Health-Related Quality of Life and Emotional Difficulties in Chronic Granulomatous Disease: Data on Adult and Pediatric Patients from Italian Network for Primary Immunodeficiency (IPINet).

Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by life-threatening infections, inflammation, and autoimmunity with an impact on health-related quality of life (HRQoL). Few data are available for children, whereas no study has been conducted in adults. Here, we investigated HRQoL and emotional functioning of 19 children and 28 adults enrolled in Italian registry for CGD. PEDsQL and SDQ were used for children and their caregivers, and adults completed the SF-12 questionnaire. Mean scores were compared with norms and with patients affected by chronic diseases. Comparisons were made for CGD patients who underwent or not hematopoietic stem cell transplantation (HSCT). When compared with norms, CGD children exhibited higher difficulties in social/school areas, peer relationship, and conduct/emotional problems (< 5 years of age), as scored by proxies. Differently, CGD adults reported higher difficulties both in mental and physical area than norms. Only for children, clinical status had a damaging effect on psychosocial and school dimensions, whereas age had a negative impact on social areas. No significant difference was observed between patients treated or not with HSCT. When compared with patients affected by chronic diseases, CGD children and adults both displayed fewer physical disabilities. Differently, in mental scale adults scored lower than those with rheumatology diseases and had similar impairment in comparison with patients with diabetes mellitus and cancer. This study emphasized the impact of CGD on HRQoL since infancy and its decline in adulthood, with emotional difficulties occurring early. HRQoL impairment should be considered in clinical picture of CGD and pro-actively assessed and managed by clinicians.

Psychological burden of pediatric primary immunodeficiency.

BACKGROUND: Primary immunodeficiency disorder (PID), being a chronic disorder, may increase the prevalence of psychopathologies, but there are few studies on the effect of disease-related factors on psychopathology in this population. The aim of this study was therefore to assess and compare three groups: children with PID who receive i.v. immunoglobulin treatment; children with juvenile idiopathic arthritis (JIA); and healthy controls with respect to their mental health status. METHODS: Forty-four children with PID, 32 children with JIA and 30 healthy controls, underwent psychiatric evaluation. The Childhood Depression Inventory and the screen for child anxiety-related emotional disorders questionnaire were completed by the participants. The child behavior checklist was completed by the mothers of the participants. In addition, disease-related factors were identified. RESULTS: The frequency of mood disorders between the three groups differed. There was no difference between the PID and JIA groups with respect to the prevalence of mood disorders and other psychopathologies. The disease-related factors were associated with the frequency of mood disorder in PID patients. CONCLUSION: The rate of psychopathology was similar in patients with PID and JIA and higher than the controls. Some of the disease-related factors were associated with the frequency of mood disorders in the PID patients.

Neonatal adoptive transfer of lymphocytes rescues social behaviour during adolescence in immune-deficient mice.

Accumulating evidence has shown that lymphocytes modulate behaviour and cognition by direct interactions with the central nervous system. Studies have shown that reconstitution by adoptive transfer of lymphocytes from wild type into immune-deficient mice restores a number of neurobehavioural deficits observed in these models. Moreover, it has been shown that these effects are mostly mediated by T lymphocytes. Studies of adoptive transfer thus far have employed adult mice, but whether lymphocytes may also modulate behaviour during development remains unknown. In this study, neonate lymphocyte-deficient Rag2-/- mice were reconstituted within 48 hours after birth with lymphoid cells from transgenic donors expressing green fluorescent protein, allowing for their identification in various tissues in recipient mice while retaining all functional aspects. Adolescent Rag2-/- and reconstituted Rag2-/- along with C57BL/6J wild-type mice underwent a series of behavioural tests, including open field, social interaction and sucrose preference tests. At 12 weeks, they were evaluated in the Morris water maze (MWM). Reconstituted mice showed changes in almost all aspects of behaviour that were assessed, with a remarkable complete rescue of impaired social behaviour displayed by adolescent Rag2-/- mice. Consistent with previous reports in adult mice, neonatal reconstitution in Rag2-/- mice restored spatial memory in the MWM. The presence of donor lymphocytes in the brain of neonatally reconstituted Rag2-/- mice was confirmed at various developmental points. These findings provide evidence that lymphocytes colonize the brain during post-natal development and modulate behaviour across the lifespan supporting a role for adaptive immunity during brain maturation.

