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Background: Common variable immunodeficiency disorder (CVID) is a condition associated with recurrent infections and non-infectious outcomes, including lung disease like bronchiectasis and granulomatous and lymphocytic interstitial lung diseases (GLILD), autoimmune disease, enteropathy, and lymphoma. Treatment involves initiation of replacement immunoglobulin (Ig), which is a lifelong commitment. Prior to Ig replacement, life expectancy for patients with CVID was less than 15 years. With replacement Ig, it has improved to over 50 years. In most cases, patients present to a clinician with a history of recurrent infections, and treatment is indicated. However, in patients with asymptomatic disease, the best timing to start treatment can be difficult to determine. Case: We present a case of an otherwise healthy male who had an incidental diagnosis of CVID. Results: Workup revealed hypogammaglobulinemia for over 30 year. Discussion: Though successful in reducing infections, Ig replacement can come with many side effects, as well as a heavy medical burden to the patient and the healthcare system. It is also a big life adjustment, and can greatly affect a patient's quality of life. In the military, a diagnosis of an immunodeficiency, and the need for monthly intravenous immunoglobulin (IVIG) can be detrimental to deployment readiness, and a patient's military career. Risks and benefits need to be weighed prior to initiating Ig therapy.

Antibodydeficiencies Epidemiology, Clinical manifestation, Diagnostics and Therapy Abstract. Primary Immune Deficiencies (PID) are caused by a genetically induced malformation/dysfunction of the immune system. Leading symptoms include susceptibility to infection, autoimmune diseases, lymphoproliferative, allergic as well as malignant diseases. They can be divided into ten main groups, including the primary antibody deficiency syndromes (PAD) in adults. The most well-known PADs include the variable immunodeficiency syndrome (CVID), Bruton's agammaglobulinaemia, IgG subclass deficiencies, immunoglobulin A deficiency, Antibody deficiency and transient childhood hypogammaglobulinaemia. Secondary hypogammaglobulinaemia by medicinal products, haematological diseases, malignancies and infections should be excluded. Delayed diagnosis of CVID is associated with a significant increase in morbidity and an increase in mortality. In addition to vaccinations, immunoglobulin replacement therapy is used therapeutically.

