Rituximab-mediated late-onset neutropenia in systemic lupus erythematosus - distinct roles of BAFF and APRIL.

Objective Rituximab-mediated late-onset neutropenia (LON) has been described in various diseases. We investigated its occurrence, consequences and contributing factors in patients with systemic lupus erythematosus (SLE). Methods Rituximab-treated patients from the Karolinska University Hospital ( n = 107) were surveyed. LON was defined as an absolute neutrophil count <1500 cells/µl, occurring four weeks to two years following rituximab treatment, or later during sustained B-cell depletion. Serum levels of B-cell-related cytokines and growth factors of the myeloid lineage were determined using enzyme-linked immunosorbent assay. Results Thirty-two patients (29.9%) developed LON after a median time of 201.5 days. Thirteen patients were admitted to the hospital; 10 due to fever. Three patients developed critical conditions. BAFF levels increased from baseline (median: 0.62 ng/ml) to the post-treatment evaluation (median: 1.16 ng/ml; p < 0.001); post-treatment levels were higher in the LON group ( p = 0.021). APRIL levels were higher in the LON group both at baseline (median: 1.54 versus 1.15 ng/ml; p = 0.027) and post-treatment (median: 2.39 versus 1.11 ng/ml; p = 0.011). IL-6 and GM-CSF levels decreased in the non-LON group ( p < 0.001), but not in LON patients. High baseline disease activity predicted LON development (OR: 4.1; 95% CI: 1.1-15.2 for SLEDAI-2K > 8). No association with neutropenia prior to rituximab treatment was documented. Conclusion Post-rituximab LON was a common complication. Although the phenomenon was predominantly self-limiting, several patients developed severe conditions. Distinct roles of BAFF and APRIL are implicated: BAFF may contribute to LON development, whereas high APRIL levels may be predictive. Rituximab-treated SLE patients should be monitored for neutrophil counts, fever and infections.

Adult bacterial meningitis: aetiology, penicillin susceptibility, risk factors, prognostic factors and guidelines for empirical antibiotic treatment.

Episodes of adult bacterial meningitis (ABM) at a Danish hospital in 1991-2000 were identified from the databases of the Department of Clinical Microbiology, and compared with data from the Danish National Patient Register and the Danish National Notification System. Reduced penicillin susceptibility occurred in 21 (23%) of 92 cases of known aetiology, compared to an estimated 6% in nationally notified cases (p < 0.001). Ceftriaxone plus penicillin as empirical treatment was appropriate in 97% of ABM cases in the study population, and in 99.6% of nationally notified cases. The notification rate was 75% for penicillin-susceptible episodes, and 24% for penicillin-non-susceptible episodes (p < 0.001). Cases involving staphylococci, Pseudomonas spp. and Enterobacteriaceae were under-reported. Among 51 ABM cases with no identified risk factors, nine of 11 cases with penicillin-non-susceptible bacteria were community-acquired. Severe sequelae correlated independently with age, penicillin non-susceptibility, mechanical ventilation and non-transferral to a tertiary hospital (p < 0.05; logistic regression). Other factors that correlated with severe sequelae by univariate analysis only were inappropriate clinical handling, abnormal consciousness, convulsions and nosocomial infection. Overall, the data indicated that neither age alone, community-acquired infection nor absence of identified risk factors can predict susceptibility to penicillin accurately. Recommendations for empirical antibiotic treatment for ABM should not be based exclusively on clinical notification systems with possible unbalanced under-reporting.

[Hepatitis A in Denmark. Notified cases 1996-1999]. / Hepatitis A i Danmark. Anmeldte tilfaelde 1996-1999.

INTRODUCTION: The aim of the study was to describe the incidence of hepatitis A in Denmark with the emphasis on the role of immigrants in relation to transmission and prevention of the disease. METHOD: A retrospective study of notified cases of hepatitis A during the period, 1.1.1996-31.12.1999. RESULTS: A total of 398 notified cases were examined, 45% of which occurred in immigrants. The average incidence per year was 13.2 per 100,000 for immigrants and 1.1 per 100,000 for Danes. The incidence for immigrants from Pakistan and Turkey was 4-5 times that for immigrants as a whole. The median age in immigrants was eight years and in Danes 29 years. Immigrants were hospitalised in 35% of the cases. Of children below ten years of age 31% were admitted. Danes were hospitalised in 43% of the cases, and of children below ten years of age 44% were admitted. Infection was acquired abroad for 71% of immigrants, 49% of whom visited Pakistan or Turkey. Of those infected in Denmark, person-to-person transmission was the most common mode of infection for both groups. Immigrants who had been travelling to endemic areas were involved in 21 of 34 outbreaks. CONCLUSION: The incidence of hepatitis A in Denmark seems to relate highly to the children of immigrants, who come from high endemic areas. Vaccination of those above one year of age is recommended when travelling abroad if anticipated. Economic compensation could be considered.