Exercise Perception and Behaviors in Individuals Living with Primary Immunodeficiency Disease.

BACKGROUND: Routine exercise has been established as an effective way to improve overall health. The value of exercise has been established in many diseases, however, there are no studies investigating the impact of exercise for individuals with primary immunodeficiency disease (PID). The purpose of this study was to investigate exercise perceptions and behaviors in individuals diagnosed with PID. METHODS: An online survey was distributed over a four-week period. RESULTS: Of the 264 responses collected, most were females, 45-54 years old. Respondents reported a measurable loss of function impairing their daily activities due to loss of mobility/physical activity (41.32%), or loss of lung/pulmonary function (40.08%,). They felt exercise decreased stress level and improved their mental well-being (46.25%). Some indicated they participate in exercise (33.20%), while 36.84% had not participated in exercise for at least 1 year. Exercise was limited primarily due to fatigue (86.97%). CONCLUSION: Exercise is important for those with chronic medical conditions. Most individuals living with PID can participate in low/moderate physical activity, but struggle with vigorous physical activity, since fatigue is the greatest barrier. Respondents view exercise as beneficial, and would like to increase participation in an exercise program.

Genetic Counseling in Primary Immunodeficiency Disorders: An Emerging Experience in Egypt.

BACKGROUND: Primary immunodeficiency disorders (PIDs) are a heterogeneous group of diseases of the immune system leading to life-threatening infections, and, unless urgently treated with immune reconstitution, patients do not usually survive. With the continuing progress in molecular diagnosis, many mutations have been described in more than 300 genes. Genetic counseling has recently been considered an essential part of the management of PIDs. This study presents the experience of genetic counseling services in the largest PID center in Egypt, and reports on our management plan and the impact of prenatal diagnosis (PND) on families. METHODS: Based on the biochemical and molecular diagnosis of index cases, PND was offered for 10 families in 12 subsequent pregnancies. Five different genes were sequenced by Sanger sequencing in fetal samples. RESULTS: Seven fetuses were either normal or were carriers, while five fetuses were affected and human leukocyte antigen typing was performed, seeking a suitably related donor for stem cell transplantation. CONCLUSION: In spite of the genetic heterogeneity behind PIDs, genetic counseling should play a critical role in the management and future decisions of affected families.

The long-term quality of life in patients with persistent inflammation-immunosuppression and catabolism syndrome after severe acute pancreatitis: A retrospective cohort study.

PURPOSE: To explore clinical characteristics and long-term quality of life (QOL) in severe acute pancreatitis (SAP) patients with persistent inflammation-immunosuppression and catabolism syndrome (PICS). MATERIALS AND METHODS: SAP patients admitted to ICU were eligible for the retrospective cohort study if they needed prolonged intensive care (>14days). Post-ICU QOL was assessed by a questionnaire, including 36-item Short Form Health Survey (SF-36) and record of re-work in a long-term follow-up. RESULTS: 214 SAP patients were enrolled, in which 149 (69.6%) patients met the criteria of PICS. PICS patients had more complications and ICU days compared to non-PICS patients (P<0.001), and their post-ICU mortality was higher (P=0.046). When adjusted for confounders, PICS was independently associated with higher post-ICU mortality (hazard ratio 4.5; 95% CI, 1.2 to 16.3; P=0.024). The 36-item Short Form Health Survey (SF-36) score was lower for PICS group in six subscales (P<0.001). Only 28.8% patients in the PICS group returned to work compared to 60% patients in the non-PICS group (P=0.001) CONCLUSIONS: SAP patients with prolonged ICU stay had a high morbidity of PICS, which was a risk factor for the post-ICU mortality and poor long-term QOL.

