The pathophysiology of anti-glomerular basement membrane (anti-GBM) disease before clinical presentation is unknown. The presence of anti-GBM, anti-proteinase 3 (PR3), and anti-myeloperoxidase (MPO) antibodies associate with the disease at the time of diagnosis, but little is known about the presence of these autoantibodies before diagnosis. We used serum samples from the Department of Defense Serum Repository to conduct a case-control study involving 30 patients diagnosed with anti-GBM disease and 30 healthy controls matched for the age, gender, race, and age of the serum samples. We analyzed a maximum of three samples from each subject: the most recent sample before diagnosis, the penultimate sample before diagnosis, and the oldest sample available; the average time between the most recent sample and diagnosis was 195 days (range, 4 to 1346 days). Elevated anti-GBM levels (Ն3 U/ml) were present in four patients, all less than 1 year before diagnosis but in no controls. Detectable anti-GBM antibody levels (Ն1 U/ml but Ͻ3 U/ml) in a single serum sample before diagnosis were more frequent in cases than controls (70% versus 17%, P Ͻ 0.001). Only study patients had detectable anti-GBM levels in multiple samples before diagnosis (50% versus 0%, P Ͻ 0.001). Almost all patients had detectable anti-PR3 and/or anti-MPO that preceded the onset of disease. Among patients with a clear antecedent antibody, anti-PR3 or anti-MPO always became detectable before the anti-GBM antibody. In summary, our data describe the subclinical formation of autoantibodies, which improves our understanding of the pathophysiology of anti-GBM disease.

SummaryBackground and objectives The subclinical pathogenesis of granulomatosis with polyangiitis (GPA) has not been completely elucidated. Proteinase 3 (PR3) antibodies are strongly associated with GPA, but have not been evaluated before disease presentation.Design, setting, participants, & measurements This was a retrospective case-control serum bank study in which PR3 antibodies and C-reactive protein (CRP) in up to three longitudinal serum samples for 27 GPA patients before diagnosis (1 day-19 years) were compared with 27 controls whose serum samples were matched for age, sex, and race. This study analyzed all patients with American College of Rheumatology criteria-confirmed disease identified in the Department of Defense electronic medical records between 1990 and 2008.Results A greater percentage of GPA patients had at least one elevated PR3 antibody level ($6 U/ml) as well as at least one detectable PR3 antibody level (.1 U/ml) before diagnosis compared with matching controls ( Conclusions Subclinical PR3 antibody presence, trajectory, and temporal relationship to CRP associates with the future diagnosis of GPA. This data set further elucidates the pathogenesis of GPA.

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A 22-year-old African-American man with AIDS who had recently started on trimethoprim/sulfamethoxazole daily for pneumocystis jirovecii pneumonia prophylaxis presented with an altered mental state, malaise and nausea was found to have hepatitis, pancreatitis, rhabdomyolitis, acute kidney injury and haemolytic anaemia. Cessation of Bactrim and supportive care with volume expansion resolved his clinical symptoms and laboratory abnormalities.

Radionuclide scanning with Technetium 99-m HIDA was performed in eighty-nine patients with suspected acute cholecystitis. In twenty-three patients (25.8%), the study demonstrated evidence of cystic duct obstruction and non-visualisation of the gallbladder. Almost all of these patients subsequently were shown to have acute cholecystitis at surgery. The sensitivity and specificity of the procedure for the diagnosis of acute cholecystitis was 95.8% and 100% respectively. The use of radionuclide cholescintigraphy in the assessment of hepatobiliary disorders is reviewed, and it is suggested that it is the test of choice at present for diagnosis of acute cholecystitis.