Accurate and timely diagnosis of primary immunodeficiencies (PID) is an ongoing effort. Individuals with PID can be severely impacted by their disease and many experience chronic complications, treatment burden, and reduced quality of life (QoL). This review focuses on the impact of delayed diagnosis and treatment burden on patient QoL and outcomes. Adults tend to experience longer delays in diagnosis than pediatric populations. The median diagnostic delay has reduced over recent decades, but remains high for some antibody deficiency variants, such as common variable immunodeficiency. The largest burden impacting QoL tends to be poorly controlled disease and persistent chronic conditions rather than treatment burden. Hospitalization, physician/emergency room visits, and bronchiectasis were the most expensive PID complications prior to diagnosis and cost analyses estimate cost reductions once appropriate treatment is initiated. A combination of poor awareness, lack of infrastructure, and resources supporting national registries play a major role in delayed diagnosis., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Reports on the immunogenicity and efficacy of the Spikevax® vaccine against SARS-CoV-2 in immunodeficient patients are still scarce. We aimed to evaluate the safety and immunogenicity of the vaccine in patients with primary humoral immunodeficiency., Methods: We enrolled 46 patients, including 34 patients with common variable immunodeficiency (CVID), 10 patients with unclassified hypogammaglobulinemia (HypoIg), and 2 patients with X-linked agammaglobulinemia. We collected the blood samples before vaccination (D 0), and 10 days (D +38) and 90 days (D +118) after the second vaccination. Further, we quantified SARS-CoV-2-specific T-cell response (QuantiFERON ELISA test), serum anti-RBD IgG, and anti-RBD IgA-specific antibodies (enzyme immunoassay)., Results: We found that the vaccination elicited predominantly mild adverse events, comparable to healthy population. Vaccination response negatively correlated with a value of Immune Deficiency and Dysregulation Activity in all measured parameters. D +38, seroconversion for anti-RBD IgG and anti-RBD IgA was observed in 65% and 21% CVID patients, respectively. SARS-CoV-2-specific T-cell response was detected in less than 50% of CVID patients. Meanwhile, HypoIg patients had 100%, 90%, and 60% positivity rates for anti-RBD IgG, anti-RBD IgA, and T-cell response, respectively. Three months after the second vaccination, 82% of the responders remained positive for anti-RBD IgG, but only less than 50% remained positive for T-cell activity in CVIDs. Low immunogenicity was observed in patients with lung involvement and/or rituximab treatment history. No SARS-CoV-2 infection was reported within 6 months after the second vaccination., Conclusion: Spikevax® seems to be safe with satisfactory immunogenicity in patients with primary humoral immunodeficiency., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Background: Intravenous immunoglobulins (IVIg) are the major treatment in inborn errors of immunity (IEI) disorders; However, IVIg infusions show some adverse effects. We aimed to assess the adverse reactions of IVIg infusions., Methods: Data of IVIg infusions in IEI patients were collected from 2011 to 2021. Totally, 363 IEI patients received IVIg regularly in Iran entered the study. The adverse reactions are classified regarding their severity and chronicity., Results: 22,667 IVIg infusions were performed in the study. 157 patients (43.2%) and 1349 (5.9%) infusions were associated with at least one type of adverse reaction. The highest rates of adverse reactions were seen in severe combined immunodeficiency. Myalgia, chills, headache, fever, and hypotension were the most frequent adverse effects of IVIg., Conclusion: The reactions affect almost half of the patients mainly in the first infusions which necessitate the close observation of IEI patients receiving IVIg., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Common variable immunodeficiency (CVID) is a kind of hypoimmunoglobulinemia of different spectrum with a dominant decrease of IgG with heterogeneity of clinical manifestations. In this publication, we provide an analysis of some world research sources on the diagnosis and treatment of the CVID and description of a clinical case of the CVID and the structural analysis of its frequency among primary immunodeficiencies in the adult population. We described the clinical case that demonstrates unusual manifestation of adult's outcome of CVID with cellular immune deficiencies and immunoglobulin А deficiency and RAG-2 gene mutation. There is the prevalence of CVID and hereditary hypo-/agammaglobulinemias among the primary diagnosed immunodeficiencies in the inhabitants of the Kyiv region, that is given the severity of clinical manifestations and need of replacement immunoglobulinotherapy. As early prognostic marker for the development of CVID and other defects of antibodies an immunoglobulin E deficiency can be considered.

Objective: Predictive factors associated with clinical outcomes of chronic norovirus infection (CNI) in primary immunodeficiency diseases (PIDD) are lacking., Method: We sought to characterize CNI using a multi-institutional cohort of patients with PIDD and CNI using the Clinical Immunology Society's CIS-PIDD Listserv e-mail group., Results: Thirty-four subjects (21 males and 13 females) were reported from centers across North America, Europe, and Asia. All subjects were receiving high doses (median IgG dose: 1200 mg/kg/month) of supplemental immunoglobulin therapy. Fifty-three percent had a complete absence of B cells (median B-cell count 0; range 0-139 cells/μL). Common Variable Immune Deficiency (CVID) subjects manifested a unique phenotype with B-cell lymphopenia, non O+ blood type, and villous atrophy (logistic regression model, P = 0.01). Five subjects died, all of whom had no evidence of villous atrophy., Conclusion: While Norovirus (NoV) is thought to replicate in B cells, in this PIDD cohort of CNI, B-cell lymphopenia was common, indicating that the presence of B lymphocytes is not essential for CNI., (Copyright © 2018. Published by Elsevier Inc.)

Deficient antibody production in patients with common variable immunodeficiency (CVID) is accompanied by an inability to produce free light chains (FLCs), particularly kappa (κ) FLC, due to B-cell dysfunction. We found that intravenous immunoglobulin (IVIg) administration, in a patient with CVID and (κ) FLC deficiency, for o short period of only 6 months, induced after discontinuation of treatment some kind of "long-lasting active immunity", leading to the secretion of immunoglobulin (κ) FLCs. A remarkable finding of our study is how effectively IVIg therapy led to a calculable (κ/λ) FLCs ratio, within the reference range. IVIg therapy may have functioned as an idiotype vaccine which induced a humoral response. To date, several questions remain open. For instance, from a clinical standpoint, we do not know whether this form of active immunotherapy has the potential to cure or just to control the immunoglobulin (κ) FLC deficiency. Further studies are necessary to confirm these findings.

