Management of therapy-resistant systemic lupus erythematosus with rituximab: report of a case and review of the literature.

Therapy of systemic lupus erythematosus (SLE) with major organ involvement consists of aggressive immunosuppression with glucocorticoids and cytotoxic agents. When remission is achieved, maintenance therapy is begun to reduce the risk of relapse while minimizing toxicity. Remission with standard therapy is, however, not always achieved. We discribe a women with SLE and microangiopathic haemolytic anaemia and thrombocytopenia, pneumonitis and nephritis refractory to high-dose steroids, pulse cyclophosphamide, plasmapheresis and intravenous immunoglobulins. The anti-CD20 monoclonal antibody rituximab was administered, resulting in major clinical and biochemical improvement. Therapy-resistant SLE generally has an ominous prognosis. A few anecdotal reports and small open studies describe beneficial effects of rituximab in these cases. Rituximab may be a promising new approach to improve the dismal outcome of therapy-resistant SLE.

Extensive acronecrosis as a manifestation of mixed cryoglobulinaemia: a case report.

Cryoglobulinaemia is a systemic disorder characterized by circulating antibodies that precipitate in the cold and resolve on rewarming. Three different types have been described, distinct in the class of immunoglobulins and their clonality. The clinical expression varies from purpura and arthralgia to progressive renal failure and even acronecrosis (1-3). Associated conditions are lymphoproliferative disorders, auto-immune diseases and chronic infections, but several cases occur in the absence of identifyable other disease states. The present communication reports on a case of mixed cryoglobulinaemia. Of particular interest are the rapidly progressive clinical evolution to acronecrosis of the four limbs, necessitating amputation, the presence of spurious leucocytosis and the absence of other systemic symptoms.

Perinatal cortical infarction within middle cerebral artery trunks.

AIM: To define neonatal pial middle cerebral artery infarction. METHODS: A retrospective study was made of neonates in whom focal arterial infarction had been detected ultrasonographically. A detailed study was made of cortical middle cerebral artery infarction subtypes. RESULTS: Forty infarctions, with the exception of those in a posterior cerebral artery, were detected ultrasonographically over a period of 10 years. Most were confirmed by computed tomography or magnetic resonance imaging. Factor V Leiden heterozygosity was documented in three. The onset was probably antepartum in three, and associated with fetal distress before labour in one. There were 19 cases of cortical middle cerebral artery stroke. The truncal type (n=13) was more common than complete (n = 5) middle cerebral artery infarction. Of six infarcts in the anterior trunk, four were in term infants and five affected the right hemisphere. Clinical seizures were part of the anterior truncal presentation in three. One of these infants, with involvement of the primary motor area, developed a severe motor hemisyndrome. The Bayley Mental Developmental Index was above 80 in all of three infants tested with anterior truncal infarction. Of seven patients with posterior truncal infarction, six were at or near term. Six of these lesions were left sided. Clinical seizures were observed in three. A mild motor hemisyndrome developed in at least three of these infants due to involvement of parieto-temporal non-primary cortex. CONCLUSIONS: Inability to differentiate between truncal and complete middle cerebral artery stroke is one of the explanations for the reported different outcomes. Severe motor hemisyndrome can be predicted from neonatal ultrasonography on the basis of primary motor cortex involvement. Clinical seizures were recognised in less than half of the patients with truncal infarction; left sided presentation was present in the posterior, but not the anterior truncal type of infarction. Asphyxia is a rare cause of focal arterial infarction.

Neonatal focal temporal lobe or atrial wall haemorrhagic infarction.

AIMS: To describe two variants of infarction within the temporal lobe, associated with local matrix bleeding and mild to moderate intraventricular haemorrhage. METHODS: The files of 10 neonates, extracted from a sonographic study of 560 very low birthweight infants conducted between 1993 and 1997, were retrospectively examined. RESULTS: Seven lesions were located in the middle to posterior area of the temporal lobe, three others faced the atrium. All except two of those with a temporal site were VLBW infants with hyaline membrane disease. Except for one fatal case, intraventricular bleeding was mild to moderate. Computed tomograms or magnetic resonance imaging were used to illustrate the haemorrhagic nature of three lesions. Survivors of this so far undescribed entity who were followed up for more than 18 months did not have a uniform type of cerebral palsy but some scored in the low normal range on the Bayley Mental Development Index. One girl developed temporal lobe epilepsy. CONCLUSIONS: This pattern of injury seems to be one of venous infarction associated with temporal or para-atrial matrix haemorrhage. The temporal site fits the picture of venous infarction within the area drained by the inferior ventricular vein. A less constant lateral atrial vein, either draining into the basal or internal cerebral vein, is probably involved in the para-atrial lesion. Sonography may be the only practical tool currently available for detection in life.

