The United Kingdom Primary Immune Deficiency (UKPID) registry 2012 to 2017.

This is the second report of the United Kingdom Primary Immunodeficiency (UKPID) registry. The registry will be a decade old in 2018 and, as of August 2017, had recruited 4758 patients encompassing 97% of immunology centres within the United Kingdom. This represents a doubling of recruitment into the registry since we reported on 2229 patients included in our first report of 2013. Minimum PID prevalence in the United Kingdom is currently 5·90/100 000 and an average incidence of PID between 1980 and 2000 of 7·6 cases per 100 000 UK live births. Data are presented on the frequency of diseases recorded, disease prevalence, diagnostic delay and treatment modality, including haematopoietic stem cell transplantation (HSCT) and gene therapy. The registry provides valuable information to clinicians, researchers, service commissioners and industry alike on PID within the United Kingdom, which may not otherwise be available without the existence of a well-established registry.

Phenotypic heterogeneity in a family with a CD40 ligand intracellular domain mutation.

We describe a family with the rare mutation R11X that leads to a truncated CD40 ligand (CD40L) missing the intracellular domain. The index case had detectable CD40L expression and presented at the age of 41 years with cerebral toxoplasmosis. A brother and two nephews were also identified as having the same mutation but exhibited milder and variable phenotypes. The older affected nephew had a moderately depressed immunoglobulin G level and a history of pneumonia at 4 months of age. The younger nephew suffered from sinusitis with normal immunoglobulin levels. Both nephews had absent antibody responses to a protein antigen with conserved responses to polysaccharide antigens. The two sisters of the index case are carriers who had elevated levels of IgM but remain well. This mutation may affect CD40 ligand function by reducing cell surface levels, diminishing CD40 interaction or disrupting CD40L intracellular signalling in T cells. The variable phenotype in members of this family offers an opportunity to further understand the CD40-CD40L signalling pathway in human immune responses.

Cerebral toxoplasmosis in a middle-aged man as first presentation of primary immunodeficiency due to a hypomorphic mutation in the CD40 ligand gene.

Cerebral toxoplasmosis can occur outside the setting of advanced HIV immunodeficiency or drug-induced immunosuppression. A case of cerebral toxoplasmosis is reported in a previously healthy 41-year-old man who was found to have a genetic defect in CD40 ligand, resulting in the X linked hyper-IgM syndrome despite normal surface protein expression on flow cytometry. This highlights the fact that primary immunodeficiencies can first present late in life with a relatively mild phenotype and should be considered in the differential diagnosis of opportunistic infections in non-HIV infected patients; in addition, normal protein expression does not necessarily rule out hypomorphic mutations.

Management of hypogammaglobulinaemia occurring in patients with systemic lupus erythematosus.

OBJECTIVES: Systemic lupus erythematosus (SLE) is typically associated with hypergammaglobulinaemia but has been described in the setting of hypogammaglobulinaemia as well. The purpose of this article is to describe various cases of SLE and hypogammaglobulinaemia, review the literature and present management strategies for hypogammaglobulinaemia in SLE. METHODS: We describe five patients with SLE and antibody deficiency, and review the literature exploring the relationship between the two. RESULTS: Various types of antibody deficiency syndromes, including common variable immunodeficiency (CVID), IgA deficiency, IgM deficiency, drug-induced hypogammaglobulinaemia and hypogammaglobulinaemia secondary to nephrotic syndrome can occur in SLE. Antibody deficiency states can be treated with antibiotics and replacement immunoglobulin therapy (particularly CVID) but sometimes close monitoring is all that is required. CONCLUSION: Measurement of immunoglobulin levels is useful in SLE to identify coexisting antibody deficiency and the later development of hypogammaglobulinaemia. This allows monitoring and appropriate treatment to be instituted.

Molecular diagnosis of Fusobacterium necrophorum infection (Lemierre's syndrome).

Presented here is the case of a 27-year-old male with atypical features of Lemierre's syndrome in which a definitive diagnosis was achieved using molecular methods. While routine investigations, including bacterial cultures, were unhelpful, two real-time PCR assays demonstrated Fusobacterium necrophorum-specific DNA in aspirates from brain and renal abscesses. This is the first report demonstrating that a laboratory diagnosis can be made using molecular methods in suspected cases of Lemierre's syndrome. Use of these methods can thus resolve diagnostic confusion, prevent unnecessary investigation, and direct specific antimicrobial treatment.

Inequalities in access to knee joint replacements for people in need.

OBJECTIVES: To quantify the effects of socioeconomic deprivation and rurality on evidence of need for total knee joint replacement and the use of health services, after adjusting for age and sex. METHODS: A random stratified sample of 15 000 people aged > or =65 years taken from central age/sex registers for the geographical areas covered by the previous Sheffield and Wiltshire Health Authorities. A self completion validated questionnaire was then mailed directly to subjects to assess need for knee joint replacement surgery and whether general practice and hospital services were being used. Subjects were followed up for 18 months to evaluate access to surgery. RESULTS: The response rate was 78% after three mailings. In those aged 65 years and over (with and without comorbidity), the proportion with no comorbid factors and in need of knee replacement was 5.1%; the rate of need among subjects without comorbidity was 7.9%. There were inequalities in health and access to health related to age, sex, geography, and deprivation but not rurality. People who were more deprived had greater need. Older and deprived people were less likely to access health services. Only 6.4% of eligible people received knee replacement surgery after 18 months of follow up. CONCLUSIONS: There is an important unmet need in older people, with significant age, sex, geographical, and deprivation inequalities in levels of need and access to services. The use of waiting list numbers as a performance indicator is perverse for this procedure. There is urgent need to expand orthopaedic services and training.