Long-term outcomes of CMV disease treatment with valganciclovir versus IV ganciclovir in solid organ transplant recipients.

Though an important cause of morbidity and mortality in solid organ transplantation (SOT), the long-term outcomes of cytomegalovirus (CMV) disease treatment have not been well studied. In a randomized trial, 321 SOT recipients with CMV disease were followed 1 year after treatment with either twice daily intravenous ganciclovir or oral valganciclovir (for 21 days) followed by once daily valganciclovir until day 49 in all patients. Clinical and viral eradication of CMV disease was similar between groups. Clinical recurrence beyond day 49 was found in 15.1% and virological recurrence in 30.0%, no difference between groups (p > 0.77). In a multivariable logistic regression analysis, the only independent predictor for recurrence was failure to eradicate DNAemia by day 21 (clinical: OR 3.9 [1.3-11.3], p = 0.012; virological: OR 5.6 [2.5-12.6], p < 0.0001). Eight patients developed ganciclovir resistance, with no difference between groups (p = 0.62). Twenty patients (valganciclovir: 11, ganciclovir: 9, p = 0.82) died, 12 due to infections, two involving CMV disease. There were no differences in long-term outcomes between treatment arms, further supporting the use of oral valganciclovir for treatment of CMV disease. Persistent DNAemia at day 21, CMV IgG serostatus and development of resistance may be relevant factors for further individualization of treatment.

An assessment of herpesvirus co-infections in patients with CMV disease: correlation with clinical and virologic outcomes.

The effect of herpesvirus co-infections (HHV-6, HHV-7) on cytomegalovirus (CMV) disease and its response to therapy is unknown. We prospectively analyzed herpesvirus co-infections in transplant recipients with CMV disease. All patients received 3 weeks of antiviral therapy. Samples were collected at baseline (day 0) and then day 3, 7, 14 and 21 poststart of therapy. Viral load testing for CMV, HHV-6 and HHV-7 was done using quantitative PCR assays in 302 patients of whom 256 had documented symptomatic CMV viremia. In this subset, day 0 HHV-6 co-infection was present in 23/253 (9.1%) and HHV-7 in 17/253 (6.7%). Including those positive at any time point raised the prevalence to 79/256 (30.9%) for HHV-6 and 75/256 (29.3%) for HHV-7. Viral co-infection did not influence the response of CMV disease to antiviral therapy. Baseline CMV viral loads, time to eradication and risk of recurrence were similar in patients with and without HHV-6 or HHV-7 co-infection. Ganciclovir and valganciclovir had no clear effect on HHV-6 and HHV-7 viremia. In conclusion, herpesvirus co-infections are common in patients with CMV disease but with standard antiviral therapy, no clear clinical effects are discernable. Routine monitoring for viral co-infection in patients with CMV disease is not indicated.

[Hypoxemic nosocomial pneumonia developing in excavation in a patient with Cushing disease]. / Pneumopathie nosocomiale hypoxémiante évoluant vers l'excavation chez un patient atteint de maladie de Cushing.

Multifocal alveolar hypoxaemic pneumonia caused by sporadic nosocomial infection led to acute respiratory failure and development of cavitations. Legionella pneumophilia type I was isolated. The patient was not in a state of immunosuppression other than that due to Cushing's disease recently treated surgically followed by corticosteroids. Specific clinical and radiological signs of Legionellosis (particularly the development of cavitation) and their mode of infection (community acquired or noscomial, sporadic or epidemic, immunocompetence or immunodepression) are discussed.

[Severe hepatitis in a patient with adult-onset Still's disease treated with anakinra]. / Hépatite aiguë médicamenteuse à l'anakinra chez une patiente traitée pour une maladie de Still de l'adulte.

INTRODUCTION: Adult-onset Still's disease is characterized by non-specific polymorphic features. The efficacy of anakinra, an IL-1 receptor antagonist, has been shown in several studies. This medication is well-tolerated, and only one case of severe hepatitis has been previously reported. CASE REPORT: A 22-year-old woman presented with fever, rash, arthritis, and pericarditis, associated with systemic inflammatory response syndrome and elevated ferritin serum level with low glycosylated ferritin. Adult-onset Still's disease was diagnosed, but treatment with steroids did not achieve remission. The patient was then treated with anakinra, which resulted in spectacular improvement, but 3 weeks after the initiation of the treatment she experienced severe hepatitis that resolved after the discontinuation of anakinra. CONCLUSION: Hepatitis is a rare side effect of anakinra and the monitoring of liver tests should be recommended during anakinra therapy.

