Some of the more common infections are listed in Table 3. with the whole spectrum of clinical problems related to primary antibody deficiencies, with the aim of ensuring equity of access to consistently good care and has been developed for the guidance of healthcare professionals who, in their clinical practice, may encounter patients with unsuspected primary antibody deficiencies. Implications for implementation These guidelines are intended to impact primarily on education of healthcare professionals and their awareness of primary antibody deficiency. All clinical staff within the hospital setting should consider the possible diagnosis of primary antibody deficiency in a patient presenting with severe, persistent, opportunistic or recurrent infections or with other potential indicator conditions. The latter includes disorders of immune regulation (granulomatous, hypersensitivity or autoimmune disease), a restricted range of malignant diseases (lymphoma, skin or gastric cancer), vaccine failures or, occasionally, stigmata associated with specific deficiency syndromes. Recognition and referral of patients with suspected primary antibody deficiency is important as appropriate therapy can prevent or reduce infections, and delayed therapy is associated with complications. Primary antibody deficiency syndromes (Table 1) Table 1. B-cell defects. (a) Early B-cell differentiation defects; (b) later B-cell differentiation/function defects. Open in a separate window Prevalence and clinical presentation The prevalence of clinically significant primary antibody deficiency is around 1:25,000 to 1 1:110,000 of the population. Overall, 95% of patients with primary antibody deficiencies present after the age of six years. A relevant history allied to appropriate suspicion and disease awareness, are the most important elements for early recognition and diagnosis of primary antibody deficiency. Patients at any age with recurrent infections (especially in the upper and lower respiratory tracts), those with infections in more than one anatomical site and those in whom the frequency or severity of infection is unusual or out of context should be investigated for possible antibody deficiency (Table 2). More rarely, granulomatous, inflammatory or autoimmune features are the initial manifestation of primary antibody deficiency. The European Society CP 31398 2HCl for Immunodeficiencies (ESID) has developed an algorithm for clinicians to guide assessment and referral of possible primary immunodeficiencies, including primary antibody deficiencies.1 The UK Primary Immunodeficiency Network website contains a diagnostic tool developed from this algorithm to help clinicians assess potential primary immunodeficiency disorders (www.ukpin.org.uk). Table 2. Presenting symptoms of infection in cohorts of patients with primary antibody deficiencies. Open in a separate window Investigations Serum immunoglobulins are the most important investigation in initial assessment. Most patients subsequently diagnosed with primary antibody deficiency have an immunoglobulin (Ig) G level of 3 g/l or less, with an IgA Rabbit Polyclonal to BAIAP2L2 level of less than 0.1 CP 31398 2HCl g/l and in some antibody deficiencies an IgM level of less than 0.25 g/l.2,3 Over 90% of patients with the most common types of antibody deficiency, common variable immunodeficiency disorders, have an IgG level of less than 4.5 g/l at diagnosis.4 The guidelines Diagnostic delay Patients with primary antibody deficiencies present to a wide variety of clinical specialties other than clinical immunology, but the diagnosis of antibody deficiency is established in far fewer patients seen in these departments than in patients seen in immunology clinics. Diagnostic delay is associated with considerable morbidity, particularly recurrent pneumonias, with secondary structural lung damage such as bronchiectasis and associated pulmonary hypertension and, ultimately, pulmonary heart disease.5 Therapy Immunoglobulin therapy increases survival, leads to a reduction in the rate of bacterial infections, days of antibiotic usage, days of fever and hospital admissions and is equally efficacious in this respect when given by either intravenous (iv) or subcutaneous (SC) routes.2,4,6C8 Inadequate immunoglobulin replacement therapy or delayed diagnosis places the patient at greater risk of local or systemic recurrent infections. Some CP 31398 2HCl of the more common infections are listed in Table 3. The risk of infection remains even when appropriate therapy with replacement immunoglobulin is initiated, although this is.