Allergy in the elderly: A case note review of referrals to an adult allergy clinic.

The UK population is ageing and we can expect more referrals to allergy clinics for this age group. 16% of patients to our clinic are aged >60. Compared to younger patients, 3 times as many referrals were for angioedema. Overall, allergy was excluded in 79% of cases. 15% were diagnosed with previously unrecognised allergies, while allergic disease was confirmed in 6%, enabling optimised management. While the differential diagnosis of allergic conditions is wider in older people, assessment in the allergy clinic is helpful and adds value.

C1 inhibitor deficiency: 2014 United Kingdom consensus document.

C1 inhibitor deficiency is a rare disorder manifesting with recurrent attacks of disabling and potentially life-threatening angioedema. Here we present an updated 2014 United Kingdom consensus document for the management of C1 inhibitor-deficient patients, representing a joint venture between the United Kingdom Primary Immunodeficiency Network and Hereditary Angioedema UK. To develop the consensus, we assembled a multi-disciplinary steering group of clinicians, nurses and a patient representative. This steering group first met in 2012, developing a total of 48 recommendations across 11 themes. The statements were distributed to relevant clinicians and a representative group of patients to be scored for agreement on a Likert scale. All 48 statements achieved a high degree of consensus, indicating strong alignment of opinion. The recommendations have evolved significantly since the 2005 document, with particularly notable developments including an improved evidence base to guide dosing and indications for acute treatment, greater emphasis on home therapy for acute attacks and a strong focus on service organization.

Paediatric hereditary angioedema: a survey of UK service provision and patient experience.

Hereditary angioedema (HAE) is a rare disease characterized by episodes of potentially life-threatening angioedema. For affected children in the United Kingdom, there are relatively few data regarding disease prevalence, service organization and the humanistic burden of the disease. To improve knowledge in these areas, we surveyed major providers of care for children with HAE. A questionnaire was sent to major paediatric centres to determine patient numbers, symptoms, diagnostic difficulties, management and available services. In addition, all patients at a single centre were given a questionnaire to determine the experiences of children and their families. Sixteen of 28 centres responded, caring for a total of 111 UK children. Seven children had experienced life-threatening crises. One-third of patients were on long-term prophylactic medication, including C1 inhibitor prophylaxis in four children. Eight centres reported patients who were initially misdiagnosed. Broad differences in management were noted, particularly regarding indications for long-term prophylaxis and treatment monitoring. We also noted substantial variation in the organization of services between centres, including the number of consultants contributing to patient care, the availability of specialist nurses, the availability of home therapy training and the provision of patient information. Ten of 12 patient/carer questionnaires were returned, identifying three common themes: the need to access specialist knowledge, the importance of home therapy and concerns around the direct effect of angioedema on their life. To our knowledge, this study represents the first dedicated survey of paediatric HAE services in the United Kingdom and provides useful information to inform the optimization of services.

High-titre circulating tissue transglutaminase-2 antibodies predict small bowel villous atrophy, but decision cut-off limits must be locally validated.

Numerous studies suggest that high levels of circulating immunoglobulin (Ig)A tissue transglutaminase (TTG2) antibodies predict coeliac disease with high specificity. Accordingly, it has been suggested that duodenal biopsy may not be required routinely for diagnostic confirmation where quantitative serology identifies the presence of high antibody titres. However, defining a cut-off TTG2 threshold is problematic, as the multiple available assay methods are not harmonized and most studies have been focused on the paediatric population. Recent paediatric guidelines proposed a TTG2 antibody diagnostic cut-off at 10 × the upper limit of normal (ULN) for the method; however, concerns remain about errors of generalization, between both methods and laboratories. In this study, we used retrospective laboratory data to investigate the relationship between TTG2 antibody levels and Marsh 3 histology in the seropositive population of adults and children at a single centre. Among 202 seropositive patients with corresponding biopsies, it was possible to define a TTG2 antibody cut-off with 100% specificity for Marsh 3 histology, at just over 10 × ULN for the method. However, UK National External Quality Assurance Scheme returns during the study period showed a wide dispersion of results and poor consensus, both between methods and between laboratories using the same method. Our results support the view that high-titre TTG2 antibody levels have strong predictive value for villous atrophy in adults and children, but suggest that decision cut-offs to guide biopsy requirement will require local validation. TTG2 antibody assay harmonization is a priority, in order to meet the evolving requirements of laboratory users in this field.

Clinical immunology review series: An approach to the management of pulmonary disease in primary antibody deficiency.

The sinopulmonary tract is the major site of infection in patients with primary antibody deficiency syndromes, and structural lung damage arising from repeated sepsis is a major determinant of morbidity and mortality. Patients with common variable immunodeficiency may, in addition, develop inflammatory lung disease, often associated with multi-system granulomatous disease. This review discusses the presentation and management of lung disease in patients with primary antibody deficiency.

An evaluation of tests used for the diagnosis and monitoring of C1 inhibitor deficiency: normal serum C4 does not exclude hereditary angio-oedema.

Reduced levels of serum C4 have been considered a ubiquitous finding in hereditary angio-oedema (HAE), and consequently low C4 is often used to 'request manage' access to C1 inhibitor assays in the United Kingdom. However, in our experience normal C4 may occasionally be compatible with HAE. We audited the results of serum C4, C1 inhibitor antigen (C1inhA) and C1 inhibitor function (C1inhF) in 49 HAE patients, compared to a control group of 58 unaffected subjects. The sensitivity of low serum C4 for HAE among untreated patients was 81%; levels of complement C4 were within the normal range on nine separate occasions in five untreated HAE patients. Molecular genetic analysis of these individuals demonstrated novel mutations in the C1 inhibitor gene. The supplied reference ranges for the Quidel C1inhF enzyme-linked immunosorbent assay (ELISA) system appear to be too low, with a sensitivity of just 57% for HAE. Following optimization of the reference ranges using receiver operating characteristic analysis, low C1inhF was found to be 78% sensitive and 100% specific for HAE. The diagnosis of HAE is not excluded by normal levels of complement C4. We conclude that C1 inhibitor studies should be performed regardless of serum C4 where a high index of clinical suspicion exists.