Primary immunodeficiency (PID) diseases result from genetic defects of the immune system that increase a patient's susceptibility to infections. The types of infections that occur in patients with PID diseases are dictated largely by the nature of the immunodeficiency, which can be defined by dysfunction of cellular or humoral defenses. An increasing number of PID diseases, including those with both cellular and humoral defects, have antibody deficiency as a major feature, and as a result can benefit from immunoglobulin replacement therapy. In fact, the most common PID diseases worldwide are antibody deficiencies and include common variable immunodeficiency, congenital agammaglobulinemia, hyper-IgM syndrome, specific antibody deficiency, and Good syndrome. Although immunoglobulin replacement therapy is the cornerstone of treatment for the majority of these conditions, a thorough understanding of the specific infections for which these patients are at increased risk can hasten diagnosis and guide additional therapies. Moreover, the infection trends in some patients with PID disease who have profound defects of cellular immunity, such as autosomal-dominant hyper-IgE syndrome (Job/Buckley syndrome) or dedicator of cytokinesis 8 (DOCK8) deficiency, suggest that select patients might benefit from immunoglobulin replacement therapy even if their immunodeficiency is not limited to antibody defects. In this review, we provide an overview of the predisposition to infections seen in PID disease that may benefit from immunoglobulin replacement therapy., (© 2018 AABB.)

Background: Evans syndrome (ES) is a rare immune disorder in children, manifested by simultaneous or sequential autoimmune cytopenias (ACs) of unknown cause and having a chronic course with periods of exacerbation and remission. Some primary immunodeficiencies (PIDs) may present with autoimmune manifestations without infections, masking suspicion of them. The PIDs that can typically manifest as ES are autoimmune lymphoproliferative syndrome and common variable immunodeficiency (CVID)., Materials and Methods: Review of clinical charts and laboratory results of pediatric patients followed-up in the outpatient clinic of PID with a diagnosis of ES and humoral immunodeficiency., Results: Three pediatric patients, a boy and 2 girls, presented with corticosteroid-dependent ES. In the diagnostic approach, autoimmune lymphoproliferative syndrome was ruled out, and during follow-up, patients showed laboratory signs of humoral immune deficiency and were diagnosed with CVID. After initiating the recommended treatment for CVID with AC, patients improved without new exacerbations., Conclusions: These cases highlight the importance of detection of possible PID in the context of ES and the establishment of CVID treatment to control AC.

Primary immune deficiency disorders (PIDs) are rare conditions for which effective treatment is available. It is critical these patients are identified at an early stage to prevent unnecessary morbidity and mortality. Treatment of these disorders is expensive and expert evaluation and ongoing management by a clinical immunologist is essential. Until recently there has been a major shortage of clinical immunologists in New Zealand. While the numbers of trained immunologists have increased in recent years, most are located in Auckland. The majority of symptomatic PID patients require life-long immunoglobulin replacement. Currently there is a shortage of subcutaneous and intravenous immunoglobulin (SCIG/IVIG) in New Zealand. A recent audit by the New Zealand Blood Service (NZBS) showed that compliance with indications for SCIG/IVIG treatment was poor in District Health Boards (DHBs) without an immunology service. The NZBS audit has shown that approximately 20% of annual prescriptions for SCIG/IVIG, costing $6M, do not comply with UK or Australian guidelines. Inappropriate use may have contributed to the present shortage of SCIG/IVIG necessitating importation of the product. This is likely to have resulted in a major unnecessary financial burden to each DHB. Here we present the case for a national service responsible for the tertiary care of PID patients and oversight for immunoglobulin use for primary and non-haematological secondary immunodeficiencies. We propose that other PIDs, including hereditary angioedema, are integrated into a national PID service. Ancillary services, including the customised genetic testing service, and research are also an essential component of an integrated national PID service and are described in this review. As we show here, a hub-and-spoke model for a national service for PIDs would result in major cost savings, as well as improved patient care. It would also allow seamless transition from paediatric to adult services.

