Cases Of Primary Immunodeficiency Diseases Research Articles

Treating inherited bone marrow failure syndromes and primary immunodeficiency diseases

Inherited bone marrow failure syndromes (IBMFS) are caused by genetic mutations at loci associated with DNA repair, telomere maintenance, and ribosome function. Hematopoietic stem cell transplantation (HSCT) can result in a permanent cure in transfusion-dependent patients if reduced-intensity conditioning and long-term screening for relapse can be successfully implemented. Primary immunodeficiency diseases (PIDs) arise from inborn errors of the host immune system and affected patients must protect themselves against intractable infections and immune system dysregulation. HSCT is curative in many pediatric patients; however, specific immunomodulatory therapies are now available for controlling autoimmune and/or autoinflammatory diseases. Advanced clinical sequencing technologies have continued to identify novel monogenic diseases that share the phenotype of hematological and immunological abnormalities, along with adult cases of IBMFS and/or PIDs. Importantly, genetic counseling is required for carrier detection while selecting sibling donors for HSCT. Here, we describe treatment strategies for IBMFS and/or PIDs and associated pitfalls.

The impact of combining educational program with the improving of infrastructure to diagnose on early detection of primary immunodeficiencies in children.

Early detection of primary immunodeficiency diseases (PID) is vital for adequate prevention and management of PID infectious complications. The objective of this study was to evaluate the impact of a model combining physician education and public awareness with the infrastructure to diagnose PID to improve its early detection in children. Three approaches were combined and the results were followed from February 2017 to February 2019 in Ternopil region, Ukraine: the education of primary care physicians and other specialists on early PID detection using workshops, trainings, and targeted publications; organization of public events and media appearances to raise PID awareness; performing immunological testing for patients with suspected PID. Among the 150 individuals that were screened, PID was diagnosed in 19 patients (12.7%). The majority of diagnosed PID cases were combined immunodeficiency with associated or syndromic features, followed by antibody deficiencies. Patients referred by the specialist doctors had the highest percentage of confirmed PID compared with those referred by primary care physicians (p = 0.0273) and risk group patients (p = 0.0447). Among warning signs in patients with PID, two or more pneumonias within 1year occurred most often (26.3%), followed by failure of an infant to gain weight or grow normally (21.1%). Among other signs of PID, dysmorphic features and microcephaly were the most prevalent (31.6%). In conclusion, a program combining physician education and public awareness with infrastructure needed to diagnose primary immunodeficiency diseases is an effective tool for early PID diagnosis. Physician education was a more effective tool compared with rising public awareness.

Cutaneous manifestations of primary immunodeficiency

Primary immunodeficiency diseases (PIDs) are a group of rare, chronic disorders with deficient or malfunctioning immune system. It commonly affects the hematopoietic system, with skin the second most affected organ. Skin involvement is observed in half of pediatric PID cases and often precedes the final diagnosis. Skin infections and eczemas are the two most common manifestations in PID.[1] Skin manifestations associated with PIDs can be of infectious and noninfectious causes. Common noninfectious causes are eczema, erythroderma, cutaneous granulomas, dysplasia, vasculitis, and telangiectasia. It is important to be aware of skin manifestations in pediatric patients as early detection of PID may aid in the management of serious immunologic conditions and prevent associated morbidity and mortality.

Vaccine immunization in children with primary immunodeficiency diseases

Primary immunodeficiency diseases (PID)are a heterogeneous group of congenital and genetically determined conditions caused by one or more defects of innate and/or adaptive immunity, which are a common retarding factor of vaccines immunization.The infections, however, play a major role in the final prognosis of most PID.The immune response after the vaccine injection may be impaired in some PID cases, even no protection is evoked.Moreover, some disease caused by the live vaccine virus or bacteria strains could occur after immunization.The contents of this paper is to introduce the consensus of the vaccine immunization based on the category of PID, immunization of the contacts and other concerns. Key words: Primary immunodeficiency disease; Vaccine; Immunization; Child

Investigation and management of primary immunodeficiency in South African children.

The primary immunodeficiency diseases (PIDs) are inherited, non-communicable diseases that cause immunological dysfunction. PIDsare seldom reported in South Africa (SA). Based on a mid-2013 population estimate of 52.98 million and assuming that the prevalenceof PIDs is similar to that in well-resourced settings, the total number of individuals with PIDs in our country should range between2 850 and 45 723. However, fewer than 500 cases of PID have been reported in SA. Between five and 15 new, fully characterised PIDs arereported annually. Our understanding of the physiology of the immune system has been substantially enhanced by these discoveries, andconsequently the international classification of PIDs has been updated.