Lyme disease in a child presenting with bilateral facial nerve palsy: MRI findings and review of the literature.

We report a 7-year-old boy with neuroborreliosis presenting with headache and bilateral facial nerve palsy. MRI demonstrated tentorial and bilateral facial and trigeminal nerve enhancement.

Retarded and aberrant splicings caused by single exon mutation in a phosphoglycerate kinase variant.

The molecular abnormality of a phosphoglycerate kinase variant which was associated with severe tissue enzyme deficiency and episodes of muscle contractions and myoglobinuria was examined. Analysis of the patient's DNA showed the existence of a nucleotide transversion A/T - C/G in exon 7. No other nucleotide change was detected in the coding region of the variant gene. The mutation should produce a single amino acid substitution Glu - Ala at protein position 251 counting from the NH2-terminal acetyl serine residue. The protein abnormality caused by the amino acid substitution cannot explain the enzyme deficiency. Northern blot hybridization indicated that the PGK mRNA content of the patient's lymphoblastoid cells was only about 10% of that of normal. Nucleotide sequence analysis revealed the existence of two PGK mRNA components in the patient's cells. The major component corresponds to the normal PGK mRNA except for A - C change at nucleotide position 755 counting from adenine of the chain initiation codon. The minor component contains 5' region (52 bases) of intron 7 between exon 7 and exon 8. An inframe chain termination codon exists in the minor mRNA component, and the COOH-terminal half is expected to be deleted in the translation product. These results indicate that the low PGK activity in the patient's tissues is mainly due to retarded and aberrant pre-mRNA splicings caused by the change of the consensus 5' splice sequence AGgt to a nonconsensus sequence CGgt at the junction between exon 7 and intron 7 of the variant gene.

High diagnostic performance of CT scan for analgesic nephropathy in patients with incipient to severe renal failure.

Recently, well performing diagnostic criteria for analgesic nephropathy in end-stage renal failure (ESRF) patients were defined by the demonstration of a bilateral decrease in renal volume combined with either bumpy contours or papillary calcifications. In this study, the diagnostic value of computed tomography (CT) scan was compared to the previously used renal imaging techniques (sonography and conventional tomography). In a first study, a cohort of 40 analgesic abusers (defined as daily use of analgesic mixtures during at least 5 years) and 40 controls, all ESRF patients without a clear renal diagnosis, were investigated with sonography, tomography and CT scan without injection of iodinated contrast material, to search for the imaging signs of analgesic nephropathy. Using CT scan, sonography and tomography, renal size could be evaluated with comparable results while CT scan was superior in the detection of papillary calcifications (sensitivity 87%, specificity 97%). In a second controlled study of 53 analgesic abusers with a serum creatinine between 1.5 to 4 mg/dl in the absence of a clear renal diagnosis, a CT scan was performed and scored for the presence of decreased renal volume, bumpy contours and papillary calcifications. It was found that the renal image of analgesic nephropathy on CT scan in an early stage of renal failure is comparable with the observations made in ESRF patients. Particularly the demonstration of papillary calcifications showed a high sensitivity of 92% with a specificity of 100% for the early diagnosis of analgesic nephropathy.

Staphylococcus aureus infections in haemodialysis patients: pathophysiology and use of nasal mupirocin for prevention.

