Longitudinal analysis of varicella-zoster virus-specific antibodies in systemic lupus erythematosus: No association with subclinical viral reactivations or lupus disease activity.

Systemic lupus erythematosus (SLE) patients are at high risk of herpes zoster. Previously, we found increased immunoglobulin (Ig)G levels against varicella-zoster virus (VZV) in SLE patients compared to controls, while antibody levels against diphtheria and cellular immunity to VZV were decreased. We aimed to test our hypothesis that increased VZV-IgG levels in SLE result from subclinical VZV reactivations, caused by stress because of lupus disease activity or immunosuppressive drug use. Methods Antibody levels to VZV (IgG, IgA, IgM), total IgG and VZV-DNA were longitudinally determined in the serum of 34 SLE patients, using enzyme-linked immunosorbent assay and polymerase chain reaction. Clinical data were retrieved from medical records. Reactivation of VZV was defined as an at least fivefold rise in VZV-IgG or presence of VZV-IgM or VZV-DNA. Generalized estimating equations (GEE) were used to longitudinally analyse associations between antibody levels, lupus disease activity and medication use. Systemic Lupus Erythematosus Disease Activity Index, anti-double-stranded DNA and complement levels were used as indicators of lupus disease activity. Results A VZV reactivation was determined in 11 patients (33%). In at least five of them, herpes zoster was clinically overt. No association between SLE disease activity or medication use and VZV-specific antibody levels was found. There was a weak association between total IgG and VZV-IgG. Conclusions Our results indicate that increased VZV-IgG levels in SLE do not result from frequent subclinical VZV reactivations, and are not associated with lupus disease activity. Increased VZV-IgG can only partially be explained by hypergammaglobulinaemia.

Rituximab impairs immunoglobulin (Ig)M and IgG (subclass) responses after influenza vaccination in rheumatoid arthritis patients.

Rituximab (RTX) treatment in rheumatoid arthritis (RA) patients severely hampers humoral response after influenza vaccination as determined by haemagglutination inhibition assay (HI). It is not known whether HI reflects both immunoglobulin (Ig)M and IgG (subclass) influenza response, and whether IgM antibodies contribute to the low rate of influenza infection seen in RA patients. Twenty RA patients on methotrexate (MTX), 23 on RTX and 28 healthy controls (HC) received trivalent influenza subunit vaccination. Before and 28 days after vaccination, H1N1- and H3N2-specific antibodies were measured by HI and by IgM and IgG (subclass) enzyme-linked immunosorbent assay (ELISA). B cell activating factor (BAFF) levels were determined in serum samples before vaccination. Vaccination induced a significant increase of IgM and IgG (IgG1 and IgG3) antibodies against both strains in the HC and MTX groups (all P < 0·01), but not in the RTX group. HI correlated significantly in all cases with IgG (IgG1) but not with IgM. In RTX late patients (RTX treatment 6-10 months before vaccination), IgG (IgG1 and IgG3) response to vaccination was restored, but not IgM response. BAFF levels were significantly increased in RA-RTX patients and correlated with total IgG levels. Haemagglutination inhibition assay, used as gold standard, detects primarily IgG (IgG1) responses. IgM- and IgG influenza-specific antibodies increase after vaccination in HC and RA patients except in patients on RTX treatment. BAFF levels are increased in both early and late RTX-treated patients, but do not correlate with an influenza-specific antibody response.

Peginterferon-alfa mono-therapy in the treatment of acute hepatitis C in HIV-infection.

The ongoing epidemic of acute hepatitis C (AHC) infection among MSM highlights the need to identify factors allowing for optimal treatment outcome in HIV co-infected individuals. Cohort study of 105 HIV-infected patients with AHC infection from five centres in two European countries was carried out. Choice of treatment with pegIFN-alfa alone (group 1; n = 36) or pegIFN-alfa and ribavirin (RBV) (group 2; n = 69) was at the discretion of the investigator. Outcome was evaluated as RVR and SVR. Fisher's exact and Mann Whitney U tests were used for statistical analysis. All patients were male, median age was 39 years, main route of transmission MSM (91%). In 69% of patients, clinical signs of acute hepatic infection were missing, dominant HCV genotypes were 1 (64%) and 4 (16%) and mean baseline HCV-RNA was 3.559.085 IU/mL. 60% received HAART and CD4 cell count was 469/mm(3) . Overall SVR rate was 64.8% (68/105). SVR was reached in 69% of treated patients in group 1 and in 63% of treated patients in group 2 (P = 0.67) while RVR was seen in 61% and 49%, respectively (P = 0.35). Interestingly, by univariate analysis, SVR rates in group 1 were significantly higher in patients initiating therapy within 4 weeks of AHC diagnosis compared to patients initiating therapy within 5-36 weeks after diagnosis (P = 0.03). PegIFN-alfa alone or in combination with ribavirin results in similar response rates in HIV-infected patients with AHC. In particular, when treatment is initiated within 4 weeks of diagnosis, pegIFN mono-therapy might be sufficient to allow for an optimal treatment response.