Oral valganciclovir is noninferior to intravenous ganciclovir for the treatment of cytomegalovirus disease in solid organ transplant recipients.

Intravenous ganciclovir is the standard treatment for cytomegalovirus disease in solid organ transplant recipients. Oral valganciclovir is a more convenient alternative. In a randomized, international trial, recipients with cytomegalovirus disease were treated with either 900 mg oral valganciclovir or 5 mg/kg i.v. ganciclovir twice daily for 21 days, followed by 900 mg daily valganciclovir for 28 days. A total of 321 patients were evaluated (valganciclovir [n = 164]; i.v. ganciclovir [n = 157]). The success rate of viremia eradication at Day 21 was 45.1% for valganciclovir and 48.4% for ganciclovir (95% CI -14.0% to +8.0%), and at Day 49; 67.1% and 70.1%, respectively (p = NS). Treatment success, as assessed by investigators, was 77.4% versus 80.3% at Day 21 and 85.4% versus 84.1% at Day 49 (p = NS). Baseline viral loads were not different between groups and decreased exponentially with similar half-lives and median time to eradication (21 vs. 19 days, p = 0.076). Side-effects and discontinuations of assigned treatment (18 of 321 patients) were comparable. Oral valganciclovir shows comparable safety and is not inferior to i.v. ganciclovir for treatment of cytomegalovirus disease in organ transplant recipients and provides a simpler treatment strategy, but care should be taken in extrapolating to organ transplant recipients not properly represented in the present study.

[Vaccinations and systemic diseases. Vaccinations and immunosuppression]. / Vaccinations et maladies systémiques. Vaccinations et immunodépression.

The hypothesis of systemic disease flare up or onset triggered by vaccination cannot be confirmed by the analysis of data from the literature. In immune deficiency of any cause, immunization is of great interest to avoid preventable infectious diseases but the risk of adverse events and suboptimal immunologic responses has to be considered. For live, attenuated vaccines the main risks are postimmunization complications, specially in persons severely immunocompromised. For killed or inactivated vaccines there are no contraindications, but the immune response is reduced leading to consider higher vaccine doses or more frequent boosters. However the response to such modifications of vaccine schedules has not been systematically evaluated and firm recommendations cannot be made at this time. In addition, in HIV infection, the effect of vaccination on viral replication has to be considered. In developing countries some live vaccines are still recommended in HIV+ children because of the prevalence of the target-diseases (measles, poliomyelitis, tuberculosis...) and the rarity of complications.

Embolization of multiple pulmonary arterial aneurysms in Behçet's disease.

Arterial manifestations of Behçet's disease carry a particularly poor prognosis, especially pulmonary arterial aneurysms. We report herein the successful embolization of multiple bilateral pulmonary arterial aneurysms in a young Algerian man, whose treatment included corticosteroids and immunosuppressive drugs.

Hyperthyroidism in two patients with Crohn disease and Takayasu arteritis.

Thyroid abnormalities and Takayasu arteritis (TA) have been reported separately in patients with Crohn disease (CD). We report two patients with hyperthyroidism, CD and Takayasu arteritis and discuss hypothetical mechanisms. Case 1. A thyrotoxic goiter was diagnosed in 1987 in a 34-year-old woman treated since 1969 for severe CD and TA. Iodine urinary excretion was 405 microg/mL (20-500). Anti-thyrotropin receptor (TRAK) and anti-thyroid antibodies were not detectable. The ultrasonography showed a nodule in the right lobe of the thyroid and two nodules in the left lobe. A 123I thyroid scan showed a multinodular goiter with no hot nodule. She was treated successfully with propylthiouracile until 1991, when a new episode of thyrotoxicosis led to a subtotal thyroidectomy. Case 2. Hyperthyroidism was diagnosed in February 2000 in a 49-year-old woman treated for CD and TA, both diagnosed in 1980. TRAK and anti-thyroid peroxydase antibodies were not detectable. The ultrasonography disclosed a normal thyroid volume with an inhomogeneous parenchymal structure and nodular images in both lobes. A 123I thyroid scan showed one hot nodule in the lower part of each lobe. A subtotal thyroidectomy was performed. The association of these three diseases may not be fortuitous, possibly explained by genetic predisposing factors and disease-related iodine deficiency both involving Nuclear Factor kappaB pathway.