Does a gating policy for ANCA overlook patients with ANCA associated vasculitis? An audit of 263 patients.

BACKGROUND: Antineutrophil cytoplasm antibodies (ANCA) are used as diagnostic markers for small-vessel vasculitis of the Wegener Granulomatosis-microscopic polyangiitis (WG-MPA) spectrum, but if testing is applied indiscriminately, its value is diminished. The authors measured the effect of a targeted ANCA testing policy introduced in our institution in an attempt to improve the diagnostic value of testing in patients with suspected vasculitis. METHODS: The authors measured the rate of ANCA requests at a single regional centre in the year prior to and following the introduction of clinical guidelines to ensure appropriate test usage. The authors also audited clinical outcomes in patients in whom ANCA testing was declined. RESULT: Following implementation of the antineutrophil cytoplasm antibodies (ANCA) gating policy, the number of monthly ANCA tests carried out fell from 287+/-30 to 143+/-18 (p<0.0001) and was associated with an increased rate of positivity, from 18.5% (95% CI 17.0 to 20.1%) to 30.3% (27.5 to 33.1%; p<0.0001). The authors undertook a careful review of the case records from 263 patients in whom testing was declined according to the gating policy over an 8-month period. After 6 months' follow-up, no diagnoses of small-vessel vasculitis of the WG-MPA spectrum were reached. CONCLUSIONS: The rational use of ANCA testing to aid in the diagnosis of vasculitis should include a clinical gating policy to improve diagnostic performance. Adherence to a gating policy for ANCA testing coupled with close liaison between clinician and laboratory does not result in either a missed or delayed diagnosis of small-vessel vasculitis belonging to the WG-MPA spectrum.

A novel mutation in a patient with a deficiency of the eighth component of complement associated with recurrent meningococcal meningitis.

INTRODUCTION: Complement component C8 is one of the five terminal complement components required for the formation of the membrane attack complex. Complete absence of C8 results in increased susceptibility to gram-negative bacteria such as Neisseria species. MATERIALS AND METHODS: Two functionally distinct C8 deficiency states have been described: C8 alpha-gamma deficiency has been predominantly reported amongst Afro-Caribbeans, Hispanics, and Japanese and C8beta mainly in Caucasians. RESULTS: We report a case of functional and immunochemical deficiency of the complement component C8, diagnosed in a Caucasian adult following three episodes of meningitis. Western blotting and hemolytic assay demonstrated absence of C8beta. In genetic studies, the common exon 9 C > T transition responsible for 85% of C8beta deficiencies was not found. Two mutations were identified: a novel duplication mutation, c.1047_1053 dupGGCTGTG in exon 7 that introduces a frame shift, resulting in the addition of seven novel amino acid residues and a premature stop codon, and a previously reported mutation, c.271C > T in exon 3. The parents each expressed one of these mutations, confirming compound heterozygosity. DISCUSSION: This is the first report of a duplication mutation in C8beta deficiency and extends the molecular heterogeneity of the disorder.

GH replacement in patients with non-functioning pituitary adenoma (NFA) treated solely by surgery is not associated with increased risk of tumour recurrence.