Staphylococcus aureus is the most frequently (42%) isolated micro-organism during bacteraemic episodes in haemodialysis patients. Nasal carriage of S. aureus is of major importance in determining the risk of subsequent infections. Indeed, nasal carriage of S. aureus is highly prevalent in uraemic patients from the onset of maintenance dialysis therapy. The strains isolated simultaneously from the nares and the hands are usually the same. Likewise, infecting S. aureus strains and those isolated from nasal surveillance cultures obtained in the same patient are usually similar. S. aureus infections in haemodialysis patients are thus mostly to be considered as auto-infections. The nares are therefore an elective site for the prevention of S. aureus infections in haemodialysis patients. This has been demonstrated with oral rifampin, and more recently with nasal mupirocin, which is highly effective. Long-term application of nasal mupirocin (e.g. once per week) is cost-effective and is only rarely associated with the emergence of mupirocin-resistance in S. aureus.

Carbamazepine hypersensitivity syndrome: report of 4 cases and review of the literature.

We report 4 patients who developed a severe systemic hypersensitivity reaction when taking carbamazepine, To prove hypersensitivity to carbamazepine, we performed patch tests and in vitro lymphocyte transformation tests. Patch tests were uniformly and strongly positive in patients and negative in controls. Lymphocyte transformation tests were positive in 3 of 4 patients. We reviewed the literature on reports of carbamazepine-induced pseudolymphoma and other severe systemic hypersensitivity reactions. Considering the many common clinical, biochemical, and pathologic characteristics, we propose to group these reactions under the term "carbamazepine hypersensitivity syndrome." The syndrome is characterized by the development of fever, rash, and lymphadenopathy between 1 week and 3 months after the introduction of carbamazepine. A variety of other target organs may be involved, including the liver, kidneys, and lungs. The carbamazepine hypersensitivity syndrome is a clinical diagnosis. Patch tests and lymphocyte transformation tests are valuable tools to confirm the diagnosis, but are reliable only after all signs subside. Similar syndromes have been described with the other aromatic anticonvulsants (phenytoin, the other hydantoins, and phenobarbital), and there is evidence of a cross-reaction between carbamazepine and phenytoin. It is unknown whether the carbamazepine hypersensitivity syndrome should be considered a premalignant state, with an increased risk for the development of malignant lymphoma.

[Epidemiology and prevention of Staphylococcus aureus infections during hemodialysis]. / Epidémiologie et prévention des infections à Staphylococcus aureus en hémodialyse.

Staphylococcus aureus is the pathogen most often isolated from blood during bacteraemic episodes in haemodialysis patients (42%). The pathophysiology of these infections is discussed and a prophylactic strategy is proposed. Nasal carriage of S. aureus, found in 42% of haemodialysis patients, plays a major role in its cutaneous dissemination and hence in the risk of infection by this microorganism. Long-term use of nasal mupirocin in haemodialysis patients with nasal carriage of S. aureus (t.i.d. for 3 to 5 days, followed by once a week) led to a decrease in the yearly incidence of S. aureus bacteraemia from 0.097 to 0.024 (p < 0.01). Tolerance was excellent. This chemoprophylaxis results in substantial savings. When applied as proposed (only nasal application), the long-term use of mupirocin only very rarely leads to the emergence of mupirocin-resistance in S. aureus (1 case in 165 patient-years).

Nasal mupirocin ointment decreases the incidence of Staphylococcus aureus bacteraemias in haemodialysis patients.

The incidence of S. aureus bacteraemia in a haemodialysis unit was studied over 2 years (167.75 patient-years of follow-up) during which nasal calcium mupirocin was used to eradicate nasal S. aureus carriage; this incidence was compared to that previously observed in the same unit before the use of nasal mupirocin (185.8 patient-years). Nasal mupirocin led to eradication of nasal S. aureus carriage in 96.3% of surveillance cultures and to a fourfold reduction in the incidence of S. aureus bacteraemia per patient-year, from 0.097 before mupirocin to 0.024 with mupirocin use (P = 0.008). Once or thrice weekly maintenance regimens of mupirocin were equally efficacious. The incidence of bacteraemia caused by other micro-organisms was not significantly affected. One single mupirocin-resistant isolate was identified in a nasal surveillance culture. Eradication of S. aureus from the nares did not lead to overgrowth by other micro-organisms. Chemoprophylaxis with nasal mupirocin in haemodialysis patients is cost-effective.

Plasma apolipoprotein A-IV metabolism in patients with chronic renal disease.

