[Systemic corticosteroid treatment and risk of infectious diseases]. / Corticothérapie systémique et risque infectieux.

PURPOSE: It was shown that corticosteroids alter the inflammatory and immune responses. Many publications report on serious infections occurring in patients receiving corticosteroids or presenting with Cushing's syndrome. This information is synthesized in this article. CURRENT KNOWLEDGE AND KEY POINTS: The demonstration of the infectious risk associated with corticosteroids relies on observational data and on biological plausibility. However, this risk remains difficult to quantify, because of many confusing factors such as the patients' associated conditions and immunosuppressive treatments, and the highly variable dose and duration of the corticosteroid treatment. Taking into account the published data, the screening for a chronic infection seems licit among patients receiving a systemic corticosteroid treatment, in particular for those who will receive more than 10 mg of prednisone per day. FUTURE PROSPECTS: Although no clinical trials of prevention of infections in corticosteroid treated patients has been published, a strategy aiming at minimizing the infectious risk of corticosteroid treated patients is proposed, based on the analysis of the literature presented in this article.

Focal segmental glomerulosclerosis associated with mitochondrial cytopathy.

BACKGROUND: The nonspecific lesion of focal segmental glomerulosclerosis (FSGS) can occur as a primary disease or in a variety of secondary settings. In mitochondrial cytopathies (MCs), the phenotypic expression of the disease depends on the degree of cellular dysfunction, and this correlates with the proportion of abnormal mitochondrial DNA in the cells and the dependence of tissues on oxidative metabolism. The most common renal manifestation in MCs is tubular dysfunction; little has been reported about glomerular diseases. METHODS: Cases of four adult patients with FSGS and MC are reported. Routine histology and mitochondrial DNA analysis were carried out on renal biopsies. RESULTS: Family history and clinical manifestations in the four patients with FSGS suggested a diagnosis of MC. An A3243G transition in the mitochondrial DNA tRNA(leu(UUR)) was found in lymphocytes and kidney. Glomerular lesions of FSGS were associated with unusual hyaline lesions, which appeared to represent individual myocyte necrosis in afferent arterioles and small arteries. CONCLUSION: FSGS is a renal manifestation of MCs. The renal lesion can precede other manifestations of the genetic disease by many years. The striking arteriolar lesions in these cases may have resulted in glomerular hypertension and hyperperfusion, leading to secondary epithelial cell abnormalities and, ultimately, FSGS. However, primary epithelial cell dysfunction caused by mitochondrial defects could not be ruled out on morphological grounds. MCs should be considered in cases of so-called primary FSGS, particularly if there is a familial history of diabetes, neuromuscular disorders, or deafness.

Production of 5-lipoxygenase pathway metabolites by peripheral leucocytes in capillary leak syndrome (Clarkson disease).

Periodic systemic capillary leak syndrome (Clarkson disease) is characterized by unexplained attacks of a marked increase in capillary permeability. As leukotrienes, derived from arachidonic acid via the 5-lipoxygenase pathway, enhance capillary permeability, we studied arachidonate metabolism in leucocytes of a patient with capillary leak syndrome. Leucocyte-platelet suspensions, prepared from blood collected from the patient during asymptomatic periods (n = 11) produced greater amounts of 5-hydroxyeicosatetraenoic acid (5-HETE) than control suspensions (P less than 0.05). Peripheral leucocytes, collected during attacks (n = 3) and studied without addition of A23187 released LTB4 in vitro but not sulphidopeptides leukotrienes. This result was never observed with leucocytes from control subjects or from the patient out of a crisis. These results suggest that in the patient, peripheral leucocytes could be stimulated by an unknown, as yet to be determined, endogenous factor to produce more 5-HETE and LTB4. Whether LTB4 plays a pathogenic role in the capillary leakage remains to be determined.