Accessibility to biologics and its impact on disease activity and quality of life in patients with rheumatoid arthritis in Kuwait

Clinical Rheumatology - Biologics are indicated in rheumatoid arthritis (RA) in case of persistent high disease activity despite conventional disease-modifying anti-rheumatic drugs (cDMARDs) or...     

ICON: The Early Diagnosis of Congenital Immunodeficiencies

Primary immunodeficiencies are intrinsic defects in the immune system that result in a predisposition to infection and are frequently accompanied by a propensity to autoimmunity and/or immunedysregulation. Primary immunodeficiencies can be divided into innate immunodeficiencies, phagocytic deficiencies, complement deficiencies, disorders of T cells and B cells (combined immunodeficiencies), antibody deficiencies and immunodeficiencies associated with syndromes. Diseases of immune dysregulation and autoinflammatory disorder are many times also included although the immunodeficiency in these disorders are often secondary to the autoimmunity or immune dysregulation and/or secondary immunosuppression used to control these disorders. Congenital primary immunodeficiencies typically manifest early in life although delayed onset are increasingly recognized. The early diagnosis of congenital immunodeficiencies is essential for optimal management and improved outcomes. In this International Consensus (ICON) document, we provide the salient features of the most common congenital immunodeficiencies.     

Primary Immunodeficiency Disorders in Kuwait: First Report from Kuwait National Primary Immunodeficiency Registry (2004–2006)

Primary immunodeficiency disorders are heterogeneous group of illnesses that predispose patients to serious complications. Registries for these disorders have provided important epidemiological data and shown both racial and geographical variations. The clinical features of 76 patients with primary immunodeficiency disorders registered in Kuwait National Primary Immunodeficiency Registry from 2004 to 2006 were recorded. Ninety-eight percent of the patients presented in childhood. The prevalence of these disorders in children was 11.98 in 100,000 children with an incidence of 10.06 in 100,000 children. The distribution of these patients according to each primary immunodeficiency category is: combined T and B cell immunodeficiencies (21%), predominantly antibody immunodeficiency (30%), other well defined immunodeficiencies (30%), diseases of immune dysregulation (7%), congenital defects of phagocyte number, function or both (8%), and complement deficiencies (4%). The consanguinity rate within the registered patients was 77%. The patients had a wide range of clinical features affecting different body systems. Primary immunodeficiency disorders are prevalent in Kuwait and have a significant impact into the health system.     

Primary Immunodeficiency Disorders: Survey of Pediatricians in Kuwait

INTRODUCTION: Early diagnosis of primary immunodeficiency disorders (PID) is critical so life saving interventions can be implemented to avoid significant morbidity and mortality. Unfortunately, they are frequently misdiagnosed, which results into significant delay in diagnosis. This study aimed to determine the knowledge and practice of pediatricians in Kuwait about PID. MATERIALS AND METHODS: A 66-item self-administered questionnaire was designed and distributed to the pediatricians working at all six governmental hospitals to measure their knowledge and practice about PID. A total of 244 pediatricians (78.4%; 143 males and 101 females) participated in the study. The mean age of participants was 40 years, and the mean number of years working in pediatrics was 13 years. The mean overall score was 59.6%, whereas the mean score in clinical presentation section was 63%, in associated diseases and syndromes section 58%, and in laboratory investigations section 51%. Only 26% of the participants answered correctly at least 2/3 of the questions (67% of the questions). CONCLUSION: This survey demonstrates that there is universal deficiency in both the knowledge and practice of pediatricians in the field of PID. Implementation of strategies to improve the awareness of pediatricians about PID is critical so early therapeutic interventions can be done to improve the health and prevent morbidity and mortality.     

Survival and Predictors of Death Among Primary Immunodeficient Patients: A Registry-Based Study

Purposes

The aims of this study were to investigate survival among patients with primary immunodeficiency disorders (PID) in Kuwait and to determine whether certain variables were associated with increased risk of death.

Methods

The data of 176 patients (98 males and 78 females) were extracted from the Kuwait National Primary Immunodeficiency Disorders Registry and the observation period was from January 2004 to July 2011.

Results

The distribution of the reported patients was combined T- and B-cell immunodeficiencies (30.1%), predominantly antibody immunodeficiency (19.9%), other well-defined immunodeficiencies (25%), diseases of immune dysregulation (14.8%), congenital defects of phagocyte number, function or both (6.25%), and complement deficiencies (4.0%). In a total of 619.1 patient-years at risk, 48 patients died (mortality incidence rate 77.53 per 1,000 person-years). The overall survival in the studied cohort was 72.7% (72.4% for males and 73.1% for females). The most common cause of death was sepsis (46%) followed by pneumonia (29%). The probabilities that a patient survived 2, 4, and 6?years after onset of symptoms were 76%, 73%, and 69%, respectively. The variables that were found to be predictors for death are parental consanguinity, sepsis, adenovirus and CMV infections, failure to thrive, PID category, and onset age <6?months.

Conclusions

Patients with PID have decreased probabilities of survival that are variable between PID categories. Early diagnosis and aggressive therapeutic interventions specifically of patients with history of the variables associated with increased risk of death may help increase their chance of survival.     

Detection of Sp110 by Flow Cytometry and Application to Screening Patients for Veno-occlusive Disease with Immunodeficiency

Mutations in Sp110 are the underlying cause of veno-occlusive disease with immunodeficiency (VODI), a combined immunodeficiency that is difficult to treat and often fatal. Because early treatment is critically important for patients with VODI, broadly usable diagnostic tools are needed to detect Sp110 protein deficiency. Several factors make establishing the diagnosis of VODI challenging: (1) Current screening strategies to identify severe combined immunodeficiency are based on measuring T cell receptor excision circles (TREC). This approach will fail to identify VODI patients because the disease is not associated with severe T cell lymphopenia at birth; (2) the SP110 gene contains 17 exons, making it a challenge for Sanger sequencing. The recently developed next-generation sequencing (NGS) platforms that can rapidly determine the sequence of all 17 exons are available in only a few laboratories; (3) there is no standard functional assay to test for the effects of novel mutations in Sp110; and (4) it has been difficult to use flow cytometry to identify patients who lack Sp110 because of the low level of Sp110 protein in peripheral blood lymphocytes. We report here a novel flow cytometric assay that is easily performed in diagnostic laboratories and might thus become a standard assay for the evaluation of patients who may have VODI. In addition, the assay will facilitate investigations directed at understanding the function of Sp110.