BACKGROUND: Subjects with non-functioning pituitary adenomas (NFAs) frequently develop GH deficiency due to tumour expansion or as a consequence of tumour therapy. The safety of GH replacement (GHR) in these individuals remains unclear. OBJECTIVE: To assess the effect of GHR on tumour recurrence in patients with NFAs solely treated by surgical removal. PATIENTS AND METHODS: The study involved all patients with NFA who presented to the Department of Endocrinology in Oxford between January 1989 and July 2005 and were treated solely by surgical removal of the tumour. Patients with follow up < 1 year were excluded. Recurrence was diagnosed on the basis of radiological appearances (detectable tumour after gross total removal or regrowth of pre-existing residue) on regular imaging surveillance. RESULTS: One hundred and thirty patients were included in the study, and were followed up for a mean period of 6.8 +/- 4.2 years (median 5.7, range 1.2-17.6). Twenty-three patients received GHR [16 male, 7 female, mean age at tumour diagnosis 53.7 +/- 14.6 years (range 20-80)]. The mean duration of GHR was 4.6 +/- 2.5 years (median 5.3, range 0.4-8.7). One hundred and seven subjects did not receive GH therapy [61 male, 46 female, mean age at tumour diagnosis 56.2 +/- 14.0 years (range 20-87)]. Tumour regrowth occurred in 38 non-GH treated subjects (36%) and 8 GHR subjects (35%). Regrowth was detected at a mean of 4.8 +/- 2.8 years (range 1-11 years) in the non-GH treated group, and at 6.5 +/- 2.3 years in the GHR group. In the GHR group, recurrence occurred after a mean of 2.9 +/- 2.2 years (range 0.4-5.9 years) following commencement of GH treatment. The Cox regression analysis showed that after adjusting for sex, age at tumour diagnosis, cavernous sinus invasion at diagnosis and type of tumour removal (partial or complete based on postoperative scan), GH treatment was not a significant independent predictor of recurrence (P = 0.09; hazard ratio = 0.51; 95% CI, 0.24-1.12). CONCLUSION: GH replacement in patients with NFA treated by surgery alone is not associated with an increased risk of tumour recurrence.

An 'n-of-1' placebo-controlled crossover trial of intravenous immunoglobulin as adjuvant therapy in refractory pemphigus vulgaris.

BACKGROUND: Pemphigus vulgaris (PV) is an organ-specific autoimmune blistering mucocutaneous disorder that is potentially fatal. High-dose intravenous immunoglobulin (IVIg) is increasingly used in the treatment of autoimmune diseases and it has been reported that it may also be effective in PV. OBJECTIVES: To evaluate prospectively the efficacy of IVIg for PV using an 'n-of-1' placebo-controlled trial. METHODS: A randomized, placebo-controlled, crossover trial of IVIg was conducted in a single patient with severe PV, comprising two phases of six consecutive months of either IVIg or placebo infusion. Before the commencement of the trial, the patient had received 18 months of IVIg but concerns about the continuing therapeutic efficacy of IVIg led to the double-blind placebo-controlled 'n-of-1' trial of IVIg. RESULTS: Pemphigus autoantibody titres were significantly higher when on placebo compared with IVIg treatment (median 1 : 80 vs. 1 : 20, P = 0.007), desmoglein 3 (126 vs. 79, P = 0.004) and desmoglein 1 antibody levels (126 vs. 94, P = 0.004). There was a significant improvement in subjective disease activity scores while on IVIg compared with placebo (mean overall score 11.6 vs. 20.6, P < 0.0001). CONCLUSIONS: The results of this study confirm a beneficial effect of IVIg in the management of refractory PV.

Loop diathermy excision compared with cervical laser vaporisation for the treatment of intraepithelial neoplasia: a randomised controlled trial.

OBJECTIVE: To determine whether loop diathermy excision of the transformation zone and laser vaporisation are equally effective in the treatment of cervical intraepithelial neoplasia. DESIGN: Randomised controlled trial. POPULATION: Women referred for evaluation of cytological abnormality who were considered suitable for outpatient local destructive treatment. SETTING: Seven colposcopy units in the North West Region. METHODS: Loop diathermy excision of the transformation zone and laser vaporisation. MAIN OUTCOME MEASURE: Smear reported as moderate dyskariosis or worse following treatment. RESULTS: Of 289 women randomised, 285 had one or more smears following treatment. Women were more likely to have a smear reported as moderate dyskariosis or worse following laser vaporisation [hazard ratio 3.01 (95% CI 1.27 to 7.12)]. The cumulative risk of a smear reported as moderate dyskariosis or worse was 6.0% at six months and 12.1% at three years in those allocated laser vaporisation, and 2.0% at six months, and 3.3% at three years in those allocated loop diathermy excision of the transformation zone. CONCLUSIONS: Loop diathermy excision is a more effective treatment of cervical intraepithelial neoplasia than laser vaporisation.