Salvatore Sollima

Recommendations for the management of mixed cryoglobulinemia syndrome in hepatitis C virus-infected patients.

OBJECTIVE The objective of this review was to define a core set of recommendations for the treatment of HCV-associated mixed cryoglobulinemia syndrome (MCS) by combining current evidence from clinical trials and expert opinion. METHODS Expert physicians involved in studying and treating patients with MCS formulated statements after discussing the published data. Their attitudes to treatment approaches (particularly those insufficiently supported by published data) were collected before the consensus conference by means of a questionnaire, and were considered when formulating the statements. RESULTS An attempt at viral eradication using pegylated interferon plus ribavirin should be considered the first-line therapeutic option in patients with mild-moderate HCV-related MCS. Prolonged treatment (up to 72 weeks) may be considered in the case of virological non-responders showing clinical and laboratory improvements. Rituximab (RTX) should be considered in patients with severe vasculitis and/or skin ulcers, peripheral neuropathy or glomerulonephritis. High-dose pulsed glucocorticoid (GC) therapy is useful in severe conditions and, when necessary, can be considered in combination with RTX; on the contrary, the majority of conference participants discouraged the chronic use of low-medium GC doses. Apheresis remains the elective treatment for severe, life-threatening hyper-viscosity syndrome; its use should be limited to patients who do not respond to (or who are ineligible for) other treatments, and emergency situations. Cyclophosphamide can be considered in combination with apheresis, but the data supporting its use are scarce. Despite the limited available data, colchicine is used by many of the conference participants, particularly in patients with mild-moderate MCS refractory to other therapies. Careful monitoring of the side effects of each drug, and its effects on HCV replication and liver function tests is essential. A low-antigen-content diet can be considered as supportive treatment in all symptomatic MCS patients. Although there are no data from controlled trials, controlling pain should always be attempted by tailoring the treatment to individual patients on the basis of the guidelines used in other vasculitides. CONCLUSION Although there are few controlled randomised trials of MCS treatment, increasing knowledge of its pathogenesis is opening up new frontiers. The recommendations provided may be useful as provisional guidelines for the management of MCS.

Histoplasmosis among human immunodeficiency virus-infected people in Europe : Report of 4 cases and review of the literature

Abstract: We reviewed the clinical, microbiologic, and outcome characteristics of 72 patients with human immunodeficiency virus (HIV)-associated histoplasmosis (4 newly described) reported in Europe over 20 years (1984-2004). Seven cases (9.7%) were acquired in Europe (autochthonous), whereas the majority involved a history of travel or arrival from endemic areas. The diagnosis of progressive disseminated histoplasmosis (PDH) was made during life in 63 patients (87.5%) and was the acquired immunodeficiency syndrome (AIDS)-presenting illness in 44 (61.1%). Disease was widespread in 66 patients (91.7%) and localized in 6 (8.3%), with the skin being the most frequent site of localized infection. Overall skin involvement was reported in 47.2% of the patients regardless of whether histoplasmosis was acquired in Africa or South America. Reticulonodular or diffuse interstial infiltrates occurred in 52.8%. The diagnosis was made during life by histopathology plus culture in 44 patients (69.8%), histopathology alone in 18 (28.5%), and culture alone in 1 (1.5%). During the induction phase amphotericin B and itraconazole (74.6%) were the single most frequently used drugs. Both drugs were also used either in combination (10.2%) or in sequential therapy (11.8%). Cumulative mortality rate during the induction phase of treatment was 15.2%. Overall, 37 patients died (57.8%); death occurred early in the course in 18 (28.1%). Seven of 40 patients (17.5%) who responded to therapy subsequently relapsed. Autopsy data in 13 patients confirmed the widespread disseminated nature of histoplasmosis (85%) among AIDS patients with a median of 4.5 organs involved. The results of the present report highlight the need to consider the diagnosis of PDH among patients with AIDS in Europe presenting with a febrile illness who have traveled to or who originated from an endemic area. Abbreviations: AIDS = acquired immunodeficiency syndrome; CMV = cytomegalovirus, Hcc = H. capsulatum var. capsulatum; Hcd = H. capsulatum var. duboisii; HIV = human immunodeficiency virus; PCP = Pneumocystis pneumonia; PCR = polymerase chain reaction; PDH = progressive disseminated histoplasmosis; PR = present report.

Protease inhibitors and erectile dysfunction.