Transitioning the Allergy/Immunology Patient from Childhood to Adulthood.

Allergic disorders and immunodeficiencies are generally chronic and even lifelong conditions, often changing over time, making the cautious transition of care from childhood to adulthood particularly important. Many, but not all, patients can continue to receive their care from the same physician as they transition through adolescence and emerging adulthood, made possible because allergy/immunology training programs require cross-training in the care of both pediatric and adult patients. Although keeping the same physician makes the transition easier for many allergy/immunology patients, even these patients face psychosocial issues unique to adolescents and emerging adults, including increased autonomy, risk-taking behavior, and medical self-management. Successful transition for patients with chronic allergic and immunologic conditions involves an understanding of the natural history of these conditions by patients and physicians alike, a gradual increase in self-management depending on individual readiness, and careful communication between pediatric and adult specialists as care is transitioned. [Pediatr Ann. 2017;46(6):e229-e234.].

Clinical Profile, Dosing, and Quality-of-Life Outcomes in Primary Immune Deficiency Patients Treated at Home with Immunoglobulin G: Data from the IDEaL Patient Registry.

BACKGROUND: Patients with primary immune deficiency (PID) often require immunoglobulin G (IgG, commonly referred to as Ig) replacement therapy to prevent infections and associated comorbidities. Ig therapy can be given either through intravenous or subcutaneous routes, and both can be done in the home setting. There is limited information available on the real-world diagnosis, management, and outcomes of this patient population, given the variable disease presentation and treatment options. The Immunoglobulin Diagnosis, Evaluation, and key Learnings (IDEaL) Patient Registry is designed to capture nursing, pharmacy, and patient-reported data for patients receiving Ig at home. OBJECTIVES: To (a) present a real-world population of patients with PID who have received Ig at home and (b) examine how differences in administration, dosing, and insurance affect health and quality-of-life outcomes in these patients. METHODS: As of July 2015, 383 patients receiving Ig therapy from Coram/CVS specialty infusion services, across multiple disease states, signed consent forms and enrolled in the IDEaL Patient Registry. Patients' referral paperwork, including lab values, and standard of care nursing and pharmacy follow-up forms were collected. Patients were mailed quality-of-life surveys at the time of enrollment and every 6 months after their enrollment. RESULTS: The most common diagnosis (78%) in these PID patients was common variable immunodeficiency (CVID). For Ig-naive adult patients, the average age at the start of treatment was 59 years. For pediatric patients, average age at start of treatment was 9 years. A majority of these PID patients (80%) received subcutaneous Ig (SCIg) at home, and 20% received intravenous Ig (IVIg). The average SCIg dose was 10 grams per week, or 130 mg per kg, and the average IVIg dose was 36 grams every 4 weeks, or 472 mg per kg. In the IVIg patient population, 34% had a dose or frequency change while on treatment, while 30% of the SCIg patients had a dose or frequency change. Patient-reported health and quality-of-life scores were generally positive. Route of administration did not affect patient perception of cost (P = 0.171), but whether the patient had private or government-backed health care did affect perception of cost (P = 0.036). CONCLUSIONS: For a disease state with an extremely variable presentation, data from the IDEaL Patient Registry provides further insights into the real-world clinical and diagnostic characteristics of this population, as well as dosing and treatment outcomes of home administration of Ig therapy. The majority of patients received SCIg infusions. SCIg dosing was on the lower end of the recommended mg per kg dose range, while IVIg patients were more in the middle of the recommended dose range. Patient outcomes on treatment were correlated with baseline status, suggesting that earlier detection and treatment of primary immune deficiencies may be critical in achieving beneficial outcomes on Ig therapy. DISCLOSURES: No outside funding supported this study. Seidu was compensated by Coram Clinical Trials for acting as primary investigator and reviewing data. Study concept and design were contributed by all the authors. Kearns, Kristofek, and Kiles collected the data, and data interpretation was performed by Kearns, Seidu, and Kristofek, along with Bolgar. The manuscript was written and revised primarily by Kearns, along with Kristofek, Bolgar, and Seidu.