The plasma concentration and distribution of apolipoprotein A-IV were investigated in normotriglyceridaemic patients with end-stage renal disease and compared with those in a sex- and age-matched control group with normal renal function. A three-fold elevated plasma mean concentration of apolipoprotein A-IV was found in patients with end-stage renal disease treated by haemo- or peritoneal dialysis (58.5 +/- 18.9 mg dl-1 or 50.5 +/- 12.2 mg dl-1, respectively) compared with the controls (18.3 +/- 6.4 mg dl-1). The plasma distribution of apolipoprotein A-IV was studied in patients treated by haemodialysis and in controls by gel permeation chromatography. In the haemodialysis group, 40.3% of the apolipoprotein A-IV was found to be associated with the fraction of high density lipoproteins, whereas the rest (59.7%) was not associated with lipoproteins. This distribution was significantly different from that in the control group (24.8% vs. 75.2%, 0.01 less than P less than 0.05). The elevated plasma concentrations of apolipoprotein A-IV in the patients are not related to triglyceride levels and therefore are unlikely to result from an impaired catabolism of triglyceride-rich lipoproteins. The accumulation of apolipoprotein A-IV in high density lipoproteins from patients with end-stage renal disease might reflect the impaired reversed cholesterol transport mechanisms which are believed to be a major cause of the high prevalence of atherosclerotic diseases in these patients.

Diagnostic criteria of analgesic nephropathy in patients with end-stage renal failure: results of the Belgian study.

Diagnostic criteria of analgesic nephropathy with well-defined sensitivity and specificity are not available. During a 2-year period all new patients (n = 273) starting renal replacement therapy in 13 Belgian dialysis units were investigated aiming to select diagnostic criteria of analgesic nephropathy with acceptable performance. Using several interview techniques, a history of analgesic abuse was found in 31% of the patients. Analgesic abusers presenting a clear non-analgesic-related renal diagnosis were excluded from analysis (n = 25). Comparing the remaining abusers (n = 60) and patients without a history of analgesic abuse (n = 188) it was found that renal imaging investigations (sonography plus tomography), showing a decrease in length combined with bumpy contours of both kidneys, presented a sensitivity of 90% and a specificity of 95%. The additional finding of signs of renal papillary necrosis resulted in an overall sensitivity of 72% and a specificity of 97%, giving a positive predictive value of 92%. Other signs frequently mentioned in the literature (hypertension, anaemia, sterile pyuria, bacteriuria, proteinuria) showed insufficient sensitivity and/or specificity to be of help for diagnosing analgesic nephropathy in end-stage renal failure (ESRF) patients starting renal replacement therapy.

Effect of simvastatin treatment on the dyslipoproteinemia in CAPD patients.

HMG-CoA reductase inhibitors have been proven effective in decreasing the plasma cholesterol levels in patients affected with various forms of hypercholesterolemia, familial dysbetalipoproteinemia, familial combined hyperlipidemia and in nephrotic and diabetic dyslipidemia. The purpose of this study was to monitor and evaluate the efficiency and safety of the therapy with simvastatin, an HMG-CoA reductase inhibitor, in a group of patients treated by continuous ambulatory peritoneal dialysis (CAPD) with severe hypercholesterolemia. Monitoring of the changes occurring in the various lipids and apolipoproteins in these patients included the measurements of the plasma lipids and apolipoproteins A-I, A-II, B, C-II, A-IV and Lp(a). Lipoproteins were separated by gel filtration, on a Superose 6HR column, before and after 24 weeks of treatment. The patterns were compared to those observed in a group of primary hyperlipidemic patients treated with Lovastatin, a compound of the same class. The drug was well tolerated by the CAPD patients and no adverse reaction was observed. In addition to the decrease of the total and LDL cholesterol, similar to that reported in other groups of patients, we further observed a decrease of the apo E concentration in both the CAPD and the hyperlipidemic patients. This decrease was especially pronounced in the HDLE fraction and could involve an upregulation of the apo B-E and/or apo E receptor. These results should provide information about the mechanism of action of this drug in patients with end-stage renal disease.

Effect of a serotonin blocking agent on renal hemodynamics in the normal rat.