Immunization of patients with autoimmune inflammatory rheumatic diseases (the EULAR recommendations).

The European League Against Rheumatism (EULAR) recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) have been recently published. These evidence-based recommendations were based on existing literature in combination with expert opinion. Although patients with AIIRD are at increased risk of suffering from (complicated) infectious diseases--and vaccination seems a tool to reduce this risk--still many questions and controversies remain for the individual patient. In this overview, taking influenza as an example, the background of the recommendations, their clinical implications, and the direction of future research are discussed. The increase in knowledge on vaccine-preventable infections will allow us to further improve vaccination strategies.

EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases.

OBJECTIVES: To develop evidence-based European League Against Rheumatism (EULAR) recommendations for vaccination in patients with autoimmune inflammatory rheumatic diseases (AIIRD). METHODS: A EULAR task force was composed of experts representing 11 European countries, consisting of eight rheumatologists, four clinical immunologists, one rheumatologist/clinical immunologist, one infectious disease physician, one nephrologist, one paediatrician/rheumatologist and one clinical epidemiologist. Key questions were formulated and the eligible spectrum of AIIRD, immunosuppressive drugs and vaccines were defined in order to perform a systematic literature review. A search was made of Medline from 1966 to October 2009 as well as abstracts from the EULAR meetings of 2008 and 2009 and the American College of Rheumatology (ACR) meetings of 2007 and 2008. Evidence was graded in categories I-IV, the strength of recommendations was graded in categories A-D and Delphi voting was applied to determine the level of agreement between the experts of the task force. RESULTS: Eight key questions and 13 recommendations addressing vaccination in patients with AIIRD were formulated. The strength of each recommendation was determined. Delphi voting revealed a very high level of agreement with the recommendations among the experts of the task force. Finally, a research agenda was proposed. CONCLUSION: Recommendations for vaccination in patients with AIIRD based on the currently available evidence and expert opinion were formulated. More research is needed, particularly regarding the incidence of vaccine-preventable infectious diseases and the safety of vaccination in patients with AIIRD.

Intravenous voriconazole after toxic oral administration.

In a male patient with rhinocerebral invasive aspergillosis, prolonged high-dosage oral administration of voriconazole led to hepatotoxicity combined with a severe cutaneous reaction while intravenous administration in the same patient did not. High concentrations in the portal blood precipitate liver enzyme abnormalities, and therefore, oral administration of voriconazole may have a hepatotoxicity profile different from that of intravenous (i.v.) administration. Intravenously administered voriconazole might still be an option after oral-voriconazole-induced toxicity has resolved.

[Bruises, loose teeth and fatigue in a patient with schizophrenia]. / Blauwe plekken, uitvallende tanden en vermoeidheid bij een patiënte met schizofrenie.

A 53-year-old woman was referred because of progressive haematomas of the lower extremities and fatigue. Her medical history included hyperplastic gums and tooth loss. Scurvy was diagnosed; this was the result of an insufficient diet due to a paranoid psychosis. There was a dramatic improvement within a few days after addition of vitamin C and starting highly nutritious food. Scurvy is easily treated, but is not a disease of the past.

Favourable SVR12 rates with boceprevir or telaprevir triple therapy in HIV/HCV coinfected patients.

BACKGROUND: Recent publications have reported superior efficacy of telaprevir- or boceprevir-based triple therapy over conventional peginterferon-alfa/ribavirin therapy, albeit with varying rates of adverse events and treatment discontinuations in HIV/HCV coinfected patients. Therefore, the aim of this study is to describe the effectiveness of triple therapy in an HIV/HCV coinfection cohort in the Netherlands. METHODS: HIV-infected patients with chronic HCV genotype 1 starting triple therapy including either boceprevir or telaprevir were enrolled, 26% had F3-F4 fibrosis. Data were assessed at Week 4, 8, 12, 24, 48 and SVR12 (i.e. absence of detectable plasma HCV RNA 12 weeks after completion of treatment). Failure was defined as discontinuation of treatment due to virological failure, adverse events or loss to follow-up. RESULTS: A total of 53 HIV/HCV coinfected patients started peginterferon-alfa/ribavirin therapy with either boceprevir (n = 29) or telaprevir (n = 24). SVR12 was achieved in 19 (66%) of the boceprevir-treated and 15 (63%) of the telaprevir-treated patients. Both prior relapse and achievement of a rapid virological response were associated with a higher SVR12 rate. Non- response, breakthrough and relapse occurred in 4, 1 and 5 patients on boceprevir and 3, 2, 2 on telaprevir, respectively. One patient was lost to follow-up and one patient died due to progression of liver failure. Except for these two patients, no treatment discontinuations were observed due to adverse events. CONCLUSION: In HIV/HCV coinfected patients, boceprevir or telaprevir triple therapy was well tolerated and resulted in favourable SVR12 rates comparable with previous publications concerning HCV mono-infected patients.

