A 1-Year Prospective French Nationwide Study of Emergency Hospital Admissions in Children and Adults with Primary Immunodeficiency.

PURPOSE: Patients with primary immunodeficiency (PID) are at risk of serious complications. However, data on the incidence and causes of emergency hospital admissions are scarce. The primary objective of the present study was to describe emergency hospital admissions among patients with PID, with a view to identifying "at-risk" patient profiles. METHODS: We performed a prospective observational 12-month multicenter study in France via the CEREDIH network of regional PID reference centers from November 2010 to October 2011. All patients with PIDs requiring emergency hospital admission were included. RESULTS: A total of 200 admissions concerned 137 patients (73 adults and 64 children, 53% of whom had antibody deficiencies). Thirty admissions were reported for 16 hematopoietic stem cell transplantation recipients. When considering the 170 admissions of non-transplant patients, 149 (85%) were related to acute infections (respiratory tract infections and gastrointestinal tract infections in 72 (36%) and 34 (17%) of cases, respectively). Seventy-seven percent of the admissions occurred during winter or spring (December to May). The in-hospital mortality rate was 8.8% (12 patients); death was related to a severe infection in 11 cases (8%) and Epstein-Barr virus-induced lymphoma in 1 case. Patients with a central venous catheter (n = 19, 13.9%) were significantly more hospitalized for an infection (94.7%) than for a non-infectious reason (5.3%) (p = 0.04). CONCLUSION: Our data showed that the annual incidence of emergency hospital admission among patients with PID is 3.4%. The leading cause of emergency hospital admission was an acute infection, and having a central venous catheter was associated with a significantly greater risk of admission for an infectious episode.

Cardiac device implantation in Fabry disease: A retrospective monocentric study.

The incidence and predictive factors of arrhythmias and/or conduction abnormalities (ACAs) requiring cardiac device (CD) implantation are poorly characterized in Fabry disease (FD). The aim of our retrospective study was to determine the prevalence, incidence, and factors associated with ACA requiring CD implantation in a monocentric cohort of patients with confirmed FD who were followed up in a department of internal medicine and reference center for FD.Forty-nine patients (20M, 29F) were included. Nine patients (4M, 5F; 18%) had at least one episode of ACA leading to device therapy. Six patients (4M/2F) required a pacemaker (PM) for sinus node dysfunction (n = 4) or atrioventricular disease (n = 2). One female patient required an internal cardioverter-defibrillator (ICD) to prevent sudden cardiac death because of nonsustained ventricular tachycardia (nSVT). One female patient required PM-ICD for sinus node dysfunction and nSVT. One patient underwent CD implantation before the diagnosis of FD. The annual rate of CD implantation was estimated at 1.90 per 100 person years. On univariate analysis at the end of the follow-up period, the factors associated with ACAs requiring CD implantation were as follows: delayed diagnosis of FD, delayed initiation of enzyme replacement therapy, age at the last follow-up visit, and severe multiorgan phenotype (hypertrophic cardiomyopathy, chronic kidney disease, and/or sensorineural hearing loss). On multivariate analysis, age at diagnosis of FD and age at the last follow-up visit were independently associated with an increased risk of ACAs requiring CD (P < 0.05).Considering the high frequency of ACAs requiring CD implantation and the risk of sudden death in patients with FD, regular monitoring is mandatory, especially in patients with a late diagnosis of FD and/or with a severe phenotype. Regular Holter ECGs, therapeutic education of patients, and deliverance of an emergency card including a phenotype summary are crucial in the care of FD patients.Available guidelines for device therapy and the efficacy of enzyme replacement therapy for arrhythmias or conduction abnormalities are discussed.

Posterior reversible encephalopathy syndrome and systemic vasculitis: report of six cases.

OBJECTIVES: Our objective was to describe the characteristics of posterior reversible encephalopathy syndrome (PRES) associated with systemic vasculitis. METHODS: A standardised questionnaire was used for a nationwide retrospective multicentre study in 2013 to collect clinical, radiological and outcome data about PRES associated with systemic vasculitis. RESULTS: We included six patients (all women; mean age 22.6±19.8 years (20-62)): two with polyarteritis nodosa and one case of each granulomatosis with polyangiitis, cryoglobulinaemic vasculitis, hypocomplementemic urticarial vasculitis, and Takayasu arteritis. PRES was the first manifestation of systemic vasculitis in three patients. Arterial hypertension was suspected to be the cause of PRES in five patients. Several other plausible causes including drugs, renal failure, and pneumonia were found in three patients. Clinical findings included headache, seizure, blurred or loss of vision, confusion, and altered cognition. Radiological study showed oedema in the occipital region in all patients, with a reversible state in MRIs performed one week to one month after the onset of PRES. Therapies used included antihypertensive therapy (n=5), immunosuppressive therapy (corticosteroids (n=5), cyclophosphamide (n=4), azathioprine (n=1), methotrexate (n=1), plasma exchange (n=1)), antibiotics (n=1), anticonvulsant therapy (n=2)), and analgesics. No relapse of PRES was reported during the follow-up period (mean: 47.5 ±29.9 months, 13-98); one patient continued to complain of vision loss. CONCLUSIONS: Our study indicates that PRES is a rare condition associated with systemic vasculitis; which may be present at the onset vasculitis symptoms. Antihypertensive drugs should be prescribed if blood pressure is elevated. The impact of immunosuppressive therapy remains unclear.