Most primary immunodeficiency disorders (PID) are the result of single gene defects. Based on this fact, more than 240 different entities have been identified. Those PIDs with predominant antibody deficiency are treated with immunoglobulin (Ig) replacement therapy. This review focuses on the diagnosis, clinical characteristics and treatment of patients suffering from PID, or secondary immunodeficiency disorders (SID) caused, for instance, by irradiation, immunosuppressive drugs or thymectomy. Common variable immunodeficiency (CVID) is the most commonly diagnosed and least understood form of PID, with a heterogeneous range of symptoms and genotypes, requiring individualized treatment plans. This includes adjusting the dose and treatment interval, administrating Ig by intravenous or subcutaneous injection by either pump or push, and finally deciding which treatment options are best for a given patient. Ig therapy can also be used to treat immunodeficiencies resulting from lymphoproliferative and autoimmune diseases or immunosuppression following organ transplantation; however, there is an urgent need for research in this field. Accurate and early diagnosis of PID is important to ensure that optimal treatment is started early to maintain the patient's health. Detailed patient registries have been established to increase awareness of PID, as well as provide a valuable resource for further research., (© 2014 British Society for Immunology.)

Purpose: Estimating the underlying demand for immunoglobulin (Ig) is important to ensure that adequate provision is made for patients with primary immune deficiency (PID) in the context of the competing demands for Ig and to ensure optimal therapeutic regimens. The concept of latent therapeutic demand (LTD) was used to estimate evidence-based requirements and compared to the actual Ig consumption in different countries. The estimates were performed for common variable immunodeficiency (CVID) and X-linked Agammaglobulinaemia (XLA), the two most commonly studied PIDs using Ig., Methods: The LTD model for CVID and XLA was derived using decision analysis methodology. Data for the epidemiology and treatment variables were obtained from peer-reviewed publications, clinical registries and publicly-available patient surveys. Incomplete data records from registries were excluded from analysis. The variables impacting LTD were ranked in order of sensitivity through a tornado diagram. The uncertainty surrounding the variables was modeled using probabilistic distributions and evaluated using Monte Carlo simulation., Results: Treatment dosage and prevalence were determined to be the most sensitive variables driving demand. The average potential usage of Ig for the treatment of CVID and XLA was estimated at 72 g per 1,000 population, which is higher than the estimated Ig usage in CVID and XLA of 27-41 g per 1,000 population in the US., Conclusion: The potential demand for treating CVID and XLA exceeds the currently observed usage of Ig in these disorders. Variable usage in different countries is due to varying prevalence and dosage practices. Under-reporting in patient registries represents a major obstacle to calculating the true prevalence of CVID and XLA. Modeling demand relies heavily upon accurate prevalence and practice estimates which reemphasize the importance of accurate registries and improved registry methods. As better data becomes available, revision of model variables provides opportunities to anticipate and prepare for evolving patient needs.

Aim: To analyze the incidence of primary immunodeficiencies (PIDs), to reveal the specific features of the course of this condition at the present stage, and to estimate the quality of health care to patients with PIDs., Subjects and Methods: An open-label prospective trial was performed in 94 patients with different forms of PIDs (63 with selective immunoglobulin A (IgA) deficiency and 31 with other more severe primary immunodeficiencies) who had been permanent residents in the Perm Territory in the period 1990 to 2012., Results: The registered PID cases were noted to be lower than the estimated ones. Over 22 years of follow-ups, the death rates for this group of patients with these diseases were 11%, and the disability rates were 27%. In severe PIDs (exclusive of selective IgA deficiency), these rates were as high as 35.5 and 96%, respectively. The rate of untimely diagnosis of severe PIDs was high (43%). Molecular genetic studies were conducted in only one tenth of the patents with this disease. PID treatment generally complied with the accepted medical standards. However, all patients with X-linked agammaglobulinemia were observed to have periodic irregularities of replacement therapy with intravenous immunoglobulins, which was a cause of death in 2 patients. Adult patients with common variable immune deficiency received no adequate replacement therapy. Timely diagnosis and adequate therapy could not only preserve the life of many patients with severe PIDs (64.5% survived), but could achieve its relatively satisfactory quality., Conclusion: As of now, PIDs ceased to be fatal diseases. To improve the quality of health care to patients with this pathology, there is a need to increase the awareness of the diagnosis and treatment of immunodeficiencies among physicians of different specialties, to extend the application of molecular genetic techniques, including those for prenatal diagnosis, and to continuously provide patients with essential drugs.

