IgG4-related systemic sclerosing disease – an emerging and under-diagnosed condition

Autoimmune pancreatitis was first described in 1961, although it was not more widely recognized as an autoimmune condition until 1995. It has now become apparent that this form of pancreatitis is part of a clinical syndrome that is commonly multisystem in nature. One of the most common histopathological features is the presence of IgG4+ plasma cells within involved tissues. Many terms have been proposed to describe the condition, but 'IgG4-related systemic sclerosing disease' appears most appropriate. Commonly affected extrapancreatic tissues include the biliary tract, liver, kidneys and lung, but a wide range of other sites may be involved. Histological examination reveals features that are not entirely disease-specific, but that are often sufficiently characteristic to provide useful support to a clinicopathological diagnosis. The disease often responds well to systemic steroid therapy, unlike some of the conditions that it may simulate clinically. The emergence of this disease as a specific and treatable entity has favourably altered the clinical outlook for patients in whom steroid therapy might not previously have been considered appropriate.     

Leptospirosis: epidemiology,diagnosis and clinical aspects

Leptospires, world-wide distributed spirochetes, affect a great variety of mammalian hosts; several serovars belonging to the L. interrogans s.l. species can cause clinical manifestations in humans, becoming infected through the contact of skin cuts and mucous membranes with water and soil polluted by infected animals' urine; rodents serve as the main reservoirs but the epidemiological importance of pets and cattle, as leptospire shedder is increasing. While the infection remains endemic in tropical regions, there is a new epidemiological trend in developed countries where, with the typical seasonal pattern, sporadic cases and/or outbreaks occur related more to recreational activities and poor sanitation than to occupational activities. The sudden onset presents a "flu-like" syndrome; the course is usually characterised by two clearly defined stages. All of the variable clinical manifestations, often independent of the responsible serovar, arise from the effects of a general vasculitis. The prognostic factors associated with severe forms (renal failure, jaundice, haemorrhagies) are not defined. Within the first days of illness, the leptospires can be isolated from blood and cerebrospinal fluid; serological diagnosis relies on microagglutination, IFA and ELISA; PCR early in the course, before the appearance of specific antibodies, allows etiological diagnosis. Prompt treatment has an enormous impact on outcome.     

Leptospirosis

Leptospirosis is a worldwide zoonotic infection with a much greater incidence in tropical regions and has now been identified as one of the emerging infectious diseases. The epidemiology of leptospirosis has been modified by changes in animal husbandry, climate, and human behavior. Resurgent interest in leptospirosis has resulted from large outbreaks that have received significant publicity. The development of simpler, rapid assays for diagnosis has been based largely on the recognition that early initiation of antibiotic therapy is important in acute disease but also on the need for assays which can be used more widely. In this review, the complex taxonomy of leptospires, previously based on serology and recently modified by a genotypic classification, is discussed, and the clinical and epidemiological value of molecular diagnosis and typing is also evaluated.     

Melioidosis: an under-diagnosed entity in western coastal India: a clinico-microbiological analysis

Clinico-microbiological analysis of a series of 25 patients with culture proven melioidosis was done. All patients came from the coastal regions of Kerala and Karnataka and presented between June 2005 to July 2006. They were analysed with respect to clinical presentation, occupation, epidemiology and microbiological features. No single presenting clinical feature was found to be typical of melioidosis. The disease was found to mimic a variety of conditions, including tuberculosis and malignancy. Burkholderia pseudomallei was isolated from blood, sputum, pus, urine, synovial, peritoneal and pericardial fluids. Diabetes mellitus was the most common predisposing factor and 80% of the cases presented during the Southwest monsoon (June to September). It is probable that melioidosis is highly prevalent in western coastal India and yet, greatly underestimated. Better awareness, both among clinicians and microbiologists, coupled with improved diagnostic methods to allow early diagnosis and hence early treatment, will significantly reduce the morbidity and mortality associated with this disease.     