These studies were designed to explore the effects of ketanserin (K), a serotonergic S2-receptor blocker on glomerular filtration rate (GFR), renal plasma flow (RPF) and autoregulation of renal blood flow (RBF) in the normal, anesthetized rat. Two doses of ketanserin were used: a high dose that, in addition to its serotonin blocking effect, possessed alpha 1-adrenergic blocking capacities; and a low dose that acted only as a serotonin S2 blocking agent. The effects of the high dose were compared to the effects of phenotolamine. Both the high dose of K and phentolamine resulted in a similar fall of systemic blood pressure from 117 +/- 4 to 78 +/- 3 and from 121 +/- 4.5 to 76 +/- 5 mm Hg, respectively (P less than 0.01). Despite this fall, GFR and RPF remained unchanged from 2.36 +/- 0.16 +/- to 2.26 +/- 0.12 ml/min, and from 5.33 +/- 0.41 to 5.76 +/- 0.5 ml/min with K, while both parameters significantly decreased with phentolamine. A remarkable preservation of the autoregulation of RBF until a renal perfusion pressure (RPP) of 70 to 75 mm Hg was noted with K, but not with phentolamine or Ringer infusion. With the low dose of K, a significant rise in GFR and PAH clearance was noted, from 2.12 +/- 0.17 to 2.59 +/- 0.18 and from 4.81 +/- 0.35 to 5.66 +/- 0.48 ml/min, respectively (P less than 0.05). A similar preservation of autoregulation of RBF was observed. Our studies suggest that in the pressure ranges below normal autoregulation of RBF in the rat, serotonin blockade is associated with maintenance of both GFR and RBF.

Iron overload in haemodialysis patients increases the risk of bacteraemia: a prospective study.

The incidence of bacteraemia in relation to the degree of transfusional iron overload was studied prospectively in patients from one haemodialysis unit over a 2-year period, with a total follow-up of 181.3 patient-years in 158 patients. Every 3 months, the patients were classified according to the serum ferritin in one of three groups: less than 500, 500-1000 or greater than 1000 micrograms/l. Twenty-nine episodes of bacteraemia were recorded over 181.3 patient-years (yearly incidence of 0.160). The yearly incidence of bacteraemia was 0.1173 and 0.1101 for ferritin less than 500 and 500-1000 micrograms/l (no significant difference), with a cumulative incidence for both groups of 0.1164. In the ferritin greater than 1000 micrograms/l group, the incidence was 0.3404 (P less than or equal to 0.005 versus the ferritin less than or equal to 1000 micrograms/l group). After stratification for patient's age (at inclusion in the study) and duration of haemodialysis therapy, the higher incidence of bacteraemia in the ferritin greater than 1000 versus less than or equal to 1000 micrograms/l groups persisted (P less than or equal to 0.005). This prospective study confirms previous retrospective studies in showing that acquired transfusional iron overload in haemodialysis is associated with a greater risk of bacteraemia.

The influence of calcium mupirocin nasal ointment on the incidence of Staphylococcus aureus infections in haemodialysis patients.

Mupirocin was used in haemodialysis patients in an attempt to eradicate nasal carriage of Staphylococcus aureus and to prevent infection caused by this microorganism. The effectiveness of calcium mupirocin as a 2% nasal ointment OB2 (16 patients for 104 patient-months) was compared to that of placebo (18 patients for 147 patient-months) in a double-blind study. Mupirocin or placebo were applied in both anterior nares thrice daily for 2 weeks and subsequently three times weekly for a total of 9 months. During therapy, S. aureus was recovered from only 6% of the nasal cultures in the mupirocin group compared to 58% in the placebo group (P less than or equal to 0.01). Only one S. aureus infection was documented in the mupirocin group compared to six in the placebo group (P less than or equal to 0.05). The S. aureus strain causing the single infection in the mupirocin group was of a different phage type to that of the original nasal strain. In contrast, at least four of the six strains causing infection in the placebo group were of similar phage type to the original nasal strain. All S. aureus isolates remained mupirocin sensitive (MIC less than or equal to 1 mg/l). In conclusion, mupirocin nasal ointment was effective in eradicating nasal carriage of S. aureus and in preventing S. aureus infections in patients on haemodialysis.