Increasing numbers of HIV-positive men receiving protease inhibitors (PI) complain of erectile dysfunction (ED). Through the analysis of 334 HIV-1-infected male outpatients, this study shows homosexuality, CD4 cell count, viral load, and indinavir treatment to be independent variables predictive of ED. Furthermore, a neuropathy of the sacral region was detected in 12 patients with ED who underwent diagnostic investigations. For the first time, a PI-containing regimen has been associated with peripheral neuropathy causing ED.

AIDS‐associated cryptococcosis: a comparison of epidemiology, clinical features and outcome in the pre‐ and post‐HAART eras. Experience of a single centre in Italy

To assess the prevalence, clinical and immunological characteristics, risk factors and survival of patients with AIDS‐related cryptococcosis in the era of highly active antiretroviral therapy (HAART).

Aspergillus meningitis: a rare clinical manifestation of central nervous system aspergillosis. Case report and review of 92 cases.

Summary Objectives To describe the pathogenesis, clinical presentation, cerebrospinal fluid findings and outcome of Aspergillus meningitis, meningoencephalitis and arachnoiditis. Methods A case of Aspergillus meningitis is described. A comprehensive review of the English-language literature was conducted to identify all reported cases of Aspergillus meningitis described between January 1973 and December 2011. Results Ninety-three cases (including the one described herein) of Aspergillus meningitis were identified. Fifty-two (55.9%) were in individuals without any predisposing factor or known causes of immunosuppression. Acute and chronic meningitis was diagnosed in 65.6% of patients and meningoencephalitis in 24.7% of them with the remaining presenting with spinal arachnoiditis and ventriculitis. Cerebrospinal fluid cultures for Aspergillus spp. were positive in about 31% of cases and the galactomannan antigen test in 87%. Diagnosis during life was achieved in 52 patients (55.9%) with a case fatality rate of 50%. The overall case fatality rate was 72.1%. Conclusions Aspergillus meningitis may occur in both immunocompetent and immunocompromised patients and run an acute or chronic course. The findings of this systematic review extend the information on this life-threatening infection and could assist physicians in achieving an improved outcome.

Outcome of a second-line protease inhibitor-containing regimen in patients failing or intolerant of a first highly active antiretroviral therapy.

Summary: The outcome of second‐line protease inhibitor (PI)‐containing highly active antiretroviral therapy (HAART) was investigated in 263 patients who were failed by (n = 148) or intolerant of (n = 115) a first HAART regimen. The endpoints were virologic failure (decline in HIV RNA <1 log10 copies/ml after ≥2 months) and discontinuation due to intolerance/toxicity. During a median follow‐up of 483 days (33‐1087 days), 154 patients (59%) discontinued the second regimen, 86 (33%) because of intolerance/toxicity; another 135 patients (51.3%) showed virologic failure. Independent factors associated with virologic failure (Coxs model) were 7 to 12 months of first HAART (hazard ratio [HR] 1.70 versus ≥6 months: 95% confidence interval [CI], 1.08‐2.70) and gender (HR 1.58 males versus females: 95% CI, 1.04‐2.30); the negatively associated factors were advanced age (HR 0.61 >34 years versus ≤34 years: 95% CI, 0.42‐0.88), a saquinavir‐containing first HAART (HR 0.57 versus indinavir: 95% CI, 0.34‐0.93) and change due to intolerance/toxicity (HR 0.58 versus failure: 95% CI, 0.35‐0.98). The independent variables predictive of discontinuation due to intolerance/toxicity were the reason for switching (HR 1.79 intolerance versus failure: 95% CI, 1.02‐3.16) and the first protease inhibitor (PI) regimen (HR 0.42 ritonavir versus indinavir: 95% CI, 0.22‐0.80). Given that patients who are failed by a first regimen are at high risk of having rescue therapy fail as well, second‐line regimens including therapies directed by testing of drug resistance patterns of clinical viral isolates are warranted. Patients experiencing toxicity due to a first PI‐containing regimen are at risk of toxicity to other PIs and should be addressed to PI‐sparing HAART.

Direct‐acting antivirals in hepatitis C virus (HCV)‐infected and HCV/HIV‐coinfected patients: real‐life safety and efficacy

Clinical trials of all‐oral direct‐acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection reported high response rates in HCV/HIV coinfection, similar to those obtained in HCV monoinfection. We evaluated the safety and efficacy of these regimens in a clinical practice setting.