CNS involvement and treatment with interferon-α are independent prognostic factors in Erdheim-Chester disease: a multicenter survival analysis of 53 patients.

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans histiocytosis, with noncodified therapeutic management and high mortality. No treatment has yet been shown to improve survival in these patients. We conducted a multicenter prospective observational cohort study to assess whether extraskeletal manifestations and interferon-α treatment would influence survival in a large cohort of ECD patients. To achieve this goal, we thoroughly analyzed the clinical presentation of 53 patients with biopsy-proven ECD, and we performed a survival analysis using Cox proportional hazard model. Fifty-three patients (39 men and 14 women) with biopsy-proven ECD were followed up between November 1981 and November 2010. Forty-six patients (87%) received interferon-α and/or PEGylated interferon-α. Multivariate survival analysis using Cox proportional hazard model revealed that central nervous system involvement was an independent predictor of death (hazard ratio = 2.51; 95% confidence interval, 1.28-5.52; P = .006) in our cohort. Conversely, treatment with interferon-α was identified as an independent predictor of survival (hazard ratio = 0.32; 95% confidence interval, 0.14-0.70; P = .006). Although definitive confirmation would require a randomized controlled trial, these results suggest that interferon-α improves survival in ECD patients. This may be seen as a significant advance, as it is the first time a treatment is shown to improve survival in this multisystemic disease with high mortality.

Cryoglobulinaemia vasculitis in patients coinfected with HIV and hepatitis C virus.

OBJECTIVE: To describe mixed cryoglobulinaemia (MC) vasculitis in patients coinfected with hepatitis C virus (HCV) and HIV. DESIGN: Retrospective multicentre study through the GERMIVIC Database of 4005 HIV/HCV-coinfected patients. METHODS: The characteristics and outcome of 11 HIV/HCV-coinfected patients with MC vasculitis were analysed and compared with those of 118 HCV-infected patients with MC vasculitis. RESULTS: The mean age was 46 years (SD, 14), with 82% male. The median initial CD4 cell count was 367 cells/microl (range, 252-846). After a mean follow-up of 44.4 months, two deaths (18%) were noted. Clinical manifestations of MC included polyneuropathy in seven (64%), purpura in four (36%), arthralgia in four (36%), and kidney involvement in three (27%). Six patients received combination treatment with interferon-alfa and ribavirin, three of whom had sustained HCV virological response and were complete clinical responders. Four patients received corticosteroids and two showed a partial clinical response. Regardless of the HIV virological response, antiretroviral therapy did not improve MC vasculitis. Compared with patients with HCV monoinfection, coinfected patients were younger (P < 0.001), more frequently male (P = 0.03), more frequently intravenous drug users (P < 0.001), had higher HCV viraemia (P = 0.004), higher liver necroinflammation (P = 0.03), higher gammaglobulinaemia (P < 0.001) and lower cryoglobulin level (P = 0.03). The clinical manifestations of MC vasculitis did not differ significantly between the two groups. CONCLUSION: There was a beneficial effect of anti-HCV therapy for HIV/HCV-coinfected patients with MC vasculitis.

Type III cryoglobulinemia complicated by renal cortical necrosis.

Renal involvement is rare in patients with type III cryoglobulinemia. We report a case of renal cortical necrosis in a patient with type III cryoglobulinemia. Renal function improved partially after treatment with plasma exchange, steroids, and cyclophosphamide. Renal magnetic resonance imaging was a valuable tool in the evaluation of the extent of renal cortical necrosis and improvement in renal vascularization after treatment.

Prevalence of mixed cryoglobulins in relation to CD4 cell count among patients coinfected with HIV and hepatitis C virus.

Cryoglobulinemia was studied in human immunodeficiency virus-positive, hepatitis C virus (HCV)-positive patients in relation to their CD4 cell count. Cryoglobulinemia was found in 18 (31.6%) of 57 patients: 17 (44.7%) of 38 patients with a CD4 cell count of >or=200 cells/ micro L versus 1 (5.3%) of 19 patients with a CD4 cell count of <200 cells/ micro L (P=.0064). Cell-mediated immunity could, therefore, contribute to the production of HCV-associated cryoglobulins.

Thrombotic microangiopathy and hypothermia in an HIV-positive patient: importance of cytomegalovirus infection.

Cytomegalovirus (CMV) infection is a well-known frequent complication in HIV-infected patients. We report a case of thrombotic microangiopathy and severe hypothermia in a 21-y-old woman positive for HIV infection. CMV infection was diagnosed by PCR. The symptoms completely resolved after ganciclovir therapy which supports the role of CMV as a causative agent.

Evidence of genotypic resistance diversity of archived and circulating viral strains in blood and semen of pre-treated HIV-infected men.