A prospective, open-label, multicenter, single-arm, Phase III study evaluated the efficacy and safety of Hizentra(®), a 20% human IgG for subcutaneous administration, in 51 primary immunodeficiency patients over 40 weeks. Patients previously on intravenous or subcutaneous IgG were switched to weekly subcutaneous infusions of Hizentra(®) at doses equivalent to their previous treatment. IgG levels achieved with Hizentra(®) were similar to pre-study levels with subcutaneous, and higher by 17.7% than pre-study levels with intravenous IgG. No serious bacterial infections were reported in the efficacy period. The rate of all infections was 5.18/year/patient, the rates of days missed from work/school, and days spent in hospital were 8.00/year/patient and 3.48/year/patient, respectively. Local reactions (rate 0.060/infusion) were mostly mild (87.3%). No serious, Hizentra(®)-related adverse events were reported. Individual median infusion durations ranged between 1.14 and 1.27 h. Hizentra(®) maintained or improved serum IgG levels without dose increases and effectively protected patients against infections., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Introduction: The epidemiology of primary immunodeficiencies (PID) is not well documented in Africa. The objective of this study was to describe the spectrum of PID at a tertiary paediatric centre in South Africa., Methods: A retrospective study was conducted on 168 patients diagnosed with PID from 1983 to 2009., Results: Over the study period, antibody deficiencies predominated (51%) followed by well-defined syndromes (24%). Common variable immunodeficiency was the commonest antibody deficiency. The mean age of diagnosis was 51 months overall but decreased significantly to 35 months over the last 9 years. Recurrent infections were the most common presenting complaint (74%). The overall mortality rate was 25% while combined immunodeficiencies accounted for 40% of the deaths., Conclusions: The spectrum of PID in South Africa was similar to international trends. The declining mean age of diagnosis indicated improved recognition of PID. Future research should focus on identifying children with PID more effectively.

Purpose of Review: The primary antibody deficiency syndromes are a rare group of disorders presenting at any age, with complex polygenic disorders, most commonly the common variable immunodeficiency disorders (CVIDs), predominating. With increasing patient survival on immunoglobulin therapy, there is an increasing focus on the complications of these disorders. Research into the cause of CVIDs has made use of the increased understanding of immune regulatory systems and B-cell signalling events and has made significant progress in the past 12 months., Recent Findings: Prevalence data from different geographical regions have been supplemented by more detailed incidence data on primary antibody deficiencies, revealing trends in diagnosis and management. Continued exploration of the role of genetic variations in TACI in CVID populations has improved our understanding of possible pathogenic events. The key role of naturally occurring regulatory T cells in the development of immune dysregulation in CVIDs has become more apparent. The role of dysfunction of the innate immune system in pathogenesis of CVID has begun to emerge. Novel clinical presentations of these disorders continue to be described., Summary: The recent findings in these areas will allow more precise prognostic and diagnostic information to be available for individual patients. The challenge remains to separate primary disease-causing factors from secondary disease-modifying phenomena.

The immune response consists of two main components: humoral immunity represented by B lymphocytes and cellular immunity maintained by the T lymphocytes. Immunoglobulins, produced by B-lymphocytes, are the main mediators of humoral immunity, and deficiencies at this level affect the body's response to infection. Plasmocytes produce nine antibody izotypes: immunoglobulins G (IgG1, IgG2, IgG3, IgG4), immunoglobulins M (IgM), immunoglobulins A (IgA1, IgA2), immunoglobulins D (IGD) and immunoglobulins E (IgE). Primary hypogammaglobulinemias are characterized by the occurrence of recurrent infections and, paradoxically, by the occurrence of autoimmune diseases. Characteristic for these diseases is that symptoms occur at 7-9 months after birth, when transplacental antibody titers transmitted from the mother decrease, and the infant's body is unable to synthesize them to normal levels. Primary hypogammaglobulinemias are transmitted genetically, but mutations at the molecular level are still not fully understood. The most common are: Bruton agammaglobulinemia, transient newborn hypogammaglobulinemia, selective immunoglobulin deficiency and variable common immunodeficiency. Treatment consists of monthly antibiotics and immunoglobulins, depending on antibody titers (except for IgA deficiency).

