with TEN, and 4 patients (25%) with SJS/TEN overlap. The median follow-up time of the subjects was 6.5 years. The most common sequelae in the chronic period were skin changes (n = 13, 81%). Hyperpigmentation was the most common skin change (n = 9, 56%). In the last evaluation, 9 cases had eye involvement. In two cases, eye examination was normal in the acute phase, while ocular involvement was present in the chronic period. In 4 (50%) patients, there was height and/or weight percentile loss. Three patients' SCARED scores and 2 patients' CDI scores were high. According to the CDLQI survey, SJS, TEN, or SJS/TEN overlap syndrome had a small to moderate effect on the QOL in the 43% (n = 6) of the patients. The ANA values of 3 patients (60%) were positive at the follow-up and negative at the first admission. CONCLUSION: SJS, TEN, and SJS/TEN overlap syndrome may cause sequelae even after a long time of the onset of the disease. Patients' QOL and psychological status can be affected negatively. Ocular symptoms may develop in the follow-up, even without involvement in the acute period. Patients with SJS, TEN, and SJS/TEN overlap syndrome should be followed up in the chronic period and approached multidisciplinary.

The effects of health literacy on disease control in adolescents with asthma.

Objective: Increased health literacy (HL) improves the management of chronic diseases. Data on the HL levels of adolescents with asthma are limited. In this study, we aimed to investigate the HL levels of adolescents with asthma and the effect of HL levels on asthma control.Methods: Our research included 81 adolescents with asthma and 47 age and sex-matched controls. The validated version of the European Health Literacy Survey Questionnaire (HLS-EU-Q16) was utilized to estimate the participants' health literacy levels. In addition, the Asthma Control Test (ACT) was used to determine the degree of asthma control.Results: No significant difference between the asthmatic adolescents (n = 45, 55.6%) and the control group (n = 28, 59.6%) has been established in terms of the number of participants who were considered to have adequate HL (p = 0.658). The difference between the patient and control groups in health care, disease prevention, health promotion, and overall HL scores was determined non-significant. According to the ACT scores, the overall median HL score was significantly higher in patients with controlled asthma {34.4 (14.6:50)} than in those with uncontrolled asthma {32.3 (16.7:48.9)} (p = 0.037). It was determined that there was a difference in the distribution of controlled asthma, uncontrolled asthma, and controls in HL subgroups (poor, problematic-limited, sufficient, and perfect HL) (p = 0.002).Conclusion: The level of HL is associated with asthma control. A significant proportion of asthmatic adolescents who participated in our research displayed low HL scores. Further studies should be conducted to increase the HL levels of adolescents to achieve better asthma control.

The Impact of the COVID-19 Pandemic in Adolescents with Asthma.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is affecting people at any age and there is limited information about the effect of the COVID-19 pandemic on quality of life (QoL) in adolescents with asthma. In the present study, it was aimed to assess the attitudes of adolescents with asthma toward the COVID-19 pandemic and determine the effects of the pandemic on their QoL. METHODS: In total, 125 adolescents with asthma and 98 healthy adolescents participated in the present study. The questionnaire form consisted of three parts. In the first part, all the participants were asked whether they complied with the protective measures against COVID-19. The second part included questions for measuring the participants' level of concern about COVID-19, while the third part consisted of EUROHIS-QOL 8. RESULTS: The patient and control groups were similar in terms of the female/male ratio (55/70 and 48/50, respectively) and mean participant age (14.6 ± 2 and 15.1 ± 1.65 years, respectively) (P = 0.459 and P = 0.062, respectively). The prevalence of COVID-19 in the patients (n = 2, 1.6%) was lower than that in the controls (n = 6, 6.1%); however, the difference was not statistically significant (P = 0.142). The total EUROHIS-QOL score was significantly lower in the patients (31.2 ± 6.7) than in the controls (33.7 ± 4.4) (P < 0.001). The total QoL scores of asthmatic adolescents without other allergic disease (31.4 ± 6.7) was also lower than those of the controls (33.7 ± 4.4) (P = 0.009). Treatment disruption was significantly more common in patients who received subcutaneous immunotherapy (n = 20, 48.8%) than in those who did not (n = 8, 9.5%) (P < 0.001). Moreover, the patients had lower EUROHIS-QOL scores in the overall QoL, general health, finance, and home domains. CONCLUSION: Our results indicate that the mean QoL score of asthmatic adolescents during COVID-19 pandemic is lower than in the healthy population. Disruption in their treatment was most common in patients with asthma who were receiving subcutaneous immunotherapy.

Evaluation of pulmonary findings in patients with humoral immunodeficiency.

AIM: To determine the frequency of sinopulmonary infections, detect changes in the respiratory system, and measure functional capacity of the lungs in our patients with humoral immunodeficiency. MATERIAL AND METHODS: Fifty-six patients with humoral immunodeficiency were enrolled in this study. The clinical, laboratory, and radiologic data, and pulmonary function tests of the subjects were evaluated from their file records, retrospectively. RESULTS: The distribution of our patients was as follows: 25 patients had common variable immune deficiency, three patients had X-linked agammaglobulinemia, five patients had hyper immunoglobulin M syndrome, 19 patients had deficiency of immunoglobulin G subset, and four patients had selective immunoglobulin A deficiency. The most common symptom of the patients was chronic cough (n=47, 83.9%). The most common pathologies on high-resolution computed tomography of the chest were atelectasis and bronchiectasis (27.7%). The most common pathology in pulmonary function tests was the presence of moderate obstructive patterns along with restrictive patterns (n=6,12.5%). The FEV 1, FVC, and FEF 25-75 values were significantly lower in patients with common variable immunodeficiency compared with the patients who had IgG subset deficiencies (p=0.001, p=0.01, p=0.01). Among the patients who were treated with intravenous immunoglobulin, the age at the diagnosis of immunodeficiency was higher in patients with bronchiectasis (14.2±8.4 years) compared with those without bronchiectasis (10.1±11.4 years) (p=0.04). CONCLUSION: Clinical findings are not sufficient to monitor the structural and functional changes in the respiratory system, and patients should be evaluated using high-resolution computed tomography of the chest and pulmonary function tests.

Neonatal outcomes of premature infants born to preeclamptic mothers.

OBJECTIVE: Only limited studies with conflicting results are available on neonatal morbidity and mortality in infants born to preeclamptic mothers. The objective of this study was to evaluate neonatal morbidity and mortality in premature infants born to preeclamptic mothers. METHODS: Premature infants who were admitted to Uludag University, School of Medicine, Neonatal Intensive Care Unit between June 2006 and December 2007 were included in this study. The infants were evaluated according to their demographic characteristics and neonatal morbidities. RESULTS: Fifty-one infants born to preeclamptic mothers (study group) and 33 gestational age- and gender-matched infants born to normotensive mothers (control group) were included in this study. No statistical difference was found between the two groups in terms of demographic characteristics. However, frequency of neutropenia, duration of mechanical ventilation, and neonatal sepsis rates were found to be significantly higher in the study group compared with those of the control group. Although the rates of other neonatal morbidities such as bronchopulmonary dysplasia, retinopathy of prematurity, intraventricular hemorrhage and necrotising enterocolitis were found to be higher in the study group, the difference was not statistically significant. Mortality rates were also found to be similar in both groups. CONCLUSIONS: The infants born to preeclamptic mothers had significantly higher rates of neutropenia and sepsis. There were no significant difference in terms of other neonatal morbidities and neonatal mortality between the study and the control group.