The Prevalances and Patient Characteristics of Primary Immunodeficiency Diseases in Turkey—Two Centers Study

Primary immunodeficiency diseases (PIDs) are inherited disorders of the immune system resulting in increased susceptibility to unusual infections and predisposition to autoimmunity and malignancies. The European Society for Immunodeficiencies (ESID) has developed an internet-based database for clinical and research data on patients with PID. This study aimed to provide a minimum estimate of the prevalence of each disorder and to determine the clinical characteristics and outcomes of patients with PID in Turkey. Clinical features of 1435 patients with primary immunodeficiency disorders are registered in ESID Online Patient Registry by the Pediatric Immunology Departments of the Medical Faculties of Uludag University and Ege University Between 2004 and 2010. These two centers are the major contributors reporting PID patients to ESID database from Turkey. Predominantly antibody immunodeficiency (73.5 %) was the most common category followed by autoinflammatory disorders (13.3 %), other well defined immunodeficiencies (5.5 %), congenital defects of phagocyte number, function or both 3.5 %), combined T and B cell immunodeficiencies (2 %), defects in innate immunity (1 %), and diseases of immune dysregulation (0.7 %). Patients between 0 and 18 years of age constitued 94 % of total and the mean age was 9.2 ± 6 years. The consanguinity rate within the registered patients was 14.3 % (188 of 1130 patients). The prevalance of all PID cases ascertained from the registry was 30.5/100.000. The major cause of the mortality was severe infection which was seen in forty-two of seventy five deceased patients. The highest mortality was observed in patients with severe combined immunodeficiencies and ataxia-telangiectasia. Promoting the awareness of PID among the medical professionals and the general public is required if premature death and serious morbidity occurs due to late diagnosis of the wider spectrum of PID are to be avoided.

Incidence and Temporal Trends of Primary Immunodeficiency: A Population-Based Cohort Study

To determine the incidence and temporal trends of primary immunodeficiency diseases (PIDs) and examine whether an association exists between delayed diagnosis and increased morbidity. We performed a historical cohort study to describe the epidemiology of PIDs in Olmsted County, Minnesota, during a 31-year period from January 1, 1976, through December 31, 2006, using the Rochester Epidemiology Project. Incidence and trends over time, presence of comorbid conditions, and trends in management were determined. During the 31-year study period, 158 new cases of PIDs were diagnosed, with an overall incidence rate of 4.6 per 100,000 person-years. The rate of PIDs from 2001 through 2006 (10.3 per 100,000 person-years) was nearly 5 times higher than that from 1976 through 1980 (2.4 per 100,000 person-years). The associations between continuous variable(s) and categorical outcome(s) were assessed by using the Wilcoxon rank sum test. Longer delay in diagnosis was significantly associated with recurrent sinusitis (P<.001), recurrent pneumonia (P=.03), and subsequent treatment with immunoglobulins (P<.001). On the basis of Kaplan-Meier survival estimates, the proportion of patients surviving at 10 years after diagnosis was 93.5% (95% confidence interval, 85.9%-97.1%). However, older age at diagnosis was significantly associated with mortality (P=.01). This is one of the first population-based studies to examine the temporal trends of PIDs. The incidence of PIDs increased markedly between 1976 and 2006. In this cohort, a delay in diagnosis was common and was associated with increased morbidity. Despite substantial morbidity, most patients with PIDs can expect a normal life span.

Incidence and temporal trends of primary immunodeficiency: a population-based cohort study.