Androgen receptor immunoexpression in the testes of subfertile men.

The localization and intensity of androgen receptor immunostaining was studied in the testes of 37 subfertile men with oligozoospermia and normal serum gonadotropin levels using a polyclonal antibody raised against a synthetic peptide corresponding to the first 20 N-terminal amino acid residues of the androgen receptor (AR). Furthermore, we investigated whether or not the immunoexpression of the AR in human Sertoli cells, in histologically normal testis tissue, is dependent on the stage of the spermatogenic cycle, as has been found in the rat. In the human testis, AR immunoexpression was observed in Sertoli cells, peritubular myoid cells, Leydig cells, and periarteriolar cells, but not in germinal cells. We found no evidence for a stage-dependent immunoexpression of AR in Sertoli cells. The intensity of AR immunoexpression varied substantially between biopsy specimens of different patients. There was, however, no correlation of the intensity of AR immunoexpression in either Sertoli cells or peritubular myoid cells with spermatogenic adequacy as measured by the method of Johnsen. When, in this study, the intensity of peritubular myoid cell staining was used as a standard to evaluate the intensity of Sertoli cell staining, no correlation was detected as well. Furthermore, serum gonadotropin levels were not correlated with AR immunoexpression levels in Sertoli cells and peritubular myoid cells. These results indicate that immunodetectability of the AR is not related to the condition of the spermatogenic epithelium in patients with oligozoospermia. Inappropriate expression of the AR is neither a cause nor a consequence of idiopathic infertility in the present group of patients.

Tuberculous dacryoadenitis: a rare manifestation of tuberculosis.

A 41-year-old Somalian female inhabitant of The Netherlands presented with malaise and cervical lymph node swelling. Enlarged mediastinal, hilar and abdominal lymph nodes were found on CT scan. Subsequently the left lacrimal gland became swollen, accompanied by periostitis of the lateral orbit margin. Mycobacterium tuberculosis was cultured from lymph node tissue and the diagnosis of tuberculous dacryoadenitis with periostitis was made on CT images and histology. All lesions responded well to tuberculostatic treatment. Although tuberculous dacryoadenitis is a very rare manifestation of tuberculosis, it is still important to recognise this presentation, especially since the incidence of tuberculosis continues to increase in Western countries.

Severe hyponatraemia in an amiloride/hydrochlorothiazide-treated patient.

A 85-year-old woman treated with, among other drugs, a thiazide diuretic presented with a severe hyponatraemia. She met several of the criteria for SIADH and, besides drugs, no cause for SIADH was found. After stopping the thiazide diuretic and restricting fluid intake the patient recovered fully. It was later proved that the thiazide was the cause of the water intoxication by rechallenging the patient with a single dose of amiloride/hydrochlorothiazide 5/50 mg. This "thiazide provocation test" showed its usefulness in the differential diagnosis of suspected SIADH. Moreover, the test demonstrated the paradoxal effect of thiazide diuretics to cause water retention in susceptible patients.

[The treatment of gallstone disease in the elderly]. / De behandeling van galsteenlijden bij ouderen.

Gallstone diseases (asymptomatic, symptomatic and complicated) are frequently seen in the elderly; the prevalence increases proportionally with age. At higher ages (> 60 years) the presentation of symptomatic or complicated gallstone disease is frequently atypical. Complicated gallstone disease (especially cholecystitis and cholangitis) in the elderly is associated with high morbidity and mortality rates. The introduction of laparoscopic cholecystectomy has decreased the morbidity and mortality rates of symptomatic and complicated gallstone disease in the elderly; for elective procedures in particular, the risks hardly differ from those for younger patients. Percutaneous cholecystostomy is an effective and safe alternative for (laparoscopic) cholecystectomy in high-risk patients with an acute cholecystitis. Endoscopic retrograde cholangiopancreaticography (ERCP) with sphincterotomy is also the treatment of choice for common bile duct stones in the elderly. After removal of common bile duct stones (whether or not accompanied by cholangitis or pancreatitis) a laparoscopic cholecystectomy should be performed, unless contraindications are present.

Vaccination of the immune-compromised patients with focus on patients with autoimmune-inflammatory diseases.