C-reactive protein: the difference between quantitation is serum and EDTA plasma.

We report the differences between using either EDTA plasma or serum in a turbidimetric assay for quantitation of C-reactive protein (CRP). A systematic discrepancy was found for these two sample materials. This was most pronounced in the low concentration range (below 20 mg1(-1)) at which lower values were found in serum than in EDTA plasma. Conversely, in the high concentration range, serum showed slightly higher values. Addition of K3-EDTA to the reaction buffer improved the kinetics for sera with low concentrations of CRP, thus increasing the sensitivity of the assay. We found an overall constant discrepancy of approximately 8% lower values in plasma than in serum (equally for low and high levels of CRP) after the addition of K3-EDTA. The most probable explanation for this effect seems to be the differing water content of serum and EDTA plasma. We discuss the role and function of EDTA in the CRP assay and suggest some hypothetical mechanisms.

Autoantibodies to leucocyte antigens in hydralazine-associated nephritis.

Clinical and laboratory findings and drug history were studied in 17 patients with suspected hydralazine-associated nephritis, five of whom only had renal disease, while twelve also had extrarenal manifestations. Renal biopsies revealed extracapillary proliferative or focal segmental proliferative glomerulonephritis in 10 patients, and tubulo-interstitial nephritis in five patients. Antinuclear antibody (ANA) was found in 16 patients, but none of the 14 patients tested had antibodies to DNA. Tests for antibodies to myeloperoxidase (anti-MPO) and antibodies to neutrophil cytoplasm antigen (ANCA) were performed by ELISA. Twelve of the 14 patients tested had anti-MPO; five of these 14 patients had ANCA, while one had borderline levels. These findings suggest that hydralazine facilitates the induction of a systemic disease with multiple autoantibody production.

[Use of alcohol and narcotics among Danish adolescents in the 1980's]. / Alkohol-og narkotikabrug blandt danske unge i 1980'erne.

A review is presented of the results of epidemiological investigations from 1980 to 1988 concerning the use of alcohol and narcotics among adolescents in Denmark. The material includes ten anonymous questionnaire investigations in all of which school pupils participated and a qualitative interview investigation. Comparison of the age-specific prevalence rates reveals that the use of alcohol and narcotics increases with age and that the intake of alcohol is slightly higher in boys than in girls. The majority of the adolescents drink mainly at weekends and in connection with social events. The use of hash is greatest among boys and the average age for commencing is slightly higher than for alcohol. Apart from hash, the employment of narcotics is low in school pupils. Although approximately 24,000 adolescents were questioned, the investigations together provide an uncertain picture of the habits as these are not representative for Danish adolescents. It is not possible to indicate genuine risk groups. It is concluded that initiatives for prophylactic efforts do not have any basis for action. Repeated national representative questionnaire investigations are proposed supplemented by qualitative interviews with particularly selected adolescents and local key-persons.

[Reactions after MMR vaccination]. / Reaktioner efter MFR-vaccination.

Four months after introducing routine vaccination against measles, mumps and German measles (MMR-vaccination) in Denmark, a questionnaire study of reactions in vaccinated children was carried out. There were significantly fewer reactions in children who had previously developed immunity to measles, either by having had the disease or by vaccination. The reaction frequency after MMR-vaccination of children immune to measles was no greater than that after other vaccinations. Moreover, for all vaccinations, the frequency of reaction was found to decrease significantly with increasing age. The study suggests that a large proportion of the so-called reactions were not caused by vaccination, but were due to common viral infections occurring at random and concurrently with it. The reactions that arose in connection with MMR-vaccination are considered to be of minor importance when compared with often prolonged and more severe course of these diseases.

[Influenza. Consequences for health and prevention]. / Influenza. Sundhedsmaessige k9nsekvenser og forebyggelse.

Investigations from abroad and from Denmark show that epidemics of influenza are not only accompanied by considerable morbidity but also by considerable excess mortality and a sizable increase in the number of admissions to hospital. The increases in the number of deaths comprise 170-320 per million of the population per epidemic. The excess mortality occurs primarily among individuals with chronic pulmonary and circulatory disease and may be very great in nursing homes and similar institutions. Influenza vaccination will, in general, provide protection of approximately 70% and does not cause noteworthy side effects. Amantadine and rimantadine chemoprophylaxis, which is employed in some countries, provides protection of 80-90% from Influenza A. Recommendations are established for influenza vaccination and a series of situations are quoted where it would be advisable to supplement or replace vaccination with chemoprophylaxis. It is important to attempt to improve the vaccination rates, eg. by means of informative activity, improved planning of the vaccination programmes and public support to vaccination of high-risk groups.