Background and Methods: Over the past 3 years, with support by the European Union within the 6th Framework Programme and by the pharmaceutical industry, the ESID Online Database has collected data from 7,047 patients with primary immunodeficiencies (PIDs) in 30 countries. The system is available via a standard internet browser for users in registered documenting centers with their personal login. It comprises a common core dataset for 212 PIDs and large disease-specific data models for 33 diseases. These can be used for international studies on these cohorts., Results: First analyses on the Therapy and Quality of Life section have shown that 42% of the registered living patients receive immunoglobulin replacement therapy. 76% of these receive intravenous immunoglobulins (IVIG), whereas 23% use the subcutaneous method of application (SCIG). In Germany, compared to the European figures, SCIG therapy is much more common, reaching 54%, whereas 46% of the patients receive IVIG. When analyzing the large cohort of patients with common variable immunodeficiency (CVID), patients on SCIG have less sick days and less days in hospital per year than those on IVIG., Conclusion: The acceptance of this new online system within Europe has been positive over the last few years and the database has now reached a state where it can be the basis for extensive international studies. However, with 551 patients, Germany only contributes 7.81% of the entered datasets. This is mainly due to a lack of time and manpower in the documenting centers and to time-consuming procedures for ethics approval.

Subcutaneous immunoglobulin G (SCIG) infusions as life-long replacement therapy in patients with primary antibody deficiences (PAD) is being applied increasingly. However, only a few published pharmacokinetic studies are available for this route of administration. Therefore, the pharmacokinetics of a 16% immunoglobulin G (IgG) preparation intended for subcutaneous use were investigated in patients with common variable immunodeficiency and X-linked agammaglobulinaemia. SCIG infusions (200 mg/kg body weight) were administered to 12 adult patients every 14 days for 24 weeks (total of 144 infusions). Pharmacokinetic parameters were determined based on serum IgG trough levels and antibody levels against tetanus. The median half-life of the total serum IgG and for the tetanus antibodies was 40.6 and 23.3 days respectively. Median in vivo recovery of serum IgG and tetanus immunoglobulins were 36% and 46% respectively. Median, preinfusion serum IgG trough levels per patient were high without major variations between infusions and ranged from 7.24 to 7.86 g/l. Safety, in terms of adverse events including systemic adverse reactions and local tissue reactions at infusions sites, was monitored throughout the study. Six mild, local tissue reactions were observed during the study in one patient. No systemic adverse reactions related to the study drug were observed and no serious other adverse event occurred during the study. It is concluded that the bi-weekly SCIG therapy was well tolerated in the study and that it results in high and stable serum IgG levels, offering an alternative therapy regimen to patients suffering from PAD.

Objective: One hundred and nine patients with primary antibody deficiencies were selected in order to determine the frequency of ENT complications., Method: Demographic information and ENT medical histories were collected for each patient. Duration of study for each patient was divided into two periods of before diagnosis and after diagnosis and the initiation of treatment., Results: Eighty-two of 109 patients (75.2 per cent) experienced ENT infections during the course of the disease (63: otitis media, 75: sinusitis and nine: mastoiditis). At the time of diagnosis, 52 (47.7 per cent) out of 109 patients presented with an ENT symptom. The frequencies of episodes were 27 for sinusitis and 25 for otitis media (one complicated with mastoiditis). After immunoglobulin replacement therapy the incidence of otitis media was reduced from 1.75 before treatment to 0.39 after treatment per patient per year (p = 0.008). The incidence of sinusitis also significantly decreased from 2.38 to 0.78 (p value = 0.011)., Conclusion: ENT infections are common medical problems in primary antibody deficiency patients. Persistent and recurrent ENT infections should be suspected as originating from a possible underlying immunodeficiency.

Primary immunodeficiencies are challenging in primary care settings, where clinicians often encounter patients with a history of recurrent infection. With advances in diagnostics and therapeutics, these disorders have been better understood and more successfully treated, yet their prognosis depends on early recognition of the disorder and initiation of the appropriate management. Because the primary care physician is most often the first physician encountered by a patient with immunodeficiency, primary care practitioners should be familiar with these rare but important disorders. This article provides an overview of the diagnosis and treatment of primary immunodeficiencies and two of the most common primary immunodeficiencies: common variable immunodeficiency and selective IgA deficiency.