Among immunocompromised patients morbidity and mortality due to vaccine-preventable infections is high. Although vaccination seems indicated, controversy exists about which vaccines should be offered, at what moment, and to whom. Guidelines are needed as the number of immunocompromised individuals increases due to the wider use of immunosuppressive drugs and, in particular, because since the introduction of biological agents, the spectrum of immunosuppressive drugs is rapidly expanding. In this review we will highlight controversies about vaccination in immunocompromised patients and will discuss indications for the several vaccines available to prevent infectious diseases with the focus on patients with autoimmune-inflammatory diseases.

Vaccination in adult patients with auto-immune inflammatory rheumatic diseases: a systematic literature review for the European League Against Rheumatism evidence-based recommendations for vaccination in adult patients with auto-immune inflammatory rheumatic diseases.

OBJECTIVES: To present the systematic literature review (SLR), which formed the basis for the European League Against Rheumatism (EULAR) evidence-based recommendations for vaccination in adult patients with auto-immune inflammatory rheumatic diseases (AIIRD). METHODS: AIIRD, vaccines and immunomodulating drugs, as well as eight key questions were defined by the multidisciplinary expert committee commissioned by EULAR for developing the recommendations. A SLR was performed using MedLine through October 2009 and including data from meta-analyses, systematic reviews, randomized trials, and observational studies, excluding case series with ≤ 5 participants. Articles in English and regarding patients ≥ 16 years of age, were eligible. RESULTS: Several vaccine-preventable infections (VPI) occur more often in AIIRD-patients and most vaccines are efficacious in AIIRD-patients, even when treated with immunomodulating agents, except rituximab. There does not appear to be an increase in vaccination-related harms in vaccinated patients with AIIRD in comparison with unvaccinated patients with AIIRD. However, these studies are underpowered and therefore not conclusive. CONCLUSION: Based on the current evidence from the literature, recommendations for vaccination in patients with AIIRD were made. However, more research is needed in particular regarding incidence of VPI, harms of vaccination and the influence of (new and established) immunomodulating agents on vaccination efficacy.

Bilateral renal aspergillosis in a patient with AIDS: a case report and review of reported cases.

Renal aspergillosis is an extremely uncommon complication in HIV-infected patients. In general, prognosis is poor and the need for nephrectomy is emphasized. We report the case of a 37-year-old patient with AIDS since April 2003 (CD4 count 10 cells/mm(3), a high viral load, Candida esophagitis, bilateral pneumonia, HIV encephalopathy). Treatment with zidovudine, lamivudine, nevirapine, and lopinavir/ritonavir was started. Adherence to this medication proved to be a problem, but after 18 weeks of HAART the CD4 count was 110 cells/mm(3) and viral load was undetectable. One year later, he presented with hematuria and flank pain. Computed tomography (CT) scan revealed multiple lesions in both kidneys. Cultures of the abscess aspirates yielded Aspergillus fumigatus. Our review of 18 reported cases shows that prognosis of renal aspergillosis is poor if nephrectomy is not performed. However, in the present case a conservative approach was chosen to avoid life-long dialysis. The patient was treated successfully with a combination of voriconazole, percutaneous drainage, and highly active antiretroviral therapy (HAART). Renal function was completely preserved. Reported cases from the literature of renal aspergillosis in HIV-infected patients are summarized in this paper.

Prevotella bivia necrobacillosis following infectious mononucleosis.

A case of Lemierre's syndrome is reported. Although Fusobacterium species are commonly associated with this presentation, Prevotella bivia was the causative micro-organism identified in this case. The finding that disseminated anaerobic sepsis followed primary EBV infection led to the construction of a hypothetical model of infection.

Disseminated Mycobacterium gordonae infection in a renal transplant recipient.

The use of more intensive immunosuppressive regimens and the increasing number of patients that are exposed to immunosuppressive strategies in transplantation medicine have changed the spectrum of infections that is encountered by the clinician. We describe a 62-year-old female renal transplant recipient receiving immunosuppressive therapy who developed complaints of weight loss, diarrhoea, cough, and fever. Increased C-reactive protein and pancytopenia were found. The presence of Mycobacterium gordonae, a non-tuberculous mycobacterium, was eventually demonstrated in bronchoalveolar lavage fluid, bone marrow, spleen, and liver. Determination of the pathogen was accelerated using a Line Probe Assay, a reverse hybridisation technique using an RNA fragment specific for different mycobacterium species. Treatment was initiated using a combination of clarithromycin, ethambutol, and rifampicin. The initial response to treatment was good, but splenectomy and change of immunosuppressive and antimycobacterial therapy were necessary for long-term control of the infection. Problems in the diagnosis and treatment of this uncommon pathogen are discussed.