Hypertensive nephropathy - an increasing clinical problem

Arterial hypertension-related renal damage is an increasingly common problem recently, because approximately 25% of patients currently treated with dialysis were hypertensive before renal replacement therapy was started. Hypertension is also known as a metabolic disease, while carbohydrate, purine and lipid disturbances are the features of this syndrome. On the other hand, the progression of renal disease depends on the extent of tubulointerstitial injury. For this reason, we undertook a study to evaluate the relationship between excretion of the markers of tubular damage (NAG) and some parameters of carbohydrate, purine and lipid metabolism in untreated essential hypertension. Both healthy volunteers (n = 15) aged 32. 6+/-7.8 and essential hypertensives (n = 25) aged 37.24+/-11.39 underwent the same tests. These tests were performed at 2-day intervals: intravenous glucose tolerance test with 0.5 g/kg b.w. as 40% glucose solution and oral fructose load test with 1.0 g/kg b.w. Area under glucose curve (GA) and serum uric acid post-fructose (PUAA) were calculated. Fasting: insulin, total cholesterol and LDL, triglycerides, free fatty acids (FFA) and urine excretion of NAG, albumin were determined. Glomerular filtration rate was estimated as creatinine clearance. Hypertensives showed statistically higher BMI (p<0.007), NAG (p<0.02), total cholesterol (p<0.01), LDL (p<0.007), FFA (p<0.007), insulin (p<0.01), PGA (p<0.01) and PUAA (p<0.03). NAG excretion correlated positively with WHR (r = 0.40), MAP (r = 0.47) and PUAA (r = 0.47) in hypertensives only. We presume that tubular injury at an early stage of renal damage in patients with essential hypertension could be a part of metabolic syndrome X.     

Leptospirosis in Mayotte

We have got 42 leptospirosis cases from 1984 to 1989, in a retrospective study. The annual incidence is now, in a very high level (3.8/10,000 pers.). This rapid increasing is function of new diagnostics facilities. The leptospirosis epidemiology is not different from anywhere else in tropical countries, but the complicated cases are an important problem in public health in the island. The actual development of collective hygienic equipment is indispensable for any progress.     

Leptospirosis in pregnancy

Leptospirosis is a direct zoonotic disease caused by spirochetes belonging to the genus Leptospira. Many animals act as carriers or vectors. Human infection results from accidental contact with carrier animals or environment contaminated with animal urine containing the organism. Epidemics of leptospirosis result from poor sanitation in urban areas and are aggravated following natural calamities. The majority of leptospiral infections are either subclinical or result in very mild illness and patients recover without complications. In a few cases it may manifest as multiorgan failure where the mortality can go up to 40%. Infection in pregnant women may be grave leading to severe fetal and maternal morbidity and mortality. The presentation may mimic other viral, bacterial, and parasitic infections, acute fatty liver, pregnancy-induced hypertension, and HELLP syndrome. Owing to the unusual presentation, leptospirosis in pregnancy is often misdiagnosed and under-reported. Preventive public education regarding hygiene, personal practices, source reduction, environmental sanitation, early diagnosis, and treatment of the condition are needed to avoid perinatal and maternal mortality.     

Pulmonary Involvement in Leptospirosis

 The objective of this study was to assess the incidence of pulmonary involvement in a cohort of 26 patients in whom a diagnosis of leptospirosis had been made. Seventeen of the 26 patients had respiratory symptoms. Of these 17 patients, 13 had radiographs showing pulmonary abnormality. The most frequent finding was a bilateral patchy alveolar-acinar pattern in six patients. Three patients developed acute respiratory distress syndrome and died due to multiorgan failure. Only cigarette smoking was significantly associated with respiratory involvement (odds ratio, 19.2; 95% CI, 1.7–250;P<0.001). The results indicate that pulmonary manifestations are observed in a high percentage of patients with leptospirosis. Cigarette smoking is a risk factor for the development of pulmonary involvement in human leptospirosis.     

Internet databases for clinical geneticists - an overview1

In this paper, we provide an overview of databases that are of importance to clinical geneticists. Some suggestions for the fruitful use for both research and diagnosis are given. For beginning ‘web-surfers’ we also list some well-known search engines and give a short overview of how to use these and other services. In addition, the URLs of some of the most important databases, gateways and tutorials are listed.