Measurement of Health-Related Quality of Life in Primary Antibody-Deficient Patients.

BACKGROUND: Primary immunodeficiency diseases are a group of disorders that result from a variety of defects of the immune system. Primary antibody deficiencies (PADs) are the most common forms of these disorders. Occurrence of recurrent infections, autoimmune diseases, cancers, and lymphoproliferative disorders is higher in PAD patients. Chronicity of these diseases, delayed diagnosis, inadequate treatment, and treatment side effects may affect the quality of life (QoL) of PAD patients. Evaluating QoL is important for patient care, understanding the burden of these diseases, and finding the patients' major health problems. We investigated the QoL in a group of PAD patients undergoing regular follow-up and treatment at the Children's Medical Center Hospital in Tehran, Iran. METHODS: Seventy patients with a diagnosis of PAD in two age groups (younger and older than 18 years) were included. QoL was measured using PedsQL and SF-36 questionnaires. Correlation of demographic, clinical, and immunological parameters with QoL scores was assessed and patients' scores were compared with the normal population, using nonparametric tests of SPSS software. RESULTS: Patients expressed significantly reduced scores in some mental and physical components. Patients with longer follow-up periods had higher scores in mental components but physical component scores were still low. There was no significant correlation between sex, age, and disease types with scores. CONCLUSIONS: PAD patients had significantly lower scores in mental and physical components compared to normal population. By early diagnosis and long-term follow-up periods, we may be able to prevent complications and help patients to have a better QoL.

Anxiety and depression in adults with primary immunodeficiency: How much do these patients experience and how much do they attribute to their primary immunodeficiency?

INTRODUCTION: Primary immunodeficiency (PID) is a rare group of disorders that manifest similarly with infection, neoplasms, allergic, and autoimmune diseases, and are treated with injectable medications. Often the burden of disease and cost of management is excessive, and premature death is not uncommon. In light of these features of PID, it was our objective to survey our cohort to assess for factors that can influence depression and anxiety. METHODS: We used an investigator-developed survey, in addition to the Hamilton Depression Rating Scale (HAM-D) and the Hamilton Anxiety Rating Scale, after institutional review board approval of our pilot study, to determine the extent of anxiety and depression that our patients with PID experienced and variables that may have affected the difference of expression. The differences among groups were tested by using Wilcoxon rank sum tests, Kruskal-Wallis tests, and chi-square tests. RESULTS: The patients with PID had similar depression compared with the U.S. population, as assessed by the HAM-D scale. Risk factors associated with elevated HAM-D scores included the following: not driving, intravenous immunoglobulin therapy (versus subcutaneous), nurse-administered therapy (versus self-administered), having unpleasant adverse effects from therapy, previously attempted suicide, and family members with reported anxiety and/or depression. Anxiety was not significantly increased in our cohort. Risk factors for significantly elevated Hamilton Anxiety Rating Scale scores included the following: having poor health, an unhealthy diet, lack of refreshing sleep, and family members with reported anxiety and/or depression. CONCLUSION: Many factors influence depression and anxiety, and may add to the morbidity of PID. Patients should be assessed for our identified factors for depression and anxiety. Treatment or referrals should be initiated as it is hoped to improve our patients' quality of life and outcomes.

Life with a Primary Immune Deficiency: a Systematic Synthesis of the Literature and Proposed Research Agenda.