OBJECTIVE: To study the genetic diversity of drug-resistant HIV strains present in blood and in semen, especially those archived in peripheral blood mononuclear cells (PBMC) and non-sperm cells (NSC). METHODS: Paired blood and semen samples were collected from twenty heavily pre-treated HIV-infected men. HIV RNA in blood plasma (BP) and seminal plasma (SP), as well as proviral DNA in PBMC and NSC were quantified and used for resistance genotyping. Phylogenetic analysis of protease gene clones was used to explore the diversity of the viral quasi-species. RESULTS: Median BP HIV RNA, PBMC proviral DNA, SP HIV RNA and non-sperm cell proviral DNA loads were respectively: 4.77, 3.65, 3.16 and 1.77 log10 copies per ml or per 10 cells. Resistant HIV strains were found in the BP and PBMC of all the patients, in the SP of 14 patients, and in the NSC of five patients. Overall, the blood and genital compartments exhibited different genotypic resistance patterns in six patients (30%), with additional resistance mutations in the semen of four patients. Phylogenetic analysis of clones of HIV protease gene showed that viral strains in SP originated not only from passive diffusion from BP, but also from local production in semen. The storage of archived proviruses differed according to the anatomic reservoir. CONCLUSION: HIV resistant strains are frequent (70%) in the semen of heavily pre-treated men, and the diversity of genotypic resistance pattern confirms HIV compartmentalization. Thus, the risk of sexual transmission of resistant strains can only be partly predicted by standard tests applied to BP.

Impact of 5 years of maximally successful highly active antiretroviral therapy on CD4 cell count and HIV-1 DNA level.

OBJECTIVES: To evaluate the impact on CD4 cell count and HIV-1 DNA level in peripheral blood mononuclear cells (PBMC) of long-term highly active antiretroviral therapy (HAART) in the setting of maximal success, i.e., constant plasma HIV-1 RNA load suppression. DESIGN: Retrospective analysis of patients selected for a constantly undetectable plasma HIV-1 RNA load since HAART initiation. METHODS: HIV-1 DNA was measured in PBMC using a real-time polymerase chain reaction assay. Loess estimates and regression analysis were used for modelling the variations of the CD4 cell count and HIV DNA level over time. RESULTS: The study included 41 patients chronically infected with HIV-1 who had been taking HAART for a median duration of 60.4 months and had an undetectable plasma HIV RNA load ever since the first 6 months of HAART; 25 were tested for HIV-1 DNA. The mean CD4 cell count increase was high during the first 18 months on therapy (168 x 10 cells/l per year), much lower afterwards (38 x 10 cells/l per year), independently of the baseline CD4 cell count. Most of the patients (73.2%) reached a CD4 cell count constantly > or = 400 x 10/l during follow-up. HIV-1 DNA showed a mean decrease of 0.48 log10 copies/10 PBMC during the first year, of 0.18 log10 copies/10 PBMC per year during the 2nd and 3rd years, but no significant decrease afterwards. CONCLUSIONS: These results question the benefit of very long-term maintenance of HAART in terms of CD4 gain and HIV-1 DNA reduction.

Successful medical treatment of Candida albicans in mechanical prosthetic valve endocarditis.

Fungal prosthetic valve endocarditis is particularly serious, and is usually a result of nosocomial candidaemia. This report describes a patient with Candida albicans prosthetic valve endocarditis in whom surgery was believed to be contraindicated. After 45 d of amphotericin B, treatment was continued with fluconazole daily with a follow-up of 16 months, with no recurrent or adverse effects.

Rituximab therapy for HIV-associated Castleman disease.

To assess the clinical benefit of rituximab for HIV-associated Castleman disease, 5 patients infected with HIV with histologic-proven Castleman disease were prospectively enrolled to receive 4 infusions of rituximab. Clinical and biologic parameters (C-reactive protein, CD19 cell count, Kaposi sarcoma-associated herpesvirus [KSHV] viral load in peripheral blood mononuclear cells) were assessed before and at different time points following rituximab infusions. Two patients died very quickly after the beginning of rituximab therapy with no effect on both KSHV viral load and CD19 cell count. Three of 5 patients were considered in complete remission with no more clinical symptoms related to Castleman disease with a follow-up of 4 to 14 months. In 2 cases, clinical remission correlated with a dramatic decrease of KSHV viral load and C-reactive protein levels and a transitory but sharp decrease of CD19 cell count. In 2 responders, we observed an aggravation of Kaposi sarcoma. Our preliminary results suggest that rituximab may be effective in controlling Castleman disease in a subset of patients, although it may exacerbate concomitant Kaposi sarcoma.

Human herpesvirus 8-positive Castleman disease in human immunodeficiency virus-infected patients: the impact of highly active antiretroviral therapy.

We report the case histories of 7 human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART) who had a diagnosis of Castleman disease. All 6 patients who were treated responded to chemotherapy; immune reconstitution was observed in 5 patients, but it did not prevent relapse of Castleman disease. However, the mean duration of survival observed in this series (48 months) was most probably due to immune reconstitution resulting from receipt of HAART, which reduced the mortality associated with HIV disease.