Fungal Endocarditis Observed Over an 8-Year Period and a Review of the Literature

BackgroundFungal endocarditis (FE) is a “modern” disease that is considered an emerging cause of infective endocarditis (IE). The most frequently identified fungal pathogens are Candida spp., which are responsible for up to two-thirds of all cases; the remaining cases are due to Aspergillus spp., Histoplasma capsulatum or, more rarely, other yeasts and moulds.ObjectivesTo describe the prevalence, clinical characteristics and outcome of FE diagnosed in a single tertiary centre and review the literature concerning FE.Design and settingAn 8-year retrospective review of the case records of patients attending a single Italian University Centre and diagnosed as having definite or probable IE as defined by the modified Duke criteria.ResultsSix patients were identified from 229 episodes of IE: five cases involved a prosthetic valve, and one a native valve of an intravenous drug user. Five cases were caused by Candida spp. (two by C. albicans, one each by C. lusitaniae, C. dubliniensis and C. glabrata) and one by Aspergillus flavus. Three patients were treated by means of surgery plus antifungal therapy; two received antifungal therapy alone. Three patients survived, but only the patient with Aspergillus endocarditis was followed up for a long time.ConclusionsFE is difficult to diagnose but generally associated with healthcare infections. The optimal treatment is poorly characterised, and international collaborative studies are urgently needed to evaluate newer antifungal agents.

Italian consensus Guidelines for the management of hepatitis B virus infections in patients with rheumatoid arthritis

OBJECTIVES Hepatitis B (HBV) infection, which is prevalent worldwide, is also frequently seen in patients with rheumatoid arthritis (RA). The Italian Society of Rheumatology (SIR) and the Italian Society of Infectious and Tropical Diseases (SIMIT) endorsed a national consensus process to review the available evidence on HBV management in RA patients and to produce practical, hospital-wide recommendations. METHODS The consensus panel consisted of infectious disease consultants, rheumatologists and epidemiologists and used the criteria of the Oxford Center for Evidence-based Medicine to assess the quality of the evidence and the strength of their recommendations. RESULTS A core-set of statements has been developed to help clinicians in the management of patients with RA and HBV infection. Vaccination and prophylaxis of RA patients treated with biological drugs have been also discussed. CONCLUSIONS HBV infection is not rare in clinical practice; a screening for HBV in all patients with early arthritis is not universally accepted, while it is considered mandatory before starting any immunosuppressive or hepatotoxic treatment. In fact, a specific risk, associated with the use of biologic treatments, exists for patients with HBV infection, although longitudinal studies of viral reactivation are generally reassuring. RA patients with HBV infection should be referred to the hepatologist and correctly classified into active or inactive carriers. Patients with active hepatitis B should undergo antiviral treatment before starting immunosuppressive treatments. Occult HBV carriers should be monitored or receive prophylaxis on the basis of the risk of reactivation associated with the administered treatment.

Predictive role of the three-month CD4 cell count in the long-term clinical outcome of the first HAART regimen.

The aim was to evaluate whether the three-month CD4 cell counts are a reliable predictor of the long-term clinical outcome of HAART-treated patients, by an observational study of 585 patients initiating HAART in a clinical setting. Clinical failure was defined as the occurrence of new or recurrent AIDS-defining events or death, and was analysed by means of intention-to-treat, univariate and multivariate analyses. An adjusted Cox regression model was used to evaluate the effect of three-month CD4+ counts on clinical outcome. Clinical failure occurred in 65 patients (11.1%) during a median follow-up of 31 months (1-65) as a result of new AIDS-defining events (ADEs) in 48 patients, ADE recurrence in six, and death in 11. The mean (median; range) CD4+ counts were 156/microL (155; 4--529) in patients with and 362/microL (326; 18--1162) in patients without clinical failure (P < .0001). Moreover, the proportion of patients with mean CD4+ counts < 200 microL was higher in those experiencing subsequent clinical failure (chi2: 41.11; P< .00001). Multivariate analysis showed that baseline CD4+ counts < 50 microL, HIV-RNA > 100,000 copies/mL and AIDS at baseline predicted failure; after adjusting for three-month CD4+ counts, this marker was the only one independently associated with clinical failure (HR 2.93; 95% Cl: 1.16--7.38). The three-month immunologic response is a reliable predictor of long-term clinical outcome.