PURPOSE: The clinical immunology literature is punctuated with research on psychosocial dimensions of illness. Studies investigating the lived experiences and stated needs of patients with primary immune deficiencies and their families are essential to improving clinical management and determining the research questions that matter to patients and other stakeholders. Yet, to move the field forward, a systematic review of literature and proposed agenda is needed. METHODS: A systematic review was conducted via PubMed and Scopus to include original research on psychological, social, or behavioral aspects of primary immune deficiencies published between 1999 and 2015. A Title/Abstract keyword search was conducted, 317 candidate article abstracts were manually reviewed, and forward/backward reference searches were completed. RESULTS: Twenty-nine studies met inclusion criteria. These illuminate the complex psychological, social, and emotional experiences of primary immune deficiency. Themes included the potential for negative psychosocial impact from disease; adaptation over time; the multi-dimensional assessments of quality of life; familial impact; the important roles of hope, developing a sense of control, social support; and addressing anxiety/depression in our patients and their families. Methodological considerations and areas for improvement are discussed. CONCLUSION: We propose the research agenda focus on study creativity and rigor, with improved engagement with existing literature and critical study design (e.g., methodology with adequate statistical power, careful variable selection, etc.). This review highlights opportunities to advance psychosocial research and bring a brighter future to clinicians, researchers, and families affected by primary immune deficiency.

Immune deficiency influences juvenile social behavior and maternal behavior.

Mice with severe combined immunodeficiency (SCID) lack functional T and B lymphocytes, and have impaired cognitive abilities. We assessed social behaviors in male SCID and C57BL/6 (B6) juvenile mice. In a social preference task, SCID mice spent more time than B6 mice investigating a novel adult male mouse. In a social recognition task, SCID mice habituated to a novel ovariectomized mouse, but failed to show dishabituation when presented with an unfamiliar individual. We hypothesized that partial immune restoration could normalize behaviors. SCID pups (postnatal Day 7) received either saline or splenocytes from normal donors. Splenocyte-replaced SCID mice spent less time interacting with a novel mouse than saline-injected SCID or B6 control mice. Again, control SCID mice failed to dishabituate to a novel mouse, but splenocyte-replaced SCID mice showed dishabituation. In both of these studies, B6 and SCID pairs were used to produce offspring that remained with their dams until weaning. There are no studies of maternal behavior in SCID dams; therefore to investigate the potential role for this factor, we quantified maternal behavior in SCID and B6 dams; several significant differences were found. To control for differences in maternal care, we mated heterozygous SCIDs to produce offspring. These homozygous SCID and wild-type offspring reared by dams of the same genotypes displayed similar responses to a novel mouse; however, in the social recognition task, SCID males did not display dishabituation to a novel mouse. Taken together, our data indicate that Gene × Environment interactions influence social interactions in immune deficient mice.

Quality of life in children with primary antibody deficiency.

Primary antibody deficiency disorders (PADs) can have an excellent outlook if diagnosed early and treated appropriately, but require lifelong treatment with immunoglobulin replacement. Some carry risks of inflammatory complications even with optimal treatment. Quality of life (QoL) and the psychological impact of PADs has been relatively little studied, particularly in children. The purpose of this study was to evaluate QoL and psychological impact in a large group of children affected by a range of PADs, as well as a group with transient hypogammaglobulinemia of infancy (THI). Both parental and, where appropriate, child ratings, were collected using standardised questionnaires (PedsQL and SDQ). Higher rates of psychological difficulties, particularly emotional and peer-relationship difficulties were found in children with PAD when compared with healthy controls. Quality of life was poorer than in healthy controls, and also worse than in children affected by diabetes mellitus. Variations in QoL and the degree of psychological difficulties were found between specific diagnostic groups, with children affected by THI being amongst those with the lowest scores for QoL. Further studies are needed to corroborate and extend these findings, but this study confirms previous findings that primary antibody deficiency has a significant impact on quality of life and psychological well-being, and additionally suggests that the impact varies according to severity of the underlying condition. For those with significant difficulties psychological intervention at an early stage may be beneficial.

Psychiatric aspects of primary immunodeficiency diseases: the parental study.

