World Primary Immunodeficiencies Week 2012

This week is World Primary Immunodeficiencies Week. We are pleased to present the following editorial, submitted by Drs. Amos Etzioni and Ricardo Sorensen on behalf of the World Primary Immunodeficiencies Week Steering Committee:

Early Diagnosis and Appropriate Treatment – Improving and Saving Lives of Patients with Primary Immunodeficiency

Amos Etzioni MD¹, Ricardo Sorensen MD²

For the World PI Week Steering Committee 2012*

¹. Meyer Children's Hospital, 31096 Haifa, Israel

². Department of Pediatrics Children's Hospital, 200 Henry Clay Ave. New Orleans, LA 70118

Address for correspondence: World PI Week, Interel, Greencoat House, Francis Street, London SW1P 1DH, UK. Email: info@worldpiweek.org

*World PI Week (WPIW) is a global awareness initiative, which aims to raise the recognition and diagnosis of primary immunodeficiencies (PI) as an increasingly important group of diseases. World PI Week is celebrated on 22-29 April, culminating in the World Day of Immunology on 29 April.

WPIW Steering Committee members:

Bousfiha A, Drabwell J, Espinosa F, Etzioni A, Farrugia A, Holland S, Modell F,

Modell V, Prevot J, Schmidt R.E, Sorensen R, Vaughn G.

While in the past Primary immune deficiencies were thought to be a group of rare conditions affecting one in approximately 10,000 individuals, we know today that this is not the case. We now know that PIs (Primary Immunodeficiencies) are much more frequent and can occur at any age including in adults. Essentially almost all patients admitted to the hospital with severe life threatening, infections, and patients with less severe but recurrent infections have an abnormal immune response. While in many cases, with our current knowledge, we are able to find the precise defect, still, in other cases the primary immune defect is unknown. Almost every month a new genetic defect leading to another immune deficiency is discovered, but to understand completely the interaction between the various "players" in the immune system, is still a goal beyond reach.

All our efforts in solving the role of cells, molecules, and various organs in the normal function of the immune response are targeted in order to improve the condition of patients with immunodeficiency disorders. However, the most important improvement that needs to be achieved is early recognition of the many clinical presentations of primary immunodeficiencies. The early recognition of any of the various forms of PI quite clearly improves survival and morbidity. As an example, performing stem cell transplantation for severe combined immunodeficiencies, during the first 3 months of life will increase survival to more than 95%, in a condition that in the past was always lethal. Furthermore, early transplantation has a very important cost saving effect.(1)

Hypogammaglobulinemia and antibody deficiency is the most common defect in the immune system leading to serious infections mainly in the lungs. Some form of antibody abnormality is part of the vast majority of the various immunodeficiencies. Delay in the diagnosis of an antibody deficiency and recurrent pneumonia will lead to bronchiectasis which could lead to lung failure, with increased mortality and morbidity.(2) Antibody deficiencies also can lead to recurrent sinusitis, otitia and many other types of infections. Thus, immunoglobulin substitution should start as

soon as the state of hypogammaglobulinemia or antibody deficiency is made. In the last 30 years, the use of intravenous immunoglobulins (IVIG) became the recognized standard of care and the dosage should be personalized in order to achieve the trough level of above 600mg/dl or a dose to keep an individual patient free of severe infections. Recently, the use of subcutaneous immunoglobulin (SCIG) has gained popularity and in some countries up to 90% of the patients are treated with SCIG. In this way, the avoidance of IV (intravenous) route and the possibility of home treatment has increased patients’ convenience.(3) Unfortunately, in some parts of the world the supply of IVIG or SCIG is limited and patients do not get the appropriate therapy.

The increased efforts to improve the knowledge of physicians all over the world and awareness of the general population is an ongoing and continuous work done by the patients organizations, mainly the Jeffrey Modell Foundation (JMF) and the International Patient Organization for Primary Immunodeficiency (IPOPI) as well as several doctors’ organizations such as the European Society for primary Immunodeficiency (ESID), the European Federation of Immunological Societies (EFIS), the Latin American Society for Immunodeficiency (LASID), the African Society for Immunodeficiencies (ASID), and the Clinical immunology Society (CIS), nurses (INGID, the International Nursing Group for Immunodeficiencies), and the industry (PPTA, the Plasma Protein Therapeutics Association).

The upcoming “World PI Week” is an excellent opportunity to further achieve our goal of educating the medical and general community about PIs. Their awareness will increase prompt diagnosis and better access to appropriate treatment of children and adults whose past prognoses were very poor.

References:

1. Buckley RH. Transplantation of hematopoetic stem cell in human severe combined immunodeficiency- long tem followup. Immunol Res. 49:25-43,2011

2. Resnick et al. Morbidity and mortality in CVID over 4 decades. Blood 2011 (Ahead of print)

3. Berger M. Choices of IgG replacment for PID: Subcutaneous IgG vs intravenous IgG and selection of optimal dose. Curr Opin Allergy Clin Immunol 11;532-8, 2011

Do we need antibiotics in acute rhinosinusitis?