To determine the incidence and temporal trends of primary immunodeficiency diseases (PIDs) and examine whether an association exists between delayed diagnosis and increased morbidity. We performed a historical cohort study to describe the epidemiology of PIDs in Olmsted County, Minnesota, during a 31-year period from January 1, 1976, through December 31, 2006, using the Rochester Epidemiology Project. Incidence and trends over time, presence of comorbid conditions, and trends in management were determined. During the 31-year study period, 158 new cases of PIDs were diagnosed, with an overall incidence rate of 4.6 per 100,000 person-years. The rate of PIDs from 2001 through 2006 (10.3 per 100,000 person-years) was nearly 5 times higher than that from 1976 through 1980 (2.4 per 100,000 person-years). The associations between continuous variable(s) and categorical outcome(s) were assessed by using the Wilcoxon rank sum test. Longer delay in diagnosis was significantly associated with recurrent sinusitis (P<.001), recurrent pneumonia (P=.03), and subsequent treatment with immunoglobulins (P<.001). On the basis of Kaplan-Meier survival estimates, the proportion of patients surviving at 10 years after diagnosis was 93.5% (95% confidence interval, 85.9%-97.1%). However, older age at diagnosis was significantly associated with mortality (P=.01). This is one of the first population-based studies to examine the temporal trends of PIDs. The incidence of PIDs increased markedly between 1976 and 2006. In this cohort, a delay in diagnosis was common and was associated with increased morbidity. Despite substantial morbidity, most patients with PIDs can expect a normal life span.

Population Prevalence of Diagnosed Primary Immunodeficiency Diseases in the United States

Boyle JM, Buckley RH. J Clin Immunol. 2007;27(5):497–502 PURPOSE OF THE STUDY. To measure the prevalence of primary immunodeficiency diseases (PIDs) in the United States. STUDY POPULATION. A random sample of 10 005 American households (26 657 people) was included in the study. METHODS. Households were selected by random-digit dialing stratified according to time zone. Calls were placed by trained interviewers with computer assistance. Eighty percent of the households contacted completed the interview. Respondents were asked, “Has anyone in your household ever been diagnosed with a primary immunodeficiency disease such as common variable immunodeficiency, IgA [immunoglobulin A] deficiency, IgG subclass deficiency, or any other immunodeficiency? (This is not acquired immunodeficiency—AIDS).” If they replied “yes,” they were further questioned with details of the diagnosis and limited demographic information about the affected individual(s). RESULTS. Twenty-three individuals in 18 households were identified as having a specific PID (including common variable immunodeficiency, IgA deficiency, IgG subclass deficiency, X-linked agammaglobulinemia, severe combined immunodeficiency, and chronic granulomatous disease). The calculated prevalence of diagnosed immunodeficiency was 1 in 2000 children, 1 in 1200 people of all ages, and 1 in 600 households. The 95% confidence limits for the estimate for all individuals were between 1 in 824 and 1 in 1956. Several of the identified individuals with primary immunodeficiency were not receiving therapy that is standard of care for their diagnoses (γ-globulin replacement). CONCLUSIONS. Quoting the authors, “The current study suggests that these conditions are sufficiently common that primary care physicians are likely to see patients with underlying primary immunodeficiency disorders in their practice and should test for these disorders in patients with recurring, unusual or serious infections. In the absence of routine screening, physician awareness of the relative frequency of these disorders is critical to early diagnosis and treatment.” REVIEWER COMMENTS. This is an extremely important message for all primary care physicians. These patients are in your practices now. The authors also pointed out that several studies have shown that many cases of PID are diagnosed late or are “mild” enough that they are never diagnosed and that patients suffer excess morbidity and mortality as a result. Some severe cases may be missed because children die before they are diagnosed. Thus, the true prevalence of PID is likely to be higher than what was found in this study. I found it discouraging that two thirds of the people who should have been receiving γ globulin were not.

Prévalence de la pneumopathie à Pneumocystis Jiroveci au cours des déficits immunitaires héréditaires observés en Tunisie

Pneumocystis Jiroveci pneumonia (PJP) is a rare opportunistic infection in immunodeficient patients in Tunisia, as well as in other Africain countries including those with a high prevalence of AIDS. In the literature, PJP has been reported in primary immunodeficiency diseases (PID) namely SCID T –B – or T –B + or X-linked hyper-IgM syndrome. Objective To evaluate the prevalence of PJP in the different PID observed in Tunisia. Patients and methods This retrospective study concerned 290 cases of PID confirmed by immunological investigation including the study of specific and/or non-pecific humoral and cellular immunity. The identification of P. Jiroveci in patients suspected of pneumocystosis was achieved by parasitological investigation in bronchoalveolar lavages. Results A PID associated to a parasitologically confirmed pneumocystic infection was found in 9 out of 290 patients (3%) among whom the majority (7 patients) had an HLA class II combined immunodeficiency. The latter is an autosomic recessive disease which has been reported mainly in North African families. Indeed, this population is characterized by a high rate of consanguinity. Interestingly, no PJP has been observed neither in SCID T –B – or T –B + nor in X-linked hyper-IgM syndrome. Discussion and conclusion PJP seems to be particularly frequent in HLA class II deficiency patients, since 7 out of 22 patients with this deficiency had a PJP (31%). Due to this defect, antigen presenting cells are unable to present the antigen to T lymphocytes demonstrating the critical role of CD4 + T lymphocytes responses in the immune response to this pathogen.