Background: The primary immunodeficiency diseases cause a deficit in the production of antibodies. The chronic sinopulmonary disease is common and their clinic symptoms are diverse (pneumonia, bronchiectasis)., Objective: To know the frequency and type of pulmonary abnormalities in patients with primary immunodeficiency in treatment with intravenous immunoglobulin., Material and Methods: 24 files of patients with primary immunodeficiency were selected. Age, sex, primary immunodeficiency type, time of immunoglobulin treatment, chest X-ray finding, pulmonary computed tomography of high resolution (HRCT) and pulmonary function tests were registered. Measures of central tendency were calculated., Results: There was no predominance of gender; the average age was 14 years old. The common variable immunodeficiency and the Bruton's hypogammaglobulinemia represented 91% of the patients. The X-ray of thorax was abnormal in 33%, although there were not bronchiectasis. The high-resolution computed tomography scan (HRCT) was abnormal in 67%, and 75% had bronchiectasis., Conclusions: The pulmonary complications are common despite therapy with intravenous immunoglobulin. The HRCT is better than X-ray in these patients.

Making a correct diagnosis of a primary immunodeficiency disease is crucial for the selection of proper therapy. Although many cases go undiagnosed, there are also many instances of incorrect diagnosis that result in years of inappropriate treatment and failure to implement beneficial treatment. This article summarizes 2 actual cases in which incorrect diagnoses led to recommendations of unwarranted high-risk or costly treatments. Had the physicians chosen tests of immune function rather than relying on immunoglobulin levels or cell counts, they would have arrived at the true diagnoses.

Background: Although long-term intravenous immunoglobulin infusion is an effective treatment for children with antibody deficiencies, it can be complicated by systemic adverse reactions., Objective: To evaluate the adverse reactions of intravenous immunoglobulin therapy in patients with primary immunodeficiency., Methods: Seventy-one immunodeficient patients receiving intravenous immunoglobulin were evaluated during a 7-year period (1995-2002) at Children's Medical Center in Tehran, Iran. Immunological diagnoses were as follows: common variable immunodeficiency (31 patients), X-linked agammaglobulinemia (25 patients), IgG subclass deficiency (5 patients), hyper-IgM syndrome (2 patients), and ataxia-telangiectasia (8 patients)., Results: One hundred fifty-two cases (12.35%) of adverse reactions occurred following 1,231 infusions in 35 patients. The most frequent immediate adverse reactions were mild reactions (131 infusions), including chills, fever, flushing, muscle pains, nausea, headache, and anxiety. Moderate reactions, such as vomiting, chest pain, and wheezing, occurred in 19 infusions. Two patients experienced severe adverse reactions. The highest proportion (23.06%) of reaction to injection was in patients with common variable immunodeficiency., Conclusions: Intravenous immunoglobulin is a well tolerated medical agent for patients with antibody deficiency. However, to prevent occurrence of immediate adverse reactions during infusion in these patients, physicians should perform a detailed history and proper physical examination and check the titer of anti-IgA.

Congenital deficiencies of the immune system occur in children or adults and can cause severe or recurrent infections. The overall incidence of these immunodeficiency diseases is estimated at approximately 1 in 10,000, excluding selective immunoglobulin A deficiency, but this estimation is based on population studies, not hospital or clinic populations. The majority of immune defects involve antibody production; these immune deficiencies are found more often in adults than infants and children. In an allergy practice, recurrent infections are common, and determining if an immune defect is likely to be present can be problematic. Some guidelines concerning the clinical presentation and laboratory evaluation and treatment options can aid the practicing clinician.

A European multicenter study was conducted to obtain information on the current practices of immunoglobulin administration, the policies in use for the surveillance of the risk of hepatitis C virus (HCV) transmission, and the natural history of HCV infection in patients with hypogammaglobulinemia. Data from 1243 patients with primary immunodeficiencies in 16 countries demonstrated that 90% of patients with antibody deficiencies receive intravenous immunoglobulins in an inpatient setting, and 7% of patients are treated with subcutaneous immunoglobulins, mainly at home. Wide variations have been reported regarding the frequency and the type of tests monitored for the surveillance on the risk of viral hepatitis transmission. Only 60% of patients have been tested at least once for HCV RNA detection. Data from 71 HCV-infected patients demonstrated a rapid progression of HCV infection, with end-stage liver disease, in about 40% of patients. Ten percent of patients spontaneously cleared the virus, and about 30% are asymptomatic. Patients with CVID have a worse prognosis than patients with XLA.