Primary immunodeficiency diseases (PID) consist of a group of long-term illnesses which had permanent psychiatric effects on the patients and their parents. This study was designed to find out the most important origins and aspects of stressor in parents of PID patients.To assess the impact of psychiatric aspects in parents of PID patients, a valid and reliable questionnaire was compiled based on patients' complaints and consulting professionals in PID and psychology.Fathers of 26 PID patients (17 male and 9 female) were enrolled in this study. According to the result of this study, anxiety for long duration of disease of child (mean score= 4.42), anxiety for incurable diseases of child (mean score=4.23) and anxiety for side effects and complication of treatments on child (mean score=4.08) were the most important stressors of parents.The comparison between specific PID groups showed that there were significant differences between total score of groups (XLA= 92.8±31.2, CVID=78.7±19.5 and other types of PID= 90.7±22.5, p-value =0.37).Survey for finding fundamental stressors and continuation of psychological counseling are necessary to achieve successful management of PID patients and their parents.

Health-related quality of life in primary antibody deficiency.

Patients with primary antibody deficiencies (PAD) are susceptible to recurrent and chronic infections and a variety of complications. This study was performed to assess quality of life (QoL) of PAD patients who were under long term treatment and regular follow-up.Thirty six adults with proved diagnosis of PAD, who had received regular intravenous immunoglobulin replacement therapy, were enrolled in this study. The QoL of selected PAD patients was measured by Medical Outcomes Study 36-item Short-Form (SF-36) Health Survey questionnaire.The patients with PAD showed significantly reduced scores in physical component in comparison with healthy age-sex matched control subjects (60.2±20.1 vs. 85.5±4.7, P<0.001). Mental component score was also significantly decreased in the patient's group (59.8±19.5 vs. 72.3±3.4, P=0.002). There was a reverse association between SF-36 scores and number of infections episodes (r=-0.73 P=0.003). The patients with long delay diagnosis showed significantly lower SF-36 scores (r=-0.62, P=0.003).The patients with PAD who were diagnosed timely and managed appropriately seem to have lower complications and better QoL. However, the patients with severe phenotypes and long delay in diagnosis showed lower QoL, even in medical management.

Social outcome in children treated by haematopoietic cell transplant for congenital immunodeficiency.

Previous studies have reported increased rates of social difficulties in children treated by haematopoietic cell transplant (HCT). This study assessed social functioning in children with congenital immunodeficiency treated by HCT and investigated two potential underlying mechanisms that may explain social difficulties: executive function skills and physical appearance. In total, 31 children (8-16 years of age) were assessed on measures of social functioning and peer relationships, executive function and physical appearance. Results were compared with a control group of 31 healthy children, matched for age, gender, ethnicity and cognitive ability. Parent, teacher and self-report data were collected. HCT survivors were described by parents and teachers, but not by themselves, as experiencing more difficulties with social functioning than the control group. Executive function was not associated with social functioning. However, an objective measure of physical appearance was significantly associated with social functioning. Results suggest that children treated by HCT for congenital immunodeficiency do experience significant difficulties in social functioning, not solely accounted for by below average intelligence. These difficulties are associated with physical appearance, but not with executive functional skills. This has clinical implications for identifying and treating children at increased risk of difficulties with social functioning.

Subcutaneous administration of IgG.

The availability of IgG preparations that could be administered safely by the intravenous route was finally achieved in the early to mid-1980s. Intravenous immunoglobulin (IVIG) revolutionized the treatment of primary immune deficiency diseases (PIDD) and led to the discovery of the therapeutic value of high-dose IgG in autoimmune and inflammatory diseases not associated with PIDD. Improved therapy has improved outcomes and expectations, and most PIDD patients can lead fully active and productive lives. Administration of IgG by the subcutaneous route is effective and safe and overcomes obstacles to the use of IVIG in some patients. Many patients find administration of subcutaneous IgG at home more convenient than receiving IVIG at the Doctor's office or hospital. The coming years will see increased use of subcutaneous immunoglobulin in PIDD, which will be facilitated by advances leading to higher-concentration IgG products and easier delivery.