Cutaneous manifestations of primary immunodeficiency diseases in children.

Primary immunodeficiency diseases (PIDs) are rare but include severe conditions found predominantly in children, Most PIDs have cutaneous manifestations that may be important as early diagnostic features. The purpose of this study was to determine the frequency and nature of cutaneous alterations associated with PIDs. This article is a cross-sectional study at the department of allergy and clinical immunology of children's medical center conducted between December 5, 2001 and April 20, 2002. The subjects included pediatric patients with a diagnosis of PID and dermatological diagnoses were made by a dermatologist. Two hundred and ten patients were studied They consisted of 68 cases of humoral deficiency, 22 cases of cellular and combined deficiencies, 57 cases of phagocytic defects and 63 cases of other PIDs. In 67 cases (31.8%) the cutaneous alterations preceded and were the basis for clinical immunological diagnosis. Overall cutaneous alterations were infections in 99 cases and eczematous dermatitis in 27 cases. Our findings support the results of other studies that most PIDs have cutaneous features which being their typical aspects are highly suggestive for the diagnosis of PIDs.

Chronic rhinosinusitis in primary antibody immunodeficient patients

Some patients suffer from recurrent or chronic rhinosinusitis (CRS) because of previously unrecognized immunodeficiency disease. The purpose of the study was to evaluate the incidence of CRS in children with different types of primary humoral deficiency. Among 842 cases of primary immunodeficiency diseases diagnosed in the Department of Immunology of the Children's Memorial Institute in Warsaw from 1980 up to February 2006 antibody deficiencies occurred most frequently--in 50.4%. In this group the retrospective study of patients' history suggesting CRS prior to intravenous gamma-globulin substitution therapy was performed. CRS was observed most frequently in the group of patients with agammaglobulinemia less often in patients with dysgammaglobulinemia, and other antibody deficiencies. The occurrence of frequent bacterial infections, complicating common colds, should alert the physician to the possibility of immunodeficiency. Immunological testing should be an integral part of evaluation of patients with refractory CRS.

Primary Immunodeficiency Disorders in the Republic of Ireland: First Report of the National Registry in Children and Adults

Data collection for the national registry for patients with primary immunodeficiency disorders in the Republic of Ireland commenced in 1996. One hundred and fifteen cases of primary immunodeficiency diseases were registered between December 1996 and February 2003. The most frequent primary immunodeficiency disorders were antibody deficiency (n = 53) and complement deficiency (n = 32). In addition, patients with T cell deficiency (n = 11) and chronic granulomatous disease (n = 11) were identified. A small number of patients with Wiskott-Aldrich syndrome, natural killer cell deficiency, DiGeorge syndrome and chronic mucocutaneous candidiasis were also registered. Comparison of our data with that recently reported in the European registry revealed that complement deficiency was more prevalent in the Republic of Ireland compared to other European countries. Results of our registry point to a significant prevalence of primary immunodeficiency disorders in the Republic of Ireland (2.9 cases per 100,000 population). However, it is likely that these figures underestimate the true prevalence of such cases in the country. We hope, with increased awareness of the national registry among primary care physicians, that more patients will be included and we will be able to identify accurately the frequency and the distribution of these disorders.

Primary immunodeficiency diseases in children treated in the Children's Memorial Hospital, Poland.

One hundred and three cases of primary immunodeficiency diseases were diagnosed among children suffering mainly from chronic and severe infections in the period 1980-1987. Predominantly antibody defects were recognized in 48 patients (46.6%), combined immunodeficiencies in 36 patients (35%), phagocytic disorders in 12 patients (11.6%), complement defects in 6 patients (5.8%), and cell-mediated disease (Di George syndrome) in 1 patient. Allergic complications were observed in 25 patients (24.2%) and malignancy-in 3 patients (2.9%). More detailed immunological studies were performed in children with X-linked agammaglobulinemia in the course of intravenous immunoglobulin therapy and in children with ataxia telangiectasia.