We have identified 14 patients with diverse primary immunodeficiencies who have developed progressive neurodegeneration of unknown etiology. All patients had received immunoglobulin replacement therapy for a mean duration of 6.5 years (range of 0.5-13.5 years) at the time of first neurological symptoms. Diagnostic tests of blood and cerebrospinal fluid analyses included chemistry, cultures, PCR for viral genomes, and cytology. In addition, neuroimaging and electrophysiologic studies were performed. Brain tissue histology (n = 5) revealed nonspecific encephalitis with microglial infiltration and neuronal loss. Twelve patients died 6 months to 15 years (median 4.3 years) after onset of neurologic findings. No evidence of any infectious disease that could have explained our patients' progressive encephalopathy was found either during their lifetimes or postmortem. These patients may have had an unusual manifestation of primary immunodeficiency diseases, an autoimmune reaction against neuronal tissue, a yet undefined infectious agent, or a complication of IVIG therapy. To help determine the etiology of this rare complication, an international surveillance system for primary immunodeficiency patients who develop progressive neurodegeneration of unknown cause is recommended., ((c)2001 Elsevier Science.)

Objective: To characterize the clinical features of hepatitis C virus (HCV) infection associated with the administration of intravenous immunoglobulin (IVIG) in patients with varied immunodeficiencies., Design: Prospective collection of clinical and virologic data in patients determined to have HCV exposure associated with Gammagard., Setting: Outpatient department of Children's Hospital, Boston., Patients: Twenty-one patients with evidence of HCV infection were identified during a screening program initiated to detect infection in exposed individuals. They ranged from 5 to 53 years of age; 14 were children under age 18., Results: Six patients presented with severe clinical hepatitis before detection by screening, 13 were detected by screening only, and 2 were first detected by screening and subsequently developed symptomatic hepatitis. Follow-up is available on 20 patients; 4 without viremia at identification have remained clinically well. Hepatitis and viremia have resolved in 2, 2 additional subjects have developed normal alanine aminotransferase (ALT) values with persistent viremia, and 13 have biochemical and/or virologic evidence of chronic hepatitis. Eight patients (7 children) have undergone liver biopsies; 7 have histologic findings of chronic hepatitis, 5 have mild fibrosis, and 2 have moderate fibrosis. HCV genotypes 1a and 1b were observed with equal frequency in this group., Conclusions: Some HCV infections associated with IVIG had a more severe, acute course than is ordinarily described. This may be attributable to host factors, such as immunodeficiencies, or virologic factors, such as inoculum or genotype. Although a large percentage (87.5%) of these individuals developed chronic infection, the natural history is not as yet completely defined.

Immunoglobulins (IgG) as replacement therapy in primary antibody deficiencies can be given as intramuscular injections, or as intravenous or subcutaneous infusions. Our aims were to obtain information on the frequency of adverse systemic reactions during subcutaneous therapy, the occurrence and intensity of tissue reactions at the infusion sites, and serum IgG changes. Furthermore, we compared costs between the different replacement regimes. Our study included 165 patients (69 women, 96 men, aged 13-76 years) with primary hypogammaglobulinaemia or IgG-subclass deficiencies. Data were compiled from questionnaires filled in by the patients and from their medical records. 33,168 subcutaneous infusions (27,030 in home therapy) had been given. 106 (of which 16 were at home) adverse systemic reactions (100 mild, 6 moderate) were recorded in 28 patients (17%). No severe or anaphylactoid reactions occurred. Despite large immunoglobulin volumes given during 434 patient years (28,480 infusions), no signs have been found that indicate the transmission of hepatitis virus. Transient tissue reactions occurred at the infusion sites but were not troublesome to most patients and we found significant increases in mean serum IgG. The use of subcutaneous instead of intravenous infusions at home would reduce the yearly cost per patient for the health-care sector by US $10,100 in Sweden alone. We conclude that subcutaneous administration of IgG is a safe and convenient method of providing immunoglobulins. We were able to reach serum IgG concentrations similar to those by the intravenous therapy and we found that the method could also be used successfully in patients with previous severe or anaphylactoid reactions to intramuscular injections.