New guidelines for acute bacterial rhinosinusitis are now available from The Infectious Diseases Society of America. The guidelines used the GRADE system (Grading of Recommendations, Assessment, Development and Evaluation), a state-of-the
art methodology for developing evidence-based guidelines. The paper is published in Clinical Infectious Diseases (Clin Infect Dis 2012; doi: 10.1093/cid/cir1043). The guidelines aim to provide clarity and guidance that will aid physicians in diagnosis and treatment of acute bacterial rhinosinusitis, both in children and in adults. As the guidelines point out, no clinical criteria can currently differentiate between viral and bacterial rhinosinusitis, which leads to excessive antimicrobial therapy. The authors propose an algorithm for management that is based on risk assessment for antimicrobial resistance and evolution of clinical responses.

Telemonitoring in asthma: Fact or fancy?

Asthma plans are widely used to help patients control their disease. It is thought that such plans have had a major impact on the reduction of hospitalizations and deaths seen in many countries. Telemonitoring may provide an additional benefit but its effectiveness has not been tested in a large study. In a newly published study, Ryan et al (BMJ, 2012 Mar 23;344:e1756) followed 288 adolescents and adults with poorly controlled asthma seen in primary care in the UK. Mobile-phone-based monitoring was compared with standard paper-based monitoring strategies. After 6 months, the authors found that the control of asthma, acute exacerbations, oral corticosteroid courses and unscheduled visits were not improved in the group followed by cell phones by comparison to the control group. The authors conclude that “Mobile technology does not improve asthma control or increase self efficacy compared with paper based monitoring when both groups received clinical care to guidelines standards. The mobile technology was not cost effective.”

Are you using telemonitoring? If so, what have you observed?

Do we need antibiotics in acute rhinosinusitis?

This is a major question to be answered. In the US, one out of every five antibiotic prescriptions is for rhinosinusitis. However, results of studies are inconsistent and clinical benefit with antibiotic treatment is at best small due to the high rate of spontaneous improvement. The vast majority of patients are seen in primary care. The recent study by Garbutt et al (JAMA 2012;307:685-692) is therefore of major interest since it attempts to find the incremental effect of amoxicillin over symptomatic treatment on quality of life in 166 adults clinically diagnosed with acute bacterial rhinosinusitis (7 to 28 days of symptoms). They found that antibiotic treatment was not better than placebo for the control of symptoms after 3 days of treatment whereas some benefit was found after 7 days. Although a true diagnosis of sinusitis was not made, this study reflects primary care practice. Since antibiotic resistance is common, the authors propose "to avoid routine antibiotic treatment for patients with uncomplicated acute rhinosinusitis." What do you think based on your experience?

How Best to Care for Children with Allergies

The journal Archives of Disease in Childhood has recently published a supplement containing a series of articles focused on developing care pathways for children with allergies. The articles represent an attempt by the Royal College of Paediatrics and Child Health (RCPCH) Science and Research Department to develop national care pathways for these children, as requested by the UK Department of Health. The articles each focus on a different condition:

• Anaphylaxis
• Asthma and/or rhinitis
• Drug allergies
• Eczema
• Food allergy
• Latex allergies
• Urticaria, angioedema, or mastocytosis
• Venom allergies

Each article presents a pathway algorithm and a set of competences that are required to deliver high-quality care. They are intended as “a guide for training and development of services to facilitate improvements in delivery as close to the patient's home as possible.” The authors note that the pathways should be implemented by a multidisciplinary team, at a local level, and with an eye to establishing connections between primary, secondary, and tertiary care.

How Best to Care for Children with Allergies

The journal Archives of Disease in Childhood has recently published a supplement containing a series of articles focused on developing care pathways for children with allergies. The articles represent an effort by the Royal College of Paediatrics and Child Health (RCPCH) Science and Research Department to develop national care pathways for these children, as requested by the UK Department of Health. The articles each focus on a different condition:

• Anaphylaxis
• Asthma and/or rhinitis
• Drug allergies
• Eczema
• Food allergy
• Latex allergies
• Urticaria, angioedema, or mastocytosis
• Venom allergies

Each article presents a pathway algorithm and a set of competences that are required to deliver high-quality care. They are intended as “a guide for training and development of services to facilitate improvements in delivery as close to the patient's home as possible.” The authors note that the pathways should be implemented by a multidisciplinary team, at a local level, and with an eye to establishing connections between primary, secondary, and tertiary care.

Council of the European Union adopts conclusions on chronic respiratory diseases in children

On December 2, the Council of the European Union adopted a set of conclusions regarding "Prevention, early diagnosis and treatment of chronic respiratory diseases in children." This topic had been identified by the Polish Presidency of the EU as one of its public health priorities. According to the press release, the conclusions urge member states “to give appropriate consideration to the prevention, early diagnosis and treatment of chronic respiratory diseases in children in their health programmes” and “to increase public awareness of these diseases, strengthen smoking prevention and cessation programmes for pregnant women and follow the Council recommendation on smoke-free environment.” In addition, the Council asks the Commission “to support member states in developing and implementing effective policies on the prevention of chronic respiratory diseases in children, improving networking among institutions responsible for the implementation of member states' programmes, and strengthening cooperation of national centres and reinforcing existing international research networks.”